Houston, TX, United States
Houston, TX, United States

Baylor College of Medicine , located in the Texas Medical Center in Houston, Texas, US, is a health science university. It includes a medical school, Baylor College of Medicine; the Graduate School of Biomedical science; the School of Allied Health science; and the National School of Tropical Medicine. The school, located in the middle of the world's largest medical center, is part owner of Baylor St. Luke's Medical Center, part of the CHI St. Luke's Health system, and has hospital affiliations with: Harris Health System, Texas Children's Hospital, The University of Texas MD Anderson Cancer Center, Memorial Hermann - The Institute for Rehabilitation and Research, Menninger Clinic, the Michael E. DeBakey Veterans Affairs Medical Center and Children's Hospital of San Antonio.The medical school has been consistently considered in the top-tier of programs in the country, and is particularly noted for having the lowest tuition among all private medical schools in the US. Its Graduate School of Biomedical science is among the top 30 graduate schools in the United States. Within the School of Allied Health science, the nurse anesthesia ranks 5th and the physician assistant program ranks 6th. A program in Orthotics and Prosthetics began in 2013, with 18 students in the first class. The National School of Tropical Medicine is the only school in the nation dedicated exclusively to patient care, research, education and policy related to neglected tropical diseases.On June 21, 2010, Dr. Paul Klotman was named as the new President and CEO of the Baylor College of Medicine. In January 2014, the College and CHI St. Luke's became joint owners of Baylor St. Luke's Medical Center. Wikipedia.


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Patent
Baylor College of Medicine | Date: 2016-10-13

The present invention concerns immunotherapy for cancers having cells that comprise the ganglioside GD2 antigen. In specific embodiment, T cells having a chimeric receptor that targets GD2 is employed. In particular cases, the chimeric receptor comprises antibody, cytoplasmic signaling domain from the T cell receptor, and/or costimulatory molecule(s).


Patent
Rice University, Baylor College of Medicine and Texas Heart Institute | Date: 2015-02-20

Systems and methods for deploying and securing conductive materials to a region of tissue may utilize a catheter. The catheter may provide a tip with one or more detachable sections or may provide an adjustable opening. A lumen of the catheter may provide a conductive material, such as a filament, fiber, network or patch of carbon nanotubes (CNTs) or carbon nanofibers (CNFs). In some embodiments, the conductive materials may be coupled to securing mechanisms, such as screws, clips, anchors, alligator clips, or anchors with barbs, which can be actuated to attach the conductive materials to desired regions of tissue. In some embodiments, the catheter may provide a needle tip that allows the conductive material to be embedded into desired regions of tissue by inserting the needle into the tissue.


Patent
Actuated Medical, Baylor College of Medicine and Texas Heart Institute | Date: 2016-09-16

A system, device and method for insertion of a penetrating member into tissue is disclosed, which may be handheld and automated. A detector obtains data regarding subdermal locations of tissue structures, including cavities such as blood vessels. A processor calculates the distance between a preselected target point below the tissue surface, such as within a blood vessel, and the tissue surface, and adjustment data for vertical, angular and extension adjustment of the penetrating member. Vertical, angular and extension actuators carry out the adjustments in real-time as calculated and directed by the processor. Changes in the location of the target point result in automatic recalculation and adjustment by the processor and various actuators. A vibrational actuator induces vibration to the penetrating member during insertion, overcome tissue deformation and vein rolling. A guidewire may be inserted through or by the device, for dilator and catheter insertion once the penetrating member is removed.


Patent
Baylor College of Medicine | Date: 2016-12-08

A novel network of tumorigenic prognostic factors is identified that plays a critical role in advanced pancreatic cancer (PC) pathogenesis. This interactome is interconnected through a central tumor suppressive microRNA, miR-198, which is able to both directly and indirectly modulate expression of the various members of this network to alter the molecular makeup of pancreatic tumors, with important clinical implications. When this tumor signature network is intact, miR-198 expression is reduced and patient survival is dismal; patients with higher miR-198 present an altered tumor signature network, better prognosis and increased survival. Further, according to the present disclosure, MiR-198 replacement reverses tumorigenicity in vitro and in vivo. As such, an embodiment of the disclosure is a method of treating cancer in an individual, comprising the step of increasing the level of active microRNA-198 molecules in the pancreatic cancer tumor cells of the individual by an amount sufficient to cause an improvement in the pancreatic cancer in the individual


Patent
Baylor College of Medicine | Date: 2016-10-21

Embodiments of the disclosure concern methods and compositions for immunotherapy for human papillomavirus infection and diseases associated therewith. In specific embodiments, methods concern production of immune cells that target one or more antigens of HPV16 and/or HPV18, including methods with stimulation steps that employ IL-7 and IL-15, but not IL-6 and/or IL-12. Other specific embodiments utilize stimulations in the presence of certain cells, such as costimulatory cells and certain antigen presenting cells.


Patent
Baylor College of Medicine | Date: 2015-05-05

Embodiments of the disclosure include methods and compositions for treatment of prostate cancer, including metastatic prostate cancer or prostate cancer at risk for developing into metastatic prostate cancer, by providing an effective therapy to an individual that has been determined to have elevated levels of SRC-2 (also known as NCOA2, GRIP1 TIF2). In particular cases, sample from an individual known to have prostate cancer is assayed for the risk for developing metastatic prostate cancer and the individual is provided an effective therapy upon determination of elevated levels of SRC-2.


Patent
Baylor College of Medicine | Date: 2017-03-22

The present invention relates to an intraosseous nerve ablation system comprising: a boring device adapted to form a passageway in bone, thereby providing access to an intraosseous nerve within the bone; an intraosseous nerve ablation device adapted to ablate the intraosseous nerve within the bone, wherein the intraosseous nerve ablation device comprises a shaft having a first end and a second end and a length defined therebetween, wherein the first end of the shaft comprises a tip formed of an electrically conductive material, wherein the tip of the shaft is blunt; a sleeve adapted to receive the intraosseous nerve ablation device and to facilitate alignment of the nerve ablation device with the passageway; and an electric power source operatively associated with the intraosseous nerve ablation device such that electrical current from the electric power source is transmitted to the first end of the intraosseous nerve ablation device, wherein the electrical current provided by the electric power source is sufficient to ablate the intraosseous nerve.


Ellis T.E.,Baylor College of Medicine
Bulletin of the Menninger Clinic | Year: 2017

Suicide risk is an inescapable presence in the treatment of people with psychiatric disorders, a fact that applies especially in inpatient psychiatric settings. This article summarizes a several-year research initiative at The Menninger Clinic aimed at better understanding psychological contributors to suicidality and developing more effective clinical interventions. Two areas of research are described, an outcomes arm focused on assessing the feasibility and effectiveness of a suicide-specific intervention (The Collaborative Assessment and Management of Suicidality) and an exploratory arm whose objective is to learn about psychological vulnerabilities that distinguish suicidal from nonsuicidal patients, with an eye toward developing interventions that address such vulnerabilities. The author concludes that, combined with other developments in the field, this body of work strongly supports the view that suicidal patients should be treated with interventions that specifically target vulnerabilities that seem to set the stage for suicidal episodes. © 2017, The Menninger Foundation.


Durgan D.J.,Baylor College of Medicine
Current Hypertension Reports | Year: 2017

Purpose of Review: Obstructive sleep apnea (OSA) is a significant risk factor for systemic hypertension and other cardiovascular diseases. While this relationship has been firmly established, a detailed understanding of how OSA leads to hypertension is lacking. This review will examine the emerging idea that the gut microbiota plays a role in the development of hypertension, including that associated with OSA. Recent Findings: Disruption of the normal composition of the gut microbiota, termed dysbiosis, has been identified in a number of metabolic and cardiovascular diseases, including diabetes, obesity, and atherosclerosis. Recently, a number of studies have demonstrated gut dysbiosis in various animal models of hypertension as well as in hypertensive patients. Evidence is now emerging that gut dysbiosis plays a causal role in the development of OSA-induced hypertension. Summary: In this review, we will examine the evidence that gut dysbiosis plays a role in OSA-induced hypertension. We will discuss potential mechanisms linking OSA to gut dysbiosis, examine how gut dysbiosis may be linked to hypertension, and highlight how this understanding may be utilized for the development of future therapeutics. © 2017, Springer Science+Business Media New York.


Bavare A.C.,Baylor College of Medicine
Pediatric Critical Care Medicine | Year: 2017

OBJECTIVE:: We studied rapid response events after acute clinical instability outside ICU settings in pediatric cardiac patients. Our objective was to describe the characteristics and outcomes after rapid response events in this high-risk cohort and elucidate the cardiac conditions and risk factors associated with worse outcomes. DESIGN:: A retrospective single-center study was carried out over a 3-year period from July 2011 to June 2014. SETTING:: Referral high-volume pediatric cardiac center located within a tertiary academic pediatric hospital. PATIENTS:: All rapid response events that occurred during the study period were reviewed to identify rapid response events in cardiac patients. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: We reviewed 1,906 rapid response events to identify 152 rapid response events that occurred in 127 pediatric cardiac patients. Congenital heart disease was the baseline diagnosis in 74% events (single ventricle, 28%; biventricle physiology, 46%). Seventy-four percent had a cardiac surgery before rapid response, 37% had ICU stay within previous 7 days, and acute kidney injury was noted in 41% post rapid response. Cardiac and/or pulmonary arrest occurred during rapid response in 8.5%. Overall, 81% were transferred to ICU, 22% had critical deterioration (ventilation or vasopressors within 12 hr of transfer), and 56% received such support and/or invasive procedures within 72 hours. Mortality within 30 days post event was 14%. Significant outcome associations included: single ventricle physiology—increased need for invasive procedures and mortality (adjusted odds ratio, 2.58; p = 0.02); multiple rapid response triggers—increased ICU transfer and interventions at 72 hours; critical deterioration—cardiopulmonary arrest and mortality; and acute kidney injury—cardiopulmonary arrest and need for hemodynamic support. CONCLUSIONS:: Congenital heart disease, previous cardiac surgery, and recent discharge from ICU were common among pediatric cardiac rapid responses. Progression to cardiopulmonary arrest during rapid response, need for ICU care, kidney injury after rapid response, and mortality were high. Single ventricle physiology was independently associated with increased mortality. ©2017The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies


Lo Y.-H.,Baylor College of Medicine
Cell Death and Differentiation | Year: 2017

Paneth cells (PCs), a secretory population located at the base of the intestinal crypt, support the intestinal stem cells (ISC) with growth factors and participate in innate immunity by releasing antimicrobial peptides, including lysozyme and defensins. PC dysfunction is associated with disorders such as Crohn’s disease and necrotizing enterocolitis, but the specific pathways regulating PC development and function are not fully understood. Here we tested the role of the neuregulin receptor ErbB3 in control of PC differentiation and the ISC niche. Intestinal epithelial ErbB3 knockout caused precocious appearance of PCs as early as postnatal day 7, and substantially increased the number of mature PCs in adult mouse ileum. ErbB3 loss had no effect on other secretory lineages, but increased expression of the ISC marker Lgr5. ErbB3-null intestines had elevated levels of the Atoh1 transcription factor, which is required for secretory fate determination, while Atoh1+ cells had reduced ErbB3, suggesting reciprocal negative regulation. ErbB3-null intestinal progenitor cells showed reduced activation of the PI3K–Akt and ERK MAPK pathways. Inhibiting these pathways in HT29 cells increased levels of ATOH1 and the PC marker LYZ. Conversely, ErbB3 activation suppressed LYZ and ATOH1 in a PI3K-dependent manner. Expansion of the PC compartment in ErbB3-null intestines was accompanied with elevated ER stress and inflammation markers, raising the possibility that negative regulation of PCs by ErbB3 is necessary to maintain homeostasis. Taken together, our data suggest that ErbB3 restricts PC numbers through PI3K-mediated suppression of Atoh1 levels leading to inhibition of PC differentiation, with important implications for regulation of the ISC niche.Cell Death and Differentiation advance online publication, 17 March 2017; doi:10.1038/cdd.2017.27. © 2017 Macmillan Publishers Limited, part of Springer Nature.


Swann A.C.,Baylor College of Medicine
CNS Spectrums | Year: 2017

Mixed states address the relationships between episodes and the course of an illness, presenting significant clinical challenges. Recurrent affective disorders were described thousands of years ago as dimensional disturbances of the basic elements of behavior, combining the characteristics of what we would now consider manic and depressive episodes. It was recognized from the beginning that combinations of depressive and manic features are associated with a severe illness course, including increased suicide risk. Early descriptions of affective disorders formulated them as systemic illnesses, a concept supported by more recent data. Descriptions of affective disorders and their course, including mixed states, became more systematic during the 19th century. Structured criteria achieved importance with evidence that, in addition to early onset, frequent recurrence, and comorbid problems, mixed states had worse treatment outcomes than other episodes. In contrast to 2000 years of literature on recurrent affective episodes and mixed states, the unipolar–bipolar disorder distinction was formalized in the mid-20th century. Mixed-state criteria, initially developed for bipolar disorder, ranged from fully combined depression and mania to the DSM–5 criteria, no longer limited to bipolar disorder, of a primary depressive or manic episode with at least three symptoms of the other episode type. The challenges involved in understanding and identifying mixed states center largely on what drives them, including (1) their formulation as either categorical or dimensional constructs, (2) the specificity of their relationships to depressive or manic episodes, and (3) specificity for bipolar versus major depressive disorder. Their existence challenges the distinction between bipolar and major depressive disorders. The challenges involved in identifying the underlying physiological mechanisms go to the heart of these questions. © Cambridge University Press 2017


Shenoi R.P.,Baylor College of Medicine
Pediatric Emergency Care | Year: 2017

INTRODUCTION: The medical diagnoses and frequency of emergency department visits made by children who are later given a diagnosis of maltreatment do not differ much from those of nonabused children. However, the type of medical complaints and frequency of emergency medical services (EMS) use by child homicide victims before their death are not known. We compared EMS use between child homicide victims and children who died from natural causes before their death. METHODS: This was a retrospective case-control study of children 0 to 5 years old who died in Houston, Texas, from 2005 to 2010. Cases were child homicide victims. Controls were children who died from natural causes. We reviewed death data and EMS and child protective services (CPS) encounter information before the victimʼs death. The association between death type (natural vs homicide) and EMS use was assessed using Poisson regression with EMS count adjusted for exposure time. RESULTS: There were 89 child homicides and 183 natural deaths. Age at death was significantly higher for homicides than natural deaths (1.1 vs 0.2 y, P < 0.001). Homicide victims used EMS services (39% vs 14%, P < 0.001) and had previous CPS investigations (55% vs 7%, P < 0.001) significantly more often than children who died from natural causes. Poisson regression, after adjustment for age, revealed that the homicide group had more EMS calls than the natural death group (β = 0.55; 95% confidence interval, 0.04–1.07; P = 0.03). However, the EMS use frequency and working assessments were not helpful in identifying maltreatment victims. CONCLUSIONS: Child homicide victims use EMS more often and have a higher number of CPS investigations before their death than children who die from natural causes. However, the frequency and nature of EMS medical complaints are not helpful in identifying maltreatment. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Malek J.,Baylor College of Medicine
Best Practice and Research: Clinical Obstetrics and Gynaecology | Year: 2017

Decision-making during pregnancy can be ethically complex. This paper offers a framework for maternal decision-making and clinical counseling that can be used to approach such decisions in a systematic way. Three fundamental questions are addressed: (1) Who should make decisions? (2) How should decisions be made? and (3) What is the role of the clinician? The proposed framework emphasizes the decisional authority of the pregnant woman. It draws ethical support from the concept of a good parent and the requirements of parental obligations. It also describes appropriate counseling methods for clinicians in light of those parental obligations. Finally, the paper addresses how cultural differences may shape the framework's guidance of maternal decision-making during pregnancy. © 2017.


Palmer D.J.,Baylor College of Medicine | Grove N.C.,Baylor College of Medicine | Ng P.,Baylor College of Medicine
Molecular Therapy - Methods and Clinical Development | Year: 2016

Helper-dependent adenoviral vectors (HDAd) that express certain transgene products are impossible to produce because the transgene product is toxic to the producer cells, especially when made in large amounts during vector production. Downregulating transgene expression from the HDAd during vector production is a way to solve this problem. In this report, we show that this can be accomplished by inserting the target sequence for the adenoviral VA RNAI into the 3' untranslated region of the expression cassette in the HDAd. Thus during vector production, when the producer cells are coinfected with both the helper virus (HV) and the HDAd, the VA RNAI produced by the HV will target the transgene mRNA from the HDAd via the endogenous cellular RNAi pathway. Once the HDAd is produced and purified, transduction of the target cells results in unimpeded transgene expression because of the absence of HV. This simple and universal strategy permits for the robust production of otherwise recalcitrant HDAds. © 2016 Official journal of the American Society of Gene & Cell Therapy


Josefsdottir K.S.,Baylor College of Medicine | Baldridge M.T.,University of Washington | Kadmon C.S.,Baylor College of Medicine | King K.Y.,Baylor College of Medicine
Blood | Year: 2017

Bone marrow suppression is an adverse effect associated with many antibiotics, especially when administered for prolonged treatment courses. Recent advances in our understanding of steady-state hematopoiesis have allowed us to explore the effects of antibiotics on hematopoietic progenitors in detail using a murine model. Antibiotic-treated mice exhibited anemia, thrombocytosis, and leukopenia, with pronounced panlymphopenia as demonstrated by flow cytometric analysis of peripheral blood. Bone marrow progenitor analysis revealed depletion of hematopoietic stem cells and multipotent progenitors across all subtypes. Granulocytes and B cells were also diminished in the bone marrow, whereas the number of CD8+ T cells increased. Reductions in progenitor activity were not observed when cells were directly incubated with antibiotics, suggesting that these effects are indirect. Hematopoietic changes were associated with a significant contraction of the fecal microbiome and were partially rescued by fecal microbiota transfer. Further, mice raised in germ-free conditions had hematopoietic abnormalities similar to those seen in antibiotic-treated mice, and antibiotic therapy of germ-free mice caused no additional abnormalities. The effects of antibiotics were phenocopied in Stat1-deficient mice, with no additional suppression by antibiotics in these mice. We conclude that microbiome depletion as a result of broad-spectrum antibiotic treatment disrupts basal Stat1 signaling and alters T-cell homeostasis, leading to impaired progenitor maintenance and granulocyte maturation. Methods to preserve the microbiome may reduce the incidence of antibiotic-associated bone marrow suppression. © 2017 by The American Society of Hematology.


Nichols B.L.,Baylor College of Medicine
Journal of Pediatric Gastroenterology and Nutrition | Year: 2017

ABSTRACT: Although named because of its sucrose hydrolytic activity, this mucosal enzyme plays a leading role in starch digestion because of its maltase and glucoamylase activities. Sucrase deficient mutant shrews, Suncus murinus, were used as a model to investigate starch digestion in patients with Congenital Sucrase-isomaltase Deficiency (CSID). BACKGROUND:: Starch digestion is much more complex than sucrose digestion. Six enzyme activities, two α-amylases (Amy) and four mucosal α-glucosidases (maltases), including maltase-glucoamylase (Mgam) and sucrase-isomaltase (Si) subunit activities, are needed to digest starch to absorbable free glucose. Amy breaks down insoluble starch to soluble dextrins; mucosal Mgam and Si can either directly digest starch to glucose or convert the post-α-amylolytic dextrins to glucose. HYPOTHESES:: Starch digestion is reduced due to sucrase deficiency and oral glucoamylase enzyme supplement can correct the starch maldigestion. OBJECTIVE:: Measure glucogenesis in suc/suc shrews after feeding of starch and improvement of glucogenesis by oral glucoamylase supplements. METHODS:: Sucrase mutant (suc/suc) and heterozygous (+/suc) shrews were fed with C enriched starch diets. Glucogenesis derived from starch was measured as blood C-glucose enrichment and oral recombinant C-terminal Mgam glucoamylase (M20) was supplemented to improve starch digestion. RESULTS:: After feedings, suc/suc and +/suc shrews had different starch digestions as shown by blood glucose enrichment and the suc/suc had lower total glucose concentrations. Oral supplements of glucoamylase increased suc/suc total blood glucose and quantitative starch digestion to glucose. CONCLUSIONS:: 1. Sucrase deficiency, in this model of CSID, reduces blood glucose response to starch feeding. 2. Supplementing the diet with oral recombinant glucoamylase significantly improved starch digestion in the sucrase deficient shrew. © 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,


OBJECTIVE:: To describe development of a two-port fetoscopic technique for spina bifida repair in the exteriorized, carbon dioxide-filled uterus and report early results of two cohorts of patients: the first 15 treated with an iterative technique and the latter 13 with a standardized technique. METHODS:: This was a retrospective cohort study (2014–2016). All patients met Management of Myelomeningocele Study selection criteria. The intraoperative approach was iterative in the first 15 patients and was then standardized. Obstetric, maternal, fetal, and early neonatal outcomes were compared. Standard parametric and nonparametric tests were used as appropriate. RESULTS:: Data for 28 patients (22 endoscopic only, four hybrid, two abandoned) are reported, but only those with a complete fetoscopic repair were analyzed (iterative technique [n=10] compared with standardized technique [n=12]). Maternal demographics and gestational age (median [range]) at fetal surgery (25.4 [22.9–25.9] compared with 24.8 [24–25.6] weeks) were similar, but delivery occurred at 35.9 (26–39) weeks of gestation with the iterative technique compared with 39 (35.9–40) weeks of gestation with the standardized technique (P<.01). Duration of surgery (267 [107–434] compared with 246 [206–333] minutes), complication rates, preterm prelabor rupture of membranes rates (4/12 [33%] compared with 1/10 [10%]), and vaginal delivery rates (5/12 [42%] compared with 6/10 [60%]) were not statistically different in the iterative and standardized techniques, respectively. In 6 of 12 (50%) compared with 1 of 10 (10%), respectively (P=.07), there was leakage of cerebrospinal fluid from the repair site at birth. Management of Myelomeningocele Study criteria for hydrocephalus–death at discharge were met in 9 of 12 (75%) and 3 of 10 (30%), respectively, and 7 of 12 (58%) compared with 2 of 10 (20%) have been treated for hydrocephalus to date. These latter differences were not statistically significant. CONCLUSION:: Fetoscopic open neural tube defect repair does not appear to increase maternal–fetal complications as compared with repair by hysterotomy, allows for vaginal delivery, and may reduce long-term maternal risks. CLINICAL TRIAL REGISTRATION:: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02230072. © 2017 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.


Human microbial communities are characterized by their taxonomic, metagenomic and metabolic diversity, which varies by distinct body sites and influences human physiology. However, when and how microbial communities within each body niche acquire unique taxonomical and functional signatures in early life remains underexplored. We thus sought to determine the taxonomic composition and potential metabolic function of the neonatal and early infant microbiota across multiple body sites and assess the effect of the mode of delivery and its potential confounders or modifiers. A cohort of pregnant women in their early third trimester (n = 81) were prospectively enrolled for longitudinal sampling through 6 weeks after delivery, and a second matched cross-sectional cohort (n = 81) was additionally recruited for sampling once at the time of delivery. Samples across multiple body sites, including stool, oral gingiva, nares, skin and vagina were collected for each maternal–infant dyad. Whole-genome shotgun sequencing and sequencing analysis of the gene encoding the 16S rRNA were performed to interrogate the composition and function of the neonatal and maternal microbiota. We found that the neonatal microbiota and its associated functional pathways were relatively homogeneous across all body sites at delivery, with the notable exception of the neonatal meconium. However, by 6 weeks after delivery, the infant microbiota structure and function had substantially expanded and diversified, with the body site serving as the primary determinant of the composition of the bacterial community and its functional capacity. Although minor variations in the neonatal (immediately at birth) microbiota community structure were associated with the cesarean mode of delivery in some body sites (oral gingiva, nares and skin; R2 = 0.038), this was not true for neonatal stool (meconium; Mann–Whitney P > 0.05), and there was no observable difference in community function regardless of delivery mode. For infants at 6 weeks of age, the microbiota structure and function had expanded and diversified with demonstrable body site specificity (P < 0.001, R2 = 0.189) but without discernable differences in community structure or function between infants delivered vaginally or by cesarean surgery (P = 0.057, R2 = 0.007). We conclude that within the first 6 weeks of life, the infant microbiota undergoes substantial reorganization, which is primarily driven by body site and not by mode of delivery. © 2017 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Background: Mitochondrial genomes (mtDNA) of multicellular animals (Metazoa) with bilateral symmetry (Bilateria) are compact and usually carry 13 protein-coding genes for subunits of three respiratory complexes and ATP synthase. However, occasionally reported exceptions to this typical mtDNA organization prompted speculation that, as in protists and plants, some bilaterian mitogenomes may continue to lose their canonical genes, or may even acquire new genes. To shed more light on this phenomenon, a PCR-based screen was conducted to assess fast-evolving mtDNAs of apocritan Hymenoptera (Arthropoda, Insecta) for genomic rearrangements that might be associated with the modification of mitochondrial gene content. Results: Sequencing of segmental inversions, identified in the screen, revealed that the cytochrome oxidase subunit II gene (cox2) of Campsomeris (Dielis) (Scoliidae) was split into two genes coding for COXIIA and COXIIB. The COXII-derived complementary polypeptides apparently form a heterodimer, have reduced hydrophobicity compared with the majority of mitogenome-encoded COX subunits, and one of them, COXIIB, features increased content of Cys residues. Analogous cox2 fragmentation is known only in two clades of protists (chlorophycean algae and alveolates), where it has been associated with piecewise relocation of this gene into the nucleus. In Campsomeris mtDNA, cox2a and cox2b loci are separated by a 3-kb large cluster of several antiparallel overlapping ORFs, one of which, qnu, seems to encode a nuclease that may have played a role in cox2 fission. Conclusions: Although discontinuous mitochondrial protein genes encoding fragmented, complementary polypeptides are known in protists and some plants, split cox2 of Campsomeris is the first case of such a gene arrangement found in animals. The reported data also indicate that bilaterian animal mitogenomes may be carrying lineage-specific genes more often than previously thought, and suggest a homing endonuclease-based mechanism for insertional mitochondrial gene fission. © 2017 The Author(s).


INTRODUCTION: The American College of Cardiology (ACC), the American Heart Association (AHA), and the European Society of Cardiology (ESC) have been developing guidelines to assist clinicians in making evidence-based decisions. MATERIALS AND METHODS: The current ACC/AHA and ESC guidelines for non-ST-segment elevation acute coronary syndromes (NSTE-ACS) that were updated in 2014 and 2015, respectively, were compared to assess the number of recommendations on the basis of class of recommendation and level of evidence (LOE), the sources cited, and the content. RESULTS: The total number of recommendations in the ACC/AHA and ESC guidelines was 182 and 147, respectively. The recommendation class distribution of the ACC/AHA guidelines was 61.0% class I (compared with 61.9% in the ESC guidelines, P=0.865), 29.7% class II (compared with 32.0% in the ESC guidelines, P=0.653), and 9.3% class III (compared with 6.1% in the ESC guidelines, P=0.282). The LOE distribution among ACC/AHA guidelines was 15.9% LOE A (compared with 27.9% in the ESC guidelines, P=0.008), 50.0% LOE B (compared with 33.3% in the ESC guidelines, P=0.002), and 34.1% LOE C (compared with 38.8% in the ESC guidelines, P=0.377). The ACC/AHA guidelines cited 827 publications and the ESC guidelines cited 551 publications, 124 of which were shared by both sets of guidelines. The guidelines’ approaches to NSTE-ACS were consistent, with minor differences in diagnostic and medical therapy recommendations. CONCLUSION: Overall, the ACC/AHA and ESC guidelines contain a comparable number of recommendations and provide similar guidance for the management of patients with NSTE-ACS. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Matoba A.Y.,Baylor College of Medicine
Cornea | Year: 2017

PURPOSE:: To study the cure rate of fungal keratitis with moxifloxacin 0.3% monotherapy. METHODS:: A retrospective review of patients with culture-proven fungal keratitis who initially received moxifloxacin 0.3% monotherapy was performed. RESULTS:: Eleven patients with culture-proven fungal keratitis were initially treated with moxifloxacin. One case each of Curvularia and Alternaria keratitis resolved with moxifloxacin monotherapy (18%). CONCLUSIONS:: Moxifloxacin may have a significant clinical therapeutic effect in a subset of patients with fungal keratitis. Review of the literature in combination with the current study suggests that in patients with clinical features suggestive of fungal keratitis, if rapid diagnostic tests are negative or not available, pending culture results, initial therapy should include a fluoroquinolone (moxifloxacin or gatifloxacin) and/or an aminoglycoside (tobramycin or gentamicin). Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


O'Connell B.P.,Baylor College of Medicine
Otology and Neurotology | Year: 2017

OBJECTIVE:: Describe the safety profile and surgical outcomes of a combined transmastoid-middle cranial fossa suture “pull through” technique for repair of lateral skull base defects. STUDY DESIGN:: Retrospective. SETTING:: Tertiary care hospital. PATIENTS:: Patients undergoing surgery for cerebrospinal fluid (CSF) fistula and/or encephalocele. INTERVENTION:: Combined transmastoid and middle fossa approach using suture pull-through technique. MAIN OUTCOME MEASURES:: The primary outcome measures of interest were recurrence of CSF fistula or encephalocele, and postoperative air-bone gap. RESULTS:: Twenty-six patients were included; mean age at surgery was 60?±?14 years and 65% of patients were female. The majority of defects involved both the tegmen mastoideum and tympani (69%); multiple defects were present in 11 patients. Small craniotomy (2 × 3?cm) was performed and defects were repaired using composite grafts constructed with fascia, bone, and/or cartilage, and dural substitute affixed with suture. The suture tail was left long and passed from the middle fossa through the defect into the mastoid. At average follow-up of 8.3 months, no patients of recurrent CSF leak were noted. Significant improvements in both mean pure-tone average and air-bone gap were noted for the entire cohort (p?=?0.04 and p?=?0.02, respectively). CONCLUSION:: A combined transmastoid-middle cranial fossa for the repair of lateral skull base CSF fistula and encephaloceles using the suture “pull-through” technique is efficacious and the complication profile is favorable. This method facilitates reliable placement of a composite graft in the center of lateral skull base defects through a small craniotomy that minimizes temporal lobe retraction. Copyright © 2017 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company


New findings of widespread neglected diseases among the poor living in wealthy group of 20 (G20) economies and the concept of "blue marble health" offer innovative mechanisms for financing urgently new vaccines, especially for vector-borne neglected tropical diseases (NTDs). This approach could complement or parallel a recently suggested global vaccine development fund for pandemic threats. © 2017.


Thomas S.S.,Baylor College of Medicine
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2017

PURPOSE OF REVIEW: Studying organ-to-organ communications (i.e. crosstalk) uncovers mechanisms regulating metabolism in several tissues. What is missing is identification of mediators of different catabolic conditions contributing to losses of adipose and muscle tissues. Identifying mediators involved in organ-to-organ crosstalk could lead to innovative therapeutic strategies because several disorders such as chronic kidney disease (CKD), cancer cachexia, and other catabolic conditions share signals of worsening metabolism and increased risk of mortality. RECENT FINDINGS: A recent breakthrough published in Cell Metabolism leads to the conclusion that parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) cause ‘browning’ of white adipose tissue plus energy production via activation of uncoupling protein-1. Browning was associated with muscle wasting in mouse models of cancer and CKD. The pathway to browning includes PTH/PTHrP activation of protein kinase A (PKA) and lost muscle mass via the ubiquitin proteasome proteolytic system (UPS). SUMMARY: The results suggest that crosstalk between muscle and fat contributes in a major way to tissue catabolism. The pathway initiated by PTH or PTHrP is novel and it suggests potential interrelationships that control metabolism in other catabolic conditions. Identifying how the parathyroid hormone–PKA–UPS axis relates to obesity, type 2 diabetes, and other insulin-resistant conditions remains unclear. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


News Article | April 14, 2017
Site: www.scientificcomputing.com

Cryo-electron microscopy (cryo-EM)—which enables the visualization of viruses, proteins, and other biological structures at the molecular level—is a critical tool used to advance biochemical knowledge. Now Lawrence Berkeley National Laboratory (Berkeley Lab) researchers have extended cryo-EM’s impact further by developing a new computational algorithm that was instrumental in constructing a 3-D atomic-scale model of bacteriophage P22 for the first time. Over 20,000 two-dimensional cryo-EM images of bacteriophage P22 (also known as the P22 virus that infects the common bacterium Salmonella) from Baylor College of Medicine were used to make the model. The results were published by researchers from Baylor College of Medicine, Massachusetts Institute of Technology, Purdue University and Berkeley Lab in the Proceedings of the National Academies of Sciences earlier in March. “This is a great example of how to exploit electron microscopy technology and combine it with new computational methods to determine a bacteriophage’s structure,” said Paul Adams, Berkeley Lab’s Molecular Biophysics & Integrated Bioimaging division director and a co-author of the paper. “We developed the algorithms—the computational code—to optimize the atomic model so that it best fit the experimental data.” Pavel Afonine, a Berkeley Lab computational research scientist and paper co-author, took the lead in developing the algorithm using Phenix, a software suite used traditionally in X-ray crystallography for determining macromolecular structures. The successful rendering of bacteriophage P22’s 3-D atomic-scale model allows researchers to peek inside the virus’ protein coats at resolution. It is the culmination of several years of work that previously had enabled Baylor College researchers to trace out most of the protein’s backbone, but not the fine details, according to Corey Hryc, co-first author and a graduate student of Baylor biochemistry professor Wah Chiu. “Thanks to this exquisite structural detail, we have determined the protein chemistry of the P22 virus,” Chiu said. “I think it is important that we provide detailed annotations with the structure so other researchers can use it for their future experiments,” he added. Chiu’s lab has been using cryo-EM and computer reconstruction techniques to build 3-D molecular structures for almost 30 years. And the findings could have valuable biological implications as well. Thanks to the 3-D atomic-scale model, it’s now “possible to see the interactions between the pieces making up the P22 virus, which are critical to making it stable,” Adams said. This helps researchers figure out how to make chemicals that can bind to certain proteins. Adams underscores that the ability to understand the configuration of atoms in molecular space can be used to generate new insights into drug design and development.


News Article | May 2, 2017
Site: www.rdmag.com

Deep in the brains of two patients with Alzheimer's disease, the main memory structure, the hippocampus, displays episodic seizure-like electrical activity. These non-convulsive hippocampal seizures are the first signs of 'silent' brain electrical network dysfunction described in patients with Alzheimer's disease. The discovery, published in the journal Nature Medicine, provides a better understanding of the condition and can potentially lead to new treatments for this devastating disease affecting more than 5 million people in the U.S. "About 10 years ago, we were surprised to find 'silent seizures' in mouse models of Alzheimer's disease," said co-senior author Dr. Jeffrey L. Noebels, professor of neurology, neuroscience, and molecular & human genetics, and director of the Blue Bird Circle Developmental Neurogenetics Laboratory at Baylor College of Medicine. "When we measured the animal's brain electrical activity, we detected abnormal electrical discharges in the brain with a seizure-like pattern. The mice, however, did not present with convulsions. These 'clinically silent seizures' in the deep regions of the brain, we speculated, could lead to problems of memory." It's been reported that in a group of patients with Alzheimer's disease, those that have a history of the disease in their families, convulsive seizures are common, especially in advanced cases. However, for most patients with Alzheimer's the condition does not run in the family. In this group of patients, which are said to present with the sporadic form of the disease, convulsive seizures are typically absent. "For this reason, measuring the brain's electrical activity with an electroencephalogram or EEG test is not required for diagnosis and rarely performed," Noebels said. Even if the test was performed, previous studies in the epilepsy field had shown that seizures deep in the brain, such as the hippocampal region, cannot be detected with routine scalp EEG recordings. Detecting such brain activity requires placing electrodes deep in the brain. "My colleagues and I have been interested for years in determining whether 'silent seizures' are present in the hippocampus of patients with Alzheimer's disease," Noebels said. "We were able to answer this question when my colleague and senior co-author Dr. Andrew Cole, director of Massachusetts General Hospital Epilepsy Service and professor of neurology at Harvard Medical School, told me that he had two candidates for the procedure." Cole and Dr. Alice Lam, first-author of the study and a fellow at Massachusetts General Hospital Epilepsy Service, led the team that performed the test in the patients. They used a minimally invasive recording technique involving fine wires inserted through a small natural opening in the skull. This allowed the researchers to monitor this deep region continuously for several days. Simultaneously, the researchers recorded scalp EEG readings. In the two patients, who had been diagnosed with Alzheimer's disease and had no previous history of epilepsy or behaviorally obvious seizures, the hippocampal recordings showed clear clinically silent seizures. At the same time, the EEG recordings that had been taken simultaneously showed no abnormal brain activity, confirming that EEG tests do not register changes in deep brain activity. "What was fascinating was that this activity was present at night when the patients were sleeping, a time thought to be critical for the consolidation of recent memories, a trait that is most impaired in early Alzheimer's disease," Noebels said. "Based on our observations, we are particularly intrigued by the possibility that 'silent seizure' activity per se could contribute to or accelerate the degenerative process underlying Alzheimer's disease," Cole said. In addition, Noebels and his Baylor colleague, Dr. Alica Goldman, co-author and associate professor of neurology and neurophysiology, performed genetic analysis on the patients' samples. "We determined that these two patients did not have a gene known to cause epilepsy. So Alica and I, who have been studying epilepsy genes for a long time, sequenced the patients' samples for the three genes known to be linked to Alzheimer's disease," Noebels said. "It turned out that the patients didn't have those either; they present with the sporadic form of the disease." "It is very exciting that we were able to move from an observation in genetically engineered mouse models of Alzheimer's to a demonstration of the same phenomenon in patients with verified Alzheimer's disease," said Cole. "This is a critical step toward a better understanding of network dysfunction in the disease and opens the window to novel therapeutic approaches for this common condition." "From a physician's perspective, I think this work opened my eyes toward the need to look deeper into our patients' condition in order to improve the quality of their lives as well as that of their caregivers," Goldman said. "I think this work offers an opportunity for new investigations that could be relevant for moving forward the clinical practice of Alzheimer's disease." The need for future studies "This work with two patients proves the concept that 'silent seizures' can occur in patients with Alzheimer's disease," Noebels said. "Next, we need to determine whether this finding is common in Alzheimer's disease, present in other types of progressive degenerative neurocognitive diseases, and when in the course of the disease it occurs," Cole said.


News Article | April 21, 2017
Site: www.rdmag.com

A new laboratory technique developed by researchers at Baylor College of Medicine and other institutions can rapidly test the effectiveness of treatments for life-threatening breast cancer metastases in bone. The study appears in Nature Communications. "For a number of breast cancer patients, the problem is metastasis -- the dissemination of breast tumor cells to other organs -- after the primary tumor has been eliminated," said corresponding author Dr. Xiang Zhang, associate professor of molecular and cellular biology and the Lester and Sue Smith Breast Center at Baylor. "Metastases, however, tend to respond differently than the primary tumor to the treatment in part due to residing in a different organ with a different microenvironment." Until now, there has not been an effective experimental platform to study metastatic tumors in their new microenvironment. "We have created an experimental system in which we can mimic the interactions between cancer cells and bone cells, as bone is the place where breast cancer, and many other cancers too, disseminates most frequently," said Zhang, who also is a McNair Scholar at Baylor. "We have developed a system that allows us to test many different drug responses simultaneously to discover the therapy that can selectively act on metastatic cancer cells and minimize the effect on the bone." To mimic the interactions between metastatic breast cancer cells and bone cells in a living system in the lab, Zhang and his colleagues developed a bone metastasis model, called bone-in culture array, by fragmenting mouse bones that already contain breast cancer cells. The scientists determined that the bone-in culture maintains the microenvironmental characteristics of bone metastasis in living animal models, and the cancer cells maintain the gene expression profile, the growth pattern and their response to therapies. Using the bone-in model, the researchers determined that the drug danusertib preferentially inhibits bone metastasis. They also found that other drugs stimulate the growth of slow-growing cancer cells in the bone. In addition to determining the effect of drugs in the growth of metastasis in bone, the bone-in culture can be used to investigate mechanisms involved in bone colonization by cancer cells. "We think that this new system has the potential to be applied not only to breast cancer but to other cancers that also metastasize to the bone," Zhang said. "This technique can be scaled up to larger sample sizes, which would help accelerate the process of discovering metastatic cancer treatments. We have already found a few interesting drugs. We will keep looking for more and focus on those that are most promising." In the future, the scientists expect to develop this platform into a standardized system that can be used in the clinic to find specific drugs that can better treat metastatic cancer.


News Article | April 13, 2017
Site: www.scientificcomputing.com

A team led by researchers from The Center for Genome Architecture (TC4GA) at Baylor College of Medicine have used technologies from IBM, Mellanox and NVIDIA to assemble the 1.2 billion letter genome of the Culex quinquefasciatus mosquito, which carries West Nile virus. The new genome can help enable scientists to better combat West Nile virus by identifying vulnerabilities in the mosquito that the virus uses to spread. The high performance computing (HPC) system dubbed “VOLTRON,” is based on the IBM Power Systems platform, which provides scalable HPC capabilities necessary to accommodate a broad spectrum of data-enabled research activities. Baylor College of Medicine joins leading supercomputing agencies globally – the Department of Energy’s Oak Ridge and Lawrence Livermore National Labs and the U.K. government’s Science and Technology Facilities Council’s Hartree Centre – that have recently selected IBM’s Power Systems platform for cutting-edge HPC research. VOLTRON’s 3D assembly is changing the way in which researchers are able to sequence genomes, by using DNA folding patterns to trace the genome as it crisscrosses the nucleus. The resulting methodology is faster and less expensive. For example, while the original Human Genome Project took ten years and cost $4 billion, 3D assembly produces a comparable genome sequence in a few weeks and for less than $10,000. Such efforts take on increased urgency when they are needed to combat disease outbreaks, like the West Nile Virus. “Taking advantage of IBM POWER8 and Mellanox InfiniBand interconnect, we are now able to change the way we assemble a genome,” said Olga Dudchenko, a postdoctoral fellow at The Center for Genome Architecture at Baylor College of Medicine. “And while we originally created Voltron to sequence the human genome, the method can be applied to a dizzying array of species. This gives us an opportunity to explore mosquitoes, which carry diseases that impact many people around the globe.” "3D assembly and IBM technology are a terrific combination: one requires extraordinary computational firepower, which the other provides,” said Erez Lieberman Aiden, Director of The Center for Genome Architecture. The Center for Genome Architecture is working closely with Mellanox to maximize their research capabilities with the VOLTRON high-performance computing system. By leveraging Mellanox’s intelligent interconnect technology and acceleration engines, TC4GA is able to provide its researchers with an efficient and scalable platform to enhance genome sequencing in order to find cures for the world’s life-threatening diseases. Key to Baylor's research breakthrough is a multi-year collaboration between IBM and NVIDIA to design systems capable of leveraging the POWER processor’s open architecture to take advantage of the NVIDIA Tesla accelerated computing platform. Incorporated into the design of VOLTRON is POWER and Tesla technology combination that allows Baylor researchers to handle extreme amounts of data with incredible speed. Voltron consists of a cluster of four systems, each featuring a set of eight NVIDIA Tesla GPUs tuned by NVIDIA engineers to help Baylor’s researchers achieve optimum performance on their data-intensive genomic research computations.


News Article | May 1, 2017
Site: www.eurekalert.org

Deep in the brains of two patients with Alzheimer's disease, the main memory structure, the hippocampus, displays episodic seizure-like electrical activity. These non-convulsive hippocampal seizures are the first signs of 'silent' brain electrical network dysfunction described in patients with Alzheimer's disease. The discovery, published in the journal Nature Medicine, provides a better understanding of the condition and can potentially lead to new treatments for this devastating disease affecting more than 5 million people in the U.S. "About 10 years ago, we were surprised to find 'silent seizures' in mouse models of Alzheimer's disease," said co-senior author Dr. Jeffrey L. Noebels, professor of neurology, neuroscience, and molecular & human genetics, and director of the Blue Bird Circle Developmental Neurogenetics Laboratory at Baylor College of Medicine. "When we measured the animal's brain electrical activity, we detected abnormal electrical discharges in the brain with a seizure-like pattern. The mice, however, did not present with convulsions. These 'clinically silent seizures' in the deep regions of the brain, we speculated, could lead to problems of memory." It's been reported that in a group of patients with Alzheimer's disease, those that have a history of the disease in their families, convulsive seizures are common, especially in advanced cases. However, for most patients with Alzheimer's the condition does not run in the family. In this group of patients, which are said to present with the sporadic form of the disease, convulsive seizures are typically absent. "For this reason, measuring the brain's electrical activity with an electroencephalogram or EEG test is not required for diagnosis and rarely performed," Noebels said. Even if the test was performed, previous studies in the epilepsy field had shown that seizures deep in the brain, such as the hippocampal region, cannot be detected with routine scalp EEG recordings. Detecting such brain activity requires placing electrodes deep in the brain. "My colleagues and I have been interested for years in determining whether 'silent seizures' are present in the hippocampus of patients with Alzheimer's disease," Noebels said. "We were able to answer this question when my colleague and senior co-author Dr. Andrew Cole, director of Massachusetts General Hospital Epilepsy Service and professor of neurology at Harvard Medical School, told me that he had two candidates for the procedure." Cole and Dr. Alice Lam, first-author of the study and a fellow at Massachusetts General Hospital Epilepsy Service, led the team that performed the test in the patients. They used a minimally invasive recording technique involving fine wires inserted through a small natural opening in the skull. This allowed the researchers to monitor this deep region continuously for several days. Simultaneously, the researchers recorded scalp EEG readings. In the two patients, who had been diagnosed with Alzheimer's disease and had no previous history of epilepsy or behaviorally obvious seizures, the hippocampal recordings showed clear clinically silent seizures. At the same time, the EEG recordings that had been taken simultaneously showed no abnormal brain activity, confirming that EEG tests do not register changes in deep brain activity. "What was fascinating was that this activity was present at night when the patients were sleeping, a time thought to be critical for the consolidation of recent memories, a trait that is most impaired in early Alzheimer's disease," Noebels said. "Based on our observations, we are particularly intrigued by the possibility that 'silent seizure' activity per se could contribute to or accelerate the degenerative process underlying Alzheimer's disease," Cole said. In addition, Noebels and his Baylor colleague, Dr. Alica Goldman, co-author and associate professor of neurology and neurophysiology, performed genetic analysis on the patients' samples. "We determined that these two patients did not have a gene known to cause epilepsy. So Alica and I, who have been studying epilepsy genes for a long time, sequenced the patients' samples for the three genes known to be linked to Alzheimer's disease," Noebels said. "It turned out that the patients didn't have those either; they present with the sporadic form of the disease." "It is very exciting that we were able to move from an observation in genetically engineered mouse models of Alzheimer's to a demonstration of the same phenomenon in patients with verified Alzheimer's disease," said Cole. "This is a critical step toward a better understanding of network dysfunction in the disease and opens the window to novel therapeutic approaches for this common condition." "From a physician's perspective, I think this work opened my eyes toward the need to look deeper into our patients' condition in order to improve the quality of their lives as well as that of their caregivers," Goldman said. "I think this work offers an opportunity for new investigations that could be relevant for moving forward the clinical practice of Alzheimer's disease." The need for future studies "This work with two patients proves the concept that 'silent seizures' can occur in patients with Alzheimer's disease," Noebels said. "Next, we need to determine whether this finding is common in Alzheimer's disease, present in other types of progressive degenerative neurocognitive diseases, and when in the course of the disease it occurs," Cole said. Other authors that contributed to this work include Gina Deck at Massachusetts General Hospital and Harvard Medical School and Emad Eskandar at Baylor College of Medicine. Financial support for this study was provided by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health, Massachusetts General Hospital, Citizens United for Research in Epilepsy (CURE) and The Blue Bird Circle Foundation.


News Article | April 17, 2017
Site: globenewswire.com

NEW YORK, April 17, 2017 (GLOBE NEWSWIRE) -- Dr. Richard A. Hughes, Physician/Cardiothoracic Anesthesiologist at Anesthesia Practice Consultants P.C., has been selected to join the Physician Board at the American Health Council. He will be sharing his knowledge and expertise on Anesthesiology and Cardiothoracic Anesthesiology. In the industry since 2008, Dr. Hughes offers valuable insight in his role as Physician/ Cardiothoracic Anesthesiologist at Anesthesia Practice Consultants P.C. Located in Grand Rapids, Michigan, Anesthesia Practice Consultants P.C.(APC) serves to provide the best quality of care to healthcare systems, hospitals and practices. Staffed with talented and compassionate anesthesiologists, nurse anesthetists and a professional office staff, APC offers In-House twenty-four-hour care, call coverage, a free-standing periop team that provides regional anesthesia for patients undergoing surgery and to assist with postoperative pain relief in an office based anesthesia practice. As the Physician/Cardiothoracic Anesthesiologist at Anesthesia Practice Consultants P.C, Dr. Hughes’ day-to-day responsibilities include providing anesthesia services for coronary, heart and lung transplants and handling peri-operative pain management throughout Butterworth Hospital in Grand Rapids MI and Blodgett Hospital in East Grand Rapids MI. In 2007, Dr. Hughes earned his medical degree from Creighton University School of Medicine. He completed an internship at the University of Colorado in 2008. To further his professional career, Dr. Hughes completed his residency from Baylor College of Medicine in 2011. In 2012, he pursued a fellowship in Anesthesiology from the Cleveland Clinic Foundation. Dr. Hughes is American Board Certified in Anesthesiology and Transesophageal Echocardiography. Dr. Hughes maintains affiliations with the Michigan Society of Anesthesiologists, American Society of Anesthesiologists, and Society of Cardiovascular Anesthesiologists. Dr. Hughes’ became involved in his current profession through his father’s influence, a cardiothoracic surgeon. Looking back, he attributes his success to exceptional teachers and mentors. Dr. Hughes’ greatest achievement is receiving support from his wife, Emily and their three daughters. In his spare time, he enjoys reading, golfing, and coin collecting. He volunteers with the American Cancer Society. Considering the future, Dr. Hughes hopes to provide the best healthcare possible while continuing to expand his knowledge of the newest techniques and practices.


News Article | April 21, 2017
Site: www.prweb.com

The staff at Palm Beach Face is proud to announce that their practice founder, Michael Schwartz MD, FACS, will be taking part in the 2017 London Marathon. Set to take place on April 23rd, the London Marathon has a long tradition of raising funds for a variety of charitable organizations. This year, Dr. Schwartz will run as part of team EMPOWER, raising money for the international charity, Smile Train. Started in 1981 by former Olympic champion, Chris Brasher, and athlete, John Disley, the London Marathon annually hosts more than thirty thousand runners, traveling a 26 mile course around the River Thames. Sponsored by Virgin Money, the long-distance event is part of the World Marathon Majors. As the largest charity race in the world, many of those competing in the London Marathon run to raise funds for local and international causes. Dr. Schwartz ran his first marathon in 2008, after his father passed away from leukemia. Running for the Leukemia Lymphoma Society, Dr. Schwartz found raising money through his marathon racing a gratifying way to honor his loved ones while giving back to the community. Since that time, Dr. Schwartz has run in six full and more than 20 half marathons across the United States. The London Marathon will be his first international race. This year, Dr. Schwartz will run for Smile Train, an international organization, dedicated to helping those children born with a cleft lip or palate. Since 1999, Smile Train has be committed to providing a sustainable approach for cleft correction. While surgery takes less than an hour, and costs about $250 per child, the procedure is often out of reach for families in developing countries. Smile Train has provided doctors, in more than 85 countries, the training and funds needed to perform cleft repair surgery in their own community. These surgeons will then train other physicians to do the same. As part of the Smile Train 2017 Virgin Money London Marathon team, Dr. Schwartz has already raised $20,000. With donations from more than 90 individuals, Dr. Schwartz is the top fundraiser in the Smile Train team. To date, Dr. Schwartz has raised enough money to provide cleft lip and palate repair surgery for 80 children. A long-time Palm Beach facial plastic surgeon and ENT Specialist, Dr. Schwartz is double board certified by the American Board of Facial Plastic and Reconstructive Surgery and American Board of Otolaryngology. A graduate of Baylor College of Medicine, Dr. Schwartz completed his General Surgery Residency at New York’s Beth Israel Medical Center and his ENT Residency at Columbia University’s Presbyterian Medical Center. Dr. Schwartz is a Diplomate of the American Board of Otolaryngology. An esteemed author, speaker and educator, Dr. Schwartz has over 24 years experience as a surgeon. He has extensive training in the latest advancements in facial plastic surgery. Over his decades of practice, Dr. Schwartz has developed his own, innovative techniques for providing some of the most sought-after procedures in the United States, including the rhinoplasty, blepharoplasty, face lift, otoplasty and necklift. Dr. Schwartz's’ practice, Palm Beach Face, is also one of Florida’s top providers of cutting-edge, noninvasive techniques, such as Botox and soft tissue fillers. To get additional details on Dr. Schwartz’ surgical and noninvasive techniques for facial rejuvenation, contact his West Palm Beach office at 561.228.5888. Appointments can be made at the second location of Palm Beach Face, in Boynton Beach, as well. Speak with a patient coordinator about scheduling an in-person or Skype consultation with Dr. Schwartz. Read more about the April’s Virgin Money London Marathon, the international charity, Smile Train and Dr. Schwartz’ marathon fundraising campaign.


News Article | April 19, 2017
Site: www.eurekalert.org

The type of bacteria in your gut may help diagnose colorectal cancer. Researchers at Baylor College of Medicine and other institutions have identified specific types of bacteria that seem to be abundant in individuals with colorectal cancer. Using a combination of markers specific for these fecal microbes, scientists anticipate that a noninvasive, sensitive clinical diagnostic test potentially can be developed. The study is published in Gut. Colorectal cancer is the second-leading cause of cancer-associated death in the United States. Individuals diagnosed early have a 90 percent chance of survival; however, more than 30 percent of individuals 50 years old or older, the high-risk group, indicate never having been screened for the disease. Currently, recommended screening methods include an invasive procedure - colonoscopy - and noninvasive tests, such as home-based fecal occult blood tests, and Cologuard for detecting colorectal cancer DNA markers and blood in stools. Each of these methods has its shortcomings, so to meet the need for a sensitive, noninvasive diagnostic test for colorectal cancer, the team of researchers looked at gut microbes as indicators of the disease. "A number of studies have shown an association between fecal microbes and colorectal cancer; however, there is limited agreement in the types of microbes reported," said first author Dr. Manasi Shah, who was a graduate student at the University of Texas School of Public Health during the course of this project. "I was interested in finding a microbial marker for the disease. One way to do this is by carrying out a single-institution study, but this takes a long time for sample collection, involves sequencing the microbes' DNA and is expensive. I noticed that some of the published studies provided the means for accessing the raw microbial DNA sequencing data of the samples. How great it would be, I thought, if I could leverage existing raw data across multiple cohorts and come up with a generalizable marker for the disease." Shah realized that to take this approach, in addition to her biostatistical training, she would need to learn the bioinformatics tools necessary for analyzing next generation sequencing data. She approached senior author Dr. Emily Hollister, assistant professor of pathology at Baylor and Texas Children's Hospital and director of microbial ecology for the Texas Children's Microbiome Center, proposed her idea and expressed interest in learning the tools required to reprocess microbial sequence data from its original format. "Manasi had the interest, and we had the expertise," Hollister said. "In our center, we had been planning to compare a series of different statistical tools to analyze large amounts of microbiome data. Manasi's proposal fit very well with our goals." Researchers reanalyzed raw bacterial DNA sequence data from several studies and confirmed previously reported types of bacteria associated with colorectal cancer and identified other bacteria not previously associated with the disease. Easier said than done "In our experience, collecting the raw data from the published studies was an uphill task," Shah said. "Some studies shared all the sample-associated microbial DNA sequences and clinical data, others only shared partial data or did not share any data at all. After much effort, I was able to gather data from nine of 12 published studies. This highlights the need for an initiative to encourage investigators to share their data upon publication, which will help wider dissemination and reproducibility in the field." The researchers also had to overcome the difficulties posed by the diversity of technological approaches used by different laboratories analyzing the samples. "This was an incredibly large, complex multinational study," said co-author Todd DeSantis, co-founder and vice president of informatics at Second Genome Inc. "We saw many differences between medical centers in the way each collected and stored stool samples and in the methods used to process the bacterial DNA in stools. These differences can be problematic for identifying the bacterial strains that proliferate in cancer patients, but our Second Genome KnowlegeBase Team, led by co-author Thomas Weinmaier, found ways to enhance our software platform to address these differences along the way. The findings that emerged from this challenging data set helped validate our platform, and in the process we were able to deliver high-quality insights to advance our collaboration with Dr. Hollister." After reanalyzing large amounts of raw bacterial DNA sequence data from several studies uniformly using a variety of statistical tools, the scientists confirmed previously reported types of bacteria associated with colorectal cancer and identified other bacteria not previously associated with the disease. "The fact that even when we combined several different studies we could correctly classify a sample as a colorectal cancer case or control with 80 percent accuracy solely based on microbial abundances was very encouraging," Shah said. "This is a promising first step to develop a noninvasive test that might be used in the detection of colorectal cancer, supplementing colonoscopy or fecal occult blood tests," Hollister said. "The same strategy could be applied for developing diagnostic tests or therapeutics for other diseases such as inflammatory bowel disease, nonalcoholic steatohepatitis (a form of non-alcoholic fatty liver disease), type 2 diabetes and Alzheimer's disease, among others for which the microbiome is currently being investigated," Shah said. Other contributors to this work include Paul J McMurdie, Julia L Cope, Adam Altrichter and José-Miguel Yamal. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, the University of Texas School of Public Health, Texas Children's Hospital, Second Genome Inc, Whole Biome Inc and Diversigen Inc.


News Article | May 1, 2017
Site: www.chromatographytechniques.com

Deep in the brains of two patients with Alzheimer's disease, the main memory structure, the hippocampus, displays episodic seizure-like electrical activity. These non-convulsive hippocampal seizures are the first signs of 'silent' brain electrical network dysfunction described in patients with Alzheimer's disease. The discovery, published in the journal Nature Medicine, provides a better understanding of the condition and can potentially lead to new treatments for this devastating disease affecting more than 5 million people in the U.S. "About 10 years ago, we were surprised to find 'silent seizures' in mouse models of Alzheimer's disease," said co-senior author Jeffrey L. Noebels, professor of neurology, neuroscience, and molecular & human genetics, and director of the Blue Bird Circle Developmental Neurogenetics Laboratory at Baylor College of Medicine. "When we measured the animal's brain electrical activity, we detected abnormal electrical discharges in the brain with a seizure-like pattern. The mice, however, did not present with convulsions. These 'clinically silent seizures' in the deep regions of the brain, we speculated, could lead to problems of memory." It's been reported that in a group of patients with Alzheimer's disease, those that have a history of the disease in their families, convulsive seizures are common, especially in advanced cases. However, for most patients with Alzheimer's the condition does not run in the family. In this group of patients, which are said to present with the sporadic form of the disease, convulsive seizures are typically absent. "For this reason, measuring the brain's electrical activity with an electroencephalogram or EEG test is not required for diagnosis and rarely performed," Noebels said. Even if the test was performed, previous studies in the epilepsy field had shown that seizures deep in the brain, such as the hippocampal region, cannot be detected with routine scalp EEG recordings. Detecting such brain activity requires placing electrodes deep in the brain. "My colleagues and I have been interested for years in determining whether 'silent seizures' are present in the hippocampus of patients with Alzheimer's disease," Noebels said. "We were able to answer this question when my colleague and senior co-author Andrew Cole, director of Massachusetts General Hospital Epilepsy Service and professor of neurology at Harvard Medical School, told me that he had two candidates for the procedure." Cole and Alice Lam, first-author of the study and a fellow at Massachusetts General Hospital Epilepsy Service, led the team that performed the test in the patients. They used a minimally invasive recording technique involving fine wires inserted through a small natural opening in the skull. This allowed the researchers to monitor this deep region continuously for several days. Simultaneously, the researchers recorded scalp EEG readings. In the two patients, who had been diagnosed with Alzheimer's disease and had no previous history of epilepsy or behaviorally obvious seizures, the hippocampal recordings showed clear clinically silent seizures. At the same time, the EEG recordings that had been taken simultaneously showed no abnormal brain activity, confirming that EEG tests do not register changes in deep brain activity. "What was fascinating was that this activity was present at night when the patients were sleeping, a time thought to be critical for the consolidation of recent memories, a trait that is most impaired in early Alzheimer's disease," Noebels said. "Based on our observations, we are particularly intrigued by the possibility that 'silent seizure' activity per se could contribute to or accelerate the degenerative process underlying Alzheimer's disease," Cole said. In addition, Noebels and his Baylor colleague, Alica Goldman, co-author and associate professor of neurology and neurophysiology, performed genetic analysis on the patients' samples. "We determined that these two patients did not have a gene known to cause epilepsy. So Alica and I, who have been studying epilepsy genes for a long time, sequenced the patients' samples for the three genes known to be linked to Alzheimer's disease," Noebels said. "It turned out that the patients didn't have those either; they present with the sporadic form of the disease." "It is very exciting that we were able to move from an observation in genetically engineered mouse models of Alzheimer's to a demonstration of the same phenomenon in patients with verified Alzheimer's disease," said Cole. "This is a critical step toward a better understanding of network dysfunction in the disease and opens the window to novel therapeutic approaches for this common condition." "From a physician's perspective, I think this work opened my eyes toward the need to look deeper into our patients' condition in order to improve the quality of their lives as well as that of their caregivers," Goldman said. "I think this work offers an opportunity for new investigations that could be relevant for moving forward the clinical practice of Alzheimer's disease." The need for future studies "This work with two patients proves the concept that 'silent seizures' can occur in patients with Alzheimer's disease," Noebels said. "Next, we need to determine whether this finding is common in Alzheimer's disease, present in other types of progressive degenerative neurocognitive diseases, and when in the course of the disease it occurs," Cole said.


News Article | April 1, 2017
Site: www.techtimes.com

Researchers, scientists, and medical officials have been trying to bring the Zika virus epidemic under control for some time. The mosquito-borne virus negatively impacts pregnant women and unborn children. To curb the effects of the virus, the trial of an experimental Zika vaccine was successfully moved to a broader spectrum of testing — phase 2. Earlier this week, in Houston, the first clinical volunteer for this trial received a test dose of this vaccine. Health officials in the United States formally started the enrollment process for volunteers, in a bid to conduct testing of the experimental Zika vaccine. Houston's Baylor College of Medicine hosted the first volunteer to receive the test shot. The trial dubbed VRC 705, is a two-fold study and will cost $100 million. Come June, researchers are optimistic of registering at least 2,490 volunteers from Puerto Rico, Texas, and Florida. The National Institutes of Health will also be taking in volunteers from Panama, Peru, Brazil, Costa Rica, and Mexico — the most at-risk countries from the Zika virus. Scientists at the National Institute of Allergy and Infectious Diseases, or NIAID, have developed the Zika vaccine. The safety tests of this experimental vaccine started in the summer of 2016. With encouraging results from the safety tests, scientists begun the next phase of the examination, which will be conducted in two tiers. Scientists and health officials are now on a lookout for 90 non-pregnant, healthy female and male volunteers to establish the correct dosage of the vaccine. Researchers also hope to assess the safety of the vaccine further, along with its capability to trigger an immune response within the human body. The trial test will take place over a span of 12 weeks and participants will either receive a high dose of the vaccine, or standard dosage. They will be observed for two years to record any symptoms of Zika virus, or any adverse effects of the vaccine. This vaccine is one of the first experimental Zika vaccines to move forward toward a wider test trial. "We are pleased to have advanced rapidly one of NIAID's experimental Zika vaccines into this next stage of testing in volunteers. We expect this study will yield valuable insight into the vaccine's safety and ability to prevent disease caused by Zika infection. A safe and effective Zika vaccine is urgently needed to prevent the often-devastating birth defects that can result from Zika virus infection during pregnancy," said Anthony Fauci, director of NIAID. The vaccine is one of a kind as it has been created using the DNA of a Zika virus. Usually, vaccines are made from a weakened or dead virus. This is done to ensure that the immune system recognizes the infection and fights against it. The DNA of the virus includes genes taken from the Zika proteins. This placebo, when injected, triggers the immune system of our body to release T-cells and antibodies to fight the virus. Zika virus is known to create birth defects in newborn children, if the mother is infected. As of March 14, 2017, this sexually-transmitted virus affected 1,228 pregnant women in the United States, with 54 newborns having birth defects. According to a report from the Centers for Disease Control and Prevention, the virus has also resulted in stillbirths, miscarriages, and abortions. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.


News Article | April 21, 2017
Site: www.rdmag.com

A new laboratory technique developed by researchers at Baylor College of Medicine and other institutions can rapidly test the effectiveness of treatments for life-threatening breast cancer metastases in bone. The study appears in Nature Communications. "For a number of breast cancer patients, the problem is metastasis -- the dissemination of breast tumor cells to other organs -- after the primary tumor has been eliminated," said corresponding author Dr. Xiang Zhang, associate professor of molecular and cellular biology and the Lester and Sue Smith Breast Center at Baylor. "Metastases, however, tend to respond differently than the primary tumor to the treatment in part due to residing in a different organ with a different microenvironment." Until now, there has not been an effective experimental platform to study metastatic tumors in their new microenvironment. "We have created an experimental system in which we can mimic the interactions between cancer cells and bone cells, as bone is the place where breast cancer, and many other cancers too, disseminates most frequently," said Zhang, who also is a McNair Scholar at Baylor. "We have developed a system that allows us to test many different drug responses simultaneously to discover the therapy that can selectively act on metastatic cancer cells and minimize the effect on the bone." To mimic the interactions between metastatic breast cancer cells and bone cells in a living system in the lab, Zhang and his colleagues developed a bone metastasis model, called bone-in culture array, by fragmenting mouse bones that already contain breast cancer cells. The scientists determined that the bone-in culture maintains the microenvironmental characteristics of bone metastasis in living animal models, and the cancer cells maintain the gene expression profile, the growth pattern and their response to therapies. Using the bone-in model, the researchers determined that the drug danusertib preferentially inhibits bone metastasis. They also found that other drugs stimulate the growth of slow-growing cancer cells in the bone. In addition to determining the effect of drugs in the growth of metastasis in bone, the bone-in culture can be used to investigate mechanisms involved in bone colonization by cancer cells. "We think that this new system has the potential to be applied not only to breast cancer but to other cancers that also metastasize to the bone," Zhang said. "This technique can be scaled up to larger sample sizes, which would help accelerate the process of discovering metastatic cancer treatments. We have already found a few interesting drugs. We will keep looking for more and focus on those that are most promising." In the future, the scientists expect to develop this platform into a standardized system that can be used in the clinic to find specific drugs that can better treat metastatic cancer.


News Article | May 2, 2017
Site: www.biosciencetechnology.com

Deep in the brains of two patients with Alzheimer's disease, the main memory structure, the hippocampus, displays episodic seizure-like electrical activity. These non-convulsive hippocampal seizures are the first signs of 'silent' brain electrical network dysfunction described in patients with Alzheimer's disease. The discovery, published in the journal Nature Medicine, provides a better understanding of the condition and can potentially lead to new treatments for this devastating disease affecting more than 5 million people in the U.S. "About 10 years ago, we were surprised to find 'silent seizures' in mouse models of Alzheimer's disease," said co-senior author Dr. Jeffrey L. Noebels, professor of neurology, neuroscience, and molecular & human genetics, and director of the Blue Bird Circle Developmental Neurogenetics Laboratory at Baylor College of Medicine. "When we measured the animal's brain electrical activity, we detected abnormal electrical discharges in the brain with a seizure-like pattern. The mice, however, did not present with convulsions. These 'clinically silent seizures' in the deep regions of the brain, we speculated, could lead to problems of memory." It's been reported that in a group of patients with Alzheimer's disease, those that have a history of the disease in their families, convulsive seizures are common, especially in advanced cases. However, for most patients with Alzheimer's the condition does not run in the family. In this group of patients, which are said to present with the sporadic form of the disease, convulsive seizures are typically absent. "For this reason, measuring the brain's electrical activity with an electroencephalogram or EEG test is not required for diagnosis and rarely performed," Noebels said. Even if the test was performed, previous studies in the epilepsy field had shown that seizures deep in the brain, such as the hippocampal region, cannot be detected with routine scalp EEG recordings. Detecting such brain activity requires placing electrodes deep in the brain. "My colleagues and I have been interested for years in determining whether 'silent seizures' are present in the hippocampus of patients with Alzheimer's disease," Noebels said. "We were able to answer this question when my colleague and senior co-author Dr. Andrew Cole, director of Massachusetts General Hospital Epilepsy Service and professor of neurology at Harvard Medical School, told me that he had two candidates for the procedure." Cole and Dr. Alice Lam, first-author of the study and a fellow at Massachusetts General Hospital Epilepsy Service, led the team that performed the test in the patients. They used a minimally invasive recording technique involving fine wires inserted through a small natural opening in the skull. This allowed the researchers to monitor this deep region continuously for several days. Simultaneously, the researchers recorded scalp EEG readings. In the two patients, who had been diagnosed with Alzheimer's disease and had no previous history of epilepsy or behaviorally obvious seizures, the hippocampal recordings showed clear clinically silent seizures. At the same time, the EEG recordings that had been taken simultaneously showed no abnormal brain activity, confirming that EEG tests do not register changes in deep brain activity. "What was fascinating was that this activity was present at night when the patients were sleeping, a time thought to be critical for the consolidation of recent memories, a trait that is most impaired in early Alzheimer's disease," Noebels said. "Based on our observations, we are particularly intrigued by the possibility that 'silent seizure' activity per se could contribute to or accelerate the degenerative process underlying Alzheimer's disease," Cole said. In addition, Noebels and his Baylor colleague, Dr. Alica Goldman, co-author and associate professor of neurology and neurophysiology, performed genetic analysis on the patients' samples. "We determined that these two patients did not have a gene known to cause epilepsy. So Alica and I, who have been studying epilepsy genes for a long time, sequenced the patients' samples for the three genes known to be linked to Alzheimer's disease," Noebels said. "It turned out that the patients didn't have those either; they present with the sporadic form of the disease." "It is very exciting that we were able to move from an observation in genetically engineered mouse models of Alzheimer's to a demonstration of the same phenomenon in patients with verified Alzheimer's disease," said Cole. "This is a critical step toward a better understanding of network dysfunction in the disease and opens the window to novel therapeutic approaches for this common condition." "From a physician's perspective, I think this work opened my eyes toward the need to look deeper into our patients' condition in order to improve the quality of their lives as well as that of their caregivers," Goldman said. "I think this work offers an opportunity for new investigations that could be relevant for moving forward the clinical practice of Alzheimer's disease." The need for future studies "This work with two patients proves the concept that 'silent seizures' can occur in patients with Alzheimer's disease," Noebels said. "Next, we need to determine whether this finding is common in Alzheimer's disease, present in other types of progressive degenerative neurocognitive diseases, and when in the course of the disease it occurs," Cole said.


