Richmond, VA, United States
Richmond, VA, United States

Virginia Commonwealth University is a public research university located in Richmond, Virginia. VCU was founded in 1838 as the medical department of Hampden–Sydney College, becoming the Medical College of Virginia in 1854. In 1968, the Virginia General Assembly merged MCV with the Richmond Professional Institute, founded in 1917, to create Virginia Commonwealth University. Today, more than 31,000 students pursue 222 degree and certificate programs through VCU's 13 schools and one college. The VCU Health System supports the university's health care education, research and patient care mission.With a record $256 million in sponsored research funding in the fiscal year 2011, VCU is designated as a research university with very high research activity by the Carnegie Classification of Institutions of Higher Education. A broad array of university-approved centers and institutes of excellence, involving faculty from multiple disciplines in public policy, biotechnology and health care discoveries, supports the university's research mission. Twenty-eight graduate and first-professional programs are ranked by U.S. News and World Report as among the best in the country. VCU's athletic teams compete in Division I of the NCAA and are collectively known as the VCU Rams. They are members of the Atlantic 10 Conference. The VCU campus includes historic buildings such as the Ginter House, now used by the school's provost. Wikipedia.


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Patent
Virginia Commonwealth University | Date: 2016-03-24

A compound having the formula:


A family of compounds which function as selective ligands for the serotonin receptor 2B (5-HT_(2B)) is identified. Some of the compounds are synthetic non-natural ligands which have a relatively strong interaction with 5-HT2B compared to naturally occurring compounds (some of which are identified for the first time herein as ligands for 5-HT_(2B)). Because the compounds, both naturally occurring and synthetically produced, function as ligands for 5-HT_(2B )they will have application in, for example, the treatment and/or prevention of nervous system disorders such as Alzheimers disease.


Patent
Virginia Commonwealth University | Date: 2016-08-25

The system includes various embodiments of components, including (1) a sensor array, (2) a processor, (3) a transmitter, (4) a receiver-stimulator, and (5) an implantable electrode array. The gustatory implant system generates tastant fingerprints by detecting tastants with an array of chemical sensors and then transmitting variable spatiotemporal stimulation patterns for an electrode array with electrode stimulating points positioned at different locations in the gustatory cortex (e.g., stimulating the chorda tympanic nerve). Different patterns of activity in the gustatory cortex are thereby generated which mimic the sense of taste in a subject. Once trained the system should be usable by a subject to detect or correctly identify or perceive one or more tastes. The system may also include an external electronic device for processing and displaying information to monitor ingestion of various substances in a subject.


Patent
Virginia Commonwealth University | Date: 2015-05-06

L27 in Staphylococcus aureus and other Firmicutes is encoded with an N-terminal extension that is not present in most Gram-negative organisms and is absent from mature ribosomes. We have identified a cysteine protease, conserved among bacteria containing the L27 N-terminal extension, which performs post-translational cleavage of L27. The provided methods have utility for the development of new therapeutic antibiotics that target this novel pathway in order to kill pathogenic Firmicutes and related bacteria.


Patent
Virginia Commonwealth University | Date: 2015-03-25

Constructs and monitoring systems to assess the level of molecules that bind to thrombin (e.g. thrombin regulators and inhibitors) are provided. The constructs are nanosensors comprising i) a thrombin molecule to which is bound a reporter ligand comprising a fluorescent label, ii) a fluorescence-quenching metal nanoparticle, and, optionally iii) a fluorescence-quenching dye molecule attached to one or both of the nanoparticle and the thrombin molecule. The binding of a thrombin regulator or inhibitor to the thrombin molecule displaces the reporter ligand, and the signal from the fluorescent label increases. The increase is proportional to the concentration of thrombin-binding molecule in the sample.


Patent
Virginia Commonwealth University and The Regents Of The University Of Colorado | Date: 2016-08-31

In one example implementation, a method includes receiving, at a computing device, a request to grant a set of requested permissions to an application installed on the computing device, and sending, from the computing device, a permission query request to a recommendation server, where the permission query request includes an identifier for the application, and the set of requested permissions. The method may also include receiving, at the computing device, from the recommendation server, a set of permission recommendations, where the set of permission recommendations indicates whether the recommendation server recommends granting each requested permission from the set of requested permissions. The method may also include displaying the set of requested permissions and the set of permission recommendations, determining a set of granted permissions for the application, granted by a user of the computing device, from the set of requested permissions, and setting the permissions for the application on the computing device using the set of granted permissions.


Wegelin J.A.,Virginia Commonwealth University | Hoffman M.D.,University of California at Davis
European Journal of Applied Physiology | Year: 2011

We sought to determine the degree to which age, sex, calendar year, previous event experience and ambient race day temperature were associated with finishing a 100-mile (161-km) trail running race and with finish time in that race. We computed separate generalized linear mixed-effects regression models for (1) odds of finishing and (2) finish times of finishers. Every starter from 1986 to 2007 was used in computing the models for odds of finishing (8,282 starts by 3,956 individuals) and every finisher in the same period was included in the models for finish time (5,276 finishes). Factors associated with improved odds of finishing included being a first-time starter and advancing calendar year. Factors associated with reduced odds of finishing included advancing age above 38 years and warmer weather. Beyond 38 years of age, women had worse odds of finishing than men. Warmer weather had a similar effect on finish rates for men and women. Finish times were slower with advancing age, slower for women than men, and less affected by warm weather for women than for men. Calendar year was not associated with finish time after adjustment for other variables. © 2010 The Author(s).


Rottier B.L.,University of Groningen | Rubin B.K.,Virginia Commonwealth University
Paediatric Respiratory Reviews | Year: 2013

Asthma is usually treated with inhaled corticosteroids (ICS) and bronchodilators generated from pressurized metered dose inhalers (pMDI), dry powder inhalers (DPI), or nebulizers. The target areas for ICS and beta 2-agonists in the treatment of asthma are explained. Drug deposition not only depends on particle size, but also on inhalation manoeuvre. Myths regarding inhalation treatments lead to less than optimal use of these delivery systems. We discuss the origin of many of these myths and provide the background and evidence for rejecting them. © 2013.


Sanyal A.J.,Virginia Commonwealth University | Friedman S.L.,Mount Sinai School of Medicine | Mccullough A.J.,Cleveland Clinic | Dimick-Santos L.,U.S. Food and Drug Administration
Hepatology | Year: 2015

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease (CLD) in North America. It is a growing contributor to the burden of CDL requiring liver transplantation. Cirrhosis is also associated with an increased risk of hepatocellular cancer, which may occur even in the absence of cirrhosis in subjects with nonalcoholic steatohepatitis (NASH), the histological form of NAFLD associated with increased liver-related mortality. The diagnosis of NASH currently requires a liver biopsy. There are also no U.S. Food and Drug Administration (FDA)-approved therapies for NASH. Therefore, there is a need to develop better diagnostic and therapeutic strategies for patients with NASH, targeting both those with early-stage disease as well as those with advanced liver fibrosis. There are unique challenges in the design of studies for these target populations. The long relatively asymptomatic time interval in the progression of NAFLD and NASH to cirrhosis and ultimately liver failure, along with gaps in knowledge regarding disease modifiers, combine to present significant challenges in trial design. Therefore, there is an urgent need to develop methods to identify the populations at particular risk of disease progression and validate endpoints that reflect meaningful changes in health status in this population. This article summarizes the discussion at a joint workshop held September 5 and 6, 2013 in Silver Spring, Maryland, sponsored by the FDA and the American Association for the Study of Liver Diseases to develop guidance on diagnostic and therapeutic modalities for NASH. (Hepatology 2015;61:1392-1405) © 2015 by the American Association for the Study of Liver Diseases.


Negus S.S.,Virginia Commonwealth University
Life Sciences | Year: 2014

This mini-review summarizes the history of cathinone and its synthesized derivatives from early records to the present day, including the appearance of synthetic cathinones in the drug combination known as bath salts. Bath salts may consist of one compound (MDPV) or combinations of MDPV and one or more other synthetic cathinones, which may also appear alone without MDPV. We briefly review recent in vitro studies of bath salts components alone or in combination, focusing on pharmacological and biophysical studies. Finally we summarize new data from in vivo procedures that characterize the abuse-related neurochemical and behavioral effects of synthetic cathinones in rats. © 2013 Elsevier Inc. All rights reserved.


Kini R.M.,National University of Singapore | Kini R.M.,Virginia Commonwealth University
Journal of Thrombosis and Haemostasis | Year: 2011

Exogenous factors isolated from venoms of snakes and saliva of haematophagous animals that affect thrombosis and haemostasis have contributed significantly to the development of diagnostic agents, research tools and life-saving drugs. Here, I discuss recent advances in the discovery, structural and functional characterisation, and mechanism of action of new procoagulant and anti-haemostatic proteins. In nature, these factors have evolved to target crucial 'bottlenecks' in the coagulation cascade and platelet aggregation. Several simple protein scaffolds are used to target a wide variety of target proteins and receptors exhibiting functional divergence. Different protein scaffolds have also evolved to target identical, physiologically relevant key enzymes or receptors exhibiting functional convergence. At times, exogenous factors bind to the same target protein, but at distinct sites, to differentially attenuate their functions exhibiting mechanistic divergence within the same family of proteins. The structure-function relationships of these factors are subtle and complicated but represent an exciting challenge. These studies provide ample opportunities to design highly specific and precise ligands to achieve desired biological target function. Although only a small number of them have been characterised to date, the molecular and mechanical diversities of these exogenous factors and their contributions to understanding molecular and cellular events in thrombosis and haemostasis as well as developing diagnostic and research tools and therapeutic agents, is outstanding. Based on the current status, I have attempted to identify future potential and prospects in this area of research. © 2011 International Society on Thrombosis and Haemostasis.


Kendler K.S.,Virginia Commonwealth University | First M.B.,New York State Psychiatric Institute | First M.B.,Columbia University
British Journal of Psychiatry | Year: 2010

Two major approaches can be used for the up-coming revisions of DSM-V and ICD-10: an 'iterative model' in which incremental changes are made or a 'paradigm shift model' in which the existing approach is jettisoned in favour of a new nosological model. We explore each of these two approaches and conclude that although they both have strengths and limitations, our field is not currently ready for a paradigm shift.


Brown K.W.,Virginia Commonwealth University | Weinstein N.,University of Essex | Creswell J.D.,Carnegie Mellon University
Psychoneuroendocrinology | Year: 2012

Background: Individual differences in mindfulness have been associated with numerous self-report indicators of stress, but research has not examined how mindfulness may buffer neuroendocrine and psychological stress responses under controlled laboratory conditions. The present study investigated the role of trait mindfulness in buffering cortisol and affective responses to a social evaluative stress challenge versus a control task. Methods: Participants completed measures of trait mindfulness, perceived stress, anxiety, and fear of negative evaluation before being randomized to complete the Trier Social Stress Test (TSST; Kirschbaum et al., 1993) or a control task. At points throughout the session, participants provided five saliva samples to assess cortisol response patterns, and completed four self-report measures of anxiety and negative affect to assess psychological responses. Results: In accord with hypotheses, higher trait mindfulness predicted lower cortisol responses to the TSST, relative to the control task, as well as lower anxiety and negative affect. These relations remained significant when controlling for the role of other variables that predicted cortisol and affective responses. Conclusions: The findings suggest that trait mindfulness modulates cortisol and affective responses to an acute social stressor. Further research is needed to understand the neural pathways through which mindfulness impacts these responses. © 2012 Elsevier Ltd.


Lisman T.,University of Groningen | Stravitz R.T.,Virginia Commonwealth University
Seminars in Thrombosis and Hemostasis | Year: 2015

Patients with acute liver failure (ALF) have substantial alterations in their hemostatic system. Since an international normalized ratio of ≥ 1.5 is part of the definition of the syndrome, it has long been believed that patients with ALF had a hemostasis-related bleeding tendency. Recent data, however, show that spontaneous bleeding in ALF is rare. In addition, thrombotic complications may be more common than spontaneous bleeding complications. Laboratory studies have suggested that patients with ALF may be in hemostatic balance as a result of a commensurate decline in pro- and anti-hemostatic factors. The unstable nature of the hemostatic balance in ALF may explain the occurrence of both bleeding and thrombotic complications. The hemostatic profile of patients with ALF includes hypercoagulable features, including von Willebrand factor/a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 unbalance, elevated levels of highly procoagulant, platelet-derived microparticles, and a profound hypofibrinolytic status. These hypercoagulable features may contribute to systemic thrombotic complications, but may also drive intrahepatic clot formation. Studies in experimental animal models of ALF have demonstrated that intrahepatic clot formation contributes to disease progression. The clinical consequences of these new insights in the hemostatic system of patients with ALF will be discussed in this review. © 2015 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY.


McAllister J.M.,Penn Medicine | Legro R.S.,Penn Medicine | Modi B.P.,Virginia Commonwealth University | Strauss J.F.,Virginia Commonwealth University
Trends in Endocrinology and Metabolism | Year: 2015

Polycystic ovary syndrome (PCOS) is a common endocrinopathy characterized by increased ovarian androgen biosynthesis, anovulation, and infertility. PCOS has a strong heritable component based on familial clustering and twin studies. Genome-wide association studies (GWAS) identified several PCOS candidate loci including LHCGR, FSHR, ZNF217, YAP1, INSR, RAB5B, and C9orf3. We review the functional roles of strong PCOS candidate loci focusing on FSHR, LHCGR, INSR, and DENND1A. We propose that these candidates comprise a hierarchical signaling network by which DENND1A, LHCGR, INSR, RAB5B, adapter proteins, and associated downstream signaling cascades converge to regulate theca cell androgen biosynthesis. Future elucidation of the functional gene networks predicted by the PCOS GWAS will result in new diagnostic and therapeutic approaches for women with PCOS. © 2014 Elsevier Ltd.


Nobili V.,Pediatric Hospital Bambino Gesu | Sanyal A.J.,Virginia Commonwealth University
Journal of Gastroenterology | Year: 2012

Nonalcoholic fatty liver disease encompasses a spectrum of disease from asymptomatic steatosis, with or without elevated aminotransferases, to cirrhosis with relative complications and hepatocellular carcinoma. Owing to the increasing prevalence of nonalcoholic fatty liver disease and the potential for nonalcoholic steatohepatitis to progress to cirrhosis and liver-related mortality, more research has been focused on therapy of this important liver disease over the last two decades. To date, weight loss and physical activity represent the cornerstone of treatment, with interventions being limited to subjects at risk of disease progression, but the type of treatment remains a matter of debate. A few medications have shown promising results in preliminary pilot studies, but few agents have been tested rigorously. Today, multiple therapeutic approaches are considered the way to go in treating nonalcoholic steatohepatitis patients. In this paper we review the status of current and emerging therapeutic strategies for children and adult patients with nonalcoholic steatohepatitis. © 2011 Springer.


News Article | November 17, 2016
Site: www.prweb.com

Leading online higher education resource center AffordableCollegesOnline.org has released it’s ranking of the Best Online Vocational & Trade Schools for 2016-2017. Lists include the top 100 schools offering trade or vocational training programs online, with Washburn University, University of Southern Mississippi, Siena Heights University, Weber State University and Fort Hays State University earning the highest scores in the four-year school category and East Mississippi Community College, San Juan College, Hutchinson Community College, New Mexico Junior College and Tulsa Community College earning the highest scores in the two-year school category. "Trade and vocational programs are making more of an impact when it comes to online education than ever before,” said Dan Schuessler, CEO and Founder of AffordableCollegesOnline.org. "Although many trades require hands-on training, the schools on our lists are giving students more flexibility by offering vocational learning programs online.” Schools are evaluated on a variety of cost and quality standards to determine their position on the Best Online Vocational & Trade Schools list by AffordableCollegesOnline.org. Each is required to meet specific base standards; all institutions must be accredited, public or private not-for-profit entities and must offer in-state tuition below $5,000 per year at two-year schools or $25,000 per year at four-year schools. Eligible institutions are divided by whether they are two-year or four-year schools, weighed on factors such as financial aid offerings and online program variety, then scored against one another to determine rank. More information on the data points, methodology and specific scores given to each school on the Best Online Vocational & Trade Schools list can be found online at: Two-year schools receiving honors on the 2016-2017 Best Online Vocational & Trade Schools list: Atlanta Technical College Barton County Community College Bluegrass Community and Technical College Central Georgia Technical College Central Piedmont Community College Central Texas College Cincinnati State Technical and Community College Cossatot Community College of the University of Arkansas Cowley County Community College Crowder College East Arkansas Community College East Mississippi Community College Edgecombe Community College Fayetteville Technical Community College Gateway Community and Technical College Georgia Piedmont Technical College Grayson College Great Falls College Montana State University Holmes Community College Hutchinson Community College Indian Hills Community College Itawamba Community College Kansas City Kansas Community College Madisonville Community College Metropolitan Community College Moraine Park Technical College Navarro College New Mexico Junior College North Dakota State College of Science Northeast Iowa Community College-Calmar Northwest Mississippi Community College Oconee Fall Line Technical College Ozarks Technical Community College Pamlico Community College Panola College Pitt Community College San Juan College Seward County Community College and Area Technical School Shoreline Community College Sinclair College Southwest Virginia Community College Spokane Community College State Fair Community College Surry Community College Tallahassee Community College Three Rivers Community College Tulsa Community College Tyler Junior College Volunteer State Community College Western Nebraska Community College Four-year schools receiving honors on the 2016-2017 Best Online Vocational & Trade Schools list: California State University - East Bay Central Washington University Clarion University of Pennsylvania Clarkson College Clayton State University College of Southern Nevada East Carolina University East Tennessee State University Ferris State University Florida International University Fort Hays State University Granite State College Hampton University Hodges University Indiana State University Liberty University Morehead State University North Carolina Central University Northern Arizona University Northern State University Oklahoma State University-Main Campus Old Dominion University Oregon Institute of Technology Pennsylvania College of Technology Siena Heights University South Dakota State University Southern Polytechnic State University St. Petersburg College SUNY College of Technology at Canton The University of Alabama The University of Texas Health Science Center at San Antonio Tiffin University University of Cincinnati - Main Campus University of Louisiana at Monroe University of Massachusetts - Amherst University of Massachusetts - Lowell University of Michigan - Ann Arbor University of Mississippi University of North Carolina at Charlotte University of North Dakota University of Southern Mississippi Utah Valley University Vaughn College of Aeronautics and Technology Virginia Commonwealth University Washburn University Weber State University Western Carolina University Western Kentucky University Wichita State University William Woods University AffordableCollegesOnline.org began in 2011 to provide quality data and information about pursuing an affordable higher education. Our free community resource materials and tools span topics such as financial aid and college savings, opportunities for veterans and people with disabilities, and online learning resources. We feature higher education institutions that have developed online learning environments that include highly trained faculty, new technology and resources, and online support services to help students achieve educational and career success. We have been featured by nearly 1,100 postsecondary institutions and nearly 120 government organizations.


News Article | October 27, 2016
Site: www.eurekalert.org

NEW ORLEANS - That twice-yearly trip to the dentist could do more than keep teeth and gums healthy: It may decrease the risk of pneumonia by reducing bacteria in the mouth, suggests research being presented at IDWeek 2016™. Nearly one million Americans become ill with the infection every year and 50,000 die. While it is more common among older people and those with conditions such as AIDS or lung disease, anyone can get pneumonia. Based on an analysis of a national database of more than 26,000 people, the new research found that people who never get dental checkups had an 86 percent greater risk of pneumonia than to those who visit the dentist twice a year. "There is a well-documented connection between oral health and pneumonia, and dental visits are important in maintaining good oral health," said Michelle Doll, MD, lead author of the study and assistant professor of internal medicine in the Division of Infectious Disease at Virginia Commonwealth University, Richmond. "We can never rid the mouth of bacteria altogether, but good oral hygiene can limit the quanitities of bacteria present." Researchers analyzed data obtained from the 2013 Medical Expediture Panel Survey, which asks about healthcare utilization (including dental care), costs and patient satisfaction. They found 441 of 26,246 people in the database had bacterial pneumonia (1.68 percent) and that those who never had dental checkups had an 86 percent increased risk of pneumonia compared to those who had twice-yearly appointments. The body contains 10 times as many microbes (bacteria, fungi and viruses) as human cells on or in the body, from the skin to the gastrontestinal system (including the mouth). Some microbes are good and some are bad, but even bad microbes only cause disease under certain circumstances. In some cases, bacteria can be accidentally inhaled or aspirated into the lungs and cause pneumonia. Bacteria that commonly cause pneumonia include streptococcus, haemophilus, staphylococcus, and anaerobic bacteria. Routine dental visits may reduce the amount of bacteria that can be aspirated, said Dr. Doll. "Our study provides further evidence that oral health is linked to overall health, and suggests that it's important to incorporate dental care into routine preventive healthcare," said Dr. Doll. In addition to Dr. Doll, co-authors of the study are Kristen Kelly, MSc; Scott Ratliff, MS and Norman Carroll PharmD. IDWeek 2016TM is the annual meeting of the Infectious Diseases Society of America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA) and the Pediatric Infectious Diseases Society (PIDS). With the theme "Advancing Science, Improving Care," IDWeek features the latest science and bench-to-bedside approaches in prevention, diagnosis, treatment, and epidemiology of infectious diseases, including HIV, across the lifespan. IDWeek 2016 takes place October 26-30 at the Ernest N. Morial Convention Center in New Orleans. For more information, visit http://www. .


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

PARIS--(BUSINESS WIRE)--As we become more sedentary and better fed, the human race is faced with an epidemic of obesity and diseases such as type II diabetes. Although the correlation between body weight, food intake and exercise seems obvious, the regulatory mechanisms that link exercise, muscle biology, hormones and metabolism are not well understood. The focus of this year’s colloquium on Endocrinology hosted by the Fondation IPSEN is to gain an overview of the complexity of these pathways, to discuss the processes common to the various body systems involved and to identify possible therapeutic targets. Twelve international speakers will present their latest research at the meeting, which has been organised by Bruce Spiegelman (Dana Faber Cancer Institute and Harvard Medical School, Boston, USA) and the Fondation IPSEN (Paris, France). It will be held in Paris on December 5, 2016. The most obvious effects of exercise are on skeletal muscles, increasing muscle volume, strength and contractility. More importantly, exercise both maintains and increases the insulin sensitivity of muscle and affects the metabolism of the whole body by stimulating the uptake of glucose by muscles (Anna Krook, Karolinska Institutet, Stockholm, Sweden). A decrease in muscle insulin sensitivity is a big contributor to the onset of type II diabetes. The effectiveness of exercise regimes is modified by the availability of nutrients: the composition of the diet and the timing of meals in relation to exercise both alter the blood-borne signals that ultimately influence fuel metabolism and utilization (John Hawley, Mary Mackillop Institute for Health Research, Melbourne, Australia). Among these signals are the recently discovered hormones released by contracting muscles, now called myokines, such as the soluble peptide irisin. The role of steroid hormones in improving cardio-vascular fitness in response to exercise is being tested in population studies (Claude Bouchard, Pennington Biomedical Research Centre, Louisiana, USA). Metabolic stresses, such as low oxygen, ischaemia or glucose deprivation, stimulate the regulatory molecule AMP kinase, which acts as a cellular fuel gauge, providing an essential link between exercise, insulin signaling and the regulation of energy supplies. As well as its essential role in skeletal muscle, this molecule is pivotal in balancing the supply of nutrients to cells with the demand for energy throughout the body (Benoit Viollet, Institut Cochin-U1016 INSERM, Paris, France). Small RNA molecules known as micro-RNAs, which modulate the translation of DNA into proteins through their effect on messenger RNAs, also play a role in both skeletal muscle differentiation and in type II diabetes in response to exercise (Krook). Ultimately, energy production depends on the series of enzymatic reactions known as the citric acid cycle, which takes place in the mitochondria, the cell’s power generators. When the demand for energy goes up as a result of exercise, one pathway that coordinates the increase in size and number of mitochondria and optimizes the utilization of fuel requires the activation of the transcription factor EB (TFEB) (Marco Sandri, University of Padova, Padova, Italy). Muscles atrophy as a result of disuse, ageing and cachexia, the wasting experienced in terminal cancer. In rat muscles, the expression of genes involved in mitochondrial energy metabolism changes with ageing. The functional loss of muscle innervation seen in both ageing and cachexia is reflected in changes in genes responsible for the integrity of the neuro-muscular junction (David Glass, Novartis Institute for Biomedical Research, Cambridge, USA). In atrophying muscle, a set of genes is activated that produce muscle-specific enzymes responsible for labelling proteins for degradation in special organelles termed proteasomes (Alfred Goldberg, Harvard Medical School, Boston USA). Environmental stress activates compensatory mechanisms important for the maintenance of cell functions and their failure is a cause of cellular ageing, for example, the reduction in mitochondrial health that accompanies muscle atrophy. However, some of these effects can be ameliorated by exercise (Sandri). A pivotal molecule in mediating responses to external stimuli is PGC-1α, which regulates both the transcription of the genes involved in metabolism and the regulation of mitochondrial biogenesis. Increased activity of PGC-1α improves endurance, reduces fibre damage and muscle atrophy, and is important in determining muscle fibre type. PGC-1α may lie at the heart of improving the regenerative capacity of muscle through training: it activates both macrophages, which remove damaged muscle fibres, and the satellite cells that generate replacement fibres (Christoph Handschin, University of Basel, Basel, Switzerland). PGC-1 α is also important in another tissue central to energy regulation, the type of fat known as brown adipose tissue (BAT). This converts chemical energy into heat in a process known as thermogenesis, part of the body’s adaptive response to cold. Its presence in humans has been controversial but BAT is now recognized to form deposits deep in the neck and is found in some subcutaneous fatty tissue. It is distinct from white adipose tissue, the main form of fat deposited in the human body but it has recently been discovered that white fat can be converted to BAT through an intermediate ‘beige’ form (Francesco Celli, Virginia Commonwealth University, Richmond, USA). The hormonal signals that stimulate the conversion and the activation of beige and brown fats in response to cold, and how this increases the breakdown of post-prandial glucose, are being studied. The pathways through which these hormonal signals activate PGC1α and a second molecule found in BAT, termed UCP-1 (or thermogenin) may link exercise and thermogenesis: the hormone irisin produced by active skeletal muscle has been implicated stimulating the conversion of white to brown fat (Spiegelman). As well as its effects on muscle and fat body, exercise works in less obvious ways to keep the brain healthy. Problems with the breakdown of kynurenine, produced from the amino acid tryptophan and a precursor of enzymes involved in fat and carbohydrate metabolism, are implicated in several neuroinflammatory and psychiatric diseases, including stress and depression (Jorge Ruas, Karolinska Institutet, Stockholm, Sweden). During exercise, kynurenine is detoxified in skeletal muscle by conversion to kynurenic acid, which cannot cross the blood-brain barrier. This is yet another pathway involving PGC1α, a further example of the complexity of exercise-linked regulatory mechanisms. Yet another effect of exercise, at least in adult mouse brains, is to increase the birth of new neurons in the hippocampus, which helps to support learning and cognitive function. Irisin has a role here too: it increased the expression of the gene coding for the growth factor BDNF, essential for hippocampal neurogenesis (Christiane Wrann, Dana Faber Cancer Institute, Boston, USA). The research to be presented at the meeting will emphasise not only how important exercise is for maintaining a healthy metabolism but also the multiple ways in which it has its effects. Many of the results that will be discussed also provide leads for the development of therapeutics for use when exercise alone fails to have the desired effect or is inappropriate. Established in 1983 under the aegis of the Fondation de France, the ambition of the Fondation IPSEN is to initiate a reflection about the major scientific issues of the forthcoming years. The long-standing mission of the Fondation IPSEN is to contribute to the development and dissemination of scientific knowledge by fostering interaction between scientists and clinicians. It has developed an important international network of scientific experts who meet regularly at meetings known as Colloques Médecine et Recherche, dedicated to three main topics: neurosciences, endocrinology and cancer science. Moreover the Fondation IPSEN has started several series of meetings in partnership with the Salk Institute, the Karolinska Institute as well as with the science journals Cell and Science. The Fondation IPSEN produced several hundred publications and more than 250 scientists have been awarded prizes and grants.


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

All Stars Pediatric Dentistry of Cumming, GA, was recently recognized by area magazine, The Forsyth News. Pediatric Dentist Dr. John Haffner, the owner of All Stars Pediatric Dentistry, was voted by readers as the “Best Children’s Dentist” of 2017, beating out over twenty other local practices. The 2017 award marks the third year in a row that All Stars Pediatric Dentistry has been named best in its category by The Forsyth News. “It’s really such an honor to be recognized by the people in this great community,” said Dr. Haffner. “I grew up in this area, so being able to come back and help my neighbors through my work is just an incredibly rewarding experience.” Dr. Haffner is a graduate of Medical College of Georgia School of Dentistry after which he completed a pediatric dental residency program at Virginia Commonwealth University. After working at a large dental clinic for several years, Dr. Haffner was driven to open a practice that felt more patient-focused. “I’ve always had a passion for kids, and it just made sense to me to create the kind of environment I’d want to take my own children to,” explains Haffner. The office design at All Stars Pediatric Dentistry was inspired by the many summers Haffner spent enjoying the great Georgia outdoors, both on the lake and competing in sports. “Kids really seem to love all the bright colors and sports décor!” All Stars Pediatric Dentistry works hard to create an inviting atmosphere for both parents and children. The team strives to be warm and welcoming, and parents are always invited to stay with their children during appointments. The office sees patients from all over the North Georgia area including Dawsonville, Alpharetta, Gainesville, and of course, Forsyth County. The 2017 Best of Forsyth Awards were handed out in a ceremony at the Forsyth Conference Center on January 25th. The annual awards, voted on by over 140,000 local residents, are given out in categories ranging from “Best Restaurant” to “Best Law Firm” to “Best Breakfast Restaurant.” All Stars Pediatric Dentistry is a locally-owned pediatric dentistry practice focusing on patient care. With a commitment to making routine dentistry a pleasant experience for both parents and children, the practice has quickly grown to one of the most popular in the greater Cumming area. For more information on All Stars Pediatric Dentistry or details on the Best of Forsyth Magazine award contact (770) 292-9441 or visit http://www.AllStarsChildrensDentist.com.


News Article | November 2, 2016
Site: www.sciencemag.org

Mark Hutchinson could read the anguish on the participants’ faces in seconds. As a graduate student at the University of Adelaide in Australia in the late 1990s, he helped with studies in which people taking methadone to treat opioid addiction tested their pain tolerance by dunking a forearm in ice water. Healthy controls typically managed to stand the cold for roughly a minute. Hutchinson himself, “the young, cocky, Aussie bloke chucking my arm in the water,” lasted more than 2 minutes. But the methadone patients averaged only about 15 seconds. “These aren’t wimps. These people are injecting all sorts of crazy crap into their arms. … But they were finding this excruciating,” Hutchinson says. “It just fascinated me.” The participants were taking enormous doses of narcotics. How could they experience such exaggerated pain? The experiment was Hutchinson’s first encounter with a perplexing phenomenon called opioid-induced hyperalgesia (OIH). At high doses, opioid painkillers actually seem to amplify pain by changing signaling in the central nervous system, making the body generally more sensitive to painful stimuli. “Just imagine if all the diabetic medications, instead of decreasing blood sugar, increased blood sugar,” says Jianren Mao, a physician and pain researcher at Massachusetts General Hospital in Boston who has studied hyperalgesia in rodents and people for more than 20 years. But how prevalent hyperalgesia is, and whether it plays a role in the U.S. epidemic of opioid abuse and overdose, is unclear. A lack of reliable testing methods and a series of contradictory papers have created believers and skeptics. A few researchers, like Mao, think hyperalgesia is an underappreciated puzzle piece in the opioid epidemic—a force that can pile on pain, drive up doses, and make it harder for chronic users to come off their drugs. Some of those researchers are looking for ways to turn down hyperalgesia, to help patients function on lower doses of their oxycodone, for example, or make it easier to taper off it altogether. Others see OIH as an oddity in the literature—real, and a powerful clue to the workings of  pain pathways, but unlikely to tighten the grip of opioids on most patients. Hutchinson thinks the majority of physicians are either unaware of hyperalgesia or unconvinced of its importance. “I think if you surveyed prescribers of opioids, they would be divided probably 60–40.” Paradoxical as it may seem, OIH makes evolutionary sense. “Nature didn’t come up with pain just to torture mankind,” says Martin Angst, an anesthesiologist and clinical pharmacologist at Stanford University in Palo Alto, California. Pain causes us to recoil from a hot stove and to stay off an injured leg while it heals. And when it’s crucial that we temporarily ignore pain—say, when we run on that injured leg to evade a charging lion—the body has a way of numbing it, in part by releasing its own opioids. These natural molecules bind to receptors on neurons to block pain signals and activate reward centers in the brain. But doses of prescription opioids are orders of magnitude higher than our endogenous levels, Angst says. Confronted by these, “your biology fights back and says, ‘I’m blindfolded to pain by all these chemicals. I need to be able to sense pain again.’” Mao was among the first to delve into potential mechanisms of OIH in an animal model. In 1994, while at Virginia Commonwealth University in Richmond,  he and his colleagues showed that after 8 days of spinal morphine injections, rats were quicker to pull their paws away from a gradually heated glass surface. The animals’ baseline pain threshold had changed, and the effect was something more than tolerance, in which the body requires increasing doses of a drug to get the same effect. In this case, a higher dose could actually increase sensitivity to pain. The researchers found they could reverse the hyperalgesic effect by blocking certain receptors on neurons in the animals’ spinal cord. These N-methyl-D-aspartate (NMDA) receptors pick up chemical signals—notably an excitatory molecule called glutamate—released by sensory neurons projecting from the skin and organs, and transmit pain signals up to the brain. Researchers already knew that even without opioids, some people with chronic pain from nerve damage or fibromyalgia, for example, experience hyperalgesia when normal pain signaling gets reinforced and amplified over time. It appeared that, at least in animals, opioids had a similar effect. By 2000, Mao was turning his attention to patients, and the population of opioid users was expanding. Doctors had begun to consider the drugs relatively safe options for managing chronic pain. With the release and aggressive marketing of the long-acting narcotic OxyContin in 1996, a class of drugs that had largely been reserved for cancer patients was becoming a go-to treatment for conditions such as lower back pain. As prescribing skyrocketed, so did overdoses. U.S. deaths from prescription opioids have roughly quadrupled in the last 2 decades, reaching 21,000 in 2014. Making things worse, abundant prescription opioids have been diverted for recreational use, which has driven up rates of heroin addiction as users have sought cheaper or more accessible alternatives. Both prescription and illegal opioids kill when high doses slow breathing, especially when combined with alcohol or antianxiety drugs called benzodiazepines. “I’m not sure you could find an example of physicians doing more harm to human beings than we have achieved in our liberal opiate prescribing,” says David Clark, an anesthesiologist at Stanford. Mao and others wondered whether hyperalgesia was another important opioid side effect. People might be seeking a higher dose as drug-induced pain compounded the original pain, he thought. If so, doctors who ignore hyperalgesia might bump up the dose when the right decision was to reduce it. And when a patient tried to taper off a drug, a temporarily lowered pain threshold might make it harder for them to manage without it. “If they’re hyperalgesic, they can just go back to the drug again to feel okay,” says Jose Moron-Concepcion, a neuroscientist at the Washington University School of Medicine in St. Louis in Missouri. The evidence for hyperalgesia is clearest in people taking extreme doses—for instance, in opioid abusers or terminal cancer patients managing severe pain. Surgical patients given large amounts of the opioid remifentanil have shown signs of hyperalgesia; they have larger areas of soreness around their wounds and seem predisposed to chronic pain following surgery. But what about patients who take lower doses of opioids daily over months or years to manage chronic pain? As a pain specialist at a large teaching hospital, Mao frequently encounters patients who can’t find relief from increasing opioid doses and who tell him that their pain has become worse—diffuse, nagging, and harder to pinpoint. But just how many people experience OIH, and at what opioid dose, is hard to say. The phenomenon can be very hard to distinguish from tolerance, when pain increases as the drug loses its effectiveness over time. (It’s also possible that a patient’s underlying condition has changed, or that the chronic pain itself has kicked their pain signaling into high gear.) Because diagnosing hyperalgesia can be a guessing game in the clinic, some researchers have turned to the lab. They have tried to document changing pain thresholds with quantitative sensory tests, like the so-called cold pressor test Hutchinson witnessed in the methadone patients in Australia, or contraptions that apply heat or pressure to the skin. But the studies have been small and the results inconsistent. “Nobody has actually shown that that particular stimulus in a human being is a valid way to say, ‘Yes, this person has become hyperalgesic,’” Angst says. In 2006, for instance, a team that included Angst and Clark gave the cold pressor test to six people with chronic lower back pain before and after a monthlong course of morphine pills. After the drug treatment, the team found signs of hyperalgesia: On average, the subjects registered pain from the ice water about 2 seconds earlier, and removed their hands about 8 seconds earlier, than they had beforehand. But those results didn’t hold up in a larger group of 139 patients randomized to take opioids or placebo, nor did they appear in a different pain test that applied a gradually heated probe to the forearm. Then in 2013, a study with a different methodology seemed to confirm the effect. A research team in Israel reported evidence of hyperalgesia in 17 of 30 patients with radiating spinal nerve pain by asking them to rate the intensity of heat pain on a numerical scale before and after a 4-week course of hydromorphone. If you can’t reliably diagnose hyperalgesia, it’s hard to predict its long-term effects, says Michael Hooten, an anesthesiologist at the Mayo Medical School in Rochester, Minnesota. His group found evidence in 91 patients tapering off opioids that those whose doses were higher at the start, forcing them to make greater reductions over the 3-week program, had worse measures of heat pain hyperalgesia. But the team wasn’t able to track these patients long-term to ask the bigger questions: How long until their pain thresholds bounced back to normal? Do hyperalgesic patients who manage to quit taking opioids ultimately see improvements in pain? Are hyperalgesic patients more or less prone to addiction or relapse? For some, this lack of evidence makes research into hyperalgesia look like a dead end. “When I go to work every day, I don’t think about opioid-induced hyperalgesia,” says Gary Bennett, a pain researcher at the University of California in San Diego. “We know that it’s real. We don’t know how important it is, and it’s really, really hard to answer that question, so let’s move on.” Mao isn't ready to move on. He believes the risk of hyperalgesia should motivate doctors to try tapering patients off their opioids when their pain worsens without an obvious cause. But in his experience, only about a third of chronic pain patients are willing to try that. So he’s hoping for a different solution: a drug that targets the mechanisms behind hyperalgesia and that might be given alongside an opioid, either when it’s first prescribed or when a doctor suspects OIH. Mao is recruiting patients for clinical trials to test two candidate drugs. One is ketamine, an anesthetic that blocks NMDA receptors. The other, guanfacine, is currently used to treat high blood pressure and is thought to keep sensory neurons from releasing glutamate into the spinal cord. A team led by Peggy Compton of Georgetown University in Washington, D.C., meanwhile, is investigating a pain and antiseizure drug called gabapentin that may block neural transmission to reduce excessive pain signals. Other groups are attacking opioid side effects, including hyperalgesia, from a very different angle. In the early 2000s, researchers began exploring the role of glia, star-shaped immune cells in the brain and spinal cord, which were traditionally thought to function as mere “housekeepers,” offering structural support for neurons and removing debris. But when the immune system becomes activated in response to an illness or injury, glia in regions associated with pain processing seem to take on another role: They release inflammatory molecules that interact with nearby neurons to amplify pain signals. In 2001, researchers at the Chinese Academy of Sciences in Shanghai reported that chronic morphine administration in rats activated glial cells called astrocytes in the spinal cord. Subsequent studies showed that inhibiting the inflammatory molecules released by glia could reverse hyperalgesia and tolerance in the rats. The results suggested that opioids may trigger glia to set off system-wide pain signaling that both counteracts the pain relief from the drug and makes the body generally more sensitive to pain. Many see dampening this inflammatory response as a promising way to fight hyperalgesia, because it would not interfere with opioids’ pain-relieving activity on neural receptors. Several efforts are underway. The San Diego, California–based biotech company MediciNova recently completed a phase II trial of a glia-inhibiting drug called ibudilast, already approved as an asthma treatment in Japan, to relieve pain and treat withdrawal in opioid abusers. A study led by researchers at Yale University is testing the antibiotic acne medication minocycline, which is also thought to block glial activation in the brain. And research spun out of neuroscientist Linda Watkins’s group at the University of Colorado in Boulder is testing a new pain drug that may tame glia in the spinal cord by blocking a signaling protein on their surface. If inflammation turns out to be a key driver of OIH, it might also point the way to a better test for the effect, says Lesley Colvin, a pain researcher at the University of Edinburgh. Markers of inflammation in the blood might correlate with clinical signs of hyperalgesia or declining pain thresholds on sensory tests. Colvin says she already sees strong evidence of hyperalgesia in high-dose opioid users at the clinic where she works. With so much at stake, she is eager to understand the phenomenon and how it might affect them long term. “Although it’s complicated,” she says, “that doesn’t mean we shouldn’t try and work out the details.”


