Showing papers by "Virginia Commonwealth University published in 2014"
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TL;DR: Associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses.
Abstract: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.
6,809 citations
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Emory University1, University of California, San Francisco2, University of California, San Diego3, Baylor College of Medicine4, University of Minnesota5, Virginia Commonwealth University6, Rush University Medical Center7, Texas Tech University8, Duke University9, University of Texas Health Science Center at Houston10, National Institutes of Health11
TL;DR: In this article, Anderson et al. discuss the FAHA chair election process and discuss the state of the art in the field of cancer research. But they do not discuss the role of women in this process.
3,218 citations
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Food and Drug Administration1, Université Bordeaux Segalen2, Edinburgh Cancer Research Centre3, MedStar Washington Hospital Center4, European Organisation for Research and Treatment of Cancer5, Memorial Sloan Kettering Cancer Center6, University of North Carolina at Chapel Hill7, University of Texas MD Anderson Cancer Center8, Virginia Commonwealth University9, Ludwig Maximilian University of Munich10
TL;DR: In this paper, the authors compared the three most commonly used definitions of pathological complete response (ypT0 ypN0, ypT0/is ypNs0, and ypTsN0/IsYPN0) for their association with EFS and overall survival in clinical trials of neoadjuvant treatment of breast cancer.
2,793 citations
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TL;DR: The AASLD/EASL Practice Guideline Subcommittee on Hepatic Encephalopathy are: Jayant A. Talwalkar, Hari S. Conjeevaram, Michael Porayko, Raphael B. Merriman, Peter L. Jansen, Fabien Zoulim.
1,375 citations
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TL;DR: It is concluded that levothyroxine should remain the standard of care for treating hypothyroidism and no consistently strong evidence for the superiority of alternative preparations is found.
Abstract: Background: A number of recent advances in our understanding of thyroid physiology may shed light on why some patients feel unwell while taking levothyroxine monotherapy. The purpose of this task force was to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps. We wished to determine whether there are sufficient new data generated by well-designed studies to provide reason to pursue such therapies and change the current standard of care. This document is intended to inform clinical decision-making on thyroid hormone replacement therapy; it is not a replacement for individualized clinical judgment. Methods: Task force members identified 24 questions relevant to the treatment of hypothyroidism. The clinical literature relating to each question was then reviewed. Clinical reviews were supplemented, when relevant, with related...
1,128 citations
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TL;DR: The authors meta-analyzed 73 studies with a total sample size of 37,285 individuals and found a significant but a small correlation between entrepreneurship education and entrepreneurial intentions, which is also greater than that of business education.
Abstract: The research on entrepreneurship education�entrepreneurial intentions has yielded mixed results. We meta-analyzed 73 studies with a total sample size of 37,285 individuals and found a significant but a small correlation between entrepreneurship education and entrepreneurial intentions (inline image). This correlation is also greater than that of business education and entrepreneurial intentions. However, after controlling for pre-education entrepreneurial intentions, the relationship between entrepreneurship education and post-education entrepreneurial intentions was not significant. We also analyzed moderators, such as the attributes of entrepreneurship education, students' differences, and cultural values. Our results have implications for entrepreneurship education scholars, program evaluators, and policy makers.
1,032 citations
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University of Ottawa1, University of Colorado Boulder2, University of Michigan3, University Health System4, Cleveland Clinic5, Albany Medical College6, Virginia Commonwealth University7, Icahn School of Medicine at Mount Sinai8, Aarhus University Hospital9, University of Chicago10, Kyorin University11
TL;DR: This research presents a meta-anatomy of the autonomic nervous system, a probabilistic model of how the immune system regulates emotion, language, and physical activity in relation to heart disease.
999 citations
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SUNY Downstate Medical Center1, McGill University2, University of Connecticut3, Cornell University4, Umeå University5, Wayne State University6, University of Iowa7, University of Miami8, University of Pennsylvania9, Mayo Clinic10, University of Sydney11, University of Buenos Aires12, University of Chicago13, Shanghai Jiao Tong University14, North-West University15, University of Rochester16, University of Glasgow17, Virginia Commonwealth University18, University of Melbourne19
TL;DR: Clinical Practice Guidelines for the Management of Hypertension in the Community as mentioned in this paper A Statement by the American Society of hypertension and the International Society of Hyperpharmension (ISH).
Abstract: Clinical Practice Guidelines for the Management of Hypertension in the Community A Statement by the American Society of Hypertension and the International Society of Hypertension
920 citations
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TL;DR: The knowledge gained in this emerging field of sphingolipid metabolism will aid in the development of new therapeutic options for inflammatory disorders.