News Article | April 26, 2017
Site: www.eurekalert.org

MADISON, Wisconsin -- The adage "put your thinking caps on" might evoke visions of an elementary classroom, where a teacher has just admonished cherubic little learners about to embark on a particularly difficult academic adventure. In today's high-stakes world, where we all need to think, learn or act quickly, the adage still rings true: Mastering a new task, skill or information often takes the right environment, mindset, sharp focus and lots of hard work, repetition and time. Yet, in some time-sensitive or high-pressure situations, a big boost in learning ability and speed from that proverbial thinking cap would not only be welcome, but critical. At the University of Wisconsin-Madison, biomedical engineer Justin Williams is leading an effort to do just that. With up to $9.85 million in funding from the U.S. Defense Advanced Research Projects Agency (DARPA), Williams and neuroscience experts from around the country will develop a low-cost, easy-to-use system -- think "learning goggles" -- that aims to accelerate learning by stimulating nerves in the head and neck to boost neural activity in the brain. The system will be particularly useful for military personnel, whose safety and our national security depends on their ability to quickly master new skills or digest vast quantities of important information. The concept is rooted in a promising new area of research, called targeted neuroplasticity training, in which activating peripheral nerves -- those outside of the brain and spinal cord -- can promote and strengthen connections of neurons in the brain. Acupuncturists have known for centuries that the face and head are excellent places to stimulate peripheral nerves. For example, the auricular vagus nerve is located just below the skin and runs past the tragus -- the little flap on your outer ear -- and down through the neck. Stimulating nerves such as the vagus can boost brain chemicals such as acetylcholine, dopamine, serotonin, and norepinephrine. During learning, those chemicals, known as neuromodulators, regulate changes in the connections between neurons in the brain -- and brain function improves. In recent experiments, other researchers in the field demonstrated that stimulating the vagus nerve while an animal was learning a basic task dramatically increased the speed at which the animal learned the task. "It seemed to work, whether it was a motor task, memory, auditory task or something else," says Williams, UW-Madison Vilas Distinguished Service Professor in Biomedical Engineering. Williams is among the nation's leaders in neural interface technology research and optimization. In 2009, for example, Time magazine included him on its list of the year's 50 best inventions for developing a "thinking cap": a brain-computer interface that allows paralyzed or "locked-in" people to type and send a tweet using only their thoughts. With the DARPA funding, he and his collaborators initially will leverage their combined expertise to develop ways to discover, measure, monitor and optimize the brain's response during targeted neuroplasticity training. Ultimately, they hope to use that knowledge to eventually develop a noninvasive, user-friendly technology that simultaneously delivers a stimulus, monitors neural response and dramatically accelerates learning. "Can we optimize the production of neurotransmitters at the right time and in the right place in the brain during a task to enhance learning?" asks Williams. Beyond military applications, the technology also might be useful, in controlled environments, for people who have learning disorders or who are afflicted with diseases such as Alzheimer's. Williams' collaborators at UW-Madison include: Samuel Poore, professor of surgery; Zhenqiang (Jack) Ma, professor of electrical and computer engineering; and Aaron Suminski, senior scientist in neurological surgery and biomedical engineering. Collaborators from around the country include: David McCormick, professor of neuroscience and psychology at Yale University; Matthew McGinley, professor of neuroscience at Baylor College of Medicine; Robert Froemke, professor of otolaryngology and neuroscience and physiology at New York University; and Kendall Lee and Kip Ludwig, director and associate director, respectively, of the Mayo Clinic Neural Engineering Laboratory.


Massachusetts General Hospital (MGH) investigators have identified silent, seizure-like activity in the hippocampus - a brain structure significantly affected in Alzheimer's disease - in two patients with Alzheimer's disease and no known history of seizures. These alterations in the brain's electrical activity could not be detected by standard EEG readings taken on the scalp and primarily occurred during sleep, a time when the preceding day's memories are consolidated. The report is receiving advance online publication in Nature Medicine. "While it is not surprising to find dysfunction in brain networks in Alzheimer's disease, our novel finding that networks involved in memory function can become silently epileptic could lead to opportunities to target that dysfunction with new or existing drugs to reduce symptoms or potentially alter the course of the disease," says Andrew Cole, MD, director of the MGH Epilepsy Service and senior author of the Nature Medicine paper. "We now have to study more individuals to validate this finding and understand how prevalent it is in Alzheimer's patients, whether it occurs in other neurodegenerative disorders and how it responds to treatment." The investigators describe two patients - both women in their 60s - who had developed symptoms suggestive of Alzheimer's disease, such as confusion and repeatedly asking the same questions. Brain imaging studies and cerebrospinal fluid analysis for both patients were consistent with Alzheimer's disease. It is common for patients with Alzheimer's to experience fluctuations in their symptoms, but in both of these patients, those fluctuations were more exaggerated than typically seen. While scalp EEG recordings did not reveal seizure-like activity, the investigators suspected that there may be undetected seizures within the hippocampus - a key structure affected by Alzheimer's disease that is critical for memory consolidation and is a common source of seizures in people with epilepsy. They decided to try a more direct way of monitoring electrical activity in the hippocampus and related structures. Electrodes were placed adjacent to those structures on both sides of the brain through the foramen ovale (FO), naturally occurring openings at the base of the skull. Each patients' brain activity was monitored simultaneously with both implanted electrodes and with scalp EEG for more than 24 to 72 hours. In one patient, the FO electrodes revealed frequent bursts of electrical activity called spikes, often associated with seizures, most which were not detectible by scalp EEG. During a 12-hour period she experienced three seizures, all taking place during sleep but not producing any visible symptoms. Treatment with an anti-seizure medication eliminated the seizure-like activity, and in the following year, she experienced only one episode of confusion, which occurred after she missed several doses of her anti-seizure medication. FO electrode recording in the other patient also revealed frequent spiking during sleep, but anti-seizure treatment had to be discontinued because of adverse effects on her mood. "Our findings confirmed the presence of serious dysfunction of the neuronal networks affected by Alzheimer's disease and confirmed our hypothesis that epileptic phenomena are an important component of that disturbance," says Cole, who is a professor of Neurology at Harvard Medical School. "Additional recordings with FO electrodes in patients with Alzheimer's disease will help us develop better tools based on computerized analysis of EEG signals and possibly functional neuroimaging studies to ascertain how common silent seizures are in Alzheimer's disease without the need for the minimally invasive electrodes we used in these patients." A recent study led by Alice Lam, MD, PhD, also of the MGH Epilepsy Service and lead author of the current study demonstrated a novel tool for detecting hippocampal seizures not detectible by scalp EEGs in patients with epilepsy, Cole adds, and his team is working to refine this tool and apply it to Alzheimer's disease. Since there also is evidence that higher levels of neuronal activity can increase the production and deposition of Alzheimer's associated proteins such as tau and amyloid-beta, understanding whether seizure-like activity accelerates the progression of Alzheimer's disease will be a high priority for their team. Additional co-authors of the Nature Medicine paper are Gina Deck, MD, MGH Epilepsy Service; Emad Eskandar, MD, MGH Department of Neurosurgery; and Alicia Goldman, MD, PhD, and Jeffrey Noebels, MD, PhD, Baylor College of Medicine. Support for the study includes National Institute of Neurological Disorders and Stroke grants R25-NS065743, U01-NS090362, and R01-NS029709; and grants from Citizens United for Research in Epilepsy and the Blue Bird Circle Foundation. Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $800 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, genomic medicine, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals and earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2016 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of "America's Best Hospitals."


News Article | April 17, 2017
Site: co.newswire.com

The Next Generation of CBD Therapy with the Integration of Precision Medicine ​​Cannliv, LLC (Cannliv) announces the formation of a contractual joint venture with Vyripharm Biopharmaceuticals, (Vyripharm) to provide medical cannabis to support Vyripharm’s research and development program dedicated to the treatment of epilepsy, once the State of Texas Compassionate Use Act (CUP) and Compassionate Use Registry of Texas (CURT) state initiative rolls out in 2017. In addition to epilepsy, Vyripharm’s research and development program is focused on cancers, PTSD and general cognitive disorders at medical facilities across Texas. This design of the joint venture will be to produce medical cannabis for the healthcare industry that is specific to each unique person and condition through diagnostic molecular imaging of the patient and developing a molecular profile of the plant (agriculture profile). By integrating Vyripharm’s personalized platforms, this innovative approach will require the patient to undergo imaging scans as the patient is being treated to hopefully follow the efficacy of the drug during and after treatment. If the imaging procedure performed while the patient is undergoing therapy reveals that the patient is not responding to the treatment, the attending physician can use this critical information to determine if the therapy should be discontinued and a different therapy selected for the patient. This partnership continues Cannliv’s mission to produce medical grade CBD products through the use of Vyripharm’s patented platforms for medical cannabis product certification and medical cannabis research and development. Through controlled testing of medical cannabis products at a Vyripharm Cannabis Processing Center, or CPC, scientists can perform cannabinoid profiling, microbiological testing, analytical testing, food testing, acidified food testing, liquid testing, and pathogen testing. This comprehensive testing platform should provide the standard for the medical cannabis industry in terms of quality control, quality assurance and patient safety. Vyripharm will conduct its research and development using Cannliv’s medical cannabinoid products with their partnering medical institutions; UTMD Anderson, UTMB, Baylor College of Medicine and the VA Texas Healthcare System (in Houston,TX).   The first of which occurred in August 2016 at UTMD Anderson. Vyripharm President, Jerry Bryant, had this to say about the partnership, “For decades, chemotherapy and external radiation have remained an integral part of cancer therapy planning even in light of the adverse collateral effects of such therapies, however, if we can integrate medical cannabinoids with these treatments, we may be able to reduce the side effects and provide a better quality of life for cancer patients and their families. We believe cannabinoids will play a vital future role in the physician’s treatment plan addressing cancer and other types of disease disorders.” Cannliv President & CEO, John David Carrasco stated, “During the last year, our efforts to understand the emerging cannabinoid markets has poised Cannliv to offer a comprehensive solution to the State of Texas for medical cannabis.  With our partnerships in the U.S. and International partners, Cannliv facilitates proven strains of Low Level THC Cannabis and brings these products to the medical industry in research, human trials, and patient treatment, resulting in integrated personalized medicine.” Vyripharm is focusing on theranostic medicine combining diagnostic molecular imaging with target specific therapy to provide a greater degree of precision in addressing the patient’s medical condition on a personal level. Healthcare providers and patients will be able to identify specific medical cannabis strains that react best to specific conditions, resulting in better treatment outcomes. Cannliv’s first group of dispensaries will be located in Houston and Dallas, with additional locations across the state once qualified and Cannliv is awarded license.   Their complete CANNLIVE 1.0 Solution will be used to manage our Seed to Sale internal system for inventory tracking, accounting and registry integration as defined by the State of Texas. ABOUT CANNLIV, LLC  Cannliv is a Texas based biopharmaceutical manufacturer with its sole purpose to produce a natural, clean and user-friendly Cannabinoid products made with the purist ingredients for a truly consistent and reliable source of CBD.  Cannliv will be applying for the Compassionate Use Program licensing this month and will be announcing key partners resulting in proven treatment solutions for Texas. ABOUT VYRIPHARM BIOPHARMACEUTICALS Vyripharm is a biopharmaceutical firm focused on natural products, regulatory testing, pharmaceutical drug development of imaging agents, and drug delivery systems. The aim of Vyripharm is to improve clinical management through diagnosis and treatment with botanicals, synthetic pharmaceuticals, and drug delivery systems.


News Article | April 21, 2017
Site: www.eurekalert.org

A new laboratory technique developed by researchers at Baylor College of Medicine and other institutions can rapidly test the effectiveness of treatments for life-threatening breast cancer metastases in bone. The study appears in Nature Communications. "For a number of breast cancer patients, the problem is metastasis -- the dissemination of breast tumor cells to other organs -- after the primary tumor has been eliminated," said corresponding author Dr. Xiang Zhang, associate professor of molecular and cellular biology and the Lester and Sue Smith Breast Center at Baylor. "Metastases, however, tend to respond differently than the primary tumor to the treatment in part due to residing in a different organ with a different microenvironment." Until now, there has not been an effective experimental platform to study metastatic tumors in their new microenvironment. "We have created an experimental system in which we can mimic the interactions between cancer cells and bone cells, as bone is the place where breast cancer, and many other cancers too, disseminates most frequently," said Zhang, who also is a McNair Scholar at Baylor. "We have developed a system that allows us to test many different drug responses simultaneously to discover the therapy that can selectively act on metastatic cancer cells and minimize the effect on the bone." To mimic the interactions between metastatic breast cancer cells and bone cells in a living system in the lab, Zhang and his colleagues developed a bone metastasis model, called bone-in culture array, by fragmenting mouse bones that already contain breast cancer cells. The scientists determined that the bone-in culture maintains the microenvironmental characteristics of bone metastasis in living animal models, and the cancer cells maintain the gene expression profile, the growth pattern and their response to therapies. Using the bone-in model, the researchers determined that the drug danusertib preferentially inhibits bone metastasis. They also found that other drugs stimulate the growth of slow-growing cancer cells in the bone. In addition to determining the effect of drugs in the growth of metastasis in bone, the bone-in culture can be used to investigate mechanisms involved in bone colonization by cancer cells. "We think that this new system has the potential to be applied not only to breast cancer but to other cancers that also metastasize to the bone," Zhang said. "This technique can be scaled up to larger sample sizes, which would help accelerate the process of discovering metastatic cancer treatments. We have already found a few interesting drugs. We will keep looking for more and focus on those that are most promising." In the future, the scientists expect to develop this platform into a standardized system that can be used in the clinic to find specific drugs that can better treat metastatic cancer. Other contributors to this work include Hai Wang, Lin Tian, Amit Goldstein, Jun Liu, Hin-Ching Lo, Kuanwei Sheng, Thomas Welte, Stephen T. C. Wong, Zbigniew Gugala, Fabio Stossi, Chenghang Zong, Zonghai Li and Michael A. Mancini. The authors are affiliated with one or more of the following institutions: Baylor, Shanghai Jiao Tong University School of Medicine, Weill Cornell Medical College, Houston Methodist Hospital and the University of Texas Medical Branch, Galveston. Financial support was provided by the U.S. Department of Defense (DAMD W81XWH-16-1-0073, DAMD W81XWH-13-1-0296), the National Cancer Institute (CA183878), the Breast Cancer Research Foundation, Susan G. Komen (CCR14298445), and the McNair Medical Institute. This work was also made possible by the CyVerse Collaborative, funded by the National Science Foundation (No. DBI-0735191), the Integrated Microscopy Core at Baylor College of Medicine with funding from the National Institutes of Health (HD007495, DK56338, and CA125123), the Pathology Core of the Lester and Sue Smith Breast Center, the Dan L Duncan Comprehensive Cancer Center and the John S. Dunn Gulf Coast Consortium for Chemical Genomics.


Researchers at Baylor College of Medicine have uncovered a new mechanism showing how microbes can alter the physiology of the organisms in which they live. In a paper published in Nature Cell Biology, the researchers reveal how microbes living inside the laboratory worm C. elegans respond to environmental changes and generate signals to the worm that alter the way it stores lipids.


News Article | April 18, 2017
Site: www.eurekalert.org

Viruses that specifically kill bacteria, called bacteriophages, might one day help solve the growing problem of bacterial infections that are resistant to antibiotic treatment. Researchers at Baylor College of Medicine and the Michael E. DeBakey Veterans Affairs Medical Center have determined that phages can effectively reduce bacterial levels and improve the health of mice that are infected with deadly, antibiotic-resistant bacterial 'superbugs.' The study appears in Scientific Reports. "Our research team set out to determine whether phages can be effective at killing a large group of bacteria that have become resistant to antibiotics and cause deadly diseases in people," said corresponding author Dr. Anthony Maresso, associate professor of molecular virology and microbiology at Baylor. "We are running out of available options to treat patients who have these deadly bacterial infections; we need new ideas." When bacteria grow out of control, they can enter the blood stream and infect vital organs in the body. The body's immune system, an army of cells and molecules that fights back infections and other diseases, responds to the bacterial attack, defending the body from the infection. However, the immune response sometimes is excessive and can lead to tissue damage, organ failure and death, a process called sepsis. To end sepsis, bacterial growth has to stop. Antibiotic treatment usually can control bacterial growth and prevent the deadly consequences of sepsis, but increasing number of bacteria is becoming resistant to antibiotics. According to the National Institute of General Medical Sciences, sepsis affects more than 1 million people in the United States every year. About 50 percent of patients with sepsis die; this outnumbers the U.S. deaths caused by prostate cancer, breast cancer and AIDS combined. The number of sepsis cases per year is increasing, which underscores the need for new strategies to fight bacterial infections. In this study, the researchers investigated the possibility of recruiting phages in the fight against antibiotic-resistant bacteria, reviving the original idea of Felix d'Herelle, proposed in 1926. "The driving force behind this project was to find phages that would kill 12 strains of antibiotic-resistant bacteria that were isolated from patients," said co-author Dr. Robert Ramig, professor of molecular virology and microbiology at Baylor. "As the virologist on the team, my first contribution was to go phage hunting." "I have a number of phages in my lab, but none of them killed the antibiotic-resistant E. coli we were working on - the sequence type 131 currently pandemic across the globe," Ramig said. Birds and dogs often carry the bacteria the researchers were interested in, and may be one environmental reservoir of these pathogens. They also carry phages specific for those bacteria. Ramig, Maresso and Sabrina Green, a graduate student in the Molecular Virology Program at Baylor, went phage hunting in local parks and bird refuges to collect avian and canine feces. "We isolated a number of phages from animal feces," said Ramig. "No single phage would kill all the 12 bacterial strains, but collectively two or three of those phages would be able to kill all of those bacteria in cultures in the lab." This good news allowed the researchers to move on to the next step - determining whether the phages also would be able to kill the antibiotic-resistant bacteria in an animal model of sepsis. One of the animal models the researchers worked with mimics how cancer patients develop potentially life-threatening infections during their cancer treatment. "A number of cancer patients who undergo chemotherapy sometimes develop infections that come from bacteria that normally live in their own gut, usually without causing any symptoms," Green said. "Chemotherapy is intended to kill cancer cells, but one of the side effects is that it suppresses the immune system. A suppressed immune system is a major risk factor for infections with these bacteria, which sometimes also are multi-drug resistant." Working in Maresso's lab, Green developed a mouse model in which healthy mice received antibiotic-resistant bacteria that colonize their intestinal tract. "These mice showed no sign of disease," Maresso said. "But when the mice received chemotherapy," Green said, "the bacteria moved from their intestine to major organs - this led to a fatal sepsis-like infection." In this animal model in which the immune system cannot keep in check antibiotic-resistant bacteria, Green tested whether the phages were able to do so. "When the phages are delivered into the animals, their efficacy in reducing the levels of bacteria and improving health is dramatic," Maresso said. "But that is not what is truly remarkable," he continued. "What is remarkable is that these 'drugs' were discovered, isolated, identified and tested in a matter of weeks, and for less money than most of us probably spend in a month on groceries." Phages are very specific for certain species or strains of bacteria, but can be made broadly acting via cocktails, if desired. Thus, unlike antibiotics, using phages may not be associated with some of the side effects observed, such as clearing beneficial intestinal microbiota. They also don't infect human cells. Another advantage over antibiotics is that phages can evolve. Should resistance develop against one set of phages, new phages can be identified in the environment or evolved in the laboratory in a matter days. "On the other hand, an antibiotic is a chemical; it cannot change in real time," Maresso said. "It may take years to develop a new antibiotic and at costs that can run in the billions. But a phage can evolve to efficiently kill a resistant strain and then be propagated. It gives me great personal satisfaction when I think of the irony of this - the next anti-bacterial treatment may use the very same mechanisms bacteria have been using against us for 60-plus years now." Co-author Dr. Barbara Trautner, associate professor and director of clinical research in the Department of Surgery, associate professor of medicine at Baylor and also a researcher with Center for Innovations in Quality, Effectiveness and Safety at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, and Ramig previously published a paper in which they showed that it is possible to take advantage of the phages' ability to change to fight bacterial infections. "In summary, we took four phages that specifically attacked bacteria of the group Pseudomonas, and they would kill four of 26 of these bacterial strains. Then, we evolved the phages in the lab, and in a month the new ones could kill 22 of the 26," Ramig said. "Envision the following possible future clinical scenario: a patient presents with antibiotic-resistant bacterial infection that is untreatable or only treatable with the most toxic of antibiotics. During the 48 hours it takes to identify the bacterial species and strain, physicians and scientists can go to a library of phages at hand, select those that are effective against this antibiotic-resistant bacterial strain and make a personalized cocktail of phages to treat the patient. Should resistance develop again, we will evolve another phage - right back at them!" Maresso said. "There are many ways to kill bacteria, but I know of no other way that has the potential to evolve in real time like phages do. And it's the best 'green' medicine - it's natural, safe thus far, relatively cheap and can be harnessed with the technical skills of a college biology major." Whereas the upside may be high, there is still some caution. "Phages are not infallible medicines," reflects Maresso. "The host's immune system sometimes can neutralize their activity and some phages just don't work well in animals. But we understand very little about any of these dynamics compared to those of other classes of drugs. At the very least, I think the evidence supports the notion that we should be giving phages some experimental attention." Co-author Jason T. Kaelber, predoctoral fellow of biochemistry at Baylor, also contributed to this project. This work was supported by a grant from the Mike Hogg Foundation and seed funds from Baylor College of Medicine. Cryoelectron microscopy was performed at the National Center for Macromolecular Imaging at Baylor and supported by grant P41 GM103832.


News Article | May 4, 2017
Site: www.futurity.org

Even a relatively mild Zika outbreak in the continental United States could cost more than $183 million in medical bills and productivity losses, and a worse epidemic could come with a price tag of $1.2 billion or even more. Experts estimated the potential impact of epidemics of various sizes in five Southeastern states and Texas, the US locations most populated by Aedes aegypti, the mosquito most likely to carry the disease. “This is a threat that has not gone away. Zika is still spreading silently and we are just now approaching mosquito season in the United States, which has the potential of significantly increasing the spread,” says study leader Bruce Y. Lee, an associate professor of international health at Johns Hopkins University’s Bloomberg School of Public Health. “There’s still a lot we don’t know about the virus but it is becoming clear that more resources will be needed to protect public health. Understanding what a Zika epidemic might look like, however, can really help us with planning and policy-making as we prepare.” While many infected by the Zika virus suffer mild symptoms, if any, a Zika infection during a woman’s pregnancy can cause severe birth defects such as microcephaly or other brain problems. In regions affected by Zika, there have also been increased reports of Guillain-Barré syndrome, a rare illness of the nervous system. There is no treatment nor is there a vaccine to prevent Zika. Policymakers need estimates of Zika costs to help guide funding decisions, researchers say. It is unclear how many people in the United States have already been infected and how many more cases will occur this summer, but the findings, published in the journal PLOS Neglected Tropical Diseases, are further evidence that the costs of any Zika outbreak would be high. For the study, researchers developed and ran a computational model estimating the impact of different rates of spread if Zika were to hit Florida, Georgia, Alabama, Mississippi, Louisiana, and Texas. The model considered health care costs—such as visits to the doctor, laboratory tests, and the lifetime cost of caring for a child born with microcephaly—as well as productivity losses. Even assuming an attack rate—the percentage of the population eventually infected—of only 0.01 percent, the model estimates that Zika would cost more than $183 million and cause more than 7,000 infections, two cases of microcephaly, and four cases of Guillain-Barré. An attack rate of 1 percent would cause more than 704,000 infections, 200 cases of microcephaly, and 423 cases of Guillain-Barré. The 1-percent attack rate could result in $1.2 billion in medical costs and productivity losses to the economy. A 10-percent attack rate could cost more than $10.3 billion. These attack rates would be far lower than those seen in French Polynesia (66 percent), on Yap Island in Micronesia (73 percent), and in the state of Bahia in Brazil (32 percent), where the current Zika outbreak in the Americas and the Caribbean is believed to have originated. They are also lower than recent outbreaks of chikungunya, a virus spread the same way as Zika, including one in Puerto Rico (23.5 percent). After much delay last year, Congress allocated $1.1 billion for mosquito control efforts and vaccine development, as well as for emergency health care for Puerto Rico, where more than 35,000 people contracted the virus. But, Lee believes far more money may be necessary, given his estimates for medical care. “Without details regarding the Zika-prevention measures that would be implemented and how effective these may be, it is unclear what percentage of these costs may be averted,” Lee says. “But our model shows it is very likely that preventing an epidemic—or at least finding ways to slow one down—would save money, especially since epidemics like Zika have hidden costs that aren’t always considered.” Other researchers from Johns Hopkins and from Yale University and the National School of Tropical Medicine at Baylor College of Medicine are coauthors of the study. National Institutes of Health, the Agency for Healthcare Research and Quality, and the US Agency for International Development funded the work.


Patent
Strike Bio Inc. and Baylor College of Medicine | Date: 2017-03-01

The present invention includes compositions and methods for making and using a RNAi capable of reducing expression of two or more genes, comprising: a first RNAi molecule that reduces the expression of a first target gene; a second RNAi molecule that reduces the expression of the first or a second target gene; and optionally a third RNAi molecule that reduces the expression of the first, the second, or a third target gene, wherein the RNAi molecules reduce the expression level of, e.g., mutated KRAS, SRC-3, EGFR, PIK3, NCOA3, or ERalphal, and can be, e.g., miRNAs, shRNAs, or bifunctional shRNAs.


News Article | April 25, 2017
Site: www.eurekalert.org

HOUSTON - (April 25, 2017) - Higher costs for complex cancer surgery may be an indicator for worse -- rather than better -- quality of care, according to new research by experts at Rice University and the University of Texas MD Anderson Cancer Center. Their findings are published in the journal Surgery and provide multiple implications for care delivery. In the study, the authors analyzed Medicare hospital and physician claims from 2005 to 2009 for patients who were age 65 or older from all 50 states. The researchers looked at six different cancer operations: colectomy, rectal resection, pulmonary lobectomy, pneumonectomy, esophagectomy and pancreatic resection. In their initial review of the data, they found that surgeons who performed just two operations of a specific type in a given year versus one could achieve patient cost savings for four of the six cancer operations, ranging from 0.6 percent for colectomy to 2.8 percent for pancreatic resection. Savings for the highest-volume surgeons (at the 95th percentile of the volume distribution) were even greater. A surgeon performing 14 pancreatic resections had patient costs that were 8.5 percent lower ($3,286) than a surgeon who performed only one operation; and a surgeon performing 22 colectomies per year had costs that were 5.4 percent lower ($1,089). However, when the researchers accounted for the processes of care listed in each patient's treatment, the cost savings associated with high-volume surgeons decreased by 50 percent for pancreatic resection and completely disappeared for colectomy. Apparent cost savings for pulmonary lobectomy also disappeared, and cost savings for rectal resection also fell substantially, said co-author Vivian Ho, the chair in health economics at Rice's Baker Institute for Public Policy and director of the institute's Center for Health and Biosciences. Processes of care are actions that health care providers take to improve the quality of care and patient outcomes, such as placing of arterial lines or providing epidural anesthesia. Many of these are actions taken to avoid or treat complications that can occur during surgery. "Basically, our analyses indicate that the lower patient costs achieved by high-volume surgeons can be explained by their lower occurrence of processes of care that are associated with surgical complications, as well as their higher use of processes of care associated with better outcomes," said co-author Dr. Thomas Aloia, associate professor in the Department of Surgical Oncology, Division of Surgery, at MD Anderson. "People mistakenly think that higher spending in health care implies higher quality care," Ho said. "In this case, higher spending is a marker of worse patient care. The results imply that patients who need cancer surgery can expect lower costs and better outcomes with high-volume surgeons." "Can Postoperative Process-of-Care Utilization or Complication Rates Explain the Volume-Cost Relationship for Cancer Surgery?" was also co-authored by Marah Short, associate director of the Baker Institute's Center for Health and Biosciences. The study references a 2008 paper by the authors that found that patients treated by surgeons performing a higher number of particular cancer operations (such as pneumonectomy for lung cancer or esophagectomy for esophageal cancer) had lower costs for their hospital stays compared with patients operated on by low-volume surgeons. However, the authors didn't know why this inverse volume-cost relationship existed. Their new research set out to find the reasons underlying the volume-cost relationship. "Our volume-cost comparison suggests that patients treated by low-volume surgeons were less likely to receive two processes of care (epidural anesthesia and daily epidural management) that have been associated with better patient outcomes," said Ho, who is also a professor of economics at Rice and a professor of medicine at Baylor College of Medicine. "However, patients treated by low-volume surgeons almost always were significantly more likely to experience transfusions, consultations and complication-related processes of care (for example, TPN, critical care and inpatient consultations)." TPN stands for total parenteral nutrition, in which patients who are unable to eat are administered nutrients intravenously. The results provide multiple implications for care delivery, the authors said. First, it may be beneficial to refer patients to high-volume surgeons because of the surgeons' enhanced value (higher quality with lower costs). Second, government and private insurers should compare measures of processes of care and complications across surgeons and notify hospitals about surgeons with high complication rates and processes of care associated with poor patient outcomes. Hospitals could work with surgeons to improve surgical care, which should improve patient care and lessen costs. More broadly, the results suggest that action under the Affordable Care Act to shift hospital reimbursement toward bundled payment for hospitals and doctors for complex surgery should be encouraged, the authors said. "The current fee-for-service system often leads to higher payments for physicians and hospitals when patients suffer surgical complications and require higher levels of care," Ho said. "Specifying a fixed, bundled payment that doesn't vary with treatment intensity will discourage low-volume surgeons from performing operations that could generate costly complications for which they will not be compensated." For more information, to receive a copy of the study or to schedule an interview with Ho, Aloia or Short, contact Jeff Falk, associate director of national media relations at Rice, at jfalk@rice.edu or 713-348-6775. Follow the Center for Health and Biosciences via Twitter @BakerCHB. Founded in 1993, Rice University's Baker Institute ranks among the top five university-affiliated think tanks in the world. As a premier nonpartisan think tank, the institute conducts research on domestic and foreign policy issues with the goal of bridging the gap between the theory and practice of public policy. The institute's strong track record of achievement reflects the work of its endowed fellows, Rice University faculty scholars and staff, coupled with its outreach to the Rice student body through fellow-taught classes -- including a public policy course -- and student leadership and internship programs. Learn more about the institute at http://www. or on the institute's blog, http://blogs. .


News Article | May 4, 2017
Site: www.eurekalert.org

A new study using data from the Osteoarthritis Initiative, a multi-center observational study of nearly 3500 participants, indicates that people who hear grating, cracking, or popping sounds in or around their knee joint may be at increased risk of developing knee osteoarthritis. This was a study of people who were at high risk for developing knee osteoarthritis. Among those who developed it within a year, more than 75% had signs of osteoarthritis on radiographic images but no frequent knee pain at the start of the study. The findings may be helpful for identifying individuals at risk for knee osteoarthritis, potentially assisting with earlier diagnosis and intervention. "Many people who have signs of osteoarthritis on x-rays do not necessarily complain of pain, and there are no known strategies for preventing the development of pain in this group of people," said Dr. Grace Lo, lead author of the Arthritis Care & Research study and an Assistant Professor of Medicine at Baylor College of Medicine in Houston. "This study suggests that if these people have noisy knees, they are at higher risk for developing pain within the next year compared with the people who do not have noisy knees. Future studies that target people who have x-ray signs of osteoarthritis, and who do not complain of pain but do report noisy knees, hold the promise of identifying interventions that can prevent knee pain."


News Article | May 4, 2017
Site: www.eurekalert.org

Researchers at Baylor College of Medicine have discovered that changing the circadian clock in mouse liver can alter how the body responds to diet and also change the microbes living in the digestive track. In this study, which appears online in the American Journal of Obstetrics and Gynecology, the researchers show for the first time that a liver gene in mice has the ability to link the circadian system, the microbiome and the mouse metabolism under dietary restrictions. What is surprising is that it does so in a sex-specific fashion. "Organisms can change how their bodies process food in different ways," said first author Dr. Derek O'Neil, a postdoctoral fellow in obstetrics and gynecology at Baylor. "Here, we studied two of those strategies. One involves the circadian clock, the internal mechanism that helps orchestrate body activities such as going to sleep or when to eat. Another aspect that can affect how we metabolize our food is the microbiome, the bacteria that live in the body." Previous studies have shown that, independently, the circadian clock and the microbiome can affect metabolism. In this study the researchers explored whether changing the circadian clock would affect the microbiome. Disrupting the circadian clock in mouse liver alters the gut microbiome To investigate the connection between the circadian clock and the microbiome, the scientists genetically engineered mice to lack only in the liver a gene involved in circadian rhythm, the Npas2 gene. Then, they determined the effect of lacking the gene in a traditional test for circadian genes. In the test, called restricted feeding, normal feeding hours were disrupted. Instead of having access to unrestricted amounts of food for 12 hours at night (the normal feeding time for mice), the mice had access to food for four hours during the day. Two groups of mice went through the restricted feeding test for 17 days, the mice lacking the Npas2 gene and normal mice. Before, during and after the test, the researchers took stool samples where they determined the type of microbes present and measured how much food the animals ate and how much they weighted. The results showed that altering the circadian clock in the liver results in changes in the gut microbiome; the mice lacking the Npas2 gene had microbial communities in their stools that were different than those in normal mice. In addition, even though both groups of mice ate about the same amount of nutritionally balanced food and lost weight during the restricted feeding test, the mice lacking the Nasp2 gene lost less weight than the normal mice. "Lacking a gene in the liver that drives the circadian clock was sufficient to not only change the resiliency of these male mice to weight loss during restricted feeding but also to change their gut microbiome," said senior author Dr. Kjersti Aagaard professor of obstetrics and gynecology at Baylor. "This is the first scientific mechanistic study that shows clear evidence of a complex interplay between the host circadian system, the microbiome and the host metabolism when under dietary stress." The study has potential implications in the clinic. "We speculate that our findings may lead to solutions for people who are resistant to losing weight with restricted feeding as well as the opposite situation," Aagaard said. "If we manipulated the microbiome, could we see lesser or more weight loss by just changing the time of feeding? Our study could also be applied to situations in which we don't want to see weight loss, such as cancer patients receiving chemotherapy or during times in life when sleep patterns are turned upside down." Closer to their field of interest, pregnancy and neonatal life, the researchers further speculate that their findings may lead to more studies aimed at better understanding the intricate interactions between major disturbances of the circadian clock for both mother and child during neonatal life (when newborns are still learning day from night), the microbiome and preserving the mother's weight and metabolism. Other authors of this work include Christopher J. Stewart, Derrick M. Chu, Danielle M. Goodspeed, Pablo J. González-Rodríguez and Cynthia D. Shope, all from Baylor College of Medicine. This study was partially supported by the National Institutes of Health grants 1RO1DK089201-01A, R24DK090964-06, T32GM088129 and T32GM07526-37.


News Article | May 8, 2017
Site: www.prweb.com

In his book, “Edward IV, England’s Forgotten Warrior King,” Dr. Anthony Corbet draws parallels between the historical figure and modern day leaders. Many observe that leaders today lack accountability, something with which Edward IV surrounded himself. “Edward IV was always a particular hero of mine, from the moment his legacy came up in my history class,” Dr. Corbet said. During his reign, Edward IV put an end to corruption, fueled an economic boom and lowered taxes by running the country on his own wealth. He sought input from 100 advisors including the middle-class, non-nobles and non-magnates. “Young and old leaders alike can learn from Edward IV,” Dr. Corbet said, “He led with humility, sought counsel and explored all viewpoints before making a decision.” Dr. Corbet tells an intense, historical tale of one of the greatest rulers in English history. When Richard, Earl of Warwick, drove Edward IV out of the country and seized the throne, the earl manipulated England as a dictator for 6 months, until Edward IV returned with vengeance. He burned his own vessel, the Antony, to the waterline and vowed never again to be chased from England. To learn more, please http://www.edwardiv.com. About the author Growing up in Adelaide, Australia, Dr. Anthony Corbet had a passion for English history. While in high school, he won the Annie Montgomerie Martin prize for history. In 1963, Corbet graduated from the Adelaide Medical School. After training in Pediatrics and Neonatology in Sydney and Montreal, Corbet taught and researched at Baylor College of Medicine in Houston, Texas. He practiced at the Children’s Hospital in San Antonio until he retired.


News Article | May 8, 2017
Site: www.businesswire.com

NEWTOWN SQUARE, Pa.--(BUSINESS WIRE)--XyloCor Therapeutics Inc., a privately held biotech company, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to its lead product candidate XC001 (AdVEGF-All6A+), a cardiovascular angiogenic gene therapy. XC001 is a one-time treatment being investigated for improving exercise tolerance in patients who have chronic angina that is refractory to standard medical therapy and not amenable to conventional revascularization procedures such as coronary artery bypass surgery and percutaneous coronary intervention and stents. “Achieving Fast Track status validates the need for XC001, which has the potential to be a unique treatment for this serious condition with high unmet need - chronic, refractory angina,” said Al Gianchetti, President and Chief Executive Officer of XyloCor. “This designation is supported by strong scientific evidence for XC001 and clinical validation of this mechanism of action in refractory angina. This important designation is intended to contribute to an expedited development and regulatory review process, which can get the drug sooner to patients who can benefit from it.” The FDA Fast Track designation is designed to facilitate the development and expedite the review of new drugs and vaccines intended to treat or prevent serious conditions and that demonstrate the potential to address an unmet medical need. XC001 is a novel gene therapy that promotes angiogenesis, the formation of new vessels that can provide arterial blood flow to myocardial regions with inadequate blood supply. Enhancing myocardial blood flow with therapeutic angiogenesis is intended to relieve myocardial ischemia, improve regional and global left ventricular performance, alleviate angina symptoms and disability and potentially improve prognosis. “There are many patients in the United States with refractory angina and there are no available treatment options,” said Magnus Ohman, Professor of Medicine, The Kent and Siri Rawson Director, Duke Program for Advanced Coronary Disease, Duke University School of Medicine. “These patients have significant limitations in terms of their daily activities because of the chest pain associated with their ischemic disease and XC001 could be an important new option for them.” An IND for XC001 is open with the FDA and XyloCor intends to commence clinical trials upon funding. XyloCor Therapeutics is a private biopharmaceutical company developing novel gene therapy for people with unmet medical need from advanced coronary artery disease. XyloCor is focused on developing its lead product, XC001, for patients with refractory angina with no treatment options and its secondary product, XC002, for patients with cardiac tissue damage from heart attacks. XyloCor was founded by Dr. Ronald Crystal and Dr. Todd Rosengart, who both sit on XyloCor’s advisory board. Dr. Crystal is the Bruce Webster Professor and Chairman, Department of Genetic Medicine, Weill Cornell Medicine and Director of the Belfer Gene Therapy Core Facility. Dr. Rosengart is Professor and Chairman, DeBakey Bard Chair of Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine. XyloCor has a licensing agreement with Cornell University granting the company worldwide rights to develop, manufacture and commercialize XC001. With a strong scientific foundation, compelling preclinical and clinical evidence and an experienced team, XyloCor is poised for success and to help patients lead better, healthier lives. For more information, visit www.xylocor.com.


News Article | April 24, 2017
Site: globenewswire.com

HOUSTON, April 24, 2017 (GLOBE NEWSWIRE) -- Indoor Harvest Corp (OTCQB:INQD) is pleased to announce, with Alamo CBD, LLC (“Alamo”), that on April 20, 2017 both Companies entered into a definitive share exchange agreement (the “Agreement”) to acquire 100% of the member ownership in Alamo. Pursuant to the Agreement, Indoor Harvest will sell, convey, transfer and assign to Alamo, twenty five million two hundred eighty thousand and twenty seven (25,280,027) shares of common stock of Indoor Harvest, par value $0.001, in the aggregate, in exchange for the transfer of such securities by the members of Alamo. Upon completion of the exchange, all of the Alamo interests shall be held by Indoor Harvest and Alamo shall become a wholly-owned subsidiary of Indoor Harvest. On March 31, 2017, Alamo submitted an application under the Texas Compassionate Use Program (“TCUP”) to produce and dispense low-THC cannabis oils for the treatment of intractable epilepsy. Alamo has brought together prominent Texans from the United States military, Healthcare and Biopharmaceutical industries, as well as retired veterans of the Department of Public Safety (“DPS”), each committed to providing low-THC cannabis medicine to intractable epilepsy patients in Texas, while advancing the TCUP by collaborating with DPS officials. If licensed, Alamo would meet and exceed security, compliance, and quality standards set by regulators. The DPS is currently expected to notify those applicants that have been conditionally approved on April 30, 2017. Additionally, on March 23, 2017, Indoor Harvest and Alamo entered into a Contractual Joint Venture Agreement with Vyripharm Enterprises, LLC (“Vyripharm”), pursuant to which the parties agreed to participate in an unincorporated joint venture (the “Joint Venture”) to establish Alamo as a supplier of a variety of low-THC cannabis oil to Vyripharm for Vyripharm’s use in conducting research and development to create novel pharmaceutical and radiopharmaceutical compounds designed to image and treat intractable epilepsy. Under the Joint Venture, Alamo will provide low-THC cannabis oil to Vyripharm using Indoor Harvest’s patent pending HPA platform in order to provide specific chemical expression profiles needed for Vyripharm’s research and patient treatments. The Joint Venture would allow the group to provide a unique ability in the industry, personalized patient medicine, by testing patient efficacy, utilizing the full entourage effect of cannabis, to those suffering from intractable epilepsy in the State of Texas. Vyripharm has extensive patent coverage on its imaging and delivery platforms and was recently granted patent allowance by the United States Patent and Trade Office for its comprehensive medical cannabis and hemp testing methodology platform ["Integrated Systems and Methods of Evaluating Cannabis and Cannabinoid Products for Public Safety, Quality Control and Quality Assurance Purposes," Patent# US20150219610 A1]. Additionally, Vyripharm has entered into sponsored research agreements for its core platforms with the University of Texas Medical Branch Galveston, The University of Texas Health Science Center at Houston – Institute of Molecular Medicine Sponsored Research and The University of Texas M.D. Anderson Cancer Center. There is also an agreement with the National Institute of Drug Abuse and pending agreements with Baylor College of Medicine and the VA Hospital in Houston, TX. In connection with the proposed transaction, the Company will file with the Securities and Exchange Commission (the “SEC”) and furnish to the Company’s stockholders a proxy statement and a shareholder vote will be required to close the transaction. Before making any voting decision, the Company’s stockholders are urged to read the proxy statement in its entirety when it becomes available and any other documents to be filed with the SEC in connection with the proposed acquisition or incorporated by reference in the proxy statement because they will contain important information about the proposed transaction and the parties to the proposed transaction.  Investors and shareholders may obtain a free copy of documents filed by Indoor Harvest Corp with the SEC at the SEC’s website at http://www.sec.gov. In addition, investors and shareholders may obtain a free copy of Indoor Harvest Corp’s filings with the SEC from Indoor Harvest Corp’s website at http://investors.indoorharvest.com/SEC-filings. Consistent with the SEC’s April 2013 guidance on using social media outlets like Facebook and Twitter to make corporate disclosures and announce key information in compliance with Regulation FD, Indoor Harvest is alerting investors and other members of the general public that Indoor Harvest will provide weekly updates on operations and progress through its social media on Facebook and Twitter. Investors, potential investors and individuals interested in our company are encouraged to keep informed by following us on Twitter or Facebook. Indoor Harvest Corp, through its brand name Indoor Harvest®, is a full service, state of the art design-build engineering firm for the indoor farming industry. Providing production platforms and complete custom-designed build-outs for both greenhouse and building integrated agriculture (BIA) grows, tailored to the specific needs of virtually any cultivar. Our patent pending aeroponic fixtures are based upon a modular concept in which primary components are interchangeable. Visit our website at http://www.indoorharvest.com for more information about our Company. FORWARD LOOKING STATEMENTS             This release contains certain “forward-looking statements” relating to the business of Indoor Harvest and its subsidiary companies, which can be identified by the use of forward-looking terminology such as “estimates,” “believes,” “anticipates,” “intends,” expects” and similar expressions. Such forward-looking statements involve known and unknown risks and uncertainties that may cause actual results to be materially different from those described herein as anticipated, believed, estimated or expected. Certain of these risks and uncertainties are or will be described in greater detail in our filings with the Securities and Exchange Commission. These forward-looking statements are based on Indoor Harvest’s current expectations and beliefs concerning future developments and their potential effects on Indoor Harvest. There can be no assurance that future developments affecting Indoor Harvest will be those anticipated by Indoor Harvest. These forward-looking statements involve a number of risks, uncertainties (some of which are beyond the control of the Company) or other assumptions that may cause actual results or performance to be materially different from those expressed or implied by such forward-looking statements. Indoor Harvest undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required under applicable securities laws.


News Article | April 8, 2017
Site: www.techtimes.com

Ticked Off! Here's What You Need To Know About Lyme Disease Local health officials on the Hawaiian island of Maui are concerned about the potential spread of rat lungworm, an infection caused by a rare parasitic worm Angiostrongylus cantonensis. The parasite can live in the body for months and cause permanent damage as it can invade the brain and its membrane. Symptoms of infection include sensitivity to light, neck stiffness, bad headache, and vomiting, which can start more than six weeks after the worm was ingested. Those who catch the infection by eating contaminated fruits and vegetables and raw or undercooked snails may develop meningitis. The infection can be fatal in some cases. "If you could imagine, it's like having a slow-moving bullet go through your brain," said epidemiologist Sarah Park, of the Hawaii department of health."There's no rhyme or reason why it's going to hang out in this part of the brain or that part of the brain." The parasite thrives in the blood vessels of rats' lung but their larvae can be expelled in the droppings and then get eaten by slugs, snails, and other animals that can pass the young parasitic worms to humans. At least six cases of the parasitic infection have been reported in Hawaii over the past three months, a significant increase from only two cases that were reported over the previous decade. The disease has no treatment and can be difficult to diagnose because no blood test is available to confirm infection. Infectious disease specialist Constantine Tsigrelis, of the University Hospitals Cleveland Medical Center, said that treatment is complicated since the anti-parasitic drug that can kill the worm can also injure the patient's brain or nervous system. Giving this to patients can, therefore, worsen their condition. Globalization and climate change appear to contribute to the spread of the parasite and the disease. The first known case of rat lungworm was identified in Taiwan in 1944. Over the past years, the parasite has spread to other parts of the globe including the United States. Just like a number of other pathogens, the parasite is believed to have been brought and spread by rats in cargo ships. "So it's a worm infection introduced into North America through globalization," said Peter Hotez, the National School of Tropical Medicine dean at Baylor College of Medicine. "Some suggest that it's due to snails or slugs in the ship ballasts-ships coming from Asia and going through the Panama Canal." The brain-invading parasite is prevalent in tropical regions such as Southeast Asia and tropical Pacific islands but its geographical distribution has expanded in recent years. Experts fear that this could be one of the consequences of climate change as a warming world has been known to contribute to the spread of a range of diseases such as the mosquito-borne Zika virus. "Most new infections seem to be caused by pathogens already present in the environment, which have been brought out of obscurity, or given selective advantage, by changing ecological or social conditions," reads a 2004 World Health Organization report. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.


A new study by researchers at UCLA has revealed two key findings for people with irritable bowel syndrome about the relationship between the microorganisms that live in the gut and the brain. For people with IBS research shows for the first time that there is an association between the gut microbiota and the brain regions involved in the processing of sensory information from their bodies. The results suggest that signals generated by the brain can influence the composition of microbes residing in the intestine and that the chemicals in the gut can shape the human brain's structure. Additionally, the researchers gained insight into the connections among childhood trauma, brain development and the composition of the gut microbiome. Previous studies performed in mice have demonstrated effects of gut microbiota on brain function and behavior, as well as the influence of the brain on the composition of microbes in the gut. However, to date, only one study performed in human subjects has confirmed the translatability of such findings to the human brain. Studies have also reported evidence for alterations in the composition of gut microbiota in people with irritable bowel syndrome, but there has been little consistency among studies regarding the specific microbial alterations and the relationship of such alterations with the cardinal symptoms of IBS, recurring abdominal pain and altered bowel habits. In relation to a person's history with childhood trauma, it has been shown to be associated with structural and functional brain changes; trauma in young children has also been shown to alter gut microbial composition. But how they are related has been unknown. The UCLA researchers collected behavioral and clinical measures, stool samples and structural brain images from 29 adults diagnosed with IBS, and 23 healthy control subjects. They used DNA sequencing and various mathematical approaches to quantify composition, abundance and diversity of the gut microbiota. They also estimated the microbial gene content and gene products of the stool samples. Then the researchers cross-referenced these gut microbial measures with structural features of the brain. Based on the composition of the microbes in the gut, the samples from those diagnosed with IBS clustered into two subgroups. One group was indistinguishable from the healthy control subjects, while the other differed. Those in the group with an altered gut microbiota had more history of early life trauma and longer duration of IBS symptoms. The two groups also displayed differences in brain structure. Analysis of a person's gut microbiota may become a routine screening test for people with IBS in clinical practice, and in the future, therapies such as certain diets and probiotics may become personalized based on an individual's gut microbial profile. At the same time, subgroups of people with IBS distinguished by brain and microbial signatures may show different responsiveness to brain-directed therapies such as mindfulness-based stress reduction, cognitive behavioral therapy and targeted drugs. A history of early life trauma has been shown to be associated with structural and functional brain changes and to alter gut microbial composition. It is possible that the signals the gut and its microbes get from the brain of an individual with a history of childhood trauma may lead to lifelong changes in the gut microbiome. These alterations in the gut microbiota may feed back into sensory brain regions, altering the sensitivity to gut stimuli, a hallmark of people with IBS. The authors of the study are Jennifer Labus, Dr. Jonathan Jacobs, Arpana Gupta, Jonathan Acosta, Elaine Hsiao, Dr. Kirsten Tillisch, and Dr. Emeran Mayer, all of UCLA; Emily Hollister, Numan Oezguen, Ruth Ann Luna, Dr. Kjersti Aagaard, Dr. James Versalovic and Tor Savidge of Baylor College of Medicine; and Kyleigh Kirbach of Washington University. The study was published online in the peer-reviewed journal Microbiome. The National Institute of Diabetes and Digestive and Kidney Diseases and the National Center for Complementary and Alternative Medicine funded this research.


-- A new study shows that the successful strategy to get elementary school children to eat more vegetables based on use of the FIT Game, can be just as effective and less costly to implement when teachers no longer administer the game. Results of a study in which FIT Game episodes were displayed in the school cafeteria, leading to a 99.9% increase in vegetable consumption from baseline levels, are published ina peer-reviewed publication from(http://www.liebertpub.com/)The article is available free on thewebsite until June 5, 2017.The article entitled "The FIT Game III: Reduced the Operating Expenses of a Game-Based Approach to Increasing Health Eating in Elementary Schools (http://online.liebertpub.com/doi/full/10.1089/g4h.2016.0096)"is coauthored byandUtah State University, Logan,, Brigham Young University, Provo, Utah, and, Schell Games, Pittsburgh, PA. The researchers evaluated the effectiveness of the FIT Game in two elementary schools, graded K-5, measuring daily vegetable consumption. In previous studies, when teachers administered the game in the classroom, vegetable consumption increased by 44% and 33%. The current study employed a less costly approach to sharing FIT Game episodes with the students that was even more successful at increasing their vegetable consumption."Nationally, child vegetable consumption has been low, well below the levels needed to obtain the many health benefits. Since adults tend to eat what they found enjoyable as a child, increasing child vegetable consumption offers promise of influencing their health in their adult years," saysEditor-in-Chief offromUSDA/ARS Children's Nutrition Research Center, and Department of Pediatrics, Baylor College of Medicine, Houston, TX. "Joyner and colleagues adapted a very low cost game-based intervention that can be employed in elementary schools and substantially increased vegetable consumption. This is a very promising outcome that needs to be replicated and, if found to be generally effective, should be broadly distributed throughout the U.S. and beyond."breaks new ground as the first journal to address this emerging and increasingly important area of health care. The Journal provides a bimonthly forum in print and online for academic and clinical researchers, game designers and developers, health care providers, insurers, and information technology leaders. Articles explore the use of game technology in a variety of clinical applications. These include disease prevention and monitoring, nutrition, weight management, and medication adherence. Gaming can play an important role in the care of patients with diabetes, post-traumatic stress disorder, Alzheimer's disease, and cognitive, mental, emotional, and behavioral health disorders.is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, includingand. Its biotechnology trade magazine, GEN (), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 80 journals, books, and newsmagazines is available online at the. website.


News Article | April 18, 2017
Site: www.biosciencetechnology.com

In a study published today in PLoS ONE, a team of researchers reports solving a medical mystery in a day's work. In record-time detective work, the scientists narrowed down the genetic cause of intellectual disability in four male patients to a deletion of a small section of the X chromosome that had not been previously linked to a medical condition. Even with the current technological advances, solving medical mysteries such as this one usually entails a much longer period of research. "We found it very interesting how fast we went from knowing nothing about the genetic cause of one patient's condition, to discovering the cause and finding three more individuals with the same problems," said senior author Dr. Daryl A. Scott, associate professor of molecular and human genetics at Baylor College of Medicine. "It took us a year to get all the documentation for writing and publishing the report, but the actual discovery was within hours. It was essential to our discovery that we had at our disposal technology to find and search genomic databases, and to connect electronically and exchange information with other researchers around the world." It all began on a Thursday, Scott's day to visit patients with developmental disabilities in clinic. "For one of the patients, a young male with intellectual disability, developmental delay, macrocephaly (enlarged head) and very flexible joints, our genetics lab indicated that the patient did not seem to have any known genetic changes that could explain his condition," said Scott. "I saw a relatively small deletion in the X chromosome, identified as Xp11.22; it had only a few genes in it. The lab indicated that there had been no previous reports about this particular part of the genome causing any kind of medical problems." Two of the genes in the delete section of the patient's X chromosome were MAGED1 and GSPT2. "To have an idea of what these genes might do, I searched a database that describes the functions of genes in the mouse and found that mice that have a deletion of the Maged1 gene have neurocognitive behavioral abnormalities. This caught my interest as it related to my patient's condition." To make his case that deletions in Xp11.22 caused the clinical features of his patient, Scott needed to find more patients presenting similar clinical conditions and deletions. He searched two large genomic databases looking for more patients. After searching the DECIPHER database, Scott found one patient carrying almost the exact same deletion as his patient, but there was no information about the individual's clinical problems. Scott immediately sent an electronic message to the physician, co-author Dr. Alex Henderson, at The Newcastle upon Tyne Hospitals in England, in order learn more about the clinical characteristics of his patient. Then, Scott contacted co-author Dr. Seema Lalani, associate professor of molecular and human Genetics at Baylor and assistant laboratory director of cytogenetics at Baylor Genetics. Lalani searched the Baylor Genetics database of 60,000 cases for patients with the deletion. After carrying on this detective electronic work, Scott went to see his patient. By early afternoon, he was back in his office checking his email. He found a message from Henderson. He had two male patients (siblings) with the deletion, and intellectual disability, developmental delay and super mobile joints! Shortly after, Lalani informed Scott that co-author Dr. Patricia Evans, professor of pediatrics, neurology and neurotherapeutics at the University of Texas Southwestern Medical School in Dallas had a patient with the Xp11.22 deletion and the same clinical features as Scott's patient. "In a day's work we identified four patients in two continents, involving 3 families and it was all put together within 8 hours," Scott said. "None of the patients and their families had an explanation for the condition before this work. Our findings allowed us to provide them with a genetic diagnosis." "In every case the mothers are carriers for these deletions but they do not have any apparent symptoms," said Scott. "Yet, they can have male children that have significant problems. With this information, we can say to the parents that they have a 50 percent chance of passing this X chromosome with the deletion to a male child. Female children have a 50 percent chance of being carriers. This represents a significant change for the parents; they can now make informed decisions about future family planning."


News Article | April 17, 2017
Site: www.eurekalert.org

In a study published today in PLoS ONE, a team of researchers reports solving a medical mystery in a day's work. In record-time detective work, the scientists narrowed down the genetic cause of intellectual disability in four male patients to a deletion of a small section of the X chromosome that had not been previously linked to a medical condition. Even with the current technological advances, solving medical mysteries such as this one usually entails a much longer period of research. "We found it very interesting how fast we went from knowing nothing about the genetic cause of one patient's condition, to discovering the cause and finding three more individuals with the same problems," said senior author Dr. Daryl A. Scott, associate professor of molecular and human genetics at Baylor College of Medicine. "It took us a year to get all the documentation for writing and publishing the report, but the actual discovery was within hours. It was essential to our discovery that we had at our disposal technology to find and search genomic databases, and to connect electronically and exchange information with other researchers around the world." It all began on a Thursday, Scott's day to visit patients with developmental disabilities in clinic. "For one of the patients, a young male with intellectual disability, developmental delay, macrocephaly (enlarged head) and very flexible joints, our genetics lab indicated that the patient did not seem to have any known genetic changes that could explain his condition," said Scott. "I saw a relatively small deletion in the X chromosome, identified as Xp11.22; it had only a few genes in it. The lab indicated that there had been no previous reports about this particular part of the genome causing any kind of medical problems." Two of the genes in the delete section of the patient's X chromosome were MAGED1 and GSPT2. "To have an idea of what these genes might do, I searched a database that describes the functions of genes in the mouse and found that mice that have a deletion of the Maged1 gene have neurocognitive behavioral abnormalities. This caught my interest as it related to my patient's condition." To make his case that deletions in Xp11.22 caused the clinical features of his patient, Scott needed to find more patients presenting similar clinical conditions and deletions. He searched two large genomic databases looking for more patients. After searching the DECIPHER database, Scott found one patient carrying almost the exact same deletion as his patient, but there was no information about the individual's clinical problems. Scott immediately sent an electronic message to the physician, co-author Dr. Alex Henderson, at The Newcastle upon Tyne Hospitals in England, in order learn more about the clinical characteristics of his patient. Then, Scott contacted co-author Dr. Seema Lalani, associate professor of molecular and human Genetics at Baylor and assistant laboratory director of cytogenetics at Baylor Genetics. Lalani searched the Baylor Genetics database of 60,000 cases for patients with the deletion. After carrying on this detective electronic work, Scott went to see his patient. By early afternoon, he was back in his office checking his email. He found a message from Henderson. He had two male patients (siblings) with the deletion, and intellectual disability, developmental delay and super mobile joints! Shortly after, Lalani informed Scott that co-author Dr. Patricia Evans, professor of pediatrics, neurology and neurotherapeutics at the University of Texas Southwestern Medical School in Dallas had a patient with the Xp11.22 deletion and the same clinical features as Scott's patient. "In a day's work we identified four patients in two continents, involving 3 families and it was all put together within 8 hours," Scott said. "None of the patients and their families had an explanation for the condition before this work. Our findings allowed us to provide them with a genetic diagnosis." "In every case the mothers are carriers for these deletions but they do not have any apparent symptoms," said Scott. "Yet, they can have male children that have significant problems. With this information, we can say to the parents that they have a 50 percent chance of passing this X chromosome with the deletion to a male child. Female children have a 50 percent chance of being carriers. This represents a significant change for the parents; they can now make informed decisions about future family planning." Other contributors of this work include Christina Grau, Molly Starkovich, Mahshid S. Azamian, Fan Xia and Sau Wai Cheung. This work was supported by the National Institutes of Health/ National Institute of General Medical Sciences Initiative for Maximizing Student Development [R25 GM056929-16].


News Article | April 24, 2017
Site: globenewswire.com

HOUSTON, April 24, 2017 (GLOBE NEWSWIRE) -- Indoor Harvest Corp (OTCQB:INQD) is pleased to announce, with Alamo CBD, LLC (“Alamo”), that on April 20, 2017 both Companies entered into a definitive share exchange agreement (the “Agreement”) to acquire 100% of the member ownership in Alamo. Pursuant to the Agreement, Indoor Harvest will sell, convey, transfer and assign to Alamo, twenty five million two hundred eighty thousand and twenty seven (25,280,027) shares of common stock of Indoor Harvest, par value $0.001, in the aggregate, in exchange for the transfer of such securities by the members of Alamo. Upon completion of the exchange, all of the Alamo interests shall be held by Indoor Harvest and Alamo shall become a wholly-owned subsidiary of Indoor Harvest. On March 31, 2017, Alamo submitted an application under the Texas Compassionate Use Program (“TCUP”) to produce and dispense low-THC cannabis oils for the treatment of intractable epilepsy. Alamo has brought together prominent Texans from the United States military, Healthcare and Biopharmaceutical industries, as well as retired veterans of the Department of Public Safety (“DPS”), each committed to providing low-THC cannabis medicine to intractable epilepsy patients in Texas, while advancing the TCUP by collaborating with DPS officials. If licensed, Alamo would meet and exceed security, compliance, and quality standards set by regulators. The DPS is currently expected to notify those applicants that have been conditionally approved on April 30, 2017. Additionally, on March 23, 2017, Indoor Harvest and Alamo entered into a Contractual Joint Venture Agreement with Vyripharm Enterprises, LLC (“Vyripharm”), pursuant to which the parties agreed to participate in an unincorporated joint venture (the “Joint Venture”) to establish Alamo as a supplier of a variety of low-THC cannabis oil to Vyripharm for Vyripharm’s use in conducting research and development to create novel pharmaceutical and radiopharmaceutical compounds designed to image and treat intractable epilepsy. Under the Joint Venture, Alamo will provide low-THC cannabis oil to Vyripharm using Indoor Harvest’s patent pending HPA platform in order to provide specific chemical expression profiles needed for Vyripharm’s research and patient treatments. The Joint Venture would allow the group to provide a unique ability in the industry, personalized patient medicine, by testing patient efficacy, utilizing the full entourage effect of cannabis, to those suffering from intractable epilepsy in the State of Texas. Vyripharm has extensive patent coverage on its imaging and delivery platforms and was recently granted patent allowance by the United States Patent and Trade Office for its comprehensive medical cannabis and hemp testing methodology platform ["Integrated Systems and Methods of Evaluating Cannabis and Cannabinoid Products for Public Safety, Quality Control and Quality Assurance Purposes," Patent# US20150219610 A1]. Additionally, Vyripharm has entered into sponsored research agreements for its core platforms with the University of Texas Medical Branch Galveston, The University of Texas Health Science Center at Houston – Institute of Molecular Medicine Sponsored Research and The University of Texas M.D. Anderson Cancer Center. There is also an agreement with the National Institute of Drug Abuse and pending agreements with Baylor College of Medicine and the VA Hospital in Houston, TX. In connection with the proposed transaction, the Company will file with the Securities and Exchange Commission (the “SEC”) and furnish to the Company’s stockholders a proxy statement and a shareholder vote will be required to close the transaction. Before making any voting decision, the Company’s stockholders are urged to read the proxy statement in its entirety when it becomes available and any other documents to be filed with the SEC in connection with the proposed acquisition or incorporated by reference in the proxy statement because they will contain important information about the proposed transaction and the parties to the proposed transaction.  Investors and shareholders may obtain a free copy of documents filed by Indoor Harvest Corp with the SEC at the SEC’s website at http://www.sec.gov. In addition, investors and shareholders may obtain a free copy of Indoor Harvest Corp’s filings with the SEC from Indoor Harvest Corp’s website at http://investors.indoorharvest.com/SEC-filings. Consistent with the SEC’s April 2013 guidance on using social media outlets like Facebook and Twitter to make corporate disclosures and announce key information in compliance with Regulation FD, Indoor Harvest is alerting investors and other members of the general public that Indoor Harvest will provide weekly updates on operations and progress through its social media on Facebook and Twitter. Investors, potential investors and individuals interested in our company are encouraged to keep informed by following us on Twitter or Facebook. Indoor Harvest Corp, through its brand name Indoor Harvest®, is a full service, state of the art design-build engineering firm for the indoor farming industry. Providing production platforms and complete custom-designed build-outs for both greenhouse and building integrated agriculture (BIA) grows, tailored to the specific needs of virtually any cultivar. Our patent pending aeroponic fixtures are based upon a modular concept in which primary components are interchangeable. Visit our website at http://www.indoorharvest.com for more information about our Company. FORWARD LOOKING STATEMENTS             This release contains certain “forward-looking statements” relating to the business of Indoor Harvest and its subsidiary companies, which can be identified by the use of forward-looking terminology such as “estimates,” “believes,” “anticipates,” “intends,” expects” and similar expressions. Such forward-looking statements involve known and unknown risks and uncertainties that may cause actual results to be materially different from those described herein as anticipated, believed, estimated or expected. Certain of these risks and uncertainties are or will be described in greater detail in our filings with the Securities and Exchange Commission. These forward-looking statements are based on Indoor Harvest’s current expectations and beliefs concerning future developments and their potential effects on Indoor Harvest. There can be no assurance that future developments affecting Indoor Harvest will be those anticipated by Indoor Harvest. These forward-looking statements involve a number of risks, uncertainties (some of which are beyond the control of the Company) or other assumptions that may cause actual results or performance to be materially different from those expressed or implied by such forward-looking statements. Indoor Harvest undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required under applicable securities laws.


News Article | April 24, 2017
Site: globenewswire.com

HOUSTON, April 24, 2017 (GLOBE NEWSWIRE) -- Indoor Harvest Corp (OTCQB:INQD) is pleased to announce, with Alamo CBD, LLC (“Alamo”), that on April 20, 2017 both Companies entered into a definitive share exchange agreement (the “Agreement”) to acquire 100% of the member ownership in Alamo. Pursuant to the Agreement, Indoor Harvest will sell, convey, transfer and assign to Alamo, twenty five million two hundred eighty thousand and twenty seven (25,280,027) shares of common stock of Indoor Harvest, par value $0.001, in the aggregate, in exchange for the transfer of such securities by the members of Alamo. Upon completion of the exchange, all of the Alamo interests shall be held by Indoor Harvest and Alamo shall become a wholly-owned subsidiary of Indoor Harvest. On March 31, 2017, Alamo submitted an application under the Texas Compassionate Use Program (“TCUP”) to produce and dispense low-THC cannabis oils for the treatment of intractable epilepsy. Alamo has brought together prominent Texans from the United States military, Healthcare and Biopharmaceutical industries, as well as retired veterans of the Department of Public Safety (“DPS”), each committed to providing low-THC cannabis medicine to intractable epilepsy patients in Texas, while advancing the TCUP by collaborating with DPS officials. If licensed, Alamo would meet and exceed security, compliance, and quality standards set by regulators. The DPS is currently expected to notify those applicants that have been conditionally approved on April 30, 2017. Additionally, on March 23, 2017, Indoor Harvest and Alamo entered into a Contractual Joint Venture Agreement with Vyripharm Enterprises, LLC (“Vyripharm”), pursuant to which the parties agreed to participate in an unincorporated joint venture (the “Joint Venture”) to establish Alamo as a supplier of a variety of low-THC cannabis oil to Vyripharm for Vyripharm’s use in conducting research and development to create novel pharmaceutical and radiopharmaceutical compounds designed to image and treat intractable epilepsy. Under the Joint Venture, Alamo will provide low-THC cannabis oil to Vyripharm using Indoor Harvest’s patent pending HPA platform in order to provide specific chemical expression profiles needed for Vyripharm’s research and patient treatments. The Joint Venture would allow the group to provide a unique ability in the industry, personalized patient medicine, by testing patient efficacy, utilizing the full entourage effect of cannabis, to those suffering from intractable epilepsy in the State of Texas. Vyripharm has extensive patent coverage on its imaging and delivery platforms and was recently granted patent allowance by the United States Patent and Trade Office for its comprehensive medical cannabis and hemp testing methodology platform ["Integrated Systems and Methods of Evaluating Cannabis and Cannabinoid Products for Public Safety, Quality Control and Quality Assurance Purposes," Patent# US20150219610 A1]. Additionally, Vyripharm has entered into sponsored research agreements for its core platforms with the University of Texas Medical Branch Galveston, The University of Texas Health Science Center at Houston – Institute of Molecular Medicine Sponsored Research and The University of Texas M.D. Anderson Cancer Center. There is also an agreement with the National Institute of Drug Abuse and pending agreements with Baylor College of Medicine and the VA Hospital in Houston, TX. In connection with the proposed transaction, the Company will file with the Securities and Exchange Commission (the “SEC”) and furnish to the Company’s stockholders a proxy statement and a shareholder vote will be required to close the transaction. Before making any voting decision, the Company’s stockholders are urged to read the proxy statement in its entirety when it becomes available and any other documents to be filed with the SEC in connection with the proposed acquisition or incorporated by reference in the proxy statement because they will contain important information about the proposed transaction and the parties to the proposed transaction.  Investors and shareholders may obtain a free copy of documents filed by Indoor Harvest Corp with the SEC at the SEC’s website at http://www.sec.gov. In addition, investors and shareholders may obtain a free copy of Indoor Harvest Corp’s filings with the SEC from Indoor Harvest Corp’s website at http://investors.indoorharvest.com/SEC-filings. Consistent with the SEC’s April 2013 guidance on using social media outlets like Facebook and Twitter to make corporate disclosures and announce key information in compliance with Regulation FD, Indoor Harvest is alerting investors and other members of the general public that Indoor Harvest will provide weekly updates on operations and progress through its social media on Facebook and Twitter. Investors, potential investors and individuals interested in our company are encouraged to keep informed by following us on Twitter or Facebook. Indoor Harvest Corp, through its brand name Indoor Harvest®, is a full service, state of the art design-build engineering firm for the indoor farming industry. Providing production platforms and complete custom-designed build-outs for both greenhouse and building integrated agriculture (BIA) grows, tailored to the specific needs of virtually any cultivar. Our patent pending aeroponic fixtures are based upon a modular concept in which primary components are interchangeable. Visit our website at http://www.indoorharvest.com for more information about our Company. FORWARD LOOKING STATEMENTS             This release contains certain “forward-looking statements” relating to the business of Indoor Harvest and its subsidiary companies, which can be identified by the use of forward-looking terminology such as “estimates,” “believes,” “anticipates,” “intends,” expects” and similar expressions. Such forward-looking statements involve known and unknown risks and uncertainties that may cause actual results to be materially different from those described herein as anticipated, believed, estimated or expected. Certain of these risks and uncertainties are or will be described in greater detail in our filings with the Securities and Exchange Commission. These forward-looking statements are based on Indoor Harvest’s current expectations and beliefs concerning future developments and their potential effects on Indoor Harvest. There can be no assurance that future developments affecting Indoor Harvest will be those anticipated by Indoor Harvest. These forward-looking statements involve a number of risks, uncertainties (some of which are beyond the control of the Company) or other assumptions that may cause actual results or performance to be materially different from those expressed or implied by such forward-looking statements. Indoor Harvest undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required under applicable securities laws.


