Atlanta, GA, United States
Atlanta, GA, United States

Emory University is a private research university in metropolitan Atlanta, located in the Druid Hills section of unincorporated DeKalb County, Georgia, United States. The university was founded as Emory College in 1836 in Oxford, Georgia by the Methodist Episcopal Church and was named in honor of Methodist bishop John Emory. In 1915 the college relocated to metropolitan Atlanta and was rechartered as Emory University.Emory University has nine academic divisions: Emory College of Arts and science, Oxford College, Goizueta Business School, Laney Graduate School, School of Law, School of Medicine, Nell Hodgson Woodruff School of Nursing, Rollins School of Public Health, and the Candler School of Theology. Emory University and the Georgia Institute of Technology have a strong research partnership and jointly administer the Emory-Georgia Tech Predictive Health Institute and the Wallace H. Coulter Department of Biomedical Engineering Program with Peking University in Beijing, China. Emory University and the Georgia Institute of Technology's combined annual research expenditures exceed $1.25 billion.Emory University is 16th among the list of colleges and universities in the United States by endowment, 5th among universities in the United States regarding licensing revenue per dollars spent on research, and 21st in U.S. News & World Report's 2015 National Universities Rankings. The university also ranks as one of the top universities in the world. In 1995 Emory University was elected to the Association of American Universities, an association of the 62 leading research universities in the United States & Canada.The university has nearly 3,000 faculty members; Emory faculty and alumni include international leaders in the fields of politics, business and academia, and its members have been recognized with numerous national and international awards and honors. Wikipedia.


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Patent
Emory University | Date: 2016-09-22

These systems and devices can be placed on top of any commercially available standard operating table and therefore can provide a portable and inexpensive alternative to commercially available specialized operating tables. The system may include a frame body having a first end, a second end, and a length therebetween. The system may also include one or more movable platforms having a first end, a second end, and a length therebetween. Each moveable platform may be configured to move between the first end and the second end of the frame body. The system may also include one or more stabilizing support members disposed parallel to the first end and the second end of the frame body and configured to move along the length of the movable platform. Each stabilizing support member may include one or more securing members configured for removable, active and/or removable fixation with respect to the movable platform.


The disclosure relates to Prostaglandin receptor EP2 antagonists, derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing conditions and diseases in which EP2 receptor activation has a physiological role, such as but not limited to, brain injury, inflammatory diseases, neuroinflamation after a seizure, pain, endometriosis, cancer, rheumatoid arthritis, skin inflammation, vascular inflammation, colitis, and neurological disorders by administering a pharmaceutical composition comprising a compound disclosed herein to a subject in need thereof.


In certain embodiments, this disclosure relates to methods of treating or preventing HvGD comprising administering an effective amount of indole-2-carboxyaldehyde, indole-3-carboxyaldehyde, or derivative to a subject in need thereof. In certain embodiments, this disclosure relates to methods of treating a subject with a hematological malignancy or other cancer comprising transplanting allogenic bone marrow or stem cells in combination with administering an effective amount of an indole-2-carboxyaldehyde, indole-3-carboxyaldehyde, or derivative thereof to a subject in need thereof.


Patent
Emory University | Date: 2016-12-06

The disclosure relates to chemokine CXCR4 receptor modulators and uses related thereto. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising compounds disclosed herein or pharmaceutically acceptable salts or prodrugs thereof. In certain embodiments, the compositions disclosed herein are used for managing CXCR4 related conditions, typically prevention or treatment of viral infections such as HIV or for managing cancer.


Patent
Emory University and Regent University | Date: 2015-05-05

The disclosure relates to BH4 inhibitors and therapeutic uses relates thereto. In certain embodiments, the disclosure relates to methods of treating or preventing cancer, such as lung cancer, comprising administering therapeutically effective amount of a pharmaceutical composition comprising a compound disclosed herein or pharmaceutically acceptable salt to a subject in need thereof.


Patent
Emory University | Date: 2016-11-18

Provided are steroid analogues functionalized with polar substituents at the C3 and/or C20 positions of the steroid ring system that exhibit improved water solubility. Also provided are pharmaceutical compositions comprising the steroid analogues and methods using the novel steroid analogues for the treatment and prevention of neurodegeneration in a patient following injury to the central nervous system.


Patent
Emory University | Date: 2015-04-28

Systems and methods are configured to treat a tissue by automatically linearly oscillating an instrument into a target site. A system may include a body having a length and configured to receive a portion of the instrument guide member having an exposed end and/or an instrument. The system may further include an actuator member disposed within the body and configured to linearly oscillate the instrument within the instrument guide member a fixed distance past the exposed end. The systems and methods can increase patient comfort while empowering clinicians by simplifying interventions for musculoskeletal disorders.


Patent
Emory University and Georgia Institute of Technology | Date: 2016-03-18

Various embodiments of the present invention provide a conduit system including an outer lumen, an inner lumen, and an attaching device. In other embodiments, a multiple access port device adapted for communication with at least one of an outer lumen, an inner lumen, or an attaching device of a conduit system is provided. In yet other embodiments, a system including an inner lumen that is collapsible is provided. Means for closing a conduit system are also provided, including a plug for insertion through an attaching device and a variable radius coiled member associated with an attaching device.


This disclosure relates to methods of identifying subjects that have an increased likelihood of responding to a combination of a poly (ADP) ribose polymerase enzyme inhibitor and a platinum based reagent and optionally other anticancer agents in the course of chemotherapy. In certain embodiments, the disclosure relates to methods of treating cancer comprising administering an effective amount of a poly (ADP) ribose polymerase enzyme inhibitor and a platinum based reagent to the subject in need thereof, wherein the subject is in need thereof because measuring a quantity of RNA isolated from a cancer cell from the subject indicates an increased quantity of the RNA compared to a normal sample, wherein the RNA is associated with one or more of the following genes/pseudogenes GLS, UBEC2, HACL1, MSI2, and LOC100129585.


This disclosure relates to variable lymphocyte receptors (VLRs) modifications such as humanized sequences and polypeptides comprising such sequences that specifically bind a target molecule and uses related thereto. In certain embodiments, the disclosure relates to recombinant polypeptide VLRs disclosed herein and variants thereof. In certain embodiments, this disclosure relates to treating or preventing a disease or condition comprising administering an effective amount of a recombinant poly-peptide or variant disclosed herein to a subject in need thereof.


Patent
Cocrystal Pharma Inc. and Emory University | Date: 2016-04-15

The present invention is directed to compounds, compositions and methods for treating or preventing hepatitis C virus (HCV) infection in human subjects or other animal hosts. The compounds are as also pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof as pharmaceutical compositions and methods for treatment or prevention of HCV infection.


This disclosure relates to manipulating microRNA for the management of neurological disorders and compositions related thereto. In certain embodiments, the disclosure contemplates inhibition of miR324 or miR324-5p, e.g., the use of nucleobase polymers for antisense disruptions or RNA interference of miR-324 expression or for miR324-5p binding in order to increase Kv4.2 expression. In certain embodiments, the disclosure relates to methods of treating or preventing a neurological disease or condition comprising administering an effective amount of an inhibitor to a subject in need thereto.


The disclosure relates to Prostaglandin receptor EP2 antagonists, derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing conditions and diseases in which EP2 receptor activation has a physiological role, such as but not limited to, brain injury, inflammatory diseases, neuroinflammation after a seizure, pain, endometriosis, cancer, rheumatoid arthritis, skin inflammation, vascular inflammation, colitis, and neurological disorders by administering a pharmaceutical composition comprising a compound disclosed herein to a subject in need thereof.


Patent
Emory University and Children's Healthcare Of Atlanta | Date: 2015-04-13

This disclosure relates to recombinant proteins comprising a GM-CSF sequence and an interleukin sequence and nucleic acids related thereto. In certain embodiments, the disclosure relates to recombinant proteins comprises N-terminal sequences that are the result of improved production techniques and uses for treating or preventing autoimmune diseases such as multiple sclerosis and cancer.


Patent
Duke University and Emory University | Date: 2015-02-18

Provided herein are recombinant constructs, vectors and expression cassettes including a first promoter which is suitably a tRNA promoter operably connected to a first polynucleotide encoding a first single guide RNA and a second promoter operably connected to a second polynucleotide encoding a Cas9 polypeptide. The first single guide RNA includes a first portion complementary to a strand of a target sequence of a DNA virus and a second portion capable of interacting with the Cas9 polypeptide. Also provided are codon optimized Staphylococcus aureus derived Cas9 polynucleotides and polypeptides with nuclear localization signals and optionally an epitope tag. Also provided are constructs for production of sgRNAs including a tRNA. Methods of inhibiting viral replication, inhibiting expression of a target sequence from a virus or treating a viral infection or viral induced cancer using the compositions are also provided.


The disclosure relates to compounds and compositions for forming bone and methods related thereto. In one embodiment, the disclosure relates to a composition comprising a compound disclosed herein, such as 2,4-diamino-1,3,5-triazine derivatives or salts thereof, for use in bone growth processes. In a typical embodiment, a bone graft composition is implanted in a subject at a site of desired bone growth or enhancement.


Patent
Emory University | Date: 2015-05-05

This disclosure relates to methods of treating and diagnosing a tuberculosis infection as pulmonary active or latent based on biomarkers expressed on pools of CD4^(+) cells. In certain embodiments, the disclosure relates to methods of treatment of a subject diagnosed with tuberculosis comprising the steps of, measuring a pool of CD4^(+)IFN- cells for cells that also express CD38, HLA-DR, and/or Ki-67 providing a measurement; associating an increased measurement of CD4^(+)IFN- cells that also express CD38, HLA-DR, Ki-67, compared to a control, as an indication that the subject has active tuberculosis; and treating the subject with an aggressive tuberculosis treatment.


Patent
Emory University | Date: 2015-05-14

Methods and systems relate to dynamic management of a health condition based on the changing needs and status of individual patient(s) and/or provider(s). The method may include processing information to determine one or more health management factors for a patient; generating a health management plan for managing a health condition of the patient based on the one or more management factors, the management plan including one or more goals, treatment regimen information, one or more prompt conditions, one or more attributes of one or more treatment events, or a combination thereof; and generating one or more prompt(s) based on the management plan.


Pulendran B.,Emory Vaccine Center | Pulendran B.,Emory University | Li S.,Emory Vaccine Center | Nakaya H.I.,Emory Vaccine Center
Immunity | Year: 2010

Vaccination is one of the greatest triumphs of modern medicine, yet we remain largely ignorant of the mechanisms by which successful vaccines stimulate protective immunity. Two recent advances are beginning to illuminate such mechanisms: realization of the pivotal role of the innate immune system in sensing microbes and stimulating adaptive immunity, and advances in systems biology. Recent studies have used systems biology approaches to obtain a global picture of the immune responses to vaccination in humans. This has enabled the identification of early innate signatures that predict the immunogenicity of vaccines, and identification of potentially novel mechanisms of immune regulation. Here, we review these advances and critically examine the potential opportunities and challenges posed by systems biology in vaccine development. © 2010 Elsevier Inc.


Galipeau J.,Emory University
Current Molecular Medicine | Year: 2013

Cell therapy with mesenchymal stromal cells (MSCs) is the focus of intensive investigation. Several clinical trials, including large-scale placebo-controlled phase III clinical trials, are currently underway evaluating the therapeutic potential of autologous and allogeneic MSCs for treatment of catastrophic inflammatory diseases, including steroid-refractory graft-versus-host disease (GvHD), multiple sclerosis (MS) and Crohn's disease. MSCs are also being investigated as carriers of anti-cancer biotherapeutics. We here review recent developments in our understanding of the immunosuppressive properties of MSCs. We firstly discuss the effects of ex vivo culture conditions on the phenotype and functions of MSCs. Secondly, we summarize the immune functions suppressed by MSCs with a focus on T cell, B cell, natural killer cell and dendritic cell functions. Thirdly, we discuss newly identified pathways responsible for the immunosuppressive activity of MSCs, including the expression of heme-oxygenase (HO)-1, the secretion of galectins, CCL2 antagonism, T regulatory cell (Treg) cross-talk and production of TNF-a stimulated gene/protein-6 (TSG-6). Finally, we review the literature on the molecular pathways governing MSC homing and discuss recent clinical data on the use of MSCs for treatment of GvHD, MS and Crohn's disease. © 2013 Bentham Science Publishers.