Abstract: Sphingolipids are ubiquitous building blocks of eukaryotic cell membranes. Progress in our understanding of sphingolipid metabolism, state-of-the-art sphingolipidomic approaches and animal models have generated a large body of evidence demonstrating that sphingolipid metabolites, particularly ceramide and sphingosine-1-phosphate, are signalling molecules that regulate a diverse range of cellular processes that are important in immunity, inflammation and inflammatory disorders. Recent insights into the molecular mechanisms of action of sphingolipid metabolites and new perspectives on their roles in regulating chronic inflammation have been reported. The knowledge gained in this emerging field will aid in the development of new therapeutic options for inflammatory disorders.
901 citations
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TL;DR: The host and microbiome appear to regulate bile acid pool size, and members of the microbiome utilize bile acids and their conjugates resulting in agonism of FXR in intestine and liver resulting in a smaller, unconjugated hydrophobic bile Acid pool.
Abstract: Purpose of the review
We examine the latest research on the emerging bile acid-gut microbiome axis and its role in health and disease. Our focus revolves around two key microbial pathways for degrading bile salts, and the impact of bile acid composition in the gut on the gut microbiome and host physiology.
896 citations
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TL;DR: Assessing the determinants of cloud computing adoption is based on an analysis of the manufacturing and services sectors and the results show clear trends in adoption towards cloud-based services.
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TL;DR: Th thin films of hard electronic materials patterned in deterministic fractal motifs and bonded to elastomers enable unusual mechanics with important implications in stretchable device design, suggesting that fractal-based layouts represent important strategies for hard-soft materials integration.
Abstract: Stretchable electronics provide a foundation for applications that exceed the scope of conventional wafer and circuit board technologies due to their unique capacity to integrate with soft materials and curvilinear surfaces. The range of possibilities is predicated on the development of device architectures that simultaneously offer advanced electronic function and compliant mechanics. Here we report that thin films of hard electronic materials patterned in deterministic fractal motifs and bonded to elastomers enable unusual mechanics with important implications in stretchable device design. In particular, we demonstrate the utility of Peano, Greek cross, Vicsek and other fractal constructs to yield space-filling structures of electronic materials, including monocrystalline silicon, for electrophysiological sensors, precision monitors and actuators, and radio frequency antennas. These devices support conformal mounting on the skin and have unique properties such as invisibility under magnetic resonance imaging. The results suggest that fractal-based layouts represent important strategies for hard-soft materials integration.
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TL;DR: In the longitudinal matched-cohort, microbiota were significantly different between infected/uninfected cirrhotics at baseline and a low CDR was associated with death and organ failures within 30days, indicating progressive changes in the gut microbiome accompany cirrhosis and become more severe in the setting of decompensation.
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University of Florida1, University of Padua2, University of Würzburg3, Pennsylvania State University4, University of Social Sciences and Humanities5, Tilburg University6, City University of New York7, Koç University8, University of Michigan9, University of Kuala Lumpur10, Texas A&M University11, San Diego State University12, Mount Saint Vincent University13, Radboud University Nijmegen14, Virginia Commonwealth University15, Texas A&M University–Commerce16, Loyola University Chicago17, Worcester Polytechnic Institute18, London School of Economics and Political Science19, James Madison University20, Occidental College21, McDaniel College22, Connecticut College23, Wilfrid Laurier University24, University of Brasília25, California State University, Northridge26, University of Virginia27, Ohio State University28, University of Wisconsin-Madison29, Ithaca College30, Charles University in Prague31, Western Kentucky University32, Washington and Lee University33
TL;DR: The authors compared variation in the replicability of 13 classic and contemporary effects across 36 independent samples totaling 6,344 participants and found that the results of these experiments are more dependent on the effect itself than on the sample and setting used to investigate the effect.
Abstract: Although replication is a central tenet of science, direct replications are rare in psychology. This research tested variation in the replicability of 13 classic and contemporary effects across 36 independent samples totaling 6,344 participants. In the aggregate, 10 effects replicated consistently. One effect – imagined contact reducing prejudice – showed weak support for replicability. And two effects – flag priming influencing conservatism and currency priming influencing system justification – did not replicate. We compared whether the conditions such as lab versus online or US versus international sample predicted effect magnitudes. By and large they did not. The results of this small sample of effects suggest that replicability is more dependent on the effect itself than on the sample and setting used to investigate the effect.