News Article | April 24, 2017
Site: globenewswire.com

HOUSTON, April 24, 2017 (GLOBE NEWSWIRE) -- Indoor Harvest Corp (OTCQB:INQD) is pleased to announce, with Alamo CBD, LLC (“Alamo”), that on April 20, 2017 both Companies entered into a definitive share exchange agreement (the “Agreement”) to acquire 100% of the member ownership in Alamo. Pursuant to the Agreement, Indoor Harvest will sell, convey, transfer and assign to Alamo, twenty five million two hundred eighty thousand and twenty seven (25,280,027) shares of common stock of Indoor Harvest, par value $0.001, in the aggregate, in exchange for the transfer of such securities by the members of Alamo. Upon completion of the exchange, all of the Alamo interests shall be held by Indoor Harvest and Alamo shall become a wholly-owned subsidiary of Indoor Harvest. On March 31, 2017, Alamo submitted an application under the Texas Compassionate Use Program (“TCUP”) to produce and dispense low-THC cannabis oils for the treatment of intractable epilepsy. Alamo has brought together prominent Texans from the United States military, Healthcare and Biopharmaceutical industries, as well as retired veterans of the Department of Public Safety (“DPS”), each committed to providing low-THC cannabis medicine to intractable epilepsy patients in Texas, while advancing the TCUP by collaborating with DPS officials. If licensed, Alamo would meet and exceed security, compliance, and quality standards set by regulators. The DPS is currently expected to notify those applicants that have been conditionally approved on April 30, 2017. Additionally, on March 23, 2017, Indoor Harvest and Alamo entered into a Contractual Joint Venture Agreement with Vyripharm Enterprises, LLC (“Vyripharm”), pursuant to which the parties agreed to participate in an unincorporated joint venture (the “Joint Venture”) to establish Alamo as a supplier of a variety of low-THC cannabis oil to Vyripharm for Vyripharm’s use in conducting research and development to create novel pharmaceutical and radiopharmaceutical compounds designed to image and treat intractable epilepsy. Under the Joint Venture, Alamo will provide low-THC cannabis oil to Vyripharm using Indoor Harvest’s patent pending HPA platform in order to provide specific chemical expression profiles needed for Vyripharm’s research and patient treatments. The Joint Venture would allow the group to provide a unique ability in the industry, personalized patient medicine, by testing patient efficacy, utilizing the full entourage effect of cannabis, to those suffering from intractable epilepsy in the State of Texas. Vyripharm has extensive patent coverage on its imaging and delivery platforms and was recently granted patent allowance by the United States Patent and Trade Office for its comprehensive medical cannabis and hemp testing methodology platform ["Integrated Systems and Methods of Evaluating Cannabis and Cannabinoid Products for Public Safety, Quality Control and Quality Assurance Purposes," Patent# US20150219610 A1]. Additionally, Vyripharm has entered into sponsored research agreements for its core platforms with the University of Texas Medical Branch Galveston, The University of Texas Health Science Center at Houston – Institute of Molecular Medicine Sponsored Research and The University of Texas M.D. Anderson Cancer Center. There is also an agreement with the National Institute of Drug Abuse and pending agreements with Baylor College of Medicine and the VA Hospital in Houston, TX. In connection with the proposed transaction, the Company will file with the Securities and Exchange Commission (the “SEC”) and furnish to the Company’s stockholders a proxy statement and a shareholder vote will be required to close the transaction. Before making any voting decision, the Company’s stockholders are urged to read the proxy statement in its entirety when it becomes available and any other documents to be filed with the SEC in connection with the proposed acquisition or incorporated by reference in the proxy statement because they will contain important information about the proposed transaction and the parties to the proposed transaction.  Investors and shareholders may obtain a free copy of documents filed by Indoor Harvest Corp with the SEC at the SEC’s website at http://www.sec.gov. In addition, investors and shareholders may obtain a free copy of Indoor Harvest Corp’s filings with the SEC from Indoor Harvest Corp’s website at http://investors.indoorharvest.com/SEC-filings. Consistent with the SEC’s April 2013 guidance on using social media outlets like Facebook and Twitter to make corporate disclosures and announce key information in compliance with Regulation FD, Indoor Harvest is alerting investors and other members of the general public that Indoor Harvest will provide weekly updates on operations and progress through its social media on Facebook and Twitter. Investors, potential investors and individuals interested in our company are encouraged to keep informed by following us on Twitter or Facebook. Indoor Harvest Corp, through its brand name Indoor Harvest®, is a full service, state of the art design-build engineering firm for the indoor farming industry. Providing production platforms and complete custom-designed build-outs for both greenhouse and building integrated agriculture (BIA) grows, tailored to the specific needs of virtually any cultivar. Our patent pending aeroponic fixtures are based upon a modular concept in which primary components are interchangeable. Visit our website at http://www.indoorharvest.com for more information about our Company. FORWARD LOOKING STATEMENTS             This release contains certain “forward-looking statements” relating to the business of Indoor Harvest and its subsidiary companies, which can be identified by the use of forward-looking terminology such as “estimates,” “believes,” “anticipates,” “intends,” expects” and similar expressions. Such forward-looking statements involve known and unknown risks and uncertainties that may cause actual results to be materially different from those described herein as anticipated, believed, estimated or expected. Certain of these risks and uncertainties are or will be described in greater detail in our filings with the Securities and Exchange Commission. These forward-looking statements are based on Indoor Harvest’s current expectations and beliefs concerning future developments and their potential effects on Indoor Harvest. There can be no assurance that future developments affecting Indoor Harvest will be those anticipated by Indoor Harvest. These forward-looking statements involve a number of risks, uncertainties (some of which are beyond the control of the Company) or other assumptions that may cause actual results or performance to be materially different from those expressed or implied by such forward-looking statements. Indoor Harvest undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required under applicable securities laws.


TEL-AVIV, Israel, May 04, 2017 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company primarily focused on the development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, today announced the presentation of a poster at Digestive Disease Week (DDW) 2017. The poster (presentation number: Sa1200) will be presented by Ira Kalfus, MD, Medical Director at RedHill, on Saturday, May 6, 2017 from 12:00 PM to 2:00 PM CDT, in Chicago, IL. The poster1 presentation, entitled “ERADICATE Hp: A Randomized, Double-Blind, Placebo-Controlled Phase III Study to Assess the Safety and Efficacy of Rifabutin Triple Therapy (RHB-105) for Helicobacter pylori (H. pylori) Infection in Dyspepsia Patients” describes the previously reported positive final results of the ERADICATE Hp first Phase III study with RHB-105 for H. pylori infection. RHB-105 is a proprietary, fixed-dose, oral combination therapy for the eradication of H. pylori infection. The ERADICATE Hp first Phase III study with RHB-105 successfully met its protocol-defined mITT primary endpoint of superiority over historical standard-of-care (SoC) eradication rate of 70%, with high statistical significance (p<0.001). The study results demonstrated 89.4% efficacy in eradicating H. pylori infection with RHB-105. Notably, the 89.4% efficacy in eradicating H. pylori infection with RHB-105 was also superior to subsequent open-label treatment with SoC therapies of patients in the placebo arm of the ERADICATE Hp study, which demonstrated 63% eradication rate in the mITT population (p=0.006), further supporting the potential efficacy of RHB-105 as a treatment for H. pylori infection. Treatment with RHB-105 appeared to be safe and well tolerated. A confirmatory Phase III study is planned to be initiated in the second quarter of 2017. The two-arm, randomized, double-blind, active comparator confirmatory Phase III study will compare RHB-105 against a dual therapy amoxicillin and omeprazole regimen at equivalent doses. The study is planned to enroll approximately 440 patients in up to 55 clinical sites in the U.S. Subject to its successful completion, the planned confirmatory Phase III study, along with the results from the successfully completed first Phase III ERADICATE Hp study with RHB-105 and data to be obtained from an ongoing supportive PK program, are expected to support a U.S. New Drug Application (NDA) for RHB-105. About RHB-105: RHB-105 is a new and proprietary fixed-dose oral combination therapy of two antibiotics and a proton pump inhibitor (PPI) in an all-in-one oral capsule with a planned indication for the treatment of H. pylori infection. H. pylori bacterial infection is a major cause of chronic gastritis, peptic ulcer disease, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. A first Phase III study with RHB-105 was completed in the U.S. with positive results (ERADICATE Hp study). The study demonstrated an overall success rate of 89.4% in eradicating H. pylori, and met its protocol-defined primary endpoint of superiority in eradication of H. pylori infection over historical standard-of-care efficacy levels of 70%, with high statistical significance (p<0.001). A confirmatory Phase III study is planned to be initiated in the U.S in the second quarter of 2017. Additional studies may be required, subject to FDA review. RHB-105 has been granted Qualifying Infectious Disease Product (QIDP) designation by the FDA, providing a Fast-Track development pathway, as well as NDA Priority Review status, potentially leading to a shorter NDA review time by the FDA, if filed. If approved, RHB-105 will also receive an additional five years of exclusivity, in addition to the standard exclusivity period, for a total of 8 years of U.S. market exclusivity. About RedHill Biopharma Ltd.: RedHill Biopharma Ltd. (NASDAQ:RDHL) (Tel-Aviv Stock Exchange:RDHL) is a specialty biopharmaceutical company headquartered in Israel, primarily focused on the development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for the treatment of gastrointestinal and inflammatory diseases and cancer. RedHill has a U.S. co-promotion agreement with Concordia for Donnatal®, a prescription oral adjunctive drug used in the treatment of IBS and acute enterocolitis, as well as an exclusive license agreement with Entera Health for EnteraGam®, a medical food intended for the dietary management, under medical supervision, of chronic diarrhea and loose stools. RedHill’s clinical-stage pipeline includes: (i) RHB-105 - an oral combination therapy for the treatment of Helicobacter pylori infection with successful results from a first Phase III study; (ii) RHB-104 - an oral combination therapy for the treatment of Crohn's disease with an ongoing first Phase III study, a completed proof-of-concept Phase IIa study for multiple sclerosis and QIDP status for nontuberculous mycobacteria (NTM) infections; (iii) BEKINDA® (RHB-102) - a once-daily oral pill formulation of ondansetron with an ongoing Phase III study for acute gastroenteritis and gastritis and an ongoing Phase II study for IBS-D; (iv) RHB-106 - an encapsulated bowel preparation licensed to Salix Pharmaceuticals, Ltd.; (v) YELIVA® (ABC294640) - a Phase II-stage, orally-administered, first-in-class SK2 selective inhibitor targeting multiple oncology, inflammatory and gastrointestinal indications; (vi) MESUPRON - a Phase II-stage first-in-class, orally-administered protease inhibitor, targeting pancreatic cancer and other solid tumors and (vii) RIZAPORT® (RHB-103) - an oral thin film formulation of rizatriptan for acute migraines, with a U.S. NDA currently under discussion with the FDA and marketing authorization received in two EU member states under the European Decentralized Procedure (DCP). More information about the Company is available at: www.redhillbio.com. 1 The poster was authored by Ira N. Kalfus, MD, Medical Director, RedHill Biopharma; Gilead Raday, Chief Operating Officer, RedHill Biopharma; Reza Fathi, PhD, Senior VP R&D, RedHill Biopharma and David Y. Graham, MD, Professor of Medicine, Molecular Virology and Microbiology, Baylor College of Medicine. This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements may be preceded by the words “intends,” “may,” “will,” “plans,” “expects,” “anticipates,” “projects,” “predicts,” “estimates,” “aims,” “believes,” “hopes,” “potential” or similar words. Forward-looking statements are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Company’s control, and cannot be predicted or quantified and consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, risks and uncertainties associated with (i) the initiation, timing, progress and results of the Company’s research, manufacturing, preclinical studies, clinical trials, and other therapeutic candidate development efforts; (ii) the Company’s ability to advance its therapeutic candidates into clinical trials or to successfully complete its preclinical studies or clinical trials; (iii) the extent and number of additional studies that the Company may be required to conduct and the Company’s receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings, approvals and feedback; (iv) the manufacturing, clinical development, commercialization, and market acceptance of the Company’s therapeutic candidates; (v) the Company’s ability to successfully market Donnatal® and EnteraGam®, (vi) the Company’s ability to establish and maintain corporate collaborations; (vii) the Company's ability to acquire products approved for marketing in the U.S. that achieve commercial success and build its own marketing and commercialization capabilities; (viii) the interpretation of the properties and characteristics of the Company’s therapeutic candidates and of the results obtained with its therapeutic candidates in research, preclinical studies or clinical trials; (ix) the implementation of the Company’s business model, strategic plans for its business and therapeutic candidates; (x) the scope of protection the Company is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; (xi) parties from whom the Company licenses its intellectual property defaulting in their obligations to the Company; and (xii) estimates of the Company’s expenses, future revenues capital requirements and the Company’s needs for additional financing; (xiii) competitive companies and technologies within the Company’s industry. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's filings with the Securities and Exchange Commission (SEC), including the Company's Annual Report on Form 20-F filed with the SEC on February 23, 2017. All forward-looking statements included in this Press Release are made only as of the date of this Press Release. We assume no obligation to update any written or oral forward-looking statement unless required by law.


TEL-AVIV, Israel, May 04, 2017 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company primarily focused on the development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, today announced the presentation of a poster at Digestive Disease Week (DDW) 2017. The poster (presentation number: Sa1200) will be presented by Ira Kalfus, MD, Medical Director at RedHill, on Saturday, May 6, 2017 from 12:00 PM to 2:00 PM CDT, in Chicago, IL. The poster1 presentation, entitled “ERADICATE Hp: A Randomized, Double-Blind, Placebo-Controlled Phase III Study to Assess the Safety and Efficacy of Rifabutin Triple Therapy (RHB-105) for Helicobacter pylori (H. pylori) Infection in Dyspepsia Patients” describes the previously reported positive final results of the ERADICATE Hp first Phase III study with RHB-105 for H. pylori infection. RHB-105 is a proprietary, fixed-dose, oral combination therapy for the eradication of H. pylori infection. The ERADICATE Hp first Phase III study with RHB-105 successfully met its protocol-defined mITT primary endpoint of superiority over historical standard-of-care (SoC) eradication rate of 70%, with high statistical significance (p<0.001). The study results demonstrated 89.4% efficacy in eradicating H. pylori infection with RHB-105. Notably, the 89.4% efficacy in eradicating H. pylori infection with RHB-105 was also superior to subsequent open-label treatment with SoC therapies of patients in the placebo arm of the ERADICATE Hp study, which demonstrated 63% eradication rate in the mITT population (p=0.006), further supporting the potential efficacy of RHB-105 as a treatment for H. pylori infection. Treatment with RHB-105 appeared to be safe and well tolerated. A confirmatory Phase III study is planned to be initiated in the second quarter of 2017. The two-arm, randomized, double-blind, active comparator confirmatory Phase III study will compare RHB-105 against a dual therapy amoxicillin and omeprazole regimen at equivalent doses. The study is planned to enroll approximately 440 patients in up to 55 clinical sites in the U.S. Subject to its successful completion, the planned confirmatory Phase III study, along with the results from the successfully completed first Phase III ERADICATE Hp study with RHB-105 and data to be obtained from an ongoing supportive PK program, are expected to support a U.S. New Drug Application (NDA) for RHB-105. About RHB-105: RHB-105 is a new and proprietary fixed-dose oral combination therapy of two antibiotics and a proton pump inhibitor (PPI) in an all-in-one oral capsule with a planned indication for the treatment of H. pylori infection. H. pylori bacterial infection is a major cause of chronic gastritis, peptic ulcer disease, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. A first Phase III study with RHB-105 was completed in the U.S. with positive results (ERADICATE Hp study). The study demonstrated an overall success rate of 89.4% in eradicating H. pylori, and met its protocol-defined primary endpoint of superiority in eradication of H. pylori infection over historical standard-of-care efficacy levels of 70%, with high statistical significance (p<0.001). A confirmatory Phase III study is planned to be initiated in the U.S in the second quarter of 2017. Additional studies may be required, subject to FDA review. RHB-105 has been granted Qualifying Infectious Disease Product (QIDP) designation by the FDA, providing a Fast-Track development pathway, as well as NDA Priority Review status, potentially leading to a shorter NDA review time by the FDA, if filed. If approved, RHB-105 will also receive an additional five years of exclusivity, in addition to the standard exclusivity period, for a total of 8 years of U.S. market exclusivity. About RedHill Biopharma Ltd.: RedHill Biopharma Ltd. (NASDAQ:RDHL) (Tel-Aviv Stock Exchange:RDHL) is a specialty biopharmaceutical company headquartered in Israel, primarily focused on the development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for the treatment of gastrointestinal and inflammatory diseases and cancer. RedHill has a U.S. co-promotion agreement with Concordia for Donnatal®, a prescription oral adjunctive drug used in the treatment of IBS and acute enterocolitis, as well as an exclusive license agreement with Entera Health for EnteraGam®, a medical food intended for the dietary management, under medical supervision, of chronic diarrhea and loose stools. RedHill’s clinical-stage pipeline includes: (i) RHB-105 - an oral combination therapy for the treatment of Helicobacter pylori infection with successful results from a first Phase III study; (ii) RHB-104 - an oral combination therapy for the treatment of Crohn's disease with an ongoing first Phase III study, a completed proof-of-concept Phase IIa study for multiple sclerosis and QIDP status for nontuberculous mycobacteria (NTM) infections; (iii) BEKINDA® (RHB-102) - a once-daily oral pill formulation of ondansetron with an ongoing Phase III study for acute gastroenteritis and gastritis and an ongoing Phase II study for IBS-D; (iv) RHB-106 - an encapsulated bowel preparation licensed to Salix Pharmaceuticals, Ltd.; (v) YELIVA® (ABC294640) - a Phase II-stage, orally-administered, first-in-class SK2 selective inhibitor targeting multiple oncology, inflammatory and gastrointestinal indications; (vi) MESUPRON - a Phase II-stage first-in-class, orally-administered protease inhibitor, targeting pancreatic cancer and other solid tumors and (vii) RIZAPORT® (RHB-103) - an oral thin film formulation of rizatriptan for acute migraines, with a U.S. NDA currently under discussion with the FDA and marketing authorization received in two EU member states under the European Decentralized Procedure (DCP). More information about the Company is available at: www.redhillbio.com. 1 The poster was authored by Ira N. Kalfus, MD, Medical Director, RedHill Biopharma; Gilead Raday, Chief Operating Officer, RedHill Biopharma; Reza Fathi, PhD, Senior VP R&D, RedHill Biopharma and David Y. Graham, MD, Professor of Medicine, Molecular Virology and Microbiology, Baylor College of Medicine. This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements may be preceded by the words “intends,” “may,” “will,” “plans,” “expects,” “anticipates,” “projects,” “predicts,” “estimates,” “aims,” “believes,” “hopes,” “potential” or similar words. Forward-looking statements are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Company’s control, and cannot be predicted or quantified and consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, risks and uncertainties associated with (i) the initiation, timing, progress and results of the Company’s research, manufacturing, preclinical studies, clinical trials, and other therapeutic candidate development efforts; (ii) the Company’s ability to advance its therapeutic candidates into clinical trials or to successfully complete its preclinical studies or clinical trials; (iii) the extent and number of additional studies that the Company may be required to conduct and the Company’s receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings, approvals and feedback; (iv) the manufacturing, clinical development, commercialization, and market acceptance of the Company’s therapeutic candidates; (v) the Company’s ability to successfully market Donnatal® and EnteraGam®, (vi) the Company’s ability to establish and maintain corporate collaborations; (vii) the Company's ability to acquire products approved for marketing in the U.S. that achieve commercial success and build its own marketing and commercialization capabilities; (viii) the interpretation of the properties and characteristics of the Company’s therapeutic candidates and of the results obtained with its therapeutic candidates in research, preclinical studies or clinical trials; (ix) the implementation of the Company’s business model, strategic plans for its business and therapeutic candidates; (x) the scope of protection the Company is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; (xi) parties from whom the Company licenses its intellectual property defaulting in their obligations to the Company; and (xii) estimates of the Company’s expenses, future revenues capital requirements and the Company’s needs for additional financing; (xiii) competitive companies and technologies within the Company’s industry. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's filings with the Securities and Exchange Commission (SEC), including the Company's Annual Report on Form 20-F filed with the SEC on February 23, 2017. All forward-looking statements included in this Press Release are made only as of the date of this Press Release. We assume no obligation to update any written or oral forward-looking statement unless required by law.


TEL-AVIV, Israel, May 04, 2017 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company primarily focused on the development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, today announced the presentation of a poster at Digestive Disease Week (DDW) 2017. The poster (presentation number: Sa1200) will be presented by Ira Kalfus, MD, Medical Director at RedHill, on Saturday, May 6, 2017 from 12:00 PM to 2:00 PM CDT, in Chicago, IL. The poster1 presentation, entitled “ERADICATE Hp: A Randomized, Double-Blind, Placebo-Controlled Phase III Study to Assess the Safety and Efficacy of Rifabutin Triple Therapy (RHB-105) for Helicobacter pylori (H. pylori) Infection in Dyspepsia Patients” describes the previously reported positive final results of the ERADICATE Hp first Phase III study with RHB-105 for H. pylori infection. RHB-105 is a proprietary, fixed-dose, oral combination therapy for the eradication of H. pylori infection. The ERADICATE Hp first Phase III study with RHB-105 successfully met its protocol-defined mITT primary endpoint of superiority over historical standard-of-care (SoC) eradication rate of 70%, with high statistical significance (p<0.001). The study results demonstrated 89.4% efficacy in eradicating H. pylori infection with RHB-105. Notably, the 89.4% efficacy in eradicating H. pylori infection with RHB-105 was also superior to subsequent open-label treatment with SoC therapies of patients in the placebo arm of the ERADICATE Hp study, which demonstrated 63% eradication rate in the mITT population (p=0.006), further supporting the potential efficacy of RHB-105 as a treatment for H. pylori infection. Treatment with RHB-105 appeared to be safe and well tolerated. A confirmatory Phase III study is planned to be initiated in the second quarter of 2017. The two-arm, randomized, double-blind, active comparator confirmatory Phase III study will compare RHB-105 against a dual therapy amoxicillin and omeprazole regimen at equivalent doses. The study is planned to enroll approximately 440 patients in up to 55 clinical sites in the U.S. Subject to its successful completion, the planned confirmatory Phase III study, along with the results from the successfully completed first Phase III ERADICATE Hp study with RHB-105 and data to be obtained from an ongoing supportive PK program, are expected to support a U.S. New Drug Application (NDA) for RHB-105. About RHB-105: RHB-105 is a new and proprietary fixed-dose oral combination therapy of two antibiotics and a proton pump inhibitor (PPI) in an all-in-one oral capsule with a planned indication for the treatment of H. pylori infection. H. pylori bacterial infection is a major cause of chronic gastritis, peptic ulcer disease, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. A first Phase III study with RHB-105 was completed in the U.S. with positive results (ERADICATE Hp study). The study demonstrated an overall success rate of 89.4% in eradicating H. pylori, and met its protocol-defined primary endpoint of superiority in eradication of H. pylori infection over historical standard-of-care efficacy levels of 70%, with high statistical significance (p<0.001). A confirmatory Phase III study is planned to be initiated in the U.S in the second quarter of 2017. Additional studies may be required, subject to FDA review. RHB-105 has been granted Qualifying Infectious Disease Product (QIDP) designation by the FDA, providing a Fast-Track development pathway, as well as NDA Priority Review status, potentially leading to a shorter NDA review time by the FDA, if filed. If approved, RHB-105 will also receive an additional five years of exclusivity, in addition to the standard exclusivity period, for a total of 8 years of U.S. market exclusivity. About RedHill Biopharma Ltd.: RedHill Biopharma Ltd. (NASDAQ:RDHL) (Tel-Aviv Stock Exchange:RDHL) is a specialty biopharmaceutical company headquartered in Israel, primarily focused on the development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for the treatment of gastrointestinal and inflammatory diseases and cancer. RedHill has a U.S. co-promotion agreement with Concordia for Donnatal®, a prescription oral adjunctive drug used in the treatment of IBS and acute enterocolitis, as well as an exclusive license agreement with Entera Health for EnteraGam®, a medical food intended for the dietary management, under medical supervision, of chronic diarrhea and loose stools. RedHill’s clinical-stage pipeline includes: (i) RHB-105 - an oral combination therapy for the treatment of Helicobacter pylori infection with successful results from a first Phase III study; (ii) RHB-104 - an oral combination therapy for the treatment of Crohn's disease with an ongoing first Phase III study, a completed proof-of-concept Phase IIa study for multiple sclerosis and QIDP status for nontuberculous mycobacteria (NTM) infections; (iii) BEKINDA® (RHB-102) - a once-daily oral pill formulation of ondansetron with an ongoing Phase III study for acute gastroenteritis and gastritis and an ongoing Phase II study for IBS-D; (iv) RHB-106 - an encapsulated bowel preparation licensed to Salix Pharmaceuticals, Ltd.; (v) YELIVA® (ABC294640) - a Phase II-stage, orally-administered, first-in-class SK2 selective inhibitor targeting multiple oncology, inflammatory and gastrointestinal indications; (vi) MESUPRON - a Phase II-stage first-in-class, orally-administered protease inhibitor, targeting pancreatic cancer and other solid tumors and (vii) RIZAPORT® (RHB-103) - an oral thin film formulation of rizatriptan for acute migraines, with a U.S. NDA currently under discussion with the FDA and marketing authorization received in two EU member states under the European Decentralized Procedure (DCP). More information about the Company is available at: www.redhillbio.com. 1 The poster was authored by Ira N. Kalfus, MD, Medical Director, RedHill Biopharma; Gilead Raday, Chief Operating Officer, RedHill Biopharma; Reza Fathi, PhD, Senior VP R&D, RedHill Biopharma and David Y. Graham, MD, Professor of Medicine, Molecular Virology and Microbiology, Baylor College of Medicine. This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements may be preceded by the words “intends,” “may,” “will,” “plans,” “expects,” “anticipates,” “projects,” “predicts,” “estimates,” “aims,” “believes,” “hopes,” “potential” or similar words. Forward-looking statements are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Company’s control, and cannot be predicted or quantified and consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, risks and uncertainties associated with (i) the initiation, timing, progress and results of the Company’s research, manufacturing, preclinical studies, clinical trials, and other therapeutic candidate development efforts; (ii) the Company’s ability to advance its therapeutic candidates into clinical trials or to successfully complete its preclinical studies or clinical trials; (iii) the extent and number of additional studies that the Company may be required to conduct and the Company’s receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings, approvals and feedback; (iv) the manufacturing, clinical development, commercialization, and market acceptance of the Company’s therapeutic candidates; (v) the Company’s ability to successfully market Donnatal® and EnteraGam®, (vi) the Company’s ability to establish and maintain corporate collaborations; (vii) the Company's ability to acquire products approved for marketing in the U.S. that achieve commercial success and build its own marketing and commercialization capabilities; (viii) the interpretation of the properties and characteristics of the Company’s therapeutic candidates and of the results obtained with its therapeutic candidates in research, preclinical studies or clinical trials; (ix) the implementation of the Company’s business model, strategic plans for its business and therapeutic candidates; (x) the scope of protection the Company is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; (xi) parties from whom the Company licenses its intellectual property defaulting in their obligations to the Company; and (xii) estimates of the Company’s expenses, future revenues capital requirements and the Company’s needs for additional financing; (xiii) competitive companies and technologies within the Company’s industry. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's filings with the Securities and Exchange Commission (SEC), including the Company's Annual Report on Form 20-F filed with the SEC on February 23, 2017. All forward-looking statements included in this Press Release are made only as of the date of this Press Release. We assume no obligation to update any written or oral forward-looking statement unless required by law.


TEL-AVIV, Israel, May 04, 2017 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company primarily focused on the development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, today announced the presentation of a poster at Digestive Disease Week (DDW) 2017. The poster (presentation number: Sa1200) will be presented by Ira Kalfus, MD, Medical Director at RedHill, on Saturday, May 6, 2017 from 12:00 PM to 2:00 PM CDT, in Chicago, IL. The poster1 presentation, entitled “ERADICATE Hp: A Randomized, Double-Blind, Placebo-Controlled Phase III Study to Assess the Safety and Efficacy of Rifabutin Triple Therapy (RHB-105) for Helicobacter pylori (H. pylori) Infection in Dyspepsia Patients” describes the previously reported positive final results of the ERADICATE Hp first Phase III study with RHB-105 for H. pylori infection. RHB-105 is a proprietary, fixed-dose, oral combination therapy for the eradication of H. pylori infection. The ERADICATE Hp first Phase III study with RHB-105 successfully met its protocol-defined mITT primary endpoint of superiority over historical standard-of-care (SoC) eradication rate of 70%, with high statistical significance (p<0.001). The study results demonstrated 89.4% efficacy in eradicating H. pylori infection with RHB-105. Notably, the 89.4% efficacy in eradicating H. pylori infection with RHB-105 was also superior to subsequent open-label treatment with SoC therapies of patients in the placebo arm of the ERADICATE Hp study, which demonstrated 63% eradication rate in the mITT population (p=0.006), further supporting the potential efficacy of RHB-105 as a treatment for H. pylori infection. Treatment with RHB-105 appeared to be safe and well tolerated. A confirmatory Phase III study is planned to be initiated in the second quarter of 2017. The two-arm, randomized, double-blind, active comparator confirmatory Phase III study will compare RHB-105 against a dual therapy amoxicillin and omeprazole regimen at equivalent doses. The study is planned to enroll approximately 440 patients in up to 55 clinical sites in the U.S. Subject to its successful completion, the planned confirmatory Phase III study, along with the results from the successfully completed first Phase III ERADICATE Hp study with RHB-105 and data to be obtained from an ongoing supportive PK program, are expected to support a U.S. New Drug Application (NDA) for RHB-105. About RHB-105: RHB-105 is a new and proprietary fixed-dose oral combination therapy of two antibiotics and a proton pump inhibitor (PPI) in an all-in-one oral capsule with a planned indication for the treatment of H. pylori infection. H. pylori bacterial infection is a major cause of chronic gastritis, peptic ulcer disease, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. A first Phase III study with RHB-105 was completed in the U.S. with positive results (ERADICATE Hp study). The study demonstrated an overall success rate of 89.4% in eradicating H. pylori, and met its protocol-defined primary endpoint of superiority in eradication of H. pylori infection over historical standard-of-care efficacy levels of 70%, with high statistical significance (p<0.001). A confirmatory Phase III study is planned to be initiated in the U.S in the second quarter of 2017. Additional studies may be required, subject to FDA review. RHB-105 has been granted Qualifying Infectious Disease Product (QIDP) designation by the FDA, providing a Fast-Track development pathway, as well as NDA Priority Review status, potentially leading to a shorter NDA review time by the FDA, if filed. If approved, RHB-105 will also receive an additional five years of exclusivity, in addition to the standard exclusivity period, for a total of 8 years of U.S. market exclusivity. About RedHill Biopharma Ltd.: RedHill Biopharma Ltd. (NASDAQ:RDHL) (Tel-Aviv Stock Exchange:RDHL) is a specialty biopharmaceutical company headquartered in Israel, primarily focused on the development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for the treatment of gastrointestinal and inflammatory diseases and cancer. RedHill has a U.S. co-promotion agreement with Concordia for Donnatal®, a prescription oral adjunctive drug used in the treatment of IBS and acute enterocolitis, as well as an exclusive license agreement with Entera Health for EnteraGam®, a medical food intended for the dietary management, under medical supervision, of chronic diarrhea and loose stools. RedHill’s clinical-stage pipeline includes: (i) RHB-105 - an oral combination therapy for the treatment of Helicobacter pylori infection with successful results from a first Phase III study; (ii) RHB-104 - an oral combination therapy for the treatment of Crohn's disease with an ongoing first Phase III study, a completed proof-of-concept Phase IIa study for multiple sclerosis and QIDP status for nontuberculous mycobacteria (NTM) infections; (iii) BEKINDA® (RHB-102) - a once-daily oral pill formulation of ondansetron with an ongoing Phase III study for acute gastroenteritis and gastritis and an ongoing Phase II study for IBS-D; (iv) RHB-106 - an encapsulated bowel preparation licensed to Salix Pharmaceuticals, Ltd.; (v) YELIVA® (ABC294640) - a Phase II-stage, orally-administered, first-in-class SK2 selective inhibitor targeting multiple oncology, inflammatory and gastrointestinal indications; (vi) MESUPRON - a Phase II-stage first-in-class, orally-administered protease inhibitor, targeting pancreatic cancer and other solid tumors and (vii) RIZAPORT® (RHB-103) - an oral thin film formulation of rizatriptan for acute migraines, with a U.S. NDA currently under discussion with the FDA and marketing authorization received in two EU member states under the European Decentralized Procedure (DCP). More information about the Company is available at: www.redhillbio.com. 1 The poster was authored by Ira N. Kalfus, MD, Medical Director, RedHill Biopharma; Gilead Raday, Chief Operating Officer, RedHill Biopharma; Reza Fathi, PhD, Senior VP R&D, RedHill Biopharma and David Y. Graham, MD, Professor of Medicine, Molecular Virology and Microbiology, Baylor College of Medicine. This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements may be preceded by the words “intends,” “may,” “will,” “plans,” “expects,” “anticipates,” “projects,” “predicts,” “estimates,” “aims,” “believes,” “hopes,” “potential” or similar words. Forward-looking statements are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Company’s control, and cannot be predicted or quantified and consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, risks and uncertainties associated with (i) the initiation, timing, progress and results of the Company’s research, manufacturing, preclinical studies, clinical trials, and other therapeutic candidate development efforts; (ii) the Company’s ability to advance its therapeutic candidates into clinical trials or to successfully complete its preclinical studies or clinical trials; (iii) the extent and number of additional studies that the Company may be required to conduct and the Company’s receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings, approvals and feedback; (iv) the manufacturing, clinical development, commercialization, and market acceptance of the Company’s therapeutic candidates; (v) the Company’s ability to successfully market Donnatal® and EnteraGam®, (vi) the Company’s ability to establish and maintain corporate collaborations; (vii) the Company's ability to acquire products approved for marketing in the U.S. that achieve commercial success and build its own marketing and commercialization capabilities; (viii) the interpretation of the properties and characteristics of the Company’s therapeutic candidates and of the results obtained with its therapeutic candidates in research, preclinical studies or clinical trials; (ix) the implementation of the Company’s business model, strategic plans for its business and therapeutic candidates; (x) the scope of protection the Company is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; (xi) parties from whom the Company licenses its intellectual property defaulting in their obligations to the Company; and (xii) estimates of the Company’s expenses, future revenues capital requirements and the Company’s needs for additional financing; (xiii) competitive companies and technologies within the Company’s industry. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's filings with the Securities and Exchange Commission (SEC), including the Company's Annual Report on Form 20-F filed with the SEC on February 23, 2017. All forward-looking statements included in this Press Release are made only as of the date of this Press Release. We assume no obligation to update any written or oral forward-looking statement unless required by law.


CANTON, Ohio & BURLINGTON, Mass.--(BUSINESS WIRE)--Unit4 announces that Aultman College has selected Unit4 Student Management on the Microsoft Azure Cloud to modernize its students’ experience and campus-wide processes to support growth. Aultman College has been educating health care professionals for more than 120 years. Located in Canton, Ohio, it is Northeast Ohio’s only health system affiliated institution of higher learning, and shares a campus with Aultman Hospital, Stark County’s largest hospital and employer. Unit4 Student Management will replace a number of outdated legacy systems, providing students with a completely new, seamless digital and mobile experience across the entire academic lifecycle from admissions and course registration to managing financial aid. It will also provide staff with valuable aggregated insights into student performance so they can help keep students on track. “Aultman College is entering a period of significant growth and program development. Unit4 will help us not only reach new students in ways we haven’t before, but also provide outstanding service and communication to our current students,” said Jacqui Schmotzer, IT Director, Aultman College. “The Unit4 team has been fantastic to work with, and we are excited about the modern and mobile-first capabilities the solution offers throughout the student lifecycle. Unit4 gives us the right solution for cloud migration as we’re confident we’ll see a rapid and convincing return on investment. We’ll be able to significantly reduce manual and duplicate processes we’ve developed over time. As we’re anticipating significant growth in the number of enrolling students over the next few years, it’s vital we rethink and revaluate our current processes to support student success and retention.” About Unit4 Unit4 is a leading provider of enterprise applications empowering people in service organizations. Unit4 delivers ERP, industry-focused and best-in-class applications. Thousands of organizations from sectors including professional services, education, public services, not-for-profit, real estate, wholesale, and financial services benefit from Unit4 solutions. Unit4 provides student management, ERP and research management solutions to over 1000 colleges and universities globally to help them accelerate growth, boost student success, improve institutional effectiveness and deliver research excellence. Clients include Oxford and Cambridge Universities, HEC Paris, University of Waterloo, American University of Paris, Robert Morris University, Baylor College of Medicine, Hult International, and University of Dubai. Unit4 is in business for people. For more information, please visit the website at www.unit4.com, follow us on Twitter @Unit4_NA, or visit our LinkedIn page


News Article | April 28, 2017
Site: www.eurekalert.org

Bethesda, MD (April 28, 2017) -- The American Gastroenterological Association (AGA) Research Foundation is thrilled to award 52 researchers with research funding in the 2017 award year. "The AGA Research Foundation has a proven track record of funding young investigators who subsequently achieve great success in research. We are confident that the 2017 class will be no exception," said Robert S. Sandler, MD, MPH, AGAF, chair, AGA Research Foundation. "AGA is honored to invest in this year's award recipients and looks forward to seeing how each research project contributes to advancing the field of gastroenterology." The AGA Research Award Program serves to support talented investigators who are pursuing careers in digestive disease research. A grant from the AGA Research Foundation ensures that a major proportion of the recipient's time is protected for research. The awards program is made possible thanks to generous donors and funders contributing to the AGA Research Foundation. Show your support for GI research.https:/ Below are the 2017 AGA Research Foundation award recipients. To learn about upcoming research funding opportunities, visit http://www. . Shrinivas Bishu, MD, University of Michigan, Ann Arbor David Boone, PhD, Indiana University School of Medicine, Indianapolis Sarah Glover, DO, University of Florida, Gainesville Jennifer Lai, MD, MBA, The Regents of the University of California, San Francisco Jill Smith, MD, Georgetown University, Washington, D.C. Chandler Brown, Gallaudet University, Washington, D.C. Carlos Lodeiro, Texas Tech University Health Sciences Center El Paso Paul L. Foster School of Medicine Alyssa Murillo, University of Illinois at Chicago College of Medicine Kristeen Onyirioha, University of Texas San Antonio Health Sciences Center Gabriela Portilla Skerrett, San Juan Bautista School of Medicine, Puerto Rico Ray Ramirez, Eastern Virginia Medical School, Norfolk Rani Richardson, University of Pennsylvania, Philadelphia Nefertiti Tyehemba, State University of New York Upstate Medical University, Syracuse Elsie Ureta, California State University of Los Angeles Carlos Zavala, University of Illinois at Urbana-Champaign Edward Barnes, MD, MPH, University of North Carolina School of Medicine, Chapel Hill Daniel Duncan, MD, Boston Children's Hospital, MA Amy Engevik, PhD, Vanderbilt University, Nashville Tossapol Kerdsirichairat, MD, University of Michigan Health System, Ann Arbor Anne-Marie Overstreet, PhD, Indiana University School of Medicine, Indianapolis Shusuke Toden, PhD, Baylor University Medical Center/Baylor Research Institute, Houston Amy Tsou, MD, PhD, Boston Children's Hospital, MA Lavanya Viswanathan, MD, MS, Augusta University, GA Hongtao Wang, MD, PhD, Baylor College of Medicine and Texas Children's Hospital, Houston Lauren Cole, BS, University of Arizona College of Medicine, Phoenix Cindy Law, BSc, University of Ottawa, Canada Christopher Moreau, BS, University of Texas Health Science Center at San Antonio Satish Munigala, MBBS, MPH, St. Louis University, MO Rajiv Perinbasekar, MD, University of Maryland Medical Center, Baltimore Chung Sang Tse, MD, Mayo Clinic, Rochester, MN Anika Ullah, University of California, San Diego Kathy Williams, MS, Cooper Medical School of Rowan University, Camden, NJ Quan Zhou, MS, University of Michigan, Ann Arbor This year's honorees will be recognized during several AGA Research Foundation events at Digestive Disease Week® 2017, taking place May 6-9 in Chicago, IL. The American Gastroenterological Association is the trusted voice of the GI community. Founded in 1897, the AGA has grown to more than 16,000 members from around the globe who are involved in all aspects of the science, practice and advancement of gastroenterology. The AGA Institute administers the practice, research and educational programs of the organization.http://www. . Like AGA on Facebook.http://www. facebook. com/ amergastroassn> Follow us on Twitter @AmerGastroAssn.http://www. twitter. com/ amergastroassn> Check out our videos on YouTube.http://www. The AGA Research Foundation, formerly known as the Foundation for Digestive Health and Nutrition, is the cornerstone of AGA's effort to expand digestive disease research funding. Since 1984, the AGA, through its foundations, has provided more than $47 million in research grants to more than 870 scientists. The AGA Research Foundation serves as a bridge to the future of research in gastroenterology and hepatology by providing critical funding to advance the careers of young researchers between the end of training and the establishment of credentials that earn National Institutes of Health grants. Learn more about the AGA Research Foundation or make a contribution at http://www. .


News Article | April 17, 2017
Site: www.futurity.org

Whereas humans can look at a complex landscape like a mountain vista and almost immediately orient themselves to navigate its multiple regions over long distances, other mammals such as rodents orient relative to physical cues—like approaching and sniffing a wall—that build up over time. This ability to navigate our surroundings and understand our relative position includes an environment-dependent scaling mechanism, according to a new study. “Our research, based on human data, redefines the fundamental properties of the internal coordinate system,” says Zoltan Nadasdy, lead author of the study and an adjunct assistant professor in the University of Texas at Austin’s psychology department. Nadasdy is also a researcher at Eötvös Loránd University and the Sarah Cannon Research Institute at St. David’s Medical Center. “Dysfunction in this system causes memory problems and disorientation, such as we see in Alzheimer’s disease and age-related decline. So, it’s vital that we continue to further our understanding of this part of the brain,” he says. Through a partnership with Seton Healthcare Family, the researchers in the UT Austin Human Brain Stimulation and Electrophysiology Lab were able to measure relevant brain activity of epileptic patients whose diagnostic procedure requires that they have electrodes planted in the entorhinal cortex of the brain. Neurons there serve as the internal coordinate system for humans. (The brains of individuals with epilepsy function normally when not undergoing a seizure.) Patients performed a virtual navigation task on a tablet computer in four environments daily for seven to eight consecutive days. By measuring their brain activity, the researchers identified three previously unknown traits of the system: The findings illuminate the fabric of the human memory and spatial navigation, which are vulnerable to disease and deterioration. Deeper knowledge of these neuronal mechanisms can inform the development of techniques to prolong the health of this part of the brain and combat diseases such as Alzheimer’s. The study, published in the Proceedings of the National Academy of Sciences, builds on earlier Nobel Prize-winning research exploring the entorhinal cortex of rodents. Due to the differences discovered between the human and rodent systems of navigation, the researchers emphasize that generalizing results from studies on animal subjects may provide inaccurate conjectures. This study is one of the few on human subjects that report on the activity of individual neuron behavior, says György Buzsáki, an expert from New York University Medical Center who was not involved in the research. “They not only confirm a previous report but extend the findings by showing that the size of the neuronal representation by entorhinal grid cells scales with the environment,” Buzsáki says. “Our hypothesis is challenging the definition of a universal spatial scale of environment predominant in lower mammals, which may open up important avenues of discovery,” says Robert Buchanan, another lead author of the study and an associate professor at Dell Medical School. He is also an adjunct associate professor in the university’s psychology department and a chief of neurosurgery at Seton Brain and Spine Institute. “Now, we can continue to explore this key component of what it means to be human—how we think about our past and future, how we imagine and plan,” Buchanan says. By using virtual reality, the researchers also refined a new experimental technology for facilitating spatial experiences that can’t be reproduced in a laboratory. The data implies that humans can seamlessly switch between reality and virtual reality—a finding that can be applied in other studies of the brain. Additional coauthors are from Baylor College of Medicine; Eötvös Loránd University and Hungarian Academy of Sciences; and UT Austin’s Dell Medical School and Seton Brain and Spine Institute. The Brain and Behavior Research Foundation and the Seton Seed Grant for Research supported the work.


Zitnik M.,University of Ljubljana | Zupan B.,University of Ljubljana | Zupan B.,Baylor College of Medicine
IEEE Transactions on Pattern Analysis and Machine Intelligence | Year: 2015

For most problems in science and engineering we can obtain data sets that describe the observed system from various perspectives and record the behavior of its individual components. Heterogeneous data sets can be collectively mined by data fusion. Fusion can focus on a specific target relation and exploit directly associated data together with contextual data and data about system's constraints. In the paper we describe a data fusion approach with penalized matrix tri-factorization (DFMF) that simultaneously factorizes data matrices to reveal hidden associations. The approach can directly consider any data that can be expressed in a matrix, including those from feature-based representations, ontologies, associations and networks. We demonstrate the utility of DFMF for gene function prediction task with eleven different data sources and for prediction of pharmacologic actions by fusing six data sources. Our data fusion algorithm compares favorably to alternative data integration approaches and achieves higher accuracy than can be obtained from any single data source alone. © 2014 IEEE.


Metzker M.L.,Baylor College of Medicine | Metzker M.L.,LaserGen
Nature Reviews Genetics | Year: 2010

Demand has never been greater for revolutionary technologies that deliver fast, inexpensive and accurate genome information. This challenge has catalysed the development of next-generation sequencing (NGS) technologies. The inexpensive production of large volumes of sequence data is the primary advantage over conventional methods. Here, I present a technical review of template preparation, sequencing and imaging, genome alignment and assembly approaches, and recent advances in current and near-term commercially available NGS instruments. I also outline the broad range of applications for NGS technologies, in addition to providing guidelines for platform selection to address biological questions of interest. © 2010 Macmillan Publishers Limited. All rights reserved.


Yoshimura T.,Baylor College of Medicine | Yoshimura T.,National Institute for Physiological science | Rasband M.N.,Baylor College of Medicine
Current Opinion in Neurobiology | Year: 2014

The axon initial segment (AIS) is a structurally and molecularly unique neuronal compartment of the proximal axon that functions as both a physiological and physical bridge between the somatodendritic and axonal domains. The AIS has two main functions: to initiate action potentials and to maintain neuronal polarity. The cytoskeletal scaffold ankyrinG is responsible for these functions and clusters ion channels at the AIS. Recent studies reveal how the AIS forms and remarkable diversity in its structure, function, and composition that may be modulated by neuronal activity and posttranslational modifications of AIS proteins. Furthermore, AIS proteins have been implicated in a variety of human diseases. Here, we discuss these findings and what they teach us about the dynamic AIS. © 2014 Elsevier Ltd.


Sittig D.F.,University of Texas Health Science Center at Houston | Singh H.,Baylor College of Medicine
New England Journal of Medicine | Year: 2012

To create a coordinated, consistent, national strategy that will address the safety issues posed by EHRs, we propose that a concerted effort be made to improve health care safety in the context of technology use. This effort should address preventable risks that may hamper endeavors to create a safer EHR-enabled health care system. Further discussion and consensus among national agencies (e.g., the Office of the National Coordinator for Health Information Technology [ONC], the AHRQ, the Joint Commission, the Centers for Medicare and Medicaid Services) is clearly necessary for the adoption of future national patient-safety goals specific to EHR use. However, this approach must be given immediate priority considering the rapid pace of EHR adoption and the resulting changes in our nation's health care system. National EHR-related patient-safety goals are needed to address current problems with existing EHR implementations and failures to leverage current EHR capabilities. For instance, the ONC has recently taken several important steps in this direction with release of the revised 2014 EHR certification criteria (e.g., emphasis on user-centered design and application of quality management systems in the EHR design and development process58). Such efforts should be expanded in the future. Goals must be technically feasible, financially prudent, and practically achievable within current constraints and be accompanied by specific guidance on achieving them. Input on these goals must be sought not only from EHR developers and clinical end users but also from cognitive scientists, human-factors engineers, graphic designers, and informaticians with expertise in patient safety in complex health care environments. Creating unique EHR-related national patient-safety goals will provide new momentum for patient-safety initiatives in an EHR-enabled health system. Copyright © 2012 Massachusetts Medical Society.


Nolan M.S.,Baylor College of Medicine | Murray K.O.,Baylor College of Medicine
Emerging Infectious Diseases | Year: 2013

We conducted an epidemiologic analysis to document West Nile virus infections among humans in Texas, USA, during 2002-2011. West Nile virus has become endemic to Texas; the number of reported cases increased every 3 years. Risk for infection was greatest in rural northwestern Texas, where Culex tarsalis mosquitoes are the predominant mosquito species.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.3.0-1 | Award Amount: 7.67M | Year: 2013

Approximately 600-700 million people are infected by hookworm, primarily in sub-Saharan Africa, Southeast Asia, and Latin America. Hookworm infection ranks number one in terms of Years Lost from Disability from a neglected infectious disease, and among the top 3 in terms of lost Disability-Adjusted Life Years. HOOKVAC will be developing the first and only vaccine for human hookworm infection. A bivalent, low-cost vaccine candidate will be clinically tested for the first time in an African disease endemic population. This will be done in Gabon in a very typical setting within the Central African rainforest belt, where the incidence of hookworm infections is 30%. Inspired by preparatory research, HOOKVAC believes that it can develop the vaccine with at least 80% efficacy against moderate and heavy hookworm infections that lasts at five years after immunization. Cost effectiveness modelling has shown that such a vaccine will significantly improve the efficacy of the current mass drug administration programs. HOOKVAC will play a crucial role in advancing toward large scale efficacy studies in African endemic areas. Via a program of 48 months with 6 work packages, HOOKVAC will address 4 main objectives: (1) establish safety and immunogenicity of the vaccine candidate in an endemic population (2) improve the manufacturing process (3) provide clinical proof of concept (4) improve accessibility of the vaccine in endemic areas. The involvement of European SMEs in the project is a critical component to advancing a successful vaccine, and an integral part of adding private sector know-how and scientific expertise to the project. This will inspire other European SMEs to become more involved in public/private vaccine product development for neglected infectious diseases. By doing so, HOOKVAC will fuel a follow-up programme for further development of the vaccine towards into a licensed product.


Grant
Agency: European Commission | Branch: FP7 | Program: CSA-CA | Phase: HEALTH.2010.2.1.1-2 | Award Amount: 2.29M | Year: 2011

A detailed understanding of human biology will require characterisation of the human-associated microorganisms, the human microbiome, and of the roles these microbes play in health and disease. Large projects in Europe, the United States, China and Canada target these objectives, using high throughput omics approaches. Given the complexity of our microbial communities, composed of thousands of species and differing considerably between individuals, as well as the multitude of effects they have on our biology, none of the projects can hope to achieve their comprehensive characterisation. To progress most efficiently towards this ambitious goal it is of utmost importance that the data generated in each individual project be optimally comparable across all the current projects and those yet to come. Our proposal seeks to coordinate development of standard operating procedures and protocols, which will optimize data comparisons in the human microbiome field and thus improve the synergy between all the projects. It focuses on three key aspects of data generation: (i) human sample collection, processing and identification via the associated metadata; (ii) DNA sequence quality obtained by the new generation methods from complex microbial mixtures; (iii) analysis of DNA sequence in conjunction with the metadata. Importantly, it organises public access to the standard operating procedures and protocols and enables exchanges between the users and providers of the standards. It gathers very strong international partnership that includes leaders in the field and represents the current large projects, which span three continents, Europe, Asia and America. Furthermore, it interfaces via the International Human Microbiome Consortium with additional projects from Africa and Australia. The proposal is thus highly congruent with the focus of the call, which targets omics, standards and international context.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: KBBE.2013.2.2-02 | Award Amount: 13.01M | Year: 2013

Emerging evidence indicates that the gut microbiome contributes to our ability to extract energy from the diet and influences development and function of the immune, endocrine and nervous systems, which regulate energy balance and behaviour. This has led to hypothesize that developing microbiome-based dietary interventions can be cost-effective measures to prevent diet-related and behavioural disorders. Yet this approach is restricted in practice by a lack of understanding of the specific species that contribute to these disorders and their interactions with host and lifestyle determinants. To progress beyond the state of the art, the MyNewGut proposal aims to: (1) shed light on the contribution of the human microbiome to nutrient metabolism and energy expenditure; (2) identify microbiome-related features that contribute to or predict obesity and associated disorders in human epidemiological studies; (3) understand how the microbiome is influenced by environmental factors and its role in brain and immune development and function in humans; and (4) provide proof-of-concept of the disease risk-reduction potential of dietary intervention with new foods/ingredients targeting the gut microbiome in humans. To this end, a translational multidisciplinary research strategy will be developed, combining experts in omic-technologies and all other scientific disciplines required. Consequently, the MyNewGut proposal will contribute to developing new approaches to prevent diet-related diseases (metabolic syndrome and obesity) and behavioural disorders through lifestyle changes, intake of pro- and prebiotics and semi-personalised and innovative food products. This will ultimately contribute to increasing the competitiveness of the European food industry and provide consumers with reliable claims on foods. Results will also help inform new strategies on public health, support EU legislation and improve the position of the EU in the field of food-related disease prevention.


HOUSTON - (March 2, 2017) - The University of Texas Health Science Center at Houston (UTHealth), in collaboration with the Human Genome Sequencing Center at Baylor College of Medicine (HGSC), is a participant in a $500 million program of the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program to bring whole genome sequencing and other "omic" technologies that monitor the expression of the genome in response to the environment to the forefront of clinical research. Through its TOPMed program, NHLBI is expanding its dedication to advancing the understanding of the underpinnings of complex diseases and how they develop. Previously, the HGSC was awarded funding by NHLBI to sequence whole genomes for TOPMed studies such as sickle cell disease, and venous thromboembolism and will continue to expand this effort in the next phase of the program. The new contract will span five years. In addition to the whole genome sequencing component, the TOPMed program will also provide analysis of other datatypes over the course of the contract period, including RNA transcription sequencing, DNA methylation, metabolomics profiles, and other "omics," including analysis of the microbiome. The initial award from NHLBI supports the whole genome sequencing of 20,000 samples at the HGSC in the first year of the program. To support this trans-omic approach, the HGSC will continue its ongoing collaboration with the Alkek Center for Metagenomics and Microbiome Research (CMMR) at Baylor and UTHealth School of Public Health, which would aid in executing the methylation and metabolomics tasks. The team was deemed eligible to perform all elements of these additional analyses. "The TOPMed program and resulting data will allow us to better understand the link between pediatric and adult disease genes, thereby creating enhanced diagnostics for adult diseases and disorders. There are direct clinical applications to improve and individualize care for these adult diseases within the Texas Medical Center," said Eric Boerwinkle, Ph.D., dean of UTHealth School of Public Health and associate director of the HGSC. "There is a significant need for large sample sizes; a need that goes beyond the research setting and into the clinic," said Richard Gibbs, Ph.D., director of the HGSC and professor of molecular and human genetics at Baylor. "We are grateful to be a part of the TOPMed program which will allow us to access this large sample number and obtain valuable insights into adult heart disease, sickle cell disease, atrial fibrillation and other heart, lung and hematologic disorders." The HGSC has been operational for more than 20 years, gaining international recognition as a large-scale DNA sequencing and analysis center, and is currently a Center for Complex Disease Genomics supported by the National Institutes of Health and the National Human Genome Research Institute. A key mission of the HGSC is to use genetic approaches to guide discovery and diagnosis of human disease, which offers insight into new therapeutic strategies, echoing the bench-to-bedside framework that is the foundation of the national Precision Medicine Initiative. This mission has been greatly enhanced and facilitated by a collaboration with Boerwinkle, who leads a group of population and data scientists at UTHealth with expertise in analyzing genomic information to discover new disease genes and improve diagnosis. The TOPMed project will better enable the HGSC and UTHealth to pursue this mission to move adult whole genome sequencing into the clinical setting, supporting the advance of precision medicine. The whole genome and other data made available by TOPMed has the capability to be analyzed to provide a more comprehensive picture of what factors may lead to, or protect against, common disease development. The UTHealth team is one of four analysis centers in the country catalyzing new discoveries using this data. The flow of data will begin with the HGSC, which will receive samples from NHLBI investigators. The HGSC will perform the whole genome sequencing, and is eligible for RNA sequencing, operably distributing the samples to UTHealth for methylation and metabolomics profiling, and to Baylor's CMMR for metagenomic analysis as program needs dictate. The data from all three sources would then be funneled into a data sharing portal and relayed back to TOPMed. -Adapted from a news release by Baylor College of Medicine


News Article | November 21, 2016
Site: www.eurekalert.org

A cellular component known as the Golgi apparatus may play a role in how lung cancer metastasizes, according to researchers at The University of Texas MD Anderson Cancer Center whose findings were reported in the Nov. 21 online issue of the Journal of Clinical Investigation. The Golgi apparatus, often referred to as a cellular "post office" for its ability to package proteins into vesicles for transportation to other sites within or outside the cell, may offer a new therapeutic approach for preventing metastasis. Think of vesicles as miniature mail trucks composed of a fatty shell filled with secretory liquids that travel from the Golgi to destinations within the cell where their contents are put to use. The Golgi can appear as a compacted membranous "stack" near the cell's nucleus or as a dispersed system of interconnected membranes. Vesicles can "bud" from the Golgi in either form. "Our findings show that certain proteins in the Golgi that control Golgi compaction may actually promote vesicle budding and transport and enhance the tumor cell's ability to metastasize" said Jonathan Kurie, M.D., professor of Thoracic Head and Neck Medical Oncology. "These findings highlight the potential utility of targeting certain cellular processes in the Golgi." According to Kurie, tumor cells gain their metastatic ability through a Golgi-related process driving the budding and transport of secretory vesicles. Unknown before this study was whether Golgi compaction was responsible for vesicular trafficking leading to metastasis. This study shows that Golgi compaction is associated with EMT or epithelial-to-mesenchymal transition, a process that allows a cell to detach and move away from its neighbors during wound healing and other normal processes and is thought to play a role in cancer cell migration. Using lung adenocarcinoma cell lines isolated from mice and patients, Kurie's team found that EMT depends on a Golgi protein called PAQR11 for successful tumor cell migration and metastasis in lung cancers. "We concluded that, through PAQR11, tumor cells can hijack a normal Golgi compaction process in order to gain metastatic ability," said Kurie. MD Anderson study team participants included Xiaochao Tan, Ph.D.; Priyam Banerjee; Ph.D., Hou-Fu Guo, Ph.D.; Daniela Pankova, Ph.D.; Xin Liu, Ph.D.;Yongming Xue, Jonathon Roybal and Don Gibbons, M.D., all of Thoracic Head and Neck Medical Oncology; Tomasz Zal, Ph.D., Immunology; and Chad Creighton, Ph.D., Bioinformatics and Computational Biology. Other participating institutions include the University of Michigan, Ann Arbor, Mich.; Ewha Woman's University School of Medicine, Seoul, South Korea; University of York, York, U.K.; Harbin Medical University Cancer Hospital, Harbin, China; University of Houston and Baylor College of Medicine, Houston. The study was funded by the National Institutes of Health (R01CA181184, R01CA125123, GM087364, GM105920, GM112786P30, EY007551, K08CA151661, NRF-2010-0027945, CA015672, 1S10OD012304-01, and 1S10RR09552-01), the American Cancer Society (RGS-09-278-01-CSM), the Cancer Prevention Research Institute of Texas (RP120713), and MCubed and the Fastforward Protein Folding Disease Initiative at the University of Michigan.


News Article | November 22, 2016
Site: www.rdmag.com

Scientists from Rice University, Baylor College of Medicine and other institutions are using synthetic biology to capture elusive, short-lived snippets of DNA that healthy cells produce on their way to becoming cancerous. Researchers said the work could lead to the development of new drugs that could prevent cancer by neutralizing "DNA intermediates," key pieces of genetic code that are produced when healthy cells become cancerous. The research is described in a new paper in the open-access journal Science Advances. "In my lab we study how the genome -- the genes in an organism -- changes, in particular, how the genome of normal cells changes to transform the cells into cancerous cells," said project lead scientist Susan Rosenberg, Baylor's Ben F. Love Chair in Cancer Research and the leader of the Cancer Evolvability Program at Baylor's Dan L Duncan Comprehensive Cancer Center. When cells divide and make copies of the instructions encoded in their DNA, the DNA unwinds and becomes vulnerable to damage that must be repaired. Sometimes the process of repairing the DNA can also cause mutations and errors. When these errors accumulate, the cells may acquire characteristics of cancer. "The process of editing the DNA is carried out by specific enzymes -- proteins that work on DNA to fix the mistakes," said Rosenberg, who is also an adjunct professor in Rice's Department of BioSciences. She said DNA repair usually takes several steps to complete. Between the original DNA and the final product, cells produce DNA reaction intermediates, which are crucial to the reaction but are difficult to study because they are present for just a fraction of a second as an enzyme catalyzes the changing of one molecule into another. "The intermediate molecules are the most important parts of biochemical reactions," said Rosenberg, who holds appointments in Baylor's departments of Molecular and Human Genetics, Molecular Virology and Microbiology, and Biochemistry and Molecular Biology. "They define what the reaction is and how it will proceed. But because they are transient and elusive, it's really difficult to study them, especially in living cells. We wanted to do that. We decided to invent synthetic proteins that would trap DNA reaction intermediates in living cells." Qian Mei, a graduate student in Rice's Systems, Synthetic and Physical Biology program and a research assistant in the Rosenberg lab, took on the task of applying the synthetic protein that could capture the short-lived intermediates. Using the tools of synthetic biology, Rosenberg and colleagues created and added packages of genes to Escherichia coli, an organism that Rosenberg's group and others have shown to be a reliable model of the genetic changes that occur in animal cells. Rosenberg said other investigators also have attempted to trap intermediates, but they have only succeeded in a few biochemical reactions. "We want to use synthetic proteins to study mechanisms that change DNA sequence," she said. "We do that now with genetics and genomics in my lab. But genomics, which allows us to compare the genes of normal cells with those of cancerous cells, is like reading the fossil record of these processes. We want to see how the real-time processes that change DNA happen, including all the intermediate steps, which our synthetic proteins allow us to freeze in time and isolate." In their tests on , Mei, Rosenberg and colleagues from Baylor, the University of Texas at Austin and the University of Texas MD Anderson Cancer Center found they could discover molecular mechanisms underlying genome instability, a hallmark of cancer. In one instance, they discovered a new role for an protein that is related to five human cancer proteins. They then analyzed gene-expression data from human cancers and were able to implicate two of the five -related human cancer proteins in potentially promoting cancer by a similar mechanism -- one not previously implicated. "The most exciting part in this paper for me is that we can learn something new about the mechanisms of cancer from the model," said Mei, co-first author of the new paper. "Even though bacteria and human cells are very different, many DNA repair proteins are highly conserved through evolution; this makes a good model to study how cells repair DNA or accumulate mutations." Rosenberg and colleagues think that their approach offers significant advantages. For instance, with the synthetic proteins, they have been able to identify specific DNA-repair intermediate molecules, their numbers in cells, rates of formation and locations in the genome and the molecular reactions in which they participate. "It is most exciting that we are now able to trap, map and quantify transient DNA reaction intermediates in single living cells," said co-first author Jun Xia, graduate student in the Rosenberg lab and in the Integrative Molecular and Biomedical Sciences program at Baylor. "This new technology helps us reveal the origins of genome instability." "When you know these reactions and the role each intermediate plays in the mechanisms that change DNA, you can think about making drugs that will stop them," Rosenberg said. "In the future, we hope we will be able to design drugs that target specific types of cancers -- drugs that block the cells' ability to evolve into cancer cells, instead of, or in addition to, traditional chemotherapies that kill or stop cancer cells from growing."


News Article | November 11, 2016
Site: www.eurekalert.org

The feeding habits responsible for the ecological success of the Asian long-horned beetle have been pinned down to their unique genes, according to new research published by the open access journal Genome Biology. By comparing the genome of the Asian long-horned beetle with 14 other insects, the researchers were able to identify a suite of genes, some unique to this species, that aid the digestion of woody plant material and are likely responsible for the beetles ability to thrive in woodland regions all over the world. The Asian long-horned beetle is a globally invasive species capable of inflicting severe damage on many economically important trees. The potential economic impact in the United States, if uncontrolled, has been estimated at $889 billion. Dr Duane McKenna, co-lead author from the University of Memphis, said: "Our detailed genomic analysis reveals that the Asian long-horned beetle has over 1,000 genes that aren't present in any other arthropod. We identified a total of 86 genes for enzymes called glycoside hydrolases - more than have been found in any other insect. These enzymes enable the beetle to digest woody plant material and detoxify plant chemicals and so indicate a genetic reason for their apparent success in feeding on trees worldwide". Wood is a poor source of nutrients so any organism capable of surviving on a diet of woody plant material must have evolved unique characteristics that allow effective digestion and maximum extraction of energy. Dr McKenna added: "The arsenal of glycoside hydrolase enzymes that the Asian long-horned beetle has allows it to degrade all of the main polysaccharides present in plant cell walls, releasing the sugars it needs for energy. Importantly, the range of enzymes this beetle has is highly diverse, which we believe allows it to breakdown many different molecules present across a wide range of woody plants." The Asian long-horned beetle completes its entire development living and feeding within the wood of trees. In its earliest stage the larvae are specialized wood-borers, feeding on plant tissue under the bark. Later in its life cycle the larvae tunnel deeper into the wood where they continue to feed throughout their development. Adult beetles emerge from the tree and spend their relatively short life-span feeding on external parts of the tree. Dr Stephen Richards, co-lead author from Baylor College of Medicine Human Genome Sequencing Center in Texas, United States, said: "In this case, when we fed beetle larvae on wood material from sugar maple trees we found that the activity of the glycoside hydrolase genes was increased, something not seen in larvae fed on an artificial diet. This experiment, along with our complementary analysis of the beetle genome, also revealed the specific set of genes, called CYP450 genes, which are involved in the detoxification of compounds encountered by the beetle when feeding on plant tissues." The Asian long-horned beetle, also known as Anoplophora glabripennis, belongs to the longhorn beetle family, which contains over 35,000 different species, making it the most diverse group of wood-feeding animals on Earth. According to the researchers this study has established a genomic basis for the invasiveness of the Asian long-horned beetle as well as the evolutionary success of beetles that feed on woody plants. Additionally, the identification of genes linked to key digestive and detoxification processes will ultimately provide novel tools for management of the Asian long-horned beetle and other invasive wood-boring pests. Dr Richards added: "This publically available genome is part of a larger group as a pilot for the i5K initiative to sequence 1000's of insects. We hope that in the long term this foundation information about how any species works can be made available to anyone interested in biology, from researchers addressing specific questions to high-school students and hobbyist entomologists at home." 1. Images of the Asian long-horned beetle are available here: https:/ Please credit image 1, 2 and 3 to David Lance. Please credit image 4 to Yunke Wu. 2. Research article: Genome of the Asian longhorned beetle (Anoplophora glabripennis), a globally significant invasive species, reveals key functional and evolutionary innovations at the beetle-plant interface Stephen Richards, Duane McKenna et al. Genome Biology 2016 During embargo period please contact Matthew Lam for a copy of the article. After the embargo lifts, the article will be available at the journal website here: https:/ Please name the journal in any story you write. If you are writing for the web, please link to the article. All articles are available free of charge, according to BioMed Central's open access policy. 3. Genome Biology publishes outstanding research in all areas of biology and biomedicine studied from a genomic and post-genomic perspective. The current impact factor is 11.313 and the journal is ranked 4th among research journals in the Genetics and Heredity category by Thomson Reuters. Genome Biology is the highest ranked Open Access journal in the category. 4. BioMed Central is an STM (Science, Technology and Medicine) publisher which has pioneered the open access publishing model. All peer-reviewed research articles published by BioMed Central are made immediately and freely accessible online, and are licensed to allow redistribution and reuse. BioMed Central is part of Springer Nature, a major new force in scientific, scholarly, professional and educational publishing, created in May 2015 through the combination of Nature Publishing Group, Palgrave Macmillan, Macmillan Education and Springer Science+Business Media. http://www.