News Article | October 28, 2016
Site: www.eurekalert.org

The University of Illinois at Chicago College of Liberal Arts and Sciences is seeking a select group of students for a historic summer expedition that will send them from city to sea under the banner of the National Science Foundation. The one-time Northwest Passage Project, a climate and marine research and education program aimed at engaging diverse participants and audiences, is funded by a three-year, $3 million NSF grant. Set to begin in August 2017, students will join ocean scientists aboard the SSV Oliver Hazard Perry, a 200-foot sailing vessel, for an excursion across the Canadian Arctic's remote Northwest Passage. The initiative is led by researchers from the University of Rhode Island's Graduate School of Oceanography's Inner Space Center, in collaboration with UIC and five other minority-serving institutions: California State University Channel Islands; City College of New York; Florida International University; Texas State University; and Virginia Commonwealth University. Other partners include the film company David Clark, Inc.; the SSV Oliver Hazard Perry; three science museums; and PBS NewsHour Reporting Labs. Scientists from the departments of biological sciences and earth and environmental sciences will select 15 - 20 UIC undergraduates -- about half from science, technology, engineering and mathematics disciplines, and the other half from any major -- to participate in the expedition and on-shore support activities. UIC will be represented on the vessel by at least three undergraduates and one graduate student on two crews, each on a 17-day journey. At least four undergraduate student internships will be supported by NSF funds, the rest being supported by UIC College of Liberal Arts and Sciences programs. Students will learn about the changing Arctic as the ship travels; gain navigation and sailing skills; retrace lost expeditions to the passage; and work alongside the scientists as they conduct Arctic research. Participants will also contribute to 30 live broadcasts from the Arctic that will stream from the ship via satellite to the Inner Space Center, which will then send the transmissions to the Smithsonian Institution's National Museum of Natural History, the Exploratorium in San Francisco, the Alaska Sea Life Center and UIC. Audiences will be able to interact in real time with the scientists and students aboard the ship during these broadcasts. This is a once in a lifetime opportunity for UIC students, says Miquel Gonzalez-Meler, the faculty representative involved with the project. "Students will not only be part of pioneering research in the Arctic, but will also be able to place the science in the social context of a globalized world," said Gonzalez-Meler, professor of biological sciences and the college's associate dean for student academic affairs. "We've built a program where adventurous and highly motivated students will be able to observe the climate sensitivity of the Arctic and the social and climate repercussions of these changes to Chicago, Illinois, and the nation. And best of all, no experience is necessary." Max Berkelhammer, assistant professor of earth and environmental sciences, and other faculty mentors will also work with the UIC students. Some students not aboard the ship will participate in science telepresence or in the media production while based at the University of Rhode Island's oceanography institute. Other students will participate from UIC in support of onboard science activities, science communication and social media. All UIC students selected for the project will take a college-required course during the spring semester before their summer internships. An onboard film crew will capture the science discoveries and follow the students for a two-hour documentary, "Frozen Obsession," that will describe the history and implications - from climate to commerce - of the changing Arctic. In 2018, UIC's student team will host a screening of the film and other events related to the expedition. UIC undergraduates - seniors are excluded - interested in applying to the program can find more information and an application online. The deadline to apply is Nov. 18 at 5 p.m. ET. Selected students will be notified by the end of November to enroll in the mandatory topic course. Call (312) 413-7563 or email mmeler@uic.edu for further details.


News Article | November 20, 2016
Site: www.prweb.com

An analysis of collegiate graduate and post-graduate programs by AffordableCollegesOnline.org has determined the best places to earn a Master’s and Doctorate Degree Online in the nation for 2016-2017. As a leader in online higher education resources, the site measured cost and quality data to determine the top online programs for each degree level, identifying Western New Mexico University, Fort Hays State University, University of Central Arkansas, Arkansas State University and Wilmington University as the top scoring schools for earning an online master’s degree and the University of Colorado Denver, University of Mississippi, Indiana State University, University of Arkansas and Texas A&M University as the top scoring schools for earning an online doctorate degree. "As of 2013, over 23 percent of master’s and doctoral level students were completing their degrees entirely online,” said Dan Schuessler, CEO and Founder of AffordableCollegesOnline.org. "Our list pinpoints the schools around the nation who are providing students affordable, quality options when it comes to earning a post-baccalaureate degree, with the bonus of greater learning flexibility provided by online curriculum.” Schools must meet specific criteria to qualify for the Best Online Master’s Degree Programs & Best Online Doctorate Degree Programs lists. All institutions must be accredited, public or private not-for-profit entities and must offer in-state tuition and fees under $25,000 per year. Eligible institutions are further evaluated and scored based on a variety of data points, such as financial aid offerings, graduation rates and online program variety, to determine overall cost and quality rankings by school. Full rankings, as well as specific details on data and methodology used to determine school scores can be found at the following pages: All colleges highlighted for excellence in Online Master’s Programs for 2016-2017 are listed below: Adams State University Arkansas State University - Main Campus Ball State University Brenau University Chadron State College Columbus State University Concordia University-Saint Paul Delta State University East Carolina University Embry-Riddle Aeronautical University - Worldwide Emporia State University Fort Hays State University Graceland University - Lamoni Indiana State University Indiana Wesleyan University Liberty University Missouri State University - Springfield New Mexico State University - Main Campus North Carolina Central University North Carolina State University at Raleigh Northern Arizona University Northwestern State University of Louisiana Oklahoma State University - Main Campus Purdue University - Main Campus Saint Leo University Southeastern Oklahoma State University Southern Arkansas University Main Campus The University of Texas at Brownsville (University of Texas Rio Grande Valley) The University of Texas at Tyler Troy University University of Alabama at Birmingham University of Arkansas University of Arkansas at Little Rock University of Central Arkansas University of Central Missouri University of Colorado Denver University of Idaho University of Louisiana at Monroe University of Memphis University of Nebraska at Kearney University of North Carolina at Greensboro University of North Dakota University of Southern Mississippi University of West Alabama Wayland Baptist University Webster University Western Carolina University Western Kentucky University Western New Mexico University Wilmington University All colleges highlighted for excellence in Online Doctorate Programs for 2016-2017 are listed below: Allen College Amridge University Clemson University Colorado State University - Fort Collins Hampton University Harding University Indiana State University Kansas State University Keiser University - Fort Lauderdale Liberty University Mississippi State University Northern Arizona University Oregon State University Pennsylvania State University - Main Campus Rutgers University - New Brunswick Southern Illinois University - Edwardsville Stony Brook University Temple University Texas A & M University - College Station Texas A & M University - Commerce Texas Tech University The University of Alabama The University of Montana The University of Tennessee - Knoxville The University of Texas at Tyler The University of Texas Medical Branch Union Institute & University University at Buffalo University of Alabama in Huntsville University of Alaska Fairbanks University of Arizona University of Arkansas University of California - Berkeley University of Colorado Denver University of Delaware University of Florida University of Louisiana at Monroe University of Massachusetts - Amherst University of Michigan - Flint University of Minnesota - Twin Cities University of Mississippi University of Nebraska - Lincoln University of North Carolina at Chapel Hill University of North Carolina at Greensboro University of North Dakota University of Northern Colorado University of South Carolina - Columbia University of the Cumberlands Virginia Commonwealth University Wilmington University AffordableCollegesOnline.org began in 2011 to provide quality data and information about pursuing an affordable higher education. Our free community resource materials and tools span topics such as financial aid and college savings, opportunities for veterans and people with disabilities, and online learning resources. We feature higher education institutions that have developed online learning environments that include highly trained faculty, new technology and resources, and online support services to help students achieve educational and career success. We have been featured by nearly 1,100 postsecondary institutions and nearly 120 government organizations.


NEW YORK, Nov. 01, 2016 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT) (Intercept), a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat non-viral, progressive liver diseases, today announced multiple Ocaliva® (obeticholic acid) for PBC and INT-767 data presentations at the upcoming American Academy for the Study of Liver Diseases (AASLD) Annual Meeting (The Liver Meeting®), taking place November 11 – 15 in Boston, MA.  “We have numerous presentations at this year’s Liver Meeting, among them an oral presentation examining Ocaliva’s effects on non-invasive fibrosis measurements in patients with PBC,” said David Shapiro, M.D., Intercept's Chief Medical Officer & Executive Vice President, Development. “Other PBC presentations include an evaluation of Ocaliva data using a long-term prognostic model developed by the UK-PBC Study Group and analyses of Ocaliva’s safety and efficacy in PBC patient populations with end-stage liver disease and renal disease. In addition, we look forward to sharing an analysis of fibrosis data from the FLINT trial in NASH and new preclinical research examining INT-767 – our FXR/TGR5 dual agonist – in animal models of NASH and metabolic disease.” Intercept also announced its sponsorship of the new TARGET-NASH patient registry, which will advance the understanding of NASH diagnosis and management across multiple populations in a real world setting. As the NASH treatment landscape evolves, the registry will evaluate the safety and effectiveness of new agents across populations not included or underrepresented in Phase 3 clinical trials. TARGET-NASH is led by an academic steering committee chaired by Drs. Arun Sanyal of Virginia Commonwealth University, Ken Cusi of the University of Florida and Brent Tetri of St. Louis University. The registry is currently enrolling and additional details about TARGET-NASH are available at ClinicalTrials.gov. In the United States, Ocaliva was recently approved by the FDA for the treatment primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA. Obeticholic acid is also being investigated for patients with NASH and liver fibrosis, as well as primary sclerosing cholangitis and biliary atresia. Intercept will be exhibiting at booth 524 throughout the Liver Meeting. Select presentations include: A full list of sessions at AASLD, including symposia, relating to obeticholic acid is available on the AASLD website. About Primary Biliary Cholangitis Primary biliary cholangitis (PBC) is a rare, autoimmune cholestatic liver disease that puts patients at risk for life-threatening complications. PBC is primarily a disease of women, afflicting approximately one in 1,000 women over the age of 40. If left untreated, survival of PBC patients is significantly worse than the general population. About Ocaliva® Ocaliva (obeticholic acid) for the treatment of PBC is a potent and highly selective agonist of the farnesoid X receptor (FXR), a nuclear receptor expressed in the liver and intestine. FXR is a key regulator of bile acid, inflammatory, fibrotic and metabolic pathways. In May 2016, the U.S. Food and Drug Administration (FDA) granted accelerated approval to obeticholic acid for the treatment of PBC under the brand name Ocaliva based on a reduction in ALP. An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. In October 2016, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending the conditional marketing authorization of Ocaliva in PBC. Based on the CHMP’s positive recommendation, the final decision of the European Commission on the conditional marketing authorization of Ocaliva in PBC is expected by the end of 2016. The brand name Ocaliva has been provisionally approved by the EMA. Ocaliva is contraindicated in patients with complete biliary obstruction. In two 3-month, placebo-controlled clinical trials, a dose-response relationship was observed for the occurrence of liver-related adverse reactions including jaundice, ascites and primary biliary cholangitis flare with dosages of Ocaliva of 10 mg once daily to 50 mg once daily (up to 5-times the highest recommended dosage), as early as one month after starting treatment with Ocaliva. In a pooled analysis of three placebo-controlled trials in patients with PBC, the exposure-adjusted incidence rates for all serious and otherwise clinically significant liver-related adverse reactions, and isolated elevations in liver biochemical tests, per 100 patient exposure years (PEY) were: 5.2 in the Ocaliva 10 mg group (highest recommended dosage), 19.8 in the Ocaliva 25 mg group (2.5 times the highest recommended dosage) and 54.5 in the Ocaliva 50 mg group (5 times the highest recommended dosage) compared to 2.4 in the placebo group. Monitor patients during treatment with Ocaliva for elevations in liver biochemical tests and for the development of liver-related adverse reactions. Weigh the potential risks against the benefits of continuing treatment with Ocaliva in patients who have experienced clinically significant liver-related adverse reactions. The maximum recommended dosage of Ocaliva is 10 mg once daily. Adjust the dosage for patients with moderate or severe hepatic impairment. Severe pruritus was reported in 23% of patients in the Ocaliva 10 mg arm, 19% of patients in the Ocaliva titration arm and 7% of patients in the placebo arm in the POISE trial, a 12-month double-blind randomized controlled trial of 216 patients. Severe pruritus was defined as intense or widespread itching, interfering with activities of daily living, or causing severe sleep disturbance, or intolerable discomfort, and typically requiring medical interventions. In the subgroup of patients in the Ocaliva titration arm who increased their dosage from 5 mg once daily to 10 mg once daily after 6 months of treatment (n=33), the incidence of severe pruritus was 0% from months 0 to 6 and 15% from months 6 to 12. The median time to onset of severe pruritus was 11, 158 and 75 days for patients in the Ocaliva 10 mg, Ocaliva titration and placebo arms, respectively. Management strategies include the addition of bile acid resins or antihistamines, Ocaliva dosage reduction and/or temporary interruption of Ocaliva dosing. Patients with PBC generally exhibit hyperlipidemia characterized by a significant elevation in total cholesterol primarily due to increased levels of high density lipoprotein-cholesterol (HDL‑C). In the POISE trial, dose-dependent reductions from baseline in mean HDL-C levels were observed at 2 weeks in Ocaliva-treated patients, 20% and 9% in the 10 mg and titration arms, respectively, compared to 2% in the placebo arm. At month 12, the reduction from baseline in mean HDL-C level was 19% in the Ocaliva 10 mg arm, 12% in the Ocaliva titration arm and 2% in the placebo arm. Nine patients in the Ocaliva 10 mg arm and six patients in the Ocaliva titration arm, versus three patients in the placebo arm, had reductions in HDL-C to less than 40 mg/dL. Monitor patients for changes in serum lipid levels during treatment. For patients who do not respond to Ocaliva after one year at the highest recommended dosage that can be tolerated (maximum of 10 mg once daily), and who experience a reduction in HDL-C, weigh the potential risks against the benefits of continuing treatment. The most common adverse reactions from subjects taking Ocaliva (≥5%) were pruritus, fatigue, abdominal pain and discomfort, rash, oropharyngeal pain, dizziness, constipation, arthralgia, thyroid function abnormality and eczema. Bile Acid Binding Resins Bile acid binding resins such as cholestyramine, colestipol or colesevelam absorb and reduce bile acid absorption and may reduce the absorption, systemic exposure and efficacy of Ocaliva. If taking bile acid binding resins, take Ocaliva at least 4 hours before or 4 hours after (or at as great an interval as possible) taking a bile acid binding resin. About Intercept Intercept is a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat non-viral, progressive liver diseases, including primary biliary cholangitis (PBC), nonalcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC) and biliary atresia. Founded in 2002 in New York, Intercept now has operations in the United States, Europe and Canada. For more information about Intercept, please visit www.interceptpharma.com. Safe Harbor Statements This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the clinical relevance and utility of ALP and the surrogate endpoint used in the Phase 3 POISE trial to predict clinical outcomes, the acceptance of Ocaliva® (obeticholic acid) as a treatment for PBC by healthcare providers, patients and payors, the potential approval of OCA in PBC by the European Commission and other regulatory bodies and the timelines related thereto, the availability of OCA for the treatment of PBC in Europe and other jurisdictions outside the United States and timelines related thereto, the anticipated prevalence of and other epidemiological estimates and market data related to PBC, the continued development of OCA and Intercept's other product candidates, and our strategic directives under the caption "About Intercept." These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of important risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: Intercept's ability to successfully commercialize Ocaliva in PBC, and Intercept's ability to maintain its regulatory approval of Ocaliva in the United States for Ocaliva in PBC; the initiation, cost, timing, progress and results of Intercept's development activities, preclinical studies and clinical trials, including Intercept’s development program in NASH; the timing of and Intercept's ability to obtain and maintain regulatory approval of OCA in PBC in countries outside the United States and in indications other than PBC and any other product candidates it may develop such as INT-767; conditions that may be imposed by regulatory authorities on Intercept's marketing approvals for its product candidates such as the need for clinical outcomes data (and not just results based on achievement of a surrogate endpoint), and any related restrictions, limitations, and/or warnings in the label of any approved product candidates; Intercept's plans to research, develop and commercialize its product candidates; Intercept's ability to obtain and maintain intellectual property protection for its product candidates; Intercept's ability to successfully commercialize OCA in indications other than PBC and its other product candidates; the size and growth of the markets for Intercept's product candidates and its ability to serve those markets; the rate and degree of market acceptance of any of Intercept's products, which may be affected by the reimbursement that it may receive for its products from payors; the success of competing drugs that are or become available; the election by Intercept's collaborators to pursue research, development and commercialization activities; Intercept's ability to attract collaborators with development, regulatory and commercialization expertise; regulatory developments in the United States and other countries; the performance of third-party suppliers and manufacturers; Intercept's need for and ability to obtain additional financing; Intercept's estimates regarding expenses, future revenues and capital requirements and the accuracy thereof; Intercept's use of cash, short-term investments and the proceeds from the offering; Intercept's ability to attract and retain key scientific or management personnel; and other factors discussed under the heading "Risk Factors" contained in our annual report on Form 10-K for the year ended December 31, 2015 filed on February 29, 2016 as well as any updates to these risk factors filed from time to time in our other filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Intercept undertakes no duty to update this information unless required by law.


-- First time a PRO to be used as a secondary clinical endpoint in a SCD registrational study -- --Company to Host Webcast Today at 12:15 p.m. PT to Discuss ASH Data Presentations — SOUTH SAN FRANCISCO, Calif., Dec. 05, 2016 (GLOBE NEWSWIRE) -- Global Blood Therapeutics, Inc. (GBT) (NASDAQ:GBT) today announced that the methodology used to develop the Patient Reported Outcome (PRO) tool that will be used as a secondary clinical endpoint in the company’s planned pivotal Phase 3 clinical trial of GBT440 in people with sickle cell disease (SCD), titled the HOPE (Hemoglobin Oxygen Affinity Modulation to Inhibit HbS PolymErization) Study, was presented at the 58th American Society of Hematology (ASH) Annual Meeting & Exposition (abstract #4760). The nine-item Sickle Cell Disease Severity Measure (SCDSM) has been designed by GBT to assess the entire range of SCD symptoms, to distinguish between good days and bad days based on symptoms and to measure all crisis events regardless of health care utilization. “Previous SCD studies have focused on vaso-occlusive crisis (VOC) defined as a painful crisis requiring hospital or emergency room utilization as the traditional clinical endpoint. However, studies have shown that VOC is not a full measure of the burden of SCD daily symptoms because many episodes of pain are managed at home rather than in a doctor’s office, hospital or emergency room and are thus under-reported. VOC is the tip of the iceberg,” said Wally Smith, M.D., Florence Neal Cooper Smith Professor of Sickle Cell Disease Director, and Director of the comprehensive sickle cell program at Virginia Commonwealth University. “By having this new electronic patient reported outcomes (PRO) tool, we will be able to more reliably assess daily symptom severity, with a single total symptom score, potentially allowing us to accelerate the development of urgently needed new SCD therapies.” PRO development used qualitative and quantitative analyses and was undertaken in collaboration with SCD patient groups and external experts, and with active engagement with the Clinical Outcomes Assessment group of the United States Food and Drug Administration (FDA). The instrument was designed with a specific set of nine questions to produce a score to measure the full range of daily SCD severity in adult and adolescent SCD patients. The HOPE PRO includes questions specific to pain, energy level and fatigue, concentration and breathlessness- the symptoms that matters the most to patients with SCD. When qualified by following FDA guidance, a PRO instrument can be used as a clinical endpoint to establish benefit for regulatory approval. In the HOPE Study, the HOPE PRO instrument will be administered on a hand-held electronic device and will explore the clinical benefit of GBT440 in SCD. It is designed to distinguish between good days and bad days based on symptoms, which should be sensitive to all pain crises, with or without healthcare utilization. The PRO will also be able to assess an improvement in symptoms from baseline, such as improved fatigue. During Part A of the HOPE Study, the PRO instrument will quantify the magnitude of changes in daily total symptom scores over three months. The HOPE PRO complies with the FDA’s issued guidance for PRO development. “We are excited to have developed, in conjunction with the SCD community, the first PRO for SCD suitable for use as a clinical endpoint that could support potential FDA approval of a drug for the treatment of SCD. The HOPE PRO is designed to be a reliable, valid and sensitive measurement that meets regulatory requirements as a clinical outcome assessment tool, is easy for patients to use, and will generate scores that are clinically meaningful,” said Ted W. Love, M.D., president and chief executive officer of GBT. “With the utilization of the HOPE PRO, our highly innovative HOPE Study trial design will allow us to measure the core symptoms of SCD that matter most to patients - pain and fatigue - as well as other key SCD symptoms.” Also presented at ASH yesterday were data from the ongoing Phase 1/2 GBT440-001 study that further support the safety and efficacy profile of GBT440 as a potentially disease-modifying therapy for sickle cell disease (SCD) and results showing how GBT440 is metabolized in healthy subjects. Investor Event Webcast Details Today, Monday, December 5, at 12:15 p.m. PT, members of GBT’s management team and Jo Howard, MB BChir, MRCP, FRCPath, of Guy’s and St Thomas’ NHS Foundation Trust, Wally R. Smith, MD of Virginia Commonwealth University, and Jeremy Hobart, BSc PhD FRCP Dip Public Health, of Peninsula Schools of Medicine and Dentistry will review GBT440 ASH data presentations. The event will be webcast live and will be available for replay from the Investors section of GBT’s website at www.globalbloodtx.com for 30 days. About GBT440 in Sickle Cell Disease GBT440 is being developed as an oral, once-daily therapy for patients with SCD. GBT440 works by increasing hemoglobin's affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, GBT believes GBT440 blocks polymerization and the resultant sickling of red blood cells. With the potential to restore normal hemoglobin function and improve oxygen delivery, GBT believes that GBT440 may dramatically modify the course of SCD. In recognition of the critical need for new SCD treatments, the U.S. Food and Drug Administration (FDA) has granted GBT440 both fast track and orphan drug designations and the European Commission (EC) has designated GBT440 as an orphan medicinal product for the treatment of patients with SCD. In addition to the ongoing Phase 1/2 GBT440-001 trial, GBT440 is being evaluated in an open-label, single and multiple dose study in adolescents (age 12 to 17) with SCD. This study is assessing the safety, tolerability, pharmacokinetics and exploratory treatment effect of GBT440. Additionally, GBT440 will be evaluated in the pivotal Phase 3 HOPE Study. This randomized, double-blind, placebo-controlled, multi-national trial will enroll up to 400 patients age 12 and older with SCD who have had at least one episode of vaso-occlusive crisis (VOC) in the previous year. The study will be conducted in two parts: Part A will compare GBT440 administered at doses of 900 or 1,500 mg per day vs. placebo in up to 150 patients treated for at least 12 weeks, and Part B will include 250 patients randomized to placebo or a dose of GBT440 based on Part A. The main objectives of Part A are to select the optimal dose, define the final secondary endpoints for Part B, and qualify the PRO instrument. The primary efficacy endpoint of the HOPE Study is the proportion of patients who achieve a greater than 1 g/dL increase in hemoglobin at 24 weeks of treatment compared with baseline. Key secondary efficacy endpoints include the effect of GBT440 on SCD symptom exacerbation (as measured by the HOPE PRO instrument), overall SCD symptoms, traditionally defined VOCs, hospitalizations and red blood cell transfusions. About Sickle Cell Disease (SCD) SCD is a lifelong inherited blood disorder caused by a genetic mutation in the beta-chain of hemoglobin, leading to formation of abnormal hemoglobin known as sickle hemoglobin, or HbS. In its deoxygenated state, HbS has a propensity to polymerize, or bind together forming long, rigid rods within a red blood cell (RBC). The polymer rods deform RBCs to assume a sickled shape and to become inflexible, which can cause blockage in small blood vessels. Beginning in childhood, SCD patients suffer unpredictable and recurrent episodes or crises of severe pain due to blocked blood flow to organs, which often lead to psychosocial and physical disabilities. This blocked blood flow, combined with hemolytic anemia (the destruction of RBCs), can eventually lead to multi-organ damage and early death. About Global Blood Therapeutics Global Blood Therapeutics, Inc. is a clinical-stage biopharmaceutical company dedicated to discovering, developing and commercializing novel therapeutics to treat grievous blood-based disorders with significant unmet need. GBT is developing its lead product candidate, GBT440, as an oral, once-daily therapy for sickle cell disease and will initiate its Phase 3 clinical trial by the end of 2016. GBT is also investigating GBT440 for the treatment of hypoxemic pulmonary disorders in two ongoing Phase 2a studies in patients with idiopathic pulmonary fibrosis. To learn more, please visit: www.globalbloodtx.com. Forward-Looking Statements Statements we make in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended. We intend these forward-looking statements, including statements regarding the therapeutic potential and safety profile of GBT440, our ability to implement our clinical development plans for GBT440, the timing of, and our ability to generate data from, our ongoing Phase 1/2 clinical trial of GBT440 and our ability to begin and generate data from our HOPE Study, and regarding the use of the PRO in our HOPE Study, to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Securities Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. We can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved, and furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a variety of risks and factors that are beyond our control including, without limitation, the risks that our clinical and preclinical development activities may be delayed or terminated for a variety of reasons, that regulatory authorities may disagree with our clinical development plans or require additional studies or data to support further clinical investigation of our product candidates, and that drug-related adverse events may be observed in later stages of clinical development, along with those risks set forth in our Annual Report on Form 10-K for the fiscal year ended December 31, 2015, and in our Quarterly Reports on Form 10-Q for the quarters ended March 31, 2016, June 30, 2016 and September 30, 2016, as well as discussions of potential risks, uncertainties and other important factors in our subsequent filings with the U.S. Securities and Exchange Commission. Except as required by law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.


--Results Showed GBT440 Treatment Led to Rapid, Significant, Profound and Durable Reduction in Hemolysis and Sickled Cells in All Patients Treated for Up to Six Months-- --Company to Host Webcast Tomorrow at 12:15 p.m. PT to Discuss Data-- SOUTH SAN FRANCISCO, Calif., Dec. 04, 2016 (GLOBE NEWSWIRE) -- Global Blood Therapeutics, Inc. (GBT) (NASDAQ:GBT) today announced the presentation of results from its ongoing Phase 1/2 GBT440-001 study that further support the safety and efficacy profile of GBT440 as a potentially disease-modifying therapy for sickle cell disease (SCD). These data were presented at the 58th American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego. Results showing how GBT440 is metabolized in healthy subjects were also presented today. “Sickle cell disease is one of the most common inherited diseases worldwide and has a lifelong impact on those affected, who experience severe daily symptoms of pain and fatigue, organ damage and early mortality due to sickling and hemolytic anemia,” said Jo Howard, MB BChir, MRCP, FRCPath, of Guy’s and St Thomas’ NHS Foundation Trust. “The data we continue to gather, including long-term dosing of up to six months, suggest that GBT440 has the potential to improve outcomes in this serious disease. If so, that would be a major breakthrough for the SCD community, which currently has limited treatment options.” “The six-month data show that GBT440 treatment leads to clinically significant increases in hemoglobin and profound and durable reductions in hemolysis and peripheral blood sickle cells. These data, together with prior preclinical, clinical and safety data, further support the excellent safety and tolerability for GBT440 to date, and the design of the Phase 3 HOPE (Hemoglobin Oxygen Affinity Modulation to Inhibit HbS PolymErization) Study,” said Ted W. Love, M.D., president and chief executive officer of GBT. “We have begun to initiate HOPE Study clinical trial sites and are currently screening patients. The HOPE Study is designed to provide a robust assessment of the ability of GBT440 to potentially modify the course of SCD in a broad group of patients.” Long-Term Dosing in Sickle Cell Disease Subjects with GBT440, a Novel HbS Polymerization Inhibitor (abstract #2488) GBT440-001 is a randomized, placebo-controlled, double-blind, single and multiple ascending dose study. This ongoing Phase 1/2 study is evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of GBT440 in both healthy subjects and adults with SCD. The study is being conducted in three parts: Part A (single dose administration), Part B (multiple dose administration, daily for 15 days in healthy subjects and 28 days in SCD patients) and Part C (multiple dose administration, daily for 90 days in SCD patients). Some patients in Part C have taken GBT440 for up to 6 months. Absorption, Metabolism and Excretion of GBT440 a Novel Hemoglobin S (HbS) Polymerization Inhibitor for the Treatment of Sickle Cell Disease (SCD), in Healthy Male Subjects (abstract #2487) Results of a study evaluating the pharmacokinetics, metabolism and excretion of GBT440 given orally to healthy subjects showed that the drug was completely excreted from the body, with a half-life of approximately three days. This is much shorter than the lifespan of a red blood cell (about 120 days) of a healthy subject, suggesting that the binding of GBT440 to hemoglobin is a reversible process. The data also suggest that the pharmacokinetics of GBT440 are unlikely to be affected in patients with renal disorders. Investor Event Webcast Details Tomorrow, Monday, December 5, at 12:15 p.m. PT, members of GBT’s management team and Drs. Jo Howard, Wally R. Smith of Virginia Commonwealth University, and Jeremy Hobart of Peninsula Schools of Medicine and Dentistry will review the ASH data presentations. The event will be webcast live and will be available for replay from the Investors section of GBT’s website at www.globalbloodtx.com for 30 days. About GBT440 in Sickle Cell Disease GBT440 is being developed as an oral, once-daily therapy for patients with SCD. GBT440 works by increasing hemoglobin's affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, GBT believes GBT440 blocks polymerization and the resultant sickling of red blood cells. With the potential to restore normal hemoglobin function and improve oxygen delivery, GBT believes that GBT440 may dramatically modify the course of SCD. In recognition of the critical need for new SCD treatments, the U.S. Food and Drug Administration (FDA) has granted GBT440 both fast track and orphan drug designations and the European Commission (EC) has designated GBT440 as an orphan medicinal product for the treatment of patients with SCD. In addition to the ongoing Phase 1/2 GBT440-001 trial, GBT440 is being evaluated in an open-label, single and multiple dose study in adolescents (age 12 to 17) with SCD. This study is assessing the safety, tolerability, pharmacokinetics and exploratory treatment effect of GBT440. Additionally, GBT440 will be evaluated in the pivotal Phase 3 HOPE Study. This randomized, double-blind, placebo-controlled, multi-national trial will enroll up to 400 patients age 12 and older with SCD who have had at least one episode of vaso-occlusive crisis (VOC) in the previous year. The study will be conducted in two parts: Part A will compare GBT440 administered at doses of 900 or 1,500 mg per day vs. placebo in up to 150 patients treated for at least 12 weeks, and Part B will include 250 patients randomized to placebo or a dose of GBT440 based on Part A. The main objectives of Part A are to select the optimal dose, define the final secondary endpoints for Part B, and qualify the PRO instrument. The primary efficacy endpoint of the HOPE Study is the proportion of patients who achieve a greater than 1 g/dL increase in hemoglobin at 24 weeks of treatment compared with baseline. Key secondary efficacy endpoints include the effect of GBT440 on SCD symptom exacerbation (as measured by the HOPE PRO instrument), overall SCD symptoms, traditionally defined VOCs, hospitalizations and red blood cell transfusions. About Sickle Cell Disease (SCD) SCD is a lifelong inherited blood disorder caused by a genetic mutation in the beta-chain of hemoglobin, leading to formation of abnormal hemoglobin known as sickle hemoglobin, or HbS. In its deoxygenated state, HbS has a propensity to polymerize, or bind together forming long, rigid rods within a red blood cell (RBC). The polymer rods deform RBCs to assume a sickled shape and to become inflexible, which can cause blockage in small blood vessels. Beginning in childhood, SCD patients suffer unpredictable and recurrent episodes or crises of severe pain due to blocked blood flow to organs, which often lead to psychosocial and physical disabilities. This blocked blood flow, combined with hemolytic anemia (the destruction of RBCs), can eventually lead to multi-organ damage and early death. About Global Blood Therapeutics Global Blood Therapeutics, Inc. is a clinical-stage biopharmaceutical company dedicated to discovering, developing and commercializing novel therapeutics to treat grievous blood-based disorders with significant unmet need. GBT is developing its lead product candidate, GBT440, as an oral, once-daily therapy for sickle cell disease and will initiate its pivotal Phase 3 HOPE clinical trial by the end of 2016. GBT is also investigating GBT440 for the treatment of hypoxemic pulmonary disorders in two ongoing Phase 2a studies in patients with idiopathic pulmonary fibrosis. To learn more, please visit: www.globalbloodtx.com. Forward-Looking Statements Statements we make in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended. We intend these forward-looking statements, including statements regarding the therapeutic potential and safety profile of GBT440, our ability to implement our clinical development plans for GBT440, the timing of, and our ability to generate data from, our ongoing Phase 1/2 clinical trial of GBT440 and our ability to enroll patients in and begin screening in our HOPE Study, to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Securities Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. We can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved, and furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a variety of risks and factors that are beyond our control including, without limitation, the risks that our clinical and preclinical development activities may be delayed or terminated for a variety of reasons, that regulatory authorities may disagree with our clinical development plans or require additional studies or data to support further clinical investigation of our product candidates, and that drug-related adverse events may be observed in later stages of clinical development, along with those risks set forth in our Annual Report on Form 10-K for the fiscal year ended December 31, 2015, and in our Quarterly Reports on Form 10-Q for the quarters ended March 31, 2016, June 30, 2016 and September 30, 2016, as well as discussions of potential risks, uncertainties and other important factors in our subsequent filings with the U.S. Securities and Exchange Commission. Except as required by law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.