Cunningham S.A.,Emory University
American Journal of Public Health | Year: 2013

We examined evidence for friendship influences on children's physical activity (PA) through systematic searches of online databases in May 2012. We identified 106 studies (25 qualitative) published in English since 2000 that analyzed indicators of friendship influences (e.g., communication about PA, friends' PA, and PA with friends) among persons younger than 19 years. Children's PA was positively associated with encouragement from friends (43 of 55 studies indicating a positive relationship), friends' own PA (30/35), and engagement with friends in PA (9/10). These findings are consistent with friends influencing PA, but most studies did not isolate influence from other factors that could explain similarity. Understanding friendship influences in childhood can facilitate the promotion of lifelong healthy habits. PA with friends should be considered in health promotion programs. Copyright © 2012 by the American Public Health Association®.


Workowski K.A.,Emory University
Morbidity and Mortality Weekly Report | Year: 2010

These guidelines for the treatment of persons who have or are at risk for sexually transmitted diseases (STDs) were updated by CDC after consultation with a group of professionals knowledgeable in the field of STDs who met in Atlanta on April 18-30, 2009. The information in this report updates the 2006 Guidelines for Treatment of Sexually Transmitted Diseases (MMWR 2006;55[No. RR-11]). Included in these updated guidelines is new information regarding 1) the expanded diagnostic evaluation for cervicitis and trichomoniasis; 2) new treatment recommendations for bacterial vaginosis and genital warts; 3) the clinical efficacy of azithromycin for chlamydial infections in pregnancy; 4) the role of Mycoplasma genitalium and trichomoniasis in urethritis/cervicitis and treatment-related implications; 5) lymphogranuloma venereum proctocolitis among men who have sex with men; 6) the criteria for spinal fluid examination to evaluate for neurosyphilis; 7) the emergence of azithromycin-resistant Treponema pallidum; 8) the increasing prevalence of antimicrobial-resistant Neisseria gonorrhoeae; 9) the sexual transmission of hepatitis C; 10) diagnostic evaluation after sexual assault; and 11) STD prevention approaches.


Chen J.,Emory University
Oncogene | Year: 2014

Post-translational modification (PTM) is an important step of signal transduction that transfers chemical groups such as phosphate, acetyl and glycosyl groups from one protein to another protein. As most of the PTMs are reversible, normal cells use PTMs as a 'switch' to determine the resting and proliferating state of cells that enables rapid and tight regulation of cell proliferation. In cancer cells, activation of oncogenes and/or inactivation of tumor suppressor genes provide continuous proliferative signals in part by adjusting the state of diverse PTMs of effector proteins that are involved in regulation of cell survival, cell cycle and proliferation, leading to abnormally fast proliferation of cancer cells. In addition to dysregulated proliferation, 'altered tumor metabolism' has recently been recognized as an emerging cancer hallmark. The most common metabolic phenotype of cancer is known as the Warburg effect or aerobic glycolysis that consists of increased glycolysis and enhanced lactate production even in the presence of oxygen. Although Otto Warburg observed aerobic glycolysis nearly 90 years ago, the detailed molecular mechanisms how increased glycolysis is regulated by oncogenic and/or tumor suppressive signaling pathways remain unclear. In this review, we summarize recent advances revealing how these signaling pathways reprogram metabolism through diverse PTMs to provide a metabolic advantage to cancer cells, thereby promoting tumor cell proliferation, tumorigenesis and tumor growth. © 2014 Macmillan Publishers Limited.


Patent
Emory University | Date: 2013-10-30

The disclosure relates to methods of growing bone or increasing bone mineral density and/or volume comprising administering an effective amount of a therapeutic containing abatacept or belatacept or other molecule that binds with CD8O, CD86, or CD28 providing inhibition of CD28 co-stimulation to a subject in need thereof.


Patent
CANCER RESEARCH TECHNOLOGY Ltd, IMPERIAL INNOVATIONS Ltd and Emory University | Date: 2015-02-20

The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain pyrazolo[1,5-a]pyrimidine-5,7-diamine compounds (referred to herein as PPDA compounds) that, inter alia, inhibit (e.g., selectively inhibit) CDK (e.g., CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, CDK13, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CDK; and to treat disorders including: disorders that are associated with CDK; disorders that result from an inappropriate activity of a cyclin-dependent kinase (CDK); disorders that are associated with CDK mutation; disorders that are associated with CDK overexpression; disorders that are associated with upstream pathway activation of CDK; disorders that are ameliorated by the inhibition of CDK; proliferative disorders; cancer; viral infections (including HIV); neurodegenerative disorders (including Alzheimers disease and Parkinsons disease); ischaemia; renal diseases; and cardiovascular disorders (including atherosclerosis). Optionally, the treatment further comprises treatment (e.g., simultaneous or sequential treatment) with a further active agent which is, e.g., an aromatase inhibitor, an anti-estrogen, a Her2 blocker, a cytotoxic chemotherapeutic agent, etc.


Patent
Genway Biotech Inc., Emory University and MedStar Research Institute | Date: 2012-03-01

This invention relates to the area of cardiovascular disorders and specifically relates to methods of diagnostic tests using a combination of markers to predict an individuals risk for developing coronary artery disease (CAD) and related diseases, such as angina pectoris and peripheral vascular disease and, more particularly, to determine an individuals risk of myocardial infarction, death, and stroke. Exemplary biomarkers include C-reactive protein (CRP), fibrin degradation products (FDPs), Heat Shock Protein 70 (HSP70), and/or anti-CMV antibody.


Patent
Emory University | Date: 2014-12-17

This disclosure relates to managing diabetes induced visual dysfunctions or vision loss by altering levels of dopamine. In certain embodiments, the disclosure relates to methods of treating or preventing visual dysfunction or loss of vision comprising administering an effective amount of dopamine, derivative, ester, prodrug, or salt thereof to a subject wherein the subject is at risk of, exhibiting symptoms of or diagnosed with diabetes or diabetic retinopathy.


Patent
Emory University and U.S. Department Of Veterans Affairs | Date: 2011-07-11

The present invention relates to the use of oxidized nicotinamide adenine dinucleotide (NAD^(+)) or of its reduced form, NADH, as sodium channel modulators. The present invention also relates to the use of compositions containing NAD^(+) or NADH to treat conditions associated with sodium channel current, such as arrhythmia. NAD^(+) is found to increase sodium channel current, while NADH is found to decrease sodium channel current. Thus, conditions that are associated with decreased sodium channel current can be treated with NAD^(+), while conditions that is associated with increased sodium channel current can be treated with NADH.


Patent
Imperial Innovations Ltd and Emory University | Date: 2013-03-19

This invention relates to quinazoline compounds of Formula (I) which are inhibitors of the histone lysine methyltransferase (HKMTase) EZH2, and to uses of such compounds as medicaments, in particular in the treatment of a disease or disorder in which inhibition of EZH2 provides a therapeutic or prophylactic effect.


Patent
Emory University, Centers for Disease Control and Prevention | Date: 2013-12-20

We have developed DNA and viral vectors that can be used, alone or in combination, as a vaccine against one HIV clade, subtype, or recombinant form of HIV or against multiple HIV clades, subtypes, or recombinant forms. Moreover, the vectors can encode a variety of antigens, which may be obtained from one clade or from two or more different clades, and the antigens selected and/or the manner in which the vectors are formulated (e.g., mixed) can be manipulated to generate a protective immune response against a variety of clades (e.g., the clades to which a patient is most likely to be exposed; with the proportions of the components of the vaccine tailored to the extent of the patients risk to a particular clade or clades).


Patent
University of Oregon, University of Washington and Emory University | Date: 2012-10-11

The present disclosure provides methods for inhibiting the anticoagulation effect of a thrombin inhibitor in a patient in need thereof comprising administration of a therapeutically effective amount of a variant prothrombin or thrombin that is capable of binding the thrombin inhibitor and that has reduced procoagulant activity. Variant prothrombins or thrombins of use in the methods of the present disclosure include thrombin mutants W215A, W215A/E217A, or variants thereof in which the amino acids at positions 215 and/or 217 are alanine. Methods are also provided in which the thrombin mutants are administered with an additional active agent. In one embodiment, the methods are useful in the treatment of patients in which a direct thrombin inhibitor has been administered. The present disclosure further provides a method for quantifying the concentration of an anticoagulant in the plasma or whole blood of a patient using a variant prothrombin or thrombin titration assay.


Patent
INC Research, Emory University, National Institute of Environmental Health, Safety, Veterans Affairs Puget Sound Health Care System and University of Oregon | Date: 2012-10-19

The present invention relates to methods of treatment for Parkinson Disease (PD) in a person by identifying gene variants which may indicate a more favorable response to specific medicaments, thereby allowing for personalized or individualized treatment. The present invention relates to a method of screening for a genetic predisposition to PD in a person. The present invention is also directed to a method of testing a person for the presence of particular gene variants, wherein the presence of a gene variant indicates a higher predisposition to PD, and the absence of a gene variant indicates a lower predisposition to PD, compared to a control sample. The present invention further relates to methods and kits for treating, or inhibiting the development of, PD in a person. The present invention is also directed to a method of identifying the heritage of an individual based on the genetic profile of the individual.


This disclosure relates to compounds and compositions for cartilage repair and methods related thereto. In certain embodiments, the disclosure relates to methods of inducing cartilage growth and regeneration comprising administering an effective amount of a composition comprising a compound disclosed herein to the subject or implanting a cartilage matrix comprising a compound disclosed herein in the subject. In certain embodiments, the compound is used locally such as injection at any desired site of cartilage formation.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2011.1.4-4 | Award Amount: 40.88M | Year: 2011

Vaccines so far have been developed mostly by following an empiric approach. To prevent and possibly cure unresolved and emerging infectious diseases we need to fully exploit the potential of the human immune system. Progress in science and technology makes it possible to achieve what was previously deemed impossible. The scope of this project is to produce knowledge necessary to develop novel and powerful immunization technologies for the next generation of human vaccines. This goal requires a multidisciplinary approach in which diverse but complementary scientific disciplines and technologies converge. Therefore some of the most competitive European research groups from public institutions and biotechs have agreed to join forces in ADITEC, together with top US groups on systems biology and adjuvants to support this enterprise. A systems biology approach will be used to study licensed and experimental vaccines in patient characterization studies and in clinical trials, to investigate the effect of adjuvants, vectors, formulations, delivery devices, routes of immunization, homologous and heterologous primeboost schedules, as well as the impact of host factors such as age, gender, genetics and pathologies. Animal models will be used to complement human studies, and to select novel immunization technologies to be advanced to the clinic. To address these issues in a coordinated manner, ADITEC is organised on a matrix structure in which research themes and experimental approaches feed into each other. Training curricula will be created to impact on the formation of the next generation of EU researchers in the field. ADITEC scientists and institutions are part of the Sclavo Vaccines Association (SVA), which is dedicated to vaccines and vaccine research. SVA, acting as the coordinating institution, guarantees the long-term commitment and sustainability of this initiative, beyond the duration of ADITEC itself.


Patent
Emory University | Date: 2013-08-20

Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are fulvene and/or fulvalene analogs. The compounds and compositions can be used to treat and/or prevent a wide variety of cancers, including drug resistant cancers, as well as numerous inflammatory, degenerative and vascular diseases, including various ocular diseases. Representative fulvene and/or fulvalene analogs include fulvene and fulvalene analogues of various dyes, hormones, sugars, peptides, oligonucleotides, amino acids, nucleotides, nucleosides, and polyols. The compounds are believed to function, at least, by inhibiting Nox or ROS. In some embodiments, the Nox is one that is selectively expressed in cancer cells over normal cells, or one that is expressed in higher amounts in cancer cells over normal cells. Thus, the compounds are novel therapeutic agents for a variety of cancers and other diseases.