Implantable, ultra-narrow, silicon-based photonic probes described in journal from SPIE, the international society for optics and photonics BELLINGHAM, Washington, USA, and CARDIFF, UK -- The ability to stimulate neural circuits with very high precision light to control cells -- optogenetics -- is key to exciting advances in the study and mapping of the living brain. In the current state of the art, spatially patterned light projected via free-space optics stimulates small, transparent organisms and excites neurons within superficial layers of the cortex. However, light scattering and absorption in neural tissue cause light penetration to be extremely short, making it impossible to employ free-space optical methods to probe brain regions deeper than about 2 mm. In "Patterned photostimulation via visible-wavelength photonic probes for deep brain optogenetics," published today by SPIE, the international society for optics and photonics, in the journal Neurophotonics, principal author Eran Segev of professor Michael Roukes' group at Caltech, along with coauthors from Caltech, Baylor College of Medicine, and Stanford University, describe a solution. The article is available via open access. Their approach combines nanophotonics and microelectromechanical systems (MEMS) in an implantable, ultra-narrow, silicon-based photonic probe to deliver light deep within brain tissues. This minimally invasive technique avoids major tissue displacement during implantation. Using techniques of optogenetics, a protein in the brain serves as a sensory photoreceptor and can be controlled by specific wavelengths of light. These combined techniques provide a new approach to stimulation of brain circuits with remarkable resolution, enabling observation and control of individual neurons. These breakthroughs present widespread and promising applications for the neuroscience and neuromedical research communities. From characterizing the role of specific neurons and identifying neural circuits responsible for behavior to enabling new methods of operant conditioning through reward-induced circuit activations, optogenetics has become a new path for neuroscientists seeking advances in research capabilities. The article appears in a special section in Neurophotonics, Brain Mapping and Therapeutics, with Shouleh Nikzad, Jet Propulsion Laboratory, Caltech, serving as senior guest editor. The special section is part of an SPIE partnership with the Society for Brain Mapping and Therapeutics (SBMT), serving as a multidisciplinary approach for using advanced technology to solve neurological disorders and disease and to understand neuroscience. The effort was initiated during Nikzad's term as SBMT president in 2015. David Boas of Massachusetts General Hospital, Harvard Medical School, is the editor-in-chief of Neurophotonics. Launched in 2014, Neurophotonics is published digitally in the SPIE Digital Library and in print. The journal covers advances in optical technology applicable to the study of the brain and their impact on basic and clinical neuroscience applications. The SPIE Digital Library contains more than 458,000 articles from SPIE journals, proceedings, and books, with approximately 18,000 new research papers added each year. Abstracts are freely searchable, and a number of journal articles are published with open access. SPIE, the international society for optics and photonics, is an educational not-for-profit organization founded in 1955 to advance light-based science, engineering and technology. The Society serves nearly 264,000 constituents from approximately 166 countries, offering conferences and their published proceedings, continuing education, books, journals, and the SPIE Digital Library. In 2016, SPIE provided $4 million in support of education and outreach programs. http://www.


News Article | March 1, 2017
Site: www.nature.com

The experiments were not randomized and the investigators were not blinded to allocation during experiments and outcome assessment. ARC-Net, University of Verona: approval number 1885 from the Integrated University Hospital Trust (AOUI) Ethics Committee (Comitato Etico Azienda Ospedaliera Universitaria Integrata) approved in their meeting of 17 November 2010, documented by the ethics committee 52070/CE on 22 November 2010 and formalized by the Health Director of the AOUI on the order of the General Manager with protocol 52438 on 23 November 2010. APGI: Sydney South West Area Health Service Human Research Ethics Committee, western zone (protocol number 2006/54); Sydney Local Health District Human Research Ethics Committee (X11-0220); Northern Sydney Central Coast Health Harbour Human Research Ethics Committee (0612-251M); Royal Adelaide Hospital Human Research Ethics Committee (091107a); Metro South Human Research Ethics Committee (09/QPAH/220); South Metropolitan Area Health Service Human Research Ethics Committee (09/324); Southern Adelaide Health Service/Flinders University Human Research Ethics Committee (167/10); Sydney West Area Health Service Human Research Ethics Committee (Westmead campus) (HREC2002/3/4.19); The University of Queensland Medical Research Ethics Committee (2009000745); Greenslopes Private Hospital Ethics Committee (09/34); North Shore Private Hospital Ethics Committee. Baylor College of Medicine: Institutional Review Board protocol numbers H-29198 (Baylor College of Medicine tissue resource), H-21332 (Genomes and Genetics at the BCM-HGSC), and H-32711(Cancer Specimen Biobanking and Genomics). Patients were recruited and consent obtained for genomic sequencing through the ARC-Net Research Centre at Verona University, Australian Pancreatic Cancer Genome Initiative (APGI), and Baylor College of Medicine as part of the ICGC (www.icgc.org). A patient criterion for admission to the study was that they were clinically sporadic. This information was acquired through direct interviews with participants and a questionnaire regarding their personal history and that of relatives with regard to pancreas cancers and any other cancers during anamnesis. Clinical records were also used to clarify familial history based on patient indications. Samples were prospectively and consecutively acquired through institutions affiliated with the Australian Pancreatic Cancer Genome Initiative. Samples from the ARC-Net biobank are the result of consecutive collections from a single centre. All tissue samples were processed as previously described5151. Representative sections were reviewed independently by at least one additional pathologist with specific expertise in pancreatic diseases. Samples either had full face frozen sectioning performed in optimal cutting temperature (OCT) medium, or the ends excised and processed in formalin to verify the presence of tumour in the sample to be sequenced and to estimate the percentage of neoplastic cells in the sample relative to stromal cells. Macrodissection was performed if required to excise areas that did not contain neoplastic epithelium. Tumour cellularity was determined using SNP arrays (Illumina) and the qpure tool9. PanNET is a rare tumour type and the samples were collected via an international network. We estimate that with 98 unique patients in the discovery cohort, we will achieve 90% power for 90% of genes to detect mutations that occur at a frequency of ~10% above the background rate for PanNET (assuming a somatic mutation frequency of more than 2 per Mb)52. Cancer and matched normal colonic mucosa were collected at the time of surgical resection from the Royal Brisbane and Women’s Hospital and snap frozen in liquid nitrogen. A biallelic germline mutation in the MUTYH gene was detected by restriction fragment length polymorphism analysis and confirmed by automated sequencing to be the G382D mutation (or ENST00000450313.5 G396D, ClinVar#5294) in both alleles53. The primary antibodies used for immunohistochemical staining were: cytokeratin 8/18 (5D3, Novocastra), chromogranin A (DAK-A3, Dako), and CD99 (O13, Biolegend). Antibodies and staining conditions have been described elsewhere39. Whole-genome sequencing with 100-bp paired reads was performed with a HiSEQ2000 (Illumina). Sequence data were mapped to a GRCh37 using BWA and BAM files are available in the EGA (accession number: EGAS00001001732). Somatic mutations and germline variants were detected using a previously described consensus mutation calling strategy11. Mutations were annotated with gene consequence using SNPeff. The pathogenicity of germline variants was predicted using cancer-specific and locus-specific genetic databases, medical literature, computational predictions with ENSEMBL Variant Effect Predictor (VEP) annotation, and second hits identified in the tumour genome. Intogen27 was used to find somatic genes that were significantly mutated. Somatic structural variants were identified using the qSV tool as previously described10, 11, 17. Coding mutations are included in supplementary tables and all mutations have been uploaded to the International Cancer Genome Consortium Data Coordination Center. Mutational signatures were predicted using a published framework14. Essentially, the 96-substitution classification was determined for each sample. The signatures were compared to other validated signatures and the prevalence of each signature per megabase was determined. Somatic copy number was estimated using high density SNP arrays and the GAP tool12. Arm level copy number data were clustered using Ward’s method, Euclidian distance. GISTIC13 was used to identify recurrent regions of copy number change. The whole genome sequence data was used to determine the length of the telomeres in each sample using the qMotif tool. Essentially, qMotif determines telomeric DNA content by calculating the number of reads that harbour the telomere motif (TTAGG), and then estimates the relative length of telomeres in the tumour compared to the normal. qMotif is available online (http://sourceforge.net/projects/adamajava). Telomere length was validated by qPCR as previously described54. RNASeq library preparation and sequencing were performed as previously described55. Essentially, sequencing reads were mapped to transcripts corresponding to ensemble 70 annotations using RSEM. RSEM data were normalized using TMM (weighted trimmed mean of M-values) as implemented in the R package ‘edgeR’. For downstream analyses, normalized RSEM data were converted to counts per million (c.p.m.) and log transformed. Genes without at least 1 c.p.m. in 20% of the sample were excluded from further analysis55. Unsupervised class discovery was performed using consensus clustering as implemented in the ConsensusClusterPlus R package56. The top 2,000 most variable genes were used as input. Differential gene expression analysis between representative samples was performed using the R package ‘edgeR’57. Ontology and pathway enrichment analysis was performed using the R package ‘dnet’58. PanNET class enrichment using published gene signatures44 was performed using Gene Set Variation Analysis (GSVA) as described previously55. Two strategies were used to verify fusion transcripts. For verification of EWSR1–BEND2 fusions, cDNAs were synthesized using the SuperScript VILO cDNA synthesis kit (Thermofisher) with 1 μg purified total RNA. For each fusion sequence, three samples were used: the PanNET sample containing the fusion, the PanNET sample without that fusion, and a non-neoplastic pancreatic sample. The RT–PCR product were evaluated on the Agilent 2100 Bioanalyzer (Agilent Technologies) and verified by sequencing using the 3130XL Genetic Analyzer (Life Technologies). Primers specific for EWSR1–BEND2 fusion genes are available upon request. To identify the EWSR1 fusion partner in the case ITNET_2045, a real-time RT–PCR translocation panel for detecting specific Ewing sarcoma fusion transcripts was applied as described59. Following identification of the fusion partner, PCR amplicons were subjected to sequencing using the 3130XL Genetic Analyzer. EWSR1 rearrangements were assayed on paraffin-embedded tissue sections using a commercial split-signal probe (Vysis LSI EWSR1 (22q12) Dual Colour, Break Apart Rearrangement FISH Probe Kit) that consists of a mixture of two FISH DNA probes. One probe (~500 kb) is labelled in SpectrumOrange and flanks the 5′ side of the EWSR1 gene, extending through intron 4, and the second probe (~1,100 kb) is labelled in SpectrumGreen and flanks the 3′ side of the EWSR1 gene, with a 7-kb gap between the two probes. With this setting, the assay enables the detection of rearrangements with breakpoints spanning introns 7–10 of the EWSR1 gene. Hybridization was performed according to the manufacturer’s instructions and scoring of tissue sections was assessed as described elsewhere60, counting at least 100 nuclei per slide. Recurrently mutated genes identified by whole-genome sequencing were independently evaluated in a series of 62 PaNETs from the ARC-Net Research Centre, University of Verona. Four Ion Ampliseq Custom panels (Thermofisher) were designed to target the entire coding regions and flanking intron–exon junctions of the following genes: MEN1, DAXX, ATRX, PTEN and TSC2 (panel 1); DEPDC5, TSC1 and SETD2 (panel 2); ARID1A and MTOR (panel 3); CHEK2 and MUTYH (panel 4). Twenty nanograms of DNA were used per multiplex PCR amplification. The quality of the obtained libraries was evaluated by the Agilent 2100 Bioanalyzer on chip electrophoresis. Emulsion PCR was performed with the OneTouch system (Thermofisher). Sequencing was run on the Ion Torrent Personal Genome Machine (PGM, Thermofisher) loaded with 316 or 318 chips. Data analysis, including alignment to the hg19 human reference genome and variant calling, was done using Torrent Suite Software v4.0 (Thermofisher). Filtered variants were annotated using a custom pipeline based on the Variant Effector Predictor (VEP) software. Alignments were visually verified with the Integrative Genomics Viewer: IGV v2.3 (Broad Institute). There is no contiguous structure available for CHEK2, so we produced a model of isoform C using PDBid 3i6w61 as a template for predicting the structure of sequence O96017. Modelling was carried out within the YASARA suite of programs62 and consisted of an initial BLAST search for suitable templates followed by alignment, building of loops not present in selected template structure and energy minimization in explicit solvent. Modelling was carried out in the absence of a phosphopeptide ligand, which was added on completion by aligning the model with structure 1GXC and merging the ligand contained therein with the model structure. Similarly, MUTYH is represented by discontinuous structures and so this too was modelled using PDBids 3N5N and 4YPR as templates together with sequence NP_036354.1. Having constructed both models, amino acid substitutions were carried out to make the wild-type sequences conform to the variants described above. Each substitution was carried out independently and the resulting variant structures were subject to simulated annealing energy minimization using the AMBER force field. The resulting energy-minimized structures formed the basis of the predictions. CHEK2 site mutants were generated by site-directed mutagenesis of wild-type pCMV–FLAG CHEK2 (primer sequences in Supplementary Table 16). Proteins were expressed in HEK293T, a highly transfectable derivative of HEK293 cells that were retrieved from the cell culture bank at the QIMR Berghofer medical research institute. Cells were authenticated by STR profiling and were negative for mycoplasma. Transfected cells were lysed in NP-40 modified RIPA with protease and phosphatase inhibitors. Protein expression levels were analysed by western blotting with anti-FLAG antibodies and imaging HRP luminescent signal on a CCD camera (Fuji) and quantifying in MultiGauge software (Fuji). Kinase assays were performed using recombinant GST–CDC25C (amino acids 200–256) as substrate, essentially as described63. Kinase assay quantification was performed by scintillation counting of excised gel bands in OptiPhase scintillant (Perkin Elmer) using a Tri-Carb 2100TR beta counter (Packard). Counts for each reaction set were expressed as a fraction of the wild type. All experiments were performed at least three times. The date of diagnosis and the date and cause of death for each patient were obtained from the Central Cancer Registry and treating clinicians. Median survival was estimated using the Kaplan–Meier method and the difference was tested using the log-rank test. P values of less than 0.05 were considered statistically significant. The hazard ratio and its 95% confidence interval were estimated using Cox proportional hazard regression modelling. The correlation between DAXX or ATRX mutational status and other clinico-pathological variables was calculated using the χ2 test. Statistical analysis was performed using StatView 5.0 Software (Abacus Systems). Disease-specific survival was used as the primary endpoint. Genome sequencing data presented in this study have been submitted to the European Genome-Phenome Archive under accession number EGAS00001001732 (https://www.ebi.ac.uk/ega/search/site/EGAS00001001732).


News Article | August 24, 2016
Site: www.biosciencetechnology.com

A new device developed by researchers at MIT and a physician at Connecticut Children’s Medical Center could greatly improve doctors’ ability to accurately diagnose ear infections. That could drastically reduce the estimated 2 million cases per year in the United States where such infections are incorrectly diagnosed and unnecessary antibiotics are prescribed. Such overprescriptions are considered a major cause of antibiotic resistance. The new device, whose design is still being refined by the team, is expected ultimately to look and function very much like existing otoscopes, the devices most doctors currently use to peer inside the ear to look for signs of infection. But unlike these conventional devices, which use visible light and can only see a few millimeters into the tissues of the ear, the new device instead uses shortwave infrared light, which can penetrate much deeper. The findings are being reported this week in the journal PNAS, in a paper by Moungi Bawendi, the Lester Wolfe Professor of Chemistry at MIT; Jessica Carr, an MIT doctoral student; Oliver Bruns, an MIT research scientist; and Tulio Valdez, a pediatric otolaryngologist at Connecticut Children’s Medical Center  and associate professor of otolaryngology at the University of Connecticut. The one clear diagnostic sign of an infection in the ear is a buildup of fluid behind the eardrum, Carr explains. But the view through a conventional otoscope can’t penetrate deeply enough into the tissues to reveal such buildups. More expensive specialized equipment can offer more information needed for a firm diagnosis, but these tools are usually only available in the offices of specialists, who are not consulted in the vast majority of cases. “A lot of times, it’s a fifty-fifty guess as to whether there is fluid there,” Carr said. “If there’s no fluid, there’s no chance of an infection. One of the limitations of the existing technology is that you can’t see through the eardrum, so you can’t easily see the fluid. But the eardrum basically becomes transparent to our device.” Fluid within the ear, by contrast, “becomes very dark and very apparent.” While there are more advanced systems under development that do provide data on these deeper parts of the ear, Carr said, those “haven’t been widely adopted. They’re not familiar to the physicians, who have to use a whole range of technologies in their work. These are something new and unfamiliar, and some of these devices require a trained audiologist to run them.” So the MIT team worked to make the new device as familiar as possible, closely resembling the otoscopes that doctors already use. “We developed something easy to use, and that wouldn’t require much training,” she said. Studies have shown that about 8 million children each year in the U.S. are diagnosed with otitis media, the medical term for middle-ear infections, Carr said. These are especially prevalent among young children: About 80 percent of them will have at least one such diagnosis by the age of 3. But the studies show that such diagnoses are correct only 51 percent of the time — “essentially a coin toss,” Carr said. The roughly 4 million incorrect diagnoses are about evenly split between false positives and false negatives, indicating that about 2 million children every year are incorrectly thought to have such infections, and are prescribed unnecessary antibiotics. Once the presence of an infection is determined, doctors must then try to distinguish between viral and bacterial causes, something this device cannot determine, although it can provide some clues. After initial successful tests on 10 adult subjects, the team is now in the process of carrying out tests on pediatric patients to confirm the accuracy of the diagnostic results. Assuming the tests go well, the team hopes to commercialize the device. The ultimate cost, Carr says, will depend on the cost of the infrared imaging system — which is finding a variety of applications, including in the self-driving cars being developed by Google and other companies, because of its ability to see through fog and during night time. The cost of those devices, originally developed for military uses, has already fallen drastically over the last couple of years, she says, and widespread production could drop those costs rapidly. "The potential impact of this work is huge,” said Karina Cañadas, an assistant professor of pediatric otolaryngology at Baylor College of Medicine in Texas, who was not involved in this work. "Ear infections are one of the most common reasons for visits to the pediatrician, but sometimes the view of the middle ear in a wiggly irritated child is not easy, making a good exam not always possible.  With this  technology even a brief exam would be able to detect middle ear fluid more confidently.” The research was supported by the Laser Biomedical Research Center at MIT funded by the National Institutes of Health, MIT’s Institute for Soldier Nanotechnologies, and the Air Force Office of Scientific Research.


News Article | December 8, 2016
Site: phys.org

A future probe designed for brain mapping is illustrated in Figure 10. Credit: Neurophotonics , doi:10.1117/1.NPh.4.1.011002 The ability to stimulate neural circuits with very high precision light to control cells—optogenetics—is key to exciting advances in the study and mapping of the living brain. In the current state of the art, spatially patterned light projected via free-space optics stimulates small, transparent organisms and excites neurons within superficial layers of the cortex. However, light scattering and absorption in neural tissue cause light penetration to be extremely short, making it impossible to employ free-space optical methods to probe brain regions deeper than about 2 mm. In "Patterned photostimulation via visible-wavelength photonic probes for deep brain optogenetics," published today by SPIE, the international society for optics and photonics, in the journal Neurophotonics, principal author Eran Segev of professor Michael Roukes' group at Caltech, along with coauthors from Caltech, Baylor College of Medicine, and Stanford University, describe a solution. The article is available via open access. Their approach combines nanophotonics and microelectromechanical systems (MEMS) in an implantable, ultra-narrow, silicon-based photonic probe to deliver light deep within brain tissues. This minimally invasive technique avoids major tissue displacement during implantation. Using techniques of optogenetics, a protein in the brain serves as a sensory photoreceptor and can be controlled by specific wavelengths of light. These combined techniques provide a new approach to stimulation of brain circuits with remarkable resolution, enabling observation and control of individual neurons. These breakthroughs present widespread and promising applications for the neuroscience and neuromedical research communities. From characterizing the role of specific neurons and identifying neural circuits responsible for behavior to enabling new methods of operant conditioning through reward-induced circuit activations, optogenetics has become a new path for neuroscientists seeking advances in research capabilities. The article appears in a special section in Neurophotonics, Brain Mapping and Therapeutics, with Shouleh Nikzad, Jet Propulsion Laboratory, Caltech, serving as senior guest editor. The special section is part of an SPIE partnership with the Society for Brain Mapping and Therapeutics (SBMT), serving as a multidisciplinary approach for using advanced technology to solve neurological disorders and disease and to understand neuroscience. The effort was initiated during Nikzad's term as SBMT president in 2015. Explore further: Refining optogenetic methods to map synaptic connections in the brain More information: Eran Segev et al, Patterned photostimulation via visible-wavelength photonic probes for deep brain optogenetics, Neurophotonics (2016). DOI: 10.1117/1.NPh.4.1.011002


IP6, the natural inhibitor or ligand of Clostridium difficile's toxin, binds weakly to the toxin. This results in the toxin remaining active (center figure). Changing a single atom in IP6 to form IP6(S) results in stronger binding to the toxin and its inactivation (left side figure). Credit: T. Savidge (BCM); K. Prince (TCH) Infections with bacterium Clostridium difficile have rapidly become a significant medical problem in hospitals and long-term care facilities. The bacteria cause diarrhea and life-threatening inflammation of the colon by producing toxins that kill the endothelial cells that form the lining of the gut. Although a natural inhibitor of these toxins, called InsP6, works in the test tube, it is not very efficient when administered orally. Traditional methods to optimize InsP6 have until now not been successful, but researchers at Baylor College of Medicine have discovered that changing one atom in InsP6 can increase its ability to neutralize the toxins by 26-fold. The results appear in Science Advances. "The toxins, called TcdA and TcdB, are very large molecules that kill the cells very efficiently," said Dr. Tor Savidge, associate professor of pathology and immunology and of pediatrics, director of the Savidge Lab at the Texas Children's Microbiome Center and senior author of the paper. "It's like delivering a warhead into the cell. The toxins bind to the cell and the cell internalizes them in a sack of cell membrane called endosome. Not all of the toxin will exit this sack to kill the cell, just the little warhead pokes its head out. Another section of the toxin senses when the warhead is outside the sack and cleaves it. The warhead is released, interferes with basic functions and kills the cell," said Savidge. To neutralize the toxins, the researchers targeted the section that senses when the warhead is inside the cell, called allosteric modulator. "The strategy we have tried is to make the toxin 'think,' before it binds to and enters the cell, that the warhead is ready to be released, so it releases it prematurely," said Savidge. When the warhead is released outside the cell, it is neutralized. InsP6, the toxins' natural inhibitor, works this way, but is not very efficient. Finding molecules that would bind to the allosteric modulator and trigger the premature release of the warhead involved analyzing and testing half a million molecules listed in large databases. Dr. Numan Oezguen, a member of the Savidge Lab, used virtual drug screening to sift through the databases to identify candidate molecules that most likely would bind to the allosteric modulator. One of his screening strategies consists of creating virtual 3-D structures of the molecules, projecting them on a large screen and using 3-D glasses to determine the most likely interactions between molecules. The molecules whose virtual analysis suggested they would bind to the allosteric modulator were then tested in the lab. "We found that allosteric mechanisms are very complicated," said Savidge. "You can find something that binds and you think, well, this is probably a good candidate for this, but it's not right. It binds, but it doesn't trigger the premature release of the warhead." Far from discouraging their efforts, the results motivated the researchers to better understand what makes interactions between molecules stronger or weaker. Their comprehensive analysis of numerous molecules provided insights into how water contributes to molecular interactions, in particular those involving hydrogen bonds, one of the most important bonds between molecules. The roles of water and hydrogen bonding had not been considered in this way before. "When you take water into consideration you need to acknowledge that it can form hydrogen bonds, which may or may not compete or interfere with those formed between other molecules such as C. difficile toxins and their inhibitors, which interact in the gut, surrounded by water," said Savidge. "Before we considered the role of water, the predominant idea was that to strengthen the interaction between molecules the ability to form hydrogen bonds had to be made as strong as possible in the drug. It turns out this is not the case," said Oezguen. Many times drugs designed to be able to make strong hydrogen bonds bind poorly to their targets. The researchers discovered that to enhance the binding of a drug to its target, both sides of the hydrogen bond, the side on the drug and the one on the target, have to have either significantly stronger or significantly weaker hydrogen bonding capabilities. On the other hand, a mixed strong-weak hydrogen bond pairing decreases the overall binding of the drug to its target, in some cases by 3 million fold. The decrease in binding is the result, the researchers propose, of water molecules forming hydrogen bonds with the drug and its target, therefore preventing the drug and the target from forming hydrogen bonds between them. With all this information in hand, the researchers proceeded to make chemical changes in the InsP6 inhibitor to improve its hydrogen bonding capabilities with C. difficile toxins. One of the modifications, changing one single atom in InsP6, strengthened InsP6 binding to the allosteric modulator by 26-fold. This observation builds on a report published by Savidge in Science last year exploring the role of water interactions in the origin of enzymatic catalytic power. Plans are currently underway to exploit these fundamentally new concepts in the precision design of future therapeutic applications. Explore further: Researchers claim to have discovered why warm water freezes faster than cooler water More information: Regulation of protein-ligand binding affinity by hydrogen bond pairing, Science Advances, dx.doi.org/10.1126/sciadv.1501240


News Article | February 15, 2017
Site: www.prweb.com

Dermatology Associates (“DA”) is pleased to announce that it recently completed the acquisition of Texoma Dermatology Clinic (“Texoma” or “TDC”). The transaction closed in February 2017. Dermatology Associates is a dermatology-focused physician services and management organization backed by private equity firm ABRY Partners. Based in Sherman, TX, with an additional location in Paris, TX, TDC has provided patients across North Texas and Southern Oklahoma with quality health care since its foundation in 1976. Its specialized physicians provide up-to-date, evidence-based medicine supporting their combined 60+ years of experience to help treat a comprehensive array of dermatologic conditions, including inflammatory diseases, skin cancers, and infection. TDC’s physicians have a combined experience of treating over 60,000 skin cancers. Texoma Dermatology provides services to patients via three board-certified dermatologists and two physician assistants. Dr. Mark Koone has been in private dermatology practice since 1990. In addition to being with TDC since 1993, he is also a dermatologist for the Austin College Student Clinic. Dr. Koone’s educational background includes a B.S., Magna cum Laude from Houston Baptist University, Doctor of Medicine with High Honor at Baylor College of Medicine, an Internal Medicine Internship with Baylor College of Medicine at St. Luke’s Episcopal Hospital and a dermatology residency at Duke University Medical Center. Dr. Koone has been selected to “Best Doctors in America” every year from 1995-2016. Dr. Creed Stewart is a Southern Oklahoma native, and has lived in Sherman, TX since 2002. He received his medical degree and completed his residency at the University of Oklahoma Health Sciences Center, where he served as chief resident. Dr. Stewart is a board-certified dermatologist and is a member of the Alpha Omega Alpha medical honor society. Dr. Stewart has been a fellow of the American Society of Mohs Surgery since 2005. Dr. Clint Moss joined Texoma Dermatology in 2012 after spending many years in Lubbock, TX. He is a board-certified dermatologist and has expertise in both general and surgical dermatology. He received his dermatology training at Texas Tech University Health Sciences Center where he also served as Chief Resident, and was inducted into the Alpha Omega Alpha medical honor society there as well. Joining the physicians of Texoma Dermatology are their highly-experienced physician assistants, Amy Edwards, PA-C, and Ashley Chappell, PA-C. “We are honored to partner with the highly-experienced team at Texoma Dermatology,” said Geoff Wayne, CEO of Dermatology Associates. “Their great reputation and long-standing presence further bolsters our market-leading position in Texas.” If you would like more information about Dermatology Associates, or if you have any questions regarding the partnership with TDC, please contact one of the team members listed below: About Dermatology Associates Headquartered in Dallas, TX, Dermatology Associates provides comprehensive practice management services to over 85 board-certified dermatologists across more than 50 locations in Texas, Kansas and Missouri. Dermatology Associates is focused solely on supporting providers so that they can focus exclusively on delivering high-quality care to patients. By leveraging the benefits of a broad group platform, Dermatology Associates’ physicians are able to maintain professional autonomy while the business aspects of practice management are handled by its team of experts. About ABRY Partners Founded in 1989 and headquartered in Boston, Massachusetts, ABRY Partners is an experienced and successful private equity investment firm focused on media, communications, healthcare services, insurance services, business and information services. Since its founding, ABRY has completed more than $62 billion of transactions, representing investments in more than 550 properties.


News Article | November 22, 2016
Site: www.eurekalert.org

INDIANAPOLIS - A combination of the stimulant drug methylphenidate with a process known as cognitive-behavioral rehabilitation is a promising option to help people who suffer from persistent cognitive problems following traumatic brain injury, researchers at Indiana University School of Medicine have reported. The study, believed to be the first to systematically compare the combination therapy to alternative treatments, was published online in the journal Neuropsychopharmacology, a Nature publication. The researchers, led by Brenna McDonald, PsyD, associate professor of radiology and imaging sciences, and Thomas McAllister, MD, chairman of the Department of Psychiatry, compared the effectiveness of two forms of cognitive therapy with and without the use of methylphenidate, a drug used to treat attention-deficit/hyperactivity disorder and better known by its trade name, Ritalin. "We found that the combination of methylphenidate and Memory and Attention Adaptation Training resulted in significantly better results in attention, episodic and working memory, and executive functioning after traumatic brain injury," said Dr. McDonald. In the Memory and Attention Adaptation Training intervention - also used to assist patients with cognitive issues following breast cancer chemotherapy - therapists work with patients to help them develop behaviors and strategies to improve performance in memory and other cognitive tasks. In this study, this "metacognitive" approach was compared with Attention Builders Training, which Dr. McDonald likened to more of a "drill and practice" approach. The 71 participants who completed the six-week trial were adults who had experienced a traumatic brain injury of at least mild severity - a blow to the head with some alteration of consciousness - at least four months previously, and who either complained of having cognitive problems, or who had been identified with cognitive problems in testing. The participants were divided into four groups: the two cognitive therapy approaches with the drug therapy, and the two approaches with placebo. After six weeks, the researchers found that participants in the combination metacognitive-Ritalin group improved significantly better in word list learning, nonverbal learning and measures of attention-related and executive function. However, Dr. McDonald cautioned that due to the relatively small number of participants in the each of the four arms of the trial - 17 to 19 people each - the results of the trial should be considered preliminary. Nonetheless, she said, the work breaks new ground in providing evidence for the combination therapy. "There have been a few small studies suggesting methylphenidate could help with attention and executive function after traumatic brain injury, which makes senses because it's used to improve attention and focus. But this is the first to test it in combination with cognitive-behavioral therapy for treatment in traumatic brain injury," said Dr. McDonald. In addition to Drs. McDonald and McAllister, researchers contributing to the study were Gwen C. Sprehn, Flora M. Hammond, Jaroslaw Harezlak, Li Xing, Rachel N. Wall, and Andrew J. Saykin of the IU School of Medicine; Laura A. Flashman, Carrie L. Kruck, and Karen L. Gillock of the Geisel School of Medicine, Dartmouth College; David B. Arciniegas of the Baylor College of Medicine; Robert J. Ferguson of the Department of Medicine, University of Pittsburgh; Arthur C. Maerlender of the University of Nebraska and Kim Frey of Craig Hospital, Englewood, Colorado. This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (R01 HD047242). Dr. Arciniegas receives research support from the National Institute on Disability, Independent Living, and Rehabilitation Research (H133A120020, H133A130047) and Department of Veterans Affairs (CX000239) and receives compensation from American Psychiatric Association Publishing.


News Article | February 21, 2017
Site: www.eurekalert.org

Melanoma patients' response to a major form of immunotherapy is associated with the diversity and makeup of trillions of potential allies and enemies found in the digestive tract, researchers at The University of Texas MD Anderson Cancer Center report at the ASCO-Society for Immunotherapy in Cancer meeting in Orlando. Analysis of 113 fecal samples of patients with metastatic melanoma found that those who responded to a PD1 checkpoint inhibitor had a greater diversity of gut bacteria and larger volumes of a specific type of bacteria than those who did not respond. This connection between a person's microbiome - trillions of bacteria harbored to varying degrees in the human body -- and immune system could have major implications for cancer prognosis and treatment. "Anti-PD1 immunotherapy is effective for many, but not all, melanoma patients and responses aren't always durable," said Jennifer Wargo, M.D., associate professor of Surgical Oncology. "Our findings point to two potential impacts from additional research -- analyzing the diversity and composition of the microbiome to predict response to immunotherapy and modulating the gut microbiome to enhance treatment," said Wargo, senior researcher on the project and co-leader of the Melanoma Moon Shot™, part of MD Anderson's Moon Shots Program™ to reduce cancer deaths by accelerating development of therapies from scientific discoveries. PD1 is a protein on the surface of T cells, the immune system's specialized attack cells, that shuts down immune response. Anti-PD1 drugs use an antibody to block activation of PD1 by PD-L1, a ligand found on tumors and surrounding cells. Wargo and colleagues are conducting preclinical research to better understand the mechanisms that connect bacteria and the immune system. They're also designing clinical trials to test the hypothesis that modifying the gut microbiome might improve patients' responses to checkpoint inhibitors. "Evidence from preclinical research had previously indicated a relationship between solid tumors, immune response, and the microbiome. Our study was the first of its type to look at the relationship between the microbiome and immunotherapy response in patients," said Vancheswaran Gopalakrishnan, first author and doctoral student at The University of Texas Health Science Center at Houston School of Public Health. Gopalakrishnan, Wargo and colleagues examined oral and gut microbiome samples from 228 patients with metastatic melanoma. While no differences in response were found in connection with the oral samples, the 113 fecal samples told another story. Gopalakrishnan said the team conducted 16S rRNA sequencing, an analysis of the presence of 16S ribosomal RNA used to identify bacteria. Among the 93 patients treated with anti-PD1 immune checkpoint blockade, the researchers had gut microbiome samples from 30 responders and 13 non-responders. They found: The researchers also conducted immune profiling before treatment for the presence of important immune system cells in the tumors. Responders had significantly increased immune infiltrates in their tumors, including the presence of CD8+ killer T cells, correlated to the abundance of a specific bacterium. Even as they conduct deeper research into the microbiome and the metabolites produced by bacteria to affect the immune response, the team is also studying ways to change the composition of the microbiome. "The microbiome is highly targetable in a variety of ways," Gopalakrishnan said, including by diet, probiotics to boost the presence of helpful bacteria, antibiotics or by fecal transplants. In collaboration with the Parker Institute for Cancer Immunotherapy (PICI), the first clinical trial is expected to launch later this year. Research also continues funded by MD Anderson's Melanoma Moon Shot™. The Melanoma Research Alliance and PICI also provided support for this study. Co-authors with Gopalakrishnan and Wargo are Christine Spencer, Tatiana Karpinets, Ph.D., Robert Jenq, M.D., and Andrew Futreal, Ph.D., of Genomic Medicine; Alexandre Reuben, Ph.D., Peter Prieto, M.D., and Jeffrey Gershenwald, M.D., of Surgical Oncology; Kristi Hoffman, Ph.D., of Cancer Prevention; Michael Tetzlaff, Ph.D., M.D., and Alexander Lazar, M.D., Ph.D., of Pathology; Michael Davies, M.D., Ph.D., and Patrick Hwu, M.D., of Melanoma Medical Oncology; Padmanee Sharma, M.D., Ph.D., of Genitourinary Medical Oncology and Immunology; Jim Allison, Ph.D., of Immunology; Carrie Daniel-MacDougall, Ph.D., of Epidemiology; and Diane Hutchinson, Ph.D., Nadim Ajami, Ph.D., and Joseph Petrosino, Ph.D., of Baylor College of Medicine.


News Article | March 9, 2016
Site: www.nature.com

Scientists around the world are working to solve the same basic formula: what number and mix of group members makes for the most efficient and productive lab? Some principal investigators (PIs) produce a steady stream of high-impact papers with just a couple of people in the lab; others successfully oversee a team that could populate a village. Some stock up on postdocs, and others aim to balance career stages and positions: graduate students, staff scientists and technicians. One of the most important steps for new PIs to take early in their career is to identify the formula that works best for them. In the past, they have had to decide the make-up of their group largely on the basis of their instincts and, often, financial realities. But now, they have some data to turn to. Studies on how lab size and composition affect productivity give researchers guidance in their quest for better science, more publications and higher impact. Junior faculty members who are deciding how to staff their lab need to consider their priorities: do they want to maximize the number of publications, or focus instead on impact? Do they favour hands-on or hands-off management? The number and type of people in a lab can affect all these important parameters, so PIs should build their labs with care — and with a plan. Two studies published last year suggest that most labs could produce more papers and make a bigger splash by — perhaps unsurprisingly — bringing more people on board. One of these, a 2015 study of nearly 400 life-sciences PIs in the United Kingdom, found that the productivity of a lab — measured by the number of publications — increased steadily, albeit modestly, with lab size ( , , & PeerJ http://doi.org/bcwf; 2015). In terms of sheer paper production, “it's best for a lab to be as big as possible”, says co-author Adam Eyre-Walker, a geneticist at the University of Sussex, UK. Notably, the study found no sign that individual members become less productive or less efficient as labs grow. “Adding a team member to a large lab gives you the same return as adding one to a small lab,” Eyre-Walker says. The second paper, a study of 119 biology laboratories from 1966 to 2000 at the Massachusetts Institute of Technology in Cambridge, found that productivity inched forward when an average-sized lab of ten members added people ( & Res. Pol. 44, 1633–1644; 2015). But this study did detect limits: once lab size reached 25 people — an unusually high number achieved by very few labs — the addition of team members no longer conferred benefit. Further, a lab's productivity tops out with 13 postdocs, the study found. Co-author Christopher Liu, a former biochemist who now researches strategic management at the University of Toronto, Canada, points out that his study was limited to biology labs at one institution, which makes it tricky to generalize the findings. Still, he says, PIs should pay attention to the take-home message: bigger isn't always better. “Going from 15 to 20 people is probably not great,” Liu says. “But going from two people to seven is something that you should probably do. A group of two people is pretty fragile.” Sarah Teichmann, a molecular biologist at the EMBL–European Bioinformatics Institute and at the Wellcome Trust Sanger Institute in Hinxton, UK, can attest to both the pay-offs and the challenges of growing a lab. “When I started in 2001, it was just myself and a PhD student,” she says. “I grew my group slowly. After three years, I had three PhD students and a postdoc.” She might have kept that modest configuration, but a change of focus forced a change in lab size. After several years of work on the computational aspects of gene expression and protein folding, Teichmann added an experimental angle to her research. She started by hiring one postdoc to focus on experimental work, but soon realized that he needed help. “He was alone and isolated,” she says. “It didn't really work. There has to be a critical mass of experimental and computational people or it won't take off.” A €1.3-million (US$1.4-million) grant from the European Research Council in 2010 enabled her to add three people, and her lab was on the way to bigger things, including more grants, awards and high-impact publications. Today, she leads a group of five postdocs, four PhD students and two staff scientists — one for the computational side and one for the experimental side — with a steady flow of visiting scientists. Staying on top of such an enterprise has been daunting for her and her team (see 'How to pick the right group'). “The bigger your group is, the less face-to-face time you're going to have,” she says. “There are only 24 hours in a day.” Teichmann tries to keep the lab running smoothly by hiring people who work well together and support each other without her constant involvement. Her strategy is working: she has had her name on 16 publications since the start of 2015, including two articles in Science. She also won the 2015 EMBO Gold Medal, a prize awarded to outstanding young scientists in the life sciences. Still, as Liu points out, bigger labs aren't always the key to a productive career. A smaller group can work for those who prefer to manage team members themselves and whose research doesn't require a huge roster. For his part, Eyre-Walker finds comfort in the knowledge that small labs can make a big splash: his study found only a weak correlation between lab size and the average impact factor of each paper. He oversees a relatively small team of three PhD students and a postdoc, and says that he can remain deeply engaged with the analysis of all the work in his lab. “I couldn't cope with any more people,” he says. “I like it like this. I can still do science. I'm not just managing people.” Some PIs learn through experience that they prefer a less-populous team. Koen Venken, a geneticist at Baylor College of Medicine in Houston, Texas, rapidly built a team of ten lab members after starting his faculty job in 2014. But he soon realized that his team members weren't working well together. “It was a mistake, and I'm happy to admit it,” he says. After some rapid downsizing, he now has a group of two PhD students, one postdoc, one lab technician, one research associate and a non-tenure-track instructor, a mix that has proved to be productive and efficient. Looking back, Teichmann is glad that she took a slow, deliberate approach to building her lab. “Going slow is important for the sanity of the PI,” she says. Eyre-Walker agrees. “You have to feel your way into it. Start small, and see how you get on. The worst thing you can do as a new faculty member is take on five PhD students.” But size is only one measure of a lab. PIs who are assembling a team also have to consider balance — and that means weighing the relative merits of graduate students, postdocs, technicians and other potential members. According to the Research Policy study, postdocs — especially those who have external funding through fellowships — are the key drivers of productivity. Overall, adding a funded postdoc to the average lab boosts output by about 29% of a published paper every year. Graduate students don't contribute much to productivity, but they do play an important part in the group. The analysis found that students are as valuable as funded postdocs for generating 'breakthrough' papers, which the study defined as anything published in Science, Nature or Cell. Adding either a funded postdoc or a graduate student to the average lab increases the chances of such a paper by about 8%, the team found. Postdocs without their own funding, who may not be quite as accomplished as their funded peers, do not improve the odds of a breakthrough paper at all. Many PIs eventually have to concede to financial and other realities. Sergey Kryazhimskiy, an evolutionary biologist at the University of California, San Diego, was originally dead set against hiring postdocs. He recognized that many postdocs end up stuck in their positions and are not able to move on to tenure-track jobs — and he did not want to play a part in what he views as an unfair system with enormous stakes. “If you're a responsible PI, you would like your postdocs to proceed somewhere after your lab,” he says. “It's difficult to assign them risky projects. You're playing with their lives.” He had a plan for avoiding his ethical dilemma: he would bring in staff scientists who were committed to their lab careers. But when he actually got his faculty position earlier this year, he realized that pragmatic considerations outweighed the ethical ones. He estimates that at his institution, it costs nearly twice as much to hire staff scientists as it does to hire postdocs, partly because they get benefits such as paid time off and health insurance. Unable to stick with his original strategy, Kryazhimskiy has started to interview postdocs. He is looking for candidates whom he thinks will have a good shot at a faculty job, even in a tough academic market. Another option is to find someone with other career goals, such as a job in industry. From a purely practical perspective, he thinks that postdocs will be the best investment of his grant money. PIs whose labs — and grants — are on the large side may be better able to absorb the cost of staff scientists. For Teichmann, at least, her two staff members are key to her lab's success. Both are accomplished researchers who know how the lab works and how to get things done. She expects to hire two more professionals: a lab manager and a software developer. “Then I would have four core people who can support my postdocs and PhD students,” she says. Unlike postdocs and graduate students, those four professionals wouldn't be locked into a pressurized timeline to graduate or to move on to another job. Venken would eventually like to add a few people to his lab, too — perhaps some postdocs, graduate students or a mixture of both. “I just want people who are invested in everything that we're doing,” he says. The size and structure of a lab can be hugely important, but in the end, the quality of any workplace comes down to the quality of the people, PIs say. Whether they are looking for graduate students or postdocs, whether they desire a large or small research group, new PIs need to find team members who are ready to contribute. “The first set of individuals that you hire is very important,” Liu says. “They set the tone for the entire laboratory.”


Cheng-Lun Soo, MD Recognized as a Top 100 Doctor for Two Consecutive Years by Strathmore's Who's Who Worldwide Publication Oklahoma City, OK, March 02, 2017 --( About Cheng-Lun Soo, MD Dr. Soo is the Owner and a Physician for 16 years at Orthopedic Reconstruction Center which is a medical center providing orthopedic patient care in Oklahoma City, Oklahoma. He specializes in orthopedic spinal surgery. He is fluent in English and Chinese. Dr. Soo is affiliated with multiple hospitals in the area, including Deaconess Hospital and Integris Southwest Medical Center. Dr. Soo is a member of the A.A.O.S., the N.A.S.S and the Oklahoma Orthopedic Society. Born in Taipei, Taiwan on October 20, 1958, Dr. Soo obtained a M.D. from the University of Kentucky, School of Medicine in 1993 and completed his orthopedic residency and surgery internship at Baylor College of Medicine. He conducted his spine fellowship in a combined program at the University of Louisville and Tulane University. Dr. Soo is Board Certified in Orthopedic Surgery-spine. For further information, contact www.orc-ok.com. About Strathmore’s Who’s Who Worldwide Strathmore’s Who’s Who Worldwide is an international advertising, networking and publishing company based in Farmingdale, New York. They are proud to be able to satisfy their clients and continue to have repeat clientele due to their longevity and pride in their products and services. The Owners strive to connect business professionals to enhance their contact base and networking capabilities so they can get the acknowledgment and publicity within their industries and beyond. The Strathmore family has been providing these valuable services for over two decades. They target executives and professionals in all industries to be featured in their publication and on-line directory. Industries include business, law, education, healthcare and medicine, fine arts, IT, government, science, real estate, entertainment and many more accomplished fields. Professional profiles are listed in an annual hardcover journal and in a detailed, searchable database on the website www.strww.com. Oklahoma City, OK, March 02, 2017 --( PR.com )-- Cheng-Lun Soo, MD of Oklahoma City, Oklahoma has been recognized as a Top 100 Doctor for two consecutive years, 2016 and 2017, by Strathmore’s Who’s Who Worldwide Edition for his outstanding achievements and contributions for over 23 years in the field of orthopedic healthcare.About Cheng-Lun Soo, MDDr. Soo is the Owner and a Physician for 16 years at Orthopedic Reconstruction Center which is a medical center providing orthopedic patient care in Oklahoma City, Oklahoma. He specializes in orthopedic spinal surgery. He is fluent in English and Chinese.Dr. Soo is affiliated with multiple hospitals in the area, including Deaconess Hospital and Integris Southwest Medical Center. Dr. Soo is a member of the A.A.O.S., the N.A.S.S and the Oklahoma Orthopedic Society.Born in Taipei, Taiwan on October 20, 1958, Dr. Soo obtained a M.D. from the University of Kentucky, School of Medicine in 1993 and completed his orthopedic residency and surgery internship at Baylor College of Medicine. He conducted his spine fellowship in a combined program at the University of Louisville and Tulane University. Dr. Soo is Board Certified in Orthopedic Surgery-spine.For further information, contact www.orc-ok.com.About Strathmore’s Who’s Who WorldwideStrathmore’s Who’s Who Worldwide is an international advertising, networking and publishing company based in Farmingdale, New York. They are proud to be able to satisfy their clients and continue to have repeat clientele due to their longevity and pride in their products and services. The Owners strive to connect business professionals to enhance their contact base and networking capabilities so they can get the acknowledgment and publicity within their industries and beyond. The Strathmore family has been providing these valuable services for over two decades. They target executives and professionals in all industries to be featured in their publication and on-line directory. Industries include business, law, education, healthcare and medicine, fine arts, IT, government, science, real estate, entertainment and many more accomplished fields. Professional profiles are listed in an annual hardcover journal and in a detailed, searchable database on the website www.strww.com. Click here to view the list of recent Press Releases from Strathmore Worldwide


News Article | December 22, 2016
Site: www.eurekalert.org

CINCINNATI--Cancer researchers at the University of Cincinnati (UC) College of Medicine have found an obesity-associated protein's role in leukemia development and drug response which could lead to more effective therapies for the illness. The study, which will be published in the Dec. 22 online edition of Cancer Cell and led by Jianjun Chen, PhD, associate professor in the Department of Cancer Biology, provided evidence that FTO--the protein associated with fat mass and obesity--plays a critical cancer-promoting role by regulating expression of a set of genes through a mechanism involving ribonucleic acid (RNA) modification and thereby increasing the reproduction of leukemia cells and prohibiting drug response. "N6-methyladenosine (m6A) RNA methylation, the most prevalent internal modification in messenger RNAs (mRNAs, which translate DNA) in genes, was first identified in 1970s. In 2011, Dr. Chuan He, professor of chemistry at the University of Chicago, a co-senior author of this paper, discovered for the first time that FTO actually functions as an eraser of m6A methylation. This means that it can remove the modification from RNA transcripts, or RNA copies, thereby showing that m6A modification is a reversible process and is highly likely it is of biological importance. In 2012, two groups independently reported the development of novel sequencing technologies to profile all m6A modification areas in the entire genome and showed that roughly one-third of mRNAs in individual mammal cells are targets of m6A modification, highlighting the prevalence and potential functional importance of m6A modification. "Recent studies have shown that m6A modification in mRNAs or non-coding RNAs plays critical roles in virtually all major normal biological processes such as tissue development and stem cell self-renewal and differentiation. However, little is known about the biological importance of m6A modification in the regulation of cancer-causing genes and/or tumor-suppressing genes in the development of tumors." Researchers in the study analyzed a microarray dataset of 100 human acute myeloid leukemia (AML) samples from patients and nine normal control samples as well as other large-scale microarray datasets of AML samples. They found that FTO was highly expressed in various subtypes of leukemia samples such as those that contained chromosome crossover (genetic exchange between chromosomes) or mutations in certain genes. The high level of FTO expression contributed to cancer cells multiplying and surviving and also promoted the development of leukemia in animal models and the non-response of cancer cells to therapeutic agents. Additionally, researchers found that genes like ASB2 and RARA, which were reported to inhibit leukemia cell growth and/or mediate the response of leukemia cells to therapeutic agents, were suppressed in the AML samples with higher FTO expression. The suppression of these genes was attributed to FTO-controlled decreased stability of their mRNA and was connected to FTO's m6A demethylase activity. "Our study shows, for the first time, the functional importance of the m6A modification machinery in leukemia," says Chen. "In addition, given the functional importance of FTO in the formation of leukemia and drug response, targeting FTO signaling may present a new therapeutic strategy to treat leukemia. As FTO may also play a cancer-promoting role in various types of solid tumors, besides leukemia, our discoveries may have a broad impact in cancer biology and cancer therapy. Further studies are needed to advance our understanding of the critical role of FTO in various types of cancers and to develop more effective novel therapeutic strategies based on such understanding to treat cancers." In addition to researchers from the University of Cincinnati, scientists from Howard Hughes Medical Institute and the University of Chicago; Baylor College of Medicine; and the First Affiliated Hospital Zhejiang University, Wuhan University and Sun Yat-Sen University Cancer Center, all in China, were involved in the study. This study was funded by the National Institutes of Health (CA178454, CA182528,CA214965 and GM071440), the Leukemia & Lymphoma Society, the American Cancer Society, Howard Hughes Medical Institute, the Damon Runyon Cancer Research Foundation, the China Scholarship Council and the Foundation of Innovation Team for Basic and Clinical Research of Zhejiang Province. The authors cite no conflict of interest.


DENVER, CO--(Marketwired - October 28, 2016) - Denver Health (DH) and the University of Colorado School of Medicine (SOM), along with two other prestigious trauma research institutions, have been awarded a U.S. Department of Defense (DOD) contract that could lead to $90 million in research over the next decade to improve trauma care for civilians and military personnel. The contract will launch with a $10.7 million project where DH and SOM will work with the University of Pittsburgh and the University of Oregon, to establish a nationwide network of trauma systems capable of conducting detailed research to improve injury outcomes. The Linking Investigations in Trauma and Emergency Services (LITES) network will collect extensive data from thousands of trauma cases across the country. "LITES will allow us to access information across the broad spectrum of trauma care, from the pre-hospital setting through hospital discharge and beyond," said Dr. Ernest E. Moore, principal investigator for the Colorado consortium, trauma surgeon at Denver Health, and professor of surgery at the School of Medicine. "Our immediate goal will be to evaluate the information coming in and our sense is that after accruing and harmonizing the data, we'll be able to launch subsequent projects, including randomized clinical trials, at the DOD's request." The four organizations, all of which have collaborated previously, will provide leadership and oversight to the LITES network. Five additional trauma centers -- the University of Texas at Houston, Vanderbilt University, University of Louisville, Baylor College of Medicine and the University of Arizona -- will share trauma data with the system. "The initial data collected will help us to identify any regional variations in the ways trauma injuries are managed," said Dr. Mitchell Cohen, director of surgery at Denver Health and professor of surgery at CU School of Medicine. "Using that data will allow us to design future research projects to determine best practices and ultimately improve survival rates following critical injury." Other key participants on the Colorado team include Dr. Ani Banerjee, Dr. Chris Silliman, Dr. Angela Sauaia, and Dr. Jason Haukoos, who are all members of the CU School of Medicine faculty. The initial phase of LITES is expected to last six -18 months, with future studies and clinical trials being conducted over the next ten years. The goal, established by a recent report published in the National Academies of Sciences, Engineering and Medicine, is to achieve zero preventable deaths after injury and minimal trauma related disability. This material is based upon work supported by the U.S. Army Medical Research Acquisition Activity under Contract No. W81XWH-16-D-0024-0001. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the U.S. Army Medical Research Acquisition Activity. Denver Health is the Rocky Mountain Region's Level I academic trauma center, and the safety net hospital for the Denver area. The Denver Health system, which integrates acute and emergency care with public and community health, includes the Rocky Mountain Regional Trauma Center, Denver's 911 emergency medical response system, Denver Health Paramedic Division, nine family health centers, 17 school-based health centers, the Rocky Mountain Poison and Drug Center, NurseLine, Denver CARES, Denver Public Health, the Denver Health Foundation and the Rocky Mountain Center for Medical Response to Terrorism, Mass Casualties and Epidemics. Faculty at the University of Colorado School of Medicine work to advance science and improve care. These faculty members include physicians, educators and scientists at University of Colorado Health, Children's Hospital Colorado, Denver Health, National Jewish Health, and the Denver Veterans Affairs Medical Center. The school is located on the Anschutz Medical Campus, one of four campuses in the University of Colorado system. To learn more about the medical school's care, education, research and community engagement, visit its web site.


News Article | December 22, 2016
Site: www.eurekalert.org

An international team of scientists has identified variants of the gene EBF3 causing a developmental disorder with features in common with autism. Identification of these gene variants leads to a better understanding of these complex conditions and opens the possibility of diagnosing other previously undiagnosed patients with similar clinical disorders. The study appears in the American Journal of Human Genetics. "We investigate the genetic causes of complex neurological conditions of various types, such as autism spectrum disorders and intellectual disability," said first author Dr. Hsiao-Tuan Chao, postdoctoral research fellow of pediatric-neurology at Baylor College of Medicine. "Such conditions are long-lasting, manifest very early in life and range from mild to severe. They can affect different neurological functions; however, sometimes they have overlapping similarities. For many of these conditions there is no definite diagnosis, treatments are limited and there is no cure." Chao and colleagues have taken a step toward better understanding some of these conditions. They discovered new mutations of the gene EBF3 in three patients presenting with a newly described syndrome. "The patients' main features include developmental delay, coordination problems, limited facial expressions at an early age and abnormal verbal communication and social behaviors. They can also present with repetitive motor movements, high threshold to pain and cognitive impairments," said Chao. "This newly described syndrome has many similarities with what we see in autism spectrum disorders, but also important differences." The researchers used whole exome sequencing, a laboratory technique that allows the identification of all the genes in an individual's genome. In the patients, they identified two new variants of the gene EBF3 that were not present in the patients' parents. Mutations of EBF3 are rare in the general population but more common in a population of individuals with autism spectrum disorders and intellectual disability. "The gene is known to be essential for normal development of the nervous system," said Chao. "It is one of the key factors involved in how neurons develop and connect with each other, but has not been studied in detail. In animal models, mutations that cause the gene to lose its function result in death of the embryo. EBF3 had never before been associated with a disease." That the three patients with developmental disorders have mutations in the same gene is not sufficient proof that the mutations cause the condition. To determine whether the mutations can cause neurodevelopmental problems the scientists tested the effect of the mutations in the laboratory fruit fly, Drosophila melanogaster. "We genetically engineered fruit flies to carry the mutations present in the patients," said Chao. "The defective gene product was not able to carry on the functions of the normal gene; the effect is so severe that the fly embryos do not survive. On the other hand, when we introduced the normal version of the human gene, the files developed normally." The identification of variants of EBF3 that can cause neurodevelopmental disorders has improved the genetic diagnosis of these conditions."We are able to provide a genetic diagnosis for patients who did not know the cause of their condition," said Chao. "This provides some relief to their parents and the possibility of reaching for support from a community of parents whose children are affected by similar disorders. In addition, by gaining a better understanding of how people are affected by EBF3 dysfunction, we as physicians are better equipped to prognosticate the developmental outcomes for these children." "Being able to see our research in fruit flies help us diagnose a patient in our own hospital was very gratifying. Knowing the genetic basis allows for more insights into this disorder of the brain," said Dr. Michael F. Wangler, assistant professor of molecular and human genetics at Baylor, a senior author on the paper. Other contributors to this work include Mariska Davids, Elizabeth Burke, John G. Pappas Jill A. Rosenfeld, Alexandra McCarty, Taylor Davis, Lynne Wolfe, Camilo Toro, Cynthia Tifft, Fan Xia, Nicholas Stong, Travis K. Johnson, Coral G. Warr, Members of the UDN, Shinya Yamamoto, David Adams, Thomas C. Markello, William A. Gahl, Hugo J. Bellen and May Christine V. Malicdan. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Texas Children's Hospital, National Institutes of Health, National Human Genome Research Institute, New York University, Baylor Genetics Laboratories, Columbia University, the Howard Hughes Medical Institute and Monash University. This work was supported in part by U54NS093793, R24OD022005, and R01GM067858, by the Intramural Research Program of the National Human Genome Research Institute and by the Common Fund, Office of the Director of the National Institutes of Health. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from the clinical exome sequencing offered at Baylor Genetics.


News Article | December 8, 2016
Site: www.prweb.com

The ability to stimulate neural circuits with very high precision light to control cells — optogenetics — is key to exciting advances in the study and mapping of the living brain. In the current state of the art, spatially patterned light projected via free-space optics stimulates small, transparent organisms and excites neurons within superficial layers of the cortex. However, light scattering and absorption in neural tissue cause light penetration to be extremely short, making it impossible to employ free-space optical methods to probe brain regions deeper than about 2 mm. In “Patterned photostimulation via visible-wavelength photonic probes for deep brain optogenetics,” published today by SPIE, the international society for optics and photonics, in the journal Neurophotonics, principal author Eran Segev of professor Michael Roukes’ group at Caltech, along with coauthors from Caltech, Baylor College of Medicine, and Stanford University, describe a solution. The article is available via open access. Their approach combines nanophotonics and microelectromechanical systems (MEMS) in an implantable, ultra-narrow, silicon-based photonic probe to deliver light deep within brain tissues. This minimally invasive technique avoids major tissue displacement during implantation. Using techniques of optogenetics, a protein in the brain serves as a sensory photoreceptor and can be controlled by specific wavelengths of light. These combined techniques provide a new approach to stimulation of brain circuits with remarkable resolution, enabling observation and control of individual neurons. These breakthroughs present widespread and promising applications for the neuroscience and neuromedical research communities. From characterizing the role of specific neurons and identifying neural circuits responsible for behavior to enabling new methods of operant conditioning through reward-induced circuit activations, optogenetics has become a new path for neuroscientists seeking advances in research capabilities. The article appears in a special section in Neurophotonics, Brain Mapping and Therapeutics, with Shouleh Nikzad, Jet Propulsion Laboratory, Caltech, serving as senior guest editor. The special section is part of an SPIE partnership with the Society for Brain Mapping and Therapeutics (SBMT), serving as a multidisciplinary approach for using advanced technology to solve neurological disorders and disease and to understand neuroscience. The effort was initiated during Nikzad’s term as SBMT president in 2015. David Boas of Massachusetts General Hospital, Harvard Medical School, is the editor-in-chief of Neurophotonics. Launched in 2014, Neurophotonics is published digitally in the SPIE Digital Library and in print. The journal covers advances in optical technology applicable to the study of the brain and their impact on basic and clinical neuroscience applications. The SPIE Digital Library contains more than 458,000 articles from SPIE journals, proceedings, and books, with approximately 18,000 new research papers added each year. Abstracts are freely searchable, and a number of journal articles are published with open access. SPIE, the international society for optics and photonics, is an educational not-for-profit organization founded in 1955 to advance light-based science, engineering and technology. The Society serves nearly 264,000 constituents from approximately 166 countries, offering conferences and their published proceedings, continuing education, books, journals, and the SPIE Digital Library. In 2016, SPIE provided $4 million in support of education and outreach programs. http://www.spie.org


News Article | April 18, 2016
Site: www.biosciencetechnology.com

Thanks in part to the efforts of one dedicated mother, who took to Facebook to document her son’s mysterious developmental disability, an international team of researchers led by scientists at UC San Francisco and Baylor College of Medicine in Houston has now identified a new genetic syndrome that could help illuminate the biological causes of one of the most common forms of intellectual disability. In a study of 10 children published online in the American Journal of Human Genetics on April 14, the researchers linked a constellation of birth defects affecting the brain, eye, ear, heart and kidney to mutations in a single gene, called RERE. The discovery is likely to aid researchers striving to understand the cause of birth defects more broadly, the study’s authors said, but it is also a boon to families who know for the first time the reason their children share this group of developmental disabilities. “Just having an answer can be hugely beneficial for families,” said co-senior author Elliott Sherr, M.D., Ph.D., a UCSF pediatric neurologist who directs the Brain Development Research Program and the Comprehensive Center for Brain Development at UCSF. “Of course, getting a genetic answer is just the first step, but for the longest time we didn’t even have that much. It gives these families hope that we can move forward.” Finding could speed search for answers in more common genetic syndrome In their paper, the researchers demonstrate that the developmental disabilities suffered by children with RERE mutations correspond almost perfectly to the well-known pattern of intellectual disabilities, heart defects, craniofacial abnormalities, and hearing and vision problems seen in 1p36 deletion syndrome, one of the most common sources of intellectual disability in children. This syndrome occurs in approximately 1 in 5,000 newborns, and is caused by a much larger (and harder to study) pattern of genetic damage in the so-called 1p36 region at the tip of human chromosome 1. The research group of Daryl Scott, MD, PHD, an associate professor of molecular and human genetics at Baylor College of Medicine, has been working for many years to identify the specific genes that cause the medical problems in children with 1p36 deletion syndrome. “Previous research had narrowed it down to two smaller ‘critical regions’ within the 1p36 region, but even these smaller regions contain dozens of different genes,” said Scott, who was co-senior author on the new study. Scott’s group had focused on the RERE gene, which lies within one of these 1p36 critical regions, because it plays a role in retinoic acid (vitamin A) signaling, an important pathway regulating the development of many organs, including the brain, eye and heart. The Baylor researchers found that mice with Rere mutations had birth defects that were very similar to the children with 1p36 deletions, but had initially been unable to prove that damage to this gene was sufficient produce the same developmental problems in humans. Sherr and Scott credit the genesis of their collaboration to Chauntelle Trefz, the mother of one of Sherr’s patients who connected the two researchers after discovering Scott’s work on mice with Rere mutations online and whose Facebook page about her son, Harrison, became a hub for identifying other children with the same condition. Trefz says that getting the whole exome sequencing results from Sherr and learning that a single gene mutation was responsible for her son’s dizzying array of symptoms — which include global developmental delay, vision problems, hearing problems, weak muscles, and constant acid reflux — was “a game-changer.” “Learning about the mutation was like a huge weight had been lifted,” she said. “When you bring a child with special needs into the world you feel so guilty, like you’ve done something wrong. Hope can be a hard thing to find. Dr. Sherr gave us hope.” Trefz started a Facebook page documenting the joys and challenges of raising and caring for Harrison, who is now 4, hoping to find other families whose children had the same condition. “Harrison is such a happy kid, and he seems normal in many ways, but he’s really not,” she said. “I could see a lot of kids falling through the cracks without the right diagnosis. I wanted other parents to see this and say, ‘that sounds like my son.’” Soon Sherr and Scott had identified 10 children with RERE mutations through collaborators around the US, as well as several from the Netherlands who had found the researchers through Trefz’s Facebook page. The researchers began a thorough comparison of these 10 children with a cohort of 31 patients with the more common 1p36 deletion syndrome, and found that RERE mutations alone produced almost exactly the same pattern of symptoms as 1p36 syndrome, with the exception of a few of the craniofacial abnormalities and cardiomyopathies often seen in that more common syndrome. Additional experiments showed that unique brain and eye problems first observed in human patients were also seen in the mice with Rere mutations. “It’s still a shock that [a mutation in] one gene is capable of causing all these different problems,” Scott said. “But this finding really brings everything together, from molecular studies to mouse experiments and all the way to human patients. We’ve finally proved what we’ve been talking about for all these years.” Though much more study is needed to understand the syndrome fully, Scott said, RERE mutations may be capable of inducing a diverse set of developmental problems because the protein encoded by the gene interacts with important developmental processes in many organs throughout the body, such as the retinoic acid signaling crucial for proper eye and heart development. When RERE doesn’t function properly, the development of all of these organs is affected. Sherr acknowledges that the current sample of just 10 patients with RERE mutations, who each experience slightly different symptoms with notably different levels of severity, is too small to give a complete portrait of the new syndrome. “Now that we’ve seen the first 10 cases, we want to know what the next 10, the next 20 look like,” he said. “That may not take very long. Before we’d even published the paper, we’d already gotten calls from more clinics around the country whose patients have similar mutations. We suspect this syndrome may be significantly more common than we previously appreciated.” The empowerment of families through social media and the plummeting cost of of gene sequencing technologies have produced a revolution in the pace of discovery about rare genetic conditions, Sherr said. “In the last five years alone there’s been a huge explosion in the number of conditions we can decipher genetically – we can take a few kids with developmental disabilities, come up with a coherent genetic explanation for what has happened and use that as first step for how to move forward” he said. “When I started working in child neurology as a fellow back in the late ‘90s, we understood just a few of these super-rare genetic disorders but now there are hundreds. And we’re just getting started.” The authors acknowledge the following industry ties: Sherr is a member of the clinical advisory board of genetic testing company InVitae and consults for Personalis. Four of the authors are employees of GeneDx, which provides exome sequencing on a clinical basis. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from clinical laboratory testing conducted at Baylor Miraca Genetics Laboratories, which provides exome sequencing on a clinical basis.


News Article | December 12, 2016
Site: www.eurekalert.org

Scientists have linked a gene called PKD1L1 with disarrangement of human internal organs, known as laterality defects, and complex congenital heart disease. This discovery contributes to a better understanding of the genetic causes of this condition and opens the possibility for families carrying the disease genes to have children unaffected by the disease via prenatal or pre-implantation genetic diagnosis. The study appears in the American Journal of Human Genetics. "This project began when a family was referred to our Baylor Genetics laboratory for prenatal genetic assessment after ultrasound showed complex congenital malformations in the fetus," said first author Dr. Francesco Vetrini, lead clinical genomics scientist at Baylor Genetics. "The liver and spleen and stomach were in the reverse site of the fetus' body, and the heart presented with malformations." This family was searching for an answer because they already had lost one child with a similar disorder. The researchers used whole exome sequencing to analyze all the genes in the fetus' genome looking for a genetic cause of the condition. A variety of genes are already known to cause laterality defects in humans, but the researchers did not find any disease-causing mutations in these genes in the fetus' samples. "However, we found a change in a gene called PKD1L1, which until now had not been associated with any disorders in humans. This prompted us to do additional studies to confirm that the newly found mutation was the cause of the condition," said senior author Dr. Yaping Yang, senior director of Baylor Genetics and associate professor of molecular and human genetics at Baylor College of Medicine. "The role of PKD1L1 in medical genetics was completely unknown, but it was known to a small circle of developmental biologists who had found that the gene is involved in the right and left positioning of internal organs in the mouse and the medaka fish laboratory models," said Vetrini. "In these models, the loss of function of PKD1L1 causes characteristics very similar to those observed in our patient." The next step was to corroborate that this evidence in animal studies also was associated with laterality and congenital defects in humans. First, the scientists found that the previously deceased brother with the same condition carried the same mutation. In addition, thanks to the collaboration with co-authors Dr. James R. Lupski, Cullen Professor of Molecular and Human Genetics at Baylor, Dr. John W. Belmont, now senior principal medical scientist at Illumina Inc., and other colleagues, the scientists found in the Baylor-Hopkins Center for Mendelian Genomics another family in which one member with similar laterality and congenital heart defects had a different mutation in PKD1L1. "Using bioinformatics tools and extensive research in databases and literature we showed that the mutations in PKD1L1 we found in both families cause the laterality and congenital heart defects in the patients," said Vetrini. "Our novel analytical approach to validate the pathogenicity of one of the mutations looked at the genetic change not only in terms of gene-specific evolutionary conservation but also at the effect of the change in the same domain present in functionally and evolutionarily unrelated proteins," said Vetrini. "I am most excited that our work has provided an answer to the affected families and also the possibility of having an action plan for the future," said co-author Alicia Braxton, certified genetic counselor at Baylor Genetics. "Now that we do have a diagnosis, the family may be able to avoid having an affected child in the future by doing tests such as pre-implantation genetic diagnosis (PGD) or prenatal diagnosis. PGD is a test done in the laboratory where specialists determine before implantation whether an embryo carries the gene variant that we now know causes the disease in their family. Implanting embryos that do not have the disease-causing variant would allow the family to have a child that is not affected by laterality defects or heart problems caused by variants in this gene." "This is a remarkable story of how genomic studies in unique families, and even single patients, can catalyze gene discovery efforts and in the process help many other families and doctors struggling with a medical mystery," said Lupski. "This work has been the result of strong collaborations among physicians, geneticists, genetic counselors, patients and their families," said Yang. "Thanks to our research we now know that this gene is associated with this disorder. We can now use this information to counsel other families that might be affected by these gene." Other contributors to this work include Lisa C.A. D'Alessandro, Zeynep C. Akdemir, Mahshid S. Azamian, Mohammad K. Eldomery, Kathryn Miller, Chelsea Kois, Virginia Sack, Natasha Shur, Asha Rijhsinghani, Jignesh Chandarana, Yan Ding, Judy Holtzman, Shalini N. Jhangiani, Donna M. Muzny, Richard A. Gibbs, Christine M. Eng, Neil A. Hanchard, Tamar Harel and Jill A. Rosenfeld. The authors are affiliated with one or more of the following institutions: Baylor Genetics, Texas Children's Hospital, Baylor College of Medicine, Albany Medical Center and Kaiser Permanente Medical Group. The study was supported in part by the US National Human Genome Research Institute (NHGRI)/National Heart Lung and Blood Institute (NHLBI) grant no. U54HG006542 to the Baylor-Hopkins Center for Mendelian Genomics, and the NIH/NIGMS T32 GM07526 Medical Genetics Research Fellowship Program.