News Article | February 20, 2017
Site: globenewswire.com

MELBOURNE, Australia, Feb. 20, 2017 (GLOBE NEWSWIRE) -- Immuron Limited (ASX:IMC), an Australian biopharmaceutical company focused on oral immunotherapy utilizing polyclonal antibody products to target immune-mediated diseases, today announced that the Company’s IMM-124E Phase II clinical trial for the treatment of NASH (Non-Alcoholic Steatohepatitis) has successfully reached its full recruitment milestone of 120 randomized patients. The Phase II, multicenter, double blind randomized clinical study is designed to assess the safety and effectiveness of IMM-124E for the treatment of NASH.  The effectiveness element is primarily focussed on evaluating the effect of IMM-124E on patients with NASH, compared to placebo, after six (6) months of treatment.  The clinical trial protocol was developed by Immuron in partnership with its Scientific Advisory Board led by Dr. Arun Sanyal of Virginia Commonwealth University (USA).  The study is conducted in the United States, Australia, and Israel. This effectively concludes the recruitment process of the NASH Phase II clinical trial, although due to strong enrollment demand, the existing 12 patients in screening will be allowed to proceed to randomization, pending their respective eligibility. As previously announced, the Company expects to report the topline results of the clinical trial in the second half of 2017. NASH, a severe form of non-alcoholic fatty liver disease (NAFLD) that causes liver inflammation and damage, afflicts approximately 16 million people in the United States each year.  Currently, no drug has received FDA approval for the treatment of NASH, leading physicians to treat the disease by addressing underlying conditions such as diet and obesity. For this reason, NASH is widely considered a tremendous market opportunity for pharmaceutical and biotechnology companies. “This significant milestone results from the efforts of many over the past three years.  I would like to communicate my profound gratitude to Immuron’s clinical team for their tireless effort, and also to our valued principal investigators and their teams, for their dedication to the IMM-124E clinical trial. IMM-124E has a unique multifactorial mechanism of action (MOA) that we believe possesses a unique combination of safety and efficacy attributes which have the potential to greatly improve outcomes for NASH patients worldwide.” “We are thrilled that Immuron's clinical team, in partnership with the investigators and site staff, have been able to significantly improve the study’s recruitment rate over the past few months to now reach full recruitment.  I would like to especially thank our Lead Principal Investigator, Dr. Arun Sanyal, for his leadership throughout the trial.  We look forward to continuing our clinical work with Dr. Sanyal and other site principal investigators through the completion of the trial and beyond.” About Immuron Immuron Ltd (ASX:IMC) (OTCQB:IMROY) is a microbiome company focused on developing and commercialising oral immunotherapeutics for the treatment of many gut mediated diseases. Immuron has a unique and safe technology platform that enables a shorter development therapeutic cycle. The Company currently markets and sells Travelan® for the prevention of travellers’ diarrhoea, whilst its lead product candidate IMM-124E is in Phase 2b clinical trials for NASH and ASH. These products together with the Company’s other preclinical immunotherapy pipeline products targeting immune-related diseases currently under development, will meet a large unmet need in the market. Certain statements made in this release are forward-looking statements and are based on Immuron’s current expectations, estimates and projections. Words such as “anticipates,” “expects,” “intends,” “plans,” “believes,” “seeks,” “estimates,” “guidance” and similar expressions are intended to identify forward-looking statements. Although Immuron believes the forward-looking statements are based on reasonable assumptions, they are subject to certain risks and uncertainties, some of which are beyond Immuron’s control, including those risks or uncertainties inherent in the process of both developing and commercialising technology. As a result, actual results could materially differ from those expressed or forecasted in the forward-looking statements. The forward-looking statements made in this release relate only to events as of the date on which the statements are made. Immuron will not undertake any obligation to release publicly any revisions or updates to these forward-looking statements to reflect events, circumstances or unanticipated events occurring after the date of this release except as required by law or by any appropriate regulatory authority.


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

Other means besides a registry should be developed to evaluate potential health effects of military burn pits' toxic emissions on exposed service members; data from burn pit registry could be used for other purposes WASHINGTON - Inherent features of registries that rely on voluntary participation and self-reported information make them fundamentally unsuitable for determining whether emissions from military burn pits in Iraq, Afghanistan, and other locations in Southwest Asia caused health problems in service members who were exposed to them, says a new congressionally mandated report from the National Academies of Sciences, Engineering, and Medicine. While the U.S. Department of Veterans Affairs' Airborne Hazards and Open Burn Pit (AH&OBP) Registry provides a forum for collecting and recording information on those who choose to participate, a more rigorous and appropriate approach is needed to examine the relationship between the exposures and health outcomes, such as a well-designed epidemiologic study. A previous report by the former Institute of Medicine [now part of the National Academies] found inconclusive evidence on the health effects of exposure to military burn pits and contained advice and recommendations on how a study might be conducted. For some time, the disposal of trash on military bases through open-air burn pits exposed service personnel deployed in Iraq, Afghanistan, and other locations in Southwest Asia to airborne particulate matter and other potential health hazards, which in turn raised concerns about acute and chronic health consequences in these individuals. In 2013, Congress gave the VA one year to create a registry that would acquire exposure and health information on service members and veterans who may have been exposed to airborne hazards during deployment -- such as smoke from burn pits, oil-well fires, dust storms, or pollution. The VA developed an ambitious program to enroll volunteer participants and created the AH&OBP Registry. In response to a congressional mandate, the VA asked the National Academies to analyze the initial months of data collected by the registry and offer recommendations on ways to improve the instrument and the information it collects. Registries are structured systems for collecting and maintaining data on a group of people characterized by a specific disease, condition, exposure, or event as a means to facilitate research, monitor health, or provide information to registrants. Registries that rely on voluntary involvement and self-reported information on exposures and health outcomes are not suitable for assessing the health effects of exposure due to respondents' selective participation, inaccurate recall, or inadvertent or intentional under- or overestimation. Thus, they are an intrinsically poor source of information on exposures, health outcomes, and possible associations among these events, said the committee that carried out the study and wrote the report. Even under the best of circumstances, there are substantial limits to the accuracy of the data they collect and -- when the respondents make up only a small, unrepresentative fraction of the eligible population -- to the generalizability of analyses made with them. The committee stressed that even a well-designed and executed registry would have little value as a scientific tool for health-effects research and would not be an effective substitute for an epidemiologic study. The committee concluded that given the inherent weaknesses, the best use of the AH&OBP Registry is as a means for the eligible population to document their concerns of health problems that may have resulted from their service, bring those concerns to the attention of VA and their health care providers, and supply VA with a roster of people who are interested in burn pit exposure issues. The gathered data could also potentially be used to stimulate and inform new research, such as a well-designed epidemiologic study. The committee recommended that VA's messaging be explicit about the capabilities and limitations of the registry to ensure that participants and others do not form unrealistic expectations. The registry questionnaire collects a number of pieces of information -- including self-reported signs, symptoms, and diseases -- that can alert providers to concerns and problems that may be forgotten or missed during clinical encounters, without regard to whether the information might be relevant to wartime exposures. For example, someone who reported difficulty walking long distances or climbing stairs might be experiencing joint pain, respiratory problems, vascular disease with congestive heart fail¬ure, obesity, or even anxiety. The committee recommended that the VA develop a concise version of a participant's responses that can be downloaded and discussed with a health care provider. If the VA chooses to use the registry for the purposes for which is it most suitable, the committee recommended several changes to the questionnaire to improve and streamline participation. Beyond the inherent weaknesses of voluntary, self-report registries, the committee identified correctable features in the registry's structure and operation as well as in the questions that are asked and the way they are asked. For example, the questionnaire fails to ask questions that could yield improved information related to relevant exposures, such as non-burn pit trash burning, and requires respondents to complete a sometimes lengthy set of repetitive questions regarding deployments before addressing core issues like health. The cumulative effect of these flaws is evidenced by the high percentage of respondents who initiated but did not complete the instrument and the number of questions that had high non-response rates. The VA should eliminate the questionnaire sections that collect information that cannot be productively used in studies appropriate for the registry's data. A 2015 VA report indicated that nearly 40 percent of those who began filling out an AH&OBP Registry questionnaire did not complete it. This is an outcome that should be examined more fully, the committee said. It recommended that the VA evaluate whether and how registrants who did not complete the questionnaire differ from those who did; analyze the determinants of non-completion; and use this information to formulate strategies that encourage registrants to finish and submit their responses as well as improve the completion rate for future participants. An examination of the questionnaire data made available to the committee showed that registry participants who reported more exposures of all types also tended to report more health problems of all types. However, the committee's analyses suggested that such results may be a consequence of the population's selection and the limitations of the self-reported exposure and disease data and do not provide useful information for assessing the health effects of exposure. The committee emphasized that it reached this determination based on the nature of the registry and the data it collects and would have drawn the same conclusion if no or weak associations between the exposures and health outcomes had been found. More generally, the AH&OBP Registry's data collection, administration, and management efforts could be improved by developing a plan to more fully integrate relevant VA and U.S. Department of Defense data sources with the registry's data, as well as offering alternative means of completing the questionnaire, such as a mail-in form or via a computer-assisted phone interview, to ensure that the subset of eligible persons who do not use or have difficulty using the Internet have the opportunity to participate in the registry. The study was sponsored by U.S. Department of Veterans Affairs. The National Academies of Sciences, Engineering, and Medicine are private, nonprofit institutions that provide independent, objective analysis and advice to the nation to solve complex problems and inform public policy decisions related to science, technology, and medicine. The National Academies operate under an 1863 congressional charter to the National Academy of Sciences, signed by President Lincoln. For more information, visit http://national-academies. . A roster follows. Copies of Assessment of the Department of Veterans Affairs Airborne Hazards and Open Burn Pit Registry are available from the National Academies Press at http://www. or by calling 1-800-624-6242. Reporters may obtain a copy from the Office of News and Public Information (contacts listed above). Health and Medicine Division Board on the Health of Select Populations Board on Population Health and Public Health Practice David A. Savitz, Ph.D., M.D.* (chair) Vice President for Research, Professor of Epidemiology, and Professor of Obstetrics and Gynecology Brown University Providence, R.I. Vinicius C. Antão, Ph.D. Director of Patient Registries HealthCare Research Institute Hospital for Special Surgery New York City Jane E. Clougherty, M.Sc., Sc.D. Associate Professor, Department of Environmental and Occupational Health Dornsife School of Public Health Drexel University Philadelphia Montserrat Fuentes, Ph.D. Dean of College of Humanities and Sciences Virginia Commonwealth University Richmond Cecile S. Rose, M.D. Professor of Medicine Division of Environmental and Occupational Health Sciences National Jewish Health Denver David H. Trump, M.D. Chief Deputy Commissioner for Public Health and Preparedness Virginia Department of Health (retired) Richmond Mark J. Utell, M.D. Professor of Medicine and Environmental Medicine, and Director of Occupational and Environmental Medicine University of Rochester Medical Center Rochester, N.Y.


Zilberberg M.D.,University of Massachusetts Amherst | Zilberberg M.D.,EviMed Research Group | De Wit M.,Virginia Commonwealth University | Shorr A.F.,Washington Hospital Center
Critical Care Medicine | Year: 2012

Objectives: Patients requiring prolonged acute mechanical ventilation (mechanical ventilation ≥ 96 hrs) have hospital survival rates similar to those requiring <96 hrs of mechanical ventilation and consume approximately two-thirds of hospital resources devoted to mechanical ventilation care. Using 2000-2005 data, we previously estimated that their volume will go from approximately 250,000 cases in 2000 to 605,898 by year 2020. With 2006-2008 data becoming available, we explored the precision of our previous formulas and estimates. Design: We utilized National Inpatient Sample/Health Care Utilization Project of the Agency for Healthcare Research and Quality data from 2000 to 2008 to calculate historic annual age-adjusted prolonged acute mechanical ventilation incidence rates using estimated population statistics from the U.S. Census Bureau. To predict future growth by age group, we fit linear regression models to the historic incidence rate changes. Age-adjusted estimates were computed using population projections obtained from the U.S. Census Bureau. Setting: U.S. hospitals. Patients: Nationally representative sample of U.S. hospital discharges with prolonged acute mechanical ventilation (International Classification of Diseases version 9 code 96.72). Interventions: None. Measurements and Main Results: Formulas based on the 2000-2005 data predicted the 2008 prolonged acute mechanical ventilation volume within a 1.9% margin. The historic annualized increase in adult prolonged acute mechanical ventilation increased from 5.0% to 5.2% after incorporating the 2006-2008 data. Factoring in the 2006-2008 data altered our 2020 prolonged acute mechanical ventilation estimates from 605,898 (95% confidence interval 456,695-779,806) to 625,298 (95% confidence interval 552,168-698,838), an upward revision of 3.2%. Conclusion: Our original projections for growth of the adult prolonged acute mechanical ventilation population in the U.S. hospitals by the year 2020 are altered only slightly by adding the 2006-2008 data. Relatively precise prediction of the 2008 prolonged acute mechanical ventilation numbers by the original formulas lends internal validity to the methodology. By virtue of being a large, resource-intensive, and rapidly increasing population, this group of mechanical ventilation Patients requires continued close monitoring over time to optimize our preparedness to meet their growing healthcare needs. © 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.


Woolf S.H.,Virginia Commonwealth University | Braveman P.,University of California at San Francisco
Health Affairs | Year: 2011

Health disparities by racial or ethnic group or by income or education are only partly explained by disparities in medical care. Inadequate education and living conditions-ranging from low income to the unhealthy characteristics of neighborhoods and communities-can harm health through complex pathways. Meaningful progress in narrowing health disparities is unlikely without addressing these root causes. Policies on education, child care, jobs, community and economic revitalization, housing, transportation, and land use bear on these root causes and have implications for health and medical spending. A shortsighted political focus on reducing spending in these areas could actually increase medical costs by magnifying disease burden and widening health disparities. © 2011 Project HOPE-The People-to-People Health Foundation, Inc.


Hajek P.,Queen Mary, University of London | Etter J.-F.,University of Geneva | Benowitz N.,University of California at San Francisco | Eissenberg T.,Virginia Commonwealth University | Mcrobbie H.,Queen Mary, University of London
Addiction | Year: 2014

Aims: We reviewed available research on the use, content and safety of electronic cigarettes (EC), and on their effects on users, to assess their potential for harm or benefit and to extract evidence that can guide future policy. Methods: Studies were identified by systematic database searches and screening references to February 2014. Results: EC aerosol can contain some of the toxicants present in tobacco smoke, but at levels which are much lower. Long-term health effects of EC use are unknown but compared with cigarettes, EC are likely to be much less, if at all, harmful to users or bystanders. EC are increasingly popular among smokers, but to date there is no evidence of regular use by never-smokers or by non-smoking children. EC enable some users to reduce or quit smoking. Conclusions: Allowing EC to compete with cigarettes in the market-place might decrease smoking-related morbidity and mortality. Regulating EC as strictly as cigarettes, or even more strictly as some regulators propose, is not warranted on current evidence. Health professionals may consider advising smokers unable or unwilling to quit through other routes to switch to EC as a safer alternative to smoking and a possible pathway to complete cessation of nicotine use. © 2014 Society for the Study of Addiction.


Liu Q.,Brookhaven National Laboratory | Liu Q.,Virginia Commonwealth University | Hendrickson W.A.,Brookhaven National Laboratory | Hendrickson W.A.,Howard Hughes Medical Institute | Hendrickson W.A.,Columbia University
Acta Crystallographica Section D: Biological Crystallography | Year: 2013

Structure determinations for biological macromolecules that have no known structural antecedents typically involve the incorporation of heavier atoms than those found natively in biological molecules. Currently, selenomethionyl proteins analyzed using single-or multi-wavelength anomalous diffraction (SAD or MAD) data predominate for such de novo analyses. Naturally occurring metal ions such as zinc or iron often suffice in MAD or SAD experiments, and sulfur SAD has been an option since it was first demonstrated using crambin 30 years ago; however, SAD analyses of structures containing only light atoms (Z max ≤ 20) have not been common. Here, robust procedures for enhancing the signal to noise in measurements of anomalous diffraction by combining data collected from several crystals at a lower than usual X-ray energy are described. This multi-crystal native SAD method was applied in five structure determinations, using between five and 13 crystals to determine substructures of between four and 52 anomalous scatterers (Z ≤ 20) and then the full structures ranging from 127 to 1200 ordered residues per asymmetric unit at resolutions from 2.3 to 2.8 Å. Tests were devised to assure that all of the crystals used were statistically equivalent. Elemental identities for Ca, Cl, S, P and Mg were proven by f′′ scattering-factor refinements. The procedures are robust, indicating that truly routine structure determination of typical native macromolecules is realised. Synchrotron beamlines that are optimized for low-energy X-ray diffraction measurements will facilitate such direct structural analysis.


Bisognano J.D.,University of Rochester | Bakris G.,University of Chicago | Nadim M.K.,University of Southern California | Sanchez L.,University of Washington | And 4 more authors.
Journal of the American College of Cardiology | Year: 2011

Objectives: We sought to determine the effect of baroreflex activation therapy (BAT) on systolic blood pressure (SBP) in patients with resistant hypertension. Background: The Rheos Pivotal Trial evaluated BAT for resistant hypertension in a double-blind, randomized, prospective, multicenter, placebo-controlled Phase III clinical trial. Methods: This was a double-blind randomized trial of 265 subjects with resistant hypertension implanted and subsequently randomized (2:1) 1 month after implantation. Subjects received either BAT (Group A) for the first 6 months or delayed BAT initiation following the 6-month visit (Group B). The 5 coprimary endpoints were: 1) acute SBP responder rate at 6 months; 2) sustained responder rate at 12 months; 3) procedure safety; 4) BAT safety; and 5) device safety. Results: The trial showed significant benefit for the endpoints of sustained efficacy, BAT safety, and device safety. However, it did not meet the endpoints for acute responders or procedural safety. A protocol-specified ancillary analysis showed 42% (Group A) versus 24% (Group B) achieving SBP ≤140 mm Hg at 6 months (p = 0.005), with both groups achieving over 50% at 12 months, at which point Group B had received 6 months of BAT. Conclusions: A clinically meaningful measure, those achieving a SBP of ≤140 mm Hg, yielded a significant difference between the groups. The weight of the overall evidence suggests that over the long-term, BAT can safely reduce SBP in patients with resistant hypertension. Future clinical trials will address the limitations of this study and further define the therapeutic benefit of BAT. © 2011 American College of Cardiology Foundation.


News Article | March 28, 2016
Site: phys.org

Space-filling model of Reb1 bound to DNA. Image courtesy of Dr. Deepak Bastia of the Medical University of South Carolina, with the permission of the Proceedings of the National Academy of Sciences. Credit: Modified from an image originally published in the Proceedings of the National Academy of Sciences In a study published on 28 March 2016 in the Proceedings of the National Academy of Sciences, researchers at the Medical University of South Carolina (MUSC) and Virginia Commonwealth University have resolved the first protein structure in a family of proteins called transcription terminators. The crystal structure of the protein, called Reb1, provides insight into aging and cancer, according to Deepak Bastia, Ph.D., Endowed Chair for Biomedical Research in the MUSC Department of Biochemistry and Molecular Biology and co-senior author of the study. During transcription, large molecular machines read genes by traveling along double-stranded DNA. This machinery simultaneously reads out the gene code in continually lengthening chains of single-stranded RNA. The RNA code is then used to assemble proteins that cells use for growth and division. At certain times during the life of a cell, transcription must be stopped-in order to conserve cellular energy or prevent uncontrolled growth, for example. At other times, cells may be preparing to divide, during which period trouble can arise. Before a cell can divide, the DNA must be exactly replicated for use in the new cell. During part of this process, two types of machinery are now moving along the DNA strand-transcriptional machinery and replication machinery. In regions where the two machines are moving in opposite directions, collisions can occur and DNA broken, causing mutations. Harmful gene mutations can be passed into the new cell. That's where Reb1 comes in. "One way to prevent genome instability is to prevent replication from colliding with transcription," says Bastia. "That's what these terminator proteins do." Bastia's group knew that there are specific sites on the DNA strand called terminator regions to which Reb1 binds itself. Reb1 was thought of as a simple physical barrier that sits on DNA and blocks both the transcriptional and replication machinery from moving further along the DNA strand and colliding with each other. Then Bastia's group did an experiment to cut the transcription terminator region (tail) off of Reb1. Intriguingly, Reb1 was no longer able to halt the transcription machinery without its tail but was still able to bind to DNA. Therefore, the simple roadblock theory couldn't be correct. The insight came when they solved the crystal structure-a laborious process during which Carlos R. Escalante, Ph.D., Bastia's co-senior author from Virginia Commonwealth University, made monthly drives transporting freshly made crystals from MUSC to the X-ray crystallography facility at Brookhaven National Laboratory in New York. The crystal structure showed that, when bound to DNA, the transcription terminator tail of Reb1 can interact with a specific part of the transcriptional machinery, acting as a tether between the two. The work illuminates Reb1 as a traffic signal for coordinating transcription and gene replication, rather than as a simple roadblock as previously thought. Though the tether between Reb1 and the transcriptional machine is clear, the team is still not sure exactly how terminator proteins stop transcription, a question which drives their current work. And the connection between terminator proteins and colorectal cancer has been made, but work in other cancers and in aging has yet to be undertaken. Still, Bastia suspects that this coordination prevents the type of gene errors that lead to many types of cellular aging and tumor growth, both of which are processes that result from uncontrolled transcription and replication. The group is currently researching another type of terminator protein, work which Bastia hopes will lend further knowledge to the diseases of aging. Explore further: How a molecular Superman protects the genome from damage More information: Functional architecture of the Reb1-Ter complex of Schizosaccharomyces pombe, www.pnas.org/cgi/doi/10.1073/pnas.1525465113


News Article | November 10, 2016
Site: www.businesswire.com

COLUMBUS, Ohio--(BUSINESS WIRE)--Grange Insurance announced that Michael Fraizer has joined the company’s board of directors. Fraizer is an operating advisor of Blue Heron Capital, a private equity investment firm based in Richmond, Virginia. After earning his bachelor’s degree in political science from Carleton College, Fraizer worked his way up the ladder at General Electric from financial trainee to senior-level executive, with positions including CEO of GE Insurance, CEO of GE Financial Assurance and CEO of GE Capital Commercial Real Estate Financing and Services. He then went on to serve as chairman and CEO of Genworth Financial Inc., which went public from GE, where he oversaw assets of over $100 billion and revenues of $10 billion. “I’m thrilled to welcome Michael to the board,” said David Wetmore, chairman of the company’s board of directors. “Michael’s experience with investments, finance and business development — not to mention his expansive involvement in corporate governance — will prove essential as we advise on key decisions to help the company transform and grow.” Over the past 25 years, Fraizer has been a member of several boards of directors, including MUFG Americas Holding Corp., Genworth Financial Inc. and GE Capital Corporation, as well as a number of other General Electric subsidiary boards. He served on the boards of the American Council of Life Insurers, including a term as its chairman, the Financial Services Roundtable and other community service or nonprofit boards such as Richmond Performing Arts Center, Virginia Commonwealth University and the Mary and Frances Youth Center. “We rely on the unique expertise and perspectives of our board of directors to guide Grange toward future success,” said John Ammendola, Grange Insurance president and CEO. “I’m excited for Michael to join us, as I believe he will provide significant insight and our company will greatly benefit from his experience.” Grange Insurance, with $2 billion in assets and more than $1 billion in annual revenue, is an insurance provider founded in 1935 and based in Columbus, Ohio. Through its network of independent agents, Grange offers auto, home, life and business insurance protection. The company and its affiliates serve policyholders in Georgia, Illinois, Indiana, Iowa, Kentucky, Michigan, Minnesota, Ohio, Pennsylvania, South Carolina, Tennessee, Virginia and Wisconsin. For more information, visit www.grangeinsurance.com.


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

New Rochelle, NY, December 12, 2016--A new study comparing the effectiveness of oral progestogens versus a levonorgestrel-releasing intrauterine system to treat women with endometrial intraepithelial neoplasia (EIN) presents data on patient outcomes compiled over 8 years, as reported in Journal of Women's Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The article is available free on the Journal of Women's Health website until January 12, 2017. Mary Marnach, MD and coauthors from Mayo Clinic, Rochester, MN, and Mayo Clinic Hospital, Phoenix, AZ, conducted a retrospective analysis to determine which treatment approach was more effective in women with EIN who either wanted to preserve their fertility and not undergo a hysterectomy or were not optimal surgical candidates. Overall, the treatments led to disease resolution in more than 80% of patients with subcategory 1 EIN and more than 60% of patients with subcategory 2 EIN. Intrauterine hormone delivery offers greater convenience and minimal adverse effects, is rapidly reversible, and provides long-term protection of the endometrial lining. The researchers report their results in the article "Oral Progestogens Versus Levonorgestrel-Releasing Intrauterine System for Treatment of Endometrial Intraepithelial Neoplasia." "Available guidelines for the treatment of EIN have been limited due to the absence of data from comparative studies involving substantial numbers of patients," says Susan G. Kornstein, MD, Editor-in-Chief of Journal of Women's Health, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, and President of the Academy of Women's Health. "This study by Marnach et al. demonstrates the effectiveness of two nonsurgical treatment approaches in different subcategories of EIN, and the authors suggest timelines for routine endometrial surveillance." Journal of Women's Health, published monthly, is a core multidisciplinary journal dedicated to the diseases and conditions that hold greater risk for or are more prevalent among women, as well as diseases that present differently in women. Led by Editor-in-Chief Susan G. Kornstein, MD, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, and President of the Academy of Women's Health, the Journal covers the latest advances and clinical applications of new diagnostic procedures and therapeutic protocols for the prevention and management of women's healthcare issues. Complete tables of content and a sample issue may be viewed on the Journal of Women's Health website. Journal of Women's Health is the official journal of the Academy of Women's Health and the Society for Women's Health Research. Academy of Women's Health is an interdisciplinary, international association of physicians, nurses, and other health professionals who work across the broad field of women's health, providing its members with up-to-date advances and options in clinical care that will enable the best outcomes for their women patients. The Academy's focus includes the dissemination of translational research and evidence-based practices for disease prevention, diagnosis, and treatment of women across the lifespan. Journal of Women's Health and the Academy of Women's Health are co-presenters of Women's Health 2017: The 25th Anniversary Congress which will take place April 28-30, 2017 in Washington, DC. Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including LGBT Health, Transgender Health, Population Health Management, and Breastfeeding Medicine. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 80 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.


News Article | November 28, 2016
Site: www.eurekalert.org

New Rochelle, NY, November 28, 2016--The results of a new study designed to compare the severity and timing of perimenstrual symptoms among women who do or do not use cyclic hormonal contraception are reported in Journal of Women's Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The article is available free on the Journal of Women's Health website. (http://online. ) The article entitled "The Influence of Cyclic Hormonal Contraception on Expression of Premenstrual Syndrome" is coauthored by Journal of Women's Health Editor-in-Chief Susan Kornstein, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, Kimberly Yonkers, MD and Margaret Altemus, MD, Yale University School of Medicine, and Brianna Cameron and Ralitza Gueorguieva, PhD, Yale University School of Public Health, New Haven, CT. The researchers report changes in menstrual cycle symptom scores for variables such as depression, anger, irritability, and physical symptoms between cyclic hormonal contraception users and nonusers. They found that cyclic hormonal contraception may attenuate premenstrual symptoms, but that the timing of symptoms is similar regardless of whether the subjects used hormonal contraception. Better understanding the psychological and physical effects of hormonal contraception could help guide clinicians in the diagnosis and treatment of premenstrual syndrome (PMS). "Because women taking hormonal contraceptives are routinely excluded from studies of PMS and premenstrual dysphoric disorder (PMDD), this study provides a valuable examination of the influence of exogenous hormones on premenstrual symptom expression and response to treatment," says Robert Downs, MD, Deputy Editor of Journal of Women's Health, Richmond, VA. Research reported in this publication was supported by the National Institute on Mental Health under Award Number R01 MH072955, R01 MH072645, and MH072962. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Journal of Women's Health, published monthly, is a core multidisciplinary journal dedicated to the diseases and conditions that hold greater risk for or are more prevalent among women, as well as diseases that present differently in women. Led by Editor-in-Chief Susan G. Kornstein, MD, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, and President of the Academy of Women's Health, the Journal covers the latest advances and clinical applications of new diagnostic procedures and therapeutic protocols for the prevention and management of women's healthcare issues. Complete tables of content and a sample issue may be viewed on the Journal of Women's Health website. Journal of Women's Health is the official journal of the Academy of Women's Health and the Society for Women's Health Research. (http://www. ) Academy of Women's Health is an interdisciplinary, international association of physicians, nurses, and other health professionals who work across the broad field of women's health, providing its members with up-to-date advances and options in clinical care that will enable the best outcomes for their women patients. The Academy's focus includes the dissemination of translational research and evidence-based practices for disease prevention, diagnosis, and treatment of women across the lifespan. Journal of Women's Health and the Academy of Women's Health are co-presenters of Women's Health 2017: The 25th Anniversary Congress which will take place April 28-30, 2017 in Washington, DC. Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including LGBT Health, Population Health Management, and Breastfeeding Medicine. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 80 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website. (http://www. )


News Article | November 1, 2016
Site: physicsworld.com

The atomic force microscope (AFM) has played an essential role in 2D materials research since it was used to confirm the first isolation of graphene. Today’s AFMs are even more powerful, with higher spatial resolution, faster imaging rates, greater environmental control and enhanced modes for mapping physical properties. They can image crystal lattice structure as well as nanoscale morphology, and sense local electrical, mechanical and functional response in more ways than ever before. In this webinar we explore the latest AFM tools that enable higher resolution, sensitivity and more quantitative results for analysing 2D materials. We present results from measurements of a variety of 2D materials for device manufacturing, energy storage and optoelectronics including: Finally, we discuss how AFM can now be used to accurately determine the thickness of single or multiple layers of a 2D material. This challenges the misconception that AFM cannot be used to precisely measure the thickness of 2D materials. Presenter: Prof. Andras Kis, EPFL, STI-IEL-LANES Andras Kis is currently an associate professor at the École Polytechnique Fédérale de Lausanne (EPFL), School of Engineering (STI), Institute of Electrical Engineering (IEL) with a research focus in developing 2D materials. His group demonstrated the first transistor based on a 2D semiconductor. He has more than 16 years of AFM experience, including 63 peer-reviewed papers, more than 50 invited talks at scientific meetings and participation in organization committees for numerous 2D materials and graphene conferences. He has also been the editor-in-chief for Nature partner journal 2D Materials and Applications. Prof. Kis received his PhD from EPFL and did his postdoc at the University of California Berkeley, Zettl Laboratory. Presenter: Keith Jones, Oxford Instruments Asylum Research Keith Jones is currently an application scientist at Oxford Instruments Asylum Research (12 years). He has more than 18 years of SPM experience specializing in nanoelectrical characterization. He was instrumental in developing and applying electrical AFM techniques such as dopant profiling and scanning microwave impedance microscopy. Mr Jones is also a co-inventor on a patent for scanning impedance microscopy. He has co-authored 34 published papers. He received his MS in physics at Virginia Commonwealth University.


News Article | December 19, 2016
Site: www.eurekalert.org

This kind of new brain imaging study could help identify cognitive problems and psychiatric disorders very early and develop appropriate interventions CHAPEL HILL, NC - A new study led by UNC School of Medicine researchers concluded that patterns of white matter microstructure present at birth and that develop after birth predict the cognitive function of children at ages 1 and 2. "To our knowledge, this study is the first to measure and describe the development of white matter microstructure in children and its relationship to cognitive development from the time they are born until the age of 2 years," said John H. Gilmore, MD, senior author of the study and director of the Early Brain Development Program in the UNC Department of Psychiatry. The study was published online on December 19, 2016 in the Proceedings of the National Academy of Sciences. White matter is the tissue in the brain that contains axon fibers, which connect neurons in one brain region to neurons in another region. White matter is critical for normal brain function, and little is known about how white matter develops in humans or how it is related to growth of cognitive skills in early childhood, including language development. In the study, a total of 685 children received diffusion tensor imaging (DTI) scans of their brains. DTI is a magnetic resonance imaging (MRI) technique that provides a description of the diffusion of water through tissue, and can be used to identify white matter tracts in the brain and describe the organization and maturation of the tracts. The study authors used these brain scans to investigate the microstructure of 12 white matter fiber tracts important for cognitive function, their relationship to developing cognitive function and their heritability. They found all 12 of the fiber tracts in the newborns were highly related to each other. By age 1, these fiber tracts had begun to differentiate themselves from each other, and by age 2 this differentiation was further advanced. The most interesting finding from the study was that the common relationship between white matter tracts at birth predicted overall cognitive development at age 1 and language development at age 2, indicating that it may be possible to use brain imaging at birth to better understand how a child's cognitive development will proceed in the first years after birth. Because the sample included 429 twins, the study authors were also able to calculate that this predictive trait was moderately heritable, suggesting that genetics may be a factor in its development. "There is rapid growth of brain structure, cognition and behavior in early childhood, and we are just starting to understand how they are related," Gilmore said "With a better understanding of these relationships, we ultimately hope to be able to identify children at risk for cognitive problems or psychiatric disorders very early and come up with interventions that can help the brain develop in a way to improve function and reduce risk." In addition to Gilmore, authors of the study are Seung Jae Lee, Rachel J. Steiner, Yang Yu, Sarah J. Short, Michael C. Neale, Martin Styner, and Hongtu Zhu. All are at UNC except for Neale, who is in the Virginia Institute of Psychiatric and Behavioral Genetics at Virginia Commonwealth University. This study was supported by grants from the National Institute of Mental Health (MH064065, MH 070890, RR025747 and MH086633), National Institute of Child Health and Human Development (HD053000) and the National Science Foundation (SES-1357666).