Klatt N.R.,National Institute of Allergy and Infectious Diseases | Silvestri G.,Emory University
Science Translational Medicine | Year: 2012

When it comes to HIV infection, CD4 + T cells are usually thought of as the cells that are preferentially infected and killed by the virus. In a new study, Soghoian et al. now show that during the early stages of HIV infection, CD4 + T cells suppress virus replication and delay disease onset. Thus, the robustness of the CD4 + T cell response during early HIV infection could be used as a marker to determine the speed of disease progression. The new findings also have implications for the design of preventive and therapeutic AIDS vaccines.


De Cock K.M.,Centers for Disease Control and Prevention | Jaffe H.W.,Centers for Disease Control and Prevention | Curran J.W.,Emory University
AIDS | Year: 2012

Following its recognition in 1981, the HIV/AIDS epidemic has evolved to become the greatest challenge in global health, with some 34 million persons living with HIV worldwide. Early epidemiologic studies identified the major transmission routes of the virus before it was discovered, and enabled the implementation of prevention strategies. Although the first identified cases were in MSM in the United States and western Europe, the greatest impact of the epidemic has been in sub-Saharan Africa, where most of the transmission occurs between heterosexuals. Nine countries in southern Africa account for less than 2% of the world's population but now they represent about one third of global HIV infections. Where broadly implemented, HIV screening of donated blood and antiretroviral treatment (ART) of pregnant women have been highly effective in preventing transfusion-associated and perinatally acquired HIV, respectively. Access to sterile equipment has also been a successful intervention for injection drug users. Prevention of sexual transmission has been more difficult. Perhaps the greatest challenge in terms of prevention has been in the global community of MSM in which HIV remains endemic at high prevalence. The most promising interventions are male circumcision for prevention of female-to-male transmission and use of ART to reduce infectiousness, but the extent to which these interventions can be brought to scale will determine their population-level impact. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Budnitz D.S.,Centers for Disease Control and Prevention | Lovegrove M.C.,Centers for Disease Control and Prevention | Shehab N.,Centers for Disease Control and Prevention | Richards C.L.,Centers for Disease Control and Prevention | Richards C.L.,Emory University
New England Journal of Medicine | Year: 2011

Background: Adverse drug events are important preventable causes of hospitalization in older adults. However, nationally representative data on adverse drug events that result in hospitalization in this population have been limited. Methods: We used adverse-event data from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project (2007 through 2009) to estimate the frequency and rates of hospitalization after emergency department visits for adverse drug events in older adults and to assess the contribution of specific medications, including those identified as high-risk or potentially inappropriate by national quality measures. Results: On the basis of 5077 cases identified in our sample, there were an estimated 99,628 emergency hospitalizations (95% confidence interval [CI], 55,531 to 143,724) for adverse drug events in U.S. adults 65 years of age or older each year from 2007 through 2009. Nearly half of these hospitalizations were among adults 80 years of age or older (48.1%; 95% CI, 44.6 to 51.6). Nearly two thirds of hospitalizations were due to unintentional overdoses (65.7%; 95% CI, 60.1 to 71.3). Four medications or medication classes were implicated alone or in combination in 67.0% (95% CI, 60.0 to 74.1) of hospitalizations: warfarin (33.3%), insulins (13.9%), oral antiplatelet agents (13.3%), and oral hypoglycemic agents (10.7%). High-risk medications were implicated in only 1.2% (95% CI, 0.7 to 1.7) of hospitalizations. Conclusions: Most emergency hospitalizations for recognized adverse drug events in older adults resulted from a few commonly used medications, and relatively few resulted from medications typically designated as high-risk or inappropriate. Improved management of antithrombotic and antidiabetic drugs has the potential to reduce hospitalizations for adverse drug events in older adults. Copyright © 2011 Massachusetts Medical Society.


Chan M.,Emory University | Johansson M.A.,Centers for Disease Control and Prevention
PLoS ONE | Year: 2012

Dengue viruses are major contributors to illness and death globally. Here we analyze the extrinsic and intrinsic incubation periods (EIP and IIP), in the mosquito and human, respectively. We identified 146 EIP observations from 8 studies and 204 IIP observations from 35 studies. These data were fitted with censored Bayesian time-to-event models. The best-fitting temperature-dependent EIP model estimated that 95% of EIPs are between 5 and 33 days at 25°C, and 2 and 15 days at 30°C, with means of 15 and 6.5 days, respectively. The mean IIP estimate was 5.9 days, with 95% expected between days 3 and 10. Differences between serotypes were not identified for either incubation period. These incubation period models should be useful in clinical diagnosis, outbreak investigation, prevention and control efforts, and mathematical modeling of dengue virus transmission.


Brrgeon D.,University Paris - Sud | Doetsch P.W.,Emory University
Nature Reviews Cancer | Year: 2011

The majority of human cells do not multiply continuously but are quiescent or slow-replicating and devote a large part of their energy to transcription. When DNA damage in the transcribed strand of an active gene is bypassed by a RNA polymerase, they can miscode at the damaged site and produce mutant transcripts. This process is known as transcriptional mutagenesis and, as discussed in this Perspective, could lead to the production of mutant proteins and might therefore be important in tumour development. © 2011 Macmillan Publishers Limited. All rights reserved.


Tiniakos D.G.,National and Kapodistrian University of Athens | Vos M.B.,Emory University | Brunt E.M.,University of Washington
Annual Review of Pathology: Mechanisms of Disease | Year: 2010

Nonalcoholic fatty liver disease (NAFLD) is recognized as the leading cause of chronic liver disease in adults and children. NAFLD encompasses a spectrum of liver injuries ranging from steatosis to steatohepatitis with or without fibrosis. Fibrosis may progress to cirrhosis and complications including hepatocellular carcinoma. Histologic findings represent the complexity of pathophysiology. NAFLD is closely associated with obesity and is most closely linked with insulin resistance; the current Western diet, high in saturated fats and fructose, plays a significant role. There are several mechanisms by which excess triglycerides are acquired and accumulate in hepatocytes. Formation of steatotic droplets may be disordered in NAFLD. Visceral adipose tissue dysfunction in obesity and insulin resistance results in aberrant cytokine expression; many cytokines have a role in liver injury in NAFLD. Cellular stress and immune reactions, as well as the endocannabinoid system, have been implicated in animal models and in some human studies. Copyright © 2010 by Annual Reviews.


Koo D.,Centers for Disease Control and Prevention | Miner K.,Emory University
Annual Review of Public Health | Year: 2010

The broad scope of the public health mission leads to an increasingly diverse workforce. Given the range of feeder disciplines and the reality that much of the workforce does not have formal training in public health science and practice, a pressing need exists for training and education throughout the workforce. Just as we in public health take a rigorous approach to our science, so too should we take a rigorous, evidence-driven approach to workforce development. In this review, we recommend a framework for workforce education in public health, integrating three critical conceptual approaches: (a) adult learning theory; (b) competency-based education; and (c) the expanded Dreyfus model in public health, an addition to the Dreyfus model of professional skills progression. We illustrate the application of this framework in practice, using the field of applied epidemiology. This framework provides a context for designing and developing high-quality, outcome-based workforce development efforts and evaluating their impact, with implications for academic and public health practice efforts to educate the public health workforce. Copyright © 2010 by Annual Reviews. All rights reserved.


Guarner J.,Emory University | Brandt M.E.,Centers for Disease Control and Prevention
Clinical Microbiology Reviews | Year: 2011

Fungal infections are becoming more frequent because of expansion of at-risk populations and the use of treatment modalities that permit longer survival of these patients. Because histopathologic examination of tissues detects fungal invasion of tissues and vessels as well as the host reaction to the fungus, it is and will remain an important tool to define the diagnostic significance of positive culture isolates or results from PCR testing. However, there are very few instances where the morphological characteristics of fungi are specific. Therefore, histopathologic diagnosis should be primarily descriptive of the fungus and should include the presence or absence of tissue invasion and the host reaction to the infection. The pathology report should also include a comment stating the most frequent fungi associated with that morphology as well as other possible fungi and parasites that should be considered in the differential diagnosis. Alternate techniques have been used to determine the specific agent present in the histopathologic specimen, including immunohistochemistry, in situ hybridization, and PCR. In addition, techniques such as laser microdissection will be useful to detect the now more frequently recognized dual fungal infections and the local environment in which this phenomenon occurs. © 2011, American Society for Microbiology. All Rights Reserved.


Patent
Emory University and Foundation University | Date: 2015-11-06

2-Fluoro-nucleoside compounds are disclosed which are useful in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cellular proliferation, including tumors and cancer. The compounds have the general formulae: wherein


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2012.2.1.1-2 | Award Amount: 17.67M | Year: 2013

As more people survive into old age, the prevalence of heart failure (HF), one of the most common and debilitating diseases in older people, will rise still further. Delaying or preventing HF will have great benefit to those at personal risk, their families, society and the economy. HOMAGE aims to provide a biomarker (BM) approach that will a) help identify i. patients at high risk of developing HF before the onset of symptoms and ii. subsets of patients who are more likely to respond to specifically targeted therapies (personalized medicine). In available cohorts, we will identify the most promising omics-based BM profiles for the pre-symptomatic diagnosis and future prediction of HF in patients at risk. The predictive value of the BMs for other co-morbidities commonly associated with HF and ageing will also be investigated. Furthermore, in a prospective trial, we will investigate the potential for targeting preventive therapy at patients with the greatest likelihood of response and the lowest risk of adverse effects. Our selection of innovative omics-based BMs is based on knowledge of biological pathways of the disease, which may facilitate identification of Biotargets for future therapies. On the economic side, HOMAGE will act as an economic catalyst for European SMEs in the field of cardiovascular and ageing BMs, estimated to peak annual turnovers of up to 800 M.


Patent
Emory University, Dana-Farber Cancer Institute, Brigham, Women's Hospital and President And Fellows Of Harvard College | Date: 2016-08-30

The present invention provides methods and compositions for the treatment, prevention, or reduction of persistent infections, such as chronic infections, latent infections, and slow infections and cancer. The methods and compositions of the invention are also useful for the alleviation of one or more symptoms associated with such infections and cancer.


Patent
Emory University, Foundation University, Schinazi, Liotta, Chu, Mcatee, Shi, Choi, Lee and Hong | Date: 2011-12-07

2-Fluoronucleoside compounds are disclosed which are useful in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cellular proliferation, including tumors and cancer. The compounds have general formulae (I), (II), (III), (IV) wherein Base is a purine or pyrimidine base; R^(1) is OH, H, OR^(3), N_(3), CN, halogen, including F, or CF_(3), lower alkyl, amino, loweralkylamino, di(lower)alkylamino, or alkoxy, and base refers to a purine or pyrimidine base; R^(2) is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug; acyl, or other pharmaceutically acceptable leaving group which when administered in vivo, is capable of providing a compound wherein R^(2) is H or phosphate; sulfonate ester including alkyl or arylalkyl sulfonyl including methanesulfonyl, benzyl, wherein the phenyl group is optionally substituted with one or more substituents as described in the definition of aryl given above, a lipid, an amino acid, peptide, or cholesterol; and R^(3) is acyl, alkyl, phosphate, or other pharmaceutically acceptable leaving group which when administered in vivo, is capable of being cleaved to the parent compound, or a pharmaceutically acceptable salt thereof.