NEW YORK, Nov. 11, 2016 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT) (Intercept), a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases, today announced results from three new exploratory analyses of the Phase 3 POISE trial of Ocaliva® (obeticholic acid) in patients with primary biliary cholangitis (PBC). The analyses will be presented at the American Academy for the Study of Liver Diseases (AASLD) Annual Meeting (The Liver Meeting®), taking place in Boston, MA from November 11-15.  The POISE trial evaluated the safety and efficacy of once-daily treatment with Ocaliva in PBC patients with an inadequate therapeutic response to, or who are unable to tolerate, ursodeoxycholic acid (UDCA). Of 216 patients randomized to three treatment arms—placebo, Ocaliva 5 mg titrated to 10 mg or Ocaliva 10 mg—93% continued receiving UDCA. The first POISE presentation (abstract #209) evaluated the effects of Ocaliva on non-invasive assessments of liver fibrosis using both transient elastography (Fibroscan™) and the AST to Platelet Ratio (APRI). These tests have been shown to be effective in predicting clinical outcomes in PBC, and Ocaliva-treated patients experienced improvements in both compared with those receiving placebo. In patients with transient elastography assessments at baseline and month 12 (approximately 43% of the study population), only Ocaliva-treated patients experienced a reduction in liver stiffness below 16.9 kPa, a threshold associated with the presence of cirrhosis. Mean liver stiffness reduction was observed in the 10 mg Ocaliva group compared to placebo. In patients with a baseline APRI score above 0.54 (a threshold associated with increased risk of adverse clinical outcomes in PBC patients), 35% of Ocaliva-treated patients compared to 13% of placebo-treated patients experienced an improvement to below 0.54 at the end of the 12 month double-blind phase. “Because liver biopsies are not routinely used for staging patients with PBC, it is important that we explore non-invasive strategies to evaluate the effects of new therapies like Ocaliva on liver fibrosis,” said Gideon Hirschfield, M.D., Professor and Honorary Consultant Hepatologist, Centre for Liver Research at the University of Birmingham, UK, who presented the data. “These results are very promising, and the ongoing Phase 4 COBALT trial of Ocaliva will provide us with a more definitive understanding of the drug’s ability to improve non-invasive measures of liver fibrosis and reduce the risk of clinical outcomes in our patients with PBC.” The second POISE presentation (abstract #366) evaluated the efficacy and safety of Ocaliva in the subset (17%) of patients with cirrhosis who were at the greatest risk of progression to liver-related adverse outcomes or death. At month 12, more Ocaliva-treated patients with cirrhosis achieved the primary composite study endpoint compared to placebo. Ocaliva treatment improved markers of both cholestasis (alkaline phosphatase) and hepatic impairment (bilirubin) relative to placebo in patients with cirrhosis. Consistent with previous study results, pruritus (itch) was the most common adverse event associated with Ocaliva treatment. Additional side effects observed during the trial included fatigue, abdominal pain and discomfort, rash, oropharyngeal pain, dizziness, constipation, arthralgia, thyroid function abnormality, and eczema. “This exploratory analysis suggests that high-risk PBC patients with compensated cirrhosis benefited from treatment with Ocaliva, and the results were comparable to what we observed in earlier stage non-cirrhotic patients,” said John Vierling, M.D., F.A.C.P., F.A.A.S.L.D., Professor of Medicine and Surgery at Baylor College of Medicine, Past President of AASLD, and lead author of the abstract. “The bilirubin improvements in these patients are particularly meaningful because increasing bilirubin levels – even within the normal range – are one of the hallmarks of progressive disease and strongly associated with clinical outcomes.” The third POISE presentation (abstract #401) examined the effects of Ocaliva in PBC patients with mild and moderate renal impairment. In this exploratory analysis, Ocaliva demonstrated comparable efficacy regardless of renal status and enabled patients with renal impairment to achieve significant improvements in markers of cholestasis and hepatic damage. Ocaliva had no apparent effect on renal safety, with mild to moderate pruritus the most commonly occurring adverse event in all renal function groups. About Primary Biliary Cholangitis Primary biliary cholangitis (PBC) is a rare, autoimmune cholestatic liver disease that puts patients at risk for life-threatening complications. PBC is primarily a disease of women, afflicting approximately one in 1,000 women over the age of 40. If left untreated, survival of PBC patients is significantly worse than the general population. About Ocaliva® (obeticholic acid) Ocaliva (obeticholic acid) is a potent and highly selective agonist of the farnesoid X receptor (FXR), a nuclear receptor expressed in the liver and intestine. FXR is a key regulator of bile acid, inflammatory, fibrotic and metabolic pathways. In May 2016, the U.S. Food and Drug Administration (FDA) granted accelerated approval to obeticholic acid for the treatment of PBC under the brand name Ocaliva based on a reduction in ALP. An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. In October 2016, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending the conditional marketing authorization of Ocaliva in PBC. Based on the CHMP’s positive recommendation, the final decision of the European Commission on the conditional marketing authorization of Ocaliva in PBC is expected by the end of 2016. The brand name Ocaliva has been provisionally approved by the EMA. U.S. IMPORTANT SAFETY INFORMATION Contraindications Ocaliva is contraindicated in patients with complete biliary obstruction. Warnings and Precautions Liver-Related Adverse Reactions In two 3-month, placebo-controlled clinical trials, a dose-response relationship was observed for the occurrence of liver-related adverse reactions including jaundice, ascites and primary biliary cholangitis flare with dosages of Ocaliva of 10 mg once daily to 50 mg once daily (up to 5-times the highest recommended dosage), as early as one month after starting treatment with Ocaliva. In a pooled analysis of three placebo-controlled trials in patients with PBC, the exposure-adjusted incidence rates for all serious and otherwise clinically significant liver-related adverse reactions, and isolated elevations in liver biochemical tests, per 100 patient exposure years (PEY) were: 5.2 in the Ocaliva 10 mg group (highest recommended dosage), 19.8 in the Ocaliva 25 mg group (2.5 times the highest recommended dosage) and 54.5 in the Ocaliva 50 mg group (5 times the highest recommended dosage) compared to 2.4 in the placebo group. Monitor patients during treatment with Ocaliva for elevations in liver biochemical tests and for the development of liver-related adverse reactions. Weigh the potential risks against the benefits of continuing treatment with Ocaliva in patients who have experienced clinically significant liver-related adverse reactions. The maximum recommended dosage of Ocaliva is 10 mg once daily. Adjust the dosage for patients with moderate or severe hepatic impairment. Severe Pruritus Severe pruritus was reported in 23% of patients in the Ocaliva 10 mg arm, 19% of patients in the Ocaliva titration arm and 7% of patients in the placebo arm in the POISE trial, a 12-month double-blind randomized controlled trial of 216 patients. Severe pruritus was defined as intense or widespread itching, interfering with activities of daily living, or causing severe sleep disturbance, or intolerable discomfort, and typically requiring medical interventions. In the subgroup of patients in the Ocaliva titration arm who increased their dosage from 5 mg once daily to 10 mg once daily after 6 months of treatment (n=33), the incidence of severe pruritus was 0% from months 0 to 6 and 15% from months 6 to 12. The median time to onset of severe pruritus was 11, 158 and 75 days for patients in the Ocaliva 10 mg, Ocaliva titration and placebo arms, respectively. Management strategies include the addition of bile acid resins or antihistamines, Ocaliva dosage reduction and/or temporary interruption of Ocaliva dosing. Reduction in HDL-C Patients with PBC generally exhibit hyperlipidemia characterized by a significant elevation in total cholesterol primarily due to increased levels of high density lipoprotein-cholesterol (HDL‑C). In the POISE trial, dose-dependent reductions from baseline in mean HDL-C levels were observed at 2 weeks in Ocaliva-treated patients, 20% and 9% in the 10 mg and titration arms, respectively, compared to 2% in the placebo arm. At month 12, the reduction from baseline in mean HDL-C level was 19% in the Ocaliva 10 mg arm, 12% in the Ocaliva titration arm and 2% in the placebo arm. Nine patients in the Ocaliva 10 mg arm and six patients in the Ocaliva titration arm, versus three patients in the placebo arm, had reductions in HDL-C to less than 40 mg/dL. Monitor patients for changes in serum lipid levels during treatment. For patients who do not respond to Ocaliva after one year at the highest recommended dosage that can be tolerated (maximum of 10 mg once daily), and who experience a reduction in HDL-C, weigh the potential risks against the benefits of continuing treatment. Adverse Reactions The most common adverse reactions from subjects taking Ocaliva (≥5%) were pruritus, fatigue, abdominal pain and discomfort, rash, oropharyngeal pain, dizziness, constipation, arthralgia, thyroid function abnormality and eczema. Drug Interaction Bile Acid Binding Resins Bile acid binding resins such as cholestyramine, colestipol or colesevelam absorb and reduce bile acid absorption and may reduce the absorption, systemic exposure and efficacy of Ocaliva. If taking bile acid binding resins, take Ocaliva at least 4 hours before or 4 hours after (or at as great an interval as possible) taking a bile acid binding resin. To report SUSPECTED ADVERSE REACTIONS, contact Intercept Pharmaceuticals, Inc. at 1-844-782-ICPT or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. About the POISE Trial The POISE trial studied the safety and efficacy of once-daily treatment with Ocaliva in PBC patients with an inadequate therapeutic response to, or who are unable to tolerate, UDCA, the current standard of care. Of 216 patients randomized to three treatment arms—placebo, Ocaliva 5 mg titrated to 10 mg or Ocaliva 10 mg—93% continued receiving UDCA. The Ocaliva 5-10 mg titration group received Ocaliva 5 mg for six months, after which dosing was increased to 10 mg based on tolerability and biochemical response. The trial's primary endpoint was a reduction in ALP to below a threshold of 1.67 times the upper limit of normal, with a minimum of 15% reduction in ALP level from baseline, and a normal bilirubin level after 12 months of therapy. About Intercept Intercept is a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases, including primary biliary cholangitis (PBC), nonalcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC) and biliary atresia. Founded in 2002 in New York, Intercept now has operations in the United States, Europe and Canada. For more information about Intercept, please visit www.interceptpharma.com. Safe Harbor Statements This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the clinical relevance and utility of ALP and the surrogate endpoint used in the Phase 3 POISE trial to predict clinical outcomes, the acceptance of Ocaliva® (obeticholic acid) as a treatment for PBC by healthcare providers, patients and payors, the potential approval of OCA in PBC by the European Commission and other regulatory bodies and the timelines related thereto, the availability of OCA for the treatment of PBC in Europe and other jurisdictions outside the United States and timelines related thereto, the anticipated prevalence of and other epidemiological estimates and market data related to PBC, the continued development of OCA and Intercept's other product candidates, and our strategic directives under the caption "About Intercept." These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of important risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: Intercept's ability to successfully commercialize Ocaliva in PBC, and Intercept's ability to maintain its regulatory approval of Ocaliva in the United States for Ocaliva in PBC; the initiation, cost, timing, progress and results of Intercept's development activities, preclinical studies and clinical trials, including Intercept’s development program in NASH; the timing of and Intercept's ability to obtain and maintain regulatory approval of OCA in PBC in countries outside the United States and in indications other than PBC and any other product candidates it may develop such as INT-767; conditions that may be imposed by regulatory authorities on Intercept's marketing approvals for its product candidates such as the need for clinical outcomes data (and not just results based on achievement of a surrogate endpoint), and any related restrictions, limitations, and/or warnings in the label of any approved product candidates; Intercept's plans to research, develop and commercialize its product candidates; Intercept's ability to obtain and maintain intellectual property protection for its product candidates; Intercept's ability to successfully commercialize OCA in indications other than PBC and its other product candidates; the size and growth of the markets for Intercept's product candidates and its ability to serve those markets; the rate and degree of market acceptance of any of Intercept's products, which may be affected by the reimbursement that it may receive for its products from payors; the success of competing drugs that are or become available; the election by Intercept's collaborators to pursue research, development and commercialization activities; Intercept's ability to attract collaborators with development, regulatory and commercialization expertise; regulatory developments in the United States and other countries; the performance of third-party suppliers and manufacturers; Intercept's need for and ability to obtain additional financing; Intercept's estimates regarding expenses, future revenues and capital requirements and the accuracy thereof; Intercept's use of cash, short-term investments and the proceeds from the offering; Intercept's ability to attract and retain key scientific or management personnel; and other factors discussed under the heading "Risk Factors" contained in our annual report on Form 10-K for the year ended December 31, 2015 filed on February 29, 2016 as well as any updates to these risk factors filed from time to time in our other filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Intercept undertakes no duty to update this information unless required by law.


News Article | November 14, 2016
Site: globenewswire.com

BELGRADE, Mont., Nov. 14, 2016 (GLOBE NEWSWIRE) -- Xtant Medical Holdings, Inc. (NYSE MKT:XTNT), a leader in the development of regenerative medicine products and medical devices, today announced the first surgical cases of the Xspan Laminoplasty Fixation System. The first two cases were performed by Dr. Francisco Vaz-Guimaraes at the Michael E. DeBakey VA Medical Center in Houston. The open door laminoplasty procedure was performed to treat spinal stenosis without fusing the vertebrae. "The Xspan system is easy to put in, final construct was rock solid. Both patients were discharged shortly after the procedure," stated Dr. Vaz-Guimaraes. Dr. Vaz-Guimaraes is a Neurosurgeon and faculty member at Baylor College of Medicine, and contracted with the Michael E. DeBakey VA Medical Center in Houston. Dr. Fuentes and Dr. Ehni, both of the VA Medical Center in Houston, advised from concept to final implant, ensuring Xspan was designed utilizing the expertise of surgeons who routinely perform laminoplasty procedures with the expertise of Xtant Medical engineers. "The Xspan Laminoplasty System has been designed to make the open door laminoplasty technique safer, more adaptable to spondylotic variations in the dorsal element anatomy, and simpler to perform," said Dr. Ehni. Dr. David Kirschman, developer of Xspan and member of the Xtant Medical Board of Directors, states, "The Xspan system is a comprehensive set of implants and instruments to perform the cervical laminoplasty procedure. This procedure allows for direct decompression of the cervical spine, with minimum disruption to patient anatomy. This system is emblematic of Xtant's vision to maximize outcomes while minimizing patient impact." The Xspan System represents the latest generation of laminoplasty fixation. Spinal laminoplasty is a surgical procedure performed to remove pressure from the spinal cord. Unlike a laminectomy, where the entire lamina is removed and often is performed in conjunction with spinal fusion, laminoplasty involves only an opening or window made on one side of the lamina to alleviate the compression of the spinal cord. The lamina is then restructured by a small plate which allows for an expansion of the spinal canal without losing stability or movement in the vertebrae. This procedure can be completed at single or multiple levels. Xtant Medical estimates the worldwide market for laminoplasty at $128M and growing. Xspan is currently available to a limited number of key surgeons with a larger general release to follow later in 2017. Xtant Medical develops, manufactures and markets regenerative medicine products and medical devices for domestic and international markets. Xtant Medical products serve the specialized needs of orthopedic and neurological surgeons, including orthobiologics for the promotion of bone healing, implants and instrumentation for the treatment of spinal disease, tissue grafts for the treatment of orthopedic disorders, and biologics to promote healing following cranial, and foot and ankle surgeries. With core competencies in both biologic and non-biologic surgical technologies, Xtant Medical can leverage its resources to successfully compete in global neurological and orthopedic surgery markets. For further information, please visit www.xtantmedical.com. This press release contains certain disclosures that may be deemed forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to significant risks and uncertainties. Forward-looking statements include statements that are predictive in nature, that depend upon or refer to future events or conditions, or that include words such as "continue," "efforts," "expects," "anticipates," "intends," "plans," "believes," "estimates," "projects," "forecasts," "strategy," "will," "goal," "target," "prospects," "potential," "optimistic," "confident," "likely," "probable" or similar expressions or the negative thereof. Statements of historical fact also may be deemed to be forward-looking statements. We caution that these statements by their nature involve risks and uncertainties, and actual results may differ materially depending on a variety of important factors, including, among others: our ability to integrate the acquisition of X-spine Systems, Inc. and any other business combinations or acquisitions successfully; our ability to remain listed on the NYSE MKT; our ability to obtain financing on reasonable terms; our ability to increase revenue; our ability to comply with the covenants in our credit facility; our ability to maintain sufficient liquidity to fund our operations; the ability of our sales force to achieve expected results; our ability to remain competitive; government regulations; our ability to innovate and develop new products; our ability to obtain donor cadavers for our products; our ability to engage and retain qualified technical personnel and members of our management team; the availability of our facilities; government and third-party coverage and reimbursement for our products; our ability to obtain regulatory approvals; our ability to successfully integrate recent and future business combinations or acquisitions; our ability to use our net operating loss carry-forwards to offset future taxable income; our ability to deduct all or a portion of the interest payments on the notes for U.S. federal income tax purposes; our ability to service our debt; product liability claims and other litigation to which we may be subjected; product recalls and defects; timing and results of clinical studies; our ability to obtain and protect our intellectual property and proprietary rights; infringement and ownership of intellectual property; our ability to remain accredited with the American Association of Tissue Banks; influence by our management; our ability to pay dividends; our ability to issue preferred stock; and other factors. Additional risk factors are listed in the Company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q under the heading "Risk Factors." You should carefully consider the trends, risks and uncertainties described in this document, the Form 10-K and other reports filed with or furnished to the SEC before making any investment decision with respect to our securities. If any of these trends, risks or uncertainties actually occurs or continues, our business, financial condition or operating results could be materially adversely affected, the trading prices of our securities could decline, and you could lose all or part of your investment. The Company undertakes no obligation to release publicly any revisions to any forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events, except as required by law. All forward-looking statements attributable to us or persons acting on our behalf are expressly qualified in their entirety by this cautionary statement.


NEWARK, Calif.--(BUSINESS WIRE)--Revance Therapeutics, Inc. (NASDAQ:RVNC), a biotechnology company developing botulinum toxin products for use in aesthetic and therapeutic indications, today announced positive interim results from its U.S. Phase 2 open-label, dose-escalating clinical study of DaxibotulinumtoxinA Injectable (RT002) to treat moderate-to-severe isolated cervical dystonia in adults, a movement disorder of the neck. The trial enrolled 37 subjects and follows three sequential treatment cohorts for up to a total of 24 weeks after treatment for each cohort. The trial’s first cohort of 12 subjects received a single dose of up to 200 units of RT002 injectable, the second cohort of 12 subjects received between 200 and 300 units, and the third cohort received from 300 to 450 units. Later-enrolled subjects in the second and third cohorts have yet to complete the trial’s 24-week protocol. Today’s results are therefore preliminary, with final results expected in the first half of 2017. “Patients with cervical dystonia suffer from painful, embarrassing twisting movements of the neck, often impairing their ability to work, drive and perform activities of daily living,” said lead trial investigator Dr. Joseph Jankovic, Professor of Neurology, Distinguished Chair in Movement Disorders, Founder, The Parkinson's Disease Center and Movement Disorders Clinic (PDCMDC) Baylor College of Medicine, Houston, Texas. “The current treatment of cervical dystonia calls for injection of botulinum toxin about every 3 months, or 4 times per year, to provide patients with an improved quality of life. The preliminary data in the Phase 2 trial appears quite robust, showing marked improvements in symptoms and signs. I am particularly encouraged that in this trial RT002 exhibited a safety profile at least as good as currently marketed neurotoxins. Furthermore, with a sustained median duration of at least 24 weeks, there is a possibility that patients will require injections only two times a year. Although further studies are needed, RT002 may represent a major advance in neurotoxin technology, which should translate into more meaningful treatment outcomes in patients with cervical dystonia.” “Cervical dystonia is an ideal therapeutic indication for testing the attributes of RT002 injectable,” said Dan Browne, President and Chief Executive Officer at Revance. “We believe these results may have broad implications for the product profile of RT002, as we have now shown long duration in both low- and high-dose indications for small and large muscles. And we’ve also shown long duration of effect in two Phase 2 trials for the treatment of glablellar lines.” “Further, RT002 injectable, even at high doses, may deliver a strong safety profile possibly by limiting the spread of toxin, which could avoid life-altering adverse events such as general muscle weakness and difficulty swallowing,” Browne continued. “We plan to share the final safety, efficacy, and duration results in 2017 once all cohorts have completed the 24-week assessment period. We then intend to seek regulatory advice from US and EU health authorities to determine the next steps in this clinical program.” The abstract for this Phase 2 clinical trial of RT002 injectable to treat cervical dystonia was submitted to the Toxins 2017 (January 18-21, Madrid, Spain) meeting and has been accepted for presentation. Study investigator Cynthia L. Comella, MD, Professor in the Department of Neurological Sciences at Rush University Medical Center, Chicago, Illinois, is scheduled to present. Revance’s Phase 2 trial is an open-label, sequential, dose-escalating study to evaluate the safety, preliminary efficacy and duration of effect of a single treatment of DaxibotulinumtoxinA Injectable (RT002) for isolated cervical dystonia. Thirty-seven subjects with at least moderate cervical dystonia were enrolled at multiple sites in the United States. There are three treatment groups of 12, 12 and 13 subjects, respectively, each subject treated with one of three dose levels of RT002 injectable. The primary efficacy endpoint of the Phase 2 study is an improvement in dystonia symptoms as measured by change (reduction) from baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score at four weeks. TWSTRS is a composite scale that covers different features of the cervical dystonia condition. The first part of the scale is based on the physical findings and severity of dystonia, the second part rates the patient’s perceived level of disability, and the third part rates the pain. The study protocols also feature a number of secondary efficacy endpoints, including duration of effect and patient-rated quality of life as measured by change from baseline in Cervical Dystonia Impact Profile (CDIP). All subjects are followed out to nine weeks, after treatment. Subjects with sustained improvement after this initial period of nine weeks continue to be assessed for duration of efficacy and other measures until they return to baseline or for up to a total of 24 weeks after treatment. Revance management will host a conference call and webcast today at 4:30 pm ET. Individuals interested in listening to the conference call today, December 12, at 1:30 pm PT/4:30 pm ET may do so by dialing (855) 453-3827 for domestic callers, or (484) 756-4301 for international callers and reference conference ID: 37266728; or from the webcast link in the investor relations section of the Company's website at: www.revance.com. In addition, key data slides on the Phase 2 interim trial results will be discussed on the conference call and are posted to Revance’s website on the INVESTORS tab in the Presentations and Corporate Materials section. A replay of the call will be available beginning December 12, 2016 at 4:30 pm PT/7:30 pm ET through 7:30 pm ET on December 13, 2016. To access the replay, dial (855) 859-2056 or (404) 537-3406 and reference Conference ID: 37266728. The webcast will be available in the investor relations section on the Company's website for 30 days following the completion of the call. According to the Dystonia Medical Research Foundation, whose mission is to advance research, promote awareness and education, and support the needs affected individuals, cervical dystonia is a painful condition in which the neck muscles contract involuntarily, causing abnormal movements and awkward posture of the head and neck. The movements may be sustained (tonic), jerky (clonic), or a combination. Cervical dystonia (also referred to as spasmodic torticollis) may be primary (meaning that it is the only apparent neurological disorder, with or without a family history) or may be brought about by secondary causes (such as physical trauma). It can result in considerable pain and discomfort. Treatments for cervical dystonia include oral medications, botulinum toxin injections, surgery, and complementary therapies. Botulinum toxin can help block the communication between the nerve and the muscle and may alleviate abnormal movements and postures. Current botulinum toxin treatments for cervical dystonia have a duration of effect of approximately three months. Cervical dystonia can occur at any age, although most individuals first experience symptoms in middle age. It affects several hundred thousand adults and children in the United States alone. Revance estimates the global market for treating muscle movement disorders with botulinum toxins, including cervical dystonia, was nearly $1 billion in 2015. Revance, a Silicon Valley-based biotechnology company, is committed to the advancement of remarkable science. The company is developing a portfolio of products for aesthetic medicine and underserved therapeutic specialties, including dermatology, orthopedics and neurology. Revance’s science is based upon a proprietary TransMTS® peptide technology, which when combined with active drug molecules, may help address current unmet needs. Revance’s initial focus is on developing daxibotulinumtoxinA, the company’s highly purified botulinum toxin, for a broad spectrum of aesthetic and therapeutic indications, including facial wrinkles and muscle movement disorders. The company’s lead drug candidate, DaxibotulinumtoxinA for Injection (RT002), is currently in development for the treatment of glabellar lines, cervical dystonia and plantar fasciitis with the potential to be the first long-acting neurotoxin. The company holds worldwide rights for all indications of RT002 injectable and RT001 topical and the pharmaceutical uses of the TransMTS technology platform. More information on Revance may be found at www.revance.com. “Revance Therapeutics,” TransMTS®, “Remarkable Science Changes Everything,” and the Revance logo are registered trademarks of Revance Therapeutics, Inc. This press release contains forward-looking statements, including statements related to the process and timing of, and ability to complete, current and anticipated future clinical development of our investigational drug product candidates, including but not limited to initiation and design of clinical studies for current and future indications, related results and reporting of such results; statements about our business strategy, timeline and other goals and market for our anticipated products, plans and prospects; and statements about our ability to obtain regulatory approval; and potential benefits of our drug product candidates and our technologies. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from our expectations. These risks and uncertainties include, but are not limited to: the outcome, cost, and timing of our product development activities and clinical trials; the uncertain clinical development process, including the risks that interim results are not indicative of final results and that clinical trials may not have an effective design or generate positive results; our ability to obtain and maintain regulatory approval of our drug product candidates; our ability to obtain funding for our operations; our plans to research, develop, and commercialize our drug product candidates; our ability to achieve market acceptance of our drug product candidates; unanticipated costs or delays in research, development, and commercialization efforts; the applicability of clinical study results to actual outcomes; the size and growth potential of the markets for our drug product candidates; our ability to successfully commercialize our drug product candidates and the timing of commercialization activities; the rate and degree of market acceptance of our drug product candidates; our ability to develop sales and marketing capabilities; the accuracy of our estimates regarding expenses, future revenues, capital requirements and needs for financing; our ability to continue obtaining and maintaining intellectual property protection for our drug product candidates; and other risks. Detailed information regarding factors that may cause actual results to differ materially from the results expressed or implied by statements in this press release may be found in Revance’s periodic filings with the Securities and Exchange Commission (the “SEC”), including factors described in the section entitled “Risk Factors” of our quarterly report on Form 10-Q filed November 4, 2016. These forward-looking statements speak only as of the date hereof. Revance disclaims any obligation to update these forward-looking statements.


News Article | August 22, 2016
Site: news.mit.edu

Researchers can build complex, nanometer-scale structures of almost any shape and form, using strands of DNA. But these particles must be designed by hand, in a complex and laborious process. This has limited the technique, known as DNA origami, to just a small group of experts in the field. Now a team of researchers at MIT and elsewhere has developed an algorithm that can build these DNA nanoparticles automatically. In this way the algorithm, which is reported together with a novel synthesis approach in the journal Science this week, could allow the technique to be used to develop nanoparticles for a much broader range of applications, including scaffolds for vaccines, carriers for gene editing tools, and in archival memory storage. Unlike traditional DNA origami, in which the structure is built up manually by hand, the algorithm starts with a simple, 3-D geometric representation of the final shape of the object, and then decides how it should be assembled from DNA, according to Mark Bathe, an associate professor of biological engineering at MIT, who led the research. “The paper turns the problem around from one in which an expert designs the DNA needed to synthesize the object, to one in which the object itself is the starting point, with the DNA sequences that are needed automatically defined by the algorithm,” Bathe says. “Our hope is that this automation significantly broadens participation of others in the use of this powerful molecular design paradigm.” The algorithm first represents the object as a perfectly smooth, continuous outline of its surface. It then breaks the surface up into a series of polygonal shapes. Next, it routes a long, single strand of DNA, called the scaffold, which acts like a piece of thread, throughout the entire structure to hold it together. The algorithm weaves the scaffold in one fast and efficient step, which can be used for any shape of 3-D object, Bathe says. “That [step] is a powerful part of the algorithm, because it does not require any manual or human interface, and it is guaranteed to work for any 3-D object very efficiently,” he says. The algorithm, which is known as DAEDALUS (DNA Origami Sequence Design Algorithm for User-defined Structures) after the Greek craftsman and artist who designed labyrinths that resemble origami’s complex scaffold structures, can build any type of 3-D shape, provided it has a closed surface. This can include shapes with one or more holes, such as a torus. In contrast, a previous algorithm, published last year in the journal Nature, is only capable of designing and building the surfaces of spherical objects, and even then still requires manual intervention. Most previous work on DNA origami has explored 2-D and 3-D structures whose design required some steps to be done by hand, says Paul Rothemund, a research professor at Caltech, who was not involved in the paper. “The current work provides a complete pipeline, starting from a 3-D form, and arriving at a DNA design and a corresponding predicted atomic model which can be compared quantitatively with experiments,” he says. The team's strategy in designing and synthesizing the DNA nanoparticles was also validated using 3-D cryo-electron microscopy reconstructions by Bathe's collaborator, Wah Chiu at Baylor College of Medicine. The researchers are now investigating a number of applications for the DNA nanoparticles built by the DAEDALUS algorithm. One such application is a scaffold for viral peptides and proteins for use as vaccines. The surface of the nanoparticles could be designed with any combination of peptides and proteins, located at any desired location on the structure, in order to mimic the way in which a virus appears to the body’s immune system. The researchers demonstrated that the DNA nanoparticles are stable for more than six hours in serum, and are now attempting to increase their stability further. The nanoparticles could also be used to encapsulate the CRISPR-Cas9 gene editing tool. The CRISPR-Cas9 tool has enormous potential in therapeutics, thanks to its ability to edit targeted genes. However, there is a significant need to develop techniques to package the tool and deliver it to specific cells within the body, Bathe says. This is currently done using viruses, but these are limited in the size of package they can carry, restricting their use. The DNA nanoparticles, in contrast, are capable of carrying much larger gene packages and can easily be equipped with molecules that help target the right cells or tissue. The team is also investigating the use of the nanoparticles as DNA memory blocks. Previous research has shown that information can be stored in DNA, in a similar way to the 0s and 1s used to store data digitally. The information to be stored is “written” using DNA synthesis and can then be read back using DNA sequencing technology. Using the DNA nanoparticles would allow this information to be stored in a structured and protected way, with each particle akin to a page or chapter of a book. Recalling a particular chapter or book would then be as simple as reading that nanoparticle’s identity, somewhat like using library index cards, Bathe says. The most exciting aspect of the work, however, is that it should significantly broaden participation in the application of this technology, Bathe says, much like 3-D printing has done for complex 3-D geometric models at the macroscopic scale. Bathe’s co-authors on the paper are Rémi Veneziano, a postdoc in the Department of Biological Engineering; Sakul Ratanalert, a graduate student in the departments of Biological Engineering and Chemical Engineering; and others from Baylor College of Medicine and Arizona State University.


Chronic aortic aneurysms are permanent and localized dilations of the aorta that remain asymptomatic for long periods of time but continue to increase in diameter before they eventually rupture. Left untreated, the patients prognosis is dismal, since the internal bleeding of the rupture brings about sudden death. Although successful treatment cures the disease, the risky procedures can result in paraplegia from spinal cord ischaemia or even death, particularly for aneurysms extending from the thoracic to the abdominal aorta and thus involving many segmental arteries to the spinal cord, i.e. thoracoabdominal aortic aneurysms of Crawford type II. Although various strategies have achieved a remarkable decrease in the incidence of paraplegia, it is still no less than 10 to 20%. However, it has been found that the deliberate occlusion of the segmental arteries to the paraspinous collateral network finally supplying the spinal cord does not increase rates of permanent paraplegia. A therapeutic option, minimally invasive segmental artery coil embolization has been devised which proceeds in a staged way to occlude groups of arteries under highly controlled conditions after which time must be allowed for arteriogenesis to build a robust collateral blood supply. PAPA-ARTiS is a phase II trial to demonstrate that a staged treatment approach can reduce paraplegia and mortality dramatically. It can be expected to have both a dramatic impact on the individual patients quality of life if saved from a wheelchair, and also upon financial systems through savings in; 1) lower costs in EU health care; 2) lower pay-outs in disability insurance (est. at 500k in Year 1), and; 3) loss of economic output from unemployment. Approx. 2500 patients a year in Europe undergo these high risk operations with a cumulative paraplegia rate of over 15%; therefore >100M per year in costs can be avoided and significantly more considering the expected elimination of type II endoleaks.


SAN ANTONIO--(BUSINESS WIRE)--Harland Clarke Holdings (HCH) is excited to announce today its donation of $250,000 to The Children’s Hospital of San Antonio Foundation in support of pediatric emergency care. This gift demonstrates HCH’s commitment to the San Antonio community and the Foundation’s Putting Children First four-year campaign initiated to provide funding for capital, endowment and program support for the hospital. “Harland Clarke Holdings has a long-standing commitment to driving efforts that support and strengthen our communities,” said Victor Nichols, chief executive officer, Harland Clarke Holdings. “We are honored to advance children’s health by supporting a facility that is 100 percent dedicated to providing comprehensive pediatric services.” Harland Clarke Holdings’ gift was used for construction of the emergency department’s pod D and will be recognized on this unit. The emergency department’s pod D includes eight exam rooms, two of which will be used as OB triage/treatment rooms, two forensic exam/treatment rooms for the care of neglected and abused children and a trauma treatment room. The emergency department at The Children’s Hospital of San Antonio is the largest dedicated emergency department in San Antonio with 31,000 square feet and 84,000 patient visits per year. “We are extremely grateful to Harland Clarke Holdings for their generous donation to The Children’s Hospital of San Antonio, which will have an incredible impact on the level of care we are able to provide the San Antonio community,” said John Bel, president, The Children’s Hospital of San Antonio Foundation. “This gift helps continue the momentum of the Putting Children First campaign and allows us to focus on providing exemplary pediatric care, outstanding research, medical education and advocacy for children.” Harland Clarke Holdings is comprised of companies focused on optimizing client relationships through multiple channels by enabling them to acquire, retain and grow their customer base. Its major business units, Harland Clarke, Scantron and Valassis are recognized as leading providers of marketing services, transaction solutions, education services and intelligent media delivery that create millions of customer touch points annually for their clients. Harland Clarke Holdings is a wholly owned company of MacAndrews and Forbes Incorporated. About The Children’s Hospital of San Antonio The Children’s Hospital of San Antonio is the first freestanding hospital in San Antonio solely dedicated to the care of children. Located in the heart of downtown San Antonio, The Children’s Hospital of San Antonio is owned by CHRISTUS Santa Rosa Health System. Baylor College of Medicine, one of the top medical schools in the nation, is the academic partner of The Children’s Hospital with 170 pediatric subspecialists affiliated with Baylor. In addition, community physicians in private practice remain a valuable partner in the care of children in our community. Founded in 1869 by the Sisters of Charity of the Incarnate Word of Houston and San Antonio, CHRISTUS Santa Rosa is a Catholic, faith-based, nonprofit health and wellness ministry dedicated to extending the healing ministry of Jesus Christ and providing the highest quality medical care and services available. Besides The Children’s Hospital, CHRISTUS Santa Rosa has four adult hospitals that are located in the South Texas Medical Center, New Braunfels, Westover Hills, and Alamo Heights. For additional information on The Children’s Hospital of San Antonio, visit www.chofsa.org or for more information on CHRISTUS Santa Rosa, visit www.christussantarosa.org. Find us on Facebook at www.facebook.com/ChildrensHospSA and follow us on Twitter at www.twitter.com/ChildrensHospSA.


News Article | December 8, 2016
Site: www.eurekalert.org

HOUSTON - (Dec. 7, 2016) - Scientists at Baylor College of Medicine, Baylor Genetics, the University of Texas Health Science Center at Houston and Texas Children's Hospital are combining descriptions of patients' clinical features with their complex genetic information in a unified analysis to obtain more precise diagnoses of complex diseases, particularly those that involve more than one gene causing the condition. The researchers anticipate that improved clinical and genetic diagnoses could lead to patients receiving more effective treatments and families benefiting from needed counseling. The study is published in the New England Journal of Medicine. "One of the main interests of our lab is to better understand the impact of genetic variation on human health and disease," said co-first author Dr. Jennifer Posey, assistant professor of molecular and human genetics at Baylor. "Traditionally, physicians have spoken of a unifying diagnosis, meaning that genetic conditions are due to mutations in only one gene," said co-first author Dr. Tamar Harel, who was a genetics fellow at Baylor when she was working on this study and currently is a geneticist at Hadassah Medical Center in Israel. "Yet, we see here that two or more genes can be involved in a disease and produce a complex clinical picture. For many in the field, this is a revolutionary idea." The challenge of diagnosing diseases with multiple genetic causes The researchers used whole exome sequencing to analyze all the genes in the genomes of nearly 7,400 unrelated patients with the goal of identifying the genetic cause of their conditions. They found a genetic cause in 2,076 of the 7,374 patients (28 percent); among these patients, 101 (approximately 5 percent) had two or more disease genes involved. If an individual has multiple defective genes, he or she may present with a complex set of clinical features that may lead to an imprecise diagnosis. "Clinically, multiple genetic causes can be missed because a patient may present with characteristics that overlap those of two different conditions, so the patient can be diagnosed with one or the other," said Posey. "Alternatively, a patient's clinical characteristics may not match those of any described condition, so the patient may be diagnosed with what is thought to be a new condition." "In these situations, we, as physicians, have to think of the possibility that more than one gene might be involved in the patient's disease," said senior author Dr. James R. Lupski, Cullen Professor of Molecular and Human Genetics at Baylor. "Our study shows the limitations of defining a disease according to what we see in the clinic alone. Our work shows the need to consider that a patient may have two or more genetic diseases, not one, and to send for a genomic test to help sort out the patient's condition and causes of it." "One of the contributions of our work involves utilization of a structured phenotype ontology," said Posey. "This computational tool allows us to model complex clinical features (phenotypes) that can result when more than one gene is involved, in order to better understand, from the perspective of the physician, how such cases may present in the clinic." Furthermore, Dr. Regis James, now at Regeneron Pharmaceuticals, previously created OMIM Explorer while training as a graduate student at BCM. OMIM Explorer is a tool that helps analyze genomic data in the context of the clinical characteristics of the patient. Both James and his thesis advisor and mentor, Dr. Chad Shaw, director of bioinformatics at Baylor Genetics and associate professor of molecular and human genetics at Baylor, were contributors to this work. "It provides a more complete perspective of how genes and physical traits relate to each other," said Lupski. "My colleagues and I anticipate that in the future, geneticists, clinicians and mathematicians will work together using genetic and clinical information to make diagnostic and therapeutic decisions," said Harel. "This paper reinforces the need to identify the diagnosis for patients with undiagnosed rare diseases and demonstrates that an unbiased comprehensive approach, such as whole exome sequencing is essential in the 5 percent of cases where two or more disorders are present," said Dr. Ada Hamosh, Dr. Frank V. Sutland Professor and clinical director at the McKusick-Nathans Institute of Genetic Medicine (IGM), and scientific director of Online Mendelian Inheritance in Man® (OMIM) at Johns Hopkins University, who was not a contributor to this study. "This work is especially relevant in the era of precision medicine," said senior co-author Dr. Yaping Yang, senior director of Baylor Genetics and associate professor of molecular and human genetics at Baylor. "I am very happy that in addition to providing molecular diagnoses to individual patients, our data is contributing to a better understanding of genetic disorders and genomic medicine." "Helping patients and their physicians to discover the underlying genetic mechanism of their condition is our most important priority," said co-author Dr. Christine M. Eng, professor of molecular and human genetics at Baylor and chief quality officer and chief medical officer at Baylor Genetics. "The data provided by this study compels us to continue the search for genetic contributions to a patient's overall clinical presentation." Other contributors to this work include Pengfei Liu, Jill A. Rosenfeld, Zeynep H. Coban Akdemir, Magdalena Walkiewicz, Weimin Bi, Rui Xiao, Yan Ding, Fan Xia, Arthur L. Beaudet, Donna M. Muzny, Richard A. Gibbs, Eric Boerwinkle, V. Reid Sutton and Sharon E. Plon. This study was supported by the National Human Genome Research Institute-National Heart, Lung, and Blood Institute grant U54 HG006542; the National Human Genome Research Institute grant U01 HG006485, grant UM1 HG008898, and grant U54 HG003273; the National Institute of Neurological Disorders and Stroke grant R01 NS058529; the National Institutes of Health (Medical Genetics Research Fellowship T32 GM07526) and the Ting Tsung and Wei Fong Chao Foundation. Financial disclosure forms provided by the authors are available with the full text of this article at NEJM.org.


News Article | February 21, 2017
Site: www.eurekalert.org

PHILADELPHIA -- It is commonly known that testosterone levels decrease as men age, but until last year, little was known about the effects of testosterone treatment in older men with low testosterone. Today, in a group of papers published in the Journal of the American Medical Association (JAMA) and JAMA Internal Medicine, researchers found that testosterone treatment improved bone density and anemia for men over 65 with unequivocally low testosterone. However, testosterone treatment did not improve cognitive function, and it increased the amount of plaque buildup in participants' coronary arteries. A team of researchers from the Perelman School of Medicine at the University of Pennsylvania, and twelve other medical centers in the United States, in partnership with the National Institute on Aging, conducted The Testosterone Trials (TTrials), a coordinated group of seven trials, which studied the effects of testosterone treatment for one year as compared to placebo for men 65 and older with low testosterone. The first paper, which reported that testosterone treatment improved sexual function and mood, was published in February 2016. Today's publications of the Bone, Anemia, Cognition and Cardiovascular Trials conclude the primary results of the study. Researchers found that testosterone treatment improved bone density and estimated bone strength, as determined by quantitative computed tomography (CT). The treatment also increased hemoglobin concentrations, corrected the anemia of men who had no other identifiable cause of anemia and corrected the anemia of men who had an identifiable cause, such as iron deficiency. While these conclusions proved testosterone to be beneficial to the participants, testosterone treatment did not improve memory or any other measure of cognitive function. "The paper reporting the results of the first three trials published last year was the first to show there were advantages to giving testosterone treatment to older men with low testosterone levels, and the bone and anemia trial results further support a benefit," said the principal investigator Peter J. Snyder, MD, a professor of Medicine in the Division of Endocrinology, Diabetes and Metabolism. "However, the increase of plaque buildup in the coronary artery shows that this treatment may also have some risk" In the cardiovascular trial, researchers assessed coronary artery plaque buildup by CT angiography. That assessment showed more plaque buildup in men treated with testosterone than in men treated with placebo. Nonetheless, in all 788 men in the TTrials, the number of major adverse cardiovascular events was similar in the men treated with testosterone as in the men treated with placebo. However, Snyder added, "treating 788 men for one year is far too few to draw conclusions about the clinical significance of the increase in coronary artery plaque volume and the cardiovascular risk of testosterone treatment." The TTrials are now the largest trials to examine the efficacy of testosterone treatment in men 65 and older whose testosterone levels are low due seemingly to age alone. TTrials researchers screened 51,085 men to find 790 who qualified with a sufficiently low testosterone level and who met other criteria. The men enrolled were randomized into two groups: one to take a daily testosterone gel and the other a daily placebo gel, for one year. Efficacy was then evaluated at months three, six, nine and 12. "Final decisions about testosterone treatment for older men will depend on balancing the results from these seven TTrials with the results from a much larger and longer term trial designed to assess cardiovascular and prostate risk in the future," said Snyder. The TTrials were conducted at 12 additional medical centers across the country including Albert Einstein College of Medicine, Baylor College of Medicine, Brigham and Women's Hospital, Harbor-UCLA Medical Center, University of Alabama at Birmingham, Northwestern University Feinberg School of Medicine, Puget Sound Health Care System, University of California at San Diego School of Medicine, University of Florida School of Medicine, University of Minnesota School of Medicine, University of Pittsburgh School of Public Health, and Yale School of Medicine. The Testosterone Trials were supported by a grant from the National Institute on Aging (NIA), National Institutes of Health (U01 AG030644). The TTrials were also supplemented by funds from the National Heart, Lung and Blood Institute, National Institute of Neurological Diseases and Stroke, and National Institute of Child Health and Human Development. AbbVie (formerly Solvay and Abbott Laboratories) also provided funding, AndroGel, and placebo gel. Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 18 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $373 million awarded in the 2015 fiscal year. The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2015, Penn Medicine provided $253.3 million to benefit our community.


News Article | December 22, 2016
Site: www.eurekalert.org

An international team of scientists has discovered that the gene, OGDHL, a key protein required for normal function of the mitochondria -- the energy-producing factory of the cell -- and its chaperone, nardilysin (NRD1) are linked to progressive loss of neurological function in humans. Working with the fruit fly, an experimental animal model in the lab, the scientists found a mechanism by which misregulation of mitochondrial function leads to neurodegeneration. The results appear in Neuron. "In our research we look for genes whose loss of function results in deterioration of neurological functions in the fruit fly Drosophila melanogaster," said first author Dr. Wan Hee Yoon, postdoctoral fellow in the laboratory of Dr. Hugo Bellen, professor at Baylor College of Medicine, investigator at the Howard Hughes Medical Institute, and senior author of the paper. "In the fly we found that loss of function of nardilysinled to a slow, progressive neurodegeneration." Yoon and colleagues discovered that nardilysin helps the folding of an important protein, an enzyme called OGDH, present in mitochondria. Loss of nardilysin function results in loss of OGDH and a build-up of a compound called a-ketoglutarate (a-KG). High levels of a-KG increase a cellular response mechanism called mTOR that normally provides clearance of cellular components such as proteins and organelles. Yoon observed that mutation of nardilysin leads to abnormal build-up of a-KG followed by mTOR activation and eventually to slow accumulation of cellular trash. Importantly, a drug named rapamycin suppresses the neurodegenerative conditions caused by this accumulation of cellular garbage. In 2009, a group led by Dr. Eiichiro Nishi in Japan genetically engineered a mouse to lack nardilysin.The mice developed neurological problems with motor coordination, balance and memory issues, findings which at the time were not known to be linked to the mechanism described above in the fruit fly. The team led by Bellen realized that the results in fruit flies and in mice might suggest a role for nardilysin and its target protein OGDH in neurological problems in humans. At the same time that Yoon was investigating nardilysinand its target protein OGDH, across the street co-author Dr. Ender Karaca, a postdoctoral fellow in the laboratory of Dr. James R. Lupski's group at Baylor, was working to solve a rare disease by sequencing the patient's genome through the Baylor-Hopkins Center for Mendelian Genomics (BHCMG). Karaca had discovered a 16-year-old patient with a rare variant in OGDHL who was unable to walk, was bound to a wheelchair and whose head had not grown normally. Yoon and Karaca connected and realized that the mechanism in flies that Yoon was working on might explain the undiagnosed patient of Karaca. "We realized that Ender had identified OGDHL as the top candidate gene for his patient at the same time that we were identifying OGDHL as a target of nardilysin," said Yoon. "After we saw a patient with a severe disorder and variants in OGDHL, we wondered about nardilysin," said Bellen. The researchers then widened their search for similar patients by posting the information of the disease-causing variants of nardilysinin GeneMatcher, a web tool for rare disease researchers developed by the BHCMG team at Johns Hopkins University. Researchers looking for patients carrying rare disease genes post the gene in GeneMatcher. If another researcher around the world has a patient with a matching gene, the teams can contact each other to share the information and collaborate. By posting nardilysinin GeneMatcher, Yoon and colleagues identified a patient whose DNA had been sequenced at the University of California in Los Angeles Clinical Genomics Center. The patient is a 15-year-old boy who presents with symptoms that are remarkably similar to those present in the patient identified by Karaca. "We knew then that these two patients had a very similar disorder, but we had to prove that the genetic variants were causing their conditions," said Yoon and Bellen. Using flies to study how human disease genes work The data from the two patients were strong evidence that the variants in nardilysin and OGDHL are linked to neurodegenerative disease in humans. However, to establish that the disease variants can cause the condition, the researchers turned back to the flies where they could use genetic technology to test the variants. "We can test a human gene side by side with a copy containing a variant from a patient in flies," said co-author Dr. Michael F. Wangler, assistant professor of molecular and human genetics at Baylor. Using this technology, Yoon showed that mutant flies carrying a normal copy of the human gene show normal development and neuronal function. However, flies carrying genes with deleterious variants found in patients failed to rescue the loss of the genes in flies. This suggests that the mutations found in patients are indeed deleterious. "These studies show how valuable the fruit fly model is to uncover and test genes linked to human conditions, and to work out how mutations may cause diseases," said Bellen. Other contributors to this work include Hector Sandoval, Sonal Nagarkar-Jaiswal, Manish Jaiswal, Shinya Yamamoto, Nele A. Haelterman, Nagireddy Putluri, Vasanta Putluri, Arun Sreekumar, Tulay Tos, Ayse Aksoy, Taraka Donti, Brett H. Graham, Mikiko Ohno, Eiichiro Nishi, Jill Hunter, Donna M. Muzny, Jason Carmichael, Joseph Shen, Valerie A. Arboleda, Stanley F. Nelson. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Texas Children's Hospital, Dr. Sami Ulus Research and Training Hospital of Women's and Children's Health and Diseases (Turkey), Kyoto University, Valley Children's Hospital at Madera and the University of California at Los Angeles. This study was supported by grants from the National Institutes of Health (NIH R01GM067858, NIH T32 NS043124-11) and the Research Education and Career Horizon Institutional Research and Academic Career Development Award Fellowship 5K12GM084897, the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, the CPRIT Metabolomics Core Facility Support Award RP120092, NCI/ 2P30CA125123-09 Shared Resources Metabolomics core, Dan L. Duncan Comprehensive Cancer Center (DLDCC), Alkek Center for Molecular Discovery, Mass Spectrometry COE by Agilent and the NIH R01GM098387. Further support came from research grants 26293068, 26670139 and 26116715 and a research program of the P-Direct from the MEXT of Japan and the NIH K08NS076547 funded by National Institute of Neurological Disorders and Stroke. The authors acknowledge the support of the NIH (1RC4GM096355), the Robert A. and Renee E. Belfer Family Foundation, the Huffington Foundation and Target ALS and the Howard Hughes Medical Institute. This work was also supported in part by a grant from the National institute of Neurological Disease and Stroke (R01NS058529), the Baylor-Hopkins Center for Mendelian Genomics, the US National Human Genome Research Institute, National Heart Lung and Blood Institute grant U54HG006542. J.R.L. has stock ownership in 23andMe and Lasergen, is a paid consultant for Regeneron Pharmaceuticals and is a coinventor on multiple United States and European patents related to molecular diagnostics for inherited neuropathies, eye diseases and bacterial genomic fingerprinting. The Baylor College of Medicine derives revenue from the chromosomal microarray analysis and clinical exome sequencing offered in the Baylor Genetics Laboratory.


News Article | November 23, 2016
Site: www.24-7pressrelease.com

SANTA FE, NM, November 23, 2016-- Diana MacArthur has been included in Marquis Who's Who. As in all Marquis Who's Who biographical volumes, individuals profiled are selected on the basis of current reference value. Factors such as position, noteworthy accomplishments, visibility, and prominence in a field are all taken into account during the selection process.Mrs. MacArthur's professional and volunteer lives have, over the years, taken parallel paths, each reinforcing the other. She was Co-founder, Chair, and CEO of Dynamac International Inc.; CEO, Research Analysis and Management Corp.; President, Consumer Dynamics, Inc.; Program Manager, Space Division, General Electric; Vice President, Thomas J. Deegan Co. (a public relations firm in the InterPublic group); and Director, Office of Private and International Organizations, the Peace Corps. She has served as a consultant to Westinghouse, Eastman Kodak, Lever Brothers, the Hearst Corporation, the National Youth Conference on Natural Beauty and Conservation, and the National Recreation and Park Association.Complementing her professional accomplishments, Mrs. MacArthur was a member of or served on the boards of various organizations in the realms of public policy, science, education, and business. These include the following: President's Committee of Advisors on Science and Technology; Citizen's Advisory Board, President's Council on Youth Opportunity; Center for Strategic and International Studies; University of Maryland Biotechnology Institute; Smithsonian Environmental Research Center; Chancellor's Advisory Council, University System of Maryland; Tech Council of Maryland; Council on Competitiveness; Business-Higher Education Forum; Atlantic Council; Santa Fe Institute; Los Alamos National Laboratory Foundation; Science and Technology Corp., University of New Mexico; Lady Bird Johnson Wildflower Center; Menninger-Baylor College of Medicine-The Methodist Hospital Foundation; Business Advisory Committee, Center for China-U.S. Cooperation, University of Denver Graduate School of International Studies.Now retired and drawing on her wealth of experience, Mrs. MacArthur has embarked on a project in one of the most beautiful and daunting regions of the world, the Karakoram Mountains of Pakistan. On a visit to the village of MurtazaAbad, she was asked for help in constructing a building for the local school, and she agreed because her daughter had taught there. Mrs. MacArthur is now undertaking a remarkable effort to build a Center for Educational Excellence along the newly developed China-Pakistan Economic Corridor, bringing modernity to a small but economically and strategically important area of the world.She serves as the principal donor and volunteer project director of the Center, working with the local community and its representative, the Al-Murtaza Educational and Social Welfare Organization. The Center's co-ed primary/secondary schools, now under construction, will be housed in a state-of-the art, earthquake-resistant, high-tech school building, and will provide low-cost education, without discrimination based on religion, gender, ethnicity, or social status. Because a school is more than a building, the outstanding educational precepts of the Aga Khan Educational Network are being followed, and emphasis is being placed on teacher training, curriculum development, parental involvement, and efficient management and administration. Working closely with local families, Mrs. MacArthur has successfully encouraged the bringing together of the Ismaili, Shia, and Sunni Muslim communities, with the goal of providing an outstanding education to the children of the region and creating a vital civil society. Mrs. MacArthur's contributions, in time, expertise, and funding, demonstrate just how much she cares about the world and its citizens, especially children.Mrs. MacArthur has been recognized through features in Who's Who in Finance and Business, Who's Who in Science and Engineering, Who's Who of American Women, Who's Who in the East, Who's Who in the West, Who's Who in America, and Who's Who in the World.About Marquis Who's Who :Since 1899, when A. N. Marquis printed the First Edition of Who's Who in America , Marquis Who's Who has chronicled the lives of the most accomplished individuals and innovators from every significant field of endeavor, including politics, business, medicine, law, education, art, religion and entertainment. Today, Who's Who in America remains an essential biographical source for thousands of researchers, journalists, librarians and executive search firms around the world. Marquis now publishes many Who's Who titles, including Who's Who in America , Who's Who in the World , Who's Who in American Law , Who's Who in Medicine and Healthcare , Who's Who in Science and Engineering , and Who's Who in Asia . Marquis publications may be visited at the official Marquis Who's Who website at www.marquiswhoswho.com


SAN ANTONIO -- A sentinel lymph node biopsy (SLNB) during surgery that showed no signs of cancer was associated with a low risk for breast cancer recurrence in the axillary (armpit) lymph nodes for patients with large, operable breast tumors and no clinical signs of the cancer in the axillary lymph nodes prior to neoadjuvant (presurgery) chemotherapy, according to data from the GANEA 2 clinical trial presented at the 2016 San Antonio Breast Cancer Symposium, held Dec. 6-10. "Axillary lymph node dissection (ALND), which is an invasive surgical procedure in which many of the lymph nodes in the armpit are removed, is often performed to check whether a patient's cancer has spread outside the breast after neoadjuvant chemotherapy," said Jean-Marc Classe, MD, PhD, head of surgery at the Institut de Cancerologie de l'Ouest René Gauducheau in Nantes, France. "ALND has a high risk for serious complications and long-term sequelae. So we wanted to assess the feasibility and safety of the less invasive procedure of SLNB for patients treated with neoadjuvant chemotherapy for a large breast cancer. "We found that for patients with no proof of cancer in the axillary lymph nodes before neoadjuvant chemotherapy, SLNB during the surgery after neoadjuvant chemotherapy was safe because those who had a negative SNLB and did not have an ALND had a very low risk of an axillary relapse at three years after surgery," continued Classe, who is also professor of oncology at the Medical University in Nantes. "We had expected more axillary lymph node relapses than we observed, so this is very exciting and will hopefully mean that more patients are spared the potential complications of invasive ALND." Classe and colleagues enrolled in the trial 590 patients with large, operable breast tumors who had no cancer in the lymph nodes as determined by axillary sonography with fine needle cytology. All patients received neoadjuvant chemotherapy and then underwent surgery and SLNB. Cancer cells were detected in the SLNB samples from 139 patients. These patients all then underwent ALND. No cancer cells were detected in the SLNB samples from 432 patients. Among these 432 patients, follow-up was available for 416. Median follow-up for these patients was 35.8 months. At three years, disease-free survival in the patients who had no cancer in the SLNB sample and, therefore, did not receive ALND was 94.8 percent. One patient had homolateral axillary lymph node relapse. The other nine relapses were metastatic (n=3) or recurrences in the breasts (n=6). Overall survival was 98.7 percent. "The disease-free and overall survival results we observed for the patients who underwent only an SLNB after neoadjuvant chemotherapy are comparable with the historical survival rates for patients in this situation who have ALND rather than SLNB," said Classe. "Therefore, an ALND could be avoided by patients who have no signs of cancer in the axillary lymph nodes following a sonographic axillary assessment prior to neoadjuvant chemotherapy and SLNB during surgery after neoadjuvant chemotherapy." Classe noted that longer follow-up of the patients is needed to further confirm the safety of SLNB for these patients. This study was funded by a grant from the Institut National du Cancer. Classe declares no conflicts of interest. Title: Sentinel node detection after neoadjuvant chemotherapy in patient without previous axillary node involvement (GANEA 2 trial): follow-up of a prospective multi-institutional cohortPresentation: Wednesday, Dec. 7, General Session 2 - Hall 3, 4:45 p.m. CT To interview Jean-Marc Classe, contact Julia Gunther at julia.gunther@aacr.org or 267-250-5441. The mission of the 2016 San Antonio Breast Cancer Symposium is to produce a unique and comprehensive scientific meeting that encompasses the full spectrum of breast cancer research, facilitating the rapid translation of new knowledge into better care for patients with breast cancer. The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio, the American Association for Cancer Research (AACR), and Baylor College of Medicine are joint sponsors of the San Antonio Breast Cancer Symposium. This collaboration utilizes the clinical strengths of the CTRC and Baylor and the AACR's scientific prestige in basic, translational, and clinical cancer research to expedite the delivery of the latest scientific advances to the clinic. For more information about the symposium, please visit http://www. .


News Article | December 9, 2016
Site: www.eurekalert.org

SAN ANTONIO -- Breast cancer mortality rates continue to decline in many nations, but a review of mortality trends in 47 countries around the world indicates some significant disparities, particularly in South Korea and some Latin American nations, according to results presented at the 2016 San Antonio Breast Cancer Symposium, held Dec. 6-10. "Breast cancer is by far the primary cancer site in women and, worldwide, represents a quarter of all cancers in women," said the study's lead author, Cécile Pizot, MSc, at the International Prevention Research Institute in Lyon, France. "Comparing mortality trends between countries helps identify which health care systems have been the most efficient at reducing breast cancer mortality." In this study, Pizot and colleagues extracted information on breast cancer deaths from the World Health Organization database and calculated mortality rates over the years 1987-2013, stratifying results according to age groups. Overall, breast cancer mortality declined in 39 out of 47 countries, including the United States and most developed European nations. England and Wales had the sharpest drop in mortality, with a 46 percent decline. Pizot said this trend was to be expected, due to advances in detection and treatment over the past few decades. Latin American nations experienced scattered increases in mortality; for example, Brazil and Colombia saw mortality rates increase in women of all age groups, while in Argentina and Chile mortality rates decreased in all women. South Korea had the most dramatic increase in breast cancer mortality, with an 83 percent increase overall and higher mortality in every age group. However, the breast cancer mortality rate is still lower than the rate in the United States (5.3 per 100,000 women in South Korea compared with 14 per 100,000 women in the United States in the 2011-2013 period). "South Korea has experienced major societal changes since the 1950s and quickly evolved from an agricultural, developing country to a highly industrialized and Westernized country," Pizot said. "Such quick changes might explain the considerable shift in cancer mortality." Other highlights of the study: "This finding underlines the difficulty of isolating a single, common factor that would have a major influence on mortality trends," Pizot said, adding that future research on breast cancer mortality should focus on other facets of breast cancer management, including risk factors, drug therapies, access to care, and the use of multidisciplinary teams. "Differences in health care systems and patient management could explain discrepancies in mortality reduction between similar countries," Pizot said. "However, there is at present little data comparing the management of breast cancer patients across countries." Pizot said a limitation of the study is that data were unavailable for many Latin American, Asian, and African nations. This study was funded internally by the International Prevention Research Institute. Pizot has no conflicts of interest. Abstract Publication Number: P5-08-04 Title: Overview of breast cancer mortality trends in the world Presentation: Friday, Dec. 9, Poster Session 5, 5 p.m. CT The mission of the 2016 San Antonio Breast Cancer Symposium is to produce a unique and comprehensive scientific meeting that encompasses the full spectrum of breast cancer research, facilitating the rapid translation of new knowledge into better care for patients with breast cancer. The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio, the American Association for Cancer Research (AACR), and Baylor College of Medicine are joint sponsors of the San Antonio Breast Cancer Symposium. This collaboration utilizes the clinical strengths of the CTRC and Baylor and the AACR's scientific prestige in basic, translational, and clinical cancer research to expedite the delivery of the latest scientific advances to the clinic. For more information about the symposium, please visit http://www. . To interview Cécile Pizot, contact Julia Gunther at julia.gunther@aacr.org or 267-250-5441.


SAN ANTONIO -- Radiotherapy increased complications and impaired patient-reported satisfaction with reconstructed breasts in breast cancer patients who received implant reconstruction but not in those who received autologous reconstruction, according to data from a large, prospective, multicenter cohort study presented at the 2016 San Antonio Breast Cancer Symposium, held Dec. 6-10. Autologous breast reconstruction is a procedure in which a woman's own body tissues are used to create a new breast after breast cancer surgery. "There is growing evidence supporting the benefits of post-mastectomy radiotherapy in appropriate patients, but many patients still must decide whether they feel that the benefits given their particular circumstances outweigh the risks," said Reshma Jagsi, MD, DPhil, professor and deputy chair in the Department of Radiation Oncology at the University of Michigan. "One of the risks of radiation therapy is that it may affect the options and outcomes for breast reconstruction, which many women who receive mastectomy desire." Women diagnosed with early-stage breast cancer face challenging decisions that will impact both their long-term disease control and quality of life, Jagsi said. Because many women who undergo mastectomy become long-term survivors, breast reconstruction can have a lasting impact on quality of life. Optimal approaches to integrate post-mastectomy radiotherapy and breast reconstruction are not well established thus far, she added. Jagsi and colleagues conducted a multicenter cohort study called the Mastectomy Reconstruction Outcomes Consortium (MROC), in which they collected medical data and patient-reported outcomes data from 553 and 1,461 patients who did and did not receive radiotherapy, respectively. About 38 percent and 25 percent of the patients who did and did not receive radiotherapy, respectively, received autologous reconstruction, and the rest received implant reconstruction. The researchers assessed if radiotherapy was associated with developing complications after breast reconstruction, such as hematoma and wound infection, and measured patients' satisfaction with the outcome using a BREAST-Q patient-reported outcome instrument, one and two years after reconstruction. After a year of follow-up, 28.8 and 22.3 percent of the patients who did and did not receive radiotherapy, respectively, had at least one of the complications measured. After two years of follow-up, 34.1 percent of the patients who received radiotherapy and 22.5 percent of those who did not receive radiotherapy experienced reconstruction-related complications. When the researchers took several variables into account, radiotherapy was associated with more than double the odds of developing complications in patients who received implants, but it was not associated with complications in those who received autologous reconstruction. Based on BREAST-Q scores, patient-reported satisfaction was significantly lower in those who received radiation versus those who did not receive radiation among patients who received implants, but no such differences were found among patients who received autologous reconstruction. "Although women must still weigh multiple factors, including the differences in operative time and rehabilitation required for different approaches, when selecting their preferred type of reconstruction, those who plan to receive post-mastectomy radiation therapy should be informed of the substantial and significant impact of radiotherapy observed in the current study among patients who received implant reconstruction," Jagsi said. "Conversely, those who plan to pursue autologous reconstruction and are debating whether or not to receive radiotherapy may derive some reassurance from the current study findings that outcomes among patients receiving autologous reconstruction did not appear substantially worse than those of unirradiated patients by two years," she added. A limitation of this study is that it is observational and does not establish cause-effect relationship. Further, patients treated at centers that are particularly skilled in integrating implant-based approaches with radiotherapy may still do well with such an approach, Jagsi noted. This study was funded by the National Cancer Institute. Jagsi declares no conflict of interest. Abstract Publication Number: S3-07 Title: Impact of radiotherapy on complications and patient-reported satisfaction with breast reconstruction: Findings from the prospective multicenter MROC study Presentation: Thursday, Dec. 8, General Session 3 - Hall 3, 11 a.m. CT The mission of the 2016 San Antonio Breast Cancer Symposium is to produce a unique and comprehensive scientific meeting that encompasses the full spectrum of breast cancer research, facilitating the rapid translation of new knowledge into better care for patients with breast cancer. The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio, the American Association for Cancer Research (AACR), and Baylor College of Medicine are joint sponsors of the San Antonio Breast Cancer Symposium. This collaboration utilizes the clinical strengths of the CTRC and Baylor and the AACR's scientific prestige in basic, translational, and clinical cancer research to expedite the delivery of the latest scientific advances to the clinic. For more information about the symposium, please visit http://www. . To interview Reshma Jagsi, contact Julia Gunther at julia.gunther@aacr.org or 267-250-5441.


News Article | February 15, 2017
Site: www.prweb.com

NDA Partners Chairman Carl Peck, MD, announced today that Deborah Wenkert, MD a former Clinical Research Medical Director at Amgen and pediatrics, rheumatology, and bone disease expert has joined the company as an Expert Consultant. Following an immunology postdoc at Harvard University, Dr. Wenkert was an instructor at Washington University School of Medicine and then, for eleven years, an Adjunct Assistant/Associate Clinical Professor at St Louis University School of Medicine in the division of rheumatology. Concurrent with her position at St. Louis University, Dr. Wenkert conducted research in adult and pediatric metabolic bone and genetic disorders and provided care to affected children as the Associate Director of the Center for Metabolic Bone Disease and Molecular Research at Shriners Hospital for Children, St Louis. “Dr. Deborah Wenkert’s knowledge and expertise in adult and pediatric metabolic bone and genetic disorders, in addition to, her extensive experience in pediatric rheumatology and pediatric clinical trials will provide an excellent resource to our clients and to our growing Pediatric Practice,” said Dr. Peck. “We are very pleased to welcome her to NDA Partners.” Dr. Wenkert earned her MD from the University of Texas Medical Branch (Galveston, Texas), attended graduate school at Baylor College of Medicine Graduate School, and obtained a BA in Biochemistry from Rice University. She is board certified in pediatrics and pediatric rheumatology, a member of the American Society for Bone and Mineral Research, and a Fellow of the American Academy of Pediatrics and American College of Rheumatology. About NDA Partners NDA Partners is a strategy consulting firm specializing in expert product development and regulatory advice to the medical products industry and associated service industries such as law firms, investment funds and government research agencies. The highly experienced Principals and Premier Experts of NDA Partners include three former FDA Center Directors; the former Chairman of the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK; an international team of more than 100 former pharmaceutical industry and regulatory agency senior executives; and an extensive roster of highly proficient experts in specialized areas including nonclinical development, toxicology, pharmacokinetics, CMC, medical device design control and quality systems, clinical development, regulatory submissions, and development program management. Services include product development and regulatory strategy, expert consulting, high-impact project teams, and virtual product development teams.


News Article | November 18, 2016
Site: www.eurekalert.org

HOUSTON - (Nov. 17, 2016) - Texas has experienced a roughly 6 percentage-point increase in health insurance coverage from the Affordable Care Act (ACA), according to new research by experts at Rice University and the Episcopal Health Foundation (EHF). This translates into just under 1 million Texans who have gained coverage due to President Barack Obama's health care law. The new findings published in the American Journal of Public Health examined the effects of the ACA's Marketplace on Texas residents and determined which population subgroups benefited the most and the least. "The recent criticism of the program's high premiums for next year ignores the benefits the legislation has provided to many Texans and the fact that policymakers are now identifying options to slow that premium growth," said research co-author Vivian Ho, the chair in health economics at Rice's Baker Institute for Public Policy and director of the institute's Center for Health and Biosciences. The researchers analyzed insurance coverage rates among nonelderly Texas adults using the Health Reform Monitoring Survey-Texas from September 2013, just before the first open-enrollment period in the marketplace, through March 2016. They found that gains have been uneven and that the four subgroups with the largest increases in adjusted insurance coverage between 2013 and 2016 were people ages 50 to 64 years (12.1 percentage points), Hispanics (10.9 percentage points), people reporting fair or poor health status (10.2 percentage points) and those with a high school diploma as their highest educational attainment (9.2 percentage points). "Even with these gains, 3 million Texans between the ages of 19 and 64 remain uninsured," said co-author Elena Marks, EHF's president and CEO and a nonresident health policy fellow at the Baker Institute. "An estimated 766,000 of these would likely have gained coverage if Texas had elected the Medicaid expansion offered under the ACA." President-elect Donald Trump and congressional Republicans have announced their intent to repeal Obamacare. "Moving quickly to repeal the law would jeopardize the policies of the 1 million Texans who have already gained coverage, and would do nothing for the 3 million who are still uninsured," Ho said. "The ACA was designed to be budget neutral for the federal government -- subsidies for people to buy coverage were covered by taxes on insurance companies, medical device makers and others, as well as lower increases in reimbursement rates for Medicare providers. A Republican alternative that is equally successful in covering so many individuals will require careful thought on how this coverage can be paid for without adding to the federal debt." On the federal level, policymakers should focus on reining in price growth from drug manufacturers, as well as physicians and hospitals, Ho said. "At the state level, Texas may have an improved chance at obtaining an extension on its Medicaid waiver beyond 2017 that will allow it to continue receiving federal dollars to provide health care for the poor, without a formal link to President Barack Obama's Medicaid expansion," she said. "This approach is likely economically inefficient, but politically expedient to those in office." "Gain in Insurance Coverage and Residual Uninsurance Under the Affordable Care Act: Texas, 2013-2016" was also co-authored by Stephen Pickett, a doctoral student in Rice's Economics Department. Ho is also a professor of economics at Rice and a professor of medicine at Baylor College of Medicine. For more information, to receive a copy of the study or to schedule an interview with Ho, contact Jeff Falk, associate director of national media relations at Rice, at jfalk@rice.edu or 713-348-6775. Follow the Center for Health and Biosciences via Twitter @BakerCHB. Founded in 1993, Rice University's Baker Institute ranks among the top five university-affiliated think tanks in the world. As a premier nonpartisan think tank, the institute conducts research on domestic and foreign policy issues with the goal of bridging the gap between the theory and practice of public policy. The institute's strong track record of achievement reflects the work of its endowed fellows, Rice University faculty scholars and staff, coupled with its outreach to the Rice student body through fellow-taught classes -- including a public policy course -- and student leadership and internship programs. Learn more about the institute at http://www. or on the institute's blog, http://blogs. .