Scientists have used a unique computational technique that sifts through big data to identify a subset of concussion patients with normal brain scans, who may deteriorate months after diagnosis and develop confusion, personality changes and differences in vision and hearing, as well as post-traumatic stress disorder. This finding, which is corroborated by the identification of molecular biomarkers, is paving the way to a precision medicine approach to the diagnosis and treatment of patients with traumatic brain injury. Investigators headed by scientists at UC San Francisco and its partner institution Zuckerberg San Francisco General Hospital and Trauma Center (ZSFG) analyzed an unprecedented array of data, using a machine learning tool called topological data analysis (TDA), which "visualizes" diverse datasets across multiple scales, a technique that has never before been used to study traumatic brain injury. TDA, which employs mathematics derived from topology, draws on the philosophy that all data has an underlying shape. It creates a summary or compressed representation of all the data points using algorithms that map patient data into a multidimensional space. The new research relied on a TDA platform developed by Ayasdi, an advanced analytics company based in Palo Alto, Calif. "TDA is a type of machine intelligence that provides a way to easily visualize patient differences across the full spectrum of traumatic brain injury from concussion to coma," said senior co-author, Adam Ferguson, PhD, associate professor in the Department of Neurological Surgery and a member of the UCSF Weill Institute for Neurosciences. "This has potential to transform diagnosis and predict outcome by providing a new level of precision." The study, publishing in PLOS ONE on March 1, 2017, is part of a government-funded multisite initiative called TRACK-TBI, Transforming Research and Clinical Knowledge in Traumatic Brain Injury, which was established to identify new diagnostic and prognostic markers, and to refine outcome assessments. Traumatic brain injury results in approximately 52,000 deaths, 257,000 hospitalizations and 2.2 million emergency department visits in the United States annually, according to the Centers for Disease Control and Prevention's Injury Center. These injuries can lead to widespread lesions throughout the brain's white matter, as well as a "cascade of secondary injury mechanisms that evolve over times." The heterogeneity of the manifestations of these secondary injuries is one significant obstacle that thwarts the development of new treatments, the authors note in their paper. "Traumatic brain injury lags 40 to 50 years behind cancer and heart disease in terms of progress and understanding of the actual disease process and its potential aftermath," said co-senior author Geoffrey Manley, MD, PhD, vice chair of the Department of Neurological Surgery at UCSF and chief of neurosurgery at ZFGH. "More than 30 clinical trials of potential traumatic brain injury treatments have failed, and not a single drug has been approved." In the study, so-called common data elements were collected from 586 patients with acute traumatic brain injury from trauma centers at ZSFG, University of Pittsburgh Medical Center and University Medical Center Brackenridge in Austin, Texas. These elements comprised 944 variables, including demographics, clinical presentation, imaging and psychological testing. The variables were edited by "data curators," to build a robust multivariate clinical dataset that could be harnessed by biomedical data scientists. Mapping of outcome using TDA revealed that concussion, or mild traumatic brain injury, could be stratified into multiple subgroups with diverse prognoses. Among them was a large group of patients who, despite normal brain scans, demonstrated poor recovery and a tendency to get worse, three-to-six months after the injury. These patients were likely to suffer from post-traumatic stress disorder. "These are patients with clear scans that would have been discharged from the hospital with nothing more than a recommendation to take over-the-counter medications," said Ferguson. "By recognizing these patients as a distinct subgroup, clinicians may be able to anticipate future symptoms and treat them proactively." According to first author Jessica Nielson, PhD, also of the UCSF Department of Neurological Surgery and the Weill Institute, the most challenging symptoms to treat are those that are not apparent immediately after an injury. "Eventually we hope to identify treatment targets early after injury to prevent this gradual decline and boost our ability to intervene and improve outcome for patients," she said. In addition to variants in PARP1, researchers found other biomarkers in patients' blood samples that were predictive of poor recovery, including ANKK1 and COMT. These genes are associated with signaling by the neurotransmitter dopamine and may provide critical clues to recovery and drugs' responsiveness. A future goal of TRACK-TBI is to contribute to the design of clinical trials to develop therapeutic drugs for traumatic brain injury - perhaps even tailored to a patient's blood-based biomarkers. "TDA improves upon traditional outcome prediction approaches for patients with traumatic brain injury," said Nielson, who is also affiliated with ZSFG. "By leveraging the full information provided by all outcomes, TDA has the potential to improve diagnosis and therapeutic targeting." TDA technology is already being used by banks for fraud detection and in military applications, but it has not reached the mainstream in biomedicine, according to the authors. "Potentially this could change very soon," said Ferguson. "Our proof-of-concept study demonstrates the maturity of the technology and its potential use in medical decision-making when coupled with high-quality data from electronic medical records." The study was supported by funding from the National Institutes of Health - National Institute of Neurological Disorders and Stroke. The study's co-authors are Shelly Cooper, John Yue, Tomoo Inoue, MD, PhD; and Mary Vassar of ZSFG and UCSF; Esther Yuh, MD, PhD, and Pratik Mukherjee, MD, PhD, of UCSF; Tanya Petrossian, PhD; Jesse Paquette MS, Pek Lum, PhD, and Gunnar Carlsson, PhD, of or previously of Ayasdi in Palo Alto, Calif.; Hester Lingsma, PhD, of Erasmus Medical Center in the Netherlands; Wayne Gordon, PhD, of Icahn School of Medicine at Mount Sinai in New York; Alex Valadka, MD, of Virginia Commonwealth University in Richmond; and David Okonkwo, MD, PhD, of the University of Pittsburgh.


Ellenbogen K.A.,Virginia Commonwealth University | Gunderson B.D.,Medtronic | Stromberg K.D.,Medtronic | Swerdlow C.D.,University of California at Los Angeles
Circulation: Arrhythmia and Electrophysiology | Year: 2013

Background-The Lead Integrity Alert (LIA) was developed for Medtronic implantable cardioverter defibrillators to reduce inappropriate shocks for rapid oversensing caused by conductor fractures and reported for Medtronic Fidelis conductor fractures. The goal of this study was to compare the performance of LIA with conventional impedance monitoring for identifying lead system events (LSEs) and lead failures (LFs) in lead families that differ from Fidelis. Methods and Results-We analyzed data from 12 793 LIA enabled implantable cardioverter-defibrillator and lead combinations including 6123 St. Jude Riata or Durata, 5114 Boston Scientific Endotak, and 1556 Fidelis combinations followed in the CareLink remote monitoring network for LSEs and LFs. Each alert was adjudicated based on implantable cardioverterdefibrillator stored electrograms/diagnostics and clinical data as an LSE or non-lead system event by 2 physicians after reviewing the electrograms and clinical data. During 13 562 patient-years of LIA follow-up, there were 179 adjudicated alerts, of which 84 were LSEs (including 65 LFs) and 95 were non-lead system events. LIA identified >66% more LSE and >67% more LF compared with conventional impedance monitoring and did not differ by lead family for LSE (P=0.573) or LF (P=0.332). Isolated spikes on electrogram were associated more often with LF in St. Jude leads (71%) compared with Endotak (9%; P<0.001) and Fidelis leads (11%; P<0.001). The non-lead system event detection rate was different among lead families (P<0.001) ranging from 1 in every 78.5 years (Endotak), 228.9 years (St. Jude leads), and 627.6 years (Fidelis). Conclusions-LIA markedly increased the detection rate of LSE compared with conventional impedance monitoring. © 2013 American Heart Association, Inc.


Levine M.S.,University of Pennsylvania | Carucci L.R.,Virginia Commonwealth University
Radiology | Year: 2014

Obesity is a disease that has reached epidemic proportions in the United States and around the world. During the past 2 decades, bariatric surgery has become an increasingly popular form of treatment for morbid obesity. The most common bariatric procedures performed include laparoscopic Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, and laparoscopic sleeve gastrectomy. Fluoroscopic upper gastrointestinal examinations and abdominal computed tomography (CT) are the major imaging tests used to evaluate patients after these various forms of bariatric surgery. The purpose of this article is to present the surgical anatomy and normal imaging findings and postoperative complications for these bariatric procedures at fluoroscopic examinations and CT. Complications after Roux-en-Y gastric bypass include anastomotic leaks and strictures, marginal ulcers, jejunal ischemia, small bowel obstruction, internal hernias, intussusception, and recurrent weight gain. Complications after laparoscopic adjustable gastric banding include stomal stenosis, malpositioned bands, pouch dilation, band slippage, perforation, gastric volvulus, intraluminal band erosion, and port- and bandrelated problems. Finally, complications after sleeve gastrectomy include postoperative leaks and strictures, gastric dilation, and gastroesophageal reflux. The imaging features of these various complications of bariatric surgery are discussed and illustrated. © RSNA, 2014.


Smith D.H.,University of Pennsylvania | Hicks R.,U.S. National Institutes of Health | Povlishock J.T.,Virginia Commonwealth University
Journal of Neurotrauma | Year: 2013

Diffuse axonal injury (DAI) remains a prominent feature of human traumatic brain injury (TBI) and a major player in its subsequent morbidity. The importance of this widespread axonal damage has been confirmed by multiple approaches including routine postmortem neuropathology as well as advanced imaging, which is now capable of detecting the signatures of traumatically induced axonal injury across a spectrum of traumatically brain-injured persons. Despite the increased interest in DAI and its overall implications for brain-injured patients, many questions remain about this component of TBI and its potential therapeutic targeting. To address these deficiencies and to identify future directions needed to fill critical gaps in our understanding of this component of TBI, the National Institute of Neurological Disorders and Stroke hosted a workshop in May 2011. This workshop sought to determine what is known regarding the pathogenesis of DAI in animal models of injury as well as in the human clinical setting. The workshop also addressed new tools to aid in the identification of this axonal injury while also identifying more rational therapeutic targets linked to DAI for continued preclinical investigation and, ultimately, clinical translation. This report encapsulates the oral and written components of this workshop addressing key features regarding the pathobiology of DAI, the biomechanics implicated in its initiating pathology, and those experimental animal modeling considerations that bear relevance to the biomechanical features of human TBI. Parallel considerations of alternate forms of DAI detection including, but not limited to, advanced neuroimaging, electrophysiological, biomarker, and neurobehavioral evaluations are included, together with recommendations for how these technologies can be better used and integrated for a more comprehensive appreciation of the pathobiology of DAI and its overall structural and functional implications. Lastly, the document closes with a thorough review of the targets linked to the pathogenesis of DAI, while also presenting a detailed report of those target-based therapies that have been used, to date, with a consideration of their overall implications for future preclinical discovery and subsequent translation to the clinic. Although all participants realize that various research gaps remained in our understanding and treatment of this complex component of TBI, this workshop refines these issues providing, for the first time, a comprehensive appreciation of what has been done and what critical needs remain unfulfilled. © 2013, Mary Ann Liebert, Inc. 2013.


Daviskas E.,Royal Prince Alfred Hospital | Rubin B.K.,Virginia Commonwealth University
Expert Review of Respiratory Medicine | Year: 2013

Insufficient hydration at the airway surface can make mucus adherent and poorly cleared. Cough, the major mechanism of mucus clearance in disease, is ineffective when mucus is adhesive. Inhaled mannitol creates an osmotic drive for water to move into the airway lumen. The consequent increased hydration of the airway surface decreases the adherence of mucus to the epithelium, facilitates the coupling of mucus and cilia thereby increasing mucus clearance. Inhaled mannitol also promotes effective coughing and stimulates mucociliary clearance. The beneficial effect of mannitol on mucus and its clearance has been demonstrated in patients with asthma, bronchiectasis and cystic fibrosis. Inhaled dry powder mannitol (Bronchitol™) is promising to be an effective treatment for the clearance of retained airway secretions. © 2013 2013 Expert Reviews Ltd.


Marra A.R.,Hospital Israelita Albert Einstein | Edmond M.B.,Virginia Commonwealth University
Current Infectious Disease Reports | Year: 2012

Hand hygiene (HH) is an important measure in infection prevention to decrease transmission of microbial pathogens; however, HH compliance by health-care workers (HCWs) remains suboptimal. One of the principal recommendations of current guidelines is that waterless, alcohol-based hand rubs are the preferred method for HH in most situations, due to the superior efficacy of these agents in rapidly reducing bacterial counts on hands and their ease of use. Improving HH compliance is a good quality indicator for hospital patient safety programs. Observers can follow HCWs to perform direct HH observations; however, HCWs may be prompted to clean their hands when observers are nearby, which does not represent real-world conditions.Moreover, having observers walk into patient rooms violates patient privacy and is time consuming. HH strategies using indirect metrics for surveillance (e.g., measuring the volume of HH products consumed) and the use of new technologies (e.g., electronic dispenser counters, radiofrequency, alcohol sensors, and video recording) will also be discussed. © Springer Science+Business Media, LLC 2012.


Bajaj J.S.,Virginia Commonwealth University | Bajaj J.S.,Medical College of Wisconsin | Pinkerton S.D.,Medical College of Wisconsin | Sanyal A.J.,Virginia Commonwealth University | Heuman D.M.,Virginia Commonwealth University
Hepatology | Year: 2012

Minimal hepatic encephalopathy (MHE) in cirrhosis is associated with impaired driving skills and increased risk of motor vehicle accidents (MVAs). Detection and treatment of MHE has the potential to reduce costs and morbidity associated with MVAs. We conducted a cost-effectiveness analysis to assess the benefits of different strategies of MHE diagnosis and treatment for reducing MVA-related societal costs. The analyses compared five MHE management strategies: (1) presumptive treatment of all cirrhosis patients; (2) diagnosis by neuropsychological exam (NPE) with treatment; (3) diagnosis by standard psychometric tests (SPTs) with treatment; (4) diagnosis by rapid screening using inhibitory control test (ICT) with treatment; and (5) no MHE diagnosis or treatment (status quo). Treatments considered were lactulose or rifaximin, which were assumed to reduce the MVA rate to the level of similarly aged noncirrhosis patients with benefit adjusted for treatment compliance. A Markov model followed a simulated cohort of 1,000 cirrhosis patients without overt hepatic encephalopathy (OHE), from entry into treatment, through MHE development, and later OHE, when they exited the modeled cohort. Follow-up was for 5 years and included biannual MHE testing. The societal cost of a single MVA was estimated at $42,100. All four strategies with lactulose were cost-saving compared with the status quo. Diagnosis with ICT and lactulose was the most cost-effective approach (cost/MVA prevented: $24,454 ICT; $25,470 SPT; $30,469 presumptive treatment and $33,742 NPE). Net program savings over 5 years ranged from $1.7 to 3.6 million depending on the strategy. Rifaximin therapy was not cost-saving at current prices but would become so at a monthly cost of <$353. Conclusion: Detection of MHE, especially using the ICT, and subsequent treatment with lactulose could substantially reduce societal costs by preventing MVAs. © 2011 American Association for the Study of Liver Diseases.


May J.,James Madison University | Dhillon G.,Virginia Commonwealth University | Caldeira M.,University of Lisbon
Decision Support Systems | Year: 2013

The planning and subsequent implementation of Enterprise Resource Planning (ERP) systems still present a significant challenge for most organizations. Although consulting firms and customer enterprises have been aquiring more experience and expertise in the field, the level of sophistication of these systems and their wide organizational and social impact frequently leads to failed ERP implementations. In an attempt to minimize these failure rates, this paper defines a set of value-based objectives that could be used to enrich the ERP systems planning process. ERP systems planning objectives grounded by stakeholder values can be used as a conceptual guide for enhancing the decision making processes involved in ERP projects. Using Keeney's value-focused thinking approach, a set of means and fundamental objectives was identified using data collected via in-depth interviews in three large European firms. The relationships and interdependancies among these objectives are also presented and provide a starting point for further research.


Marra A.R.,Hospital Israelita Albert Einstein | Edmond M.B.,Virginia Commonwealth University
Clinical Microbiology and Infection | Year: 2014

Compliance with hand hygiene is a good quality indicator for hospital patient safety programmes. Hand hygiene is a major infection control prevention intervention, but in many medical centres compliance rates are only c. 50%. Given the enormous number of hand hygiene opportunities in hospitals, direct observation to monitor compliance is very inefficient. However, technologies are emerging to obviate the need for direct observation. These new technologies for monitoring hand hygiene compliance are discussed in this article. © 2013 European Society of Clinical Microbiology and Infectious Diseases.


Sanyal A.J.,Virginia Commonwealth University | Abdelmalek M.F.,Duke University | Suzuki A.,University of Arkansas for Medical Sciences | Suzuki A.,Central Arkansas Veterans Healthcare System | And 2 more authors.
Gastroenterology | Year: 2014

Background & Aims n-3 polyunsaturated fatty acids reduce insulin resistance, lipogenesis, and inflammation, which are features of nonalcoholic steatohepatitis (NASH). Ethyl-eicosapentanoic acid (EPA-E) is a synthetic polyunsaturated fatty acid that reduces hypertriglyceridemia. We report the final results of a phase 2b multicenter, prospective, double-blind, randomized, placebo-controlled trial of EPA-E for NASH. Methods Our study, performed at 37 sites in North America, included subjects with NASH and nonalcoholic fatty liver disease (NAFLD) activity scores ≥4, with minimum scores of 1 for steatosis and inflammation, along with either ballooning or at least stage 1a fibrosis. A total of 243 subjects were randomly assigned to groups given placebo (n = 75), low-dosage EPA-E (1800 mg/d; n = 82), or high-dosage EPA-E (2700 mg/d; n = 86) for 12 months. Subjects were examined at 4-week intervals for 3 months, 6-week intervals for the next 3 months, and every 3 months thereafter, until 1 month after the last dose was taken. Liver biopsies were collected 2 weeks after the last dose of EPA-E or placebo. The primary efficacy end point was NAFLD activity score ≤3, without worsening of fibrosis; or a decrease in NAFLD activity score by ≥2 with contribution from >1 parameter, without worsening of fibrosis, 1 year after the last dose of EPA-E or placebo was given. Results Similar proportions of subjects in each group met the primary end point (40%, 37%, and 35.9% for placebo, low-dosage, and high-dosage EPA-E, respectively). EPA-E had no significant effects on steatosis, inflammation, ballooning, or fibrosis scores. There were no significant effects on levels of liver enzymes, insulin resistance, adiponectin, keratin 18, high-sensitivity C-reactive protein, or hyaluronic acid. High-dosage EPA-E reduced levels of triglyceride (-6.5 mg/dL vs an increase of 12 mg/dL in the placebo group; P =.03). There were no treatment-related serious adverse events. Conclusions In a phase 2 trial, EPA-E had no significant effect on the histologic features of NASH. EPA-E reduced subjects' levels of triglyceride compared with placebo, without any increase in serious adverse events. Clinicaltrials.gov Number: 01154985. © 2014 by the AGA Institute.


Patent
Virginia Commonwealth University and Durect Corp. | Date: 2014-12-23

Methods of preventing and/or treating ischemia, organ dysfunction and/or organ failure, including multiple organ dysfunction syndrome (MODS), and necrosis and apoptosis associated with organ dysfunction/failure, are provided. For instance, the methods involve contacting organ(s) with an oxygenated cholesterol sulfate (OCS), e.g. 5-cholesten-3,25-diol, 3-sulfate (25HC3S). The organ(s) may be in vivo (e.g. in a patient that is treated with the OCS) or ex vivo (e.g. an organ that has been harvested from a donor and is to be transplanted).


News Article | February 23, 2017
Site: www.eurekalert.org

(Boston)--Maunil Bhatt, MD, a post graduate resident in the Department of Surgery at Boston University School of Medicine and Boston Medical Center (BMC), was recently honored with a Global Surgery Research Fellowship Award by the Association for Academic Surgery (AAS) at their 12th Annual Academic Conference. Bhatt's project, titled Innovative Method of Screening for Esophageal Squamous Cell Cancers in Rural India, was chosen from 25 applicants. He received $10,000 for his project. For his study, Bhatt will screen a high-risk population in rural Gujarat, India, for esophageal squamous cell cancer using a device called EsophaCap. This tool is a sponge, compressed into a capsule that is attached to a string. Once swallowed, the outer coating of the capsule dissolves and forms into a sponge in three to five minutes which is then retrieved using the string. The sponge collects the esophageal cells which can then be analyzed to screen for cancerous or dysplastic lesions. "Our hope is to demonstrate this new method of screening is non-invasive, requires no expertise and will be more cost effective than endoscopy as a screening tool for this deadly cancer in the low- and middle-income countries with very high incidence of esophageal cancer," explained Bhatt. Born and raised until the age of 17 in Gujarat, Bhatt and his family moved to the US in search of a better future. He attended the University of California Davis and received his undergraduate degree in neuroscience becoming the first person in his family to receive any form of higher education. He then returned to India for a year to volunteer in a range of projects to improve health awareness and access to care in rural parts of the country. Upon his return, Bhatt attended medical school at the Virginia Commonwealth University in Richmond. He matched with his No. 1 choice, BMC, for a general surgery residency. Bhatt is interested in global surgery and plans to spend some of his clinical time training and teaching in poor and low income countries that lack the surgical expertise. He hopes to work on addressing the disparities in access to surgical care that currently exists across the country.


News Article | February 23, 2017
Site: www.eurekalert.org

New Rochelle, NY, February 23, 2017--A new study shows that patients with mild traumatic brain injury (mTBI), even without evidence of brain lesions, may exhibit changes in brain connectivity detectable at the time of the injury that can aid in diagnosis and predicting the effects on cognitive and behavioral performance at 6 months. Brain connectivity maps showed differences between patients with mTBI and healthy controls, including different patterns depending on the presence of brain lesions, as reported in an article in Journal of Neurotrauma, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Journal of Neurotrauma website until March 23, 2017. The article entitled "Resting-State Functional Connectivity Alterations Associated with Six-Month Outcomes in Mild Traumatic Brain Injury" describes the prospective multicenter TRACK-TBI pilot study. Eva Palacios and coauthors from University of California, San Francisco, San Francisco General Hospital and Trauma Center, University of Texas, Austin, University of Pittsburgh Medical Center (PA), Virginia Commonwealth University (Richmond), Icahn School of Medicine at Mount Sinai (New York, NY), and Antwerp University Hospital (Edegem, Belgium) concluded that resting state functional magnetic resonance imaging (MRI) to assess brain connectivity and compare spatial maps of resting state brain networks can serve as a sensitive biomarker for early diagnosis of mTBI and later patient performance. "While, as the authors acknowledge, they are not the first group to explore the utility of resting state functional MRI in probing the morbidity associated with mild traumatic brain injury, they do elegantly capitalize on the TRACK-TBI study population to critically evaluate functional connectivity in a patient population that is well characterized and followed by traditional imaging approaches," says John T. Povlishock, PhD, Editor-in-Chief of Journal of Neurotrauma and Professor, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond. "Their finding of altered patterns of functional connectivity even in that mild TBI patient population, revealing no CT/MRI abnormalities, is an extremely important observation, as is the fact that these same changes in functional connectivity portend the development of a persistent post-concussive syndrome." Journal of Neurotrauma is an authoritative peer-reviewed journal published 24 times per year in print and online that focuses on the latest advances in the clinical and laboratory investigation of traumatic brain and spinal cord injury. Emphasis is on the basic pathobiology of injury to the nervous system, and the papers and reviews evaluate preclinical and clinical trials targeted at improving the early management and long-term care and recovery of patients with traumatic brain injury. Journal of Neurotrauma is the official journal of the National Neurotrauma Society and the International Neurotrauma Society. Complete tables of content and a sample issue may be viewed on the Journal of Neurotrauma website. Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in promising areas of science and biomedical research, including Therapeutic Hypothermia and Temperature Management, Brain Connectivity, and Tissue Engineering. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 80 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.


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

To help people who have lost their sense of taste or have difficulty monitoring what they eat, a team of researchers at Virginia Commonwealth University is working on an artificial taste-sensing system. The design will both monitor and manage the user's diet and also potentially help modify eating behaviors. "The first app is something simple," said Richard Costanzo, Ph.D., professor of physiology and biophysics and director of research in the Department of Otolaryngology in the School of Medicine. "Like, why not set up a detection system for something like salt, which is pretty easy to detect and may help people with hypertension." Costanzo is an expert in taste and smell, and first conceived this idea for an artificial taste-sensing system that goes inside the mouth a few years ago. His original design was a tooth with a miniaturized sensor that fits like a filling. Since then, he has brought in collaborators to bring his idea to life, including Woon-Hong Yeo, Ph.D., assistant professor in the Department of Mechanical and Nuclear Engineering in the School of Engineering. Yeo specializes in flexible electronics and low-profile biosensors and has been developing the exact kind of nanotechnology-driven electronics needed for Costanzo's idea. Instead of large electrodes, a tangle of wires and bulky control stations for health monitoring, Yeo works in the miniature. He designs nano-tattoos—small, ultralight, wearable monitoring devices that feel like a second skin and move with the human body. "We miniaturize everything," he said. "Microscopes are our friends." Yeo and Costanzo received funding from the MEDARVA Research Foundation in Richmond to develop a sodium-sensing system in the oral cavity. Instead of the tooth mount of Costanzo's first design, this device is designed to be worn inside the mouth, mounted on an orthodontic retainer created by James Coffey, D.D.S., associate professor of prosthodontics in the VCU School of Dentistry. Think of it as a Fitbit for the mouth. In the case of the Fitbit, the technology measures acceleration and translates that information into data such as distance, steps and calories burned. It also will encourage you to move if you've been idle too long. For the sodium-sensing device, the technology measures the concentration of sodium ions coming in through the mouth and transmits the data to a smartphone or other monitoring system. Once the sodium threshold is reached for the day, the user is alerted. So if an elderly woman with hypertension is eating potato chips (while wearing the taste-sensing retainer), and she reaches her sodium maximum for the day, she will get an alert so she knows to stop eating sodium. "This is a serious problem, hypertension—diabetes is another problem but that's more sugar related—and right now there are no devices out there that are bionically monitoring this information, feeding back this information, or beeping and saying, 'Hey, you've had enough,'" Costanzo said. He believes it could also teach people to modify their eating behavior in the way that other biofeedback apps do, again like the Fitbit. The app with feedback alert system is being developed through a collaboration with Wei Cheng, Ph.D., assistant professor of computer science in the VCU School of Engineering, and the Websmith Group in Richmond. The sodium-sensing system starts with a microcircuit pattern that Yeo designed on the computer with illustration software. There are then more than 50 steps in the microfabrication process that took Yeo a year to devise. The final sensor consists of a copper membrane circuit that's 200 nanometers thick (that's 100 times thinner than a strand of human hair), a data-processing chip that converts the analog data from the sensors into digital data, and a Bluetooth chip that transmits the digital data to a wireless receiver or smartphone. All of it fits onto a thin piece of flexible elastomer slightly thicker than a Band-Aid measuring about 2 by 1 inches. "The advantage is that it can be bendable and stretchable without fracturing the material so we can put it on pretty much any surface," Yeo said. He'll work with the retainer mount for now, but he mentions the possibility of the sensor simply being glued to the roof of the mouth. Yeo will eventually expand the taste sensor to include the other four tastes: sour, sweet, bitter and umami. "I'm working on the sodium sensor and trying to add a pH sensor for sour, and the three other tastes will come later," Yeo said. "Umami is the hardest." Eventually, Costanzo and Yeo want to connect their sensor with the body. Much like a cochlear implant stimulates cochlear nerves to help a deaf person hear again, an internal taste implant would receive data from the food molecules coming in and then stimulate the appropriate nerves to create a perception of that taste. "We're approaching an era in the next couple decades where we will be interfacing with the brain and our perceptions with electronic devices," Costanzo said. "Maybe we can even trick our brains into liking broccoli."


News Article | March 2, 2017
Site: www.eurekalert.org

New Rochelle, NY, March 1, 2017--A study of U.S. Navy healthcare personnel has shown that when comparing the prevalence of post-traumatic stress disorder (PTSD) among women and men who had similar deployment experiences, and especially combat experience, the risk of PTSD was significantly higher among women. PTSD risk rose for both men and women with an increasing number of combat exposures, as reported in Journal of Women's Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The article is available free on the Journal of Women's Health website until April 1, 2017. Andrew MacGregor, PhD, MPH, Mary Clouser, PhD, MPH, Jonathan Mayo, MPH, and Michael Galarneau, Naval Health Research Center, San Diego, CA, present their findings in the article entitled, "Gender Differences in Posttraumatic Stress Disorder Among U.S. Navy Health Care Personnel." The researchers reviewed gathered data from the deployment records and post-deployment health assessments of more than 4,200 men and women who served in the U.S. Navy and supported military operations in Iraq and Afghanistan. "As the numbers of women in the military increase and their roles continue to expand in health care and other combat-related areas, it is important to be aware of any gender differences in risk for PTSD," says Susan G. Kornstein, MD, Editor-in-Chief of Journal of Women's Health, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, and President of the Academy of Women's Health. "Understanding specific factors that may increase or reduce PTSD risk, including those related to deployment, can contribute to improved prevention and treatment strategies" Journal of Women's Health, published monthly, is a core multidisciplinary journal dedicated to the diseases and conditions that hold greater risk for or are more prevalent among women, as well as diseases that present differently in women. Led by Editor-in-Chief Susan G. Kornstein, MD, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, and President of the Academy of Women's Health, the Journal covers the latest advances and clinical applications of new diagnostic procedures and therapeutic protocols for the prevention and management of women's healthcare issues. Complete tables of content and a sample issue may be viewed on the Journal of Women's Health website. Journal of Women's Health is the official journal of the Academy of Women's Health and the Society for Women's Health Research. Academy of Women's Health is an interdisciplinary, international association of physicians, nurses, and other health professionals who work across the broad field of women's health, providing its members with up-to-date advances and options in clinical care that will enable the best outcomes for their women patients. The Academy's focus includes the dissemination of translational research and evidence-based practices for disease prevention, diagnosis, and treatment of women across the lifespan. Journal of Women's Health and the Academy of Women's Health are co-presenters of Women's Health 2017: The 25th Anniversary Congress which will take place April 28-30, 2017 in Washington, DC. Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including LGBT Health, Transgender Health, Population Health Management, and Breastfeeding Medicine. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 80 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.


News Article | February 16, 2017
Site: www.eurekalert.org

New Rochelle, NY, Feb. 16, 2017 -- A new study shows that women who spend a longer time breastfeeding during their lifetimes may be able to lower their risk of metabolic syndrome and related disorders included elevated blood pressure, glucose, and triglyceride levels. Life-long breastfeeding of 12 months or longer was associated with a lower risk of metabolic syndrome, as reported in Journal of Women's Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The article is available free on the Journal of Women's Health website until March 16, 2017. The article entitled "Association Between Duration of Breast Feeding and Metabolic Syndrome: The Korean National Health and Nutrition Examination Surveys" describes a study of more than 4,700 Korean women aged 19-50 years in which the risk of developing metabolic syndrome or its component disorders was assessed based on life-long duration of breastfeeding, divided into four groups: 24 months. Coauthors Se Rin Choi, Yong Min Kim, Min Su Cho, So Hyun Kim, and Young Suk Shim, Hallym University, College of Medicine (Seoul, Korea), report the duration of breastfeeding found to be associated with decreased risk of individual components of metabolic syndrome, such as blood pressure, blood glucose, and cholesterol. "The advantageous effects of breastfeeding for newborns and babies are well established, and this study, which suggests that breastfeeding may protect the mother against metabolic syndrome, further adds to the evidence base supporting the benefits of breastfeeding for maternal health," says Susan G. Kornstein, MD, Editor-in-Chief of Journal of Women's Health, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, and President of the Academy of Women's Health. Journal of Women's Health, published monthly, is a core multidisciplinary journal dedicated to the diseases and conditions that hold greater risk for or are more prevalent among women, as well as diseases that present differently in women. Led by Editor-in-Chief Susan G. Kornstein, MD, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, and President of the Academy of Women's Health, the Journal covers the latest advances and clinical applications of new diagnostic procedures and therapeutic protocols for the prevention and management of women's healthcare issues. Complete tables of content and a sample issue may be viewed on the Journal of Women's Health website. Journal of Women's Health is the official journal of the Academy of Women's Health and the Society for Women's Health Research. Academy of Women's Health is an interdisciplinary, international association of physicians, nurses, and other health professionals who work across the broad field of women's health, providing its members with up-to-date advances and options in clinical care that will enable the best outcomes for their women patients. The Academy's focus includes the dissemination of translational research and evidence-based practices for disease prevention, diagnosis, and treatment of women across the lifespan. Journal of Women's Health and the Academy of Women's Health are co-presenters of Women's Health 2017: The 25th Anniversary Congress which will take place April 28-30, 2017 in Washington, DC. Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including LGBT Health, Transgender Health, Population Health Management, and Breastfeeding Medicine. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 80 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.