Patent
Emory University, National Institute of Allergy and Infectious Diseases | Date: 2014-12-10

The invention provides modified virus Ankara (MVA), a replication-deficient strain of vaccinia virus, expressing human immunodeficiency virus (HIV) env, gag, and pol genes.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: STTR | Phase: Phase I | Award Amount: 149.26K | Year: 2015

DESCRIPTION provided by applicant Ocular graft versus host disease O GVHD is a particularly severe and debilitating complication of allogeneic hematopoietic stem cell transplantation HSCT O GVHD develops in of patients with chronic GVHD Currently Restasis cyclosporine A is the only FDA approved prescription topical medication to treat O GVHD In Restasis had sales of just under $ billion for the treatment dry eye however the therapeutic efficacy of Restasis is only and its use is associated with a rate of adverse events This lack of robust clinical effectiveness demonstrates that alternative therapies are needed Many HSCT patients who fail Restasis therapy have found relief from using autologous serum formulated into topical eye drops autologous serum tears AST Unfortunately the lack of standardization of AST preparations which are often prepared in doctorandapos s offices or pharmacies and challenges with its storage and administration have limited widespread adoption of this product In order to address the drawbacks of AST we have developed a proprietary method to manufacture a promising alternative a standardized platelet lysate preparation using pooled platelet collections phPL from qualified blood donors Elate OcularTM Ocular phPL We believe Elate OcularTM will be superior to Restasis or AST for treatment of patients with O GVHD and other forms of dry eye since Elate OcularTM is enriched compared to serum for a number of growth factors that promote corneal healing has robust anti inflammatory actions that can reduce ocular inflammation in patients with GVHD and possesses bacteriostatic properties This STTR Phase I application is submitted by Cambium Medical Technologies LLC a start up company founded by faculty members from Emory University School of Medicine who developed Ocular phPL Emory will be the sub contracting research organization for this application Emory University has filed a patent application to protect our proprietary manufacturing process for phPL and Cambium has exclusive rights to this patent and technology The investigators have previously received two INDs from FDA CBER for other applications of phPL IND NCT and IND NCT and we are now seeking to submit a treatment IND for Elate OcularTM and conduct a Phase I II clinical study in HSCT patients with O GVHD In order to support these clinical studies we propose in this application to first further improve and validate the safety and efficacy profiles f Elate OcularTM by i demonstrating feasibility of applying a pathogen inactivation PI process during production of Elate OcularTM ii performing in vitro work on Elate OcularTM PI treatment to compare product compositions and mechanisms of action and iii performing animal toxicology efficacy studies with Elate OcularTM PI treatment in animals with a pre existing inflammatory condition or deficient tear production Successful completion of these aims will allow us to complete our FDA IND application and initiate the Phase I II study for which we will seek Phase II STTR support in order to demonstrate that Elate OcularTM is safe and well tolerated in patients suffering O GVHD morbidity a required step toward future commercialization PUBLIC HEALTH RELEVANCE Many patients with blood cancers are increasingly being treated by allogeneic hematopoietic stem cell transplantation HSCT This type of HSCT is often curative but is not without side effects including debilitating eye problems We propose to perform the FDA required studies necessary to commercialize a new eye drop designed to treat the ocular side effects of allogeneic HSCT


Patent
Emory University, President And Fellows Of Harvard College, Brigham, Women's Hospital and Dana-Farber Cancer Institute | Date: 2013-12-30

The present invention provides methods and compositions for the treatment, prevention, or reduction of persistent infections, such as chronic infections, latent infections, and slow infections and cancer. The methods and compositions of the invention are also useful for the alleviation of one or more symptoms associated with such infections and cancer.


Patent
Emory University and University of Illinois at Urbana - Champaign | Date: 2015-04-29

This disclosure relates to endothelial or endothelial like cells cultured from fibroblasts exposed to transcription factor ETV2. In certain embodiments, the disclosure relates to methods of producing endothelial or endothelial like cells comprising exposing fibroblasts with ETV2 under conditions such that the fibroblasts are modified to form a pool of cells expressing increased levels of endothelium surface markers compared to the fibroblasts. In certain embodiments, the disclosure relates to using endothelial like cells reported herein for the treatment of vascular, cardiac, and wound healing indications.


Methods, systems and computer-readable storage media relate to determining individualized treatment planning margins. The methods may include processing motion data of a target obtained from at least one marker for one or more periods. Each period may include a plurality of time intervals. The processing may include processing the motion data to determine an isocenter for each time interval along at least one of the axes of motion. The axes can include the x axis, the y axis, and/or the z axis. The method may include determining motion prediction data for each of the at least one of the axes; and determining treatment planning margins for each of the at least one of the axes based on the motion prediction data. The individualized treatment margins can be smaller and more optimal because the treatment margins can incorporate patient specific patterns of motion of a target (e.g., an organ).


Patent
Emory University, Foundation University, Schinazi, Liotta, Chu, Mcatee, Shi, Choi, Lee and Hong | Date: 2011-11-30

2-Fluoronucleoside compounds are disclosed which are useful in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cellular proliferation, including tumors and cancer. The compounds have general formulae (I), (II), (III), (IV) wherein Base is a purine or pyrimidine base; R^(1) is OH, H, OR^(3), N_(3), CN, halogen, including F, or CF_(3), lower alkyl, amino, loweralkylamino, di(lower)alkylamino, or alkoxy, and base refers to a purine or pyrimidine base; R^(2) is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug; acyl, or other pharmaceutically acceptable leaving group which when administered in vivo, is capable of providing a compound wherein R^(2) is H or phosphate; sulfonate ester including alkyl or arylalkyl sulfonyl including methanesulfonyl, benzyl, wherein the phenyl group is optionally substituted with one or more substituents as described in the definition of aryl given above, a lipid, an amino acid, peptide, or cholesterol; and R^(3) is acyl, alkyl, phosphate, or other pharmaceutically acceptable leaving group which when administered in vivo, is capable of being cleaved to the parent compound, or a pharmaceutically acceptable salt thereof.


Patent
Emory University, Dana-Farber Cancer Institute and President And Fellows Of Harvard College | Date: 2016-09-07

PD-1 antagonists are disclosed that can be used to reduce the expression or activity of PD-1 in a subject. An immune response specific to an infectious agent or to tumor cells can be enhanced using these PD-1 antagonists in conjunction with an antigen from the infectious agent or tumor. Thus, subjects with infections, such as persistent infections can be treated using PD-1 antagonists. In additions, subjects with tumors can be treated using the PD-1 antagonists. In several examples, subjects can be treated by transplanting a therapeutically effective amount of activated T cells that recognize an antigen of interest and by administering a therapeutically effective amount of a PD-1 antagonist.


Olfson M.,Columbia University | Druss B.G.,Emory University | Marcus S.C.,University of Pennsylvania
New England Journal of Medicine | Year: 2015

BACKGROUND: Increasing mental health treatment of young people and broadening conceptualizations of psychopathology have triggered concerns about a disproportionate increase in the treatment of youths with low levels of mental health impairment. METHODS: We analyzed the 1996-1998, 2003-2005, and 2010-2012 Medical Expenditure Panel Surveys, which were nationally representative surveys of U.S. households, for trends in outpatient use of mental health services by persons 6 to 17 years of age; 53,622 persons were included in the analysis. Mental health impairment was measured with the use of the Columbia Impairment Scale (range, 0 to 52, with higher scores indicating more severe impairment); we classified youths with scores of 16 or higher as having more severe impairment and those with scores of less than 16 as having less severe impairment. RESULTS: The percentage of youths receiving any outpatient mental health service increased from 9.2% in 1996-1998 to 13.3% in 2010-2012 (odds ratio, 1.52; 95% confidence interval, 1.35 to 1.72). The proportionate increase in the use of mental health services among youths with more severe impairment (from 26.2% to 43.9%) was larger than that among youths with less severe or no impairment (from 6.7% to 9.6%). However, the absolute increase in annual service use was larger among youths with less severe or no impairment (from 2.74 million to 4.19 million) than among those with more severe impairment (from 1.56 million to 2.28 million). Significant overall increases occurred in the use of psychotherapy (from 4.2% to 6.0%) and psychotropic medications (from 5.5% to 8.9%), including stimulants and related medications (from 4.0% to 6.6%), antidepressants (from 1.5% to 2.6%), and antipsychotic drugs (from 0.2% to 1.2%). CONCLUSIONS: Outpatient mental health treatment and psychotropic-medication use in children and adolescents increased in the United States between 1996-1998 and 2010-2012. Although youths with less severe or no impairment accounted for most of the absolute increase in service use, youths with more severe impairment had the greatest relative increase in use, yet fewer than half accessed services in 2010-2012. Copyright © 2015 Massachusetts Medical Society.


Shaw G.M.,University of Pennsylvania | Hunter E.,Emory University
Cold Spring Harbor Perspectives in Medicine | Year: 2012

HIV-1 is transmitted by sexual contact across mucosal surfaces, by maternal-infant exposure, and by percutaneous inoculation. For reasons that are still incompletely understood, CCR5-tropic viruses (R5 viruses) are preferentially transmitted by all routes. Transmission is followed by an orderly appearance of viral and host markers of infection in the blood plasma. In the acute phase of infection, HIV-1 replicates exponentially and diversifies randomly, allowing for an unambiguous molecular identification of transmitted/founder virus genomes and a precise characterization of the population bottleneck to virus transmission. Sexual transmission of HIV-1 most often results in productive clinical infection arising from a single virus, highlighting the extreme bottleneck and inherent inefficiency in virus transmission. It remains to be determined if HIV-1 transmission is largely a stochastic process whereby any reasonably fit R5 virus can be transmitted or if there are features of transmitted/founder viruses that facilitate their transmission in a biologically meaningful way. Human tissue explant models of HIV-1 infection and animal models of SIV/SHIV/HIV-1 transmission, coupled with new challenge virus strains that more closely reflect transmitted/founder viruses, have the potential to elucidate fundamental mechanisms in HIV-1 transmission relevant to vaccine design and other prevention strategies. © 2012 Cold Spring Harbor Laboratory Press; all rights reserved.


Patent
The Regents Of The University Of California, University of Pennsylvania and Emory University | Date: 2012-11-28

The present invention provides methods for predicting the development of tolerance to a transplant, such as a kidney, using molecular markers that have different expression patterns in tolerant transplant recipients, as compared to non-tolerant or healthy, non-recipient controls.


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase II | Award Amount: 2.06M | Year: 2012

DESCRIPTION (provided by applicant): Today's cardiac imaging field requires diagnosticians to master an ever-expanding knowledge base (KB) while the time to master this knowledge, apply it to specific tasks and reimbursement are steadily shrinking. These constraints pose a serious healthcare problem that inevitably leads to physician's errors. Thus new tools are required to assist physicians to timely apply comprehensive, up-to-date objective knowledge and the available patient data to specific clinical problems. The long-term objective of our Fast-Track proposal is to improve the care of cardiac patients and reduce the cost of cardiac image interpretation by developing new tools for a WEB-accessible cardiac toolbox that provides decision support to increasethe accuracy of detecting coronary heart disease (CHD). Specifically, we propose a WEB-based system where acquired ECG-gated myocardial perfusion SPECT (MPS) raw images are uploaded to be automatically reconstructed and analyzed to extract regional quantitative parameters of myocardial perfusion and function. These parameters are converted to certainty factors of abnormality and submitted to an imaging decision support system (DSS) that is continuously updated with the latest scientific/clinical knowledgeto reach an impression of the patient's heart status. These conclusions reached by the DSS and justifications for each conclusion are used to automatically generate a web-based structured report for the diagnostician to easily review, learn from the justifications, and either modify and/or approve for optimal accuracy of the diagnosis and prognosis of CHD. Specifically we propose to: 1) develop a novel left ventricular (LV) quantitative algorithm that automatically extracts parameters of left LV regional perfusion and function used to diagnose CHD; 2) develop the LV expert (LVX) DSS and 3) design and implement the LV quantification and DSS algorithms using the .net platform so that they can be integrated into our Syntermed infrastructure and deployed over the web and/or used as conventional stand- alone work-stations. In Phase I we will develop a proof-of-principle system where LV perfusion information from MPS studies is analyzed and DSS interpreted for automatic report generation and physician review. In Phase II, the system will be: a) extended to include quantification and DSS of myocardial function, ischemia, viability and clinical risk factors, b) extended to include a methodology to continuously update LVX's KB, c) automated to link all the reconstruction, processing, quantification, interpretation, and reporting applications, and d) deployed in .net on the web with database and eCommerce accounting capability. Using this process we expect to confirm our primary hypothesis that diagnosticians using our decision support will provide a faster, more accurate diagnosis and prognosis of CHD than those provided by the same diagnosticians without the aid of this system. The system will be commercialized using Syntermed's successful strategy of other Emory software through: 1) licensing to major instrumentation manufacturers, 2) direct sales to clients that use PC workstations and 3) per WEB-access fee using the existing Syntermed Live network. PUBLIC HEALTH RELEVANCE: Physicians are required to master an ever-expanding knowledge base and take into account an ever increasing amount of patient-specific clinical information while time available to master this knowledge base and apply it to specific tasks is steadily shrinking. There is also an increasing shortage of cardiac diagnosticians [Fye04] who primarily interpret nuclear cardiology studies and an ever increasing number of aging Baby Boomers who are becoming patients [Kni02]. This project is to develop software tools that will use the latest pertinent clinical and imaging knowledge from the medical literature and domain experts and make it WEB-available to physicians to support their medical decisions so they can make faster and more accurate diagnosis and avoid misdiagnosis and patient mismanagement.