News Article | October 26, 2016
Site: www.eurekalert.org

Personalized therapies can potentially improve the outcomes of patients with lung cancer, but how to best design such an approach is not always clear. A team of scientists from Baylor College of Medicine and the University of Texas MD Anderson Cancer Center analyzed vast amounts of molecular data from a set of more than 1,000 non-small cell lung cancers that allowed them to break down the cancers into distinct subtypes, each with its own molecular profile and potentially different response to therapy. The results appear in Oncogene. "People may think of lung cancer as one disease, but lung cancer is a collection of diverse subtypes of cells and each subtype may respond differently to the same therapy," said senior author Dr. Chad Creighton, associate professor of medicine and member of the Dan L Duncan Comprehensive Cancer Center Division of Biostatistics at Baylor College of Medicine. By using molecular data - which would inform scientists, for instance, about which genes and proteins the cancer expresses and changes in its DNA- the researchers were able to tease out the different subtypes and have a more refined system of classification for non-small cell lung cancer. "Any two given lung cancers may have very different molecular profiles," said Creighton. "One would have certain genes turned on and produce certain proteins while the other cancer would have different genes turned on and express different proteins. This would imply that one cancer subtype might be more vulnerable to specific therapies while the other might be more susceptible to other therapies." The researchers found that the tumors are complex in more than one way. They are complex because of the diversity of alterations involving tumor cells, but also in the variety of non-tumor cells that are part of the tumor microenvironment. "One big part of the study was to try to tease out the cells in the tumor that actually are not cancer," said Creighton. "Those cells include lymphocytes - a type of immune cell that tries to attack the cancer. Lymphocytes showed up in the tumor profile and we found out that only specific subsets of lung cancer show this really strong pattern for lymphocyte infiltration. These cancer subtypes also show evidence for immune check point pathway, which is a pathway by which cancer cells learn to evade the immune system which normally would actively attack and kill cancer cells. Many cancers have learned some 'tricks' so they can turn on or off specific genes or proteins that allow them to evade the immune response." With these types of analyses the researchers identified specific subsets of cancer cells that they think might be more responsive to immunotherapy - a therapy to boost the body's natural defenses to fight the cancer. Immunotherapy has had a lot of success in a subset of human cancers. "The Cancer Genome Atlas, the cancer initiative that generated these data that we analyzed, involves data for over 10,000 cancers," said Creighton. "That information is now in the public domain and we are currently going through all of the data, not just for lung cancer, but for all the cancer types. We call this pan cancer analysis. We are trying to find features that not just apply to one type of cancer, but across multiple types. Much of our work in the next year is going to be focusing on pan cancer work that might point at ways of treating multiple types of cancer." Other contributors to this work include Fengju Chen, Yiqun Zhang, Edwin Parra, Jaime Rodríguez, Carmen Behrens, Rehan Akbani, Yiling Lu, Jon Kurie, Don Gibbons, Gordon Mills and Ignacio Wistuba, who are affiliated with Baylor and/or the University of Texas MD Anderson Cancer Center. Financial support for this project was provided by the National Institutes of Health (NIH) grant 2R01CA125123-09, MD Anderson's Institutional Tissue Bank Award 2P30CA016672, The University of Texas Lung Specialized Programs of Research Excellence grant P50CA70907, Cancer Prevention and Research Institute of Texas (CPRIT) grant RP120713 C2, P2 and RP150405 and Department of Defense PROSPECT grant W81XWH-07-1-0306.


News Article | December 26, 2016
Site: www.eurekalert.org

HOUSTON - (Dec. 26, 2016) - Scientists have discovered that networks of inhibitory brain cells or neurons develop through a mechanism opposite to the one followed by excitatory networks. Excitatory neurons sculpt and refine maps of the external world throughout development and experience, while inhibitory neurons form maps that become broader with maturation. This discovery adds a new piece to the puzzle of how the brain organizes and processes information. Knowing how the normal brain works is an important step toward understanding the nature of neurological conditions and opens the possibility of finding treatments in the future. The results appear in Nature Neuroscience. "The brain represents the external world as specific maps of activity created by networks of neurons," said senior author Dr. Benjamin Arenkiel, associate professor of molecular and human genetics and of neuroscience at Baylor College of Medicine, who studies neural maps in the olfactory system of the laboratory mouse. "Most of these maps have been studied in the excitatory circuits of the brain because excitatory neurons in the cortex outnumber inhibitory neurons." The studies of excitatory maps have revealed that they begin as a diffuse and overlapping network of cells. "With time," said Arenkiel, "experience sculpts this diffuse pattern of activity into better defined areas, such that individual mouse whiskers, for instance, are represented by discrete segments of the brain cortex. This progression from a diffuse to a refined pattern occurs in many areas of the brain." In addition to excitatory networks, the brain has inhibitory networks that also respond to external stimuli and regulate the activity of neural networks. How the inhibitory networks develop, however, has remained a mystery. In this study, Arenkiel and colleagues studied the development of maps of inhibitory neurons in the olfactory system of the mouse. Studying inhibitory brain networks of the mouse sense of smell "Unlike sight, hearing or other senses, the sense of smell in the mouse detects discrete scents from a large array of molecules," said Arenkiel, who is also a McNair Scholar at Baylor. Mice can detect a vast number of scents thanks in part to a complex network of inhibitory neurons. Inhibitory neurons are the most abundant type of cells in the mouse brain area dedicated to process scent. To support this network, newly born inhibitory neurons are continually added and integrated into the circuits. Arenkiel and colleagues followed the paths of these newly added neurons in time to determine how inhibitory circuits develop. First, they genetically labeled the cells so they would glow when the neurons were active. Then, they offered individual scents to the mice and visually recorded through a microscope the areas or networks of the brain that glowed for each scent the live, anesthetized animal smelled. The scientists repeated the experiment several times to determine how the networks changed as the animal learned to identify each scent. The scientists expected that inhibitory networks would mature in a way similar to that of excitatory networks. That is, the more the animal experienced a scent, the better defined the networks of activity would become. Surprisingly, the scientists discovered that the inhibitory brain circuits of the mouse sense of smell develop in a manner opposite to the excitatory circuits. Instead of becoming narrowly defined areas, the inhibitory circuits become broader. Thanks to this new finding scientists now better understand how the brain organizes and processes information. Arenkiel and colleagues think that the inhibitory networks work hand-in-hand with the excitatory networks. They propose that the interaction between excitatory and inhibitory networks could be compared to a network of roads (excitatory networks) whose traffic is regulated by a network of traffic lights (inhibitory networks). The scientists suggest that the formation of useful neural maps depends on inhibitory networks driving the refinement of excitatory networks, and that this new information will be essential towards developing new approaches for repairing brain tissue. Other contributors to this work include Kathleen B Quast, Kevin Ung, Emmanouil Froudarakis, Longwen Huang, Isabella Herman, Angela P Addison, Joshua Ortiz-Guzmán, Keith Cordiner, Peter Saggau and Andreas S Tolias. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, University of St. Thomas, Allen Institute of Brain Science, Rice University and Texas Children's Hospital. Financial support was provided by the McNair Medical Institute, the Charif Souki Fund, IRACDA Fellowship K12GM084897, NRSA F31NS089178, NINDS grant F31NS081805, NINDS R01NS078294, U54HD083092 to the BCM IDDRC and the Intelligence Advanced Research Projects Activity (IARPA) via Department of Interior/Interior Business Center (DoI/IBC) contract number D16PC00003.


Two studies in the February 14 issue of JAMA examine hair loss among women with breast cancer who received scalp cooling before, during and after chemotherapy. Chemotherapy may result in hair loss (alopecia), which women rate as one of the most distressing adverse effects of chemotherapy. Scalp cooling is hypothesized to reduce blood flow to hair follicles and reduce uptake of chemotherapeutic agents. Modern methods to prevent hair loss use devices that circulate fluid in a cooling cap using refrigeration. A cap is placed on the patient prior to chemotherapy and does not have to be changed or removed until the treatment is completed. Although scalp cooling devices have been used to prevent alopecia, efficacy has not been assessed in a randomized clinical trial. In one study, Julie Nangia, M.D., of the Baylor College of Medicine, Houston, and colleagues randomly assigned 182 women with breast cancer undergoing chemotherapy to scalp cooling (n = 119) or control (n = 63). Scalp cooling was done 30 minutes prior to and during and 90 minutes after each chemotherapy infusion. Hair preservation was assessed at the end of four cycles of chemotherapy. One interim analysis was planned to allow the study to stop early for efficacy. At the time of the interim analysis, 142 participants were evaluable. The researchers found that patients who received scalp cooling were significantly more likely than patients who did not receive scalp cooling to have less than 50 percent hair loss (with 51 percent of those in the scalp cooling group retaining their hair, compared with 0 percent of those in the control group). There were no significant differences in changes in any of the measures of quality of life between the groups. Only adverse events related to device use were collected; 54 adverse events were reported in the cooling group, none serious. "Further research is needed to assess longer-term efficacy and adverse effects," the authors write. In another study, Hope S. Rugo, M.D., of the University of California, San Francisco, and colleagues included women with breast cancer receiving chemotherapy (106 patients in the scalp cooling group and 16 in the control group; 14 matched by both age and chemotherapy regimen). Scalp cooling was initiated 30 minutes prior to each chemotherapy cycle, with scalp temperature maintained at 3°C (37°F) throughout chemotherapy and for 90 minutes to 120 minutes afterward. Although scalp cooling has been available for several decades in Europe, use has been limited in the United States because of several factors, including insufficient prospective efficacy data with current chemotherapy regimens and lack of U.S. Food and Drug Administration (FDA) clearance. Among the 122 patients in the study, the average duration of chemotherapy was 2.3 months. Hair loss of 50 percent or less was seen in 67 of 101 patients (66 percent) evaluable for alopecia in the scalp cooling group vs 0 of 16 patients (0 percent) in the control group. Three of five quality-of-life measures were significantly better one month after the end of chemotherapy in the scalp cooling group. Of patients who underwent scalp cooling, 27 percent reported feeling less physically attractive compared with 56 percent of patients in the control group. Of the 106 patients in the scalp cooling group, four (3.8 percent) experienced the adverse event of mild headache and three (2.8 percent) discontinued scalp cooling due to feeling cold. "Further research is needed to assess outcomes after patients receive anthracycline [a class of drugs used in chemotherapy] regimens, longer-term measures of alopecia, and adverse effects," the authors write. Editor's Note for Nangia et al study: This work was supported by Paxman Coolers Ltd., which contracted with Baylor College of Medicine to conduct the study. Dr. Lacouture is supported in part by a grant from the National Cancer Institute. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc. Editor's Note for Rugo et al study: The study was funded partially by Dignitana AB, the Lazlo Tauber Family Foundation, the Anne Moore Breast Cancer Research Fund, and the Friedman Family Foundation. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc. Related material: The editorial, "Scalp Cooling to Prevent Chemotherapy-Induced Alopecia," by Dawn L. Hershman, M.D., M.S., of Columbia University Medical Center, New York; the article, in JAMA Oncology, "Do the Data on Scalp Cooling for Patients with Breast Cancer Warrant Broad Adoption?" by Howard (Jack) West, M.D., of the Swedish Cancer Institute, Seattle, and Web Editor, JAMA Oncology; the JAMA Patient Page, "Chemotherapy and Hair Loss,"; and images of scalp cooling and photographic results of two patients treated with scalp cooling are available at the For The Media website. To place an electronic embedded link to these studies in your story These links will be live at the embargo time: http://jamanetwork. http://jamanetwork.


News Article | December 5, 2016
Site: www.eurekalert.org

SAN ANTONIO -- The American Association for Cancer Research (AACR) will honor two renowned researchers for their work in breast cancer at the 2016 San Antonio Breast Cancer Symposium, held Dec. 6-10. Fergus J. Couch, PhD, of the Mayo Clinic in Rochester, Minnesota, will receive the ninth annual AACR Outstanding Investigator Award for Breast Cancer Research, funded by Susan G. Komen, and Max S. Wicha, MD, of the University of Michigan Comprehensive Cancer Center in Ann Arbor, will receive the ninth annual AACR Distinguished Lectureship in Breast Cancer Research. The AACR Outstanding Investigator Award for Breast Cancer Research recognizes an investigator of no more than 50 years of age whose novel and significant work has had or may have a far-reaching impact on the etiology, detection, diagnosis, treatment, or prevention of breast cancer. Such work may involve any discipline across the continuum of biomedical research, including basic, translational, clinical, and epidemiological studies. Couch, who is the Zbigniew and Anna M. Scheller professor of medical research, and chair of the Division of Experimental Pathology and Laboratory Medicine in the Department of Laboratory Medicine and Pathology at the Mayo Clinic, is being honored for his seminal work in identifying the inherited genes and mutations that predispose to breast cancer. Much of his research has focused on determining the clinical relevance of inherited variants of uncertain significance (VUS) in breast cancer predisposition genes using genetic epidemiology and molecular biology approaches. Couch will present his Outstanding Investigator Award for Breast Cancer Research lecture, "Decoding Breast Cancer Predisposition Genes," Friday, Dec. 9, at 11:30 a.m. CT, in Hall 3 of the Henry B. Gonzalez Convention Center. A distinguished national leader in cancer genetics, Couch is a founder and member of the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium, and a leader in the BRCA Challenge and the Prospective Registry of Multiplex Testing (PROMPT) initiatives aimed at understanding alterations in cancer predisposition genes. He is also a co-founder of the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a Triple Negative Breast Cancer Consortium (TNBCC), and is a long-term member of the Breast Cancer Association Consortium. Working with members of these consortia, Couch has led genome-wide association studies to identify common genetic variants that influence risk of estrogen receptor (ER) negative and triple negative breast cancer and modify risks of breast cancer among carriers of germline BRCA1 and BRCA2 mutations. In more recent research, Couch has been working to estimate risks of breast cancer associated with pathogenic variants identified by clinical genetic testing using multigene panels, and is leading an effort to identify genetic factors that account for the missing heritability of breast cancer. The AACR Distinguished Lectureship in Breast Cancer Research was established to recognize outstanding science that has inspired or has the potential to inspire new perspectives on the etiology, diagnosis, treatment, or prevention of breast cancer. Wicha, director emeritus of the University of Michigan Comprehensive Cancer Center, is being recognized for his leadership in breast cancer research and as a pioneer in the field of cancer stem cells (CSCs). Wicha is among the most highly cited investigators in the field. His group was part of the team that first identified CSCs in human breast cancers, the first in any solid tumor. His laboratory has developed many of the techniques and assays used to study these cells and to elucidate the pathways which regulate their behavior. These pathways have provided targets for the development of drugs aimed at targeting CSCs. He will present his Distinguished Lectureship in Breast Cancer Research award lecture, "Targeting Breast Cancer Stem Cells: Challenges and Opportunities," Thursday, Dec. 8, at 11:30 a.m. CT, in Hall 3 of the Henry B. Gonzalez Convention Center. Wicha is co-founder of OncoMed Pharmaceuticals, a company focused on developing CSC therapeutics, which has produced five agents currently in clinical testing. After training at the National Cancer Institute in clinical oncology and cancer biology, Wicha joined the faculty of the University of Michigan in 1980, where he served as chief in the Division of Hematology/Oncology in the Department of Internal Medicine. He served as director of the University of Michigan Comprehensive Cancer Center since its inception in 1986 until 2015, when he became director emeritus. He remains an active clinician, specializing in the treatment of patients with breast cancer. The mission of the 2016 San Antonio Breast Cancer Symposium is to produce a unique and comprehensive scientific meeting that encompasses the full spectrum of breast cancer research, facilitating the rapid translation of new knowledge into better care for patients with breast cancer. The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio, the American Association for Cancer Research (AACR), and Baylor College of Medicine are joint sponsors of the San Antonio Breast Cancer Symposium. This collaboration utilizes the clinical strengths of the CTRC and Baylor and the AACR's scientific prestige in basic, translational, and clinical cancer research to expedite the delivery of the latest scientific advances to the clinic. For more information about the symposium, please visit http://www. .


News Article | December 16, 2016
Site: www.eurekalert.org

HOUSTON - (Dec. 16, 2016) - Neuroscience and artificial intelligence experts from Rice University and Baylor College of Medicine have taken inspiration from the human brain in creating a new "deep learning" method that enables computers to learn about the visual world largely on their own, much as human babies do. In tests, the group's "deep rendering mixture model" largely taught itself how to distinguish handwritten digits using a standard dataset of 10,000 digits written by federal employees and high school students. In results presented this month at the Neural Information Processing Systems (NIPS) conference in Barcelona, Spain, the researchers described how they trained their algorithm by giving it just 10 correct examples of each handwritten digit between zero and nine and then presenting it with several thousand more examples that it used to further teach itself. In tests, the algorithm was more accurate at correctly distinguishing handwritten digits than almost all previous algorithms that were trained with thousands of correct examples of each digit. "In deep-learning parlance, our system uses a method known as semisupervised learning," said lead researcher Ankit Patel, an assistant professor with joint appointments in neuroscience at Baylor and electrical and computer engineering at Rice. "The most successful efforts in this area have used a different technique called supervised learning, where the machine is trained with thousands of examples: This is a one. This is a two. "Humans don't learn that way," Patel said. "When babies learn to see during their first year, they get very little input about what things are. Parents may label a few things: 'Bottle. Chair. Momma.' But the baby can't even understand spoken words at that point. It's learning mostly unsupervised via some interaction with the world." Patel said he and graduate student Tan Nguyen, a co-author on the new study, set out to design a semisupervised learning system for visual data that didn't require much "hand-holding" in the form of training examples. For instance, neural networks that use supervised learning would typically be given hundreds or even thousands of training examples of handwritten digits before they would be tested on the database of 10,000 handwritten digits in the Mixed National Institute of Standards and Technology (MNIST) database. The semisupervised Rice-Baylor algorithm is a "convolutional neural network," a piece of software made up of layers of artificial neurons whose design was inspired by biological neurons. These artificial neurons, or processing units, are organized in layers, and the first layer scans an image and does simple tasks like searching for edges and color changes. The second layer examines the output from the first layer and searches for more complex patterns. Mathematically, this nested method of looking for patterns within patterns within patterns is referred to as a nonlinear process. "It's essentially a very simple visual cortex," Patel said of the convolutional neural net. "You give it an image, and each layer processes the image a little bit more and understands it in a deeper way, and by the last layer, you've got a really deep and abstract understanding of the image. Every self-driving car right now has convolutional neural nets in it because they are currently the best for vision." Like human brains, neural networks start out as blank slates and become fully formed as they interact with the world. For example, each processing unit in a convolutional net starts the same and becomes specialized over time as they are exposed to visual stimuli. "Edges are very important," Nguyen said. "Many of the lower layer neurons tend to become edge detectors. They're looking for patterns that are both very common and very important for visual interpretation, and each one trains itself to look for a specific pattern, like a 45-degree edge or a 30-degree red-to-blue transition. "When they detect their particular pattern, they become excited and pass that on to the next layer up, which looks for patterns in their patterns, and so on," he said. "The number of times you do a nonlinear transformation is essentially the depth of the network, and depth governs power. The deeper a network is, the more stuff it's able to disentangle. At the deeper layers, units are looking for very abstract things like eyeballs or vertical grating patterns or a school bus." Nguyen began working with Patel in January as the latter began his tenure-track academic career at Rice and Baylor. Patel had already spent more than a decade studying and applying machine learning in jobs ranging from high-volume commodities training to strategic missile defense, and he'd just wrapped up a four-year postdoctoral stint in the lab of Rice's Richard Baraniuk, another co-author on the new study. In late 2015, Baraniuk, Patel and Nguyen published the first theoretical framework that could both derive the exact structure of convolutional neural networks and provide principled solutions to alleviate some of their limitations. Baraniuk said a solid theoretical understanding is vital for designing convolutional nets that go beyond today's state-of-the-art. "Understanding video images is a great example," Baraniuk said. "If I am looking at a video, frame by frame by frame, and I want to understand all the objects and how they're moving and so on, that is a huge challenge. Imagine how long it would take to label every object in every frame of a video. No one has time for that. And in order for a machine to understand what it's seeing in a video, it has to understand what objects are, the concept of three-dimensional space and a whole bunch of other really complicated stuff. We humans learn those things on our own and take them for granted, but they are totally missing in today's artificial neural networks." Patel said the theory of artificial neural networks, which was refined in the NIPS paper, could ultimately help neuroscientists better understand the workings of the human brain. "There seem to be some similarities about how the visual cortex represents the world and how convolutional nets represent the world, but they also differ greatly," Patel said. "What the brain is doing may be related, but it's still very different. And the key thing we know about the brain is that it mostly learns unsupervised. "What I and my neuroscientist colleagues are trying to figure out is, What is the semisupervised learning algorithm that's being implemented by the neural circuits in the visual cortex? and How is that related to our theory of deep learning?" he said. "Can we use our theory to help elucidate what the brain is doing? Because the way the brain is doing it is far superior to any neural network that we've designed." The research was funded by the Director of National Intelligence's Intelligence Advanced Research Projects Activity, the National Science Foundation, the Air Force Office of Science and Research, the Army Research Office and the Office of Naval Research. High-resolution IMAGES are available for download at: http://news. CAPTION: From left, Richard Baraniuk, Tan Nguyen and Ankit Patel. (Photo by Jeff Fitlow/Rice University) http://news. CAPTION: From left, Richard Baraniuk, Tan Nguyen and Ankit Patel. (Photo by Jeff Fitlow/Rice University) This release can be found online at news.rice.edu. Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation's top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,910 undergraduates and 2,809 graduate students, Rice's undergraduate student-to-faculty ratio is 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for happiest students and for lots of race/class interaction by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger's Personal Finance. To read "What they're saying about Rice," go to http://tinyurl. .


News Article | November 18, 2016
Site: www.eurekalert.org

HOUSTON -- (Nov. 18, 2016) -- Scientists from Rice University, Baylor College of Medicine and other institutions are using synthetic biology to capture elusive, short-lived snippets of DNA that healthy cells produce on their way to becoming cancerous. Researchers said the work could lead to the development of new drugs that could prevent cancer by neutralizing "DNA intermediates," key pieces of genetic code that are produced when healthy cells become cancerous. The research is described in a new paper in the open-access journal Science Advances. "In my lab we study how the genome -- the genes in an organism -- changes, in particular, how the genome of normal cells changes to transform the cells into cancerous cells," said project lead scientist Susan Rosenberg, Baylor's Ben F. Love Chair in Cancer Research and the leader of the Cancer Evolvability Program at Baylor's Dan L Duncan Comprehensive Cancer Center. When cells divide and make copies of the instructions encoded in their DNA, the DNA unwinds and becomes vulnerable to damage that must be repaired. Sometimes the process of repairing the DNA can also cause mutations and errors. When these errors accumulate, the cells may acquire characteristics of cancer. "The process of editing the DNA is carried out by specific enzymes -- proteins that work on DNA to fix the mistakes," said Rosenberg, who is also an adjunct professor in Rice's Department of BioSciences. She said DNA repair usually takes several steps to complete. Between the original DNA and the final product, cells produce DNA reaction intermediates, which are crucial to the reaction but are difficult to study because they are present for just a fraction of a second as an enzyme catalyzes the changing of one molecule into another. "The intermediate molecules are the most important parts of biochemical reactions," said Rosenberg, who holds appointments in Baylor's departments of Molecular and Human Genetics, Molecular Virology and Microbiology, and Biochemistry and Molecular Biology. "They define what the reaction is and how it will proceed. But because they are transient and elusive, it's really difficult to study them, especially in living cells. We wanted to do that. We decided to invent synthetic proteins that would trap DNA reaction intermediates in living cells." Qian Mei, a graduate student in Rice's Systems, Synthetic and Physical Biology program and a research assistant in the Rosenberg lab, took on the task of applying the synthetic protein that could capture the short-lived intermediates. Using the tools of synthetic biology, Rosenberg and colleagues created and added packages of genes to Escherichia coli, an organism that Rosenberg's group and others have shown to be a reliable model of the genetic changes that occur in animal cells. Rosenberg said other investigators also have attempted to trap intermediates, but they have only succeeded in a few biochemical reactions. "We want to use synthetic proteins to study mechanisms that change DNA sequence," she said. "We do that now with genetics and genomics in my lab. But genomics, which allows us to compare the genes of normal cells with those of cancerous cells, is like reading the fossil record of these processes. We want to see how the real-time processes that change DNA happen, including all the intermediate steps, which our synthetic proteins allow us to freeze in time and isolate." In their tests on , Mei, Rosenberg and colleagues from Baylor, the University of Texas at Austin and the University of Texas MD Anderson Cancer Center found they could discover molecular mechanisms underlying genome instability, a hallmark of cancer. In one instance, they discovered a new role for an protein that is related to five human cancer proteins. They then analyzed gene-expression data from human cancers and were able to implicate two of the five -related human cancer proteins in potentially promoting cancer by a similar mechanism -- one not previously implicated. "The most exciting part in this paper for me is that we can learn something new about the mechanisms of cancer from the model," said Mei, co-first author of the new paper. "Even though bacteria and human cells are very different, many DNA repair proteins are highly conserved through evolution; this makes a good model to study how cells repair DNA or accumulate mutations." Rosenberg and colleagues think that their approach offers significant advantages. For instance, with the synthetic proteins, they have been able to identify specific DNA-repair intermediate molecules, their numbers in cells, rates of formation and locations in the genome and the molecular reactions in which they participate. "It is most exciting that we are now able to trap, map and quantify transient DNA reaction intermediates in single living cells," said co-first author Jun Xia, graduate student in the Rosenberg lab and in the Integrative Molecular and Biomedical Sciences program at Baylor. "This new technology helps us reveal the origins of genome instability." "When you know these reactions and the role each intermediate plays in the mechanisms that change DNA, you can think about making drugs that will stop them," Rosenberg said. "In the future, we hope we will be able to design drugs that target specific types of cancers -- drugs that block the cells' ability to evolve into cancer cells, instead of, or in addition to, traditional chemotherapies that kill or stop cancer cells from growing." Other contributors to the work include Li-Tzu Chen, Chien-Hui Ma, Jennifer Halliday, Hsin-Yu Lin, David Magnan, John Pribis, Devon Fitzgerald, Holly Hamilton, Megan Richters, Ralf Nehring, Xi Shen, Lei Li, David Bates, P.J. Hastings, Christophe Herman and Makkuni Jayaram. The research was supported by the WM Keck Foundation, the National Institutes of Health, NASA, the Cancer Prevention and Research Institute of Texas, the National Science Foundation, the Welch Foundation, Baylor College of Medicine, the Dan L Duncan Comprehensive Cancer Center and the John S. Dunn Gulf Coast Consortium for Chemical Genomics. VIDEO is available at: High-resolution IMAGES are available for download at: CAPTION: (From left) Baylor College of Medicine's Susan Rosenberg discusses research aimed at capturing elusive, short-lived "DNA intermediates," key pieces of genetic code that are produced when healthy cells become cancerous, with Baylor graduate student Jun Xia and Rice University graduate student Qian Mei, who are co-first authors on a new paper about the work in Science Advances. (Photo courtesy of Baylor College of Medicine) CAPTION: The orange wheel shows the circular chromosome or genome of bacteria. The spikes indicate where a molecular intermediate in DNA repair -- four-way DNA junctions -- accumulate near a reparable double strand break in the genome. (Image courtesy of Jun Xia and Qian Mei) The DOI of the Science Advances paper is: 10.1126/sciadv.1601605 A copy of the paper is available at: http://advances. This release can be found online at news.rice.edu. Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation's top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,910 undergraduates and 2,809 graduate students, Rice's undergraduate student-to-faculty ratio is 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for happiest students and for lots of race/class interaction by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger's Personal Finance. To read "What they're saying about Rice," go to http://tinyurl. .


Nanotechnology - What You Should Know Top Scientific Minds You Probably Never Heard Of The Breakthrough Prizes 2017 were given away at an Oscars-like function in the NASA Ames Research Center in Mountain View on Sunday, Dec. 4, to honor outstanding research in life sciences, mathematics and fundamental physics. Attended by the Who's Who of the technology industry and scientific honchos, the award function was hosted by actor Morgan Freeman. At the ceremony, a total of $25 million was awarded to the winners. The event had Grammy winner Alicia Keys rendering live pop entertainment. "There has never been a more important time to support science," said Facebook founder Mark Zuckerberg, one of the patrons of the foundation. For conceiving the gala event in science, credit goes to Yuri Milner, the Russian billionaire and investor, and his wife, Julia, who instituted the debut award in 2012 to reward theoretical physicists for outstanding scientific achievements. Since then, the number of disciplines for awards expanded with more sponsors stepping in to support the cause. Among the new patrons are Google's Sergey Brin, Mark Zuckerberg of Facebook, biotech firm 23andMe's Anne Wojcicki and Jack Ma and his wife Cathy Zhang of Alibaba. The 2017 Breakthrough Prizes ceremony also marked the organization's fifth anniversary. Since 2012, the Breakthrough Prize has disbursed close to $200 million in honoring paradigm-shifting research in science. The awardees this year in life sciences, fundamental physics and mathematics are the following. These winners get individual $3 million in prizes. - Stephen J. Elledge, Professor of Genetics and Medicine in the Department of Genetics at Harvard Medical School, for probing the role of damage detection proteins in yielding mutated DNA replication and increasing cancer risk. - Harry F. Noller, Director, Center for Molecular Biology at the University of California. His work investigates the central role of RNA in the ribosome and origin of life. - Roeland Nusse, Professor at Stanford University. He explored the Wnt gene pathway and its implications in cancer. - Yoshinori Ohsumi, Honorary Professor, Institute of Innovative Research at Tokyo Institute of Technology. The work included the investigation of autophagy by which cells recycle their components to create nutrients. - Huda Yahya Zoghbi, Professor of Pediatrics, Baylor College of Medicine. The work was the discovery of biological underpinnings of spinocerebellar ataxia. The following three recipients shared a single $3 million award for their advances in string theory, quantum field theory and quantum gravity. - Joseph Polchinski, Professor of Physics at the University of California, Santa Barbara The following three winners shared a single $1 million prize, while $2 million was divided among 1,012 members of their research team. - Ronald Drever, Professor at the California Institute of Technology, Pasadena - Kip Thorne, Feynman Professor of Physics at the California Institute of Technology, Pasadena - Rainer Weiss, Professor at the Massachusetts Institute of Technology - Jean Bourgain, Professor, Institute for Advanced Study, Princeton, for contributions to high-dimensional geometry and other theoretical areas. One of the highlights of the awarding ceremony was the speeches by female students Antonella Masini, 18 (Peru) and Deanna See, 17 (Singapore). They were the winners of the Breakthrough Junior Challenge and got $250,000 for their inspiring science videos that promoted creative thinking on life sciences, physics and mathematics. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.


2017 Breakthrough Prize in Life Sciences Awarded to Stephen J. Elledge, Harry F. Noller, Roeland Nusse, Yoshinori Ohsumi, and Huda Yahya Zoghbi 2017 Breakthrough Prize in Fundamental Physics Awarded to Joseph Polchinski, Andrew Strominger, and Cumrun Vafa New Horizons in Physics Prize awarded to Asimina Arvanitaki, Peter W. Graham, and Surjeet Rajendran; Simone Giombi and Xi Yin; and Frans Pretorius New Horizons in Mathematics Prize awarded to Mohammad Abouzaid, Hugo Duminil-Copin, and Benjamin Elias and Geordie Williamson Second Annual, International Breakthrough Junior Challenge Won by Female Students Antonella Masini, 18 (Peru) and Deanna See, 17 (Singapore) 2016 Special Breakthrough Prize in Fundamental Physics, awarded in May to founders and team members of LIGO, awarded to Kip Thorne, Rainer Weiss and family of Ronald Drever Laureates to be honored at glittering awards gala hosted by Morgan Freeman, with live performance by Alicia Keys and presentations from Daniel Ek (CEO of Spotify), Jeremy Irons, Mark and Scott Kelly, Hiroshi Mikitani (CEO of Rakuten), Sienna Miller, Bryce Dallas Howard, Vin Diesel, Kevin Durant, Dev Patel, Sundar Pichai (CEO of Google), Alex Rodriguez, Will.i.am, Susan Wojcicki (CEO of YouTube) and the founders of the Breakthrough Prize SAN FRANCISCO, Dec. 5, 2016 /PRNewswire/ -- The Breakthrough Prize and founders Sergey Brin and Anne Wojcicki, Yuri and Julia Milner, and Mark Zuckerberg and Priscilla Chan, tonight announced the recipients of the 2017 Breakthrough Prizes, marking the organization's fifth anniversary recognizing top achievements in Life Sciences, Fundamental Physics and Mathematics. A combined total of $25 million was awarded at the gala ceremony in Silicon Valley, hosted by Morgan Freeman. Each of the Breakthrough Prizes is worth $3 million, the largest individual monetary prize in science. This year, a total of seven of these prizes were awarded to nine individuals, along with a $3 million Special Breakthrough Prize in Fundamental Physics, which was split between three founders and more than a thousand members of the LIGO team. In addition, three $100,000 New Horizons in Physics Prizes were awarded to six early-career physicists, and a further three $100,000 New Horizons in Mathematics Prizes were awarded to four young mathematicians. And this year there were two winners of the Breakthrough Junior Challenge, each receiving up to $400,000 in educational prizes for them, their teacher and their school. Since its inception in 2012, the Breakthrough Prize has awarded close to $200 million to honor paradigm-shifting research in the fields of fundamental physics, life sciences, and mathematics. "There has never been a more important time to support science," said Facebook founder Mark Zuckerberg. "The 2017 Breakthrough Prize laureates represent the leaders in scientific research in physics, math and life sciences. Their breakthroughs will unlock new possibilities and help make the world a better place for everyone." The 2017 Breakthrough Prize in Life Sciences was awarded to Stephen J. Elledge (Harvard Medical School); Harry F. Noller (University of California, Santa Cruz); Roeland Nusse (Stanford University); Yoshinori Ohsumi (Tokyo Institute of Technology); Huda Yahya Zoghbi (Baylor College of Medicine). The 2017 Breakthrough Prize in Fundamental Physics was awarded to Joseph Polchinski (University of California, Santa Barbara); Andrew Strominger (Harvard University); and Cumrun Vafa (Harvard University). The three honorees joined the recipients of the previously announced Special Prize in Fundamental Physics, released in May 2016. Ronald Drever (California Institute of Technology, Pasadena), Kip Thorne (California Institute of Technology, Pasadena) and Rainer Weiss (Massachusetts Institute of Technology), were recognized in May for their detection of gravitational waves, opening new horizons in astronomy and physics. The three winners of the Special Prize will share a $1 million prize, and 1,012 LIGO team members will share $2 million. The 2017 Breakthrough Prize in Mathematics was awarded to Jean Bourgain (Institute for Advanced Study). This year's ceremony will mark the fifth anniversary of the organization, and laureates will take to the stage tonight at an exclusive gala co-hosted by founders Sergey Brin and Anne Wojcicki, Yuri and Julia Milner, Mark Zuckerberg and Priscilla Chan, and Vanity Fair editor Graydon Carter. Academy Award®-winning actor Morgan Freeman will host the show, which will feature a performance by 15-time Grammy Award® winner Alicia Keys, and celebrity presenters Jeremy Irons, Mark and Scott Kelly, Hiroshi Mikitani (CEO of Rakuten), Sienna Miller, Bryce Dallas Howard, Vin Diesel, Kevin Durant, Dev Patel, Sundar Pichai (CEO of Google), Alex Rodriguez, Will.i.am, Susan Wojcicki (CEO of YouTube), as well as the founders of the Breakthrough Prize. The theme of the evening will be "the universal reach of ideas." "Science is universal," said Yuri Milner. "Tonight it brought together some of the world's greatest actors, sportsmen, musicians, academics, entrepreneurs, astronauts and, last but not least, scientists, to celebrate what the human mind can achieve. And it brought in a live audience from across the planet." One of the highlights will be the speeches by the two female students who won the Breakthrough Junior Challenge, Antonella Masini, 18 (Peru) and Deanna See, 17 (Singapore). The Breakthrough Junior Challenge is a global science video competition designed to inspire creative thinking about fundamental concepts in the life sciences, physics, or mathematics. In recognition of their winning submissions, both students received up to $400,000 in educational prizes, including a scholarship worth up to $250,000, $50,000 for an inspiring teacher, and a state-of-the-art science lab valued at $100,000. Entries from 146 countries were received in the 2016 installment of the global competition, which kicked off on September 1, 2016. The Breakthrough Junior Challenge is funded by Mark Zuckerberg and Priscilla Chan, and Yuri and Julia Milner, through the Breakthrough Prize Foundation, based on a grant from Mark Zuckerberg's fund at the Silicon Valley Community Foundation, and a grant from the Milner Global Foundation. "The Breakthrough Junior Challenge encourages students to better understand the worlds of science and mathematics and to have some fun along the way," said Breakthrough Prize co-founder Dr. Priscilla Chan. "Antonella and Deanna both have bright futures in science and I am so excited to honor their work. They are also incredible storytellers, whose ability to capture these complex ideas in accessible and exciting ways is truly inspiring. I cannot wait to see how they will change the world." In addition, six New Horizons prizes – an annual prize of $100,000 each, recognizing the achievements of early-career physicists and mathematicians – were awarded. The New Horizons in Physics Prize was awarded to: The New Horizons in Mathematics Prize was awarded to: The ceremony will be directed and produced, for the fourth time, by Don Mischer alongside executive producers Charlie Haykel and Juliane Hare of Don Mischer Productions. Broadcast live in its entirety on NATIONAL GEOGRAPHIC at 10/9c on Sunday, Dec. 4, an edited one-hour version of the ceremony will also air on FOX on Sunday, Dec. 18, at 7:00-8:00 PM ET/PT and globally on NATIONAL GEOGRAPHIC in 171 countries and 45 languages. The Breakthrough Prize in Life Sciences honors transformative advances towards understanding living systems and extending human life, with one prize dedicated to work that contributes to the understanding of neurological diseases. Each of the five Life Science winners received a $3 million prize. Stephen J. Elledge, Gregor Mendel Professor of Genetics and Medicine in the Department of Genetics at Harvard Medical School and in the Division of Genetics at the Brigham and Women's Hospital and Investigator with the Howard Hughes Medical Institute, for elucidating how eukaryotic cells sense and respond to damage in their DNA and providing insights into the development and treatment of cancer. Harry F. Noller, Director of the Center for Molecular Biology of RNA, Robert L. Sinsheimer Professor of Molecular Biology and Professor Emeritus of MCD Biology at the University of California, Santa Cruz, for discovering the centrality of RNA in forming the active centers of the ribosome, the fundamental machinery of protein synthesis in all cells, thereby connecting modern biology to the origin of life and also explaining how many natural antibiotics disrupt protein synthesis. Roeland Nusse, Professor of Developmental Biology at Stanford University and Investigator at Howard Hughes Medical Institute, for pioneering research on the Wnt pathway, one of the crucial intercellular signaling systems in development, cancer and stem cell biology. Yoshinori Ohsumi, Honorary Professor, Institute of Innovative Research at Tokyo Institute of Technology for elucidating autophagy, the recycling system that cells use to generate nutrients from their own inessential or damaged components. Huda Yahya Zoghbi, Professor in the Departments of Pediatrics, Molecular and Human Genetics, Neurology and Neuroscience at Baylor College of Medicine, Investigator at the Howard Hughes Medical Institute and Director of the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children's Hospital, for discoveries of the genetic causes and biochemical mechanisms of spinocerebellar ataxia and Rett syndrome, findings that have provided insight into the pathogenesis of neurodegenerative and neurological diseases. The Breakthrough Prize in Fundamental Physics recognizes major insights into the deepest questions of the universe. The three winners, sharing the $3 million prize, are: Joseph Polchinski, Professor in the Department of Physics and Member of the Kavli Institute for Theoretical Physics at the University of California, Santa Barbara; Andrew Strominger, Director of the Center for the Fundamental Laws of Nature at Harvard University; and, Cumrun Vafa, Donner Professor of Science in the Department of Physics at Harvard University, All three received the Prize for transformative advances in quantum field theory, string theory, and quantum gravity. The Breakthrough Prize in Mathematics honors the world's best mathematicians who have contributed to major advances in the field. Jean Bourgain, IBM von Neumann Professor in the School of Mathematics at the Institute for Advanced Study, Princeton, New Jersey, for multiple transformative contributions to analysis, combinatorics, partial differential equations, high-dimensional geometry and number theory. The New Horizons in Physics Prize is awarded to promising early-career researchers who have already produced important work in fundamental physics. The New Horizons in Mathematics Prize is awarded to promising early-career researchers who have already produced important work in mathematics. The second annual Breakthrough Junior Challenge recognizes two winners this year - Antonella Masini, 18, from Peru, and Deanna See, 17, from Singapore. Antonella and Deanna will each receive up to $400,000 in educational prizes. Antonella's video, submitted in the physics category, focused on quantum entanglement. Deanna's life sciences video, titled "Superbugs! And Our Race against Resistance," tackled antibiotic resistance. Images and select video from the 2017 Breakthrough Prize Gala -red carpet and ceremony- can be downloaded for media use at: For the fifth year, the Breakthrough Prizes will recognize the world's top scientists. Each prize is $3 million and awarded in the fields of Life Sciences (up to five per year), Fundamental Physics (up to one per year) and Mathematics (up to one per year). In addition, up to three New Horizons in Physics and up to three New Horizons in Mathematics Prizes are given out to junior researchers each year. Laureates attend a televised awards ceremony designed to celebrate their achievements and inspire the next generation of scientists. As part of the ceremony schedule, they also engage in a program of lectures and discussions. The Breakthrough Prizes were founded by Sergey Brin and Anne Wojcicki, Mark Zuckerberg and Priscilla Chan, and Yuri and Julia Milner. Selection Committees composed of previous Breakthrough Prize laureates choose the winners. Information on the Breakthrough Prizes is available at www.breakthroughprize.org.


Le Breakthrough Prize in Life Sciences 2017 est décerné à Stephen J. Elledge, Harry F. Noller, Roeland Nusse, Yoshinori Ohsumi et Huda Yahya Zoghbi Le Breakthrough Prize in Fundamental Physics 2017 est décerné à Joseph Polchinski, Andrew Strominger et Cumrun Vafa Le Breakthrough Prize in Mathematics 2017 est décerné à Jean Bourgain Le prix New Horizons in Physics est décerné à Asimina Arvanitaki, Peter W. Graham et Surjeet Rajendran ; Simone Giombi et Xi Yin ; et Frans Pretorius Le prix New Horizons in Mathematics est décerné à Mohammad Abouzaid, Hugo Duminil-Copin, et Benjamin Elias et Geordie Williamson Le deuxième Breakthrough Junior Challenge annuel est remporté par les étudiantes Antonella Masini, 18 ans (Pérou) et Deanna See, 17 ans (Singapour) Le Special Breakthrough Prize in Fundamental Physics 2016 a été décerné en mai aux fondateurs et aux membres de l'équipe de LIGO, et attribué à Kip Thorne, Rainer Weiss et à la famille de Ronald Drever Les lauréats seront récompensés lors d'un brillant gala de remise des prix présenté par Morgan Freeman, qui verra un spectacle en direct d'Alicia Keys et des interventions de Daniel Ek (PDG de Spotify), Jeremy Irons, Mark et Scott Kelly, Hiroshi Mikitani (PDG de Rakuten), Sienna Miller, Bryce Dallas Howard, Vin Diesel, Kevin Durant, Dev Patel, Sundar Pichai (PDG de Google), Alex Rodriguez, Will.i.am, Susan Wojcicki (PDG deYouTube) et des fondateurs des Breakthrough Prize SAN FRANCISCO, 5 décembre 2016 /PRNewswire/ -- Le Breakthrough Prize et ses fondateurs Sergey Brin et Anne Wojcicki, Yuri et Julia Milner, Mark Zuckerberg et Priscilla Chan, ont annoncé ce soir les lauréats des Breakthrough Prizes 2017, qui marquent le cinquième anniversaire de cette organisation reconnaissant les meilleures réussites en sciences de la vie, physique fondamentale et mathématiques. Ce sont au total 25 millions de dollars qui ont été décernés lors de la cérémonie de gala qui a eu lieu dans la Silicon Valley et a été présentée par Morgan Freeman. Chaque Breakthrough Prize représente un montant de 3 millions de dollars, ce qui en fait la récompense monétaire individuelle la plus élevée dans le domaine de la science. Cette année, un total de sept prix a été décerné à neuf personnes, alors que le Special Breakthrough Prize in Fundamental Physics, d'une valeur de 3 millions de dollars, a été divisé entre les trois fondateurs et les quelque mille membres de l'équipe de LIGO. Par ailleurs, trois prix New Horizons in Physics d'un montant de 100 000 USD ont été décernés à six physiciens en début de carrière, et trois autres prix New Horizons in Mathematics de 100 000 dollars ont été attribués à quatre jeunes mathématiciens. Et cette année il y a eu deux gagnantes du Breakthrough Junior Challenge, et chaque lauréate a reçu jusqu'à 400 000 dollars en prix destiné à la formation, pour elles-mêmes, pour leur professeur respectif et leur école. Depuis sa création en 2012, le Breakthrough Prize a attribué près de 200 millions de dollars pour récompenser des recherches qui bousculent les paradigmes de la physique fondamentale, des sciences de la vie et des mathématiques. « Il n'y a jamais eu d'époque plus importante pour soutenir les sciences », a déclaré le fondateur de Facebook, Mark Zuckerberg. « Les lauréats du Breakthrough Prize 2017 représentent les leaders de la recherche scientifique en physique, mathématiques et sciences de la vie. Leurs avancées vont ouvrir de nouvelles possibilités et contribuer à faire du monde un endroit meilleur pour tout le monde. » Le Breakthrough Prize in Life Sciences 2017 a été décerné à Stephen J. Elledge (École de médecine de Harvard) ; Harry F. Noller (Université de Californie, Santa Cruz) ; Roeland Nusse (Université Stanford) ; Yoshinori Ohsumi (Institut de Technologie de Tokyo) ; Huda Yahya Zoghbi (Baylor College of Medicine). Le Breakthrough Prize in Fundamental Physics 2017 a été décerné à Joseph Polchinski (Université de Californie, Santa Barbara) ; Andrew Strominger (Université de Harvard) et Cumrun Vafa (Université de Harvard). Les trois lauréats ont rejoint ceux du Special Prize in Fundamental Physics précédemment annoncé et attribué en mai 2016. Ronald Drever (Institut de Technologie de Californie, Pasadena), Kip Thorne (Institut de Technologie de Californie, Pasadena) et Rainer Weiss (Institut de technologie du Massachusetts) ont été reconnus en mai pour leur détection des vagues gravitationnelles, ce qui ouvre de nouveaux horizons en astronomie et en physique. Les trois gagnants du Prix spécial se partageront un montant d'un million de dollars, et les 1 012 membres de l'équipe de LIGO se partageront 2 millions de dollars. Le Breakthrough Prize in Mathematics 2017 a été décerné à Jean Bourgain (Institute for Advanced Study). La cérémonie de cette année marquera le cinquième anniversaire de l'organisation, et les lauréats seront sur le devant de la scène ce soir lors d'un gala exclusif organisé conjointement par les fondateurs Sergey Brin et Anne Wojcicki, Yuri et Julia Milner, Mark Zuckerberg et Priscilla Chan, et par le rédacteur en chef de Vanity Fair, Graydon Carter. L'acteur qui a remporté un Award® de l'Académie, Morgan Freeman, présentera le gala, qui verra un spectacle de l'actrice quinze fois primée par les Grammy Award®, Alicia Keys, et les interventions de personnalités comme Jeremy Irons, Mark et Scott Kelly, Hiroshi Mikitani (PDG de Rakuten), Sienna Miller, Bryce Dallas Howard, Vin Diesel, Kevin Durant, Dev Patel, Sundar Pichai (PDG de Google), Alex Rodriguez, Will.i.am, Susan Wojcicki (PDG de YouTube), ainsi que des fondateurs du Breakthrough Prize. La soirée sera placée sous le thème de « la portée universelle des idées ». « La science est universelle », a déclaré Yuri Milner. « Ce soir elle a rassemblé certains des plus grands acteurs, sportifs, musiciens, universitaires, entrepreneurs, astronautes et, bien entendu, scientifiques du monde entier, pour célébrer ce que l'esprit humain est capable de faire. Et cela a attiré un public venu des quatre points de la planète. » L'un des moments forts sera les discours prononcés par les deux étudiantes qui ont remporté le Breakthrough Junior Challenge, Antonella Masini, 18 ans (Pérou) et Deanna See, 17 ans (Singapour). Le Breakthrough Junior Challenge est un concours mondial de vidéos scientifiques conçu pour inspirer la pensée créative sur les concepts fondamentaux en sciences de la vie, physique ou mathématiques. En reconnaissance de leurs candidatures gagnantes, les deux étudiantes ont reçu jusqu'à 400 000 dollars en prix pour la formation, dont une bourse d'une valeur de 250 000 dollars, 50 000 dollars pour les professeurs qui les ont respectivement inspirées, ainsi qu'un laboratoire de pointe évalué à 100 000 dollars. Des candidatures venant de 146 pays ont été reçues pour l'édition 2016 du concours mondial, qui a démarré le 1er septembre 2016. Le Breakthrough Junior Challenge a été fondé par Mark Zuckerberg et Priscilla Chan, Yuri et Julia Milner, à travers la Breakthrough Prize Foundation, et se fonde sur une bourse provenant du fonds de Mark Zuckerberg à la Silicon Valley Community Foundation, et sur une bourse de Milner Global Foundation. « Le Breakthrough Junior Challenge encourage les étudiants à mieux comprendre les mondes des sciences et des mathématiques et à trouver du plaisir à les explorer », a déclaré la cofondatrice du Breakthrough Prize, la Dr Priscilla Chan. « Antonella et Deanna ont toutes les deux un brillant avenir dans les sciences et je suis ravie de récompenser leur travail. Ce sont aussi de grandes oratrices, dont les capacités à exprimer ces idées complexes d'une façon accessible et captivante est une vraie source d'inspiration. J'ai vraiment hâte de voir comment elles vont changer le monde. » Par ailleurs, six prix New Horizons – un prix annuel doté de de 100 000 dollars, qui reconnait les réussites de physiciens et de mathématiciens en début de carrière, ont été attribués. Le prix New Horizons in Physics a été décerné à : Le prix New Horizons in Mathematics a été décerné à : La cérémonie sera réalisée et produite, pour la quatrième fois, par Don Mischer, aux côtés des producteurs exécutifs Charlie Haykel et Juliane Hare de Don Mischer Productions. La cérémonie sera intégralement diffusée en direct sur NATIONAL GEOGRAPHIC à 10 h, heure de l'Est américain et 9 h, heure du centre, le dimanche 4 décembre. Un montage d'une heure de la cérémonie sera également retransmis sur FOX le dimanche 18 décembre, à 19 heures, heure de l'Est et 20 heures, heure du Pacifique, et à l'échelle mondiale sur NATIONAL GEOGRAPHIC dans 171 pays et en 45 langues. Le Breakthrough Prize in Life Sciences récompense des avancées qui transforment la compréhension des systèmes vivants et de l'extension de la vie humaine, avec un prix consacré au travail contribuant à la compréhension des maladies neurologiques. Chacun des cinq lauréats des prix de Sciences de la vie a reçu une récompense de 3 millions de dollars. Stephen J. Elledge, professeur de génétique et de médecine, titulaire de la chaire Gregor Mendel, au département de génétique à l'École de médecine de Harvard et de la division de génétique au Brigham and Women's Hospital et chercheur au Howard Hughes Medical Institute, pour expliciter la façon dont les cellules eucaryotes sentent et répondent aux dommages faits dans leur ADN et pour donner des informations sur le développement et le traitement du cancer. Harry F. Noller, directeur du Center for Molecular Biology of RNA (Centre de la biologie moléculaire de l'ARN), Robert L. Sinsheimer, professeur de biologie moléculaire et professeur émérite de biologie moléculaire, cellulaire et du développement à l'Université de Californie, Santa Cruz, pour avoir découvert le rôle central de l'ARN dans la formation des centres actifs du ribosome, la machinerie fondamentale de la synthèse des protéines dans toutes les cellules, connectant ainsi la biologie moderne à l'origine de la vie et expliquant également combien d'antibiotiques naturels perturbent la synthèse des protéines. Roeland Nusse, professeur de biologie du développement à l'université Stanford et chercheur au Howard Hughes Medical Institute, pour sa recherche pionnière sur la voie des protéines Wnt, l'un des systèmes de signalement intercellulaire fondamentaux dans le développement, le cancer et la biologie des cellules souche. Yoshinori Ohsumi, professeur honoraire, Institut de la recherche innovante de l'Institut de technologie de Tokyo pour élucider l'autophagie, le système de recyclage que les cellules utilisent pour générer des substances nutritives provenant de leurs composants non essentiels ou endommagés. Huda Yahya Zoghbi, professeur du département de pédiatrie, de génétique moléculaire et humaine, de neurologie et de neurosciences au Baylor College of Medicine, chercheur au Howard Hughes Medical Institute et directeur du Jan and Dan Duncan Neurological Research Institute (NRI) à l'Hôpital pour enfants du Texas, pour ses découvertes sur les causes génétiques et les mécanismes biochimiques de l'ataxie spinocérébelleuse et du syndrome de Rett, découvertes qui ont ouvert des fenêtres sur la pathogénèse des maladies neurodégénératives et neurologiques. Le Breakthrough Prize in Fundamental Physics reconnait les plus grandes idées sur les questions les plus profondes que nous pose l'univers. Les trois gagnants, qui se partagent un prix de 3 millions de dollars, sont : Joseph Polchinski, professeur au département de physique et membre du Kavli Institute for Theoretical Physics à l'Université de Californie, Santa Barbara ; Andrew Strominger, directeur du Center for the Fundamental Laws of Nature de l'université Harvard ; et, Cumrun Vafa, professeur de sciences, titulaire de la chaire Donner, au département de physique de l'université Harvard. Tous les trois ont reçu le prix pour les avancées transformatrices en théorie quantique des champs, théorie des cordes et gravité quantique. Le Breakthrough Prize in Mathematics récompense les meilleurs mathématiciens au monde qui ont contribué à des avancées majeures dans ce domaine. Jean Bourgain, professeur de mathématiques, titulaire de la chaire IBM von Neumann, à l'École de mathématiques de l'Institute for Advanced Study, Princeton, New Jersey, pour ses multiples contributions qui transforment l'analyse, la combinatoire, les équations différentielles partielles, la géométrie hautement dimensionnelle et la théorie des numéros. Le New Horizons in Physics Prize est décerné à de prometteurs chercheurs en début de carrière qui ont déjà produit un travail important en physique fondamentale. Le prix New Horizons in Mathematics est décerné à de prometteurs chercheurs en début de carrière qui ont déjà produit un travail important en mathématiques. Le deuxième Breakthrough Junior Challenge annuel reconnaît deux vainqueurs cette année - Antonella Masini, 18 ans, du Pérou, et Deanna See, 17 ans, de Singapour. Antonella et Deanna recevront chacune jusqu'à 400 000 dollars en prix pour la formation. La vidéo d'Antonella, présentée dans la catégorie « physique », est axée sur l'intrication quantique. La vidéo de sciences de la vie de Deanna, intitulée « Superbugs! And Our Race against Resistance » (Superbactéries ! Et notre course contre la résistance) abordait la résistance aux antibiotiques. Les images et les vidéos choisies du gala du Breakthrough Prize 2017 – tapis rouge et cérémonie – peuvent être téléchargées à des fins d'utilisation par la presse sur : Pour la cinquième année consécutive, les Breakthrough Prizes vont reconnaître les meilleurs scientifiques au monde. Chaque prix a une valeur de 3 millions de dollars et récompense dans les domaines des sciences de la vie (jusqu'à cinq prix par an), de la physique fondamentale (un prix par an) et des mathématiques (un prix par an). Par ailleurs, jusqu'à trois prix New Horizons in Physics et jusqu'à trois prix New Horizons in Mathematics sont décernés à de jeunes chercheurs chaque année. Les lauréats participent à une cérémonie de remise des prix télévisée conçue pour célébrer leurs réussites et pour inspirer la nouvelle génération de scientifiques. Dans le cadre de l'agenda de la cérémonie, ils participent aussi à un programme de conférences et de débats. Les Breakthrough Prizes ont été fondés par Sergey Brin et Anne Wojcicki, Mark Zuckerberg et Priscilla Chan, Yuri et Julia Milner. Des comités de sélection composés de précédents lauréats du Breakthrough Prize choisissent les vainqueurs. Vous trouverez des informations sur les Breakthrough Prizes en cliquant sur www.breakthroughprize.org.


To enable this ambitious project, the U.S. government's Intelligence Advanced Research Projects Activity(IARPA) has awarded a $21 million contract to an interdisciplinary team of neuroscientists, computer scientists, physicists and mathematicians, led by principal investigator Dr. Andreas Tolias, associate professor of neuroscience at Baylor. The research team includes scientists from Baylor, the California Institute of Technology, Columbia University, Cornell University, Rice University, the University of Toronto and the University of Tuebingen. The program supporting this research is known as Machine Intelligence from Cortical Networks (MICrONS) and was envisioned and organized by Jacob Vogelstein, a neuromorphic engineer and program manager with IARPA. It is part of the broader BRAIN Initiative, launched in 2013 by President Obama with the goal of understanding devastating brain diseases and developing new technology, treatments and cures. "Our goal is to discover the algorithms and learning rules that the brain implements and use these discoveries to create fundamentally smarter artificial neural networks" said Tolias. Artificial Intelligence (AI) has been a dream for a long time, but an elusive one. People have consistently underestimated how hard it is to construct intelligent systems, Tolias said. Famously, in 1955, cognitive scientists proposed to solve AI as a summer project for several Dartmouth undergraduates. It didn't turn out to be that easy. But in the past few years, AI has been booming, and applications have blossomed everywhere. Handheld devices now use machine learning algorithms to recognize faces and speech, the first self-driving cars already are on the roads, and computer systems regularly wade through Big Data to find new medicines and anticipate geopolitical and financial trends. Despite their new successes, "these artificial neural networks are still incredibly primitive compared to biological neural networks, and don't learn the way real brains do," said Dr. Xaq Pitkow, co-principal investigator of the MICrONS project, and an assistant professor of neuroscience and McNair Scholar at Baylor as well as an assistant professor of electrical and computer engineering at Rice University. "By modeling the brain's computations and extracting their key features, we think we can give computers the ability to do much better." Researchers have been trying to develop brain-like intelligence for years, so what has changed that makes this more achievable today? Tolias's answer: bigger and better data. Jacob Reimer, assistant professor of neuroscience at Baylor and one of the lead scientists and project manager of the team, agrees. "Technologies in both physics and molecular biology have advanced so much that we can now record from many hundreds of neurons at a time, with even more extensive recordings on the horizon," he said. "This lets us analyze neural circuits in ways that we couldn't dream of just a few years ago." In order to accomplish their ambitious goals, the team musters an impressive range of experts, each directing a research group in different aspects of the project. Chris Xu, a physicist at Cornell University, has pioneered 3-photon imaging, a novel method to monitor neural activity non-invasively and more deeply in the brain than ever before. Thanos Siapas of Caltech will focus his team's efforts on unraveling the learning rules in the brain. On the theoretical and mathematical modeling side, Mathias Bethge of the University of Tuebingen and Liam Paninski of Columbia, will develop mathematical models and statistical methods to help interpret the complex data collected by the team's experimentalists. Even with the massive trove of data they will collect by recording neural activity, it can be hard to tell which neurons are connected to each other, directly exchanging information. That type of wiring information is critical to understanding the brain's algorithms that are embodied in its biological wetware. Accordingly, the Baylor-led team also is partnering with two other groups to reconstruct the complete wiring diagram for a cube of brain whose activity they measure. Clay Reid and Nuno da Costa from the Allen Institute for Brain Science will use electron microscopy to image biological structures down to scales reaching just billionths of a meter. They will then hand off about 1,000 large hard disks full of these massive images to Sebastian Seung from Princeton University, who will extract the three-dimensional structure of the neurons, including their shapes and connections. All together, the team will create one of the most exhaustive neuroscience data set in history. The ultimate key to succeeding in the goals of the MICrONS project is to implement neuroscience principles in computer algorithms. Working closely with the neuroscientists, team members Ankit Patel, assistant professor of neuroscience at Baylor College of Medicine and Rice University, Richard Baraniuk from Rice University, and Raquel Urtasun and Richard Zemel from the University of Toronto, are machine learning experts, tasked with integrating the computational building blocks the neuroscientists discover into new kinds of artificial neural networks. This endeavor represents a monumental challenge and opportunity for both neuroscience and computer science. There is no better test of neuroscience principles than to see whether machines built from those principles actually solve real-world problems, Tolias said. "The project demonstrates what is possible when we bring together world-class interdisciplinary researchers to solve fundamental problems. This bold endeavor could provide enormous benefits to society, including new computer technologies, new understanding of the brain, and new medical breakthroughs," said Dr. Paul Klotman, Baylor College of Medicine president, CEO and executive dean. The team's grand aims are to understand one cubic millimeter of a mouse brain, and if they are successful their new algorithms will revolutionize machine learning. But it will still be the product of human ingenuity and creativity, and it will take more understanding than we can squeeze from a tiny cube of mouse brain to match that feat. Explore further: How maths can help explain the workings of our brain


-       Breakthrough Prize celebra su 5 aniversario con los principales logros en ciencias y otorga premios por 25 millones de dólares en una ceremonia de gala celebrada en Silicon Valley New Horizons in Physics Prize otorgado a Asimina Arvanitaki, Peter W. Graham y Surjeet Rajendran; Simone Giombi y Xi Yin y Frans Pretorius New Horizons in Mathematics Prize otorgado a Mohammad Abouzaid, Hugo Duminil-Copin y Benjamin Elias y Geordie Williamson La segunda edición anual del International Breakthrough Junior Challenge se ha otorgado a las estudiantes femeninas Antonella Masini, 18 (Perú) y Deanna See, 17 (Singapur) 2016 Special Breakthrough Prize in Fundamental Physics, otorgado en mayo a los fundadores y miembros del equipo de LIGO, otorgado a Kip Thorne, Rainer Weiss y la familia de Ronald Drever Los premiados serán galardonados en la resplandeciente gala de premios hospedada por medio Morgan Freeman, con actuaciones en directo de Alicia Keys y presentaciones a cabo de Daniel Ek (consejero delegado de Spotify), Jeremy Irons, Mark y Scott Kelly, Hiroshi Mikitani (consejero delegado de Rakuten), Sienna Miller, Bryce Dallas Howard, Vin Diesel, Kevin Durant, Dev Patel, Sundar Pichai (consejero delegado de Google), Alex Rodriguez, Will.i.am, Susan Wojcicki (consejera delegada de YouTube) y los fundadores del Breakthrough Prize SAN FRANCISCO, 9 de diciembre de 2016 /PRNewswire/ -- El Breakthrough Prize y los fundadores Sergey Brin y Anne Wojcicki, Yuri y Julia Milner, y Mark Zuckerberg y Priscilla Chan, anunciaron anoche a los receptores de los 2017 Breakthrough Prizes, marcando así el 5 aniversario de la organización que reconoce los logros principales en Ciencias de la Vida, Física Fundamental y Matemáticas. Una cifra combinada total de 25 millones de dólares se otorgó en la ceremonia de gala en Silicon Valley, hospedada por medio de Morgan Freeman. Cada uno de los Breakthrough Prizes tiene un valor de 3 millones de dólares, el premio en metálico individual más grande dentro de la ciencia. Este año, se han otorgado un total de siete premios a nueve personas, junto con un Special Breakthrough Prize in Fundamental Physics de 3 millones de dólares, que se dividió entre los tres fundadores y más de 1.000 miembros del equipo LIGO. Además, se otorgaron tres New Horizons in Physics Prizes de 100.000 dólares para seis físicos en sus inicios de carrera, y otros tres New Horizons in Mathematics Prizes de 100.000 dólares otorgados a cuatro jóvenes matemáticos. Y este año, hubo dos ganadores del Breakthrough Junior Challenge, recibiendo cada uno de ellos hasta 400.000 dólares en premios de formación para ellos, su profesor y su escuela. Desde su creación en el año 2012, el Breakthrough Prize ha otorgado cerca de 200 millones de dólares para honrar el avance de la investigación del paradigma en los campos de la física fundamental, ciencias de la vida y matemáticas. "Nunca ha habido un momento más importante en el que apoyar la ciencia", destacó el fundador de Facebook, Mark Zuckerberg. "Los premiados con el 2017 Breakthrough Prize representan a los líderes en los campos de la investigación científica en física, matemáticas y ciencias de la vida. Sus descubrimientos desvelarán nuevas posibilidades y ayudarán a conseguir que el mundo sea un lugar mejor para todos". El 2017 Breakthrough Prize in Life Sciences fue otorgado a Stephen J. Elledge (Harvard Medical School); Harry F. Noller (University of California, Santa Cruz); Roeland Nusse (Stanford University); Yoshinori Ohsumi (Tokyo Institute of Technology); Huda Yahya Zoghbi (Baylor College of Medicine). El 2017 Breakthrough Prize in Fundamental Physics fue otorgado a Joseph Polchinski (University of California, Santa Barbara); Andrew Strominger (Harvard University) y Cumrun Vafa (Harvard University). Los tres premiados se unieron a los receptores del Special Prize in Fundamental Physics anunciados anteriormente, lanzado en mayo de 2016. Ronald Drever (California Institute of Technology, Pasadena), Kip Thorne (California Institute of Technology, Pasadena) y Rainer Weiss (Massachusetts Institute of Technology), fueron reconocidos en mayo por su detección de las olas gravitacionales, abriendo con ello nuevos horizontes en astronomía y física. Los tres ganadores del Special Prize compartirán un premio de 1 millón de dólares, y los 1.012 miembros del equipo LIGO compartirán 2 millones de dólares. El 2017 Breakthrough Prize in Mathematics fue otorgado a Jean Bourgain (Institute for Advanced Study). La ceremonia de este año marcará el 5 aniversario de la organización, y los premiados tomarán el escenario esta noche durante una gala exclusiva celebrada de forma conjunta con los fundadores Sergey Brin y Anne Wojcicki, Yuri y Julia Milner, Mark Zuckerberg y Priscilla Chan, además del editor de Vanity Fair, Graydon Carter. El actor ganador del Academy Award®, Morgan Freeman, hospedará el show, que contará con la actuación de la ganadora de 15 Grammy Award®, Alicia Keys, y los famosos presetadores Jeremy Irons, Mark y Scott Kelly, Hiroshi Mikitani (consejero delegado de Rakuten), Sienna Miller, Bryce Dallas Howard, Vin Diesel, Kevin Durant, Dev Patel, Sundar Pichai (consejero delegado de Google), Alex Rodriguez, Will.i.am, Susan Wojcicki (consejera delegada de YouTube), además de los fundadores del Breakthrough Prize. El tema de la noche será "the universal reach of ideas". "La ciencia es universal", destacó Yuri Milner. "Esta noche ha reunido a algunos de los mejores actores, deportistas, músicos, académicos, empresarios, astronautas y finalmente pero no por ello menos importante, científicos, para celebrar lo que la mente humana puede conseguir. Y lo ha hecho por medio de un evento en directo emitido en todo el planeta". Uno de estos puntos álgidos serán los discursos de dos estudiantes femeninas que han ganado el Breakthrough Junior Challenge, Antonella Masini, 18 (Perú) y Deanna See, 17 (Singapur). El Breakthrough Junior Challenge es una competición de video de ciencias de nivel mundial diseñado para inspirar el pensamiento creativo acerca de los conceptos fundamentales en las ciencias de la vida, física o matemáticas. Como reconocimiento a sus envíos ganadores, ambas estudiantes recibieron hasta 400.000 dólares en premios de formación, incluyendo una beca con un valor de 250.000 dólares, 50.000 dólares para un profesor inspirador y un laboratorio de última tecnología valorado en 100.000 dólares. Las participaciones procedentes de 146 países fueron recibidas en la entrega de 2016 de la competición final, que se puso en marcha el 1 de septiembre de 2016. El Breakthrough Junior Challenge cuenta con los fondos Mark Zuckerberg y Priscilla Chan, y Yuri y Julia Milner, a través de la Breakthrough Prize Foundation, basándose en una beca del fondo de Mark Zuckerberg en la Silicon Valley Community Foundation, además de una beca de la Milner Global Foundation. "El Breakthrough Junior Challenge insta a los estudiantes a comprender mejor los mundos de la ciencia y las matemáticas y divertirse durante ese viaje", destacó la cofundadora del Breakthrough Prize, la doctora Priscilla Chan. "Antonella y Deanna cuentan ambas con un futuro brillante en ciencias, y estoy emocionada de honrar su trabajo. Se trata además de dos increíbles contadoras de historias, cuya capacidad para capturar estas ideas complejas de forma accesible y emocionante es realmente inspiradora. No encuentro el momento de ver cómo van a cambiar el mundo". Además, se han otorgado seis premios New Horizons – un premio anual de 100.000 dólares cada uno, que reconocen los logros de los médicos de carrera primaria y matemáticos. El New Horizons in Physics Prize fue otorgado a: El New Horizons in Mathematics Prize fue otorgado a: La ceremonia estará dirigida y producida, por cuarta ocasión, por medio de Don Mischer junto a los productores ejecutivos Charlie Haykel y Juliane Hare de Don Mischer Productions. La emisión en directo corre a cargo de NATIONAL GEOGRAPHIC a las 10/9c del domingo 4 de diciembre, con una versión editada de una hora de la ceremonia emitida además por medio de FOX el domingo 18 de diciembre a las 7:00-8:00 PM ET/PT y a nivel mundial en NATIONAL GEOGRAPHIC en 171 países y 45 idiomas. El Breakthrough Prize in Life Sciences honora los avances transformadores hacia el conocimiento de los sistemas de vida y ampliación de la vida humana, con un premio dedicado al trabajo que contribuye al conocimiento de cara a las enfermedades neurológicas. Cada uno de los cinco ganadores de Life Science recibió un premio de 3 millones de dólares. Stephen J. Elledge, profesor Gregor Mendel de Genética y Medicina del Departamento de Genética de la Harvard Medical School y de la División de Genética del Brigham and Women's Hospital e investigador del Howard Hughes Medical Institute, por esclarecer cómo las células eucariotas sienten y responden a los daños en su ADN y proporcionar visiones sobre el desarrollo y tratamiento del cáncer. Harry F. Noller, director del Center for Molecular Biology of RNA, profesor Robert L. Sinsheimer de Biología Molecular y Profesor Emérito de Biología MCD de la University of California, Santa Cruz, por descubrir la centralidad del ARN en la formación de centros activos del ribosoma, la maquinaria fundamental de síntesis de proteína en todas las células, conectando con ello la biología moderna al origen de la vida y explicando además cómo muchos de los antibióticos naturales interrumpen la síntesis de proteínas. Roeland Nusse, profesor de Biología de Desarrollo de la Stanford University e investigador del Howard Hughes Medical Institute, por ser pionero en la investigación de la ruta Wnt, uno de los sistemas de señalización intercelular más importantes en la biología de desarrollo, cáncer y células madre. Yoshinori Ohsumi, profesor honorario del Institute of Innovative Research del Tokyo Institute of Technology por descubrir la autofagia, sistema de reciclaje que usan las células para generar nutrientes por sí mismas en componentes esenciales o dañados. Huda Yahya Zoghbi, profesor de los Departamentos de Pediatría, Molecular y genetic Humana, Neurología y Neurociencias del Baylor College of Medicine, investigador del Howard Hughes Medical Institute y director del Jan and Dan Duncan Neurological Research Institute (NRI) del Texas Children's Hospital, por sus descubrimientos de las causas genéticas y mecanismos bioquímicos de la ataxia espinocerebral y síndrome Rett, descubrimientos que han proporcionado visión dentro de la patogénesis de las enfermedades neurodegenerativas y neurológicas. El Breakthrough Prize in Fundamental Physics reconoce las mayores visiones dentro de las preguntas más profundas acerca del universo. Los tres ganadores, que comparten el premio de 3 millones de dólares, son: Joseph Polchinski, profesor del Departamento de Física y Miembro del Kavli Institute for Theoretical Physics de la University of California, Santa Bárbara; Andrew Strominger, director del Center for the Fundamental Laws of Nature de la Harvard University; y, Cumrun Vafa, profesor donner de Ciencias del Departamento de Física de la Harvard University, Los tres recibieron el premio por los avances transformadores en la teoría del campo cuántico, teoría de cuerdas y gravedad cuántica. El Breakthrough Prize in Mathematics honra a los mejores matemáticos del mundo, que han contribuido de cara a los avances más importantes en el campo. Jean Bourgain, profesor IBM von Neumann en la Escuela de Matemáticas del Institute for Advanced Study, Princeton, Nueva Jersey, por sus múltiples contribuciones de transformación para el análisis, combinatoria, ecuaciones diferenciales parciales, geometría de alta dimensión y teoría de números. El New Horizons in Physics Prize se otorga a los investigadores prometedores que empiezan sus carreras que yah an producido un trabajo importante en la física fundamental. El New Horizons in Mathematics Prize se concede a los investigadores prometedores en el principio de sus carreras que ya han producido importantes trabajos en matemáticas. La segunda edición anual del Breakthrough Junior Challenge reconoce a dos ganadores este año - Antonella Masini, 18, de Perú, y Deanna See, 17, de Singapur. Antonella y Deanna recibirán cada una hasta 400.000 dólares en premios de formación. El video de Antonella, enviado en la categoría de física, se centra en la implicación cuántica. El video de las ciencias de la vida de Deanna, titulado "Superbugs! And Our Race against Resistance", hace frente a la resistencia a los antibióticos. Las imágenes y video seleccionado de la 2017 Breakthrough Prize Gala – alfombra roja y ceremonia – se pueden descargar para su uso de medios a través de: Por quinto año, los premios Breakthrough Prize darán su reconocimiento a los mejores científicos del mundo. Cada premio tiene una dotación de 3 millones de dólares y se presenta en las áreas de Ciencias de la Vida (hasta cinco por año), Física Fundamental (máximo uno por año) y Matemáticas (máximo uno por año). Además, cada año se entregan hasta tres premios New Horizons de Física y hasta tres New Horizons de Matemáticas a jóvenes investigadores. Los ganadores asisten a una ceremonia de entrega de premios que se emite por televisor pensada para celebrar sus logros e inspirar a la nueva generación de científicos. Como parte de la programación de la ceremonia, también entran en un programa de ponencias y debates. Los premios al descubrimiento fueron fundados por Sergey Brin y Anne Wojcicki, Mark Zuckerberg y Priscilla Chan, y Yuri y Julia Milner. Los comités de selección están compuestos por ganadores anteriores de los premios Breakthrough Prize y quienes eligen a los ganadores. Información acerca de los Breakthrough Prizes disponible a través de www.breakthroughprize.org.