News Article | March 23, 2016
Site: phys.org

Gerling and dozens of other nurses, doctors, students and staffers flocked to a spacious entrance hall at Rush University Medical Center after learning about special animal therapy sessions the hospital has organized. Three huggable pups named Rocco, Minnie and Dallis greeted almost 100 white-coat and scrubs-clad visitors at a recent session, happily accepting cuddles, ear rubs and treats. Big grins on the human faces suggested the feelings were mutual. Minnie, a fluffy white and gray Labradoodle mix, had "the softest fur I'd ever felt, like a little cloud," Gerling said dreamily as he headed back to work. Many hospitals use animal therapy for patients—Rush has even brought in miniature horses. And many workplaces allow pets on site to boost employee satisfaction, but heelers for healers offers a different twist. The medical center has held the monthly Pet Pause sessions for over a year, using dogs from a local shelter and an animal therapy group. Recently, Rush nurses launched a study to see if the program has tangible effects on employee stress. Research in other settings has shown benefits from interacting with animals, including lowering stress hormone levels, blood pressure and heart rate. Early indications are that it may have similar benefits for hospital workers. In the study, the human visitors get blood pressure measurements and fill out questionnaires rating their stress levels before and after the canine cuddle sessions. "My blood pressure was kind of high when I came in, and it was lower when I left by about 10 points, so that was good," he said. Melissa Browning, a Rush nursing director involved in the study, rattles off a long list when asked about what makes hospital work particularly stressful: constant beeping from medical device alarms, dealing with gravely ill patients and worried families, triple checking the accuracy of patients' medicines and doses—it can all add up, Browning said. For Benjamin Gonzales, a graduate student in health systems management at Rush, the heavy course workload can be taxing and he called the dog session a welcome break—even if his blood pressure was a little higher afterward. "I could feel the big sighs coming out of me when I was with the dogs, so I know that just coming to this has made my day less stressful," Gonzales said. "This is amazing. I wish it could be every day." A management professor emeritus at Virginia Commonwealth University is among researchers who have found improvements in employee stress, satisfaction and productivity when dogs are allowed in the workplace. His name is Randolph Barker and he laughs that maybe he was destined to study the topic. His research was at a dinnerware company but Barker said there's no reason to think hospital workers wouldn't gain similar benefits. Dogs can potentially serve as a "low-cost wellness intervention," Barker said. The "pet a pooch" program for staffers at University of Pennsylvania's hospital inspired the Chicago program. Emergency room nurse Heather Matthew started the Penn program three years ago, bringing in dogs from local animal shelters. Besides boosting morale, Matthew said there's an added bonus—Penn hospital workers have adopted more than a dozen shelter dogs involved in the program. Explore further: Benefits of taking Fido to work may not be far 'fetched'


News Article | December 21, 2016
Site: www.marketwired.com

Six recent residency graduates are welcomed, six Fellows move on to new opportunities in medicine VAIL, CO--(Marketwired - December 21, 2016) - The Steadman Philippon Research Institute (SPRI) and The Steadman Clinic are known for their groundbreaking research and innovative methods of diagnosing, treating and rehabilitating orthopaedic patients. While advanced treatment methods and scientific breakthroughs are significant, it remains the people -- doctors, scientists, therapists and researchers -- that continue to drive the mission and purpose of SPRI and The Steadman Clinic. This summer SPRI and The Steadman Clinic welcomed six new MDs as Fellows who began their work assisting some of the world's finest orthopaedic surgeons and researchers in the Vail laboratories and clinics. At the same time, SPRI and The Steadman Clinic proudly said goodbye to their graduating class of six other Fellows who moved on to continue pursuing their professional goals of furthering advancement in their medical specialties. "At SPRI and The Steadman Clinic, we are so fortunate to attract some of the finest young medical practitioners and surgeons in the country," said Dr. Marc Philippon, co-chair of SPRI and managing partner of The Steadman Clinic. "Each year we get the opportunity to have these young physicians and scientists come to Vail and assist us with our research and help us find new and more effective ways to treat people suffering from a variety of joint injuries and other related medical issues. "What is even more satisfying to our staff here in Vail," continued Philippon, "is that we are then able to place these fine doctors in positions at some of the top hospitals, clinics and universities around the country." Dr. Salvatore Frangiamore and Dr. Sandeep Manava are two members of the 2016-17 class of Fellows and both young doctors are tremendously impressed with their experiences at SPRI and The Steadman Clinic so far. "The Fellowship program has been everything that we were promised it would be," said Frangiamore, who came to Vail from The Cleveland Clinic. "We knew that the program was designed to help us hone our skills in sports medicine and orthopaedic surgery but it also gives us the rare opportunity to work with some of the world's leaders in those fields. Not only are we working with the finest surgeons and researchers, but we are doing so in an environment that greatly challenges us due to the complexity of some of the cases that we are working." "One of the big attractions to me about this Fellowship program was the research opportunity," said Manava, who came to Steadman from Wake Forest University. "We get the chance to work with world-class physicians who treat a variety of sports-related injuries. After we observe and give initial treatment to the injury, we then have the ability to come back to our laboratory and utilize the finest and most cutting-edge technology available to find solutions for those injuries. "I've always viewed myself as not just a surgeon," added Manava, "but actually more of a scientist. The experiences here at The Steadman Clinic and SPRI have only strengthened my convictions." "I had high expectations before I even started the program several months ago," said Frangiamore. "I immediately became aware that the training and knowledge gleaned from these world-class doctors would far exceed those lofty expectations. The mentorship is top notch. The dedication that the staff devotes to our development is clearly indicative of the incredible reputation that The Steadman Clinic and SPRI have built in the medical field." "There is unparalleled leadership here," added Manava. "And it shows not just in the operating rooms and the laboratories but also in the manner with which all the doctors and staff members interact with the patients, the patients' families and the people of our community." This year's incoming fellows, all recent medical residency graduates, came to Vail from some of the top residency programs in the medical field. The recent additions, along with Frangiamore and Manava, are: Jon Godin, MBA, Duke University; Patrick Kane, MD, Thomas Jefferson University; Andrew Geeslin, MD, Western Michigan University and Geof Lebus, MD, Vanderbilt University. Sports medicine clinics and medical groups in Tacoma, Wash., Rapid City, S.D., La Crosse, Wis., Boulder, Colo., and Los Angeles represent the new professional homes of some of the outgoing class of SPRI and TSC Fellows. One member of the class also joined the faculty as an assistant professor at Virginia Commonwealth University. Frangiamore already has accepted a position upon his completion of the Fellowship program and Manava has narrowed his potential next job to just a few candidates. Both credit the experience at Steadman for helping make their placement process simpler and more enjoyable. "The Steadman name alone really boosted my ability to sell myself," said Frangiamore. "It's more than just the reputation. It is also a testament to the dedication the staff has for helping those of us in the Fellowship program move on to new challenges in our medical careers." "I am eagerly looking forward to my next stop," said Manava, "because I know that I will be able to effectively utilize what I have learned here in Vail and continue to represent The Steadman Clinic and SPRI. Steadman's reputation is among the best in the field and I will be honored to carry it forward when I conclude the Fellowship program." "Being able to help train the leaders in orthopaedic sports medicine is just one of the many great attributes of SPRI and The Steadman Clinic," said Dan Drawbaugh, CEO of SPRI and The Steadman Clinic. "We are honored that the youngest and brightest minds in the field seek to further their education and professional training with us in Vail. Their contributions are significant in our research endeavors. "We wish our outgoing Fellows the best of luck in their professional careers and always look forward to continuing our work with our new class of physicians."


News Article | November 3, 2016
Site: www.eurekalert.org

New Rochelle, NY, November 3, 2016--Women who avoided foods, cosmetics, and other products packaged in BPA-containing plastic containers for 3 weeks had significant reductions in urinary levels of BPA, a commonly used "endocrine disruptor" associated with negative health effects including weight gain. Over the 3-week study period, the women who participated in an intervention designed to minimize BPA exposure also had significant weight loss, as reported in Journal of Women's Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The article is available free on the Journal of Women's Health website. The article, entitled "Randomized Intervention Trial to Decrease Bisphenol A Urine Concentrations in Women: Pilot Study", shows that among the participants, the women in the control group who did not take part in the BPA-limiting intervention, had significant increases in both urinary BPA levels and weight gain after 3 weeks. Todd Hagobian, PhD and coauthors from California Polytechnic State University (San Luis Obispo, CA), propose future large-scale randomized trials to confirm these findings and to determine the potential positive health effects of reduced exposure to endocrine disrupting chemicals on risk factors for disorders such as type 2 diabetes and cardiovascular disease. "This study shows that by switching to BPA-free products it is, in fact, possible for women who have been exposed to BPA to reduce their body burden of the compound, as measured by urinary BPA levels," says Susan G. Kornstein, MD, Editor-in-Chief of Journal of Women's Health, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, and President of the Academy of Women's Health. "Although many consumers tend to reject products made of plastics containing BPA, there are unfortunately still many other endocrine disrupting chemicals in our environment." Journal of Women's Health, published monthly, is a core multidisciplinary journal dedicated to the diseases and conditions that hold greater risk for or are more prevalent among women, as well as diseases that present differently in women. Led by Editor-in-Chief Susan G. Kornstein, MD, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, and President of the Academy of Women's Health, the Journal covers the latest advances and clinical applications of new diagnostic procedures and therapeutic protocols for the prevention and management of women's healthcare issues. Complete tables of content and a sample issue may be viewed on the Journal of Women's Health website. Journal of Women's Health is the official journal of the Academy of Women's Health and the Society for Women's Health Research. Academy of Women's Health is an interdisciplinary, international association of physicians, nurses, and other health professionals who work across the broad field of women's health, providing its members with up-to-date advances and options in clinical care that will enable the best outcomes for their women patients. The Academy's focus includes the dissemination of translational research and evidence-based practices for disease prevention, diagnosis, and treatment of women across the lifespan. Journal of Women's Health and the Academy of Women's Health are co-presenters of Women's Health 2017: The 25th Anniversary Congress which will take place April 28-30, 2017 in Washington, DC. Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including LGBT Health, Population Health Management, and Breastfeeding Medicine. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 80 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.


News Article | December 14, 2015
Site: www.techtimes.com

According to a new study, the social media site Pinterest has a depression problem, and little is being done to treat it. The research, conducted by communications scholars from the University of Georgia and Virginia Commonwealth University, showed that fully 10 percent of the images "pinned" on the social media platform refer to thoughts of suicide, and "more than half of the pins referred to the seriousness and severity of depression." Given the apparent epidemic of depression on the site, you might think that public health organizations would take advantage of the service to spread counter-messages of hope and options for dealing with stress, anxiety and sadness. Yet, the authors of the study say that the vast majority of "coping strategies" offered were "dysfunctional," and posted by individuals rather than organizations. "There is a lack of representation from other health or medical organizations, and few have been engaged in this kind of dialogue or conversation on Pinterest with individuals who are suffering from or talking about depression," explained study co-author Yan Jin, an associate professor of public relations in the Grady College of Journalism and Mass Communication and associate director of the Center for Health and Risk Communication. "What kind of healing processes, support or lifestyle activities do health professionals recommend to these people that they can seek out?" Apparently, not many. A quick search for "depression coping skills" returns dozens of Pinterest results, but many are unscientific recommendations and assertions, like, "Natural antidepressant: two handfuls of cashews is the equivalent of a prescription dose of Prozac" (which has no scientific backing) and "probiotics heal depression" (which is a drastic oversimplification). While these recommendations are posted by individuals and not health agencies, they are not countered with helpful messages from reputable sources. Pinterest has 100 million monthly active users, about a third as many as Twitter, yet, according to this data, Pinterest is an under-tapped resource for mental health information. "This is a great opportunity for health professionals and health public relations professionals," Jin said, suggesting organizations provide "health tips on how to deal with depression [and] facilitate more positive discussions in this community." The study was published in the journal Public Relations Review, and is available online through ScienceDirect.


CHARLOTTESVILLE, Va. and MILWAUKEE, Nov. 02, 2016 (GLOBE NEWSWIRE) -- Journalists and political leaders from Eastern Europe and Central Asia will be observing U.S. elections in Virginia and Wisconsin as guests of Friendship Force International next week. The Friendship Force club of Milwaukee, Wis., will host five Serbian TV, radio and print journalists Nov. 4-12 who will be observing the effect of media on the U.S. elections. The Serbian journalists will be interviewed on radio the day before the Nov. 8 national election, and then will meet with the editorial board of the Milwaukee Journal Sentinel, as well as leaders of various political parties. Senior level government and political party officials, along with a university sociologist from Tajikistan, are observing election events in Charlottesville and Richmond while being hosted by the Friendship Force club of Charlottesville.  The guests will meet with Charlottesville political leaders and professors from the University of Virginia and Virginia Commonwealth University. “One of the core missions of Friendship Force International for almost 40 years is to build bridges of understanding among people from different parts of our world,” said Jeremi Snook, CEO and President of Friendship Force International, headquartered in Atlanta. “What better way for foreign journalists and political leaders to understand American democracy than to personally observe a presidential election – which some are calling the most intense and divisive in memory. It will be interesting to learn what their impressions are.” In typical Friendship Force fashion, the Serbs and Tajiks are staying in private homes experiencing typical American family life. Their schedules include visits to museums, universities, churches and restaurants. The guests are in the United States participating in a program managed by the Open World Leadership Center. With almost 16,000 members in more than 60 countries worldwide, Friendship Force International provides opportunities to explore new countries and cultures from the inside by bringing people together at the personal level. Through the signature program of home hospitality pioneered by The Friendship Force, local hosts welcome international visitors into their culture, sharing with them meals, conversation, and the best sights and experiences of their region. Celebrating its 40th anniversary in 2017, Friendship Force has brought together more than 1 million people in homestay and cultural immersion experiences that have helped to promote global understanding across the barriers that separate people. To learn more about how Friendship Force International can enrich your life, please visit http://friendshipforce.org/index.php/who_we_are The Open World Leadership Center, an agency of the U.S. Congress, awards exchange grants to local host organizations throughout the United States, such as Friendship Force. These grantees host business, health, policy and cultural delegations from post-Soviet Russia, Azerbaijan, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia, Ukraine, Tajikistan, and Turkmenistan. According to Open World, 8,200 American families have hosted participants in more than 2,400-plus communities around the country.


Young K.J.,University of Virginia | Bennett J.P.,Virginia Commonwealth University
Journal of Alzheimer's Disease | Year: 2010

Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by progressive decline in memory and cognition and pathologically by extracellular amyloid-β (Aβ) deposits and intraneuronal aggregates of hyperphosphorylated tau. Since its proposal in 1992, the amyloid cascade hypothesis implicates Aβ overproduction as a causative event in disease pathogenesis, and this thinking has predominated the field's understanding of AD pathogenesis and the development of potential therapeutics (i.e., Aβ-reducing agents). Though Aβ has been shown to induce AD pathology, unanswered questions for sporadic AD development suggests this hypothesis is best applied to familial disease only. The more recent mitochondrial cascade hypothesis is supported by data showing that early impairments of mitochondrial dysfunction and oxidative stress may precede Aβ overproduction and deposition. However, the development of Aβ-reducing agents continues. Unfortunately, these agents have not been efficiently tested for their effect on one of the earliest AD pathologies, i.e., mitochondrial dysfunction. This paper will review supporting data for the amyloid and mitochondrial cascade hypotheses, reports of the effects of secretase inhibitors on AD-phenotypic cells and animals, and begin to look at a potential role for γ-secretase, which is localized to mitochondria, in AD-related mitochondrial dysfunction. © 2010 IOS Press and the authors. All rights reserved.


Pickett J.T.,University at Albany | Baker T.,Virginia Commonwealth University
Criminology | Year: 2014

Scholars widely agree that the public is pragmatic about criminal justice. The empirical basis for this conclusion is the failure in several previous studies to find a sizable negative relationship between dispositional and situational crime attributions, or between support for punitive and rehabilitative crime policies. We suggest, however, that public pragmatism may be an artifact of the use of unidirectional question batteries in prior research to measure attribution styles and policy support. When such questions are used, acquiescent responding can introduce systematic error that is positively correlated across items and scales. Drawing on data from an experiment with a national sample (N = 826) of Internet panelists, we examine how this methodological approach impacts the bivariate correlations and multivariate relationships between attribution styles and between support for punitive and rehabilitative crime policies. The findings reveal that using unidirectional sets of questions to measure these concepts likely results in 1) inflated alpha reliability coefficients, 2) an underestimation of the magnitude of the negative relationships between attribution styles and between punitiveness and support for rehabilitation, and 3) an underestimation of the extent to which punitiveness and support for rehabilitation are driven by the same factors, working in opposite directions. © 2014 American Society of Criminology.


Sakao S.,Chiba University | Tatsumi K.,Chiba University | Voelkel N.F.,Virginia Commonwealth University
American Journal of Respiratory Cell and Molecular Biology | Year: 2010

Vascular remodeling is an important pathological feature of pulmonary arterial hypertension (PAH), which leads to increased pulmonary vascular resistance, with marked proliferation of pulmonary artery smooth muscle cells (SMC) and/or endothelial cells (EC). Successful treatment of experimental PAH with a platelet-derived growth factor (PDGF) receptor tyrosine kinase inhibitor offers the perspective of "reverse remodeling" (i.e., the regression of established pulmonary vascular lesions). Here we ask the question: which forms of pulmonary vascular remodeling are reversible and can such remodeling caused by angiogenic proliferation of EC be reversed? It is important to emphasize that the report showing reduction of vascular remodeling by PDGF receptor tyrosine kinase inhibitor showed only a reduction of the pulmonary artery muscularization in chronic hypoxia and monocrotaline models, which lack the feature of clustered proliferated EC in the lumen of pulmonary arteries. The regression of vascular muscularization is an important manifestation, whereby proliferative adult SMC convert back to a nonproliferative state. In contrast, in vitro experiments assessing the contribution of EC to the development of PAH demonstrated that phenotypically altered EC generated as a consequence of a vascular endothelial growth factor receptor blockade did not reverse to normal EC. Whereas it is suggested that the proliferative state of SMC may be reversible, it remains unknown whether phenotypically altered EC can switch back to a normal monolayer-forming EC. This article reviews the pathogenetic concepts of severe PAH and explains the many forms in PAH with reversible or irreversible remodeling.


Chun J.,Scripps Research Institute | Hla T.,Cornell University | Lynch K.R.,University of Virginia | Spiegel S.,Virginia Commonwealth University | Moolenaar W.H.,Netherlands Cancer Institute
Pharmacological Reviews | Year: 2010

Lysophospholipids are cell membrane-derived lipids that include both glycerophospholipids such as lysophosphatidic acid (LPA) and sphingoid lipids such as sphingosine 1-phosphate (S1P). These and related molecules can function in vertebrates as extracellular signals by binding and activating G protein-coupled receptors. There are currently five LPA receptors, along with a proposed sixth (LPA 1-LPA 6), and five S1P receptors (S1P 1-S1P 5). A remarkably diverse biology and pathophysiology has emerged since the last review, driven by cloned receptors and targeted gene deletion ("knockout") studies in mice, which implicate receptor-mediated lysophospholipid signaling in most organ systems and multiple disease processes. The entry of various lysophospholipid receptor modulatory compounds into humans through clinical trials is ongoing and may lead to new medicines that are based on this signaling system. This review incorporates IUPHAR Nomenclature Committee guidelines in updating the nomenclature for lysophospholipid receptors (http://www.iuphar-db.org/DATABASE/ FamilyMenuForward?familyId=36). Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics.


Medina-Ramos J.,Virginia Commonwealth University | Oyesanya O.,Norfolk State University | Alvarez J.C.,Virginia Commonwealth University
Journal of Physical Chemistry C | Year: 2013

The oxidation of glutathione (GSH) by the electrogenerated mediator [IrCl6]2- in the presence of bases (B) to produce the radical GS•, [IrCl6]3- and BH+, was studied by cyclic voltammetry in buffered and unbuffered solution using glassy carbon electrodes. This proton-coupled electron transfer (PCET) is the first step in the oxidation of GSH to produce the disulfide GSSG. The reaction exhibits a slight acceleration of the rate when the phosphate buffer (PB) concentration is raised at constant pH (5.0 or 7.0). The evidence indicates that proton acceptors whose conjugate acids have a pKa lower than GSH (8.7) but higher than GSH•+ can catalyze the reaction even though direct deprotonation of GSH is thermodynamically unfavorable. The value of kobs at 0.005 M of PBpH = 7.0 was equal to 4.3 ± 0.7 × 104 M-1 s-1 whereas at 0.200 M, was 2.56 ± 0.03 × 105 M-1 s-1. A kinetic isotope effect (KIE) dependent on [PB] was observed at pD 7.0, confirming that the S-H bond breaks during the rate-determining step. The predominance of a concerted PCET is postulated based on the compliance with the libido rule of general base catalysis, the KIE observed and the finding that stepwise pathways occur in lesser degree. Digital simulations were used to evaluate this mechanism. © 2012 American Chemical Society.


OBJECTIVE: To review the literature regarding the pharmacokinetic (PK) and clinical implications of the use of dabigatran in severe renal impairment for stroke prevention in nonvalvular atrial fibrillation (AF). DATA SOURCES: Searches of MEDLINE (2000-April 2012) and the Cochrane Database (2000-April 2012) were conducted. Key search terms included dabigatran, renal impairment, renal failure, and renal dysfunction. Additional limits included articles written in English and those involving human subjects. Bibliographic reviews were conducted to identify other pertinent data. STUDY SELECTION AND DATA EXTRACTION: Primary data were considered eligible for inclusion if they were from studies that evaluated the PKs of dabigatran in renal impairment or the effect of renal impairment on the risk for major bleeding with dabigatran. DATA SYNTHESIS: Dabigatran is an oral direct thrombin inhibitor indicated for the prevention of stroke and systemic thromboembolism in patients with nonvalvular AF, at a dose of 150 mg twice daily. Renal elimination is responsible for approximately 80% of dabigatran's clearance; thus, dose adjustment is required for patients with severe renal impairment. The approved dosing regimen for patients with creatinine clearance 15-30 mL/min (75 mg twice daily) was derived from PK modeling studies, limiting its applicability to the clinical setting. CONCLUSIONS: At this time, there is limited evidence to support safety or efficacy outcomes with the use of dabigatran for stroke prevention in patients with severe renal impairment and nonvalvular AF. Postmarketing data and large clinical trials are needed to determine the role of dabigatran in this population.


Wood A.C.,University of Alabama at Birmingham | Neale M.C.,Virginia Commonwealth University
Journal of the American Academy of Child and Adolescent Psychiatry | Year: 2010

Objective: To describe the utility of twin studies for attention-deficit/ hyperactivity disorder (ADHD) research and demonstrate their potential for the identification of alternative phenotypes suitable for genomewide association, developmental risk assessment, treatment response, and intervention targets. Method: Brief descriptions of the classic twin study and genetic association study methods are provided, with illustrative findings from ADHD research. Biometrical genetics refers to the statistical modeling of data gathered from one or more group of known biological relation; it was apparently coined by Francis Galton in the 1860s and led to the "Biometrical School" at the University of London. Twin studies use genetic correlations between pairs of relatives, derived using this theoretical framework, to parse the individual differences in a trait into latent (unmeasured) genetic and environmental influences. This method enables the estimation of heritability, i.e., the percentage of variance due to genetic influences. It is usually implemented with a method called structural equation modeling, which is a statistical technique for fitting models to data, typically using maximum likelihood estimation. Genetic association studies aim to identify those genetic variants that account for the heritability estimated in twin studies. Measurements other than those used for the clinical diagnosis of the disorder are popular phenotype choices in current ADHD research. It is argued that twin studies have great potential to refine phenotypes relevant to ADHD. Results: Prior studies have consistently found that the majority of the variance in ADHD symptoms is due to genetic factors. To date, genomewide association studies of ADHD have not identified replicable associations that account for the heritable variation. Possibly, the application of genomewide association studies to these alternative phenotypic measurements will assist in identifying the pathways from genetic variants to ADHD. Conclusion: Power to detect associations should be improved by the study of highly heritable endophenotypes for ADHD and by reducing the number of phenotypes to be considered. Therefore, twin studies are an important research tool in the development of endophenotypes, defined as alternative, more highly heritable traits that act at earlier stages of the pathway from genes to behavior. Although genetic variation in liability to ADHD is likely polygenic, the proposed approach should help to identify improved alternative measurements for genetic association studies. © 2010 American Academy of Child and Adolescent Psychiatry.


Kendler K.S.,Virginia Commonwealth University | Aggen S.H.,Virginia Commonwealth University | Patrick C.J.,Florida State University
Archives of General Psychiatry | Year: 2013

Context: Prior studies suggest that antisocial behavior in childhood and adolescence reflects multiple symptomatic dimensions. However, to our knowledge, no prior study has evaluated the underlying nature of the etiologic influences contributing to conduct disorder (CD) symptoms as defined in the DSM. Objective: To determine the structure of genetic and environmental risk factors for CD. Design: Population-based twin registry. Setting: Virginia. Participants: Two thousand seven hundred sixty-nine members of male-male twin pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Main Outcome Measure: Retrospective self-reported symptoms of CD. Results: The best-fitting multivariate twin model included 2 genetic factors, 1 shared environmental common factor, and 1 nonshared environmental common factor, along with criterion-specific genetic and nonshared environmental effects. The CD criteria with the strongest loadings on the 2 genetic factors were, respectively, those reflecting rule breaking (eg, playing hooky) and overt aggressive acts (eg, hurting people). The shared environmental common factor had salient loadings on a distinct set of criteria reflecting covert delinquent acts (eg, stealing and hurting animals). Loadings on the single nonshared environmental common factor were more uniform and less selective. Scores on the 3 familial CD factors were differentially associated with a range of personality, psychopathology, and demographic factors. Conclusions: From a genetic perspective, the DSM criteria for CD do not reflect a single dimension of liability. The familial risk to CD is composed of 2 discrete dimensions of genetic risk, reflecting rule breaking and overt aggression, and 1 dimension of shared environmental risk, reflecting covert delinquency. These 3 familial factors differ meaningfully in their association with a range of relevant validators. ©2013 American Medical Association. All rights reserved.


Goncy E.A.,Virginia Commonwealth University | Mrug S.,University of Alabama at Birmingham
Journal of Studies on Alcohol and Drugs | Year: 2013

Objective: This study examined the location and time of adolescent use of cigarettes, alcohol, and marijuana. Age, gender, and racial differences in location and time of use were studied for each substance. Method: Using cross-sectional data collected through the school-wide Pride Survey, 20,055 students between the ages of 10 and 19 years (53.6% female, 55.1% Black, 44.9% White) in one metropolitan area reported on their frequency of cigarette, alcohol, and marijuana use, as well as the location and time of use of each substance. Chi-square tests compared the rates, locations, and times for each substance across boys and girls; Black and White students; and early, middle, and late adolescents. Results: Older adolescents reported higher rates of substance use at friends' homes, at school, and in cars and lower rates of alcohol use at home compared with younger youth. Males were more likely to report alcohol and marijuana use at school and on weeknights and alcohol use in cars, whereas females were more likely to report alcohol and marijuana use on the weekends. No gender differences emerged for times and locations of cigarette use. Compared with Black youth, White adolescents were more likely to use all substances at friends' homes and on weekends; to smoke cigarettes at school, in the car, and on week-nights; and to use alcohol at home. Black adolescents were more likely to report using alcohol at home, at school, in cars, during and after school, and on weeknights and were more likely to report using marijuana at school. Conclusions: The location and time of adolescent substance use vary substantially by age, gender, and race. These differences may help tailor substance use prevention and intervention programs to specific subgroups of youth to improve program effectiveness.


Pickett J.T.,University at Albany | Mancini C.,Virginia Commonwealth University | Mears D.P.,Florida State University
Criminology | Year: 2013

With the possible exception of terrorists, sex offenders in the United States experience a greater degree of punishment and restriction than any other offender group, nonviolent or violent. Members of the public overwhelmingly support "get tough" sex crime policies and display an intense hostility toward persons labeled "sex criminals." The theoretical literature has identified three models potentially explaining public opinion on the social control of sex crime: the victim-oriented concerns model, the sex offender stereotypes model, and the risk-management concerns model. However, empirical work that directly tests these models is absent. This article addresses that gap by analyzing national survey data that includes measures of the key concepts outlined in the different theoretical models and items gauging support for punitive sex crime laws as well as support for sex offender treatment. The findings provide partial support for all three models but suggest that extant theories can better explain support for punitive sex crime policies than views about sex offender treatment. © 2013 American Society of Criminology.


Chen Q.,Virginia Commonwealth University | Lesnefsky E.J.,Virginia Commonwealth University | Lesnefsky E.J.,Veterans Affairs Medical Center
FEBS Letters | Year: 2011

Myocardial ischemia damages the electron transport chain and augments cardiomyocyte death during reperfusion. To understand the relationship between ischemic mitochondrial damage and mitochondrial-driven cell death, the isolated perfused heart underwent global stop-flow ischemia with and without mitochondrial protection by reversible blockade of electron transport. Ischemic damage to electron transport depleted bcl-2 content and favored mitochondrial permeability transition (MPT). Reversible blockade of electron transport preserved bcl-2 content and attenuated calcium-stimulated mitochondrial swelling. Thus, the damaged electron transport chain leads to bcl-2 depletion and MPT opening. Chemical inhibition of bcl-2 with HA14-1 also dramatically increased mitochondrial swelling, augmented by exogenous H 2O 2 stress, indicating that bcl-2 depleted mitochondria are poised to undergo MPT during the enhanced oxidative stress of reperfusion.


Klausner A.P.,Virginia Commonwealth University | Steers W.D.,University of Virginia
Medical Clinics of North America | Year: 2011

Patients with lesions of the central nervous system often have neurogenic bladder dysfunction. Lifelong bladder monitoring and management in these patients is necessary to prevent severe complications, including renal damage. The urodynamic test, performed by neurourologists or other specially trained providers, is the definitive test for diagnosis and management of neurogenic bladder dysfunction. This article describes the indications and technique of urodynamic testing and the interpretation of the results of such testing. The management of patients with neurogenic bladder dysfunction is also discussed. © 2011.


Brannan M.E.,Virginia Commonwealth University | Petrie T.A.,University of North Texas
Eating Behaviors | Year: 2011

Research has examined psychological moderators of the body dissatisfaction-bulimic symptomatology relationship, but the focus has been on variables thought to worsen the relationship. In this study, we examined self-esteem, optimism, satisfaction with life, and self-determination as potential buffers. Participants were 847 female undergraduates. Using hierarchical multiple regression (HMR), we controlled for the influences of social desirability and body mass index on bulimic symptomomatology and then determined the main and interactive effects of body dissatisfaction and each moderator. Self-determination, optimism, self-esteem, and satisfaction with life all buffered the deleterious effects of body dissatisfaction, such that when levels of the moderators were high, the relationship between body dissatisfaction and bulimic symptomatology was weakest. Knowing what psychological variables moderate women's body dissatisfaction can assist psychologists and other health professionals in developing effective treatments for lessening disordered eating among women. © 2011 Elsevier Ltd.


Laplante B.L.,Virginia Spine Research Institute Inc | Ketchum J.M.,Virginia Commonwealth University | DePalma M.J.,Virginia Spine Research Institute Inc
Pain Physician | Year: 2012

Background: Discogenic, facet joint, and sacroiliac joint mediated axial low back pain may be associated with overlapping pain referral patterns into the lower limb. Differences between pain referral patterns for these three structures have not been systematically investigated. Objective: To examine the individual and combined relationship of age, hip/girdle pain, leg pain, and thigh pain and the source of internal disc disruption (IDD), facet joint pain (FJP), or sacroiliac joint pain (SIJP) in consecutive chronic low back pain (CLBP) patients. Design: Retrospective chart review. Setting: Community based interventional spine practice. Patients: 378 cases from 358 consecutive patients were reviewed and 157 independent cases from 153 patients who underwent definitive diagnostic injections were analyzed. Methods: Charts of consecutive low back pain patients who underwent definitive diagnostic spinal procedures were retrospectively reviewed. Patients underwent provocation lumbar discography, dual diagnostic medial branch blocks, or intra-articular diagnostic sacroiliac joint injections based on clinical presentation. Some subjects underwent multiple diagnostic injections until the source of their chronic low back pain (CLBP) was identified. Main Outcome Measurements: Based on the results of diagnostic injections, subjects were classified as having IDD, FJP, SIJP, or other. The mean age/standard deviation and the count/percentage of patients reporting hip girdle pain, leg pain, or thigh pain were estimated for each diagnostic group and compared statistically among the IDD, FJP, SIJP, and other source groups. Next, the 4 predictor variables were simultaneously modeled with a single multinomial logistic regression model to explore the adjusted relationship between the predictors and the source of CLBP. Results: The mean age was significantly different among the source groups. IDD cases were significantly younger than FJP, SIJP, and other source groups and FJP cases were significantly younger than other sources. The age by thigh pain interaction effect was statistically significant (P = 0.021), indicating that the effect of age on the source of CLBP depends on thigh pain, and similarly, that the effect of thigh pain on the source of CLBP depends on age. Limitations: Retrospective study design. Conclusions: The presence or absence of thigh pain possesses a significant correlation on the source of CLBP for varying ages, whereas the presence of hip/girdle pain or leg pain did not significantly discriminate among IDD, FJP, or SIJP as the etiology of CLBP. Younger age was predictive of IDD regardless of the presence or absence of thigh pain.


Grant
Agency: Department of Defense | Branch: Army | Program: STTR | Phase: Phase II | Award Amount: 425.14K | Year: 2011

There is a well-understood need for a small bioinformatics based wearable critical care monitor allowing for the remote monitoring and triage of wounded warfighters. Our Phase I research demonstrated that by augmenting a commercial wearable body monitoring device (BodyMedia"s SenseWear Armband) with ECG and sophisticated signal processing including the wavelet transform invented at Virginia Commonwealth University, the hemorrhagic shock status of a wounded warfighter was accurately detectable in a simulated shock setting. Algorithms were also developed to predict useful critical parameters such as pulse pressure, shock index, stroke volume, and blood pressure from the armband signals. Subsequent research suggests that adding arm impedance to the existing set of sensors (ECG, heat flux, galvanic skin response, skin temperature, ambient temperature, and motion-based-parameters) further improves the accuracy of the system. Our Phase II proposal is to incorporate all of these sensors into a commercially ready wearable platform with additional memory and networking capabilities and to further improve and validate the prediction algorithms using existing collaborative efforts with the US Army Institute of Surgical Research (USAISR) as well as on critically ill and injured trauma and surgical patients at a busy urban Level I Trauma Center (VCU Medical Center).


News Article | November 4, 2016
Site: www.prweb.com

Evolution Labs announced today that Gannon has adopted its SA360 platform as a required part of its student-athlete experience across all of its men’s and women’s NCAA teams. SA360 provides student-athletes with engaging mobile app and web-based content on topics ranging from health and wellness to avoiding risk behavior, to assessing and improving their academic skills. Gannon joins other top intercollegiate athletic departments that have integrated the platform into their core programming, including Louisiana State University, Virginia Commonwealth University and the University of Maryland. “The university and the athletic department are committed to fostering students’ success as scholars, athletes and citizens,” said Lisa Goddard McGuirk, Director of Athletics at Gannon. “SA360 uses smart technology to deliver content in a manner that’s more compelling and convenient to student-athletes, while enabling the athletic department to provide timely support throughout the academic year. SA360 can assist student-athletes whether they’re on campus or traveling to an away game.” SA360 covers important success topics, including mental health, physical fitness, study and test-taking skills, time management skills, drug and alcohol use, sexual assault, NCAA compliance and career preparedness. It employs pulse surveys, social media, interactive self-tests and digital video to keep students returning for regular updates. In addition, the platform can be configured to work as part of an existing course or as an independent required curriculum. “Gannon is extremely forward-thinking in their efforts to support student-athletes,” said Peter Kraft, CEO at Evolution Labs. “SA360 will enable Gannon to strengthen its engagement with student-athletes and increase their likelihood of furthering their success both on and off the field.” About Gannon University Athletics Gannon is a Catholic, Diocesan university dedicated to excellence in teaching, scholarship and service. Its faculty and staff prepare students to be global citizens through programs grounded in the liberal arts and sciences and professional specializations. Inspired by the Catholic Intellectual Tradition, it offers a comprehensive, values-centered learning experience that emphasizes faith, leadership, inclusiveness and social responsibility. The Gannon Athletics Department serves over 600 student-athletes and 20 varsity teams. The Golden Knights are a proud member of the NCAA Division II, Pennsylvania State Athletic Conference (PSAC), Eastern College Athletic Conference (ECAC), Collegiate Water Polo Association (CWPA), Western Water Polo Association (WWPA) and National Collegiate Acrobatics & Tumbling Association (NCATA). The department produced a 3.24 cumulative grade point average during the 2015-16 academic year with 65 percent of Gannon’s student-athletes achieving a 3.0 GPA or better during the 2016 Spring semester. In competition, 16 ofGannon’s 20 programs qualified for the postseason last year, including 12 of its 16 PSAC sports. Seven teams participated in the national postseason. Athletic honors during the 2015-16 academic year included 85 conference players of the week, 62 all-conference selections, 20 all-region selections and 17 All-Americans. About Evolution Labs Spanning the entire student lifecycle, Evolution Labs is vastly improving the engagement experience between schools and students. The company’s proprietary S360 and P360 programs help schools drive enrollment and retention, and also gain the alliance and influence of parents. It’s SA360 program delivers critical success content to college student-athletes, and the company’s Suite360 program engages K-12 students in highly immersive content around character development and social & emotional learning.


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

The Center for Innovative Technology (CIT) announced today that Robert Brooke, CIT’s Federal Funding Director, has been selected as a U.S. Small Business Administration (SBA) 2016 Tibbetts Award winner for his unique contributions to the Small Business Innovation Research (SBIR) Program. Named after “father of the SBIR Program” Roland Tibbetts, the prestigious Tibbetts Award recognizes those individuals and organizations that have made a visible technological impact on the socio-economic front and exemplify the very best in SBIR achievements. Brooke formed CIT’s Federal Funding Assistance Program in 2002 to help Virginia’s early stage science and technology-based companies pursue and capture non-dilutive grant and contract financing from the federal government. Since formation, Brooke’s Program has provided instruction, federal agency connections and consultation to thousands of Virginia entrepreneurs encompassing tech, life science, clean tech and other emerging technology sectors and spanning all regions of the Commonwealth. Under Brooke’s leadership, Virginia has been recipient and four SBA Federal and State Technology Partnership Program (FAST) grants and has consistently ranked among the nation’s top state recipients of SBIR and STTR grant and contract funding. “Robert’s tireless work with Virginia entrepreneurs to raise their awareness of federal funding options and to help position them for federal funding wins has been an invaluable part of CIT’s efforts to ensure that Virginia’s emerging companies receive adequate funding to meet their growth objectives,” said Tom Weithman, CIT’s GAP Funds Managing Director and Vice President. “I would like to congratulate Robert on behalf of the Board of Directors, management and staff of CIT. This distinguished national award is the result of his dedication, hard work and creativity to the support of innovators and entrepreneurs across the Commonwealth. This recognition attests to the significant impact Robert’s Program has had on every region and demographic segment of the Commonwealth and the importance of his Program as a nation-wide model that other states seek to emulate,” said Ed Albrigo, CIT’s President and Chief Executive Officer. The SBIR Program represents the nation's largest source of early stage research and development funding for small businesses. The programs are administered by the SBA in collaboration with 11 federal agencies, which collectively supported more than $2.5 billion in federal research and development funding in fiscal year 2015. Companies supported by the SBIR and STTR programs often generate some of the most important breakthroughs each year in the United States. Over the course of the last few months, CIT has held multiple SBIR/STTR virtual webinars and on-site workshops at universities across the state, including sessions at Virginia Commonwealth University and George Mason University. Additional workshops will be held at the University of Virginia (February 21-22, 2017) and Virginia Tech (February 23-24, 2017). To learn more details or to register for these workshops, visit the CIT Events Calendar on our website. About the Center for Innovative Technology, http://www.cit.org Since 1985, CIT, a nonprofit corporation, has been Virginia’s primary driver of innovation and entrepreneurship. CIT accelerates the next generation of technology and technology companies through commercialization, capital formation, market development and revenue generation services. To facilitate national innovation leadership and accelerate the rate of technology adoption, CIT creates partnerships between innovative technology start-up companies and advanced technology consumers. CIT’s CAGE Code is 1UP71. To learn more, please visit http://www.cit.org. Follow CIT on Twitter @CITorg and add the Center for Innovative Technology on LinkedIn and Facebook.