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 216.08K | Year: 2011

DESCRIPTION (provided by applicant): Today's cardiac imaging field requires diagnosticians to master an ever-expanding knowledge base (KB) while the time to master this knowledge, apply it to specific tasks and reimbursement are steadily shrinking. These constraints pose a serious healthcare problem that inevitably leads to physician's errors. Thus new tools are required to assist physicians to timely apply comprehensive, up-to-date objective knowledge and the available patient data to specific clinical problems. The long-term objective of our Fast-Track proposal is to improve the care of cardiac patients and reduce the cost of cardiac image interpretation by developing new tools for a WEB-accessible cardiac toolbox that provides decision support to increasethe accuracy of detecting coronary heart disease (CHD). Specifically, we propose a WEB-based system where acquired ECG-gated myocardial perfusion SPECT (MPS) raw images are uploaded to be automatically reconstructed and analyzed to extract regional quantitative parameters of myocardial perfusion and function. These parameters are converted to certainty factors of abnormality and submitted to an imaging decision support system (DSS) that is continuously updated with the latest scientific/clinical knowledgeto reach an impression of the patient's heart status. These conclusions reached by the DSS and justifications for each conclusion are used to automatically generate a web-based structured report for the diagnostician to easily review, learn from the justifications, and either modify and/or approve for optimal accuracy of the diagnosis and prognosis of CHD. Specifically we propose to: 1) develop a novel left ventricular (LV) quantitative algorithm that automatically extracts parameters of left LV regional perfusion and function used to diagnose CHD; 2) develop the LV expert (LVX) DSS and 3) design and implement the LV quantification and DSS algorithms using the .net platform so that they can be integrated into our Syntermed infrastructure and deployed over the web and/or used as conventional stand- alone work-stations. In Phase I we will develop a proof-of-principle system where LV perfusion information from MPS studies is analyzed and DSS interpreted for automatic report generation and physician review. In Phase II, the system will be: a) extended to include quantification and DSS of myocardial function, ischemia, viability and clinical risk factors, b) extended to include a methodology to continuously update LVX's KB, c) automated to link all the reconstruction, processing, quantification, interpretation, and reporting applications, and d) deployed in .net on the web with database and eCommerce accounting capability. Using this process we expect to confirm our primary hypothesis that diagnosticians using our decision support will provide a faster, more accurate diagnosis and prognosis of CHD than those provided by the same diagnosticians without the aid of this system. The system will be commercialized using Syntermed's successful strategy of other Emory software through: 1) licensing to major instrumentation manufacturers, 2) direct sales to clients that use PC workstations and 3) per WEB-access fee using the existing Syntermed Live network. PUBLIC HEALTH RELEVANCE: Physicians are required to master an ever-expanding knowledge base and take into account an ever increasing amount of patient-specific clinical information while time available to master this knowledge base and apply it to specific tasks is steadily shrinking. There is also an increasing shortage of cardiac diagnosticians [Fye04] who primarily interpret nuclear cardiology studies and an ever increasing number of aging Baby Boomers who are becoming patients [Kni02]. This project is to develop software tools that will use the latest pertinent clinical and imaging knowledge from the medical literature and domain experts and make it WEB-available to physicians to support their medical decisions so they can make faster and more accurate diagnosis and avoid misdiagnosis and patient mismanagement.


Patent
Emory University, Mercer University and Union College at Schenectady | Date: 2015-07-08

This disclosure relates to solenopsin derivatives, pharmaceutical compositions, and therapeutic uses related thereto. In certain embodiments, the disclosure relates to compounds of the following formula:


Patent
Emory University, Union College at Schenectady and Mercer University | Date: 2014-05-07

This disclosure relates to solenopsin derivatives, pharmaceutical compositions, and therapeutic uses related thereto. In certain embodiments, the disclosure relates to compounds of the following formula:


Patent
Gilead Pharmasset Llc, Beth Israel Deaconess Medical Center and Emory University | Date: 2013-12-04

A method and composition for the treatment, prevention and/or prophylaxis of a host, and in particular, a human, infected with Epstein-Barr virus (EBV), is provided that includes administering an effective amount of a 5-substituted uracil nucleoside or its pharmaceutically acceptable salt or prodrug, optionally in a pharmaceutically acceptable diluent or excipient.


Linzer D.A.,Emory University | Lewis J.B.,University of California at Los Angeles
Journal of Statistical Software | Year: 2011

poLCA is a software package for the estimation of latent class and latent class regression models for polytomous outcome variables, implemented in the R statistical computing environment. Both models can be called using a single simple command line. The basic latent class model is a finite mixture model in which the component distributions are assumed to be multi-way cross-classification tables with all variables mutually independent. The latent class regression model further enables the researcher to estimate the effects of covariates on predicting latent class membership. poLCA uses expectation-maximization and Newton-Raphson algorithms to find maximum likelihood estimates of the model parameters.


Meiklejohn C.D.,University of Rochester | Tao Y.,Emory University
Trends in Ecology and Evolution | Year: 2010

Chromosomal sex determination systems create the opportunity for the evolution of selfish genetic elements that increase the transmission of one sex chromosome at the expense of its homolog. Because such selfish elements on sex chromosomes can reduce fertility and distort the sex ratio of progeny, unlinked suppressors are expected to evolve, bringing different regions of the genome into conflict over the meiotic transmission of the sex chromosomes. Here we argue that recurrent genetic conflict over sex chromosome transmission is an important evolutionary force that has shaped a wide range of seemingly disparate phenomena including the epigenetic regulation of genes expressed in the germline, the distribution of genes in the genome, and the evolution of hybrid sterility between species. © 2009 Elsevier Ltd. All rights reserved.


Puetz T.W.,Emory University | Herring M.P.,University of Alabama at Birmingham
American Journal of Preventive Medicine | Year: 2012

Context: Exercise-induced improvements in cancer-related fatigue may be moderated differentially in patients during and following treatment. These effects have not been reviewed systematically. In accordance with PRISMA guidelines, the population effect size for exercise training on cancer-related fatigue during and following treatment was estimated and the extent to which the effect is differentiated across the time course of treatment and recovery was determined. Evidence acquisition: Articles published before August 2011 were retrieved using Google Scholar, MEDLINE, PsycINFO, PubMed, and Web of Science databases. Seventy studies involving 4881 cancer patients during or following treatment were selected. Articles included a cancer-related fatigue outcome measured at baseline and post-intervention and randomized allocation to exercise or non-exercise comparison. From August to October 2011, Hedges' d effect sizes were computed, study quality was evaluated, and random effects models were used to estimate sampling error and population variance. Evidence synthesis: Exercise significantly reduced cancer-related fatigue by a mean effect Δ (95% CI) of 0.32 (0.21, 0.43) and 0.38 (0.21, 0.54) during and following cancer treatment, respectively. During treatment, patients with lower baseline fatigue scores and higher exercise adherence realized the largest improvements. Following treatment, improvements were largest for trials with longer durations between treatment completion and exercise initiation, trials with shorter exercise program lengths, and trials using wait-list comparisons. Conclusions: Exercise reduces cancer-related fatigue among patients during and following cancer treatment. These effects are moderated differentially over the time course of treatment and recovery. Exercise has a palliative effect in patients during treatment and a recuperative effect post-treatment. © 2012 American Journal of Preventive Medicine.


Middlekauff H.R.,University of California at Los Angeles | Park J.,Emory University | Moheimani R.S.,University of California at Los Angeles
Journal of the American College of Cardiology | Year: 2014

This review summarizes the detrimental effects of cigarette and noncigarette emission exposure on autonomic function, with particular emphasis on the mechanisms of acute and chronic modulation of the sympathetic nervous system. We propose that the nicotine and fine particulate matter in tobacco smoke lead to increased sympathetic nerve activity, which becomes persistent via a positive feedback loop between sympathetic nerve activity and reactive oxidative species. Furthermore, we propose that baroreflex suppression of sympathetic activation is attenuated in habitual smokers; that is, the baroreflex plays a permissive role, allowing sympathoexcitation to occur without restraint in the setting of increased pressor response. This model is also applicable to other nontobacco cigarette emission exposures (e.g., marijuana, waterpipes [hookahs], electronic cigarettes, and even air pollution). Fortunately, emerging data suggest that baroreflex sensitivity and autonomic function may be restored after smoking cessation, providing further evidence in support of the health benefits of smoking cessation. © 2014 American College of Cardiology Foundation.


O'Reilly Zwald F.,Emory University | Brown M.,University of Rochester
Journal of the American Academy of Dermatology | Year: 2011

Skin cancer is the most frequent malignancy in organ transplant recipients, 95% of which are nonmelanoma skin cancer, especially squamous cell and basal cell carcinomas. This paper also discusses the incidence of other tumors (eg, melanoma, Merkel cell carcinoma, and Kaposi sarcoma) that are also increased in organ transplant patients compared to the general population. Part I of this two-part series describes the latest data concerning the epidemiologic and pathogenic aspects of nonmelanoma skin cancer development in solid organ transplant recipients. This review also highlights the concept of "field cancerization," represented by extensive areas of actinic damage and epidermal dysplasia, which accounts for increased risk of aggressive skin cancer development in susceptible patients. © 2010 by the American Academy of Dermatology, Inc.


Unemo M.,Örebro University | Shafer W.M.,Emory University | Shafer W.M.,Veterans Affairs Medical Center
Clinical Microbiology Reviews | Year: 2014

Neisseria gonorrhoeae is evolving into a superbug with resistance to previously and currently recommended antimicrobials for treatment of gonorrhea, which is a major public health concern globally. Given the global nature of gonorrhea, the high rate of usage of antimicrobials, suboptimal control and monitoring of antimicrobial resistance (AMR) and treatment failures, slow update of treatment guidelines in most geographical settings, and the extraordinary capacity of the gonococci to develop and retain AMR, it is likely that the global problem of gonococcal AMR will worsen in the foreseeable future and that the severe complications of gonorrhea will emerge as a silent epidemic. By understanding the evolution, emergence, and spread of AMR in N. gonorrhoeae, including its molecular and phenotypic mechanisms, resistance to antimicrobials used clinically can be anticipated, future methods for genetic testing for AMR might permit region-specific and tailor- made antimicrobial therapy, and the design of novel antimicrobials to circumvent the resistance problems can be undertaken more rationally. This review focuses on the history and evolution of gonorrhea treatment regimens and emerging resistance to them, on genetic and phenotypic determinants of gonococcal resistance to previously and currently recommended antimicrobials, including biological costs or benefits; and on crucial actions and future advances necessary to detect and treat resistant gonococcal strains and, ultimately, retain gonorrhea as a treatable infection. © 2014, American Society for Microbiology. All Rights Reserved.


Min J.K.,Cornell University | Shaw L.J.,Emory University | Berman D.S.,Cedars Sinai Medical Center
Journal of the American College of Cardiology | Year: 2010

In the past 5 years since the introduction of 64-detector row cardiac computed tomography angiography (CCTA), there has been an exponential growth in the quantity of scientific evidence to support the feasibility of its use in the clinical evaluation of individuals with suspected coronary artery disease (CAD). Since then, there has been considerable debate as to where CCTA precisely fits in the algorithm of evaluation of individuals with suspected CAD. Proponents of CCTA contend that the quality and scope of the available evidence to date support the replacement of conventional methods of CAD evaluation by CCTA, whereas critics assert that clinical use of CCTA is not yet adequately proven and should be restricted, if used at all. Coincident with the scientific debate underlying the clinical utility of CCTA, there has developed a perception by many that the rate of growth in cardiac imaging is disproportionately high and unsustainable. In this respect, all noninvasive imaging modalities and, in particular, more newly introduced ones, have undergone a higher level of scrutiny for demonstration of clinical and economic effectiveness. We herein describe the latest available published evidence supporting the potential clinical and cost efficiency of CCTA, drawing attention not only to the significance but also the limitations of such studies. These points may trigger discussion as to what future studies will be both necessary and feasible for determining the exact role of CCTA in the workup of patients with suspected CAD. © 2010 American College of Cardiology Foundation.