2017 Breakthrough Prize in Life Sciences an Stephen J. Elledge, Harry F. Noller, Roeland Nusse, Yoshinori Ohsumi und Huda Yahya Zoghbi verliehen 2017 Breakthrough Prize in Grundlagenphysik geht an Joseph Polchinski, Andrew Strominger und Cumrun Vafa New Horizons in Physics Prize an Asimina Arvanitaki, Peter W. Graham und Surjeet Rajendran; Simone Giombi und Xi Yin sowie Frans Pretorius verliehen New Horizons in Mathematics Prize geht an Mohammad Abouzaid, Hugo Duminil-Copin sowie Benjamin Elias und Geordie Williamson Zweiter jährlich verliehener International Breakthrough Junior Challenge von zwei Schülerinnen gewonnen Antonella Masini, 18 (Peru) und Deanna See, 17 (Singapur) Im Mai 2016 an Gründer und Teammitglieder von LIGO verliehener Special Breakthrough Prize in Grundlagenphysik an Kip Thorne, Rainer Weiss und die Familie von Ronald Drever überreicht Ehrung der Preisträger mit glanzvoller, von Morgan Freeman moderierter Awards Gala mit Live-Auftritt von Alicia Keys und Preisübergabe durch Daniel Ek (CEO von Spotify), Jeremy Irons, Mark und Scott Kelly, Hiroshi Mikitani (CEO von Rakuten), Sienna Miller, Bryce Dallas Howard, Vin Diesel, Kevin Durant, Dev Patel, Sundar Pichai (CEO von Google), Alex Rodriguez, Will.i.am, Susan Wojcicki (CEO von YouTube) und die Gründer des Breakthrough Prize. SAN FRANCISCO, 6. Dezember 2016 /PRNewswire/ -- Der Breakthrough Prize und seine Begründer Sergey Brin und Anne Wojcicki, Yuri und Julia Milner sowie Mark Zuckerberg und Priscilla Chan haben am heutigen Abend die Empfänger der Breakthrough Prizes 2017 bekanntgegeben. Dies steht zugleich für den fünften Jahrestag der Organisation, die Spitzenleistungen in den Biowissenschaften, der Grundlagenphysik und der Mathematik würdigt. Insgesamt wurden auf der von Morgan Freeman moderierten Gala-Veranstaltung in Silicon Valley 25 Millionen USD vergeben. Jeder der der Breakthrough Prizes ist mit einer Summe von 3 Millionen USD dotiert, der finanziell höchstdotierte Einzelpreis im Bereich der Wissenschaften. Diesjährig wurden, neben einem mit 3 Millionen USD dotierten, zwischen drei Gründern und mehr als tausend Mitgliedern des LIGO Team aufgeteilten Special Breakthrough Prize in Grundlagenphysik, insgesamt sieben Preise an neun Personen verliehen. Zusätzlich wurden drei mit 100.000 USD ausgeschriebene „New Horizons in Physics"-Preise an sechs Physiker, die am Anfang ihrer Karriere stehen und weitere drei mit 100.000 USD dotierte „New Horizons in Mathematics"-Preise an vier junge Mathematiker vergeben. In diesem Jahr gab es zwei Gewinner des Breakthrough Junior Challenge, die jeder jeweils bis zu 400.000 USD in Bildungspreisen für sich selbst, ihre Lehrer und ihre Schulen in Empfang nehmen konnten. Der im Jahre 2012 ins Leben gerufene Breakthrough Prize hat annähernd 200 Millionen USD vergeben, um einen Paradigmenwechsel in den Bereichen Grundlagenphysik, Biowissenschaften und Mathematik zu würdigen. „Die Wissenschaft zu unterstützen ist so wichtig wie nie zuvor", erklärte Facebook-Gründer Mark Zuckerberg. „Die Preisträger des 2017 Breakthrough Prize stehen für die führende wissenschaftliche Forschung in Physik, Mathematik und Life Sciences. Ihre bahnbrechenden Erkenntnisse werden neue Möglichkeiten erschließen und zu einer für uns alle besseren Welt beitragen". Der 2017 Breakthrough Prize in Life Sciences ging an Stephen J. Elledge (Harvard Medical School); Harry F. Noller (University of California, Santa Cruz); Roeland Nusse (Stanford University); Yoshinori Ohsumi (Technische Hochschule Tokio); Huda Yahya Zoghbi (Baylor College of Medicine). Der 2017 Breakthrough Prize in Grundlagenphysik wurde an Joseph Polchinski (University of California, Santa Barbara); Andrew Strominger (Harvard University); und Cumrun Vafa (Harvard University) verliehen. Die drei Preisträger konnten sich den bereits im Mai 2016 bekanntgegebenen Empfängern des Sonderpreises in Grundlagenphysik anschließen. Ronald Drever (California Institute of Technology, Pasadena), Kip Thorne (California Institute of Technology, Pasadena) und Rainer Weiss (Massachusetts Institute of Technology) waren im Mai für den Nachweis von Gravitationswellen ausgezeichnet worden, der neue Horizonte in der Astronomie und Physik eröffnet. Die drei Preisträger des Special Prize teilen sich eine 1 Million USD an Preisgeld, zwei Millionen gehen zu gleichen Teilen an 1012 Mitglieder des LIGO-Teams. Der 2017 Breakthrough Prize in Mathematik wurde an Jean Bourgain (Institute for Advanced Study) vergeben. Die diesjährige Zeremonie steht für das fünfte Jubiläum der Organisation. Die Preisträger werden heute Abend im Rahmen von den Gründern Sergey Brin und Anne Wojcicki, Yuri und Julia Milner, Mark Zuckerberg und Priscilla Chan sowie Vanity Fair-Herausgeber Graydon Carter mitausgerichteten einer exklusiven Gala auf der Bühne stehen. Schauspieler und Academy Award®-Gewinner Morgan Freeman wird als Gastgeber der Veranstaltung fungieren, in deren Rahmen es einen Auftritt der mit 15 Grammy Awards® ausgezeichneten Alicia Keys geben wird. Als prominente Preisverleiher treten Jeremy Irons, Mark und Scott Kelly, Hiroshi Mikitani (CEO von Rakuten), Sienna Miller, Bryce Dallas Howard, Vin Diesel, Kevin Durant, Dev Patel, Sundar Pichai (CEO von Google), Alex Rodriguez, Will.i.am, Susan Wojcicki (CEO von YouTube) sowie die Begründer des Breakthrough Prize in Erscheinung. Der Abend wird unter dem Motto „die universelle Reichweite von Ideen" stehen. „Wissenschaft ist universell", sagte Yuri Milner. „Sie hat heute Abend einige der weltweit größten Schauspieler, Sportler, Musiker, Akademiker, Entrepreneure, Astronauten und, nicht zu vergessen, Wissenschaftler, zusammengebracht, um zu feiern, was der menschliche Geist erreichen kann. Und sie macht möglich, dass hier ein planetenweites Live-Publikum mit dabei ist". Eines der Highlights sind die Reden der beiden Schülerinnen, die den Breakthrough Junior Challenge gewonnen haben, Antonella Masini, 18 (Peru) und Deanna See, 17 (Singapur). Der Breakthrough Junior Challenge ist ein globaler Videowettbewerb im Bereich der Wissenschaften, der zu kreativem Denken hinsichtlich Grundkonzepten in den Biowissenschaften, der Physik oder der Mathematik anregen soll. In Anerkennung ihrer siegreichen Einreichungen erhielten beide Schülerinnen bis zu 400.000 USD in Bildungspreisen einschließlich eines Stipendiums im Wert von bis zu 250.000 USD, 50.000 USD für einen inspirierenden Lehrer und ein wissenschaftliches Labor auf dem neuestem Stand der Technik im Wert von 100.000 USD. Für die 2016 Ausgabe des globalen Wettbewerbs gingen mit Starttermin zum 1. September 2016 Beiträge aus 146 Ländern ein. Der Breakthrough Junior Challenge wird von Mark Zuckerberg und Priscilla Chan sowie Yuri und Julia Milner über die Breakthrough Prize Foundation mit einer Förderung durch Mark Zuckerbergs Fonds in der Silicon Valley Community Foundation und finanzieller Unterstützung der Milner Global Foundation finanziert. „Der Breakthrough Junior Challenge ermutigt die Schüler, die Welten von Wissenschaft und Mathematik besser zu verstehen und Spaß daran zu haben", erklärte Breakthrough Prize Mitbegründerin Dr. Priscilla Chan. „Antonella und Deanna haben beide beste Zukunftsaussichten in der Welt der Wissenschaften, und ich bin hocherfreut, sie für ihre Arbeit derart würdigen zu können. Sie können darüber hinaus hervorragend Geschichten erzählen und besitzen eine Fähigkeit, diese komplexen Ideen zugänglich und aufregend zu erfassen und zu vermitteln, die wirklich inspirierend ist. Ich bin äußerst gespannt darauf, mitzuerleben, wie sie die Welt verändern werden". Zusätzlich wurden sechs New Horizons-Preise verliehen, eine jährlich vergebene und mit jeweils 100.000 USD dotierte Auszeichnung, die die Leistungen von Physikern und Mathematikern würdigen, die am Anfang ihrer Karriere stehen. Der New Horizons in Physics Prize ging an: Der New Horizons in Mathematics Prize ging an: Die Preisverleihung steht zum vierten Male unter der Leitung und Regie von Don Mischer, gemeinsam mit den ausführenden Produzenten Charlie Haykel und Juliane Hare von Don Mischer Productions. Die Gala wurde in vollem Umfang live auf NATIONAL GEOGRAPHIC am Sonntag, 4. Dezember um 22:00 Uhr/21:00 Uhr ET/CT übertragen. Eine auf eine Stunde editierte Version der Preisverleihung wird ebenfalls über FOX am Sonntag, 18. Dezember, von 19:00 Uhr - 20:00 Uhr ET/PT und global über NATIONAL GEOGRAPHIC in 171 Ländern und 45 Sprachen zu sehen sein. Der Breakthrough Prize in Life Sciences ehrt transformative Fortschritte zum Verständnis lebender Systeme und zur Verbesserung des menschlichen Lebens, wobei einer der Preise der Arbeit gewidmet ist, die zum Verständnis der neurologischen Erkrankungen beiträgt. Jeder der fünf Gewinner des Life Science-Preises hat 3 Millionen USD erhalten. Stephen J. Elledge, Gregor Mendel Professor für Genetik und Medizin in der Abteilung für Genetik an der Harvard Medical School und an der Abteilung für Genetik am Brigham and Women's Hospital und Investigator am Howard Hughes Medical Institute, für seine Darlegung, wie eukaryotische Zellen Schäden in ihrer DNA spüren und auf diese reagieren, und Erkenntnisse zur Entwicklung und Behandlung von Krebs. Harry F. Noller, Direktor des Zentrums für Molekularbiologie der RNA, Robert L. Sinsheimer Professor für Molekularbiologie und Professor Emeritus für MCD Biologie an der University of California, Santa Cruz, für die Entdeckung der zentralen Rolle, die RNA bei der Bildung der aktiven Zentren des Ribosoms zukommt, der grundlegenden Maschinerie der Proteinsynthese in allen Zellen, was die moderne Biologie mit dem Ursprung des Lebens verknüpft und auch erklärt, auf welche Weise viele natürliche Antibiotika die Proteinsynthese stören. Roeland Nusse, Professor für Entwicklungsbiologie an der Stanford University und Investigator am Howard Hughes Medical Institute, für Pionierforschung zum Wnt-Signalweg, eines der entscheidenden interzellulären Signalisierungssysteme in der Entwicklungs-, Krebs- und Stammzellbiologie. Yoshinori Ohsumi, Honorarprofessor am Institut für Innovative Forschung an der Technischen Hochschule Tokio, für die Darlegung der Autophagie, des Recycling-Systems, das Zellen verwenden, um Nährstoffe aus ihren eigenen unwesentlichen oder beschädigten Komponenten zu erzeugen. Huda Yahya Zoghbi, Professorin an den Abteilungen für Pädiatrie, Molekulare und Humangenetik, Neurologie und Neurowissenschaften am Baylor College of Medicine, Investigator am Howard Hughes Medical Institute und Direktorin des Jan and Dan Duncan Neurological Research Institute (NRI) am Texas Children's Hospital, für die Entdeckung der genetischen Ursachen und biochemischen Mechanismen der spinozerebellären Ataxie und des Rett-Syndroms, Erkenntnisse, die einen Einblick in die Pathogenese neurodegenerativer und neurologischer Erkrankungen gegeben haben. Der Breakthrough Prize in Fundamental Physics würdigt wichtige Erkenntnisse zu den tiefstgründigen Fragestellungen des Universums. Die drei Gewinner, die sich die Summe von 3 Millionen USD teilen, sind: Joseph Polchinski, Professor am Fachbereich für Physik und Mitglied des Kavli Institut für Theoretische Physik an der University of California, Santa Barbara; Andrew Strominger, Direktor des Center for the Fundamental Laws of Nature an der Harvard University; und, Cumrun Vafa, Donner Professor für Wissenschaft am Fachbereich für Physik an der Harvard University, Alle drei erhielten den Preis für transformative Fortschritte in der Quantenfeldtheorie, Stringtheorie und Quantengravitation. Der Breakthrough Prize in Mathematics ehrt die besten Mathematiker der Welt, die zu großen Fortschritten in diesem Bereich beigetragen haben. Jean Bourgain, IBM von Neumann Professor an der Fakultät für Mathematik am Institute for Advanced Study, Princeton, New Jersey, für mehrere transformative Beiträge zu Analyse, Kombinatorik, partiellen Differentialgleichungen, hochdimensionaler Geometrie und Zahlentheorie. Der New Horizons in Physics Prize wird vielversprechenden Forschern verliehen, die am Anfang ihrer Karriere stehen und bereits wichtige Arbeit in der Grundlagenphysik geleistet haben. The New Horizons in Mathematics Prize wird vielversprechenden Forschern verliehen, die am Anfang ihrer Karriere stehen und bereits wichtige Arbeit in der Mathematik geleistet haben. Der zweite, jährlich vergebene Breakthrough Junior Challenge würdigt in diesem Jahr zwei Gewinner - Antonella Masini, 18, aus Peru, und Deanna See, 17, aus Singapur. Antonella und Deanna erhalten jeweils bis zu 400.000 USD an Bildungspreisen. Das von Antonella in der Kategorie Physik eingereichte Video fokussiert sich auf Quantenverschränkung. Deannas Video für Life Sciences trägt den Titel „Superbugs! And Our Race against Resistance" (Superbugs! Unser Wettlauf mit der Resistenz) und beschäftigt sich mit Antibiotikaresistenz. Bilder und ausgewähltes Videomaterial der 2017 Breakthrough Prize Gala mit Begrüßung auf dem rotem Teppich und Preisverleihung können für Pressezwecke unter folgendem Link heruntergeladen werden: Die Breakthrough Prizes zeichnen mittlerweile im fünften Jahr die weltweit führenden Wissenschaftler aus. Jeder Preis ist mit einer Summe von 3 Millionen USD dotiert und wird für die Bereiche Life Sciences (bis zu fünf pro Jahr), Grundlagenphysik (ein Preis pro Jahr) und Mathematik (ein Preis pro Jahr) vergeben. Darüber hinaus werden jährlich bis zu drei „New Horizons"-Preise in Physik und bis zu drei „New Horizons"-Preise in Mathematik an vielversprechende junge Wissenschaftler verliehen. Die Preisträger nehmen an einer im Fernsehen übertragenen Award-Verleihung zur Anerkennung ihrer Verdienste teil, die auch die nächste Generation von Wissenschaftlern inspirieren soll. Im Rahmen der Feierlichkeit nehmen sie ebenfalls an einem Programm von Vorlesungen und Diskussionen teil. Begründer der Breakthrough Prizes waren Sergey Brin und Anne Wojcicki, Mark Zuckerberg und Priscilla Chan sowie Yuri und Julia Milner. Auswahlgremien, die sich aus früheren Preisträgern der Breakthrough Prizes zusammensetzen, wählen die Gewinner aus. Informationen über die Breakthrough Prizes erhalten Sie unter www.breakthroughprize.org.


News Article | December 5, 2016
Site: www.newscientist.com

At the fifth annual Breakthrough Prize ceremony last night, 12 scientists received a total of $25 million in science prizes for fundamental contributions to human knowledge. The ceremony, held at NASA’s Ames Research Center in Mountain View, California, featured all the glitz and glam of the Oscars: a red carpet, musical guests such as Alicia Keys and will.i.am, and Morgan Freeman as host. “This project is really mostly about public outreach,” says billionaire internet investor Yuri Milner, who co-founded the prize. “That’s why we have a televised ceremony and everything around it, because the founders want to send a signal that fundamental science is important.” The Breakthrough Prize was founded in 2012 and is financed by Silicon Valley billionaires such as Milner, Google’s Sergey Brin and Facebook’s Mark Zuckerberg. One of the prizes was already announced earlier this year. The physicists behind the LIGO experiment, which revealed the first detection of Einstein’s long-sought gravitational waves in February, will share the $3 million Breakthrough Prize in fundamental physics. Of that, $1 million will be split between three of LIGO’s founders: Ronald Drever and Kip Thorne at the California Institute of Technology, and Rainer Weiss at the Massachusetts Institute of Technology. The other $2 million will be equally split between 1012 contributors to the experiment. Another $3 million prize in fundamental physics will be split between three physicists. Joseph Polchinski at the University of California, Santa Barbara, was recognised for his theories of what happens at the event horizons of black holes, and Andrew Strominger and Cumrun Vafa at Harvard University were honoured for contributions to quantum gravity and string theory. The Breakthrough Prize in mathematics – another $3 million – went to Jean Bourgain at the Institute for Advanced Study in Princeton, New Jersey, for his contributions to analysis, combinatorics, partial differential equations, high-dimensional geometry and number theory. Five prizes of $3 million each went to researchers in the life sciences. Stephen Elledge at Harvard Medical School and the Brigham and Women’s Hospital in Boston, Massachusetts, received a prize for insights into how cells sense and respond to damage in their DNA, and how that relates to the development and treatment of cancer. Harry Noller at the University of California, Santa Cruz, was recognised for discovering how central RNA is in the fundamental machinery of protein synthesis in all cells, connecting modern biology to the origin of life and explaining how many natural antibiotics work. Roeland Nusse at Stanford University and the Howard Hughes Medical Institute was honoured for pioneering work on the Wnt pathway, which encourages cells to divide and is one of the crucial intercellular signalling systems in developmental, cancer and stem cell biology. Yoshinori Ohsumi at Tokyo Institute of Technology in Japan received a prize for his discovery of the mechanisms behind autophagy, a fundamental process in which cells degrade, recycle and repair themselves. Ohsumi also received the 2016 Nobel Prize in Physiology or Medicine. The fifth life-sciences prize went to Huda Yahya Zoghbi at Baylor College of Medicine in Houston, Texas, for her discoveries related to the genetic causes and biochemical mechanisms of neurodegenerative and neurological diseases, including Rett syndrome and spinocerebellar ataxia. The final $1 million in prize money will go to six “New Horizons” winners for early-career achievements in physics and maths, and one Breakthrough Junior Prize for a teenager’s original science video. After five years of pushing for scientists to be treated like celebrities, Milner thinks the project is off to a good start. “If a few kids in a high school will get inspired by those incredible people, I think this effort is worth pursuing,” he says. “I think it’s really about the priorities of society: where we should put more resources in, and where the smartest people should go. If we can reach even half the audience of the Super Bowl globally, that would be amazing. But that’s a high bar.”


News Article | December 20, 2016
Site: globenewswire.com

Dublin, Dec. 20, 2016 (GLOBE NEWSWIRE) -- Research and Markets has announced the addition of the "HDAC Inhibitors Market, 2016 - 2026" report to their offering. The HDAC Inhibitors Market, 2016-2026 report was commissioned to examine the current landscape and the future outlook of the growing pipeline of products in this area. HDACs have been studied in cellular processes such as apoptosis, autophagy, metabolism, DNA damage repair, cell cycle control and senescence. Altered expression of HDACs has been observed in different tumors; this makes them a potential target for treatment of cancer and other genetic or epigenetic related disorders. Inhibition of HDACs has shown positive results in disruption of multiple cell signaling pathways and prevention of tumor growth. The study provides a detailed market forecast and opportunity analysis for the time period 2016-2026. The research, analysis and insights presented in this report include potential sales of the approved drugs and the ones in late stages of development (phase III and phase II). To add robustness to our model, we have provided three scenarios for our market forecast; these include the conservative, base and optimistic scenarios. Our opinions and insights, presented in this study were influenced by several discussions we conducted with experts in this area. All actual figures have been sourced and analyzed from publicly available information forums and primary research discussions. Financial figures mentioned in this report are in USD, unless otherwise specified. Example Highlights - Nearly 90 HDAC inhibitors are currently in clinical / preclinical stages of development; the clinical molecules account for over 30% of the pipeline while over 60% is captured by molecules in the preclinical / discovery stage. - With 66% of the pipeline molecules targeting oncological indications, cancer remains one of the most widely studied field for HDAC inhibitors. Within oncology, hematological malignancies such as PTCL and CTCL are popular targets; three HDAC inhibitors (Zolinza, ISTODAX® and BELEODAQ®) are approved for these indications. Other therapeutic areas such as autoimmune disorders, infectious diseases, inflammatory disorders, neurological disorders, are also gradually gaining traction. - Although the market was initially led by the large-size pharma players (such as Celgene, Merck, Novartis), the current market is characterized by the presence of several small / mid-sized pharma players. Notable examples of the small and mid-sized firms include 4SC, Chroma Therapeutics, CrystalGenomics, Curis, Evgen Pharma, FORUM Pharmaceuticals, Karus Therapeutics, Mirati Therapeutics, MEI Pharma, Shenzhen Chipscreen Biosciences, Syndax Pharmaceuticals and TetraLogic Pharmaceuticals. - In addition, there are several non-industry institutes and universities that are primarily carrying out preclinical research. Examples of these include Harvard Medical School (BG45), Imperial College London (C1A), Kyoto University (Jd, Sd), National Taiwan University (Quinazolin-4-one derivatives), Taipei Medical University (MPT0E028), University of Messina (MC-1575, MC-1568). - Four of the five approved drugs are pan-HDAC inhibitors targeting HDAC isoforms non-specifically. However, in the past few years, several class selective HDAC inhibitors have entered the clinic; these are associated with a higher efficacy and result in decreased toxicity from the treatment. Of the total HDAC inhibitors identified, 52% of the molecules are class specific; of these, 33% molecules target Class I specific isoforms and the rest target Class II specific isoforms of HDACs. Notable examples of molecules targeting class-specific HDACs includeentinostat (phase III), resminostat (phase II), SHP-141 (phase II), mocetinostat (phase II), CHR-3996 (phase I/II) and ricolinostat (phase I/II). - The HDAC inhibitors market is expected to grow at a healthy annual rate of 32% over the next decade.With multiple potential target indications, Istodax® is expected to capture the largest market share (close to 21%) in 2026, followed by entinostat, Farydak® and Beleodaq®. Key Topics Covered: 1. Preface 1.1. Scope Of The Report 1.2. Research Methodology 1.3. Chapter Outlines 2. Executive Summary 3. Introduction 3.1. The Central Dogma of Molecular Biology and Cell Cycle 3.2. DNA: Structure and Functions 3.3. Fundamentals of Epigenetics 3.3.1. Effect of Histone Modification on DNA Based Processes 3.3.2. Chromatin Structure Modification and its Enzymes 3.4. Histone Deacetylases (HDACs) 3.4.1. Classification of HDACs 3.4.2. Role of HDACs and HDAC Inhibitors in Cellular Processes 3.5. HDAC Inhibitors 3.5.1. Structure and Classification 3.5.2. Different Types of HDAC Inhibitors 3.5.3. Therapeutic Applications of HDAC Inhibitors 4. HDAC Inhibitors: Market Landscape 4.1. Chapter Overview 4.2. Development Pipeline of HDAC Inhibitors 4.3. Distribution by Phase of Development 4.4. Distribution by Therapeutic Area 4.5. Distribution by Class Specificity 4.6. Distribution by Type of Developer 4.7. Distribution by Geography 4.8. Active Industry Players 5. Drug Profiles: Marketed And Late-Stage HDAC Inhibitors 5.1. Chapter Overview 5.2. Company and Drug Profiles: Marketed and Phase III Molecules 5.2.1. Celgene Corporation 5.2.3. Novartis 5.2.4. Shenzhen Chipscreen Biosciences 5.2.5. Syndax Pharmaceuticals 5.3. Drug Profiles: Phase II Molecules 5.3.1. Abexinostat (PCI-24781) 5.3.2. CUDC-907 5.3.3. FRM-0334 (EVP-0334) 5.3.4. Givinostat (ITF2357) 5.3.5. Mocetinostat (MGCD103) 5.3.6. Pracinostat (SB939) 5.3.7. Resminostat (4SC-201) 5.3.8. SFX-01 5.3.9. SHAPE (SHP-141) 5.3.10. Tefinostat (CHR-2845) 6. Key Insights: Therapeutic Area, Class Specificity, Clinical Endpoints 6.1. Clinical Development Analysis: Class Specificity and Therapeutic Areas 6.2. Clinical Development Analysis: Developer Landscape 6.3. Clinical Development Analysis: Trial Endpoint Comparison 7. Market Forecast And Opportunity Analysis 7.1. Chapter Overview 7.2. Scope and Limitations 7.3. Forecast Methodology 7.4. Overall HDAC Inhibitors Market 7.5. HDAC Inhibitors Market: Individual Forecasts 7.5.1. Zolinza (Merck) 7.5.2. Istodax® (Celgene Corporation) 7.5.3. Beleodaq® (Onxeo) 7.5.4. Farydak® (Novartis) 7.5.5. Epidaza® (Shenzhen Chipscreen Biosciences) 7.5.6. Entinostat (Syndax Pharmaceuticals) 7.5.7. Abexinostat (Pharmacyclics) 7.5.8. CUDC-907 (Curis) 7.5.9. FRM-0334 (FORUM Pharmaceuticals) 7.5.10. Mocetinostat (Mirati Therapeutics) 7.5.11. Pracinostat (MEI Pharma) 7.5.12. Resminostat (4SC, Menarini, Yakult Honsha) 7.5.13. SFX-01 (Evgen Pharma) 7.5.14. SHP-141 (TetraLogic Pharmaceuticals) 7.5.15. Tefinostat (Chroma Therapeutics) 8. Publication Analysis 8.1. Chapter Overview 8.2. HDAC Inhibitors: Publications 8.3. Publication Analysis: Quarterly Distribution 8.4. Publication Analysis: Distribution by HDAC Inhibitor Class 8.5. Publication Analysis: Distribution by Drugs Studied 8.6. Publication Analysis: Distribution by Therapeutic Area 8.7. Publication Analysis: Distribution by Journals 8.8. Publication Analysis: Distribution by Phase of Development 8.9. Publication Analysis: Distribution by Type of Therapy 9. Social Media: Emerging Trends 9.1. Chapter Overview 9.1.1. Trends on Twitter 9.1.2. Trends on Facebook 10. Conclusion 10.1. The Pipeline is Healthy with Several Molecules in Preclinical Stages of Development 10.2. HDAC Inhibitors Cater to a Wide Spectrum of Disease Areas 10.3. Class Specific HDAC Inhibitors Have Been Explored for a More Targeted Approach 10.4. The Interest is Gradually Rising Amongst Both Industry and Non-Industry Players 10.5. Supported by a Robust Preclinical Pipeline, HDAC Inhibitors are Expected to Emerge as A Multi-Billion Dollar Market 11. Interview Transcripts 11.1. Chapter Overview 11.2. Dr. Simon Kerry, CEO, Karus Therapeutics 11.3. Dr. James Christensen, CSO and Senior VP, Mirati Therapeutics 11.4. Dr. Hyung J. Chun, MD, FAHA, Associate Professor of Medicine, Yale School of Medicine 12. Appendix 1: Tabulated Data 13. Appendix 2: List Of Companies And Organizations Companies Mentioned - 4SC - AACR - AbbVie - Acceleron Pharma - Acetylon Pharmaceuticals - Active Biotech - Agios Pharmaceuticals - ASH - Arno Therapeutics - Astellas Pharma - Bayer Schering Pharma - Baylor College of Medicine - BioMarin - Bionor Immuno - bluebird bio - Case Comprehensive Cancer Center - Celera Genomics - Celgene - Celleron Therapeutics - Centre de Recherche en Cancérologie - CETYA Therapeutics - CHDI Foundation - Chipscreen Biosciences - Chong Kun Dang Pharmaceutical - Chroma Therapeutics - Croix-Rousse Hospital - CrystalGenomics - Curis - DAC - Diaxonhit - DNA Therapeutics - Duke University - ECOG-ACRIN Cancer Research Group - Eddingpharm - Eisai - Epizyme - Errant Gene Therapeutics - European Calcified Tissue Society - Evgen Pharma - FORMA Therapeutics - FORUM Pharmaceuticals - Fudan University - Genentech - Genextra - Gilead - Gloucester Pharmaceuticals - GNT Biotech - GSK - Harvard Medical School - Henan Cancer Hospital - HUYA Biosciences - Ikerchem - Imperial College London - In2Gen - International Bone and Mineral Society - Israel Cancer Association and Bar Ilan University - Italfarmaco - Johnson and Johnson - Kalypsys - Karus Therapeutics - King's College, University of London - Kyoto Prefectural University of Medicine - Kyoto University - Kyowa Hakko Kirin - Leukemia and Lymphoma Society - Lymphoma Academic Research Organization - Massachusetts General Hospital - Mayo Clinic - MedImmune - MEI Pharma - Memorial Sloan-Kettering Cancer Center - Menarini - Merck - MethylGene - Mirati Therapeutics - Morphosys - Mundipharma-EDO - National Brain Research Centre - National Comprehensive Cancer Network - National Taiwan University - NCI - Novartis - NuPotential - Oceanyx Pharma - Oncolys Biopharma - Onxeo - Onyx - Orchid Pharma - Paterson Institute for Cancer Research - Pfizer - Pharmacyclics - Pharmion Corporation - Quimatryx - Quintiles - Repligen - Respiratorius - Roche - Rodin Therapeutics - Royal Veterinary College, University of London - Ruijin Hospital - S*Bio - Sarcoma Alliance for Research through Collaboration - Seattle Genetics - Servier Canada - Shape Pharmaceuticals - Sidney Kimmel Comprehensive Cancer Center - Sigma Tau Pharmaceuticals - Signal Rx - SpeBio - Spectrum Pharmaceuticals - Stanley Center for Psychiatric Research - Sutro Biopharma - Syndax Pharmaceuticals - Synovo GmbH - Taipei Medical University - TetraLogic Pharmaceuticals - University of Liverpool - University of Messina - University of Miami - Vanderbilt University School of Medicine - Ventana Medical Systems - Vilnius University - Yakult Honsha - Yale University - Yonsei University College of Medicine For more information about this report visit http://www.researchandmarkets.com/research/srvj3j/hdac_inhibitors


News Article | January 20, 2016
Site: www.nature.com

No statistical methods were used to predetermine sample size. All procedures were performed in accordance with the law on animal protection issued by the German Federal Government (Tierschutzgesetz) and approved by the institutional animal welfare committee of the University of Tübingen. For all experiments, we used 4- to 8-week-old mice of either sex. In addition to C57Bl6 (wild-type) mice, we used the transgenic lines PvalbCre (‘PV’, JAX 008069, The Jackson Laboratory; ref. 43), Pcp2Cre (‘Pcp2’, JAX 006207; ref. 44) and ChATCre (JAX 006410; ref. 51), cross-bred with the red fluorescence Cre-dependent reporter line Ai9:tdTomato (JAX 007905). Owing to the exploratory nature of our study, we did not use randomization and blinding. Animals were housed under a standard 12 h day/night rhythm. For activity recordings, animals were dark-adapted for ≥1 h, then anaesthetized with isoflurane (Baxter) and killed by cervical dislocation. The eyes were enucleated and hemisected in carboxygenated (95% O , 5% CO ) artificial cerebral spinal fluid (ACSF) solution containing (in mM): 125 NaCl, 2.5 KCl, 2 CaCl , 1 MgCl , 1.25 NaH PO , 26 NaHCO , 20 glucose, and 0.5 l-glutamine (pH 7.4). Bulk electroporation of the fluorescent Ca2+ indicator Oregon-Green BAPTA-1 (OGB-1) into the ganglion cell layer (GCL) was carried out as described before19, 47. In brief, the retina was dissected from the eyecup, flat-mounted onto an Anodisc (#13, 0.2 μm pore size, GE Healthcare) with the GCL facing up, and placed between two 4-mm horizontal plate electrodes (CUY700P4E/L, Nepagene/Xceltis). A 10 μl drop of 5 mM OGB-1 (hexapotassium salt; Life Technologies) in ACSF was suspended from the upper electrode and lowered onto the retina. After application of 10–12 pulses (+9 V, 100 ms pulse width, at 1 Hz) from a pulse generator/wide-band amplifier combination (TGP110 and WA301, Thurlby handar/Farnell), the tissue was moved to the recording chamber of the microscope, where it was continuously perfused with carboxygenated ACSF at ~37 °C and left to recover for ~60 min before the recordings started. In all experiments with wild-type mice, ACSF contained ~0.1 μM Sulforhodamine-101 (SR101, Invitrogen) to reveal blood vessels and any damaged cells in the red fluorescence channel20. All procedures were carried out under very dim red (>650 nm) light. We used a MOM-type two-photon microscope (designed by W. Denk, MPI, Martinsried; purchased from Sutter Instruments/Science Products). Design and procedures were described previously20. In brief, the system was equipped with a mode-locked Ti:Sapphire laser (MaiTai-HP DeepSee, Newport Spectra-Physics) tuned to 927 nm, two fluorescence detection channels for OGB-1 (HQ 510/84, AHF/Chroma) and SR101 (HQ 630/60, AHF), and a water immersion objective (W Plan-Apochromat 20x/1,0 DIC M27, Zeiss). For image acquisition, we used custom-made software (ScanM, by M. Müller, MPI, Martinsried, and T.E.) running under IGOR Pro 6.3 for Windows (Wavemetrics), taking 64 × 64 pixel image sequences (7.8 frames per s) for activity scans or 512 × 512 pixel images for high-resolution morphology scans. For light stimulation, we focused a DLP projector (K11, Acer) through the objective, fitted with band-pass-filtered light-emitting diodes (LEDs) (‘green’, 578 BP 10; and ‘blue’, HC 405 BP 10, AHF/Croma) that roughly match the spectral sensitivity of moose M- and S-opsins. LEDs were synchronized with the microscope’s scan retrace. Stimulator intensity (as photoisomerisation rate, 103 P* per s per cone) was calibrated as described previously52 to range from 0.6 and 0.7 (black image) to 18.8 and 20.3 for M- and S-opsins, respectively. Owing to two-photon excitation of photopigments, an additional, steady illumination component of ~104 P* per s per cone was present during the recordings (for detailed discussion, see ref. 22). For all experiments, the tissue was kept at a constant intensity level (see stimuli below) for at least 30 s after the laser scanning started before light stimuli were presented. Four types of light stimulus were used (Fig. 1b, top): (i) full-field ‘chirp’ stimulus consisting of a bright step and two sinusoidal intensity modulations, one with increasing frequency and one with increasing contrast; (ii) 0.3 × 1 mm bright bar moving at 1 mm s−1 in eight directions19; (iii) alternating blue and green 3-s flashes; and (iv) binary dense noise, a 20 × 15 matrix with 40 μm pixel-side length; each pixel displayed an independent, perfectly balanced random sequence at 5 Hz yielding a total running time of 5 min for receptive field (RF) mapping. In some experiments, we used in addition dark moving bars (like (ii) but contrast-inversed), and stationary bright or dark 0.2 × 0.8 mm bars flashed for 1 s in six orientations (see Extended Data Fig. 7h–s). Except for (iii), stimuli were achromatic, with matched photo-isomerization rates for M- and S-opsins. TdTomato- or OGB-1-labelled RGCs were targeted using two-photon imaging for juxtacellular recordings using borosilicate electrodes (4–6 MΩ) filled with ACSF with added SR101 (250 μM). Data were acquired using an Axoclamp-900A or Axopatch 200A amplifier in combination with a Digidata 1440 (all: Molecular Devices), digitized at 10 kHz and analysed offline using IGOR Pro. We presented the same light stimuli as for the Ca2+ imaging. In some experiments, electrical recordings and Ca2+ imaging was performed simultaneously. After the recording, the membrane under the electrode was opened using a voltage ‘buzz’ to let the cell fill with dye by diffusion for approximately 30 min; then two-photon image stacks were acquired to document the cell’s morphology. Filled cells were traced semi-automatically offline using the Simple Neurite Tracer plugin implemented in Fiji (http://fiji.sc/Fiji), yielding cell skeletons. If necessary, we used the original image stack to correct the skeletons for any warping of the IPL using custom-written scripts in IGOR Pro. To this end, we employed the SR101-stained blood vessel plexuses on either side of the IPL as landmarks to define the IPL borders (see below). Only cells where the filling quality allowed full anatomical reconstruction were used for analysis (see below). Following Ca2+ imaging, retinas were mounted onto filter paper (0.8 μm pore size, Millipore) and fixed in 4% paraformaldehyde (in PBS) for 15 min at 4 °C. Immunolabelling was performed using antibodies against ChAT (choline-acetyltransferase; goat anti-ChAT, 1:100, AB144P, Millipore), GAD67 (glutamate decarboxylase; mouse anti-GAD67, 1:100, MAB5046, Millipore), SMI-32 (mouse anti-SMI32, 1:100, SMI-32R-100, Covance), and melanopsin (rabbit anti-melanopsin, 1:4000, AB-N38, Advanced Targeting Systems) for 4 days. Secondary antibodies were Alexa Fluor conjugates (1:750, 16 h, Life Technologies). For each retina, the recorded region was identified by the local blood vessel pattern and confirmed by comparing size and position of individual somata in the GCL. Image stacks were acquired on a confocal microscope (Nikon Eclipse C1) equipped with a ×60 oil objective (1.4 NA). The degree of immunolabelling of GCL cells was evaluate and rated (from 0, negative, to 4 positive) using z-stacks. Attribution of labelled somata to recorded ones was performed manually using ImageJ (http://imagej.nih.gov/ij) and IGOR Pro. Data analysis was performed using Matlab 2012 and 2014a (The Mathworks Inc.), and IGOR Pro. Data were organized in a custom written schema using the DataJoint for Matlab framework (http://datajoint.github.io/; D. Yatsenko, Tolias lab, Baylor College of Medicine). Regions of interest (ROIs), corresponding to somata in the GCL, were defined semi-automatically by custom software (D. Velychko, CIN) based on a high-resolution (512 × 512 pixels) image stack of the recorded field. Then, the Ca2+ traces for each ROI were extracted (as ΔF/F) using the IGOR Pro-based image analysis toolbox SARFIA (http://www.igorexchange.com/project/SARFIA). A stimulus time marker embedded in the recording data served to align the Ca2+ traces relative to the visual stimulus with a temporal precision of 2 ms. Stimulus-aligned Ca2+ traces for each ROI were imported into Matlab for further analysis. First, we de-trended the Ca2+ traces by high-pass filtering above ~0.1 Hz. For all stimuli except the dense noise (for RF mapping), we then subtracted the baseline (median of first eight samples), computed the median activity r(t) across stimulus repetitions (typically three to five repetitions) and normalized it such that . We mapped the linear RFs of the neurons by computing the Ca2+ transient-triggered average. To this end, we resampled the temporal derivative of the Ca2+ response ċ(t) at 10-times the stimulus frequency and used Matlab’s findpeaks function to detect the times t at which Ca2+ transients occurred. We set the minimum peak height to 1 s.d., where the s.d. was robustly estimated using: We then computed the Ca2+ transient-triggered average stimulus, weighting each sample by the steepness of the transient: Here, S(x, y, t) is the stimulus, τ is the time lag (ranging from approximately −320 to 1,380 ms) and M is the number of Ca2+ events. We smoothed this raw RF estimate using a 5 × 5 pixel Gaussian window for each time lag separately. RF maps shown correspond to a s.d. map, where the s.d. is calculated over time lags τ: To extract the RF’s position and scale, we fitted it with a 2D Gaussian function using Matlab’s lsqcurvefit. The time course of the receptive field F (τ) was estimated by the average of the eight pixels closest to the fitted RF centre (according to the Mahalanobis distance) weighted by a Gaussian profile. RF quality (QI ) was measured as one minus the fraction of variance explained by the Gaussian fit To extract time course and directional tuning of the Ca2+ response to the moving bar stimulus, we performed a singular value decomposition (SVD) on the T by D normalized mean response matrix M (times samples by number of directions; T = 32; D = 8; Extended Data Fig. 7a, b): This procedure decomposes the response into a temporal component in the first column of U and a direction dependent component or tuning curve in the first column of V, such that the response matrix can be approximated as an outer product of the two: An advantage of this procedure is that it does not require manual selection of time bins for computing direction tuning, but extracts the direction tuning curve given the varying temporal dynamics of different neurons. To measure direction selectivity (DS) and its significance, we projected the tuning curve V on a complex exponential , where α is the direction in the kth condition: This is mathematically equivalent to computing the vector sum in the 2D plane or computing the power in the first Fourier component. We computed a DS index as the resulting vector length correcting for the direction spacing. We additionally assessed the statistical significance of direction tuning using a permutation test53. To this end, we created surrogate trials (that is, stimulus repetitions) by shuffling the trial labels (that is, destroying any relationship between condition and response), computed the tuning curve for each surrogate trial and projected it on the complex exponential ϕ. Carrying out the procedure 1,000 times generated a null distribution for K, assuming no direction tuning. We used the percentile of the true K as the P value for direction tuning (Extended Data Fig. 7c). Importantly, a large DSi does not necessarily result in a small P value, for example, in the case of large trial to trial variability. As a result, the DSi distributions of significantly and not significantly direction tuned neurons show substantial overlap (Extended Data Fig. 7d, e). Therefore, a simple threshold as a DS criterion (for example, DSi > 0.4) does not provide a good separation into direction selective cell types and others. Orientation selectivity (OS) was assessed in an analogous way. However, we used the complex exponential , corresponding to the second Fourier component. To measure how well a cell responded to a stimulus (chirp, moving bar, colour), we computed the signal-to-noise ratio where C is the T by R response matrix (time samples by stimulus repetitions) and 〈 〉 and Var[ ] denote the mean and variance across the indicated dimension, respectively. If all trials are identical such that the mean response is a perfect representative of the response, QI is equal to 1. If all trials are completely random with fixed variance (so that the mean response is not informative about the individual trial responses at all), QI is proportional to 1/R. For further analysis, we used only cells that responded well to the chirp and/or the moving bar stimulus (QI  > 0.45 or QI  > 0.6). The full-field index was computed as comparing the response quality to a local stimulus (moving bar) and a global stimulus (chirp). where r and r are defined as the activity during the response to the leading edge of the moving bar (the first 400 ms of the ON response) and the trailing edge of the moving bar (the first 400 ms of the OFF response). Colour selectivity was measured for the ON response using and for the OFF response using an analogous definition. Here, r and r are the responses in a time window of 1,280 ms after onset of the green and blue stimulus, respectively. We used sparse principle component analysis54, as implemented in the SpaSM toolbox by K. Sjöstrang et al. (http://www2.imm.dtu.dk/projects/spasm/), to extract sparse response features from the responses to the chirp, colour, and moving bar stimulus, resulting in features which use only a small number of time bins. The extracted features are localized in time and therefore readily interpretable (for example, ‘high-frequency feature’), although this constraint was not explicitly enforced by the algorithm (Extended Data Fig. 2e). We also explored alternative feature extraction techniques such as regular PCA, but these resulted in inferior cluster quality. In addition, they required manually defining regions corresponding to specific parts of the stimulus (for example, frequency chirp) to yield localized and interpretable features. We extracted 20 features with 10 non-zero time bins from the mean response to the chirp (averaging across trials) and 6 features with 10 non-zero time bins from the mean response to the colour stimulus. For the moving bar stimulus, we extracted 8 features with 5 non-zero time bins from the response time course (see above) and 4 features with 6 non-zero time bins from its temporal derivative. All features were in the temporal domain, ensuring spatial invariance. In addition, we used two features from the time course of the RF, extracted with regular PCA. Overall, this procedure resulted in a 40 dimensional feature vector for each cell. Before clustering, we standardized each feature separately across the population of cells. DS and non-DS cells were clustered independently, classifying cells as DS if the permutation test resulted in P < 0.05 (see above). We fit each data set with a Mixture of Gaussians model using the expectation-maximization algorithm (Matlab’s gmdistribution object). We constrained the covariance matrix for each component to be diagonal, resulting in 80 parameters per component (40 for the mean, 40 for the variances). We further regularized the covariance matrix by adding a constant (10−5) to the diagonal. To find the optimal number of clusters, we evaluated the Bayesian information criterion55 where L is the log-likelihood of the model, N is the number of cells and M is the number of parameters in the model, that is, M = 81C − 1 where C is the number of clusters and the contributions that arose from means, variances and mixture proportions (which have to add to 1). Although other choices such as the Aikaike information criterion (AIC) would have been possible, we found the BIC to yield a good compromise between model complexity and quality, since the AIC is known to find too many clusters for large sample sizes. We also computed log Bayes factors as 2ΔBIC for each candidate cluster number to test how strong the evidence for further splitting is. Values >6 were treated as strong evidence in favour of further splitting. The minimum of the BIC coincided well with the number of clusters after which there was no strong evidence for further adding more clusters. To avoid local minima, we restarted the EM algorithm 20 times per candidate number of clusters and used the solution with the largest likelihood. This procedure resulted in 24 and 48 clusters for DS and non-DS cells, respectively (Extended Data Fig. 2a). To evaluate cluster quality, we rank-ordered the posterior probabilities for cluster assignment for each cluster, normalized for cluster size and averaged across clusters for non-DS and DS cells separately (Extended Data Fig. 2b). The steep decays of the sigmoidal functions indicate good cluster separability. To check how consistent the clustering was against subsampling of the data, we created 20 surrogate data sets containing random selections of 90% of the cells. We fit these surrogate data sets with a Mixture of Gaussians model with the optimal number of clusters determined on the original data set. For each cluster mean in these models, we computed the correlations with the most similar cluster for the model fit on the original data set. To summarize the similarity of clusterings, we computed the median correlation across clusters (Extended Data Fig. 2c). On average, the clusterings obtained on the surrogate and the original data set were very similar (mean median correlation: 0.96 ± 0.19 and 0.97 ± 0.01; mean ± s.d.; for DS and non-DS cells separately). In addition, we performed an alternative clustering version, where we did not split the data in DS and non-DS cells but added DSi, OSi, soma and receptive field size as features. The identified clusters were very similar, but this strategy failed to identify most DS types as separate clusters, except for the ON–OFF DS cell. Therefore, we decided to first isolate significant DS cells and cluster them separately, before merging similarly responding DS and non-DS clusters (see below), if we did not find a reason to keep the DS group as a separate RGC type. Nevertheless, a strategy equally justified as ours could start with the alternative clustering and then split those clusters containing large fractions of DS cells. A subset of cells was stained against GAD67 to identify dACs (see above). The intensity of this staining was manually rated as follows: −2 (absent), −1 (probably absent), 0 (uncertain), 1 (probably present), and 2 (present). For each cluster, we computed the average staining from the labelled cells (average number of cells with GAD67 information per cluster: 16.8 ± 10.0, mean ± s.d.). Clusters with an average staining <-0.2 were labelled RGCs (n = 30 clusters), those with average staining >0.2 were labelled ACs (n = 26). Clusters with average staining in-between those values (n = 5), or those that contained 6 or less cells with GAD67 information (n = 8) were labelled as uncertain, unless other clear criteria such as soma size or genetic labels indicated that they are ACs or RGCs. In this case they were manually allocated to RGC or AC (n = 3 and n = 2, respectively). Two clusters automatically classified as AC were included in the uncertain group due to their functional similarity with the OFF-suppressed types (G ). This procedure resulted in 33 RGC clusters, 10 uncertain clusters and 26 AC clusters. We extracted all cells with large cell bodies (>136 μm2; mean + 1 s.d. of total soma size distribution; Extended Data Fig. 2i, j) from RGC and uncertain clusters. Predominantly, these cells had been assigned to nine of the clusters. We re-clustered those cells using a Mixture of Gaussians model as described above, resulting in 16 clusters (Extended Data Fig. 2j). Receptive field size was not used in this process. Five of these clusters could be clearly associated with the three known alpha-RGC types and their response profiles31 (trans. OFF alpha, 2; sust. OFF alpha, 2; ON alpha, 1). Cells in these clusters were SMI-32-positive, as expected from alpha RGCs (Fig. 3i, k). Probably, this procedure missed some alpha cells, as somata close to the edge of scan fields were cut and we thus underestimate the soma size of these cells (for example, G c, see Fig. 2a–c). Remaining cells were kept in their original cluster. Logistic regression was used to assess the effect cell type (alpha vs. mini) on SMI-32 staining (absent vs. present). We used the Matlab implementation fitglm with a binomial nonlinearity. 95%-confidence intervals on the proportion of SMI32-positive cells were computed using bootstrapping with 1,000 samples. We used a standard linkage algorithm on the means of the RGC groups in the standardized feature space with correlation distance and average unweighted distance and plotted the result as a dendrogram (using Matlab functions linkage and dendrogram). The leaf order was optimized using the Matlab function optimalleaforder and modified for clarity of presentation. with the number of cells in a group (n ), the median RF size (A ) within a group counting only cells that surpassed a RF quality criterion of 0.3, and the total scan area across all experiments (A ). We corrected n for 29% cells discarded by our quality criterion as well as an empirically estimated 8% of cells that did not yield a ROI in the first place due to weak or absent labelling. In addition, A was corrected for an empirically estimated 34.8% RF overhang (that is, where a cell’s RF exceeds the scan field edge). This procedure yielded a CF of 2.0 ± 0.7 for most RGC groups (Gaussian fit; see Fig. 2e, right). However, differences between studies in approaches to measure RFs (for example, checkerboards vs. bars), in the assumptions used for RF fitting (for example, homogenous RFs best fitted by Gaussians), or in the methods to estimate dendritic arbor area can easily yield different absolute estimates of CF (see also Supplementary Table 1). To determine a cell’s IPL stratification profile, we calculated dendritic density as described previously10 with spatial smoothing of 1 μm3. The resultant 3D density cloud was projected on the z axis to estimate the mean IPL depth profile. The relationship between the depth profiles and the two ChAT bands was estimated in independent experiments using mice that express tdTomato in cholinergic ACs (ChATCre × Ai9:tdTomato). We compared the IPL depth of the tdTomato-labelled dendritic plexi to the two SR101-labelled blood vessel planes that line the inner retina. We estimated the error to be ~1.5 μm (s.d.), corresponding to 3–4% IPL depth (n = 13 measurements in 2 mice). To relate each cell’s IPL profile to functional groups we calculated the mean correlation coefficient between a cell’s response to the chirp and moving bar stimuli and each group’s mean response. The correlation coefficient (−1…1) for each pair was then multiplied with the cell’s depth profile and a correlation-rank based weighting factor W = 0.9rank −1. Thus, each individual recording yielded a complete two-dimensional map, with IPL depth on one axis and functional group on the other. Next, we averaged across the maps for those cells that passed our response quality criterion (n  = 31/51; n  = 24/33; see above). The resultant matrices were normalized in two steps: First, we divided each group’s IPL depth profile by the mean depth profile of all included cells to eliminate any bias in sampling depth. Second, we divided each depth profile by its own maximum. This resulted in an automatic and unbiased estimate of dendritic stratification depth for all RGC groups (Fig. 5). Note that this automated approach is based on a relatively small sample of reconstructed cells and therefore can only provide an approximate prediction of stratification levels. This approach is invariant to differences in lateral dendritic field dimensions that may be associated with retinal position (for example, refs 10,23).


Dallas, TX (December 1, 2016) -- Over the Thanksgiving holiday in 2012, John Rodakis, a father of a child with autism, observed his son's condition dramatically improve while taking a common antibiotic. This marked the beginning of a four year quest to understand how an antibiotic might affect behaviors associated with autism. Today, on the four year anniversary of that observation, Baylor College of Medicine is launching a national study funded by the non-profit the father started, N of One: Autism Research Foundation, to investigate this routinely observed phenomenon. The first-of-its kind study will investigate why some children with autism spectrum disorder (ASD) experience improvements or changes in their autism symptoms when taking antibiotics. The study will follow children over a two-year period and capture information anytime antibiotics are prescribed by their regular physicians and compare changes in the gut microbiome (bacteria, yeasts and fungi found in the gut) and metabolome (small biological molecules produced by the microbes) during antibiotic use of those who experience a change in symptoms during to those who do not. The study seeks to understand when and why these changes occur and how this information can be harnessed for future interventions. Autism Spectrum Disorder is a neuro-developmental disorder with a steadily growing prevalence that affects more than 2 percent of children. Many parents have reported that their children experienced significant changes in their ASD symptoms, typically improvements, though sometimes a worsening of symptoms, when taking antibiotics, aka the "antibiotic effect." Recent research has documented abnormalities in the gut microbiome of children with autism. Researchers have speculated that changes in the gut bacteria caused by antibiotics may be behind the changes in symptoms observed in some children with autism. The gut-brain axis is now being widely investigated by researchers in many fields of medicine. The study marks the first collaboration between N of One: Autism Research Foundation and Baylor College of Medicine and is the brain-child of two parents of affected children, Dr. Ruth Ann Luna and John Rodakis, who have both been investigating the microbiome's role in autism. Dr. Luna is one of the nation's leading investigators of the role of the microbiome in autism and is the Director of Medical Metagenomics at the Texas Children's Microbiome Center at Texas Children's Hospital in Houston. Dr. Luna is also an Assistant Professor in the Department of Pathology & Immunology at Baylor College of Medicine. Mr. Rodakis is a former medical venture capitalist who founded the N of One: Autism Research Foundation. Both Luna and Rodakis have observed changes in their children's autism symptoms while taking antibiotics. "Working with Dr. Luna has been very energizing because as a fellow affected parent, we share a real passion to get this right for our children as well as millions of others," says Rodakis. "The support of N of One is enabling a much needed study that would have been unlikely to be funded elsewhere. Because we have both witnessed the antibiotic effect in our own children, we knew this was a natural starting point targeting a gap in published autism research. Our goals reach far beyond this first study and include using these initial data to more effectively subtype autism and thereby develop and deliver more effective microbial-based interventions." There is a growing recognition that the microbiome plays a role in autism. In 2000, a clinical trial conducted at Chicago Rush Children's Hospital demonstrated that eight out of 10 children experienced a significant improvement while taking the antibiotic vancomycin. Despite this and numerous reports published in the media and medical literature of children with ASD unexpectedly improving while taking antibiotics, there have been no systematic attempts to investigating this antibiotic effect until now. "The question of why some children's autism symptoms improve is important to me scientifically and personally. We saw this in our own child in 2012 and I published a paper describing what I saw. Soon, I began hearing from parents all over the world who had observed same thing," Rodakis says. "It was stunning to me that there was a frequently reported phenomenon of improvement that was not being used as a clue to guide further research. Today we begin that process." The phenomenon has parallels to the "fever-effect," an observation that some children with ASD experience improvements when they had a fever. Parents had been reporting this for decades, but the reports were not followed up on until 2007 when a Johns Hopkins researcher, Dr. Andy Zimmerman, (a scientific advisor to N of One) documented the effect and later in 2014 used the observations as the basis for a successful treatment trial using sulforaphane, a compound found in broccoli. N of One: Autism Research Foundation was also a sponsor of that trial. The trial is open to children nationwide. Parents who are interested in participating in the trial can visit: https:/ or contact Dr Luna at raluna@bcm.edu N of One: Autism Research Foundation's mission is to facilitate and sponsor breakthrough autism medical research. N of One emphasizes research that treats the observations of parents and doctors as potential clues to how autism works and seeks to turn those into breakthroughs. Headquartered in Dallas, TX in 2014, it has been a leader in focusing on the role of the microbiome in autism. Learn more at http://www. Follow us on Facebook


Research and Markets has announced the addition of the "Neuroscience in Intensive Care International Symposium - NICIS - AMERICA - Industry/Commercial Rate" conference to their offering. This year's conference is devoted to the theme of Precision Medicine for Neurocritical Care and Stroke. Advances in genetics and in image-guided therapy are already leading to major changes in the classification, management and outcomes of patients with ischemic stroke. New management paradigms are being actively explored in the domains of acute neurological injury intracerebral haemorrhage, subarachnoid haemorrhage, anoxic-ischemic brain injury, traumatic brain injury. However, more effective predictive modelling and treatment strategies are desperately needed in these populations. THE ORGANIZERS Robert Stevens, MD, Ph.D., Associate Professor of Anesthesiology and Critical Care Medicine, Johns Hopkins University Jan Claassen, MD, Ph.D., Associate Professor of Neurology, Department of Neurology, Columbia University Jose Suarez, MD, Professor, Neurology-Vascular Critical Care, Baylor College of Medicine Tarek Sharshar, MD, Senior Consultant, Department of Intensive Care Medicine, Raymond Poincaré Hospital, Professor, The University of Versailles Agenda: The following is a preliminary agenda. Please check back in the coming weeks for additions to the agenda, for additional information regarding the presentations and the full two-day tiimeline of events. March 2nd, 2017 THE POTENTIAL FOR TRANSFORMATION KEYNOTE ADDRESS: The BRAIN Initiative Walter Koroshetz, MD, Director, National Institute of Neurological Disorders and Stroke (NINDS), NIH Towards a Molecular Taxonomy of Cancer Chetan Bettegowda, MD, Ph.D., Associate Professor of Neurosurgery, Johns Hopkins University Precision Medicine for Critical Care Tim Buchman, Ph.D., MD, Director, Emory Critical Care Center, Emory University BIG SCIENCE The Precision Medicine Initiative Joni Rutter, Ph.D., Division Director, DBNBR, National Institutes of Health (NIH) Consortia for Stroke Genetics Jonathan Rosand, MD, MSc, Chief, Division of Neurocritical Care & Emergency Neurology, Harvard University Transforming Research and Clinical Knowledge (TRACK) in TBI Ramon Diaz-Arrastia, MD, Ph.D., Clinical Associate Professor of Neurology, University of Pennsylvania Cardiovascular Research Grid Rai Winslow, Ph.D., Director, Center for Cardiovascular Bioinformatics & Modeling, Johns Hopkins University The Human Connectome Project Todd Constable, Ph.D., Professor of Radiology and Neurosurgery, Director MRI Research, Yale University METHODOLOGIES Statistical Models for Dense Biosignal Analysis Ciprian Crainiceanu, Ph.D., Professor of Biostatistics, Johns Hopkins University Systems Biology for Biomarker Discovery and Validation Akhilesh Pandey, MD, Ph.D., Professor, Johns Hopkins University Adaptive Clinical Trial Design in Acute Neurology Jose Suarez, MD, Professor of Neurology-Vascular Critical Care, Baylor College of Medicine Modeling Approaches to Physiologic Data Thomas Heldt, Ph.D., MS, Mphil, Assistant Professor Electrical and Biomedical Engineering, Massachusetts Institute of Technology Machine Learning for Clinical Prediction Saria Suchi, Ph.D., Assistant Professor, Johns Hopkins University Precision Medicine in the Neuro ICU: Multiparametric Prediction of Vasospasm After Subarachnoid Hemorrhage Soojin Park, MD, FAHA, FNCS, Assistant Professor of Neurology, Neurocritical Care Fellowship Director Columbia University College of Physicians and Surgeons    BIOLOGICAL METHODS Computational Modeling of Stroke Recovery in Humans John Krakauer, MA, MD, Professor of Neurology and Rehabilitation Medicine, Johns Hopkins University Brain-microbiome Crosstalk in Ischemic Stroke Constantino Iadecola, MD, Director, Brain & Mind Research Institute, Cornell University Biological Model of Brain Dysfunction in Sepsis Tarek Sharshar, Ph.D., Senior Consultant, Intensive Care Medicine, University of Versailles, France March 3rd, 2017 CLINICAL TRIALS Goals for Blood Pressure Management in Intracerebral Hemorrhage Adnan Qureshi, MD, Professor of Neurology, Neurosurgery and Radiology, University of Minnesota Personalized Targets for Hemodynamic Management in Neurocritical Care Christos Lazaridis, MD, Assistant Professor, Neurology, Baylor College of Medicine Selection of Intracerebral Hemorrhage Patients for Minimally Invasive Surgery Daniel Hanley, MD, Professor of Neurology, Johns Hopkins University PREDICTION Predictive Analytics for Impending Clinical Deterioration Dana Edelson, MD, Assistant Professor of Medicine, University of Chicago Quantitative Electroencephalographic Signatures for Prediction in Severe Brain Injury Jan Claassen, MD, Ph.D., FNCS, Head of Neurocritical Care and Medical Director of the Neurological ICU, Columbia University MRI Pattern Classification for TBI Detection and Prediction Yvonne Lui, MD, Associate Professor, Radiology, New York University Discriminative Mapping for Coma Recovery Prediction Robert Stevens, MD, Associate Professor, Anesthesiology & Critical Care Medicine, Johns Hopkins University Speakers: Chetan Bettegowda, MD, Ph.D., Associate Professor Neurosurgery, Johns Hopkins University Tim Buchman, Ph.D., MD, Director, Emory Critical Care Center, Emory University Jan Claassen, MD, Ph.D., FNCS, Head of Neurocritical Care, Columbia University Ciprian Crainiceanu, Ph.D., Professor of Biostatistics, Johns Hopkins University Ramon Diaz-Arrastia, MD, Ph.D., Clinical Associate Professor of Neurology, University of Pennsylvania Dana Edelson, MD, Assistant Professor of Medicine, University of Chicago Daniel Hanley, MD, Professor of Neurology, Johns Hopkins University Constantino Iadecola, MD, Director, Brain & Mind Research Institute, Cornell University Walter Koroshetz, MD, Director, NINDS John Krakauer, MA, MD, Professor of Neurology and Rehabilitation Medicine, Johns Hopkins University Christos Lazaridis, MD, Assistant Professor, Neurology, Baylor College of Medicine Yvonne Lui, MD, Associate Professor of Radiology, New York University Akhilesh Pandey, MD, Ph.D., Professor, Johns Hopkins University Adnan Qureshi, MD, Professor of Neurology, Neurosurgery and Radiology, University of Minnesota Jonathan Rosand, MD, MSc, Chief, Division of Neurocritical Care & Emergency Neurology, Harvard University Joni Rutter, Ph.D., Division Director, DBNBR, National Institutes of Health Tarek Sharshar, Ph.D., Senior Consultant, Intensive Care Medicine, University of Versailles, France Robert Stevens, MD, Associate Professor of Anesthesiology & Critical Care Medicine, Johns Hopkins University Jose Suarez, MD, Professor of Neurology-Vascular Critical Care, Baylor College of Medicine Rai Winslow, Ph.D., Director, Center for Cardiovascular Bioinformatics and Modeling, Johns Hopkins University For more information about this conference visit http://www.researchandmarkets.com/research/9mbnwd/neuroscience_in Research and Markets Laura Wood, Senior Manager press@researchandmarkets.com For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716


CLEVELAND: A researcher from University Hospitals Seidman Cancer Center will discuss his upcoming immunotherapy clinical trial for triple-negative breast cancer at the 2016 San Antonio Breast Cancer Symposium. The annual symposium is the premier meeting for more than 7,500 physicians and scientists dedicated to breast cancer treatment, featuring state-of-the-art breast cancer research such as experimental biology, etiology, prevention, diagnosis, and therapy of both breast cancer and premalignant breast disease. Joseph Baar, MD, PhD, Director of Breast Cancer Research at UH Seidman Cancer Center and Associate Professor at Case Western Reserve University School of Medicine, will share details about a phase II clinical trial testing the effectiveness of combining the chemotherapy drugs carboplatin and nab-paclitaxel with an immunotherapeutic agent called pembrolizumab (Keytruda) for use in patients with metastatic triple-negative breast cancer. Dr. Baar's poster presentation will be part of the Ongoing Trials-Targeted Therapy session on December 8, 2016 from 5 pm to 7 pm. "Up until now, women with triple-negative breast cancer have only had one treatment option, which is chemotherapy. However, more recently, we've seen that the immune modulator pembrolizumab improves outcomes in patients with metastatic triple-negative breast cancer," said Dr. Baar. "As a result, it is now critical to explore how the addition of pembrolizumab to chemotherapy might improve survival in patients with this type of breast cancer." Triple-negative breast cancer is a highly aggressive form which comprises 10-15 percent of newly diagnosed early-stage breast cancer. Most triple-negative tumors are high grade and have a high incidence of recurrence and metastases (spreading to other organs). Unlike other types of breast cancer, there is no standard follow-up treatment for triple-negative breast cancer to prevent recurrence. As triple-negative breast cancer progresses, tumor cells express a protein ligand called PD-L1, which interacts with the PD-1 receptor on T-cells. T-cells are the immune system's primary mechanism for fighting back against harmful foreign invaders. The PD-L1 to PD-1 interaction prevents the T-cell from responding to the tumor as a threat. Pembrolizumab binds to the T-cell's PD-1 receptors and therefore blocks the PD-1 to PD-L1 interaction, allowing the T-cells to be activated against the tumor cells. The research team hypothesizes that the addition of such an immunotherapeutic agent to chemotherapy will allow the body's natural immune response to reduce disease recurrence to a greater extent than either modality alone. This is the first phase II trial to study the effectiveness of combining these two chemotherapeutic agents with the immunotherapeutic agent pembrolizumab for this type of cancer. The trial will enroll approximately 30 patients beginning in early 2017. Eligible patients must have radiologically measurable and documented metastatic triple negative breast cancer, be mostly functional day to day as measured by an ECOG performance status of between zero and one, must not have received more than two prior therapies for this disease, and must be willing to undergo a preliminary biopsy for research purposes. The trial is sponsored by Merck, which produces pembrolizumab as Keytruda. "Trials our faculty members present at SABCS and other research meetings around the world illustrate the remarkable advances in oncology taking place today," says Neal J. Meropol, MD, Chief, Division of Hematology and Oncology, University Hospitals Seidman Cancer Center and Associate Director for Clinical Research, Case Comprehensive Cancer Center at Case Western Reserve. The symposium takes place December 6-10, 2016, and is hosted by The Cancer Therapy & Research Center at the University of Texas Health Science Center at San Antonio, the American Association for Cancer Research, and Baylor College of Medicine. Founded in 1866, University Hospitals serves the needs of over 1 million patients per year through an integrated network of 18 hospitals, more than 40 outpatient health centers and 200 physician offices in 15 counties throughout northern Ohio. The system's flagship academic medical center, University Hospitals Cleveland Medical Center, located on a 35-acre campus in Cleveland's University Circle, is affiliated with Case Western Reserve University School of Medicine. The main campus also includes University Hospitals Rainbow Babies & Children's Hospital, ranked among the top children's hospitals in the nation; University Hospitals MacDonald Women's Hospital, Ohio's only hospital for women; and University Hospitals Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, including cancer, pediatrics, women's health, orthopedics, radiology, neuroscience, cardiology and cardiovascular surgery, digestive health, dermatology, transplantation and urology. UH Cleveland Medical Center is perennially among the highest performers in national ranking surveys, including "America's Best Hospitals" from U.S. News & World Report. UH is also home to Harrington Discovery Institute at University Hospitals - part of The Harrington Project for Discovery & Development. UH is the second largest employer in northern Ohio with 26,000 employees. For more information, go to UHhospitals.org.