News Article | December 14, 2016
Site: www.newscientist.com

MILLIONS of people worldwide use e-cigarettes or vaping equipment instead of smoking tobacco. But nicotine isn’t the only drug people are vaping. Some vapers are experimenting with recreational drugs, mixing them into the e-liquid that goes into vapes and sharing their experiences online. This, along with advances in vaping technology, has led to an increase in drug-based e-liquids advertised for sale on dark web marketplaces. Cannabis is a common choice but vendors on dark web marketplace Alphabay also sell e-liquid containing cocaine, morphine, MDMA (ecstasy) and temazepam, a drug sometimes prescribed for insomnia. There are even listings for fentanyl, a potent opiate responsible for thousands of fatal overdoses in recent years. Michelle Peace at Virginia Commonwealth University is leading a project that examines drug use and abuse involving vaping, with a view to educating the public and providing information to law enforcement, medical examiners and forensic scientists. Her team is investigating which substances these e-liquids contain and whether they can be vaporised. The project is supported by grants from the US National Institute of Justice. “The users believe they are experiencing better drug delivery,” says Peace. “Part of our work has been to understand why they think that is the case.” Peace and her colleagues tested e-liquids containing everything from legal substances such as nicotine, vitamins and caffeine to illicit drugs, including cannabis, heroin and methamphetamine. They used mass spectrometry to see what is actually contained in e-liquids available for sale on the dark web. For instance, they have found synthetic cannabinoids in some liquids that weren’t labelled as containing any drug other than nicotine but were suspiciously expensive. “Vaping e-liquids that contain drugs could make already dangerous drugs even more dangerous” They also tested how effectively different drugs vaporise. To do this, they used a machine that “inhales” the e-liquid and then analyses which chemicals are present in the vapour. The researchers haven’t yet published their results, but Peace says it seems that many drugs can be vaporised. Tests with methamphetamine, for example, showed the drug was present in the vapour. Vaping recreational drugs poses public health concerns. As drug delivery via the lungs is generally more effective than some other methods, says Peace, vaping could make “already dangerous drugs even more dangerous”. There are other risks, too. The lungs are a sensitive organ and drugs or other constituents of these e-liquids could cause inflammation, says John Britton at the University of Nottingham, UK. But vaping could also have legitimate medical applications. “If the pharmaceutical industry can figure how to control dosing, it may be an effective tool to deliver therapeutic pharmaceuticals in the future,” says Peace. This article appeared in print under the headline “High on vapour”


News Article | January 4, 2016
Site: www.theenergycollective.com

Virginia may be the only state in the U.S. with a law creating a public-private partnership structure whose mission is to strengthen and promote its nuclear energy and technology industries. There are two components of the partnership, the Virginia Nuclear Energy Consortium Authority (VNECA) and the Virginia Nuclear Energy Consortium (VNEC), which is a private, not for profit corporation that is answerable to the authority. The VNECA Board composition was defined by statute to be composed of the following: The authorizing legislation passed with little opposition in early 2013, and the VNECA hosted the first of a series of meetings that October. Following the authority’s lead, VNEC devised a shared funding mechanism, signed up a group of eight founding, fee-paying members, produced a mission statement and hired an executive director. Those entities are AREVA, BWXT, Dominion, GE-Hitachi, Newport News Shipbuilding, University of Virginia, Virginia Commonwealth University and Virginia Tech. On December 10, 2015, the consortium’s executive director Marshall Cohen spoke at the annual joint meeting of the Virginia chapters of the American Nuclear Society and the American Society of Mechanical Engineers. Cohen walked the crowd of 70 interested professionals through VNEC’s history, described its current activities, talked about near term priorities and solicited the involvement of everyone with a vested interest in seeing the organization make progress in achieving its mission. That mission is to sustain and enhance the Commonwealth of Virginia as a national and global leader in nuclear energy and serving as an interdisciplinary business development, research, training, and information resource on nuclear energy issues. I attended the meeting and listened carefully to the presentation. During his talk Cohen spoke to the importance of the Ex-Im Bank reauthorization and VNEC’s active role as one of many supporters of the effort. That involvement was successful and provided VNEC an opportunity to build its brand and prove its worth to members and potential members. It also enabled the organization to begin building a national network and organizational identity. The VNEC executive described an effort in cooperation with NEI that will result in a conference in the first quarter of 2016 for interested individuals and organizations to discuss nuclear technology issues in Virginia. The event is being treated as a prototype for similar events around the country. He then recounted a conversation with Gov. Terry McAuliffe (D) that some of my fellow Virginians (and Americans) might find a little incredible. Cohen: I was with the governor on Monday morning [Dec 7] at a conference. He says, “Oh yeah, nuclear in Virginia. That’s critical. That’s important. I love nuclear. I wish we had 100% nuclear. What can I do to help?” It’s the governor. He’s ebullient. But you know what, he will help. When Cohen finished talking and solicited questions, my hand shot up. Here is a transcript of the resulting conversation. Adams: One of the things that I’ve worked on over the last cou- ple of years is helping people understand that mining uranium is a useful and vital part of our industry and that people who try to make it out as a health issue are harming the prospects for the rest of us. You talk about a nuclear cluster in Virginia. We have at least 119 million pounds of uranium on private property with good roads and good infrastructure. Is the Virginia Nuclear Energy Consortium going to work on that issue and help the Coles access their private property? Cohen: It is not an issue that’s come to us. I would be more than happy to take the issue to the board. Somehow just make a request or give me some background information and we can cer- tainly have a board discussion. I follow the policies that they want to set. I try to help guide them so that they can see what’s going on so they are aware of things. I’m familiar enough with it; I’ve lived in Virginia for a long time so I’m familiar enough with a little of the history. But in all of the nuclear stuff that I’ve done for the last 12-13 years, I’ve not really dealt with mining issues per se. But I did a lot of work in New Mexico on uranium enrichment and am aware of the mine history and legacy and all of the issues that come at us even though we weren’t involved in that. Adams: And it’s very important for us as communicators to help people understand that history is not what we’re doing today. We don’t do mining the same way they were doing it in New Mexico in the 1950s. It’s a completely different animal. Cohen: But we have to be cognizant of experiences. You know there are no boundaries on those things, even more so now with the Internet. So we need to be prepared. Well educated, well in- formed and prepared if we’re going to move forward. And even if we’re going to make presentations to the VNEC board, we’re going to want to give a thorough presentation. I’d be happy to bring it to them. Adams: I’ll recommend to Virginia Uranium that they talk to you and also that they talk to you about becoming a member. If this was not a nuclear thing, it would seem very strange indeed to realize that a state whose government has created a structure like VNECA and VNEC also has rejected efforts to overturn a three decade old “temporary” moratorium on uranium mining. Since we’re talking about nuclear, no one should be at all surprised. Note: A slightly different version of the above first appeared in the Nuclear Buzz column of the December 17, 2015 edition of Fuel Cycle Week. This version includes an expanded description of the VNECA membership and a correction of a typo in the list of corporations from “Hitachi” to “GE-Hitachi.” It is reprinted here with permission. The post Virginia Loves Nuclear But Hates Uranium – Why? appeared first on Atomic Insights.


Magnetic material is commonly used for data storage—think of magnetic strips on the back of a credit card—and the ability to flip the "polarity" (magnetization direction) of magnetic particles that are retained for long periods of time without needing power is essential to nonvolatile magnetic memory. A group of researchers at the Virginia Commonwealth University School of Engineering has developed a process to bring about this flipping of magnetic "polarity." The group's method offers a significant reduction in energy required for big data and cloud memory storage. "When you look at the energy reduction that this affords, it's a major change," said Jayasimha Atulasimha, Ph.D., Qimonda associate professor in the Department of Mechanical and Nuclear Engineering. "This has the potential to significantly reduce the energy consumption in switching non-volatile magnetic memory devices." The system that Atulasimha and doctoral candidates Dhritiman Bhattacharya and Md Mamun Al-Rashid have designed uses an electric field to reverse the direction of magnetic skyrmions. A magnetic skyrmion is a magnetic state characterized by a core that points either upward or downward, and progressively rotates from its core to its periphery. Bhattacharya discovered that an electrical field alone could bring about a flip in core magnetization. Using an electric field, instead of current or a magnetic field, presents the possibility of more energy-efficient magnetic memory for computing. "The exciting thing about this kind of magnetic encoding is that it only takes a small amount of energy to flip and once you have the direction you want, it can stay there for a long time. No additional energy is needed," Bhattacharya said. "We were surprised at the early results that an electric field alone could reverse the skyrmion core but now understand why this happens," said Al-Rashid. In the next phase of the group's research, they will investigate how this process works in the presence of thermal noise at room temperature. They will also determine how controlled the process is in order to assess whether the polarities can be reversed every time in the presence of such disturbances. In addition to energy savings for big data storage, this technology may have applications in body-embedded devices so that they can run with less frequent battery replacements. It may also provide a tool for more sophisticated logic in data processing and retrieval. "Right now we have an idea backed by rigorous simulations," Atulasimha said. "We hope to study this system more extensively as well as work in collaboration with other experimental groups to establish a solid proof-of-concept in the hope that this idea sees applications in one of these areas." Explore further: MEPhI helps to create memory nanoelements for satellites


News Article | December 9, 2015
Site: www.nature.com

As a palliative-care researcher, Susan McClement has talked to many people dying of cancer and their families — and some of their stories are burned into her brain. One man was so concerned by the sight of his emaciated wife, whose body had been ravaged by metastatic breast cancer, that he resorted to force feeding her — pinching her nose and slipping in a spoonful of food when she opened her mouth. Convinced that food would give her the energy to fight the cancer, his daily visits became protracted battles. She died a few weeks later. McClement, who works at the University of Manitoba in Winnipeg, Canada, says that nutritional conflicts can become a source of regret for relatives. “They said, ‘You know, if I could do it over again, I would have spent much less time fighting about tapioca pudding and much more time telling my wife that I loved her.’” The woman in this case had cachexia, a metabolic disorder that affects some 9 million people worldwide, including as many as 80% of people with advanced cancer. It typically involves extreme weight- and muscle-loss, makes routine activities difficult and increases the risk of deadly complications such as infections. Adding calories doesn’t reverse cachexia, and McClement says that the disorder sometimes provokes extreme reactions from family members because it serves as visual confirmation of their worst fears. “It’s a constant reminder that the person is sick and is not going to get better,” says McClement. Cachexia is seen in the late stages of almost every major chronic illness, affecting 16–42% of people with heart failure, 30% of those with chronic obstructive pulmonary disease and up to 60% of people with kidney disease. But for many years it was overlooked, as physicians and researchers focused their attention on the primary illness instead. Now, scientists are increasingly viewing cachexia as a distinct, treatable condition. Basic research has revealed how it is driven by inflammation and metabolic imbalances, and has generated drug targets, says Stefan Anker, a cardiologist and cachexia specialist at the University Medical Center Göttingen in Germany. “Now we have quite a number of powerful options to test,” he says. This has spurred investment from drug developers who aim to reduce suffering, and possibly give patients the strength to withstand chemotherapy or surgery. But some high-profile clinical trials in the past two years have produced disappointing results, prompting much self-reflection in the young field. “I’m a little bit worried that if we don’t see a successful clinical trial in the next five years, the dollars from the pharmaceutical industry to develop a treatment will go somewhere else,” says Jose Garcia, a clinical researcher focused on wasting disorders at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas. “In my view, that would be a missed opportunity.” The term cachexia is derived from the Greek kakos and hexis, meaning ‘bad condition’. It is thought that Hippocrates recognized the syndrome — but it took until 2006 for the cachexia field to start working up a formal definition, which includes a loss of 5% or more of body weight over 12 months, and reduced muscle strength. In the clinic, it remains under-recognized by oncologists, says Egidio Del Fabbro, a palliative-care physician and researcher at Virginia Commonwealth University in Richmond. There are no standard guidelines for treatment. In the past decade, researchers have made strides in learning about the causes of cachexia, thanks to funding from the US National Cancer Institute and some advocacy groups. New international conferences (including one that wrapped up this week in Paris) and the launch of a research journal — the Journal of Cachexia, Sarcopenia and Muscle — have also drummed up interest in the field. It is now clear that a key mechanism underlying cachexia is the increased breakdown of muscle protein, along with dampened protein synthesis, which leads to overall muscle loss. Studies in 2001 helped to jump-start the field when they identified genes that were more active in atrophying rodent muscles than in normal ones1, 2. These genes encode enzymes called E3 ubiquitin ligases, which tag proteins for destruction in the cell. Mice without these enzymes were resistant to muscle loss. Muscle cells seem to make more of these ligases when hit with certain inflammatory signals from tumours or from immune cells responding to cancer or other illness. Abnormalities in apoptosis (programmed cell death) and in the muscle cell’s energy-producing organelles, mitochondria, have also been implicated. Several drug-makers have homed in on the protein myostatin, which blocks muscle growth. In a 2010 paper3 that got many people excited about a possible cachexia drug, researchers from biotechnology company Amgen in Thousand Oaks, California, showed that they could reverse muscle loss and extend the lives of mice with tumours and cachexia by blocking signalling through the myostatin pathway. Research since then suggests that cachexia is more than a muscle disease. Studies4 have identified problems in the brain’s regulation of appetite and feeding, and even ways in which the liver might be contributing to the energy imbalance that sees the body burn its own tissue to sustain itself. Others have looked at fat tissue, which can also waste away in cachexia. They showed that inflammation5 and molecules made by tumours6 cause white fat cells to turn into brown fat cells, which burn more energy to generate heat than white fat cells. The question that researchers are now tackling is how tissues and organs — muscle, brain, fat, even bone — are communicating with one another. A paper published last week7 suggests that fat signalling could be involved in muscle atrophy. All this research has brought more representatives of biotechnology and pharmaceutical companies to cachexia meetings in recent years, says Denis Guttridge, a cell biologist at the Ohio State University in Columbus, who organizes one such conference. “That’s exciting for a basic scientist like myself,” he says. “I can see the increase in the translational pipeline.” Despite the excitement in labs, clinical research has so far proved disappointing. In 2011, biotech firm GTx of Memphis, Tennessee, launched two late-stage clinical trials of enobosarm, a molecule that binds to the same receptor as testosterone but only in muscle and bone, mimicking the hormone’s ability to stimulate muscle build-up but without its undesirable side effects. Results from earlier, smaller trials looked promising: people taking the drug had increased lean body mass and improved physical function, as measured by their speed at climbing stairs8. But in the larger tests of the drug, on people with advanced lung cancer, the benefits in function disappeared. The firm has since abandoned muscle wasting, and is instead testing larger doses of enobosarm to treat breast cancer. A pair of unpublished studies on people with lung cancer and cachexia tested a compound called anamorelin, which mimics ghrelin, an appetite-stimulating peptide hormone produced mainly by the stomach. The trials were sponsored by pharmaceutical company Helsinn in Lugano, Switzerland, which reported that participants in the treatment group put on weight and muscle mass compared with those taking a placebo, but showed no difference in hand grip strength. Still, the company announced last week that the European Medicines Agency is reviewing its drug for approval. There is a lot of debate about why the trials failed to show functional improvements. Some researchers say that the teams did not use the most clinically relevant measures of muscle function. “We don’t really know what is the best test for this,” says Garcia. “If you can climb up a set of stairs one second faster, what does that mean?” This confusion about trial design is a problem for the field, says Anker. “We need to reach consensus on endpoints and what to aim for in our treatments.” Another problem is that animal data on cachexia may not translate into humans. Some work has tried to make a case that the mechanisms found in rodents might be similar to those in humans, by looking at human tissue samples, says Vickie Baracos, a clinical translational researcher in muscle wasting at the University of Alberta in Edmonton, Canada. “But held up to scrutiny, this clinical evidence is often rather sketchy.” Researchers in the field lament the dearth of human data and clinical samples. Baracos says that studies are needed that follow people with cachexia over time, collecting blood and muscle samples along the way. “A cachexia data repository with a biobank would sure be a great thing,” she says. Perhaps the biggest challenge is that the field has to compete for funding and recognition with research into other major diseases, says Anker. “Cachexia is competing for internal resources within big companies, fighting with cancer, cardiology,” he says. Few companies have dedicated cachexia groups or departments. GTx stopped its work on muscle wasting in part because insurers did not seem interested in covering a medication that was only going to target cachexia and not cancer, says Mary Ann Johnston, the company’s vice-president for clinical development. “There’s a lack of interest in supportive care.” But an effective treatment would be transformative, says Garcia. It might spur physicians to talk more to patients and their families about the troubling symptoms of cachexia. Without the tools to treat the syndrome, many doctors don’t address it, he says. And that vacuum of information can be distressing. McClement, for her part, has been interviewing more families of people with cachexia. She hopes to find ways to better inform them about the condition and help them to cope. Given the absence of pharmacological interventions, such psychosocial ones are important, she says. “That’s all we’ve got.”


News Article | January 28, 2016
Site: www.biosciencetechnology.com

Scientists pursuing the biological roots of schizophrenia have zeroed in on a potential factor - a normal brain process that gets kicked into overdrive. The finding could someday lead to ways to treat the disease or even prevent it. The result - accomplished by analysis of genetics, autopsy brain tissue and laboratory mice - is "going to be a game-changer" in terms of understanding schizophrenia and offering routes for treatment and potential for prevention, said Bruce Cuthbert, acting deputy director of the National Institute of Mental Health, which helped fund the research. An expert unconnected to the research said the study's conclusion was not yet proven, but plausible. Almost 1 percent of the general population will have schizophrenia at some point in their lives. They may hear voices or hallucinate, talk about strange ideas, and believe others are reading their minds or plotting against them. Nobody knows what causes the disorder, so the new result offers a possible peek into a black box. The work is reported in a paper released Wednesday by the journal Nature. The finding might pertain to "a very substantial fraction of cases, maybe most cases, even," said senior author Steven McCarroll, of Harvard Medical School and the Broad Institute in Cambridge, Massachusetts. The result links schizophrenia risk to a problem with a normal process that happens in adolescence and early adulthood, when disease symptoms often appear. That age range is when the brain trims back the number of specialized places on brain cells where the cells signal each other, called synapses. The new work suggests a connection to schizophrenia when this process gets out of hand, deleting too many synapses. "It's like you have a gardener who was supposed to prune the bushes and just got overactive," Cuthbert observed. "You end up with bushes that are pruned way too much." The result doesn't mean over-pruning causes schizophrenia on its own. It could promote the disease in combination with other factors in the brain, McCarroll said. The work began with a genetic investigation. Previous analysis of the human DNA indicates over 100 places that influence the risk of getting schizophrenia, but detailed biological explanations for those influences are very rare. The new work identified a risk gene and found evidence for the over-pruning idea. Drawing on DNA data from 28,799 people with schizophrenia and 35,986 people without it, the researchers found that a gene called C4 can raise a person's risk by about 30 percent over that of the general population. The gene comes in several forms, and researchers examining brain tissue found evidence that the forms that pose the most risk of schizophrenia were also the most active in the brain. In lab mice, they found that the gene plays a key role in pruning synapses. The study doesn't directly demonstrate that that excessive pruning of synapses plays a role in schizophrenia, but the idea makes sense, McCarroll said. It ties together previous observations, among them that schizophrenia most often develops during youth and that patients' brains show unusually few synapses, he said. Dr. Kenneth Kendler, a schizophrenia genetics expert at Virginia Commonwealth University in Richmond who didn't participate in the project, said the work presents an impressive array of results. The evidence that C4 can raise schizophrenia risk is strong, he said. The proposal that it does so through excessive pruning of synapses is "plausible and interesting, but not yet fully convincing," he said. "We don't yet know (whether) their hypothesis is completely true," Kendler said, but the work is still "a pretty big deal." If it's true, scientist can think about finding drugs that would intervene, McCarroll said. They might be useful to give when young people show symptoms that suggest they may be on the road to developing schizophrenia, he said. And even after the diagnosis, such drugs might keep the disease from getting worse, he said. But any such treatments are years away, he cautioned.


Roth E.M.,Sterling Research Group | McKenney J.M.,Virginia Commonwealth University | Hanotin C.,Sanofi S.A. | Asset G.,Sanofi S.A. | Stein E.A.,Metabolic and Atherosclerosis Research Center
New England Journal of Medicine | Year: 2012

BACKGROUND: Serum proprotein convertase subtilisin/kexin 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, increasing the degradation of LDL receptors and reducing the rate at which LDL cholesterol is removed from the circulation. REGN727/SAR236553 (designated here as SAR236553), a fully human PCSK9 monoclonal antibody, increases the recycling of LDL receptors and reduces LDL cholesterol levels. METHODS: We performed a phase 2, multicenter, double-blind, placebo-controlled trial involving 92 patients who had LDL cholesterol levels of 100 mg per deciliter (2.6 mmol per liter) or higher after treatment with 10 mg of atorvastatin for at least 7 weeks. Patients were randomly assigned to receive 8 weeks of treatment with 80 mg of atorvastatin daily plus SAR236553 once every 2 weeks, 10 mg of atorvastatin daily plus SAR236553 once every 2 weeks, or 80 mg of atorvastatin daily plus placebo once every 2 weeks and were followed for an additional 8 weeks after treatment. RESULTS: The least-squares mean (±SE) percent reduction from baseline in LDL cholesterol was 73.2±3.5 with 80 mg of atorvastatin plus SAR236553, as compared with 17.3±3.5 with 80 mg of atorvastatin plus placebo (P<0.001) and 66.2±3.5 with 10 mg of atorvastatin plus SAR236553. All the patients who received SAR236553, as compared with 52% of those who received 80 mg of atorvastatin plus placebo, attained an LDL cholesterol level of less than 100 mg per deciliter, and at least 90% of the patients who received SAR236553, as compared with 17% who received 80 mg of atorvastatin plus placebo, attained LDL cholesterol levels of less than 70 mg per deciliter (1.8 mmol per liter). CONCLUSIONS: In a randomized trial involving patients with primary hypercholesterolemia, adding SAR236553 to either 10 mg of atorvastatin or 80 mg of atorvastatin resulted in a significantly greater reduction in LDL cholesterol than that attained with 80 mg of atorvastatin alone. (Funded by Sanofi and Regeneron Pharmaceuticals; ClinicalTrials. gov number, NCT01288469.) Copyright © 2012 Massachusetts Medical Society. All rights reserved.


Wang L.,College of William and Mary | Clavero C.,College of William and Mary | Huba Z.,Virginia Commonwealth University | Carroll K.J.,Virginia Commonwealth University | And 3 more authors.
Nano Letters | Year: 2011

We present theoretical and experimental studies that explain the observed strong enhancement of the magneto-optical (MO) Faraday rotation in all-metal core-shell Co-Ag nanoparticles (NPs) attributed to localized surface plasmon resonance (LSPR). We also explain why the optical absorption and MO spectra peaks appear blue-shifted with increased Co core size while keeping the NP size constant. Further, we demonstrate direct correlation between the strong LSPR induced electromagnetic fields and the enhanced MO activity of the NPs. © 2011 American Chemical Society.


Chu S.,ire Veterans Affairs Medical Center | Schubert M.L.,ire Veterans Affairs Medical Center | Schubert M.L.,Virginia Commonwealth University
Current Opinion in Gastroenterology | Year: 2013

Purpose of Review: The review summarizes the past year's literature, basic science and clinical, regarding the neural, paracrine, hormonal, and intracellular regulation of gastric acid secretion. Recent Findings: Gastric acid facilitates the digestion of protein as well as the absorption of iron, calcium, vitamin B12, and certain medications (e.g. thyroxin). It also kills ingested microorganisms and prevents bacterial overgrowth, enteric infection, and possibly spontaneous bacterial peritonitis. Stimulants of acid secretion include histamine, gastrin, acetylcholine, and ghrelin. Inhibitors include somatostatin, nefstatin-1, interleukin-11, and calcitonin gene-related peptide. Helicobacter pylori stimulates or inhibits acid secretion depending upon the time course of infection and the area of the stomach predominantly infected. Acute infection activates calcitonin gene-related peptide sensory neurons coupled to inhibition of histamine and acid secretion. Serum chromogranin A, a marker for neuroendocrine tumors, is elevated in patients taking proton pump inhibitors. Summary: Progress continues in our understanding of the regulation of gastric acid secretion in health and disease, as well as the function of gastric neuroendocrine cells. The recognition that gastrin is not only a secretagogue but also a trophic hormone has led to new research into the role of gastrin and its receptor (cholecystokinin-2 receptor) in carcinogenesis and the development of cholecystokinin-2 receptor antagonists. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Zhou H.,Virginia Commonwealth University | Zhou H.,ire Veterans Affairs Medical Center | Liu R.,Virginia Commonwealth University
Frontiers in Genetics | Year: 2014

The endoplasmic reticulum (ER) is an important player in regulating protein synthesis and lipid metabolism. Perturbation of ER homeostasis, referred as "ER stress," has been linked to numerous pathological conditions, such as inflammation, cardiovascular diseases, and metabolic disorders. The liver plays a central role in regulating nutrient and lipid metabolism. Accumulating evidence implicates that ER stress disrupts lipid metabolism and induces hepatic lipotoxicity. Here, we review the major ER stress signaling pathways, how ER stress contributes to the dysregulation of hepatic lipid metabolism, and the potential causative mechanisms of ER stress in hepatic lipotoxicity. Understanding the role of ER stress in hepatic metabolism may lead to the identification of new therapeutic targets for metabolic diseases. © 2014 Zhou and Liu.


Parrill A.L.,University of Memphis | Lima S.,Virginia Commonwealth University | Spiegel S.,Virginia Commonwealth University
Science Signaling | Year: 2012

The sphingosine 1-phosphate receptor 1 (S1P1) and its ligand, sphingosine 1-phosphate (S1P), have now emerged as critical regulators of lymphocyte trafficking, vascular development and integrity, and immunity. S1P1 is targeted by the phosphorylation product of fingolimod, which has been approved for the treatment of multiple sclerosis. The recent progress in the structural biology of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors has now enabled the elucidation of the structure of S1P1. Analysis of the structure, along with structure activity and mutagenesis analysis, highlighted key interactions associated with the binding of S1P and agonists and suggested that the ligand may gain access to the binding pocket by lateral diffusion within the plasma membrane. The S1P1 crystal structure will be helpful for designing ligands that specifically target S1P1.


Reynolds S.,Virginia Commonwealth University | Urruela M.,University of Florida | Devine D.P.,University of Florida
Autism Research | Year: 2013

Lower order and higher order repetitive behaviors have been documented in the BTBR T+tf/J (BTBR) mouse strain, a mouse model that exhibits all three core behavioral domains that define autism. The purpose of this study was to evaluate the effectiveness of environmental enrichment for reducing repetitive behaviors in BTBR mice. Lower order behaviors were captured by assaying the time and sequence of grooming, while higher order behaviors were measured using pattern analysis of an object exploration task from digital recordings. Baseline scores were established at 7 weeks of age, followed by 30 days of housing in either a standard or enriched cage. As expected, BTBR mice spent significantly more time grooming and had a more rigid grooming sequence than control C57BL/6J mice did at baseline. After 30 days of enrichment housing, BTBR mice demonstrated a significant reduction in time spent grooming, resulting in levels that were lower than those exhibited by BTBR mice in standard housing. However, no changes were noted in the rigidity of their grooming sequence. In contrast to previous findings, there was no difference in repetitive patterns of exploration at baseline between BTBR and C57BL/6J mice in the object exploration test. Subsequently, enrichment did not significantly alter the number of repetitive patterns at posttest. Overall, the results suggest that environmental enrichment may be beneficial for reducing the time spent engaging in lower order repetitive behaviors, but may not change the overall quality of the behaviors when they do manifest. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.


Adler R.A.,ire Veterans Affairs Medical Center | Adler R.A.,Virginia Commonwealth University
Maturitas | Year: 2011

Osteoporosis is a common consequence of androgen deprivation therapy (ADT) for prostate cancer. Up to 20% of men on ADT for localized prostate cancer will fracture within 5 years. Fortunately, generally safe and effect therapy is available. Although once considered non-controversial, there is some concern about calcium supplementation, but all studies of osteoporosis therapy in men have included calcium. In most older men, serum 25-hydroxyvitamin D levels are likely to be low, although again there is controversy about the ideal level. Many experts believe that all older men, including those on ADT, need to have a level of >30 ng/ml, which is easily accomplished. Bone mineral density (BMD) testing by dual energy X-ray absorptiometry (DXA) is indicated for men on ADT. Interestingly, forearm DXA may be particularly important in ADT men, in addition to spine and hip. Some experts have suggested that men on ADT with a T-score of ≤-1.5 should be treated. Alternatively FRAX or another risk calculator can be used. Oral and intravenous bisphosphonates are FDA approved treatments for men with osteoporosis and increase BMD in men on ADT. Potential off-label agents include raloxifene and toremifene. The latter and denosumab have been shown to increase bone density and decrease vertebral fractures in men on ADT. Raloxifene and denosumab are only FDA approved for postmenopausal osteoporosis. Thus, prevention of fractures can be accomplished in this high risk population.


Etter J.-F.,University of Geneva | Eissenberg T.,Virginia Commonwealth University
Drug and Alcohol Dependence | Year: 2015

Objective: To assess dependence levels in users of e-cigarettes, and compare them with dependence levels in users of nicotine gums and tobacco cigarettes. Design: Self-reports from cross-sectional Internet and mail surveys. Comparisons of: (a) 766 daily users of nicotine-containing e-cigarettes with 30 daily users of nicotine-free e-cigarettes; (b) 911 former smokers who used the e-cigarette daily with 451 former smokers who used the nicotine gum daily (but no e-cigarette); (c) 125 daily e-cigarette users who smoked daily (dual users) with two samples of daily smokers who did not use e-cigarettes (2206 enrolled on the Internet and 292 enrolled by mail from the general population of Geneva). We used the Fagerström test for nicotine dependence, the nicotine dependence syndrome scale, the cigarette dependence scale and versions of these scales adapted for e-cigarettes and nicotine gums. Results: Dependence ratings were slightly higher in users of nicotine-containing e-cigarettes than in users of nicotine-free e-cigarettes. In former smokers, long-term (>3 months) users of e-cigarettes were less dependent on e-cigarettes than long-term users of the nicotine gum were dependent on the gum. There were few differences in dependence ratings between short-term (≤3 months) users of gums or e-cigarettes. Dependence on e-cigarettes was generally lower in dual users than dependence on tobacco cigarettes in the two other samples of daily smokers. Conclusions: Some e-cigarette users were dependent on nicotine-containing e-cigarettes, but these products were less addictive than tobacco cigarettes. E-cigarettes may be as or less addictive than nicotine gums, which themselves are not very addictive. © 2014 Elsevier Ireland Ltd.


Ibrahim O.M.,University of Florida | Polk R.E.,Virginia Commonwealth University
Infectious Disease Clinics of North America | Year: 2014

Measurement of antimicrobial use before and after an intervention and the associated outcomes are key activities of antimicrobial stewardship programs. In the United States, the recommended metric for aggregate antibiotic use is days of therapy/1000 patient-days. Clinical outcomes, including response to therapy and bacterial resistance, are critical measures but are more difficult to document than economic outcomes. Interhospital benchmarking of risk adjusted antimicrobial use is possible, although several obstacles remain before it can have an impact on patient care. Many challenges for stewardship programs remain, but the methods and science to support their efforts are rapidly evolving. © 2014 Elsevier Inc.


Patent
Virginia Commonwealth University and Nanomatrix Inc. | Date: 2010-04-12

The present invention relates to sealants for skin and other tissues. The sealants include an electroprocessed material. The sealants may contain more than one electroprocessed materials and may contain additional substances. The invention further relates to methods of making and using such sealants.


News Article | October 28, 2016
Site: www.prweb.com

First Choice Emergency Room, the largest network of independent freestanding emergency rooms in the United States, named Dr. Lars Thestrup, as the Medical Director of its new Katy – Spring Green facility. “We are pleased to announce Dr. Thestrup will be the facility Medical Director of our new Katy location,” said Dr. James M. Muzzarelli, Executive Medical Director of First Choice Emergency Room. Dr. Thestrup received his medical degree from Virginia Commonwealth University-Medical College of Virginia in Richmond, Virginia. He completed his Residency in Emergency Medicine at Johns Hopkins University, in Baltimore, Maryland. Prior to joining First Choice Emergency Room, Dr. Thestrup served as Assistant Medical Director for the Houston Fire Department. Dr. Thestrup is certified in emergency medicine and has over ten years of clinical experience. First Choice Emergency Room Katy- Spring Green will open as an outpatient department of First Texas Hospital and will accept all insurance, including Medicare, Medicaid, and Tricare. For a list of all First Choice Emergency Rooms in the greater Houston area that now accept all insurance, please visit http://www.firsttexashospitalcyfair.com/locations. All First Choice Emergency Room facilities are open 24 hours per day, 7 days per week. The facilities are staffed exclusively with board-certified physicians and emergency trained registered nurses. First Choice Emergency Room facilities are equipped with a full radiology suite, including CT scanner, Digital X-ray, Ultrasound, as well as on-site laboratories certified by the Clinical Laboratory Improvements Amendments (CLIA) and accredited by the Commission on Office Laboratories Accreditation (COLA). The Katy- Spring Green facility will be located at 1713 Spring Green Blvd., Katy, Texas 77494. For more information, visit http://fcer.com/locations/houston-map. About First Choice Emergency Room First Choice Emergency Room (FCER.com) is the nation’s leading network of independent freestanding emergency rooms; it is both the largest and the oldest. First Choice Emergency Room is revolutionizing the delivery of emergency medical services for adult and pediatric emergencies by offering patients convenient, neighborhood access to emergency medical care. First Choice Emergency Room facilities are innovative, freestanding, and fully equipped emergency rooms with a complete radiology suite of diagnostic technology (CT scanner, Ultrasound, and Digital X-ray) and on-site laboratory. All First Choice Emergency Room locations are staffed with board-certified physicians and emergency trained registered nurses. First Choice Emergency Room has facilities in Austin, Houston, and San Antonio. According to patient feedback collected by Press Ganey Associates Inc., First Choice Emergency Room provides the highest quality emergency medical care and received the 2013, 2014 and 2015 Press Ganey Guardian of Excellence Award for exceeding the 95th percentile in patient satisfaction nationwide. First Choice Emergency Room is an Adeptus Health (NYSE:ADPT) company. First Texas Hospital is a full service general hospital in Houston, TX. First Texas Hospital is equipped with 50 inpatient beds, three Operating Rooms, an emergency department, onsite laboratories and pharmacy, and an imaging department equipped with the latest in imaging equipment. The new hospital is capable of inpatient and outpatient surgical procedures and is providing the community 24/7 access to emergency medical care. For more information visit http://firsttexashospitalcyfair.com


McKenney J.M.,Virginia Commonwealth University | Koren M.J.,Jacksonville Center for Clinical Research | Kereiakes D.J.,Christ Hospital Heart and Vascular Center | Hanotin C.,Sanofi S.A. | And 2 more authors.
Journal of the American College of Cardiology | Year: 2012

Objectives: The primary objective of this study was to evaluate the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy of 5 SAR236553/REGN727 (SAR236553) dosing regimens versus placebo at week 12 in patients with LDL-C <100 mg/dl on stable atorvastatin therapy. Secondary objectives included evaluation of effects on other lipid parameters and the attainment of LDL-C treatment goals of <100 mg/dl (2.59 mmol/l) and <70 mg/dl (1.81 mmol/l). Background: Serum proprotein convertase subtilisin kexin 9 (PCSK9) binds to low-density lipoprotein receptors, increasing serum LDL-C. SAR236553 is a fully human monoclonal antibody to PCSK9. Methods: This double-blind, parallel-group, placebo-controlled trial randomized 183 patients with LDL-C <100 mg/dl (2.59 mmol/l) on stable-dose atorvastatin 10, 20, or 40 mg for <6 weeks to: subcutaneous placebo every 2 weeks (Q2W); SAR236553 50, 100, or 150 mg Q2W; or SAR236553 200 or 300 mg every 4 weeks (Q4W), alternating with placebo for a total treatment period of 12 weeks. Results: SAR236553 demonstrated a clear dose-response relationship with respect to percentage LDL-C lowering for both Q2W and Q4W administration: 40%, 64%, and 72% with 50, 100, and 150 mg Q2W, respectively, and 43% and 48% with 200 and 300 mg Q4W. LDL-C reduction with placebo at week 12 was 5%. SAR236553 also substantially reduced non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a). SAR236553 was generally well tolerated. One patient on SAR236553 experienced a serious adverse event of leukocytoclastic vasculitis. Conclusions: When added to atorvastatin, PCSK9 inhibition with SAR236553 further reduces LDL-C by 40% to 72%. These additional reductions are both dose- and dosing frequency-dependent. © 2012 American College of Cardiology Foundation.