Chassaing B.,Georgia State University | Koren O.,Bar - Ilan University | Goodrich J.K.,Cornell University | Poole A.C.,Cornell University | And 3 more authors.
Nature | Year: 2015

The intestinal tract is inhabited by a large and diverse community of microbes collectively referred to as the gut microbiota. While the gut microbiota provides important benefits to its host, especially in metabolism and immune development, disturbance of the microbiota-host relationship is associated with numerous chronic inflammatory diseases, including inflammatory bowel disease and the group of obesity-associated diseases collectively referred to as metabolic syndrome. A primary means by which the intestine is protected from its microbiota is via multi-layered mucus structures that cover the intestinal surface, thereby allowing the vast majority of gut bacteria to be kept at a safe distance from epithelial cells that line the intestine. Thus, agents that disrupt mucus-bacterial interactions might have the potential to promote diseases associated with gut inflammation. Consequently, it has been hypothesized that emulsifiers, detergent-like molecules that are a ubiquitous component of processed foods and that can increase bacterial translocation across epithelia in vitro, might be promoting the increase in inflammatory bowel disease observed since the mid-twentieth century. Here we report that, in mice, relatively low concentrations of two commonly used emulsifiers, namely carboxymethylcellulose and polysorbate-80, induced low-grade inflammation and obesity/metabolic syndrome in wild-type hosts and promoted robust colitis in mice predisposed to this disorder. Emulsifier-induced metabolic syndrome was associated with microbiota encroachment, altered species composition and increased pro-inflammatory potential. Use of germ-free mice and faecal transplants indicated that such changes in microbiota were necessary and sufficient for both low-grade inflammation and metabolic syndrome. These results support the emerging concept that perturbed host-microbiota interactions resulting in low-grade inflammation can promote adiposity and its associated metabolic effects. Moreover, they suggest that the broad use of emulsifying agents might be contributing to an increased societal incidence of obesity/metabolic syndrome and other chronic inflammatory diseases. © 2015 Macmillan Publishers Limited.


Garrod R.T.,Cornell University | Widicus Weaver S.L.,Emory University
Chemical Reviews | Year: 2013

The past decade has seen great advances in the simulation of hot-core chemistry. Significant efforts have been made to understand the formation of complex organic molecules in starforming regions, in light of the apparent deficiency of gas-phase processes. As a result, a greater emphasis has been placed on the detailed treatment of grain-surface and bulk-ice processes and their interactions with the gas phase. Chemical kinetics models based on rate equations can be used to examine the complex chemistry of hot-core regions, and great advances have been made in the implementation of Monte Carlo simulations, although, in both cases, the treatment of detailed physical structure within the dust-grain ice mantles remains a challenge. Sophisticated models are now routinely used to combine gasphase, grain-surface, and bulk-ice chemical treatments, while their integration with more realistic physical models of specific sources has become important for the simulation of molecular emission spectra. Additionally, chemical networks used for hot-core models now incorporate chemistry of direct biological significance, including formation mechanisms for amino acids and sugars. The results of these modeling studies can be directly compared to the complexity observed with the newest generation of observational instruments, which provide quantitative information that can be benchmarked against the models. Despite these successes, there remains a large gap between current modeling capabilities and the objective of a full, comprehensive model of star-formation environments. Chemical reaction networks are far from complete, and many of the parameters therein are educated guesses at best, while detailed treatments of ice structure are yet in their infancy. Likewise, physical models that properly account for the hydrodynamical processes occurring in hot cores have not yet been coupled with the more comprehensive chemical networks necessary to examine the chemistry of star-forming regions; indeed, the dynamics of high-mass star formation are currently a matter of considerable debate. Nonetheless, the results from the current chemical models of hot cores are valuable tools for comparison with observations; the simulations agree well with observations for the most abundant molecular species, and advances in the translation of chemical model results into directly observable quantities will allow more specific predictions to be made for individual sources. In the coming years, models of hot-core chemistry will need to advance and expand in several different directions, both to address current challenges and to incorporate new information from high-quality astronomical observations and chemical experiments. However, one might also expect that these advances will place yet greater technical demands on the computational models, some of which already operate close to the limits of feasible run times. The breadth of chemical and physical processes considered, and the resultant constraints placed upon the models, will require that astrochemists not be too dogmatic in the demand that every part of a model be stateof- the-art; even with the best computers in the world, such models of astrophysical sources will never be entirely comprehensive. The choice of whether detailed chemistry, detailed ice structure, detailed dynamics, and/or detailed radiative transfer are used must depend on the choice of problem and the abilities of individual scientists to best exploit their own capabilities. However, in spite of the inevitable incompleteness of astrochemical models, the past few years have demonstrated that the models can reliably reproduce many facets of the observational data, that they can explain the microscopic processes occurring on astronomical scales, and that they can be used to guide future observational strategies for hot-core sources.


Patent
Emory University, The Research Foundation Of State Of New York and Woodward - Clyde Group | Date: 2015-01-27

The disclosure relates to novel C4 and C6 substituted androst-4-ene diones as well as andros-1,4-diene diones and derivatives thereof, their process of preparation, pharmaceutical compounds containing them, and the use of said compounds for the treatment of hormone-related disorders in mammals. This includes hormone-dependent cancers, particularly those caused by elevated levels of estrogen and its intermediates. These compounds can also be used in the treatment of other hormone-related disorders, including benign prostatic hyperplasia, cardiovascular disease, and neurodegenerative disorders.


Patent
Emory University, Woodward - Clyde Group and The Research Foundation Of State Of New York | Date: 2011-04-07

The disclosure relates to novel C4 and C6 substituted androst-4-ene diones as well as andros-1,4-diene diones and derivatives thereof, their process of preparation, pharmaceutical compounds containing them, and the use of said compounds for the treatment of hormone-related disorders in mammals. This includes hormone-dependent cancers, particularly those caused by elevated levels of estrogen and its intermediates. These compounds can also be used in the treatment of other hormone-related disorders, including benign prostatic hyperplasia, cardiovascular disease, and neurodegenerative disorders.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: STTR | Phase: Phase II | Award Amount: 1.50M | Year: 2015

DESCRIPTION provided by applicant Stroke is a leading cause of human death and disability in the United States while clinical therapy for acute stroke is limited and unsatisfactoy The many failures in clinical trials strongly endorse the idea that to battle this multifaceted bran disorder novel strategies that target multiple cell types and different mechanisms are needed to achieve therapeutic effects in humans Among a few potential treatments of this approach hypothermia has shown remarkable neuroprotective up to effects against brain ischemia in animal and human studies Unfortunately available physical cooling techniques are ineffectual and often impractical Thus pharmacological compounds that can be utilized for hypothermia therapy have long been sought for the treatment of stroke It is expected that using pharmacologically induced hypothermia PIH the treatment can be initiated much earlier while even a small oC decrease in body temperature during early hours after stroke should prevent detrimental post stroke hyperthermia A mild to moderate hypothermia oC reduction will delay the evolution of ischemic injury and may extend the therapeutic window for other interventions such as the only FDA approved thrombolytic treatment using recombinant tissue plasminogen activator tPA In our Phase I investigation we demonstrated hypothermic effects of several novel neurotensin receptor NTR compounds and their marked neuroprotective effects against brain damage induced by ischemic stroke hemorrhage stroke and traumatic brain injury TBI in mouse and rat models We have identified two leading compounds for moving to the proposed Phase II investigation Our pilot study has also demonstrated the hypothermic effect of the leading compounds in non human primates In the Phase II study Specific Aim will test our hypothesis that the PIH therapy as a possible on site acute treatment is not only neuroprotective but also can prolong the therapeutic window of tPA treatment We will investigate this possibility in an embolic stroke model of mice that mimics clinical situations Specific Aim will identify possible side effects and toxicity of our compouns in order to confirm their suitability for further preclinical and clinical development and complete experiments necessary for IND preparation Specific Aim will examine the hypothermic effect of the selected NTR derivatives in monkeys to understand the dose response relationship and determine the duration and rewarming kinetics of their hypothermic effects MRI imaging in monkeys will provide valuable data for the drug effect on brain temperature cerebral blood flow the blood brain barrier gray and white matter changes and hemorrhage transformation after PIH It is expected that or more leading compounds will be validated for a future study in stroke monkey models and clinical trials in humans The translational research is pursued by a group of scientists with complementary expertise in basic and pre clinical stroke fields and will provide compelling evidence for a potential breakthrough in clinical stroke therapy PUBLIC HEALTH RELEVANCE Stroke is the third leading cause of human death and disability in the US To develop a clinically effective and feasible hypothermia therapy our Phase I study has synthesized and identified novel leading neurotensin receptor I derivatives for a novel pharmacological hypothermia therapy for ischemic and hemorrhage stroke This Phase II proposal is to improve the therapeutic window of tPA using pharmacological hypothermia and to evaluate the hypothermic effect in non human primate for clinical translation


Grant
Agency: Department of Defense | Branch: Defense Advanced Research Projects Agency | Program: STTR | Phase: Phase I | Award Amount: 98.99K | Year: 2013

Having demonstrated the feasibility of fMRI in awake dogs, we are now ready to move forward with a program aimed at extending this technology to the point that a reliable training regimen can be deployed to a wide range of service and working dogs. The ad


Grant
Agency: Department of Defense | Branch: Defense Advanced Research Projects Agency | Program: STTR | Phase: Phase II | Award Amount: 998.81K | Year: 2014

In Phase II, we will partner with CCI to deploy our fMRI protocol in 50 of their dogs entering advanced training, and determine neural biomarkers that predict successful completion of the course and placement with a human. Because MRI is expensive and lab


Choisy M.,IRD Montpellier | De Roode J.C.,Emory University
American Naturalist | Year: 2010

Mixed-genotype parasite infections are common in nature. Theoretical studies analyze the effects of such infections over evolutionary time and predict an increase in virulence due to the competitive advantage of virulent parasites. In contrast, experimental studies compare the overall virulence of mixed and single infections within one generation. Although these within-generation comparisons have limited relevance to existing theory, they demonstrate that within-host parasite interactions are not restricted to competition for resources, as envisaged by theory. Instead, mixed infections may result in phenotypic changes in growth rate or impaired immune clearance. Developing and using a two-parasite epidemiological model with recovery, we confirm that within-host competition for resources selects for higher virulence. However, parasite phenotypic plasticity and impaired host immunity can select for lower virulence. Because these latter two mechanisms would be detected by experimentalists as an increase in pathology, our results warn against the temptation to draw inferences on virulence evolution on the basis of single-generation experiments. © 2010 by The University of Chicago.


McMahon D.G.,Vanderbilt University | Iuvone P.M.,Emory University | Tosini G.,Morehouse School of Medicine
Progress in Retinal and Eye Research | Year: 2014

The retinal circadian system represents a unique structure. It contains a complete circadian system and thus the retina represents an ideal model to study fundamental questions of how neural circadian systems are organized and what signaling pathways are used to maintain synchrony of the different structures in the system. In addition, several studies have shown that multiple sites within the retina are capable of generating circadian oscillations. The strength of circadian clock gene expressionand the emphasis of rhythmic expression are divergent across vertebrate retinas, with photoreceptors as the primary locus of rhythm generation in amphibians, while in mammals clock activity is most robust in the inner nuclear layer. Melatonin and dopamine serve as signaling molecules to entrain circadian rhythms in the retina and also in other ocular structures. Recent studies have also suggested GABA as an important component of the system that regulates retinal circadian rhythms. These transmitter-driven influences on clock molecules apparently reinforce the autonomous transcription-translation cycling of clock genes. The molecular organization of the retinal clock is similar to what has been reported for the SCN although inter-neural communication among retinal neurons that form the circadian network is apparently weaker than those present in the SCN, and it is more sensitive to genetic disruption than the central brain clock. The melatonin-dopamine system is the signaling pathway that allows the retinal circadian clock to reconfigure retinal circuits to enhance light-adapted cone-mediated visual function during the day and dark-adapted rod-mediated visual signaling at night. Additionally, the retinal circadian clock also controls circadian rhythms in disk shedding and phagocytosis, and possibly intraocular pressure. Emerging experimental data also indicate that circadian clock is also implicated in the pathogenesis of eye disease and compelling experimental data indicate that dysfunction of the retinal circadian system negatively impacts the retina and possibly the cornea and the lens. © 2013 Elsevier Ltd.