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TL;DR: The addition of trastuzumab to paclitaxel after doxorubicin and cyclophosphamide in early-stage HER2-positive breast cancer results in a substantial and durable improvement in survival as a result of a sustained marked reduction in cancer recurrence.
Abstract: Purpose Positive interim analysis findings from four large adjuvant trials evaluating trastuzumab in patients with early-stage human epidermal growth factor receptor 2 (HER2) –positive breast cancer were first reported in 2005. One of these reports, the joint analysis of North Central Cancer Treatment Group NCCTG N9831 (Combination Chemotherapy With or Without Trastuzumab in Treating Women With HER2-Overexpressing Breast Cancer) and the National Surgical Adjuvant Breast and Bowel Project NSABP B-31 (Doxorubicin and Cyclophosphamide Plus Paclitaxel With or Without Trastuzumab in Treating Women With Node-Positive Breast Cancer That Overexpresses HER2), was updated in 2011. We now report the planned definitive overall survival (OS) results from this joint analysis along with updates on the disease-free survival (DFS) end point. Methods In all, 4,046 patients with HER2-positive operable breast cancer were enrolled to receive doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab i...
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Johns Hopkins University1, University of Calgary2, The George Institute for Global Health3, Royal Prince Alfred Hospital4, University of Sydney5, University of Salerno6, Geisinger Medical Center7, Saarland University8, Tufts Medical Center9, University of Minnesota10, University of California, San Diego11, University of Tennessee Health Science Center12, Veterans Health Administration13, University of Aberdeen14, Teikyo University15, Tohoku University16, Shiga University of Medical Science17, Tel Aviv University18, Virginia Commonwealth University19, China Medical University (Taiwan)20, National Health Research Institutes21, University Medical Center Groningen22, University of Paris-Sud23
TL;DR: Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in Estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.
Abstract: IMPORTANCE: The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event.OBJECTIVE: To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated.DATA SOURCES AND STUDY SELECTION: Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data.DATA EXTRACTION AND SYNTHESIS: Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012.MAIN OUTCOMES AND MEASURES: End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR.RESULTS: The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern.CONCLUSIONS AND RELEVANCE: Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.
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University of Connecticut1, University of Adelaide2, Winthrop-University Hospital3, University of Texas MD Anderson Cancer Center4, City of Hope National Medical Center5, Virginia Commonwealth University6, University of Tennessee Health Science Center7, National and Kapodistrian University of Athens8, Brigham and Women's Hospital9, University of Rochester10
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State University of New York System1, McGill University2, University of Connecticut3, Cornell University4, Umeå University5, Wayne State University6, University of Iowa7, University of Miami8, University of Pennsylvania9, Mayo Clinic10, University of Sydney11, University of Buenos Aires12, University of Chicago13, Shanghai Jiao Tong University14, North-West University15, University of Rochester16, University of Glasgow17, Virginia Commonwealth University18, University of Melbourne19
TL;DR: Clinical practice guidelines for the management of hypertension in the community a statement by the American Society of Hypertension and the International Society of hypertension as mentioned in this paper, which is based on guidelines from the National Institute of Neurological Disorders and Strochastic Hemorrhage.
Abstract: Clinical practice guidelines for the management of hypertension in the community a statement by the American society of hypertension and the International society of hypertension
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Royal Free Hospital1, Carlos III Health Institute2, University of California, San Diego3, Paris Diderot University4, University of Padua5, University of Graz6, Université libre de Bruxelles7, University of Bologna8, Saarland University9, Katholieke Universiteit Leuven10, University of Barcelona11, King's College London12, Virginia Commonwealth University13, Yale University14, University College London15
TL;DR: An in-depth review and a position statement on bacterial infections in cirrhosis are reported, which suggest that research on biomarkers of early infection may be useful in early diagnosis and treatment of infections.
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Emory University1, University of California, San Francisco2, University of California, San Diego3, Baylor College of Medicine4, University of Minnesota5, Virginia Commonwealth University6, Rush University Medical Center7, Texas Tech University8, Duke University9, Harvard University10, University of Texas Health Science Center at Houston11, National Institutes of Health12
TL;DR: In this paper, early hospital care, hospital discharge, and post-hospital discharge care are recommended for Acs, based on myocardial revascularization and initial evaluation and management.
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Harvard University1, Tom Baker Cancer Centre2, University of Chicago3, Mayo Clinic4, Complutense University of Madrid5, Johns Hopkins University6, University of Bordeaux7, Virginia Commonwealth University8, University of Udine9, Kantonsspital St. Gallen10, University of Bern11, University of Milan12, University of Sydney13, University of Melbourne14
TL;DR: In premenopausal women with hormone-receptor-positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppressed, significantly reduced recurrence.