Ratziu V.,University Pierre and Marie Curie | Goodman Z.,Inova Fairfax Hospital | Sanyal A.,Virginia Commonwealth University
Journal of Hepatology | Year: 2015

Of all the aspects of non-alcoholic fatty liver disease (NAFLD), the slowest advances have occurred in the therapeutic field. Thirty-five years after its formal description and after 15 years of intense scrutiny from researchers worldwide, there is still no approved drug for the treatment of non-alcoholic steatohepatits (NASH). In the meantime, progress in the understanding of pathophysiology, diagnosis - both invasive and non-invasive, epidemiology and even natural history have been substantial or, at times, spectacular. In contrast, hepatitis C virus (HCV) therapy underwent constant improvement and even before the great acceleration of the past few years, patients were already being offered approved therapies that were increasingly more efficient. What then explains such a slow pace of therapeutic advances in NASH, and will this change in the near future? Here we will review commonly-held myths that have diverted attention from therapy of NASH, obstacles that have slowed down industrial development of drugs for this indication, and recent achievements that will create better conditions for drug development programs. We will also briefly review current knowledge of non-pharmacological and pharmacological management in this early era of NASH therapies. © 2015 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.


Atulasimha J.,Virginia Commonwealth University | Flatau A.B.,University of Maryland University College
Smart Materials and Structures | Year: 2011

A unique combination of low hysteresis, moderate magnetostriction at low magnetic fields, good tensile strength, machinability and recent progress in commercially viable methods of processing iron-gallium alloys make them well poised for actuator and sensing applications. This review starts with a brief historical note on the early developments of magnetostrictive materials and moves to the recent work on FeGa alloys and their useful properties. This is followed by sections addressing the challenges specific to the characterization and processing of FeGa alloys and the state of the art in modeling their actuation and sensing behavior. © 2011 IOP Publishing Ltd.


Lee A.S.,Virginia Commonwealth University | Baskerville R.L.,Georgia State University
MIS Quarterly: Management Information Systems | Year: 2012

Tsang and Williams offer some good and provocative ideas in their critique of our earlier article on generalizing and generalizability. In this essay we will advance some new ideas by building on those collected in both Tsang and Williams and our original article (Lee and Baskerville 2003). Because IS is a pluralist scientific discipline, one in which both qualitative and quantitative (and both interpretive and positivist) research approaches are valued, "generalize" is unlikely to be a viable term or concept if only one IS research paradigm may lay claim to it and excludes others from using it. Both papers agree on this point, but approach the problem differently. Where we originally generalized generalizability by offering new language, Tsang and Williams conceptualize generalizability by framing it more closely to its older, more statistically oriented form. We agree about the importance of induction and about the classification or taxonomy of different types of induction. We build further in this essay, advancing the ethical questions raised by generalization: A formulation of judgment calls that need to be made when generalizing a theory to a new setting. We further demonstrate how the process of generalizing may actually proceed, based on the common ground between Tsang and Williams and our original article. Copyright © 2012.


Benotsch E.G.,Virginia Commonwealth University | Snipes D.J.,Virginia Commonwealth University | Martin A.M.,Virginia Commonwealth University | Bull S.S.,University of Colorado at Denver
Journal of Adolescent Health | Year: 2013

Purpose: Cell phone use has become more widespread over the past decade. Young adults are frequently early adopters of new technologies, including cell phones. Most previous research examining sexting, the act of sending sexually explicit or suggestive images via text message, has focused on the legal or social consequences of this behavior. The current study focused on the public health implications of sexting by examining associations between sexting, substance use, and sexual risk behavior in youth. Methods: Young adults (N = 763) completed online questionnaires assessing demographics, cell phone use (e.g., texting, sexting), substance use, and sexual risk behaviors. Results: Sexting was reported by a substantial minority of participants (44%). Compared with their nonsexting counterparts, participants who engaged in sexting were more likely to report recent substance use and high-risk sexual behaviors, including unprotected sex and sex with multiple partners. Of those who engaged in sexting, a considerable percentage (31.8%) reported having sex with a new partner for the first time after sexting with that person. In multivariate analyses, sexting was associated with high-risk sexual behavior, after accounting for demographic factors, total texting behaviors, and substance use. Conclusions: Results suggest that sexting is robustly associated with high-risk sexual behavior. Many individuals exchange explicit or provocative photos with long-term sexual partners, but at least some participants in this study were incurring new sexual risks after sexting. Additional research is needed to understand the contexts in which sexting occurs, motivations for sexting, and relationship of sexting to risk behavior. © 2013 Society for Adolescent Health and Medicine. All rights reserved.


Dellon E.S.,University of North Carolina at Chapel Hill | Irani A.-M.,Virginia Commonwealth University | Hill M.R.,Meritage Pharma | Hirano I.,Northwestern University
Alimentary Pharmacology and Therapeutics | Year: 2013

Background Dysphagia is the hallmark of eosinophilic esophagitis (EoE), but no validated dysphagia instruments in this population exist. Aim To develop and field test a patient-reported outcome (PRO) for dysphagia in subjects with EoE. Methods This was a multi-centre/multi-phase prospective study. The first phase developed a dysphagia questionnaire using qualitative methods. The second phase was a 30-day field trial to test the instrument and assess content validity. Adolescents and adults with EoE, active symptoms of dysphagia and oesophageal eosinophilia (≥15 eosinophils per high-power field) were enrolled. Solid-food-avoidance days, dysphagia days and actions taken to get relief were recorded. A dysphagia score was calculated and compared to the Straumann Dysphagia Instrument (SDI). Results Ten adolescents and 10 adults were included in the first phase and the Dysphagia Symptom Questionnaire (DSQ), a three-item daily electronic diary, was developed. In the second phase, 35 subjects finished the field trial (18 adults, 17 adolescents, mean age 24, 54% male, 95% white, 54% currently on topical corticosteroids). The median number of dysphagia days per week was 2 for adolescents vs. 4 for adults (P < 0.001), and 2 for those on topical steroids vs. 4 for those not on topical steroids (P < 0.001). The DSQ score strongly correlated with the number of dysphagia days (R = 0.96; P < 0.001) and the SDI (R = 0.77; P < 0.001). Conclusions The DSQ, a three-question patient-reported outcome, was successfully developed and field tested. The DSQ had content validity and the score accurately measured dysphagia frequency and intensity. The Dysphagia Symptom Questionnaire is suitable for use in clinical trials of EoE patients with dysphagia. © 2013 John Wiley & Sons Ltd.


Lazos D.,Beth Israel Deaconess Medical Center | Williamson J.F.,Virginia Commonwealth University
Medical Physics | Year: 2010

Purpose: To investigate the efficacy of two widely used scatter mitigation methods: antiscatter grids (ASGs) and beam modulating with bowtie filters (BTFs), in combination with subtractive scatter correction or zeroth order normalization phantom calibration, for improving image noise, contrast, contrast-to-noise ratio (CNR), and image uniformity for on-board cone-beam CT (CBCT) imaging systems used for image-guided radiation therapy. Methods: PTRAN Monte Carlo CBCT x-ray projections of head and pelvic phantoms were calculated for combinations of beam-modulation and scatter rejection methods and images were reconstructed by in-house developed software. In addition, a simple one-dimensional analytic model was developed to predict scatter-to-primary ratio (SPR) and CNR as a function of cylindrical phantom thickness, ASG transmission, and beam modulation with bow-tie filters. Results: ASGs were found to have slightly negative or no effect on head phantom image CNR and to modestly improve CNR (10%-20%) in pelvic phantom images. However, scatter subtraction and norm-phantom calibration perform better when applied on data acquired with ASGs. Scatter subtraction improves CT number accuracy, but increases noise, and in high SPR/low primary-photon transmission scenarios can dramatically reduce CNR and introduce streaking artifacts. The BTF is found to reduce SPR and image noise, resulting in a better trade-off between CNR and imaging dose, but introduces a circular band artifact. Conclusions: Our study shows that ASGs have a modest positive impact in pelvic scans and negative in head scans, scatter subtraction improves the HU accuracy but reduces CNR, while BTF has a clearly positive effect. © 2010 American Association of Physicists in Medicine.


Bradwell K.,University of Valencia | Sanjuan R.,Virginia Commonwealth University
Genetics | Year: 2013

Genome sizes and mutation rates covary across all domains of life. In unicellular organisms and DNA viruses, they show an inverse relationship known as Drake's rule. However, it is still unclear whether a similar relationship exists between genome sizes and mutation rates in RNA genomes. Coronaviruses, the RNA viruses with the largest genomes (~30 kb), encode a proofreading 39 exonuclease that allows them to increase replication fidelity. However, it is unknown whether, conversely, the RNA viruses with the smallest genomes tend to show particularly high mutation rates. To test this, we measured the mutation rate of bacteriophage Qβ, a 4.2-kb levivirus. Amber reversion-based Luria-Delbrück fluctuation tests combined with mutant sequencing gave an estimate of 1.4 × 10-4 substitutions per nucleotide per round of copying, the highest mutation rate reported for any virus using this method. This estimate was confirmed using a direct plaque sequencing approach and after reanalysis of previously published estimates for this phage. Comparison with other riboviruses (all RNA viruses except retroviruses) provided statistical support for a negative correlation between mutation rates and genome sizes. We suggest that the mutation rates of RNA viruses might be optimized for maximal adaptability and that the value of this optimum may in turn depend inversely on genome size. © 2013 by the Genetics Society of America.


Betrapally N.S.,George Mason University | Gillevet P.M.,George Mason University | Bajaj J.S.,Virginia Commonwealth University
Gastroenterology | Year: 2016

The prevalence of fatty liver diseases is increasing rapidly worldwide; after treatment of hepatitis C virus infection becomes more widespread, fatty liver diseases are likely to become the most prevalent liver disorders. Although fatty liver diseases are associated with alcohol, obesity, and the metabolic syndrome, their mechanisms of pathogenesis are not clear. The development and progression of fatty liver, alcoholic, and nonalcoholic liver disease (NAFLD) all appear to be influenced by the composition of the microbiota. The intestinal microbiota have been shown to affect precirrhotic and cirrhotic stages of liver diseases, which could lead to new strategies for their diagnosis, treatment, and study. We review differences and similarities in the cirrhotic and precirrhotic stages of NAFLD and alcoholic liver disease. Differences have been observed in these stages of alcohol-associated disease in patients who continue to drink compared with those who stop, with respect to the composition and function of the intestinal microbiota and intestinal integrity. NAFLD and the intestinal microbiota also differ between patients with and without diabetes. We also discuss the potential of microbial therapy for patients with NAFLD and ALD. © 2016 AGA Institute.


Patent
Inc. c o Enzo Biochem and Virginia Commonwealth University | Date: 2016-06-14

Provided are inhibitors of sphingosine kinase Type I that are useful in a number of applications, indications and diseases, as well as for monitoring pharmacokinetics and patient management. These compounds are applicable to treating tumors of the central nervous system, such as glioblastoma multiforme (GBM).


Patent
INC Research and Virginia Commonwealth University | Date: 2013-12-14

A recombinant Flagrp170 protein and pharmaceutical compositions comprising a Flagrp170 protein and related molecules encoding same, and cells presenting such a protein are provided. The Flagrp170 protein comprises an NF-_(K)B-activating domain of Flagellin and an ATP-binding domain truncated Grp170. The pharmaceutical compositions of the invention can be used for the treatment or prevention of cancer or infectious disease.


Brantley S.T.,Virginia Commonwealth University | Zinnert J.C.,U.S. Army | Young D.R.,Virginia Commonwealth University
Remote Sensing of Environment | Year: 2011

Accurate measurement of leaf area index (LAI), an important characteristic of plant canopies directly linked to primary production, is essential for monitoring changes in ecosystem C stocks and other ecosystem level fluxes. Direct measurement of LAI is labor intensive, impractical at large scales and does not capture seasonal or annual variations in canopy biomass. The need to monitor canopy related fluxes across landscapes makes remote sensing an attractive technique for estimating LAI. Many vegetation indices, such as Normalized Difference Vegetation Index (NDVI), tend to saturate at LAI levels > 4 although tropical and temperate forested ecosystems often exceed that threshold. Using two monospecific shrub thickets as model systems, we evaluated the potential of a variety of algorithms specifically developed to improve accuracy of LAI estimates in canopies where LAI exceeds saturation levels for other indices. We also tested the potential of indices developed to detect variations in canopy chlorophyll to estimate LAI because of the direct relationship between total canopy chlorophyll content and LAI. Indices were evaluated based on data from direct (litterfall) and indirect measurements (LAI-2000) of LAI. Relationships between results of direct and indirect ground-sampling techniques were also evaluated. For these two canopies, the indices that showed the highest potential to accurately differentiate LAI values > 4 were derivative indices based on red-edge spectral reflectance. Algorithms intended to improve accuracy at high LAI values in agricultural systems were insensitive when LAI exceeded 4 and offered little or no improvement over NDVI. Furthermore, indirect ground-sampling techniques often used to evaluate the potential of vegetation indices also saturate when LAI exceeds 4. Comparisons between hyperspectral vegetation indices and a saturated LAI value from indirect measurement may overestimate accuracy and sensitivity of some vegetation indices in high LAI communities. We recommend verification of indirect measurements of LAI with direct destructive sampling or litterfall collection, particularly in canopies with high LAI. © 2010 Elsevier Inc.


Patent
Virginia Commonwealth University, George Mason University and The U.S. Department Of Vetrans Affairs | Date: 2012-05-18

A systems biology approach is used to characterize and relate the intestinal (gut) microbiome of a host organism (e.g. a human) to physiological processes within the host. Information regarding the types and relative amounts of gut microflora is correlated with physiological processes indicative of e.g., a patients risk of developing a disease or condition, likelihood of responding to a particular treatment, for adjusting treatment protocols, etc. The information is also used to identify novel suitable therapeutic targets and/or to develop and monitor the outcome of therapeutic treatments. An exemplary disease/condition is the development of hepatic encephalopathy (HE), particularly in patients with liver cirrhosis.


News Article | October 26, 2016
Site: www.newscientist.com

All it takes is a splash. Brain-eating amoebas can enter an unwary swimmer’s brain via their nose, and once that happens, their chances of survival are slim. “They have these food cups on their surface, which are like giant suckers,” says Francine Cabral of Virginia Commonwealth University in Richmond. “They’ll just start eating the brain.” Now, researchers have discovered why this deadly amoeba has such an affinity for the brain – a breakthrough that could lead to life-saving drug treatments. The amoeba, Naegleria fowleri (shown in orange in the picture above), tends to lurk in fresh water, although infections can also result from swimming in hot springs or improperly chlorinated pools. Of the 35 reported cases in the US between 2005 and 2014, there were only two survivors. Last month, a 19-year-old woman died after being infected in Maryland. After the amoeba enters the body, it bypasses the nose and related tissues and heads straight to the brain, where the first areas it destroys are the olfactory regions we use to smell, and parts of the frontal lobe, which are crucial for cognition and controlling our behaviour. Why they specifically target the brain is a mystery. Abdul Mannan Baig at the Aga Khan University in Karachi, Pakistan, suspected the amoeba might be attracted to a chemical called acetylcholine or ACh, which is released in large amounts by cells at the front of the brain. This chemical is already known to act as a magnet for some immune cells and growing neurons. To test this theory, Mannan looked for receptors on the amoeba that might attach to ACh. He and his colleagues started with Acanthamoeba – a similar genus that tends to infect people through skin wounds. The team isolated 126 proteins from the amoeba and ran them through a database to find other proteins with similar components or structures. One of these had a structure similar to the human receptor for Ach. The team have since repeated their search in Naegleria and found the same result. This suggests that the amoebas have their own, ancient receptor for ACh, says Mannan. It is this attraction that probably causes the amoeba to bypass nasal tissues and head straight for the brain. Cabral, who was not involved in the research, agrees that ACh could be the culprit, although she would like to see more evidence to support the theory. In her own work, she has seen how the amoebas race toward brain cells in a lab dish. “It could be ACh,” she says. Mannan hopes that drugs that block the receptor could offer a new form of treatment for brain-eating amoeba infections. Such drugs already exist, and are used for treating irritable bowel syndrome or regulating heart rate, for example. Mannan is now testing them in mice infected with the amoeba. But there’s one final hurdle. If these drugs can stop the amoeba from getting into the brain, they will have to be administered as soon as a person is infected, when the infection is all but impossible to diagnose. “Severe headache is usually the first sign, but by that point the amoeba is already in the brain,” says Cabral. “We need an early diagnostic test.” This could become a more urgent problem in the coming years – infections are predicted to rise as the climate warms.


News Article | November 17, 2016
Site: www.24-7pressrelease.com

KANSAS CITY, MO, November 17, 2016 /24-7PressRelease/ -- With nearly a half-million visitors a year to his Kansas City area restaurants, STRETCH, creator of Grinders Pizza, Grinders @ Stonewall, in Lenexa, Grinders High Noon & Brewery in Leavenworth and the popular music venue CrossroadsKC, located in the heart of the Crossroads District at 18th & Locust, is no stranger to attracting attention, but Sunday, November 20th, 2016 at 7PM Central time more than a million fans will tune in to see him appear on Guys Grocery Games in an episode aptly named "Guy's Unforgettable Chefs." Food Network's website describes the episode as: "Four of Triple G's most unforgettable chefs are back to compete in two challenges jam-packed with un expected turns. First, the deck is stacked against then as they create a memorable meal in a game of Wild Cards. Then, in the second and final game, the chefs shop for a Sunday family dinner with some back-breaking restrictions. (Episode GK1108H) Read more at: http://www.foodnetwork.com/shows/guys-grocery-games/1100-series/guys-unforgettable-chefs.html?oc=linkback " Commenting on this, his second appearance, STRETCH states, "I am NOT a Chef - but, I play one on TV." He goes on to add, "the first time I was on GUYS GROCERY GAMES, I arrived with a custom built, flame throwing, "Death Cart" designed to give me a great shopping advantage over my opponents, as well as an onboard air-horn & gas grill, but... we didn't get to use it during the competition - something about ... rules, fairness, fire codes, & maiming the competition -- blah blah blah. However, it was such a hoot on set, that they ended up featuring a short clip of the Death Cart in action during the opening credits on all episodes aired last season. During the shooting of this episode - there was this amazing ... Oh-wait - I can't share that with you. I guess you will just have to tune in to see for yourselves." "STRETCH", is an Artist, Entrepreneur, Restaurateur, TV Personality & the visionary creator of Grinders Pizza. Grinders Restaurants, CrossroadsKC @ Grinders, (USA Today's #1 Pick for "Best Kansas City Nightlife") and even their retail support "sister company," STRETCH Specialties, LLC, which creates and sells Grinders Signature Hot Sauces, T-shirts and other fun merchandise, have each gained world-wide notoriety, thanks in part, to owner STRETCH's appearances on hit television shows like: Food Network's Diners, Drive-Ins & Dives; Guys Big Bite; Cutthroat Kitchen; Travel Channel's "Pizza Paradise", Spike TV's "Bar Rescue", Animal Planet's "Eating the Enemy," (which he hosted,) Discovery Channel's Monster House, Destination America's BBQ Pitmasters, and even multiple episodes of ABC's Extreme Makeover: Home Edition. STRETCH has twice toured with Guy Fieri on his national "Foodapalooza Roadshow" and the South Beach Wine and Food Festival, showcasing his custom-made 25-gallon Monster Margarita Machine. STRETCH continues to tour the globe several times a year, entertaining & feeding US military personnel with Messlords, a globetrotting troop of fellow celebrity chefs, in conjunction with Navy Entertainment MRW. In its first years of business, Grinders Signature Hot Sauces has won more than 25 prestigious awards & honors, including 2015 Screaming Mimi's - from the New York City Hot Sauce Expo, Peoples Choice Awards at Houston Hot Sauce Festival, multiple 2014 International Scovie Awards; appearing on CBS's 60 Minutes, CBS New York, NBC Albuquerque, and has become available in hundreds of stores around the world, like Whole Foods Markets, Bed, Bath & Beyond & many specialty stores, not to mention quite a few military bases, including ones in Guantanamo Bay, Cuba [GITMO,] Guam & Japan. Before opening his first Grinders restaurant in 2004, STRETCH was a working sculptor, who first moved to Kansas City to attend the Kansas City Art Institute. He went on to earn his Masters of Fine Arts at Virginia Commonwealth University in Richmond, Virginia in 1990, and while there befriended and collaborated with the shock-rock band GWAR. In fact, STRETCH portrayed "Flattus Maximus" in the short film/ long form video entitled, "Phallus In Wonderland" which was nominated for a Grammy Award in 1993. [Flattus Wiki ] In 1991, he opened his sculpture studio in a run down area south of downtown Kansas City, now called the "Crossroads Arts District". His passion for transforming this blighted neighborhood was all encompassing, as he solicited other artists, entertainers, gallery owners and entrepreneurs to move into the neighborhood and open businesses. Before STRETCH, there were two art galleries, and now there are over 70. Before STRETCH, there were only 2 hamburger stands & a Mexican food restaurant in the entire district, and now there are over 50 restaurants. These efforts in the early days earned him the nickname, "The Mayor of the Crossroads" and he began serving on many organization's Boards of Directors, culminating in a 2006 "Urban Hero Award," presented by the Downtown Council of Kansas City, Missouri. Then, in 2009 was appointed by then Kansas City, Missouri Mayor Mark Funkhouser to the prestigious and occasionally controversial Tax Increment Financing (TIF) Commission, where STRETCH worked to ensure greater transparency and access for small businesses. Most days, STRETCH can be seen creating new public art, chasing after his adorable three-year-old twins, developing & hosting exciting new TV shows, growing the Grinders Pizza brand, brewing craft beers at the new Grinders High Noon Brewery, and slow-smoking some award-winning BBQ on the National KCBS BBQ Circuit. Follow STRETCH on Facebook or twitter @STRETCHartist, and visit Grinders online store at GRINDERSPIZZA.com "Who the hell would have ever even thought this Philadelphia boy would end up on TV?" says STRETCH.


Paduani C.,Federal University of Santa Catarina | Jena P.,Virginia Commonwealth University
Chemical Physics Letters | Year: 2013

First-principles calculations based on the density functional theory (DFT) are performed to study the structure, stability and electron affinity of sodium and magnesium borohydrides. With successive attachments of BH4 complexes to the metal atom a superhalogen behavior is identified for the Na(BH4)2 and Mg(BH4)3 clusters, whose electron affinities reach 5.07 eV and 5.13 eV, respectively. As Mg(BH 4)3 cluster is used as a building block to decorate the Mg atom the electron affinity is pushed up to a higher level (6.18 eV) which classifies the Mg[Mg(BH4)3]3 moiety as a hyperhalogen. © 2012 Elsevier B.V. All rights reserved.


Gronert S.,Virginia Commonwealth University | Keeffe J.R.,San Francisco State University | More O'Ferrall R.A.,University College Dublin
Journal of the American Chemical Society | Year: 2011

Thermodynamic stabilities of 92 carbenes, singlets and triplets, have been evaluated on the basis of hydrogenation enthalpies calculated at the G3MP2 level. The carbenes include alkyl-, aryl-, and heteroatom-substituted structures as well as cyclic 1,3-diheteroatom carbenes. Over a wide energy range, a good correlation is seen between the singlet-triplet gaps and the hydrogenation enthalpies of the singlets, but there are some clear outliers, which represent cases where the triplet has unusual stability or instability. By use of hydrogenation enthalpies, separate carbene stabilization enthalpy scales (CSEs) have been developed for singlets and triplets, and these highlight structural features that affect the stability of each. The treatment also allows estimates of aromaticity in cyclic carbenes. In this way, imidazol-2-ylidene is estimated to have an aromatic stabilization energy of about 20 kcal/mol. © 2011 American Chemical Society.


Mansingh G.,University of the West Indies | Osei-Bryson K.-M.,Virginia Commonwealth University | Reichgelt H.,Southern Polytechnic State University
Information Sciences | Year: 2011

Data mining is used to discover hidden patterns or structures in large databases. Association rule induction extracts frequently occurring patterns in the form of association rules. However, this technique has a drawback as it typically generates a large number of association rules. Several methods have been proposed to prune the set of extracted rules in order to present only those which are of interest to the domain experts. Some of these methods involve subjective analysis based on prior domain knowledge, while others can be considered to involve objective, data-driven analysis based on numerical measures that provide a partial description of the interestingness of the extracted association rules. Recently it has been proposed that ontologies could be used to guide the data mining process. In this paper, we propose a hybrid pruning method that involve the use of objective analysis and subjective analysis, with the latter involving the use of an ontology. We demonstrate the applicability of this hybrid method using a medical database. © 2010 Elsevier Inc. All rights reserved.


Deng Y.,Virginia Commonwealth University | Deng Y.,Dartmouth College | Fong S.S.,Virginia Commonwealth University
Metabolic Engineering | Year: 2011

Biofuel production from renewable resources can potentially address lots of social, economic and environmental issues but an efficient production method has yet to be established. Combinations of different starting materials, organisms and target fuels have been explored with the conversion of cellulose to higher alcohols (1-propanol, 1-butanol) being one potential target. In this study we demonstrate the direct conversion of untreated plant biomass to 1-propanol in aerobic growth conditions using an engineered strain of the actinobacterium, Thermobifida fusca. Based upon computational predictions, a bifunctional butyraldehyde/alcohol dehydrogenase was added to T. fusca leading to 1-propanol production during growth on glucose, cellobiose, cellulose, switchgrass and corn stover. The highest 1-propanol titer (0.48. g/L) was achieved for growth on switchgrass. These results represent the first demonstration of direct conversion of untreated lignocellulosic biomass to 1-propanol in an aerobic organism and illustrate the potential utility of T. fusca as an aerobic, cellulolytic bioprocess organism. © 2011 Elsevier Inc.


Meredith M.A.,Virginia Commonwealth University | Allman B.L.,State University of New York at Buffalo
Neural Plasticity | Year: 2012

Numerous investigations of cortical crossmodal plasticity, most often in congenital or early-deaf subjects, have indicated that secondary auditory cortical areas reorganize to exhibit visual responsiveness while the core auditory regions are largely spared. However, a recent study of adult-deafened ferrets demonstrated that core auditory cortex was reorganized by the somatosensory modality. Because adult animals have matured beyond their critical period of sensory Development and plasticity, it was not known if adult-deafening and early-deafening would generate the same crossmodal results. The present study used young, ototoxically-lesioned ferrets (n = 3) that, after maturation (avg. =173 days old), showed significant hearing Deficits (avg. threshold=72dB SPL). Recordings from single-units (n = 132) in core auditory cortex showed that 72 were activated by somatosensory stimulation (compared to 1 in hearing controls). In addition, tracer injection into early hearing-impaired core auditory cortex labeled essentially the same auditory cortical and thalamic projection sources as seen for injections in the hearing controls, indicating that the functional reorganization was not the result of new or latent projections to the cortex. These data, along with similar observations from adult-deafened and adult hearing-impaired animals, support the recently proposed brainstem theory for crossmodal plasticity induced by hearing loss. © Copyright 2012 M. Alex Meredith and Brian L. Allman.


Samaha M.A.,Princeton University | Gad-el-Hak M.,Virginia Commonwealth University
Polymers | Year: 2014

We review recent developments in nature-inspired superhydrophobic and omniphobic surfaces. Water droplets beading on a surface at significantly high static contact angles and low contact-angle hystereses characterize superhydrophobicity. Microscopically, rough hydrophobic surfaces could entrap air in their pores resulting in a portion of a submerged surface with air-water interface, which is responsible for the slip effect. Suberhydrophobicity enhances the mobility of droplets on lotus leaves for self-cleaning purposes, so-called lotus effect. Amongst other applications, superhydrophobicity could be used to design slippery surfaces with minimal skin-friction drag for energy conservation. Another kind of slippery coatings is the recently invented slippery liquid-infused porous surfaces (SLIPS), which are one type of omniphobic surfaces. Certain plants such as the carnivorous Nepenthes pitcher inspired SLIPS. Their interior surfaces have microstructural roughness, which can lock in place an infused lubricating liquid. The lubricant is then utilized as a repellent surface for other liquids such as water, blood, crude oil, and alcohol. In this review, we discuss the concepts of both lotus effect and Nepenthes slippery mechanism. We then present a review of recent advances in manufacturing polymeric and non-polymeric slippery surfaces with ordered and disordered micro/nanostructures. Furthermore, we discuss the performance and longevity of such surfaces. Techniques used to characterize the surfaces are also detailed. We conclude the article with an overview of the latest advances in characterizing and using slippery surfaces for different applications. © 2014 by the authors; licensee MDPI, Basel, Switzerland.


Woolf S.H.,Virginia Commonwealth University | Harris R.P.,University of North Carolina at Chapel Hill | Campos-Outcalt D.,Mercy Care Plan
JAMA Internal Medicine | Year: 2014

In 2013, the US Preventive Services Task Force (USPSTF) recommended low-dose computed tomographic (CT) screening for high-risk current and former smokers with a B recommendation (indicating a level of certainty that it offered moderate to substantial net benefit). Under the Affordable Care Act, the USPSTF recommendation requires commercial insurers to fully cover low-dose CT. The Centers for Medicare & Medicaid Services (CMS) is now considering whether to also offer coverage for Medicare beneficiaries. Although the National Lung Screening Trial (NLST) demonstrated the efficacy of low-dose CT, implementation of national screening may be premature. The magnitude of benefit from routine screening is uncertain; estimates are based on data from a single study and simulation models commissioned by the USPSTF. The potential harms-which could affect a large population-include false-positive results, anxiety, radiation exposure, diagnostic workups, and the resulting complications. It is unclear if routine screening would result in net benefit or net harm. The NLSTmay not be generalizable to a national screening program for the Medicare age group because 73%of NLST participants were younger than 65 years. Moreover, screening outside of trial conditions is less likely to be restricted to high-risk smokers and qualified imaging centers with responsible referral protocols. Until better data are available for older adults who are screened in ordinary (nontrial) community settings, CMS should postpone coverage of low-dose CT screening for Medicare beneficiaries. Copyright 2014 American Medical Association. All rights reserved.


Rutan S.C.,Virginia Commonwealth University | Davis J.M.,Southern Illinois University Carbondale | Carr P.W.,University of Minnesota
Journal of Chromatography A | Year: 2012

Optimization of comprehensive two-dimensional separations frequently relies on the assessment of the peak capacity of the system. A correction is required for the fact that many pairs of separation systems are to some degree correlated, and consequently the entire separation space is not chemically accessible to solutes. This correction is essentially a measure of the fraction of separation space area where the solutes may elute. No agreement exists in the literature as to the best form of the spatial coverage factor. In this work, we distinguish between spatial coverage factors that measure the maximum occupiable space, which is characteristic of the separation dimensionality, and the space actually occupied by a particular sample, which is characteristic of the sample dimensionality. It is argued that the former, which we call fcoverage, is important to calculating the peak capacity. We propose five criteria for a good fcoverage metric and use them to evaluate various area determination methods that are used to measure animal home ranges in ecology. We consider minimum convex hulls, convex hull peels, α-hulls, three variations of local hull methods, and a kernel method and compare the results to the intuitively satisfying but subjective Stoll-Gilar method. The most promising methods are evaluated using two experimental LC×LC data sets, one with fixed separation chemistry but variable gradient times, and a second with variable first dimension column chemistry. For the 12 separations in the first data set, in which fcoverage is expected to be constant, the minimum convex hull is the most precise method (fcoverage=0.68±0.04) that gives similar results to the Stoll-Gilar method (fcoverage=0.67±0.06). The minimum convex hull is proposed as the best method for calculating fcoverage, because it has no adjustable parameters, can be scaled to different retention time normalizations, is easily calculated using available software, and represents the expected area of solute occupation based on a proposed linear free energy formalism. © 2011 Elsevier B.V.


Fagerstrom K.,Fagerstrom Consulting AB | Eissenberg T.,Virginia Commonwealth University
Nicotine and Tobacco Research | Year: 2012

The International Classification of Diseases and the Diagnostic and Statistical Manual for diagnosing tobacco/nicotine dependence emphasize the dependence-producing drug nicotine. These diagnostic tools have been challenged on grounds of poor predictive validity, and they do not differentiate across various forms of nicotine-containing products. In fact, nicotine-containing products (e.g., tobacco cigarettes, smokeless tobacco [ST], waterpipe, electronic cigarettes [ECIGs], and nicotine replacement [NR] products) have very different characteristics both in terms of sensory and behavioral involvement and also in pharmacokinetic and pharmacodynamic effects. For example, a cigarette and a nicotine patch are very different on almost every one of these dimensions. When ability to stop using a nicotine/tobacco product is used as a criterion for dependence, success rates vary considerably across products: Tobacco cigarette cessation is more difficult than ST cessation that in turn is more difficult than NR product cessation. Based on these results, we hypothesize that there is a continuum of dependence as much as there is a continuum of harm, with tobacco cigarettes and NR products on opposite ends of both continua and other products (waterpipe and ECIGs) somewhere in between. In order to capture more precisely the dependence produced by both nicotine and its administration forms, product-specific instruments may be required. The pros and cons of this approach are discussed. © The Author 2012. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.


Bienvenu O.J.,Johns Hopkins University | Davydow D.S.,University of Washington | Kendler K.S.,Virginia Commonwealth University
Psychological Medicine | Year: 2011

Background Psychiatric conditions in which symptoms arise involuntarily (diseases) might be assumed to be more heritable than those in which choices are essential (behavioral disorders). We sought to determine whether psychiatric diseases (Alzheimer's disease, schizophrenia, and mood and anxiety disorders) are more heritable than behavioral disorders (substance use disorders and anorexia nervosa).Method We reviewed the literature for recent quantitative summaries of heritabilities. When these were unavailable, we calculated weighted mean heritabilities from twin studies meeting modern methological standards.Results Heritability summary estimates were as follows: bipolar disorder (85%), schizophrenia (81%), Alzheimer's disease (75%), cocaine use disorder (72%), anorexia nervosa (60%), alcohol dependence (56%), sedative use disorder (51%), cannabis use disorder (48%), panic disorder (43%), stimulant use disorder (40%), major depressive disorder (37%), and generalized anxiety disorder (28%).Conclusions No systematic relationship exists between the disease-like character of a psychiatric disorder and its heritability; many behavioral disorders seem to be more heritable than conditions commonly construed as diseases. These results suggest an error in common-sense assumptions about the etiology of psychiatric disorders. That is, among psychiatric disorders, there is no close relationship between the strength of genetic influences and the etiologic importance of volitional processes. © 2010 Cambridge University Press.