Alizon S.,IRD Montpellier | de Roode J.C.,Emory University | Michalakis Y.,IRD Montpellier
Ecology Letters | Year: 2013

Infections that consist of multiple parasite strains or species are common in the wild and are a major public health concern. Theory suggests that these infections have a key influence on the evolution of infectious diseases and, more specifically, on virulence evolution. However, we still lack an overall vision of the empirical support for these predictions. We argue that within-host interactions between parasites largely determine how virulence evolves and that experimental data support model predictions. Then, we explore the main limitation of the experimental study of such 'mixed infections', which is that it draws conclusions on evolutionary outcomes from studies conducted at the individual level. We also discuss differences between coinfections caused by different strains of the same species or by different species. Overall, we argue that it is possible to make sense out of the complexity inherent to multiple infections and that experimental evolution settings may provide the best opportunity to further our understanding of virulence evolution. © 2013 Blackwell Publishing Ltd/CNRS.


Zhang H.,Zhejiang University | Jin M.,Xi'an University of Science and Technology | Xia Y.,Emory University
Chemical Society Reviews | Year: 2012

Bimetallic nanocrystals consisting of two distinct metals such as Pd and Pt are attractive for a wide variety of catalytic and electrocatalytic applications as they can exhibit not only a combination of the properties associated with both metals but also enhancement or synergy due to a strong coupling between the two metals. With Pd as the base metal, many methods have recently been demonstrated for the synthesis of Pd-Pt bimetallic nanocrystals having a wide variety of different structures in the form of alloys, dendrites, core-shells, multi-shells, and monolayers. In this tutorial review, we begin with a brief discussion on the possible structures of Pd-Pt bimetallic nanocrystals, followed by an account of recent progress on synthetic approaches to such nanocrystals with controlled structures, shapes and sizes. In addition to the experimental procedures and mechanistic studies, a number of examples are presented to highlight the use of such bimetallic nanocrystals as catalysts or electrocatalysts for various applications with enhanced performance relative to their monometallic counterparts. © 2012 The Royal Society of Chemistry.


Patent
Rutgers University and Emory University | Date: 2014-05-01

Methods of producing and using Hepatitis C virus (HCV) eE2 polypeptides are described.


Ju T.,Emory University | Otto V.I.,ETH Zurich | Cummings R.D.,Emory University
Angewandte Chemie - International Edition | Year: 2011

Glycoproteins in animal cells contain a variety of glycan structures that are added co- and/or posttranslationally to proteins. Of over 20 different types of sugar-amino acid linkages known, the two major types are N-glycans (Asn-linked) and O-glycans (Ser/Thr-linked). An abnormal mucin-type O-glycan whose expression is associated with cancer and several human disorders is the Tn antigen. It has a relatively simple structure composed of N-acetyl-D- galactosamine with a glycosidic αlinkage to serine/threonine residues in glycoproteins (GalNAcα1-O-Ser/Thr), and was one of the first glycoconjugates to be chemically synthesized. The Tn antigen is normally modified by a specific galactosyltransferase (T-synthase) in the Golgi apparatus of cells. Expression of active T-synthase is uniquely dependent on the molecular chaperone Cosmc, which is encoded by a gene on the X chromosome. Expression of the Tn antigen can arise as a consequence of mutations in the genes for T-synthase or Cosmc, or genes affecting other steps of O-glycosylation pathways. Because of the association of the Tn antigen with disease, there is much interest in the development of Tn-based vaccines and other therapeutic approaches based on Tn expression. An abnormal sugar: The expression of the abnormal O-glycan called Tn antigen (see structure) in animal glycoproteins typically represents a disease condition. This Review discusses a broad range of chemical and biological studies on the Tn antigen that could lead to new diagnostics and therapeutics. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Brosnan S.F.,Georgia State University | De Waal F.B.M.,Emory University
Science | Year: 2014

The human sense of fairness is an evolutionary puzzle. To study this, we can look to other species, in which this can be translated empirically into responses to reward distribution. Passive and active protest against receiving less than a partner for the same task is widespread in species that cooperate outside kinship and mating bonds. There is less evidence that nonhuman species seek to equalize outcomes to their own detriment, yet the latter has been documented in our closest relatives, the apes. This reaction probably reflects an attempt to forestall partner dissatisfaction with obtained outcomes and its negative impact on future cooperation.We hypothesize that it is the evolution of this response that allowed the development of a complete sense of fairness in humans, which aims not at equality for its own sake but for the sake of continued cooperation.


Moreno-de-Luca A.,Genomic Health | Ledbetter D.H.,Genomic Health | Martin C.L.,Emory University
The Lancet Neurology | Year: 2012

Cerebral palsy-the most common physical disability of childhood-is a clinical diagnosis encompassing a heterogeneous group of neurodevelopmental disorders that cause impairments of movement and posture that persist throughout life. Despite being commonly attributed to a range of environmental factors, particularly birth asphyxia, the specific cause of cerebral palsy remains unknown in most individuals. A growing body of evidence suggests that cerebral palsy is probably caused by multiple genetic factors, similar to other neurodevelopmental disorders such as autism and intellectual disability. Recent advances in next-generation sequencing technologies have made possible rapid and cost-effective sequencing of the entire human genome. Novel cerebral palsy genes will probably be identified as more researchers and clinicians use this approach to study individuals with undiagnosed neurological disorders. As our knowledge of the underlying pathophysiological mechanisms of cerebral palsy increases, so will the possibility of developing genomically guided therapeutic interventions. © 2012 Elsevier Ltd.


Boehm T.,Max Planck Institute of Immunobiology and Epigenetics | McCurley N.,Emory University | Sutoh Y.,Hokkaido University | Schorpp M.,Max Planck Institute of Immunobiology and Epigenetics | And 2 more authors.
Annual Review of Immunology | Year: 2012

Lampreys and hagfish are primitive jawless vertebrates capable of mounting specific immune responses. Lampreys possess different types of lymphocytes, akin to T and B cells of jawed vertebrates, that clonally express somatically diversified antigen receptors termed variable lymphocyte receptors (VLRs), which are composed of tandem arrays of leucine-rich repeats. The VLRs appear to be diversified by a gene conversion mechanism involving lineage-specific cytosine deaminases. VLRA is expressed on the surface of T-like lymphocytes; B-like lymphocytes express and secrete VLRB as a multivalent protein. VLRC is expressed by a distinct lymphocyte lineage. VLRA-expressing cells appear to develop in a thymus-like tissue at the tip of gill filaments, and VLRB-expressing cells develop in hematopoietic tissues. Reciprocal expression patterns of evolutionarily conserved interleukins and chemokines possibly underlie cell-cell interactions during an immune response. The discovery of VLRs in agnathans illuminates the origins of adaptive immunity in early vertebrates. © 2012 by Annual Reviews. All rights reserved.


Patent
Georgia State University, Emory University and Children's Healthcare Of Atlanta | Date: 2013-07-10

Rhein analogues that exhibit anti-proliferative activity, particular against cancer cells, are described herein. In some embodiments, the compounds contain a flat or planar ring system. Such rings system by facilitate non-covalent binding of the compounds to the DNA complex, such as by intercalation. In some embodiment, the compounds contain a flat or planar ring system as described above and one or more substituents which are alkylating moieties, electrophilic groups or Michael acceptors or groups which contain one or more alkylating moieties, electrophilic groups and/or Michael acceptors. The compounds described herein can also contain one more functional groups to improve the solubility of the compounds.


Patent
Emory University and Beth Israel Deaconess Medical Center | Date: 2013-10-11

This disclosure relates to materials fabricated from collagen and uses relates thereto. Typically, layers of collagen are stretched during a curing period and optionally coated or impregnated with an elastin like protein. In certain embodiments, these materials can be used in tissue repair or arranged into cylinders and utilized as a prosthetic vascular graft.


Patent
Georgia State University and Emory University | Date: 2011-08-24

The invention relates to the innate immune pathway and anti-inflammatory molecules with therapeutic properties. In some embodiments, the invention relates to compounds and pharmaceutical compositions and methods of using the compounds and compositions to treat inflammatory diseases including inflammation associated with auto-immune diseases.


Patent
Emory University and Beth Israel Deaconess Medical Center | Date: 2014-05-23

This disclosure relates to selectin inhibitors, compositions, and methods related thereto. In certain embodiments, the disclosure relates to glycopeptides that contain one more modified amino acids conjugated to a saccharide or polysaccharide. In certain embodiments, the disclosure relates to uses of the glycopeptides as anti-inflammatory, anti-thrombotic, or anti-metastatic agents.


Patent
Cedars Sinai Medical Center, Emory University and Georgia State University | Date: 2016-01-26

The present invention describes small molecule ligand-drug conjugates and methods of using the small molecule ligand-drug conjugates for targeted treatment of cancer in a patient in need thereof. Further described are methods of sterilizing circulating tumor cells and determining drug concentration in cancer tissue.


Patent
INC Research and Emory University | Date: 2012-07-19

The disclosure relates to TAK1 inhibitors, compositions, and uses related thereto. In certain embodiments, the disclosure relates to compounds of formula (I), pharmaceutical compositions having a compound of formula (I), and methods of treating or preventing cancer by administering an effective amount of a pharmaceutical composition having a compound of formula (I) to a subject in need thereof.


Patent
Emory University and Georgia State University | Date: 2015-07-31

This invention relates generally to cyanine-containing compounds; pharmaceutical compositions comprising cyanine-containing compounds; and methods of using cyanine-containing compounds for cancer cell imaging, cancer cell growth inhibition, and detecting cancer cells, for example. Compounds of the invention are preferentially taken up by cancer cells as compared to normal cells. This allows many uses in the cancer treatment, diagnosis, tracking and imaging fields.


Patent
Georgia State University and Emory University | Date: 2011-04-20

Inhibitors of the Hypoxia Inducible Factor (HIF) and angiogenesis and their methods of use including the treatment of cancer, hypoxia related pathologies, disorders leading to ischemia, for example stroke and ischemic heart disease, and non-cancerous angiogenic diseases are provided.


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 883.73K | Year: 2011

DESCRIPTION (provided by applicant): Stroke is the third leading cause of death in the United States. In spite of intensive investigations, clinical therapies for treating acute stroke patients remain limited and unsatisfactory. There are consistent animal and human data that mild to moderate hypothermia (reducing body temperature to 32-34oC) is generally safe and improves outcome after brain ischemia even when initiated hours after ischemia occurs. Different from most neuroprotective drugs that usuallytarget only one mechanism, hypothermia therapy has the advantage of global protection on all cell types and tissues in both gray and white matters. Several important limitations, however, have precluded the widespread use of hypothermia therapy in strokepatients. The major obstruction is that existing forced cooling techniques are ineffectual and/or impractical in clinical settings. To overcome the shortcomings of current methods, the concept of regulated hypothermia induced by pharmacological means has been proposed as a new strategy in hypothermia therapy; although there have been no drugs that can be used for regulated hypothermia therapy. To this end, we have synthesized and tested novel neurotensin(NT)[8-13] derivatives, such as ABS201 and ABS601,that are potent hypothermic compounds and have dramatic neuroprotective activity in animal stroke models. These NT compounds show no toxic effects, attenuate infarct formation by nearly 50% even when administered 45 min after the onset of ischemia. The mechanism of protection appears to involve their ability to cross the blood brain barrier, bind to the NT receptor as agonists, and reduce the set point of the central temperature control so that systemic hypothermia in the absence of shivering is promoted. It is thus hypothesized that NT/ABS derivatives have strong potential of being developed for regulated hypothermia therapy. In the Phase I study, we will compare the hypothermic potency of six NT/ABS derivatives. Two leading compounds without detectableside effects will be tested and compared for their neuroprotection in aged rats of two stroke models of transient and permanent ischemia. This translational investigation is not intended to delineate the mechanism of hypothermia protection, which has beenextensively studied so far. Rather, we aim to demonstrate the feasibility of the chemical-induced hypothermia therapy and move to more systematic preclinical examinations of a Phase II investigation. Our ultimate goal is to advance the drug-induced hypothermia therapy to the clinic. PUBLIC HEALTH RELEVANCE: Ischemic stroke is the third leading cause of human death and disability in the US. This investigation will develop a chemical-induced hypothermia therapy for stroke patients. The comprehensive neuroprotective effects of clinically feasible hypothermia therapy will be studied in two different stroke models, which will facilitate the translation of the therapy to clinical applications.