Goodell M.A.,Baylor College of Medicine | Rando T.A.,Stanford University | Rando T.A.,Center for Regenerative Rehabilitation
Science | Year: 2015

Research into stem cells and aging aims to understand how stem cells maintain tissue health, what mechanisms ultimately lead to decline in stem cell function with age, and how the regenerative capacity of somatic stem cells can be enhanced to promote healthy aging. Here, we explore the effects of aging on stem cells in different tissues. Recent research has focused on the ways that genetic mutations, epigenetic changes, and the extrinsic environmental milieu influence stem cell functionality over time.We describe each of these three factors, the ways in which they interact, and how these interactions decrease stem cell health over time.We are optimistic that a better understanding of these changes will uncover potential strategies to enhance stem cell function and increase tissue resiliency into old age.


Molofsky A.V.,University of California at San Francisco | Deneen B.,Baylor College of Medicine
GLIA | Year: 2015

Astrocytes are the predominant cell type in the brain and perform key functions vital to CNS physiology, including blood brain barrier formation and maintenance, synaptogenesis, neurotransmission, and metabolic regulation. To fully understand the contributions of astrocytes to brain function, it will be important to bridge the existing gap between development and physiology. In this review, we provide an overview of Astrocyte development, including recent insights into molecular mechanisms of astrocyte specification, regional patterning and proliferation. This developmental perspective is complemented with recent findings that describe the functional maturation of astrocytes and their prospective diversity. Future progress in understanding Astrocyte development will depend on the development of astrocyte- stage specific markers and tools for manipulating astrocytes without affecting neuron production. Ultimately, a mechanistic approach to Astrocyte development will be crucial to developing new treatments for the many neurodevelopmental, neurodegenerative, neuroimmune, and neoplastic diseases involving astrocyte dysfunction. © 2015 Wiley Periodicals, Inc.


Healy C.M.,Texas Childrens Hospital | Healy C.M.,Baylor College of Medicine | Pickering L.K.,Centers for Disease Control and Prevention
Pediatrics | Year: 2011

Development of safe and effective vaccines is one the greatest medical triumphs. However, despite high immunization rates in the United States, 85% of health care providers (HCPs) will have a parent refuse a vaccine for his or her child each year. HCPs have the greatest influence on a parent's decision to vaccinate his or her child. To effectively communicate with vaccine-hesitant parents, HCPs must first understand the concerns of parents regarding immunization and understand influences that can lead to misinformation about the safety and effectiveness of vaccines. HCPs should establish an open, nonconfrontational dialogue with vaccine-hesitant parents at an early stage and provide unambiguous, easily comprehensible answers about known vaccine adverse events and provide accurate information about vaccination. Personal stories and visual images of patients and parents affected by vaccine-preventable diseases and reports of disease outbreaks serve as useful reminders of the need to maintain high immunization rates. Ongoing dialogue including provider recommendations may successfully reassure vaccine-hesitant parents that immunization is the best and safest option for their child. Copyright © 2011 by the American Academy of Pediatrics.


El-Serag H.B.,Baylor College of Medicine | Sweet S.,Research Evaluation Unit | Winchester C.C.,Research Evaluation Unit | Winchester C.C.,University of Aberdeen | Dent J.,Royal Adelaide Hospital
Gut | Year: 2014

Objective: To update the findings of the 2005 systematic review of population-based studies assessing the epidemiology of gastro-oesophageal reflux disease (GERD). Design: PubMed and Embase were screened for new references using the original search strings. Studies were required to be population-based, to include ≥200 individuals, to have response rates ≥50% and recall periods <12 months. GERD was defined as heartburn and/or regurgitation on at least 1 day a week, or according to the Montreal definition, or diagnosed by a clinician. Temporal and geographic trends in disease prevalence were examined using a Poisson regression model. Results: 16 studies of GERD epidemiology published since the original review were found to be suitable for inclusion (15 reporting prevalence and one reporting incidence), and were added to the 13 prevalence and two incidence studies found previously. The range of GERD prevalence estimates was 18.1%-27.8% in North America, 8.8%-25.9% in Europe, 2.5%-7.8% in East Asia, 8.7%-33.1% in the Middle East, 11.6% in Australia and 23.0% in South America. Incidence per 1000 person-years was approximately 5 in the overall UK and US populations, and 0.84 in paediatric patients aged 1-17 years in the UK. Evidence suggests an increase in GERD prevalence since 1995 (p<0.0001), particularly in North America and East Asia. Conclusions: GERD is prevalent worldwide, and disease burden may be increasing. Prevalence estimates show considerable geographic variation, but only East Asia shows estimates consistently lower than 10%.


Long E.O.,National Institute of Allergy and Infectious Diseases | Sik Kim H.,National Institute of Allergy and Infectious Diseases | Sik Kim H.,University of Ulsan | Liu D.,National Institute of Allergy and Infectious Diseases | And 3 more authors.
Annual Review of Immunology | Year: 2013

Understanding how signals are integrated to control natural killer (NK) cell responsiveness in the absence of antigen-specific receptors has been a challenge, but recent work has revealed some underlying principles that govern NK cell responses. NK cells use an array of innate receptors to sense their environment and respond to alterations caused by infections, cellular stress, and transformation. No single activation receptor dominates; instead, synergistic signals from combinations of receptors are integrated to activate natural cytotoxicity and cytokine production. Inhibitory receptors for major histocompatibility complex class I (MHC-I) have a critical role in controlling NK cell responses and, paradoxically, in maintaining NK cells in a state of responsiveness to subsequent activation events, a process referred to as licensing. MHC-I-specific inhibitory receptors both block activation signals and trigger signals to phosphorylate and inactivate the small adaptor Crk. These different facets of inhibitory signaling are incorporated into a revocable license model for the reversible tuning of NK cell responsiveness. © Copyright 2013 by Annual Reviews. All rights reserved.


Dabaghian Y.,Baylor College of Medicine | Brandt V.L.,Baylor College of Medicine | Frank L.M.,University of California at San Francisco
eLife | Year: 2014

The role of the hippocampus in spatial cognition is incontrovertible yet controversial. Place cells, initially thought to be location-specifiers, turn out to respond promiscuously to a wide range of stimuli. Here we test the idea, which we have recently demonstrated in a computational model, that the hippocampal place cells may ultimately be interested in a space's topological qualities (its connectivity) more than its geometry (distances and angles); such higher-order functioning would be more consistent with other known hippocampal functions. We recorded place cell activity in rats exploring morphing linear tracks that allowed us to dissociate the geometry of the track from its topology. The resulting place fields preserved the relative sequence of places visited along the track but did not vary with the metrical features of the track or the direction of the rat's movement. These results suggest a reinterpretation of previous studies and new directions for future experiments. Copyright © 2014, Dabaghian et al.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-02-2015 | Award Amount: 5.70M | Year: 2016

Despite of their great promise, high-throughput technologies in cancer research have often failed to translate to major therapeutic advances in the clinic. One challenge has been tumour heterogeneity, where multiple competing subclones coexist within a single tumour. Genomic heterogeneity renders it difficult to identify all driving molecular alterations, and thus results in therapies that only target subsets of aggressive tumour cells. Another challenge lies in the integration of multiple types of molecular data into mathematical disease models that can make actionable clinical statements. We aim to develop predictive computational technology that can exploit molecular and clinical data to improve our understanding of disease mechanisms and to inform clinicians about optimized strategies for therapeutic intervention. We propose to focus on prostate cancer, a leading cause of cancer death amongst men in Europe, but also prone to over-treatment. Our approach combines the exploitation of genomic, transcriptomic, proteomic, and clinical data in primary and metastatic tumours, prospective cohorts of well characterized prostate cancer patients, drug screenings in cell lines, and the use of the Watson technology, a last generation cognitive computer developed at IBM. The translational objective of this study is to develop technology for identifying disease mechanisms and produce treatment recommendations for individual patients based on a therapeutic biomarker panel. The proposed software framework will be accessible through a graphical interface that will facilitate its dissemination and use by researchers, clinicians, and biomedical industries. The framework will provide intuitive tools to deposit, share, analyze, and visualize molecular and clinical data; as well as to infer prognosis, elucidate implicated mechanisms and recommend therapy accordingly. This software framework will serve as a proof of concept for future development by industrial partners in Europe.


Schlomer B.J.,Baylor College of Medicine | Copp H.L.,University of California at San Francisco
Journal of Urology | Year: 2014

Purpose Secondary data analysis is the use of data collected for research by someone other than the investigator. In the last several years there has been a dramatic increase in the number of these studies being published in urological journals and presented at urological meetings, especially involving secondary data analysis of large administrative data sets. Along with this expansion, skepticism for secondary data analysis studies has increased for many urologists. Materials and Methods In this narrative review we discuss the types of large data sets that are commonly used for secondary data analysis in urology, and discuss the advantages and disadvantages of secondary data analysis. A literature search was performed to identify urological secondary data analysis studies published since 2008 using commonly used large data sets, and examples of high quality studies published in high impact journals are given. We outline an approach for performing a successful hypothesis or goal driven secondary data analysis study and highlight common errors to avoid. Results More than 350 secondary data analysis studies using large data sets have been published on urological topics since 2008 with likely many more studies presented at meetings but never published. Nonhypothesis or goal driven studies have likely constituted some of these studies and have probably contributed to the increased skepticism of this type of research. However, many high quality, hypothesis driven studies addressing research questions that would have been difficult to conduct with other methods have been performed in the last few years. Conclusions Secondary data analysis is a powerful tool that can address questions which could not be adequately studied by another method. Knowledge of the limitations of secondary data analysis and of the data sets used is critical for a successful study. There are also important errors to avoid when planning and performing a secondary data analysis study. Investigators and the urological community need to strive to use secondary data analysis of large data sets appropriately to produce high quality studies that hopefully lead to improved patient outcomes. © 2014 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.


Hoersch D.,University of California at San Francisco | Roh S.-H.,Baylor College of Medicine | Chiu W.,Baylor College of Medicine | Kortemme T.,University of California at San Francisco
Nature Nanotechnology | Year: 2013

Natural protein assemblies have many sophisticated architectures and functions, creating nanoscale storage containers, motors and pumps. Inspired by these systems, protein monomers have been engineered to self-assemble into supramolecular architectures including symmetrical, metal-templated and cage-like structures. The complexity of protein machines, however, has made it difficult to create assemblies with both defined structures and controllable functions. Here we report protein assemblies that have been engineered to function as light-controlled nanocontainers. We show that an adenosine-5′-triphosphate-driven group II chaperonin, which resembles a barrel with a built-in lid, can be reprogrammed to open and close on illumination with different wavelengths of light. By engineering photoswitchable azobenzene-based molecules into the structure, light-triggered changes in interatomic distances in the azobenzene moiety are able to drive large-scale conformational changes of the protein assembly. The different states of the assembly can be visualized with single-particle cryo-electron microscopy, and the nanocages can be used to capture and release non-native cargos. Similar strategies that switch atomic distances with light could be used to build other controllable nanoscale machines. © 2013 Macmillan Publishers Limited.


News Article | March 1, 2017
Site: www.24-7pressrelease.com

WILLIAMSBURG, VA, March 01, 2017-- Dr. Mary L. Voorhess is a celebrated Marquis Who's Who biographee. As in all Marquis Who's Who biographical volumes, individuals profiled are selected on the basis of current reference value. Factors such as position, noteworthy accomplishments, visibility, and prominence in a field are all taken into account during the selection process.Marquis Who's Who, the world's premier publisher of biographical profiles, is proud to name Dr. Voorhess a Lifetime Achiever. An accomplished listee, Dr. Voorhess celebrates many years' experience in her professional network, and has been noted for achievements, leadership qualities, and the credentials and successes she has accrued in her field.Dr. Voorhess, Professor Emerita, Dept. of Pediatrics, College of Medicine and Biomedical Sciences, State University of New York at Buffalo, prepared for her role as co-chief of the Division of Endocrinology at Children's Hospital of Buffalo by earning a Doctor of Medicine degree from Baylor College of Medicine (Houston); a Bachelor of Arts in Zoology from the University of Texas (Austin); and became an RN after graduating from City Hospital School of Nursing in Binghamton, NY.Dr. Voorhess received a Research Career Development Award from the National Cancer Institute (NIH), and the Dean's Award for Service to the University from SUNY Buffalo. She has been featured in numerous Marquis Who's Who publications, including Who's Who of American Women, Who's Who in the World, Who's Who in the South and Southwest, Who's Who in Science and Engineering, Who's Who in Medicine and Healthcare and Who's Who in America.In recognition of outstanding contributions to her profession and the Marquis Who's Who community, Dr. Voorhess has been featured on the Marquis Who's Who Lifetime Achievers website. Please visit https://wwlifetimeachievement.com/2016/12/12/mary-voorhess/ to view this distinguished honor.About Marquis Who's Who :Since 1899, when A. N. Marquis printed the First Edition of Who's Who in America , Marquis Who's Who has chronicled the lives of the most accomplished individuals and innovators from every significant field of endeavor, including politics, business, medicine, law, education, art, religion and entertainment. Today, Who's Who in America remains an essential biographical source for thousands of researchers, journalists, librarians and executive search firms around the world. Marquis publications may be visited at the official Marquis Who's Who website at www.marquiswhoswho.com


News Article | October 27, 2016
Site: techcrunch.com

A Houston-based startup called BrainCheck has raised $3 million in seed funding for an app that helps users understand, by simply playing some games on an iPad, if they or a loved one may have suffered a concussion. Founded in 2014 by Dr. David Eagleman, a neuroscientist at Baylor College of Medicine, BrainCheck adapts to an interactive format the accepted assessments that neuropsychologists and neurologists administer to patients offline. If concussion sounds like a health problem limited to pro football players, it is not, said Eagleman, and BrainCheck CEO Yael Katz, who has a PhD in biological informatics. There are 1.6 million to 3.8 million sport-related concussions, also known as mild traumatic brain injuries, in the U.S. every year, according to data cited by the Journal of Head Trauma and Rehabilitation. In 2009, Washington state became the first state to attempt to stem the public health epidemic of concussion among student athletes with its Zackery Lystedt Law, requiring policies for the “management of head injury in youth sports.” Since then, the issue has gotten more notice thanks to a PBS Frontline documentary in 2013, League of Denial, and a Hollywood film called Concussion last year starring Will Smith. Now, the president’s 2017 budget proposal requests $5 million for the Centers for Disease Control and Prevention (CDC) to establish and run a National Concussion Surveillance System, which would allow the organization to more precisely grasp how mildly traumatic brain injuries are effecting the U.S. population. Data gathered by BrainCheck could contribute to such studies and our collective understanding about neurocognitive health, the founders said. While BrainCheck has seen early traction in the U.S., selling to school districts, athletic trainers and families whose kids participate in sports, the company is seeking to expand internationally and beyond concussion monitoring, Katz said. Specifically, BrainCheck is developing features and functionality to assess older users at risk of dementia. There are 46.8 million people suffering with dementia worldwide today, according to Alzheimer’s Disease International. “This is projected to double over 20 years,” the CEO noted, reaching 74.7 million by 2030. Dementia assessments will be accessible through BrainCheck as of January 2017. BrainCheck is currently part of the Texas Medical Center accelerator (TMCx) at Texas Medical Innovation Center. An advisor to the center and investor in BrainCheck’s seed round, Brett Giroir, said, “There is an absolute need for a simple, personal take-home neurologic assessment that is complete and has complexity and sophistication to it, but can be done rapidly and by anyone, for dementia, especially.” He sees BrainCheck as democratizing sophisticated, psychological neuro-testing in a way that can help an aging world population to identify and treat dementia earlier than ever before. Giroir, who was previously the director of DARPA’s science office, lauded BrainCheck’s “scientific  pedigree,” and the potential extensibility of its app. “Beyond concussion and dementia, there are things you can study like the side effects and safety of drugs, and polypharmacy. There are things that can cause people not to remember well, or lose coordination that are not brain injury related, or dementia but would be related to the drugs that they are taking.” Rather than move into new areas of digital technology, like virtual reality, Katz and Eagleman say BrainCheck will invest its seed capital and resources into doing the most it can via the mobile platform. The company’s app is a health “tracking” app, rather than diagnostic tool for clinical use at this point. But the company intends to work with the FDA to become a class 2 medical device, soon. But even without further classifications, Eagleman said the app is making a positive difference to families simply because it can be used at home. He said: “With dementia, especially, most people don’t go into a neurologist until it is too late. If you ever have someone with this problem in your life, you’ll see there’s a lot of denial and rationalization that happens. People will say they are feeling sleep deprived, and that’s why they couldn’t remember a word, or had trouble putting their clothes on. A lot of that is because nobody wants to go to the doctor, it’s just too much of a pain in the ass. We put this in people’s hands, and they can take the best of what’s known in the science and have that at home.”


News Article | November 18, 2016
Site: www.rdmag.com

The Brazilian doctor who has been at the forefront of the fight against Zika for the past year has weighed in on some of the potential birth defects. Dr. Vanessa van der Linden, the physician who was one of the first researchers linking Zika to microcephaly—a birth defect where infants are born with smaller and misshapen heads—has expressed concerns over many of her patients she has observed in the last year. Van der Linden, a pediatric neurologist at the Barão de Lucena Hospital, in Recife, Brazil, said in a Science News for Students article that while microcephaly remains the most common symptom, she has observed a number of other symptoms including muscle spasms, extreme irritability, difficulty swallowing and the possibility of crying for 24 hours straight. Another issue van der Linden observed is a deformity called arthrogryposis, which can leave a child with contractures or joints stuck in contorted positions.  This disease has shown up in babies both with and without microcephaly. Van der Linden described much of her findings and observations during a Sept. 22 workshop hosted by the National Institute of Health in North Bethesda, Md. In the article, Peter Hotez, a pediatrician and microbiologist at Baylor College of Medicine in Houston, Texas, said some of the long-term impacts of Zika are still relatively unknown and symptoms including learning disabilities or developmental delays might emerge in the future. Zika has become a growing concern in South America, the Caribbean and Florida. Other symptoms observed include ear and eye problems in newborns. In a Sept. 2 report from the U.S. Centers for Disease Control and Prevention (CDC), one in every 10 of the 70 Zika-exposed infants with microcephaly also experienced some hearing loss. Another study shows of 29 Brazilian babies observed with microcephaly more than one in every three had some eye oddity. Other scientists have begun to study how Zika could impact the brain. Marco Onorati, a scientist at Yale University, said in the article that he and colleagues found that the virus can invade and kill two different brain cells in neuroepithelial stem cells and radial glial cells.


News Article | December 21, 2016
Site: www.eurekalert.org

Crafting a vaccine against RSV (respiratory syncytial virus) has been a minefield for 50 years, but scientists believe they have found the right balance. Researchers at Emory University School of Medicine and Children's Healthcare of Atlanta report that they have engineered a version of RSV that is highly attenuated - weakened in its ability to cause disease - yet potent in its ability to induce protective antibodies. The researchers examined the engineered virus using cryo-electron microscopy and cryo-electron tomography techniques, and showed that it is structurally very similar to wild type virus. When used as a vaccine, it can protect mice and cotton rats from RSV infection. The results are scheduled for publication in Nature Communications on December 21. "Our paper shows that it's possible to attenuate RSV without losing any immunogenicity," says senior author Martin Moore, PhD, associate professor of pediatrics at Emory University School of Medicine and a Children's Healthcare of Atlanta Research Scholar. "This is a promising live-attenuated vaccine candidate that merits further investigation clinically." The next steps for this vaccine are to produce a clinical grade lot and conduct a phase 1 study of safety and immunogenicity in infants, Moore says. RSV is the number one cause of pneumonia deaths in children worldwide and one of the top causes of infant hospitalization in the United States. Most children in the USA become infected in the first year of life. Even so, there is no vaccine against RSV available. In the 1960s, an attempt to develop an RSV vaccine by chemically inactivating the virus, like in a standard flu shot, backfired. Exposure to this vaccine actually made natural RSV infection in infants worse. More recently, a clinical trial of a protein-only RSV vaccine in older adults showed disappointing results. Several successful vaccines against other viruses, likes measles, polio, and mumps, have been created by weakening the viruses in cell culture. A strain that is safe enough for use as a vaccine, but still stimulates the immune system, is supposed to result. "Achieving that balance is a challenge," Moore says. "Weakening RSV by passage hasn't worked out satisfactorily. It turns out that for RSV, the natural virus does not induce a lot of immunity itself." Instead, Moore and his colleagues engineered RSV to enhance production of a key protein, called F (for fusion). F is critical for RSV's ability to enter cells and is the target of several vaccines in development. By making mutations in the viral gene that encodes F, the researchers also made the virus more stable with respect to heat, which could help vaccine manufacturing and distribution. At the same time, the researchers removed or weakened several other viral genes that promote infection and suppress the immune system. One measure of this is that the modified virus, called OE4, stimulates high levels of antibody production. Moore and his team rewrote several of the viral genes in the OE4 strain using a process called codon-deoptimization, which makes it less likely for a re-engineered virus to mutate back to its original form. When examined via cryo-electron microscopy and cryo-electron tomography, OE4 virions were structurally very similar to standard RSV virions. The researchers used techniques that allow the virions to be preserved in their native states, says co-senior author Elizabeth R. Wright, PhD, associate professor of pediatrics at the Emory University School of Medicine. Wright is director of the Robert P. Apkarian Integrated Electron Microscopy Core and a Georgia Research Alliance Distinguished Investigator. Immuno-EM experiments revealed that OE4 had higher levels of the pre-fusion, form of the F protein and lower levels of the attachment protein called G. In addition, a Georgia Tech graduate student in Wright's lab, Zunlong Ke, analyzed cryo-ET data and found that that the majority of F proteins on both viruses preserved immediately after budding was in the pre-fusion conformation. This is the structural evidence that the vaccine candidate (OE4) is highly immunogenic though highly attenuated, Wright says. OE4 vaccination could completely protect mice and cotton rats against later infection by standard forms of RSV. In contrast with a chemically inactivated RSV vaccine, OE4 did not result in enhanced lung disease in cotton rats. Christopher Stobart, PhD, now assistant professor of biology at Butler University, and instructor Christina Rostad, PhD are co-first authors of the paper. Cotton rat studies were performed at Baylor College of Medicine and at Sigmovir Biosystems. Emory has optioned the vaccine technology to a startup company, Meissa Vaccines, Inc. Moore co-founded and serves as chief scientific officer for Meissa Vaccines, Inc. Moore, Stobart, Rostad, and co-authors Anne Hotard and Jia Meng are co-inventors in a patent application describing the RSV vaccine reported in the Nature Communications paper. Emory and Moore could benefit financially from this technology, and this relationship has been reviewed and approved by Emory University School of Medicine. The research was supported by the National Institute of Allergy and Infectious Diseases (R01AI087798, U19AI095227, T32AI074492), the Atlanta Pediatric Scholars program (K12HD072245) and a pilot grant from the Emory/Children's/Georgia Tech Center for Childhood Infections and Vaccines.


News Article | April 27, 2016
Site: www.nature.com

Not many graduate students who spend 50–60 hours in the laboratory each week are eager to take on an outside job — especially one that pays nothing. But Michael Lang, a PhD student in cell and developmental biology at the University of Michigan in Ann Arbor, has added two part-time, unpaid positions to his workload. He's the president of miLEAD Consulting, an independent, non-profit company based in Ann Arbor that connects the university's graduate students and postdoctoral researchers with local biotechnology and health-care companies that need help with product development, market analysis or branding. And he works directly for miLEAD to provide his own insights and analyses to companies. Lang thinks that the long hours are worth it. The consulting work helps him to build leadership and management skills that would come in handy if he were to reach his ideal goal of running an academic lab. And if that doesn't work out, he'll have a fall-back position: “I've always wanted to be a scientist, but a US$130,000 job at a top consulting firm sounds pretty good too.” Lang's group is one of several consulting organizations that have sprung up on US campuses in the past few years. They supply teams of postdocs and graduate students who can take a scientific approach to common questions faced by local biotechnology and pharmaceutical start-ups — what is the demand for a new product, what is the competition, what can be done to make a product better and what is the best way to profit from a good idea? Consultants do not always know how companies use their input or whether their advice makes a difference, but the value of the experience is undeniable. “We want to give people another bullet point on their CV,” Lang says. “It can get them over the hurdle to getting a job.” A few of these consulting groups, including miLEAD, are independent, non-profit companies with no official ties to their home institute. But most are affiliated with their host institutions, including Harvard University in Cambridge, Massachusetts, Stanford University in California and the University of Pennsylvania in Philadelphia. Such campus-based organizations haven't caught on outside the United States, but at least one global company, 180 Degrees Consulting, recruits postdocs and graduate students for consulting projects and gives scientific trainees in the United Kingdom and elsewhere a chance to add to their skill set. Whatever group they work for, trainees in consulting get valuable experience in analysis, decision making and team-based problem solving that can give them a boost in the job market. It is also a break from the normal routine. “Fast-paced teamwork can be a lot of fun,” says Huadi Zhang, a medical-science PhD student and co-president of Harvard Graduate Consulting Club. “I didn't have that kind of experience in the laboratory.” But on-the-side consulting is also a serious commitment and time drain — and there are several hoops to be jumped through if students want to start a group from scratch (see 'How to start a consultancy'). The field is not for everyone, but an increasing number of trainees have found that it is possible to consult their way into a career. For Lang, consulting has turned into a second life outside the lab. He estimates that he spends 10–15 hours a week fulfilling his duties as president of miLEAD: overseeing the search for clients, recruiting consultants and, importantly, training them in the basics of business. Working on a project — which might involve meeting with a company's board, talking to doctors or digging through research articles — generally takes him another 10–15 hours each week. These are huge time commitments for a graduate student with experiments to run and papers to write. But it's worth it, he says, for the boost it gives to his CV and research. “The additional work has helped me streamline my science,” he says. “There's not a lot of downtime in the lab.” Lang's recent projects include an eight-week gig for a Michigan pharmaceutical company that is developing a therapeutic drug for newborns. (Because of non-disclosure agreements, he cannot name the company.) He and his team studied the market for the drug, scoped out the competition and gauged its potential applications in neonatal medicine. Previously, he was on a team that spent four weeks assessing an app-based learning tool for college students that was developed at the University of Michigan. Lang says that miLEAD brought in $6,000 in revenue in 2015 and is aiming for $12,000 in 2016. The board uses all of the revenue for group-related activities, including flying in speakers for panel discussions and funding team-building gatherings. If the coffers get sufficiently full, Lang hopes to start a grant programme to help local businesses to get off the ground. miLEAD's fees for client companies are a tiny fraction of what a big-time consulting company would charge, but they underscore the professionalism of the process. “We treat this like a business,” he says. “If money is involved, better work gets done.” Conversely, Zhang says that the Harvard Graduate Consulting Club has no plans to start charging clients. “It's a way for us to give back to the community,” he notes. Although it is likely that local start-ups get some value from their consulting, improving a company's bottom line is not the main point of the exercise. “It's a learning experience for us,” says Zhang. Consulting organizations are starting to pop up on other campuses, giving more postdocs and graduate students a chance to try out the field. Simran Madan, a PhD student in translational biology at Baylor College of Medicine in Houston, Texas, is helping to kick-start consulting services as senior vice-president of the Consulting Club at the Texas Medical Center in Houston. This independent, non-profit group is drawing talent from several local institutions, including Baylor and the University of Texas Heath Science Center and MD Anderson Cancer Center in Houston. The group aims to begin offering consulting services by the end of the year. For now, Madan and club president Redwan Huq, a Baylor PhD student in molecular physiology and biophysics, are learning how to recruit potential consultants, provide training, structure consulting teams and attract clients. The plan is to charge local companies about $500 for 6 weeks of work analysing a product and coming up with a marketing or development plan, a price that should be attractive to cash-strapped start-ups. “Professional consultants are expensive, and you almost never see a start-up hiring a firm,” Madan says. “But they can get the same sort of analysis from a trainee.” One source of inspiration for Madan and Huq is the BALSA (Biotechnology and Life Sciences Advising) group, a successful consulting organization at Washington University in St Louis, Missouri. BALSA, which started in 2011, has 100 active members who participate in around 40 projects a year. About 60% of the members are science PhD students, 30% are science postdocs and a few are business or law students. Each job lasts six weeks, and each team includes three consultants, a project manager and an adviser. Most of the work involves product development and market analysis for local start-ups and entrepreneurs in the biotechnology, agriculture and health-care industries. The group also has clients in South Dakota; San Francisco, California; and Philadelphia, Pennsylvania, says Shivam Shah, who is the BALSA president and a PhD student in biomedical engineering at Washington University. A frequent BALSA client is Washington University's Office of Technology Management, which has often hired the team to help evaluate patent applications from faculty members. Shah says that the group tries to avoid having students evaluate their direct supervisors, but that is not always possible. Students aim to judge patent applications strictly on their scientific merit and real-world potential, he says. Since joining the group in 2013, Shah has worked on more than 20 projects as either a consultant or a project manager. Working on multiple projects has given him a chance to fine-tune his management style and learn more about the scientific marketplace, he says. He hopes to land a consulting job soon after getting his degree, perhaps with a health-care venture-capital firm looking for advice about wise places to invest. But a consulting career is hardly the only destination for BALSA members. Many have ended up working in industry as research scientists, patent specialists or consultants for companies such as the multinational agrochemical company Monsanto, based in St Louis, Missouri, and the New York-based computing giant IBM. And of the roughly 200 alumni of the programme, he estimates that about one-third have continued in academic careers. The skills learned in the consulting game — management, leadership and teamwork — would prove valuable to anyone running their own lab, Shah says. There is a paucity of organizations such as miLEAD and BALSA outside the United States, but early-career scientists in the United Kingdom, Europe and elsewhere can still get real-life consulting training. One option is a position with 180 Degrees Consulting, a global organization with branches in Cambridge, UK; King's College London; Munich, Germany; the University of Tokyo; the University of Sydney; and the University of California, Los Angeles, among many other sites. The company enlists students and postdocs to provide pro bono consulting to non-profit and humanitarian organizations around the world. Although the work generally is not focused on scientific issues, science PhD students and postdocs can bring valuable skills to the organization, says Daniel Jiang, a PhD student in computer science who in 2015 founded the 180 Degrees Consulting branch at King's College London. “I know more about data sets than a political-science major does,” he says. Jiang's group is working with a children's charity and sports charity in London, and a school in the Philippines. The company attracts people who want to make a positive difference in the world, Jiang says, but there are benefits for the consultants themselves. “It's a great opportunity for students to find out about a different career before they graduate,” he says. Lang of miLEAD is still technically a student, but he's racking up professional-grade experience and isn't slowing down: he'll jump into two new projects as an adviser this summer. He can't discuss details, but the big picture is clear: he'll be working long hours, thinking about tough problems and moving closer to a postgraduate career. Are the long days worth it? That's a cost–benefit analysis that he has figured out on his own, no consultant required.


News Article | November 10, 2016
Site: www.eurekalert.org

EL PASO, Texas -- Co-principal investigators Richard McCallum, M.D., and Irene Sarosiek, M.D., have received a five-year, $1.8 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The funds will support basic research and clinical trials on patients living with a digestive disorder named gastroparesis. "Gastroparesis is prevalent here in El Paso; about 100,000 people in our region are affected by it," says Dr. McCallum, a professor at Texas Tech University Health Sciences Center El Paso (TTUHSC El Paso). "This grant will help us collect new and important data on how the disorder affects Hispanics and others, but it will also help us provide health care to more patients." Gastroparesis is a disorder in which food moves through the stomach much slower than normal. The condition affects more than 10 million Americans and symptoms include chronic nausea, vomiting and abdominal pain. In severe cases, a permanent feeding tube is required to ensure adequate nutrition; a medical implant to stimulate the digestive system can also be provided for patients with profoundly severe, drug-resistant symptoms. With the funding, the TTUHSC El Paso team will enroll patients to help test a new drug that may reduce the severity and frequency of their gastrointestinal problems. They'll also examine the effectiveness of a novel diagnostic procedure for the condition. The technique was invented by the TTUHSC El Paso team, and if successful, could replace an invasive surgical procedure that's currently used in patients with gastroparesis. Individuals with gastroparesis who opt to participate in the TTUHSC El Paso studies will receive free health care related to the disorder, such as access to diagnostic tests like endoscopies and the latest treatment options. "Many El Paso patients appreciate the opportunity to participate in our NIH-funded research," Dr. Sarosiek says. "It gives them access to cutting-edge health care that they otherwise would not receive, and at the same time, it helps us find possible risk factors that could play a role in initiating the progression of gastroparesis in affected patients." Drs. McCallum and Sarosiek are studying the disease as part of their membership in the Gastroparesis Clinical Research Consortium (GpCRC), a prestigious national partnership that focuses on the cause of gastroparesis and therapies for the disorder. Membership includes Baylor College of Medicine, Johns Hopkins University and the Mayo Clinic, as well as TTUHSC El Paso.


News Article | November 1, 2016
Site: www.eurekalert.org

PITTSBURGH, Nov. 1, 2016 - A University of Pittsburgh-developed program successfully boosts vaccination rates in adult patients seen at primary care offices, two recent studies demonstrated. Physician offices participating in the 4 Pillars Practice Transformation Program had nearly three times the increase in patients getting the Tdap vaccine for protection against pertussis (whooping cough) compared to non-participating offices, according to research published in the journal Vaccine. Another study, published in the Journal for Healthcare Quality, demonstrated that certain characteristics already embedded into some primary care practices, such as open leadership and staff communication, organizational flexibility and experience with quality improvement, predicted which practices would garner the most vaccination rate improvement from the 4 Pillars program. "Vaccination is the single best way to prevent communicable diseases," said Richard K. Zimmerman, M.D., M.P.H., professor in the Pitt School of Medicine's Department of Family Medicine, and senior or co-author on the two studies. "In recent years, we've seen surges in cases of whooping cough, which can be deadly in newborns who can contract it from unvaccinated adults. And we recently learned from federal health officials that the rate of people getting vaccinated against the flu -- another virus that kills hundreds annually -- fell last season. We need to find ways to get more people immunized." The 4 Pillars program is a step-by-step guide, backed by decades of research, for increasing adult immunizations at primary care clinics by using an online tool that tracks vaccination rates. It's based on four key pillars: convenient vaccination services; communication with patients about the importance of immunization; enhanced office systems to facilitate immunization; and motivation through an office "Immunization Champion" who is charged with implementing the strategies and maintaining the program. In the first-ever study to focus on increasing Tdap immunization rates since it was universally recommended for all adults by the federal Advisory Committee on Immunization Practices in 2012, the researchers enrolled 25 primary care practices in Pittsburgh and Houston. Half received the 4 Pillars program in the first year, while the other half acted as a control group and didn't receive the program until the second year. At the beginning of the study, the practices had Tdap immunization rates ranging from a low of 6.8 percent to a high of 79.5 percent. With the 4 Pillars program, the practices increased their immunization rates by an average of 7.6 percent in the first year compared to a national increase of about 3 percent. One practice increased by 17 percent in the first year. In a different analysis using the same enrolled practices, Mary Hawk, Dr.P.H., assistant professor of behavioral and community health sciences at Pitt's Graduate School of Public Health, examined factors that made the 4 Pillars program more effective at some practices. Those that had the highest implementation of the 4 Pillars program strategies, resulting in the best immunization rate improvement, were those with: "The ability to implement change within primary care settings requires more than simply intent to participate, especially when it comes to improving immunization rates," said Dr. Hawk. "Even with a proven, research-backed program like 4 Pillars, practices also may need to make internal adjustments for the program to work to its full ability." Additional researchers on both studies are Mary Patricia Nowalk, Ph.D., Krissy K. Moehling, M.P.H., Jonathan M. Raviotta, M.P.H., and Edmond E. Ricci, Ph.D., all of Pitt; and Valory Pavlik, Ph.D., and Anthony E. Brown, M.D., both of Baylor College of Medicine. The Vaccine study also included Chyongchiou J. Lin, Ph.D., Song Zhang, M.S., Jeannette E. South-Paul, M.D., Donald B. Middleton, M.D., all of Pitt; and Suchita A. Patel, D.O., and Faruque Ahmed, Ph.D., both of the U.S. Centers for Disease Control and Prevention (CDC). This work was supported by CDC grant U011P000662 and National Institutes of Health grants UL1RR024153 and UL1TR000005. About the University of Pittsburgh Schools of the Health Sciences The University of Pittsburgh Schools of the Health Sciences include the schools of Medicine, Nursing, Dental Medicine, Pharmacy, Health and Rehabilitation Sciences and the Graduate School of Public Health. The schools serve as the academic partner to the UPMC (University of Pittsburgh Medical Center). Together, their combined mission is to train tomorrow's health care specialists and biomedical scientists, engage in groundbreaking research that will advance understanding of the causes and treatments of disease and participate in the delivery of outstanding patient care. Since 1998, Pitt and its affiliated university faculty have ranked among the top 10 educational institutions in grant support from the National Institutes of Health. For additional information about the Schools of the Health Sciences, please visit http://www. .


News Article | November 15, 2016
Site: www.sciencedaily.com

West Nile virus may be much more deadly than previously believed, with deaths attributable to the mosquito-borne disease occurring not just in the immediate aftermath of the infection but also years later, long after patients seem to have recovered from the initial illness, according to a new study presented at the 2016 Meeting of the American Society of Tropical Medicine and Hygiene (ASTMH). "While we understand the current focus on Zika virus, for many people in the United States today, West Nile virus is the much more serious mosquito-borne threat and that threat may persist even for patients who appear to have survived the infection unscathed," said Kristy O. Murray, DVM, PhD, of Baylor College of Medicine and Texas Children's Hospital, who is the principal author of the study. Murray and her colleagues looked at 4,144 West Nile virus (WNV) infections that occurred in Texas between 2002 and 2012, focusing on both "acute" deaths recorded in the first 90 days after infection and also on WNV patients who died months to years later -- yet far sooner than other people of similar age and overall health condition. The researchers found there were 286 people who died in the acute phase of WNV. But after examining causes of deaths and symptoms from the initial infection, Murray and her colleagues concluded that 268 people who survived infection subsequently died early (they call it "delayed mortality") due to the virus. Overall, counting both the acute and delayed group, the researchers attributed 554 deaths to WNV during the 10-year period, a 13 percent fatality rate. That's much higher than the 4 percent national fatality rate for WNV recorded between 1999 and 2015 by the U.S. Centers for Disease Control and Prevention (CDC), though those statistics accounted only for deaths that occurred during the acute phase of illness. WNV, which also can infect birds that help spread the virus further, has been detected in all of the lower 48 states since it was introduced into the United States in 1999. It belongs to the same family of viruses as Zika and yellow fever. Like Zika, most people infected with WNV never experience symptoms. Those who do typically have a fever, nausea, fatigue or a rash, though in rare cases, it can cause severe neurological complications that can lead to swelling of the brain and spinal cord. There is not a specific treatment for WNV infections nor is there a vaccine to prevent it. Murray noted that the Texas study is the largest study to date to investigate what has been seen in much smaller groups of WNV patients, which is that the disease appears capable of causing health problems years after someone is over the initial infection. "For several years, we had followed smaller groups of patients and felt that many had died prematurely," Murray said. "We saw many people who were otherwise healthy until they had West Nile virus -- and then their health just went downhill." Murray said most of the delayed deaths were clustered around a large outbreak of WNV in Texas in 2012, which means they occurred just a few years after the initial infections. But Murray said other early deaths were recorded up to 10 years after the initial epidemic of West Nile. She said her research team feels confident in its conclusions because, for each patient, they had access to both information about the course of the initial infection and records maintained by the Texas state death registry that document cause of death. Murray said that the delayed deaths appeared to be more common in patients who had suffered significant neurological complications during the acute phase of their illness. Also, for patients suffering delayed deaths, Murray said kidney disease, increasingly suspected as a potential long-term complication of WNV, was statistically found to be a significant cause of death. Murray was the principal investigator of a 2012 study that followed 139 patients diagnosed with WNV and found 40 percent of them developed chronic kidney disease. Murray said kidney issues caused by WNV could also explain why it was not just elderly patients who were found to be at risk of delayed death but especially patients under 60 years old. "We had been surprised in the 2012 study to see so much chronic kidney disease develop in younger West Nile patients because it's not that common in people under 60," she said. "In much the same way that research into Zika virus is showing a more destructive virus than originally thought, we are still discovering previously unreported long-term destructive effects of West Nile," said Stephen Higgs, PhD, president of the American Society of Tropical Medicine and Hygiene. "Those of us in the tropical medicine community have long been concerned that West Nile is a significant public health problem and that U.S. federal investments are warranted in finding better ways to treat and prevent it."


News Article | March 1, 2017
Site: www.eurekalert.org

HOUSTON ? Anyone who uses an employee badge to enter a building may understand how a protein called ENL opens new possibilities for treating acute myeloid leukemia (AML), a fast-growing cancer of bone marrow and blood cells and the second most common type of leukemia in children and adults. Findings from a study at The University of Texas MD Anderson Cancer Center revealed the leukemia-boosting abilities of ENL, which contains a protein component called YEATS that "reads" histone proteins. Histone proteins make up chromatin, large clusters of DNA- and RNA-containing molecules comprising our body's chromosomes. Just as a scanner "reads" data on an identification badge, ENL recognizes a type of histone modification known as acetylation. Research results, which build upon a previous MD Anderson study of histone-reading proteins, are published in the March 1 online issue of Nature. The findings indicated treatment against ENL with a class of experimental drugs called bromodomain and extra-terminal (BET) inhibitors may be effective for treating AML. "Our study showed that ENL is required for disease maintenance in AML," said Xiaobing Shi, Ph.D., associate professor of Epigenetics and Molecular Carcinogenesis. "Depletion of ENL led to anti-leukemic effects, suppressing growth both in vivo and in vitro. Notably, disrupting ENL further sensitized leukemia cells to BET inhibitors." Histone modifications like acetylation serve as docking sites for reader proteins which recognize specific modifications, influencing downstream biological outcomes. While many such reader proteins have been identified for histone modifications called methylation, few are known to recognize histone acetylation. Shi's team employed CRISPR, a gene-editing tool, to deplete ENL and suppress cancer gene expression, which was crucial given that cancer cells often co-opt chromatin regulatory pathways. "Targeting epigenetic readers represents a class of anti-cancer therapy that we believe holds clinical promise," said Hong Wen, Ph.D., research assistant professor of Epigenetics and Molecular Carcinogenesis and co-first author of the paper. "Our study revealed ENL as a chromatin reader that regulates oncogenic programs, thus establishing ENL as a potential drug target for AML." MD Anderson study team members included Xiaolu Wang of the Department of Epigenetics and Molecular Carcinogenesis. Other participating institutions included The Rockefeller University, New York; Memorial Sloan Kettering Cancer Center, New York; Dana-Farber Cancer Institute, Boston; Tsinghua University, Beijing; Baylor College of Medicine, Houston; Icahn School of Medicine at Mount Sinai, New York; and Harvard Medical School; Boston. The study was funded by the National Institutes of Health (P30CA016672, RO1CA204639-01, CA66996, CA140575, 1R01CA204020, R01HG007538 and R01CA193466), the Cancer Prevention Research Institute of Texas (RP160237 and RP170285), the Leukemia and Lymphoma Society (LLS-SCOR 7006-13), the Robert A. Welch Foundation (G1719), the Major State Basic Research Development Program in China (2016FA0500700 and 2015CB910503), and the Tsinghua University Initiative Research program.


News Article | February 24, 2017
Site: www.eurekalert.org

The genetic material of an organism encodes the instructions that guide its development. These codes are not written in stone; they can change or mutate any time during the life of the organism. Single changes in the code can occur spontaneously, as a mutation, causing developmental problems. Others, as an international team of researchers has discovered, are too numerous to be explained by random mutation processes present in the general population. When such multiple genetic changes occur before or early after conception, they may inform scientists about fundamental knowledge underlying many diseases. The study appears in Cell. "As a part of the clinical evaluation of young patients with a variety of developmental issues, we performed clinical genomic studies and analyzed the genetic material of more than 60,000 individuals. Most of the samples were analyzed at Baylor Genetics laboratories," said lead author Dr. Pengfei Liu, assistant professor of molecular and human genetics Baylor College of Medicine and assistant laboratory director of Baylor Genetics. "Of these samples, five had extreme numbers of genetic changes that could not be explained by random events alone." The researchers looked at a type of genetic change called copy number variants, which refers to the number of copies of genes in human DNA. Normally we each have two copies of each gene located on a pair of homologous chromosomes. "Copy number variants in human DNA can be compared to repeated or missing paragraphs or pages of text in a book," said senior author Dr. James R. Lupski, Cullen Professor of Molecular and Human Genetics at Baylor. "For instance, if one or two pages are duplicated in a book it could be explained by random mistakes. On the other hand, if 10 different pages are duplicated, you have to suspect that it did not happen by chance. We want to understand the basic mechanism underlying these multiple new copy number variant mutations in the human genome." A rare, early and transitory phenomenon that can affect human development The researchers call this phenomenon multiple de novo copy number variants. As the name indicates, the copy number variants are many and new (de novo). The latter means that the patients carrying the genetic changes did not inherit them from their parents because neither the mother nor the father carries the changes. In this rare phenomenon, the copy number variants are predominantly gains - duplications and triplications - rather than losses of genetic material, and are present in all the cells of the child. The last piece of evidence together with the fact that the parents do not carry the alterations suggest that the extra copies of genes may have occurred either in the sperm or the egg, the parent's germ cells, and before or very early after fertilization. "This burst of genetic changes happens only during the early stages of embryonic development and then it stops," Liu said. "Interestingly, despite having a large number of mutations, the young patients present with relatively mild neurological problems." The researchers are analyzing more patient samples looking for additional cases of multiple copy number variants to continue their investigation of what may trigger this rare phenomenon. "We hope that as more researchers around the world learn about this and confirm it, the number of cases will increase," Liu said. "This will improve our understanding of the underlying mechanism and of why and how pathogenic copy number variants arise not only in developmental disorders but in cancers." "A new era of clinical genomics-supported medicine and research" This discovery has been possible in great measure thanks to the breadth of genetic testing performed and genomic data available at Baylor Genetics laboratory. "The diagnostics lab Baylor Genetics is one of the pioneers in this new era of clinical genomics-supported medical practice and disease gene discovery research," Lupski said. "They are developing the clinical genomics necessary to foster and support the Precision Medicine Initiative of the National Institutes of Health, and generating the genomics data that further drives human genome research." Using state-of-the art technologies and highly-trained personnel, Baylor Genetics analyzes hundreds of samples daily for genetic evaluation of patients with conditions suspected to have underlying genetic factors potentially contributing to their disease. Having this wealth of information and insight into the genetic mechanisms of disease offers now the possibility of advancing medicine and basic research in ways that were not available before. "There is so much that both clinicians and researchers can learn from the data generated in diagnostic labs," Liu said. "Clinicians receive genomic information that can aid in diagnosis and treatment of their patients, and researchers gather data that can help them unveil the mechanisms underlying the biological perturbations resulting in the patients' conditions." Other contributors to this work include Bo Yuan, Claudia M.B. Carvalho, Arthur Wuster, Klaudia Walter, Ling Zhang, Tomasz Gambin, Zechen Chong, Ian M. Campbell, Zeynep Coban Akdemir, Violet Gelowani, Karin Writzl, Carlos A. Bacino, Sarah J. Lindsay, Marjorie Withers, Claudia Gonzaga-Jauregui, Joanna Wiszniewska, Jennifer Scull, Pawel Stankiewicz, Shalini N. Jhangiani, Donna M. Muzny, Feng Zhang, Ken Chen, Richard A. Gibbs, Bernd Rautenstrauss, Sau Wai Cheung, Janice Smith, Amy Breman, Chad A. Shaw, Ankita Patel and Matthew E. Hurles. The researchers are affiliated with one of more of the following institutions Baylor, Wellcome Trust Sanger Institute in the U.K., Fudan University in China, the University of Texas MD Anderson Cancer Center Houston, the Clinical Institute of Medical Genetics in Slovenia and the Medical Genetics Center in Germany. This work was supported in part by grants from the US National Institute of Neurological Disorders and Stroke (R01NS058529), the National Human Genome Research Institute (U54HG003273), a joint NHGRI/National Heart Blood and Lung Institute grant (U54HG006542) to the Baylor Hopkins Center for Mendelian Genomics, and the BCM Intellectual and Developmental Disabilities Research Center, IDDRC Grant Number 5P30HD024064-23, from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The work was also partially supported by the Wellcome Trust (WT098051).


News Article | November 16, 2016
Site: www.techtimes.com

The West Nile Virus infection could be deadlier than previously thought, reports a recent study presented at the 2016 American Society of Tropical Medicine and Hygiene meeting. The mosquito-borne disease is found to cause fatalities even years after initial exposure to the virus. Kristy O. Murray, the lead author of the study from the Baylor College of Medicine and Texas Children's Hospital said that, amid Zika virus threats prevailing in the United States, it was found that WNV is potentially fatal in people affected with the virus years after infection. WNV infection that first appeared in the United States in 1999 infected around 45,000 people and claimed the lives of about 2,000 people accounting to four percent of fatality rate in the country. The WNV also belongs to the family of viruses that cause yellow fever and Zika. People infected with WNV do not experience any symptoms much similar to Zika infection. However, in rare cases some people experience symptoms like fatigue, rash, fever and nausea. The complications of WNV infection include swelling of brain and spinal cord. Though WNV is known to be potentially fatal, no vaccine to prevent or treatment to contain the infection is found by far. For the purpose of the study, Murray and her team studied 4,144 WNV cases reported in Texas between 2002 and 2012. The researchers reviewed acute fatalities that occurred in first 90 days of infection as well as deaths that were reported months and years after infection. About 286 people were reported to have died of acute WNV infection and around 268 patients were found to have survived the disease. However, on deliberate analysis, it was found that all the patients that survived initial infection have died subsequently in upcoming months. The overall deaths from WNV infection from both acute and delayed mortalities between 2002 and 2012 were found to be 554, which accounts to 13 percent of fatality rate in the country. The figure is much higher than four percent fatality rate between 1999 and 2015 reported by the U.S. Centers for Disease Control and Prevention. In addition Murray found in a study in 2012 that among 139 patients infected with WNV about 40 percent of them developed kidney diseases. It is therefore clear that the WNV infection leads to chronic kidney diseases not only in elderly but also in patients under 60 years of age. "We had been surprised in the 2012 study to see so much chronic kidney disease develop in younger West Nile patients because it's not that common in people under 60," Murray said. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.


News Article | October 26, 2016
Site: www.eurekalert.org

New Rochelle, NY, October 24, 2016--When Smart Snacks sold in schools-reformulated versions of less nutritious snacks sold in stores--are packaged to look like their commercial counterparts, consumer confusion is likely, compromising dietary health gains and affecting perceptions about both brands and schools, according to an article in Childhood Obesity, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Childhood Obesity website until November 28, 2016. Jennifer Harris, PhD, MBA and Marlene Schwartz, PhD, University of Connecticut, Hartford, and Maia Hyary, MPA, Brandeis University, Waltham, MA, examine these issues in the article entitled "Effects of Offering Look-Alike Products as Smart Snacks in Schools". The researchers compared how students and parents rated look-alike Smart Snacks and store versions of the same snacks based on taste, healthfulness, and intent to purchase. The finding that most of the study participants wrongly believed that they had seen Smart Snacks sold in stores demonstrated consumer confusion. The authors caution that the look-alike Smart Snacks available in schools could lead people to believe that the same brands sold in stores meet similar nutritional standards. "This important study highlights the confusion students and parents experience when viewing nutritionally different versions of similar food items marketed in schools versus in stores," says Childhood Obesity Editor-in-Chief Tom Baranowski, PhD, Baylor College of Medicine, Houston, TX. "The fact that students rated the healthier versions of the snacks as equal in taste to the unhealthy versions is an important milestone for healthy snacks. Hopefully this article will lead to a national discussion about what types of foods parents, students, and citizens in general want offered in schools." Childhood Obesity is a bimonthly peer-reviewed journal, published in print and online, and the journal of record for all aspects of communication on the broad spectrum of issues and strategies related to weight management and obesity prevention in children and adolescents. Led by Editor-in-Chief Tom Baranowski, PhD, Baylor College of Medicine, and Editor Elsie M. Taveras, MD, MPH, Massachusetts General Hospital for Children & Harvard Medical School, the Journal provides authoritative coverage of new weight management initiatives, early intervention strategies, nutrition, clinical studies, comorbid conditions, health disparities and cultural sensitivity issues, community and public health measures, and more. Complete tables of content and a sample issue may be viewed on the Childhood Obesity website. Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative medical and biomedical peer-reviewed journals, including Metabolic Syndrome and Related Disorders, Population Health Management, Diabetes Technology & Therapeutics (DTT), and Journal of Women's Health. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 80 journals, newsmagazines, and books is available on the Mary Ann Liebert, Inc., publishers website.


News Article | October 12, 2016
Site: www.nature.com

No statistical methods were used to predetermine sample size. When relevant (such as experiments requiring multiple trials), randomization was carried out. Behavioural trial experiments were randomized. There was blinding of initial allocation of animals into groups, but not thereafter. Cell counts were blinded. All animals used in this study were treated in compliance with US Department of Health and Human Services and Baylor College of Medicine IACUC guidelines. For the studies reported here, both male and female mice were considered for analyses. Standard pellet mouse chow (Harlan, 2920X) was used for all experiments, and all animals were maintained on a normal 12-h light–dark cycle. Chat-cre (B6;129S6-Chattm2(cre)Lowl/J), Pomc-EGFP (C57BL/6J-Tg(Pomc-EGFP)1Low/J), Npy-hrGFP (B6.FVB-Tg(Npy-hrGFP)1Lowl/J), ChatloxP/loxP (B6.129-Chattm1Jrs/J), R26LSL-tdTomato (B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J), and Vgat-cre (Slc32a1tm2(cre)Lowl/J) mice were originally purchased and are available from Jackson Laboratories. Chat-cre+/−; R26LSL-tdTomato/+ mice were generated by crossing heterozygous male Chat-cre+/− mice with female homozygous R26LSL-tdTomato mice. ChatloxP/loxP animals were bred and maintained as homozygotes. A Vgat-cre homozygous male was crossed to female C57BL/6J mice to generate heterozygous Vgat-cre+/− animals. Chat-cre+/−, Pomc-EGFP+/− and Npy-hrGFP+/− mice used in this study were maintained as heterozygotes and bred to wild-type C57BL/6J female mice. Genotyping for ChatloxP/loxP, Pomc-EGFP, and Npy-hrGFP animals was done according to available Jackson Laboratory protocols for these strains. Genotyping for Cre was done using primers for Cre recombinase detection (forward primer: 5′-GCATTTCTGGGGATTGCTTA-3′, reverse primer: 5′-GTCATCCTTAGCGCCGTAAA-3′). Animals were deeply anaesthetized using isoflurane and were transcardially perfused with PBS followed by 10% neutral buffered formalin (NBF, Azer Scientific). Brains were dissected and post-fixed in 10% NBF overnight at 4 °C. Brains were cryoprotected in a 20% sucrose/PBS solution at 4 °C for one day, followed by a 30% sucrose/PBS solution at 4 °C for one more day. Brains were then embedded and frozen in OCT and stored at −80 °C. Brains visualized using endogenous or virally-expressing fluorescent reporters were cut using a cryostat (Leica CM1860) in coronal sections at 25–30 μm. For ChAT and β-endorphin immunohistochemistry, 40 μm free-floating sections were blocked for 1 h at room temperature in 10% horse serum blocking solution, made in PBS-TC (1× PBS, 0.5% Triton-X 100, 0.1 mM CaCl , pH 7.35). Sections were then incubated overnight at 4 °C at a 1:200 dilution of block solution containing goat anti-ChAT primary antibody (Millipore, AB144P) or rabbit anti-β-endorphin primary antibody (Phoenix Pharmaceuticals, H-022-33). Sections were then washed 4 times, 30 min each in plain PBS-TC. Sections were then incubated in secondary antibody (donkey anti-goat Alexafluor-488 or Alexafluor-555, Life Technologies) at a 1:200 dilution for 3 h at room temperature. Sections were then washed 4 times for 30 min each in PBS-TC. All sections were mounted using DAPI Fluoromount-G (Southern Biotech, 0100-20). Detection of fluorescent expression was performed using a Leica TCS SPE confocal microscope under a 10× or 20× objective. For all stereotaxic injections, mice were anesthetized using a ketamine/dormitore mixture and were maintained under anaesthesia using vaporized isoflurane with O . All injections were performed using a stereotaxic apparatus synced to Angle Two software for coordinate guidance. For DTR-mediated cell death of cholinergic neurons, female Chat-cre+/− or Chat-cre+/−; R26LSLtdTomato/+ mice (8–10 weeks old) were bilaterally injected into the horizontal limb of the diagonal band of Broca (HDB, right hemisphere, from bregma: AP = +0.14, DV = −5.80, ML = −1.29; left hemisphere, from bregma: AP = +0.14, DV = −5.74, ML = +1.17) with 500 nl per hemisphere of a Cre-dependent AAV-EF1α-FLEX-DTR-P2A-EYFP-WPRE-hGHpA, serotype DJ/8. For conditional Chat knockout experiments, ChatloxP/loxP animals (8–10 weeks old) were bilaterally injected into the HDB with 300 nl per hemisphere of AAV-EF1α-EGFP-P2A-CRE-WPRE-hGHpA for experimental animals, or AAV-EF1α-EGFP-WPRE-hGHpA for control animals (serotype DJ/8 for both AAVs). For synaptophysin tracing experiments using the EGFP variant, Chat-cre+/− mice (8–16 weeks old) were injected bilaterally into the HDB with 500 nL per hemisphere of a Cre-dependent AAV-EF1α-FLEX-Syn::EGFP-WPRE-hGHpA, serotype DJ/8. For synaptophysin tracing experiments using the mRuby2 variant, Chat-cre+/; Pomc-EGFP+/− mice (12 weeks old) were injected bilaterally into the HDB with 500 nl per hemisphere of a Cre-dependent AAV-EF1α-FLEX-Syn::mRuby2-WPRE-hGHpA, serotype DJ/8. Lastly, for in vivo ChR2 behaviour experiments, male Chat-cre+/− mice (12–14 weeks old) were bilaterally injected into the HDB with 500 nl per hemisphere of a Cre-dependent AAV-EF1α-DIO-hChR2(H134R)-EYFP-WPRE-hGHpA (Addgene, plasmid number 20298) serotype 2/9. Male wild-type animals were fasted overnight before being presented with standard pellet mouse chow (Harlan, 2920X) for 3 h the following morning (fed group), while a second group of mice was fasted overnight but not presented with chow (fasted group). Mice were then immediately euthanized and perfused with PBS and 10% NBF. Brains were fixed overnight in 10% NBF before two overnight fixations in 20% and 30% sucrose/PBS solutions. Brains were frozen in OCT cutting compound and cryosectioned at 35 μm. Sections were then blocked for 1 h at room temperature in 10% horse serum blocking solution, made in PBS-TC (1× PBS, 0.5% Triton-X 100, 0.1 mM CaCl , pH 7.35). Sections were then incubated overnight at 4 °C at a 1:200 dilution of block solution containing goat anti-ChAT primary antibody (Millipore, AB144P) and 1:500 dilution of rabbit anti-c-Fos antibody (Calbiochem, PC38). Sections were then washed 4 times for 30 min each in plain PBS-TC. Sections were then incubated in secondary antibodies (donkey anti-goat Alexafluor-488, and donkey anti-rabbit Alexafluor-546) at a 1:200 dilution each for 3 h at room temperature. Sections were then washed 4 times for 30 min each in PBS-TC. All sections were mounted using DAPI Fluoromount-G (Southern Biotech, 0100-20). Detection of fluorescent expression was performed using a Leica TCS SPE confocal microscope under a 20× objective. After allowing 10–14 days for conditional viral expression (injections and viral construct described previously), mice were intraperitoneally (i.p.) injected 3 times daily for 5 days with 800 ng (4 ng μl−1 working solution) of diphtheria toxin (Sigma, D0564) for optimal cell death of targeted cholinergic neurons. Female Chat-cre+/−; R26LSL-tdTomato/+ mice were used initially to validate DTR-mediated cell death by visualizing DBB cholinergic cell loss. For remaining experiments, female Chat-cre+/− animals were used. For controls, age- and gender-matched Chat-cre+/− mice (stereotaxically injected identically into the DBB with AAV-FLEX-DTR-P2A-EYFP) were injected with equal volume (200 μl per injection) of sterile saline. Body weights and daily food intake were measured and averaged per group for each time point presented. For Chat conditional knockout assays, ChatloxP/loxP mice were injected bilaterally into the HDB as previously described with either AAV-EF1α-EGFP-P2A-CRE-WPRE-hGHpA for conditional knockout animals or AAV-EF1α-EGFP-WPRE-hGHpA for controls. Body weights and daily food intake were measured and averaged per group for each time point presented. For cell counts after Chat conditional knockout, 3 mice from each group were euthanized and brains were sectioned at 40 μm for ChAT immunohistochemistry. 10 sections representing the anterior, central, and posterior areas of the DBB were chosen, and blinded, total cell counts based on ChAT immunoreactivity were tallied. A count from all 10 sections from a single mouse brain were totalled and averaged for each group of 3 mice. Data were normalized to control levels of expression and represented as a mean percentage ± s.e.m. Activity (reported as time active per day), O consumption, and metabolic blood assays were performed by the Baylor College of Medicine Mouse Metabolism Core before obesity phenotypes (3 days after diphtheria toxin (DT) treatment), during early stages of obesity and hyperphagia (3 weeks post-DT treatment), and at late stages of obesity and hyperphagia (3 months post-DT treatment). Activity and O consumption assays were performed using the Oxymax Comprehensive Laboratory Animal Monitoring System (CLAMS, Columbus instruments). Lean mass and body fat content was assessed using quantitative MRI. Blood panel assays for cholesterol, leptin, insulin, and glucose were also performed by the Baylor College of Medicine Mouse metabolism core. Blood was collected via the tail vein. Mice were fasted for 4 h before measuring blood glucose. Paired feeding assays were performed with individually-housed, male DT-treated (DBB-ablated) and saline-treated (non-ablated) animals. Assays for determining the contribution of food intake on maintaining obesity were conducted on animals 12-weeks post-ablation. First, daily body weight and ad libitum food intake for all animals was recorded for 7 days to establish baselines for all animals. Then 1 control mouse and 1 experimental mouse were then randomly paired. All food from experimental cages was removed and only an equivalent amount of food consumed the previous day by a mouse’s respective control partner was introduced to the cage. This restrictive period was done for 21 days. Afterwards, all experimental mice were allowed to resume to feed ad libitum once again and food intake and body weight were measured daily for 2 weeks. Change in body weight over time was normalized as a percentage of day 1 initial starting weight for each individual animal. For paired feeding conducted on animals used for Agrp and Pomc transcript analysis, assays were performed 3 days post-ablation to prevent significant weight gain from hyperphagia. A restrictive feeding period was conducted for 21 days, after which mice were euthanized on the morning after the final day, and hypothalamic tissue was harvested for RNA purification and subsequent qRT–PCR (see below). Concurrent with AAV-EF1α-DIO-hChR2(H134R)-EYFP-WPRE-hGHpA injections (as described previously), male Chat-cre+/− mice were bilaterally implanted with 200 μm silica fibre optic implants made in-house (Thor Labs, TS1249968); 230 μm ferrules (Precision Fibre Products, MM-FER2007C-2300) and situated 0.1 mm above the viral injection site. Fibre optic implants were held in place by a cap made from adhesive cement (C&B Metabond Quick! Cement System (Parkell)) for initial base, and crosslinked flash acrylic (Yates-Motloid, 44115 and 44119) for headcap. Mice were allowed at least two weeks for recovery and expression of the virus before assays were performed. For prolonged 2-day stimulation, each mouse was allowed 48 h to acclimate in a behaviour box with free access to food and water (days 1 and 2: acclimation). In addition, acclimation occurred while tethered to a dual fibre optic cord (Doric Lenses) attached to a 473 nm laser source (CrystaLaser CL-2005). After the 48-h acclimation period, a pre-measured amount of food was placed into the chamber and weighed once every 24 h for two days without stimulation (days 3 and 4: pre-stimulation). Over the next 48 h, food was weighed once each day while mice were chronically stimulated with trains of blue light (5 mW, 10 ms pulses, 20 Hz, 5 s trains, 30 s intervals) (days 5 and 6: stimulation). Finally, food was weighed once every 24 h for two final days with no blue light stimulation (days 7 and 8: post-stimulation). As a control group, non-ChR2-expressing mice were injected and implanted in the identical way used for experimental mice. Control mice were acclimated identically and were subsequently subjected to a mock stimulation for 48 h, and food intake was measured each day. For comparisons between pre-stimulation, stimulation, and post-stimulation conditions, paired Student’s t-tests were used. For comparisons between experimental conditions and the control (mock-stimulation) condition, unpaired Student’s t-tests were used. For short-term 2-h stimulation experiments, mice were given 48 h to acclimate in their behaviour chamber. After acclimation, mice were fasted overnight and subsequently presented with a pre-measured amount of food in the morning. For control conditions, mice were not stimulated and food intake was recorded every 30 min for 2 h total. For experimental conditions, mice were stimulated with trains of blue light (5 mW, 10 ms pulses, 20 Hz, 5 s trains, 30 s intervals) for 15 min before presentation of pre-measured chow, and food intake was recorded every 30 min for 2 h total in presence of continued blue light illumination. Trials were randomized and conducted one week apart on the same animals. For experiments targeted at terminal stimulation in the arcuate nucleus of the hypothalamus, male animals were bilaterally injected into the HDB with AAV-EF1α-DIO-hChR2(H134R)-EYFP-WPRE-hGHpA, and a single fibre optic was implanted into the third ventricle at the level of the arcuate (from bregma: AP = −1.70, DV = −5.75, ML = 0.00). For behavioural assays, animals were first allowed 48 h to acclimate to their behaviour cage while tethered to a fibre optic cord. After acclimation, mice were fasted overnight. In the morning, mice were presented with standard pre-measured pellet chow and food intake was recorded every 30 min for 2 h total either under conditions of light stimulation (5 mW, 10 ms pulses, 20 Hz, 5 s trains, 30 s intervals) or no stimulation. Trials were randomized and conducted one week apart on the same animals. Paired statistics were used to compare ‘stim’ and ‘no-stim’ conditions on these animals. As a control group, Cre-negative male littermates were injected with virus and implanted in the same way as experimental mice. Behavioural assays on these mice were done the same way under conditions of light illumination. Comparisons between mock-stimulated and experimental cohorts were done using unpaired statistics. For terminal stimulation experiments in the presence of mecamylamine (Tocris, catalogue number 2843), mice were fasted overnight and presented with a pre-measured amount of chow in the morning. Mecamylamine was administered by i.p. injection at 1 mg per kg 15 min before the start of a 2-h feeding in the presence or absence of blue light illumination. Control (sterile 1× PBS i.p. injections) and experimental trials were conducted 1 week apart. Brain slices containing the hypothalamic arcuate nucleus were prepared from 6–8-week-old Pomc-EGFP+/− or Npy-hrGFP+/− transgenic mice of either gender. For ChR2 stimulation and hM4d-mediated inhibition, brain slices containing the DBB were prepared from 12–16-week-old male animals expressing either ChR2::EYFP or hM4D–EGFP in the DBB, respectively. Animals were anaesthetized with isoflurane and brains were rapidly removed and transferred into sucrose-based cutting solution, containing (in mM): 250 sucrose, 25 NaHCO , 1.25 NaH PO , 2.5 KCl, 1.5 MgCl , 2 CaCl , 10 glucose, and continuously bubbled with 5% CO / 95% O . 300-μm-thick coronal brain slices were prepared using a Leica VT 1200 vibratome and placed for recovery in a 5% CO / 95% O bubbled regular ACSF solution, containing (in mM): 128 NaCl, 24 NaHCO , 1 NaH PO , 3 KCl, 1 MgCl , 1.6 CaCl , 8 glucose. After at least 1-h recovery and 20–30 min before recording, slices were transferred into a recording chamber continuously perfused at 2 ml min−1 with aforementioned ACSF at 24 °C. POMC-, NPY-, ChR2::EYFP-, and hM4D-expressing neurons were identified by transmitted light DIC and EGFP fluorescent imagi