Abstract: BACKGROUND Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor–positive breast cancer. METHODS In two phase 3 trials, we randomly assigned premenopausal women with hormonereceptor–positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials. RESULTS After a median follow-up of 68 months, disease-free survival at 5 years was 91.1% in the exemestane–ovarian suppression group and 87.3% in the tamoxifen–ovarian suppression group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.72; 95% confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast cancer at 5 years was 92.8% in the exemestane–ovarian suppression group, as compared with 88.8% in the tamoxifen–ovarian suppression group (hazard ratio for recurrence, 0.66; 95% CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1% of the patients), overall survival did not differ significantly between the two groups (hazard ratio for death in the exemestane–ovarian suppression group, 1.14; 95% CI, 0.86 to 1.51; P = 0.37). Selected adverse events of grade 3 or 4 were reported for 30.6% of the patients in the exemestane–ovarian suppression group and 29.4% of those in the tamoxifen–ovarian suppression group, with profiles similar to those for postmenopausal women. CONCLUSIONS In premenopausal women with hormone-receptor–positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence. (Funded by Pfizer and others; TEXT and SOFT ClinicalTrials.gov numbers, NCT00066703 and NCT00066690, respectively.)
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TL;DR: This review provides a general overview of the available information about the contact angle values of experimental and of marketed implant surfaces, some of the techniques used to modify surface wettability of implants, and results from in vitro and clinical studies.
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TL;DR: Pharmacotherapies that increase PDGF-BB secretion from preosteoclasts offer a new therapeutic target for treating osteoporosis by promoting angiogenesis and thus bone formation.
Abstract: Osteogenesis during bone modeling and remodeling is coupled with angiogenesis. A recent study showed that a specific vessel subtype, strongly positive for CD31 and endomucin (CD31(hi)Emcn(hi)), couples angiogenesis and osteogenesis. Here, we found that platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts induces CD31(hi)Emcn(hi) vessel formation during bone modeling and remodeling. Mice with depletion of PDGF-BB in the tartrate-resistant acid phosphatase-positive cell lineage show significantly lower trabecular and cortical bone mass, serum and bone marrow PDGF-BB concentrations, and fewer CD31(hi)Emcn(hi) vessels compared to wild-type mice. In the ovariectomy (OVX)-induced osteoporotic mouse model, serum and bone marrow levels of PDGF-BB and numbers of CD31(hi)Emcn(hi) vessels are significantly lower compared to sham-operated controls. Treatment with exogenous PDGF-BB or inhibition of cathepsin K to increase the number of preosteoclasts, and thus the endogenous levels of PDGF-BB, increases CD31(hi)Emcn(hi) vessel number and stimulates bone formation in OVX mice. Thus, pharmacotherapies that increase PDGF-BB secretion from preosteoclasts offer a new therapeutic target for treating osteoporosis by promoting angiogenesis and thus bone formation.
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TL;DR: The study found that facilitating conditions and behavioral intentions directly influence mBanking adoption, and initial trust, performance expectancy, technology characteristics, and task technology fit have total effect on behavioral intention.
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University of Toronto1, German Cancer Research Center2, Dartmouth College3, Boston Children's Hospital4, University of Texas MD Anderson Cancer Center5, Ontario Institute for Cancer Research6, GlaxoSmithKline7, University of British Columbia8, Uniformed Services University of the Health Sciences9, University of Utah10, The Catholic University of America11, Stanford University12, Virginia Commonwealth University13, University of Warsaw14, McMaster University15, Heidelberg University16, University of Michigan17, University of California, San Francisco18, McGill University19
TL;DR: It is concluded that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.
Abstract: Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.
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TL;DR: Genome-wide association and linkage results provide constraints on the allele frequencies and effect sizes of susceptibility loci, which are used to interpret the voluminous candidate gene literature.
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Wageningen University and Research Centre1, Maastricht University2, University of Amsterdam3, Katholieke Universiteit Leuven4, University of Melbourne5, Leiden University Medical Center6, Virginia Commonwealth University7, Open University8, VCU Medical Center9, Ghent University Hospital10, Auburn University at Montgomery11
TL;DR: The results support the hypothesis that mood may have alternative stable states separated by tipping points, and suggest an approach for assessing the likelihood of transitions into and out of depression.