Patent
Emory University and Georgia State University | Date: 2015-03-12

This invention relates generally to cyanine-containing compounds; pharmaceutical compositions comprising cyanine-containing compounds; and methods of using cyanine-containing compounds for cancer cell imaging, cancer cell growth inhibition, and detecting cancer cells, for example. Compounds of the invention are preferentially taken up by cancer cells as compared to normal cells. This allows many uses in the cancer treatment, diagnosis, tracking and imaging fields.


Patent
Georgia State University and Emory University | Date: 2014-05-02

In one embodiment, a system and method for assisting a physician with a hospital discharge decision pertain to collecting patient data from a patient under consideration who is staying at a hospital, estimating a mathematical probability of the patient under consideration being readmitted to the hospital within a predetermined amount of time if the patient under consideration were discharged on that day, the collected patient data and patient data collected from a population of former hospital patients who had previously been discharged and whose readmission status is known, and providing information to the physician that assists the physician in deciding whether or not to discharge the patient under consideration, the information being based upon the results of the mathematical probability estimate.


Patent
Emory University and Beth Israel Deaconess Medical Center | Date: 2012-03-12

The present invention relates to antibodies specific for a particular epitope on CD40 and antibodies that bind CD40 and have particular functional characteristics. The present invention also relates to fragments of these antibodies, uses of the antibodies for reduction or treatment of transplant rejection and graft-versus-host disease, and methods for making the antibodies.


Yang Z.,Emory University | Zhang N.,University of Massachusetts Amherst
Medical Care | Year: 2014

BACKGROUND: The obesity rate among the elderly long-term care (LTC) residents in the United States is increasing rapidly. However, there is a paucity of research investigating the burden of obesity on LTC and Medicaid financing. The purpose of this study is to fill the knowledge gap by estimating the burden of overweight and obesity on LTC and Medicaid financing. METHODS: Using nationally representative Cost and Use Files of Medicare Current Beneficiary Survey from 1997 to 2005, we used 2-part model and cohort-based simulation to evaluate the effect of overweight and obesity on LTC days and Medicaid expenditures across the lifespan among the current elderly population. Combining the per capita estimates with 2010 census, we project future aggregate burden of obesity on LTC demand and Medicaid cost among baby boomers. RESULTS: Obesity and related chronic diseases lead to higher probability to enter LTC facility in a younger age, more LTC days before death, and higher lifetime LTC cost reimbursed by Medicaid. However, such effect is only statistically significant among women, not significant among men. At the population level, we project that overweight and obesity will induce 1.3 billion or more LTC patient days and $68 billion or more Medicaid costs (in 2012 value) among baby boomers. CONCLUSIONS: Overweight and obesity among the elderly will bring tremendous burden to LTC providers and Medicaid. Policy makers should keep the burden of obesity on LTC in mind when planning LTC and Medicaid policy reform. Copyright © 2014 by Lippincott Williams & Wilkins.


Hagan L.M.,Emory University | Sulkowski M.S.,Johns Hopkins University | Schinazi R.F.,Emory University
Hepatology | Year: 2014

Treatment guidance for chronic hepatitis C (CHC) released by the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) offers two options for interferon (IFN)-ineligible/intolerant individuals with genotype 1 infection: sofosbuvir/ribavirin (SOF/RBV) for 24 weeks or sofosbuvir/simeprevir (SOF/SMV) for 12 weeks. A 24-week course of SOF/RBV costs approximately US$169,000, with sustained virologic response (SVR) rates ranging from 52% to 84%; 12 weeks of SOF/SMV costs approximately $150,000, with SVR between 89% and 100%. Because SOF/SMV is currently used off-label, debate exists among physicians and payers about whether it should be prescribed and covered. This article presents a cost-effectiveness analysis of these two treatment regimens accounting for costs of drugs, treatment-related medical care, retreatment for individuals who do not achieve SVR, and natural history of continued HCV infection after failed retreatment. Analysis uses a Markov model with a lifetime horizon and a societal perspective. In the base-case scenario, SOF/SMV dominated SOF/RBV in a modeled 50-year-old cohort of treatment-naïve and -experienced subjects, excluding those who failed earlier therapy with telaprevir or boceprevir. SOF/SMV yielded lower costs and more quality-adjusted life years (QALYs) for the average subject, compared to SOF/RBV ($165,336 and 14.69 QALYs vs. $243,586 and 14.45 QALYs, respectively). In base-case cost analysis, the SOF/SMV treatment strategy saved $91,590 per SVR, compared to SOF/RBV. Under all one-way sensitivity scenarios, SOF/SMV remained dominant and resulted in cost savings. Conclusions: These results suggest that a 12-week course of SOF/SMV is a more cost-effective treatment for genotype 1 CHC than 24 weeks of SOF/RBV among IFN-ineligible/intolerant individuals, supporting the AASLD/IDSA guidance and offering implications for both clinical and regulatory decision making as well as pharmaceutical pricing. © 2014 by the American Association for the Study of Liver Diseases.


Kane G.C.,Chestnut Hill College | Alavi M.,Emory University | Labianca G.,University of Kentucky | Borgatti S.P.,University of Kentucky
MIS Quarterly: Management Information Systems | Year: 2014

In recent years, we have witnessed the rapid proliferation and widespread adoption of a new class of information technologies, commonly known as social media. Researchers often rely on social network analysis (SNA) when attempting to understand these technologies, often without considering how the novel capabilities of social media platforms might affect the underlying theories of SNA, which were developed primarily through studies of offline social networks. This article outlines several key differences between traditional offline social networks and online social media networks by juxtaposing an established typology of social network research with a well-regarded definition of social media platforms that articulates four key features. The results show that at four major points of intersection, social media has considerable theoretical implications for SNA. In exploring these points of intersection, this study outlines a series of theoretically distinct research questions for SNA in social media contexts. These points of intersection offer considerable opportunities for researchers to investigate the theoretical implications introduced by social media and lay the groundwork for a robust social media agenda potentially spanning multiple disciplines.


Lonial S.,Emory University | Anderson K.C.,Dana-Farber Cancer Institute
Leukemia | Year: 2014

Since the introduction of the proteasome inhibitor bortezomib and the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, more patients with multiple myeloma are achieving deep, durable responses and disease control, and are living longer. These improvements have afforded more robust analyses of the relationship between response and survival. Generally, these studies have demonstrated that improvements in the quality of response across all stages of treatment are associated with better disease control and longer survival. Thus, achievement of maximal response should be strongly considered, particularly in the frontline setting, but must also be balanced with tolerability, quality of life and patient preferences. In select patients, achievement of a lesser response may be adequate to prolong survival, and attempts to treat these patients to a deeper response may place them at unnecessary risk without significant benefit. Maintenance therapy has been shown to improve the quality of response and disease control and, in some studies, survival. Studies support maintenance therapy for high-risk patients as a standard of care, and there are emerging data supporting maintenance therapy in standard-risk patients to improve progression-free and possibly overall survival. Multidrug regimens combining a proteasome inhibitor and an IMiD have shown exceptional response outcomes with acceptable increases in toxicity in both the frontline and salvage settings, and are becoming a standard treatment approach. Moving forward, the use of immunophenotypic and molecular response criteria will be essential in better understanding the impact of highly active and continuous treatment regimens across myeloma patient populations. Future translational studies will help to develop antimyeloma agents to their fullest potential. The introduction of novel targeted therapies, including the IMiD pomalidomide and the proteasome inhibitors carfilzomib and ixazomib (MLN9708), will provide greater options to individualize treatment and help patients achieve a clinically meaningful response. © 2014 Macmillan Publishers Limited.


Patent
Dana-Farber Cancer Institute, Brigham, Women's Hospital, Emory University and The President And Fellows Of Harvard College | Date: 2011-12-21

The present invention provides methods and compositions for the treatment, prevention, or reduction of persistent infections, such as chronic infections, latent infections, and slow infections and cancer. The methods and compositions of the invention are also useful for the alleviation of one or more symptoms associated with such infections and cancer.


Patent
Emory University and Dana-Farber Cancer Institute | Date: 2015-03-06

PD-1 antagonists are disclosed that can be used to reduce the expression or activity of PD-1 in a subject. An immune response specific to an infectious agent or to tumor cells can be enhanced using these PD-1 antagonists in conjunction with an antigen from the infectious agent or tumor. Thus, subjects with infections, such as persistent infections can be treated using PD-1 antagonists. In addition, subjects with tumors can be treated using the PD-1 antagonists. In several examples, subjects can be treated by transplanting a therapeutically effective amount of activated T cells that recognize an antigen of interest and by administering a therapeutically effective amount of a PD-1 antagonist. Methods are also disclosed for determining the efficacy of a PD-1 antagonist in a subject administered the PD-1 antagonist. In some embodiments, these methods include measuring proliferation of memory B cells in a sample from a subject administered the PD-1 antagonist.


Patent
Dana-Farber Cancer Institute, Brigham, Women's Hospital, Emory University and The President & Fellows Of Harvard College | Date: 2011-12-21

The present invention provides methods and compositions for the treatment, prevention, or reduction of persistent infections, such as chronic infections, latent infections, and slow infections and cancer. The methods and compositions of the invention are also useful for the alleviation of one or more symptoms associated with such infections and cancer.


Osteoporosis, is an exceedingly common malady that leads to bone fracture and results from an imbalance in the rate of osteoblastic bone formation with respect to osteoclastic bone degradation. Nanotechnology has raised exciting possibilities for the development of novel therapeutic agents. Embodiments of the disclosure provide silica-based fluorescent nanoparticles endowed with natural bone targeting capabilities and expressing potent pro-osteoblastogenic and concomitant anti-osteoclastogenic activities in vitro and the capacity to increase bone mineral density in vivo. Embodiments of the disclosure can achieve their stimulatory effects on osteoblasts, and inhibitory effects on osteoclasts, in part by suppressing NF-KB signal transduction. Embodiments of the present disclosure provide for derivatives of silica-based nanoparticles that represent a novel class of dual anti-catabolic and pro-anabolic agents that may be applicable to the amelioration of numerous osteoporotic conditions.


Patent
Johns Hopkins University and Emory University | Date: 2014-02-17

This disclosure relates to analyzing the end-to-end sequence and the relative distributions in heterogeneous mixtures of polynucleotides and methods and enabling reagents related thereto. In certain embodiments this method relates to the complete full length sequencing and quantitative profiling of mRNAs present in the transcriptomes of cells or tissues of but not limited to, higher multicellular organisms that possess interrupted genes subject to complex post-transcriptional RNA processing


Patent
Emory University and Dana-Farber Cancer Institute | Date: 2013-03-13

The present invention is based, in part, on the identification of novel human anti-PD-1, PD-L1, and PD-L2 antibodies. Accordingly, the invention relates to compositions and methods for diagnosing, prognosing, and treating conditions that would benefit from modulating PD-1, PD-L1, and/or PD-L2 activity (e.g., persistent infectious diseases, autoimmune diseases, asthma, transplant rejection, inflammatory disorders and tumors) using the novel human anti-PD-1, PD-L1, and PD-L2 antibodies described herein.


Patent
Dana-Farber Cancer Institute and Emory University | Date: 2015-08-10

The present invention is based, in part, on the identification of novel human anti-PD-1, PD-L1, and PD-L2 antibodies. Accordingly, the invention relates to compositions and methods for diagnosing, prognosing, and treating conditions that would benefit from modulating PD-1, PD-L1, and/or PD-L2 activity (e.g., persistent infectious diseases, autoimmune diseases, asthma, transplant rejection, inflammatory disorders and tumors) using the novel human anti-PD-1, PD-L1, and PD-L2 antibodies described herein.

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