Bouffard L.A.,Washington State University | Piquero N.L.,Virginia Commonwealth University
Crime and Delinquency | Year: 2010

Criminologists have long grappled with the varying effect of sanctions. In an effort to clarify these divergent effects, Sherman (1993) delineated a general theory of sanction effects, termed defiance theory. Defiance theory anticipates that there are four necessary conditions for defiance to occur: (a) the sanction must be perceived as unfair; (b) the offender must be poorly bonded; (c) the sanction must be perceived as stigmatizing; and (d) the offender denies the shame produced by the sanction. This study provides one of the first empirical assessments of defiance theory. In addition, defiance theory is examined within the life-course perspective, and analyses address trajectories of offending. Using data from the 1945 Philadelphia Birth Cohort, the results yield promising support for the theory. © 2010 SAGE Publications.


Voelkel N.F.,Virginia Commonwealth University | Gomez-Arroyo J.,Johns Hopkins University
American Journal of Respiratory Cell and Molecular Biology | Year: 2014

Pulmonary arterial hypertension (PAH) is characterized by dysfunctional angiogenesis leading to lung vessel obliteration.PAHis widely considered a proangiogenic disease; however, the role of angiogenic factors, such as the vascular endothelial growth factor (VEGF) and its receptors, in the pathobiology of PAH remains incompletely understood. This Review attempts to untangle some of the complex multilayered actions of VEGF to provide a VEGF-centered perspective of PAH. Furthermore, we provide a cogent explanation for the paradox of VEGF receptor blockade-induced pulmonary hypertension that characterizes the SU5416-hypoxia rat model of PAH, and attempt to translate the knowledge gained from the experimental model to the human disease by postulating the potential role of endogenous (SU5416-like) VEGF inhibitors. The main objective of this Review is to promote discussion and investigation of the opposing and complementary actions of VEGF in PAH. Understanding the balance between angiogenic and antiangiogenic factors and their role in the pathogenesis of PAH will be necessary before antiangiogenic drugs can be considered for the treatment of PAH. Copyright © 2014 by the American Thoracic Society.


Patent
Virginia Commonwealth University and Johns Hopkins University | Date: 2014-06-04

The presently disclosed subject matter relates to compositions and methods directed to cancer theranostic nucleic acid constructs that permit simultaneous cancer-specific viral replication, expression of a diagnostic gene product, and expression of a therapeutic gene.


Patent
Johns Hopkins University and Virginia Commonwealth University | Date: 2014-06-04

The presently disclosed subject matter generally relates to genetic constructs and methods for their use in cancer imaging, cancer treatment, and combined imaging and treatment protocols. In particular, the presently disclosed subject matter relates to tripartite cancer theranostic nucleic acid constructs that permit simultaneous cancer specific viral replication, expression of a diagnostic gene product, and expression of a therapeutic gene.


Patent
Johns Hopkins University and Virginia Commonwealth University | Date: 2014-02-18

Genetic constructs comprising reporter genes operably linked to cancer specific or cancer selective promoters (such as the progression elevated gene-3 (PEG-3) promoter and astrocyte elevated gene 1 (AEG-1) promoter) are provided, as are methods for their use in cancer imaging, cancer treatment, and combined imaging and treatment protocols, e.g. for imaging and/or treating spontaneous metastasis. Transgenic animals in which a reporter gene is linked to a cancer specific or cancer selective promoter, and which may be further genetically engineered, bred or selected to have a predisposition to develop cancer, are also provided.


Borges N.J.,Wright State University | Navarro A.M.,Association of American Medical Colleges | Grover A.C.,Virginia Commonwealth University
Academic Medicine | Year: 2012

Purpose: Despite recent efforts to understand the complex process of physician career development, the medical education community has a poor understanding of why, how, and when women physicians embark on careers in academic medicine. Method: In 2010, the authors phone-interviewed women physicians in academic medicine regarding why, how, and when they chose academic medicine careers. Project investigators first individually and then collectively analyzed transcripts to identify themes in the data. Results: Through analyzing the transcripts of the 53 interviews, the investigators identified five themes related to why women choose careers in academic medicine: fit, aspects of the academic health center environment, people, exposure, and clinical medicine. They identified five themes related to how women make the decision to enter academic medicine: change in specialty, dissatisfaction with former career, emotionality, parental influence, and decision-making styles. The authors also identified four themes regarding when women decide to enter academic medicine: as a practicing physician, fellow, resident, or medical student. Conclusions: Choosing a career in academic medicine is greatly influenced by the environment in which one trains and by people-be they faculty, mentors, role models, or family. An interest in teaching is a primary reason women choose a career in academic medicine. Many women physicians entering academic medicine chose to do so after or during fellowship, which is when they became more aware of academic medicine as a possible career. For many women, choosing academic medicine was not necessarily an active, planned decision; rather, it was serendipitous or circumstantial. Copyright © 2012 by the Association of American Medical Colleges.


Patent
Johns Hopkins University and Virginia Commonwealth University | Date: 2011-10-28

Genetic constructs comprising reporter genes operably linked to cancer specific or cancer selective promoters (such as the progression elevated gene-3 (PEG-3) promoter) are provided, as are methods for their use in cancer imaging, cancer treatment, and combined imaging and treatment protocols. Transgenic animals in which a reporter gene is linked to a cancer specific or cancer selective promoter, and which may be further genetically engineered, bred or selected to have a predisposition to develop cancer, are also provided.


Meredith M.A.,Virginia Commonwealth University | Allman B.L.,University of Western Ontario
European Journal of Neuroscience | Year: 2015

The recent findings in several species that the primary auditory cortex processes non-auditory information have largely overlooked the possibility of somatosensory effects. Therefore, the present investigation examined the core auditory cortices (anterior auditory field and primary auditory cortex) for tactile responsivity. Multiple single-unit recordings from anesthetised ferret cortex yielded histologically verified neurons (n = 311) tested with electronically controlled auditory, visual and tactile stimuli, and their combinations. Of the auditory neurons tested, a small proportion (17%) was influenced by visual cues, but a somewhat larger number (23%) was affected by tactile stimulation. Tactile effects rarely occurred alone and spiking responses were observed in bimodal auditory-tactile neurons. However, the broadest tactile effect that was observed, which occurred in all neuron types, was that of suppression of the response to a concurrent auditory cue. The presence of tactile effects in the core auditory cortices was supported by a substantial anatomical projection from the rostral suprasylvian sulcal somatosensory area. Collectively, these results demonstrate that crossmodal effects in the auditory cortex are not exclusively visual and that somatosensation plays a significant role in modulation of acoustic processing, and indicate that crossmodal plasticity following deafness may unmask these existing non-auditory functions. © 2015 Federation of European Neuroscience Societies and John Wiley and Sons Ltd.


Wu H.,Duke University | Sun S.,Cold Spring Harbor Laboratory | Tu K.,Duke University | Gao Y.,Virginia Commonwealth University | And 3 more authors.
Molecular Cell | Year: 2010

Both splicing factors and microRNAs are important regulatory molecules that play key roles in posttranscriptional gene regulation. By miRNA deep sequencing, we identified 40 miRNAs that are differentially expressed upon ectopic overexpression of the splicing factor SF2/ASF. Here we show that SF2/ASF and one of its upregulated microRNAs (miR-7) can form a negative feedback loop: SF2/ASF promotes miR-7 maturation, and mature miR-7 in turn targets the 3′UTR of SF2/ASF to repress its translation. Enhanced microRNA expression is mediated by direct interaction between SF2/ASF and the primary miR-7 transcript to facilitate Drosha cleavage and is independent of SF2/ASF's function in splicing. Other miRNAs, including miR-221 and miR-222, may also be regulated by SF2/ASF through a similar mechanism. These results underscore a function of SF2/ASF in pri-miRNA processing and highlight the potential coordination between splicing control and miRNA-mediated gene repression in gene regulatory networks. © 2010 Elsevier Inc. All rights reserved.


Brunzell D.H.,Virginia Commonwealth University | Mcintosh J.M.,University of Utah | Papke R.L.,Florida College
Annals of the New York Academy of Sciences | Year: 2014

Preclinical studies suggest that a diversity of nicotinic acetylcholine receptors (nAChRs) with different sensitivities to nicotine may contribute to tobacco addiction. Using rodent intravenous nicotine self-administration as a preclinical model with good predictive validity for therapeutic efficacy for tobacco cessation, investigators have identified heteromeric α6β2* and homomeric α7 nAChRs as promising novel therapeutic targets to promote smoking abstinence (*denotes possible assembly with other subunits). The data suggest that diverse strategies that target these subclasses of nAChRs, namely inhibition of α6β2* nAChRs and stimulation of α7 nAChRs, will support tobacco cessation. α6β2* nAChRs, members of the high-affinity family of β2* nAChRs, function similarly to α4β2* nAChRs, the primary target of the FDA-approved drug varenicline, but have a much more selective neuroanatomical pattern of expression in catecholaminergic nuclei. Although activation of β2* nAChRs facilitates nicotine self-administration, stimulation of α7 nAChRs appears to negatively modulate both nicotine reinforcement and β2* nAChR function in the mesolimbic dopamine system. Although challenges and caveats must be considered in the development of therapeutics that target these nAChR subpopulations, an accumulation of data suggests that α7 nAChR agonists, partial agonists, or positive allosteric modulators and α6β2* nAChR antagonists, partial agonists, or negative allosteric modulators may prove to be effective therapeutics for tobacco cessation. © 2014 New York Academy of Sciences.


Noar S.M.,University of Kentucky | Mehrotra P.,Virginia Commonwealth University
Patient Education and Counseling | Year: 2011

Objective: Traditional theory testing commonly applies cross-sectional (and occasionally longitudinal) survey research to test health behavior theory. Since such correlational research cannot demonstrate causality, a number of researchers have called for the increased use of experimental methods for theory testing. Methods: We introduce the multi-methodological theory-testing (MMTT) framework for testing health behavior theory. Results: The MMTT framework introduces a set of principles that broaden the perspective of how we view evidence for health behavior theory. It suggests that while correlational survey research designs represent one method of testing theory, the weaknesses of this approach demand that complementary approaches be applied. Such approaches include randomized lab and field experiments, mediation analysis of theory-based interventions, and meta-analysis. Conclusion: These alternative approaches to theory testing can demonstrate causality in a much more robust way than is possible with correlational survey research methods. Such approaches should thus be increasingly applied in order to more completely and rigorously test health behavior theory. Practice implications: Greater application of research derived from the MMTT may lead researchers to refine and modify theory and ultimately make theory more valuable to practitioners. © 2010 Elsevier Ireland Ltd.


Yang S.,Virginia Commonwealth University | Eaton C.B.,Brown University | McAlindon T.E.,Tufts Medical Center | Lapane K.L.,University of Massachusetts Medical School
Arthritis and Rheumatology | Year: 2015

Objective The purpose of this study was to estimate the effectiveness of the combination of glucosamine and chondroitin in relieving knee symptoms and slowing disease progression among patients with knee osteoarthritis (OA). Methods The 4-year followup data from the Osteoarthritis Initiative data set were analyzed. We used a "new-user" design, for which only participants who were not using glucosamine/chondroitin at baseline were included in the analyses (n = 1,625). Cumulative exposure was calculated as the number of visits when participants reported use of glucosamine/chondroitin. Knee symptoms were measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and structural progression was determined by measuring the joint space width (JSW). To control for the time-varying confounders that might be influenced by previous treatments, we used marginal structural models to estimate the effects on OA of using glucosamine/chondroitin for 3 years, 2 years, and 1 year. Results During the study period, 18% of the participants initiated treatment with glucosamine/chondroitin. After adjustment for potential confounders with marginal structural models, we found no clinically significant differences between users at all assessments and never-users of glucosamine/chondroitin in WOMAC pain (β = 0.68 [95% confidence interval (95% CI)-0.16 to 1.53]), WOMAC stiffness (β = 0.41 [95% CI 0 to 0.82]), and WOMAC function (β = 1.28 [95% CI-1.23 to 3.79]) or JSW (β = 0.11 [95% CI-0.21 to 0.44]). Conclusion Use of glucosamine/chondroitin did not appear to relieve symptoms or modify disease progression among patients with radiographically confirmed OA. Our findings are consistent with the results of meta-analyses of clinical trials and extend those results to a more general population with knee OA. Copyright © 2015 by the American College of Rheumatology.


Wade N.G.,University of Iowa | Hoyt W.T.,University of Wisconsin - Madison | Kidwell J.E.M.,University of Iowa | Worthington Jr. E.L.,Virginia Commonwealth University
Journal of Consulting and Clinical Psychology | Year: 2014

Objective: This meta-analysis addressed the efficacy of psychotherapeutic interventions to help people forgive others and to examine moderators of treatment effects. Method: Eligible studies reported quantitative data on forgiveness of a specific hurt following treatment by a professional with an intervention designed explicitly to promote forgiveness. Random effects meta-analyses were conducted using k = 53 posttreatment effect sizes (N = 2,323) and k = 41 follow-up effect sizes (N = 1,716) from a total of 54 published and unpublished research reports. Results: Participants receiving explicit forgiveness treatments reported significantly greater forgiveness than participants not receiving treatment (Δ+ = 0.56 [0.43, 0.68]) and participants, receiving alternative treatments (Δ+ = 0.45 [0.21, 0.69]). Also, forgiveness treatments resulted in greater changes in depression, anxiety, and hope than no-treatment conditions. Moderators of treatment efficacy included treatment dosage, offense severity, treatment model, and treatment modality. Multimoderator analyses indicated that treatment dosage (i.e., longer interventions) and modality (individual > group) uniquely predicted change in forgiveness compared with no-treatment controls. Compared with alternative treatment conditions, both modality (individual > group) and offense severity were marginally predictive (ps <.10) of treatment effects. Conclusions: It appears that using theoretically grounded forgiveness interventions is a sound choice for helping clients to deal with past offenses and helping them achieve resolution in the form of forgiveness. Differences between treatment approaches disappeared when controlling for other significant moderators; the advantage for individual interventions was most clearly demonstrated for Enright-model interventions, as there have been no studies of individual interventions using the Worthington model. © 2013 American Psychological Association.


News Article | November 4, 2016
Site: www.sciencedaily.com

Women who avoided foods, cosmetics, and other products packaged in BPA-containing plastic containers for 3 weeks had significant reductions in urinary levels of BPA, a commonly used "endocrine disruptor" associated with negative health effects including weight gain. Over the 3-week study period, the women who participated in an intervention designed to minimize BPA exposure also had significant weight loss, as reported in Journal of Women's Health. The article, entitled "Randomized Intervention Trial to Decrease Bisphenol A Urine Concentrations in Women: Pilot Study," shows that among the participants, the women in the control group who did not take part in the BPA-limiting intervention, had significant increases in both urinary BPA levels and weight gain after 3 weeks. Todd Hagobian, PhD and coauthors from California Polytechnic State University (San Luis Obispo, CA), propose future large-scale randomized trials to confirm these findings and to determine the potential positive health effects of reduced exposure to endocrine disrupting chemicals on risk factors for disorders such as type 2 diabetes and cardiovascular disease. "This study shows that by switching to BPA-free products it is, in fact, possible for women who have been exposed to BPA to reduce their body burden of the compound, as measured by urinary BPA levels," says Susan G. Kornstein, MD, Editor-in-Chief of Journal of Women's Health, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, and President of the Academy of Women's Health. "Although many consumers tend to reject products made of plastics containing BPA, there are unfortunately still many other endocrine disrupting chemicals in our environment."


News Article | February 15, 2017
Site: globenewswire.com

RICHMOND, Va., Feb. 15, 2017 (GLOBE NEWSWIRE) -- Kinsale Capital Group (NASDAQ:KNSL), announced today the promotions of Benjamin F. Pully and Clayton W. Rhoades to Senior Vice President.  Brian Haney, Chief Operating Officer, stated, “Ben and Clay’s leadership, dedication, and expertise have greatly contributed to Kinsale’s development from a start-up operation to a mature company.  These well-deserved promotions better position Kinsale for the future.” Mr. Pully has responsibility for Kinsale’s Allied Health, Health Care and Life Sciences Divisions.  Prior to joining Kinsale, Mr. Pully held actuarial and leadership positions with James River Insurance Company, Virginia Hospital & Healthcare Association and The Reciprocal Group.  Mr. Pully earned a Bachelor of Science Degree in Mathematics/Statistics and a minor in Economics from Virginia Commonwealth University. Mr. Rhoades has responsibility for Kinsale’s Management Liability, Professional Liability and Public Entity Divisions.  Prior to joining Kinsale, Mr. Rhoades held various leadership and underwriting assignments within Argo Pro and Colony Specialty, member companies of Argo Group.  Mr. Rhoades earned a Bachelor of Science Degree in Business Administration from Virginia Commonwealth University. He also holds the Registered Professional Liability Underwriter (RPLU) and Associate in Surplus Lines Insurance (ASLI) designations. Mr. Pully and Mr. Rhoades are employees of Kinsale Management, Inc., the management services company of Kinsale Capital Group, Inc.  The Underwriting Divisions that Mr. Pully and Mr. Rhoades lead are Divisions within Kinsale Insurance Company, a subsidiary of Kinsale Capital Group, Inc. Kinsale Capital Group, Inc. is a specialty insurance group headquartered in Richmond, VA, focusing on the excess and surplus lines market.


Banks M.L.,Virginia Commonwealth University | Blough B.E.,Research Triangle Institute
Neuropsychopharmacology | Year: 2015

Preclinical and human laboratory choice procedures have been invaluable in improving our knowledge of the neurobiological mechanisms of drug reinforcement and in the drug development process for candidate medications to treat drug addiction. However, little is known about the neuropharmacological mechanisms of methamphetamine vs food choice. The aims of this study were to develop a methamphetamine vs food choice procedure and determine treatment effects with two clinically relevant compounds: the monoamine uptake inhibitor bupropion and the dopamine antagonist risperidone. Rhesus monkeys (n=6) responded under a concurrent schedule of food delivery (1-g pellets, fixed-ratio (FR) 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, FR10 schedule) during 7-day bupropion (0.32-1.8 mg/kg/h) and risperidone (0.001-0.0056 mg/kg/h) treatment periods. For comparison, effects of removing food pellets or methamphetamine injections and FR response requirement manipulations were also examined. Under saline treatment conditions, food was preferred over no methamphetamine or small unit methamphetamine doses (0.01-0.032 mg/kg/injection). Larger methamphetamine doses resulted in greater methamphetamine preference and 0.32 mg/kg/injection methamphetamine maintained near exclusive preference. Removing food availability increased methamphetamine choice, whereas removing methamphetamine availability decreased methamphetamine choice. Methamphetamine choice was not significantly altered when the FR response requirements for food and drug were the same (FR100:FR100 or FR10:FR10). Risperidone treatment increased methamphetamine choice, whereas bupropion treatment did not alter methamphetamine choice up to doses that decreased rates of operant behavior. Overall, these negative results with bupropion and risperidone are concordant with previous human laboratory and clinical trials and support the potential validity of this preclinical methamphetamine vs food choice model. © 2015 American College of Neuropsychopharmacology. All rights reserved.


Langberg J.M.,Virginia Commonwealth University | Langberg J.M.,Childrens Hospital Medical Center | Becker S.P.,Miami University Ohio | Dvorsky M.R.,Virginia Commonwealth University
Journal of Abnormal Child Psychology | Year: 2014

The purpose of the study was to evaluate the relation between Sluggish Cognitive Tempo (SCT) and academic functioning in a sample of 52 adolescents (40 males, 12 females) with Attention-Deficit/Hyperactivity Disorder (ADHD; M age = 13.75). This study builds on prior work by utilizing an empirically-based and psychometrically validated measure of SCT, collecting ratings of SCT from both parents and teachers, and examining associations with multiple domains of academic functioning from both the parent and teacher perspective as well as grade point average (GPA). Both SCT and DSM-IV symptoms of inattention were significantly correlated with domains of academic functioning. Multiple regression analyses demonstrated that the parent-rated SCT Slow subscale predicted overall academic functioning, organizational skills impairment, and homework problems above and beyond ADHD symptoms and child and demographic characteristics known to be associated with academics, including intelligence, academic achievement, and family income. The teacher-rated SCT Low Initiation/Persistence subscale also predicted homework problems and was the only SCT variable to predict school grades above and beyond ADHD symptoms and relevant covariates. Both the SCT Slow and Low Initiation/Persistence subscales include items related to youth seeming apathetic, unmotivated, and lacking initiative, behaviors that are strongly related to ADHD symptoms of inattention but not currently captured by the DSM-IV. Implications of these findings towards supporting the external validity of the SCT construct are discussed along with potential implications for intervention. © 2013 Springer Science+Business Media New York.


Banks M.L.,Virginia Commonwealth University | Blough B.E.,Research Triangle Institute | Stevens Negus S.,Virginia Commonwealth University
Neuropsychopharmacology | Year: 2013

Behavioral and pharmacotherapeutic approaches constitute two prominent strategies for treating cocaine dependence. This study investigated interactions between behavioral and pharmacological strategies in a preclinical model of cocaine vs food choice. Six rhesus monkeys, implanted with a chronic indwelling double-lumen venous catheter, initially responded under a concurrent schedule of food delivery (1-g pellets, fixed-ratio (FR) 100 schedule) and cocaine injections (0-0.1 mg/kg/injection, FR 10 schedule) during continuous 7-day treatment periods with saline or the agonist medication phenmetrazine (0.032-0.1 mg/kg/h). Subsequently, the FR response requirement for cocaine or food was varied (food, FR 100; cocaine, FR 1-100; cocaine, FR 10; food, FR 10-300), and effects of phenmetrazine on cocaine vs food choice were redetermined. Decreases in the cocaine FR or increases in the food FR resulted in leftward shifts in the cocaine choice dose-effect curve, whereas increases in the cocaine FR or decreases in the food FR resulted in rightward shifts in the cocaine choice dose-effect curve. The efficacy of phenmetrazine to decrease cocaine choice varied systematically as a function of the prevailing response requirements, such that phenmetrazine efficacy was greatest when cocaine choice was maintained by relatively low unit cocaine doses. These results suggest that efficacy of pharmacotherapies to modulate cocaine use can be influenced by behavioral contingencies of cocaine availability. Agonist medications may be most effective under contingencies that engender choice of relatively low cocaine doses. © 2013 American College of Neuropsychopharmacology. All rights reserved.


Langberg J.M.,Virginia Commonwealth University | Langberg J.M.,Cincinnati Childrens Hospital Medical Center | Becker S.P.,Miami University Ohio
Clinical Child and Family Psychology Review | Year: 2012

Youth with Attention-Deficit/Hyperactivity Disorder (ADHD) frequently experience academic impairment, including lower grades than their peers and elevated risk for grade retention and school dropout. Medication is the most commonly used treatment for youth with ADHD, and it is therefore essential to understand the extent to which medication use improves long-term academic functioning. This paper reviews the literature on the relation between long-term medication use and the academic outcomes of youth with ADHD. A systematic literature search was conducted to identify pertinent studies published since 2000 that followed youth with ADHD for 3 or more years. Academic outcomes of interest included school grades, achievement test scores, and grade retention. Nine studies were identified reporting on eight distinct longitudinal samples (N across studies = 8,721). These studies demonstrate that long-term medication use is associated with improvements in standardized achievement scores. However, the magnitude of these improvements is small and the clinical or educational significance is questionable. Evidence for long-term improvements in school grades and grade retention is less compelling. This review highlights methodological considerations in providing directions for future research. The importance of using multiple sources to gather information about medication adherence is discussed, including use of methodologies such as electronic monitors, rather than relying solely on parent report or chart review. Future research should also examine a range of medication adherence definitions in order to determine whether age of onset, duration of use, dose, and/or consistency of use moderates the relation between long-term medication use and academic outcomes. © 2012 Springer Science+Business Media, LLC.


Masazade E.,Syracuse University | Niu R.,Virginia Commonwealth University | Varshney P.K.,Syracuse University
IEEE Transactions on Signal Processing | Year: 2012

In this paper, we study the target tracking problem in wireless sensor networks (WSNs) using quantized sensor measurements where the total number of bits that can be transmitted from sensors to the fusion center is limited. At each time step of tracking, a total of available bits need to be distributed among the sensors in the WSN for the next time step. The optimal solution for the bit allocation problem can be obtained by using a combinatorial search which may become computationally prohibitive for large and . Therefore, we develop two new suboptimal bit allocation algorithms which are based on convex optimization and approximate dynamic programming (A-DP). We compare the mean squared error (MSE) and computational complexity performances of convex optimization and A-DP with other existing suboptimal bit allocation schemes based on generalized Breiman, Friedman, Olshen, and Stone (GBFOS) algorithm and greedy search. Simulation results show that, A-DP, convex optimization and GBFOS yield similar MSE performance, which is very close to that based on the optimal exhaustive search approach and they outperform greedy search and nearest neighbor based bit allocation approaches significantly. Computationally, A-DP is more efficient than the bit allocation schemes based on convex optimization and GBFOS, especially for a large sensor network. © 2012 IEEE.


Iyengar S.G.,Syracuse University | Niu R.,Virginia Commonwealth University | Varshney P.K.,Syracuse University
IEEE Transactions on Signal Processing | Year: 2012

In this paper, we consider a binary decentralized detection problem where the local sensor observations are quantized before their transmission to the fusion center. Sensor observations, and hence their quantized versions, may be heterogeneous as well as statistically dependent. A composite binary hypothesis testing problem is formulated, and a copula-based generalized likelihood ratio test (GLRT) based fusion rule is derived given that the local sensors are uniform multilevel quantizers. An alternative computationally efficient fusion rule is also designed which involves injecting a deliberate random disturbance to the local sensor decisions before fusion. Although the introduction of external noise causes a reduction in the received signal-to-noise ratio (SNR), it is shown that the proposed approach can result in a detection performance comparable to the GLRT detector without external noise, especially when the number of quantization levels is large. © 1991-2012 IEEE.


Wang X.-Y.,Virginia Commonwealth University | Subjeck J.R.,Roswell Park Cancer Institute
International Journal of Hyperthermia | Year: 2013

Although the large stress/heat shock proteins (HSPs), i.e. Hsp110 and Grp170, were identified over 30 years ago, these abundant and highly conserved molecules have received much less attention compared to other conventional HSPs. Large stress proteins act as molecular chaperones with exceptional protein-holding capability and prevent the aggregation of proteins induced by thermal stress. The chaperoning properties of Hsp110 and Grp170 are integral to the ability of these molecules to modulate immune functions and are essential for developing large chaperone complex vaccines for cancer immunotherapy. The potent anti-tumour activity of the Hsp110/Grp170-tumour protein antigen complexes demonstrated in preclinical studies has led to a phase I clinical trial through the National Cancer Institute's rapid access to intervention development (RAID) programme that is presently underway. Here we review aspects of the structure and function of these large stress proteins, their roles as molecular chaperones in the biology of cell stress, and prospects for their use in immune regulation and cancer immunotherapy. Lastly, we will discuss the recently revealed immunosuppressive activity of scavenger receptor A that binds to Hsp110 and Grp170, as well as the feasibility of targeting this receptor to promote T-cell activation and anti-tumour immunity induced by large HSP vaccines and other immunotherapies. © 2013 Informa UK Ltd.


Freitas K.,Virginia Commonwealth University | Carroll F.I.,Research Triangle Institute | Damaj M.I.,Virginia Commonwealth University
Journal of Pharmacology and Experimental Therapeutics | Year: 2013

The α7 nicotinic acetylcholine receptor (nAChR) subtype is abundantly expressed in the central nervous system and in the periphery. Recent evidence suggests that α7 nAChR subtypes, which can be activated by an endogenous cholinergic tone, comprising acetylcholine and the α7 nAChR agonist choline, play an important role in subchronic pain and inflammation. This study's objective was to test whether α7 nAChR positive allosteric modulators (PAMs) produce antinociception in in vivo mouse models of acute and persistent pain. Testing type I [N-(5- chloro-2-hydroxyphenyl)-N'-[2-chloro-5- (trifluoromethyl)phenyl] (NS1738)] and type II [1-(5-chloro-2,4-dimethoxy- phenyl)-3-(5- methyl-isoxazol-3-yl) (PNU-120596)] α7 nAChR PAMs in acute and persistent pain, we found that, although neither reduced acute thermal pain, only PNU-120596 dose-dependently attenuated paw-licking behavior in the formalin test. The long-acting effect of PNU-120596 in this test was in discordance with its pharmacokinetic profile in mice, which suggests the involvement of postreceptor signaling mechanisms. Our results with selective mitogen-activated protein kinase kinase inhibitor 1,4- diamino-2,3-dicyano-1,4- bis(o-aminophenylmercapto)butadiene monoethanolate (U0126) argues for an important role of extracellular signal-regulated kinase-1/2 pathways activation in PNU-120596's antinociceptive effects. The α7 antagonist MLA, administered intrathecally, reversed PNU-120596's effects, confirming PNU-120596 's action, in part, through central α7 nAChRs. Importantly, tolerance to PNU-120596 was not developed after subchronic treatment of the drug. Surprisingly, PNU-120596's antinociceptive effects were blocked by NS1738. Our results indicate that type II α7 nAChR PAM PNU-120596, but not type I α7 nAChR PAM NS1738, shows significant antinociception effects in persistent pain models in mice. Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics.


Rosenberg M.B.,Virginia Commonwealth University | Carroll F.I.,Research Triangle Institute | Negus S.S.,Virginia Commonwealth University
Journal of Pain | Year: 2013

Pain is associated with stimulation of some behaviors (eg, withdrawal reflexes) but depression of many other behaviors (eg, feeding, locomotion, positively reinforced operant behavior). Drugs that block reuptake of serotonin, norepinephrine, and/or dopamine are widely used to treat depression, and they have also emerged as useful drugs for treatment of pain. This study compared effects of selective and mixed-action inhibitors of serotonin, norepinephrine, and/or dopamine reuptake in assays of acute pain-stimulated and pain-depressed behavior. Intraperitoneal injection of dilute acid served as a noxious stimulus to stimulate a writhing response or depress intracranial self-stimulation (ICSS) in Sprague Dawley rats. Selective reuptake inhibitors of serotonin (citalopram, clomipramine) and norepinephrine (nisoxetine, nortriptyline) and a mixed-action reuptake inhibitor of serotonin and norepinephrine (milnacipran) blocked acid-stimulated writhing but failed to block acid-induced depression of ICSS. Selective dopamine reuptake inhibitors (RTI-113 [3ß-(4-chlorophenyl) tropane-2ß-carboxylic acid phenyl ester hydrochloride], bupropion) and a triple reuptake inhibitor of dopamine, serotonin, and norepinephrine (RTI-112 [3ß-(3-methyl-4-chlorophenyl)tropane-2ß-carboxylic acid methyl ester hydrochloride]) blocked both acid-stimulated writhing and acid-induced depression of ICSS, although these drugs also produced an abuse-related facilitation of ICSS in the absence of the noxious stimulus. These results support further consideration of dopamine reuptake inhibitors as candidate analgesics, although abuse liability remains a concern. Perspective: Monoamine reuptake inhibitors are used to treat depression and some forms of pain. This study examined effects of monoamine reuptake inhibitors in a preclinical assay of pain-related behavioral depression. The results support further consideration of dopamine reuptake inhibitors as candidate analgesics under selected circumstances, although abuse liability remains a concern. © 2013 by the American Pain Society.


Benton G.,Trevigen, Inc. | Arnaoutova I.,Trevigen, Inc. | George J.,Trevigen, Inc. | Kleinman H.K.,George Washington University | Koblinski J.,Virginia Commonwealth University
Advanced Drug Delivery Reviews | Year: 2014

The basement membrane is an important extracellular matrix that is found in all epithelial and endothelial tissues. It maintains tissue integrity, serves as a barrier to cells and to molecules, separates different tissue types, transduces mechanical signals, and has many biological functions that help to maintain tissue specificity. A well-defined soluble basement membrane extract, termed BME/Matrigel, prepared from an epithelial tumor is similar in content to authentic basement membrane, and forms a hydrogel at 24-37. °C. It is used in vitro as a substrate for 3D cell culture, in suspension for spheroid culture, and for various assays, such as angiogenesis, invasion, and dormancy. In vivo, BME/Matrigel is used for angiogenesis assays and to promote xenograft and patient-derived biopsy take and growth. Studies have shown that both the stiffness of the BME/Matrigel and its components (i.e. chemical signals) are responsible for its activity with so many different cell types. BME/Matrigel has widespread use in assays and in models that improve our understanding of tumor biology and help define therapeutic approaches. © 2014 Elsevier B.V.


Pakyz A.L.,Virginia Commonwealth University | Jawahar R.,Virginia Commonwealth University | Wang Q.,Virginia Commonwealth University | Harpe S.E.,Midwestern University
Journal of Antimicrobial Chemotherapy | Year: 2014

Objectives: The main objective of this study was to determine patient- and hospital-level medication risk factors associated with Clostridium difficile infection (CDI) occurrence among patients clustered within hospitals using a multilevel model. Methods: Patients with healthcare-associated (HA)-CDI were identified from among 64 academic medical centres in 2009. A frequency match was conducted; for each case, up to two controls were selected, matched on similar pre-infection length of stay and clinical service line. Patient- and hospital-level medication use, including antibacterial and gastric acid-suppressant agents, was assessed using a two-level logistic regression model. Results: A total of 5967 CDI cases and 8167 controls were included in the analysis. The odds of acquiring HA-CDI increased with the following medications [OR (95% CI)]: anti-methicillin-resistant Staphylococcus aureus agents [1.38 (1.22-1.56)]; third- or fourth-generation cephalosporins [1.75 (1.62-1.89)]; carbapenems [1.60 (1.44-1.79)]; β-lactam/β-lactamase inhibitor combinations [1.49 (1.36-1.64)]; vancomycin [1.73 (1.57-1.89)]; and proton pump inhibitors [1.43 (1.30-1.57)]. The odds of acquiring HA-CDI decreased with the following medications: clindamycin [0.74 (0.63-0.87)]; and macrolides [0.88 (0.77-0.99)]. Controlling for patient-level covariates, no hospital-level medication covariates that we analysed had statistically significant effects on HA-CDI. The odds of acquiring HA-CDI increased with the hospital proportion of patients aged ≥65 years [1.01 (1.00-1.02)]. Conclusions: We found several medications that were associated with the risk of patients developing HA-CDI, including β-lactam/β-lactamase inhibitor combinations, third- or fourth-generation cephalosporins, carbapenems, vancomycin, proton pump inhibitors and anti-methicillin-resistant S. aureus agents. There were no medication effects significant at the hospital level. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Patent
Research Triangle Institute, University of Michigan and Virginia Commonwealth University | Date: 2012-12-26

Compounds and compositions for promoting smoking cessation or decreasing tobacco use or nicotine addiction are provided. The compounds are 2-fluoro-3-(substituted phenyl) deschloroepibatidine analogs. The compounds have been found to modulate neuronal nicotine acetylcholine receptors and are useful in methods for the treatment of conditions or disorders influenced by the modulation of neuronal nicotinic acetylcholine receptors.


Patent
Research Triangle Institute, Virginia Commonwealth University and Barrow Neurological Institute | Date: 2012-11-19

The invention provides hydroxybupropion analogues capable of inhibiting the reuptake of one or more monoamines and/or acting as antagonists at nicotinic acetylcholine receptors. The compounds may selectively bind to one or more monoamine transporters, including those for dopamine, norepinephrine, and serotonin and/or may selectively bind to one or more nicotinic acetylcholine receptor subtypes. Such compounds may be used to treat conditions that are responsive to modification of monoamine levels and/or antagonism of nicotinic acetylcholine receptors, including drug dependency, depression, and obesity.


Patent
Research Triangle Institute, University of Michigan and Virginia Commonwealth University | Date: 2012-12-26

Compounds and compositions for promoting smoking cessation or decreasing tobacco use or nicotine addiction are provided. The compounds are 2-fluoro-3-(substituted phenyl) deschloroepibatidine analogs. The compounds have been found to modulate neuronal nicotine acetylcholine receptors and are useful in methods for the treatment of conditions or disorders influenced by the modulation of neuronal nicotinic acetylcholine receptors.

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