Abstract: About 17% of humanity goes through an episode of major depression at some point in their lifetime. Despite the enormous societal costs of this incapacitating disorder, it is largely unknown how the likelihood of falling into a depressive episode can be assessed. Here, we show for a large group of healthy individuals and patients that the probability of an upcoming shift between a depressed and a normal state is related to elevated temporal autocorrelation, variance, and correlation between emotions in fluctuations of autorecorded emotions. These are indicators of the general phenomenon of critical slowing down, which is expected to occur when a system approaches a tipping point. Our results support the hypothesis that mood may have alternative stable states separated by tipping points, and suggest an approach for assessing the likelihood of transitions into and out of depression.
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TL;DR: Allowing EC to compete with cigarettes in the market-place might decrease smoking-related morbidity and mortality and 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.
Abstract: 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.
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Pennsylvania State University1, University of Texas Health Science Center at San Antonio2, Georgia Regents University3, University of Pennsylvania4, Anschutz Medical Campus5, University of Vermont6, University of Michigan7, Yale University8, University of Virginia9, University of Alabama at Birmingham10, Carolinas Medical Center11, Virginia Commonwealth University12, Stanford University13, State University of New York Upstate Medical University14, Wayne State University15, National Institutes of Health16
TL;DR: Letrozole was associated with higher live-birth and ovulation rates among infertile women with the polycystic ovary syndrome and with higher incidences of fatigue and dizziness compared with clomiphene.
Abstract: In this double-blind, multicenter trial, we randomly assigned 750 women, in a 1:1 ratio, to receive letrozole or clomiphene for up to five treatment cycles, with visits to determine ovulation and pregnancy, followed by tracking of pregnancies. The polycystic ovary syndrome was defined according to modified Rotterdam criteria (anovulation with either hyperandrogenism or polycystic ovaries). Participants were 18 to 40 years of age, had at least one patent fallopian tube and a normal uterine cavity, and had a male partner with a sperm concentration of at least 14 million per milliliter; the women and their partners agreed to have regular intercourse with the intent of conception during the study. The primary outcome was live birth during the treatment period. Results Women who received letrozole had more cumulative live births than those who received clomiphene (103 of 374 [27.5%] vs. 72 of 376 [19.1%], P = 0.007; rate ratio for live birth, 1.44; 95% confidence interval, 1.10 to 1.87) without significant differences in overall congenital anomalies, though there were four major congenital anomalies in the letrozole group versus one in the clomiphene group (P = 0.65). The cumulative ovulation rate was higher with letrozole than with clomiphene (834 of 1352 treatment cycles [61.7%] vs. 688 of 1425 treatment cycles [48.3%], P<0.001). There were no significant between-group differences in pregnancy loss (49 of 154 pregnancies in the letrozole group [31.8%] and 30 of 103 pregnancies in the clomiphene group [29.1%]) or twin pregnancy (3.4% and 7.4%, respectively). Clomiphene was associated with a higher incidence of hot flushes, and letrozole was associated with higher incidences of fatigue and dizziness. Rates of other adverse events were similar in the two treatment groups. Conclusions As compared with clomiphene, letrozole was associated with higher live-birth and ovulation rates among infertile women with the polycystic ovary syndrome. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00719186.)
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TL;DR: It is found that human observers reliably agree when discriminating low versus high degrees of engagement and that engagement labels of 10-second video clips can be reliably predicted from the average labels of their constituent frames, suggesting that static expressions contain the bulk of the information used by observers.
Abstract: Student engagement is a key concept in contemporary education, where it is valued as a goal in its own right. In this paper we explore approaches for automatic recognition of engagement from students’ facial expressions. We studied whether human observers can reliably judge engagement from the face; analyzed the signals observers use to make these judgments; and automated the process using machine learning. We found that human observers reliably agree when discriminating low versus high degrees of engagement (Cohen’s $\kappa = 0.96$ ). When fine discrimination is required (four distinct levels) the reliability decreases, but is still quite high ( $\kappa = 0.56$ ). Furthermore, we found that engagement labels of 10-second video clips can be reliably predicted from the average labels of their constituent frames (Pearson $r=0.85$ ), suggesting that static expressions contain the bulk of the information used by observers. We used machine learning to develop automatic engagement detectors and found that for binary classification (e.g., high engagement versus low engagement), automated engagement detectors perform with comparable accuracy to humans. Finally, we show that both human and automatic engagement judgments correlate with task performance. In our experiment, student post-test performance was predicted with comparable accuracy from engagement labels ( $r=0.47$ ) as from pre-test scores ( $r=0.44$ ).