Showing papers by "Virginia Commonwealth University published in 2010"
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TL;DR: The Tailored Design Method as mentioned in this paper aims to achieve high-quantity and high-quality survey response by minimizing four sources of survey error (coverage, sampling, nonresponse, and measurement) and motivating respondents using features informed by scientiÞc evidence.
Abstract: Dillman, Smyth, and Christian offer in the third edition a practical guide to survey research across content areas. The Tailored Design Method aims to achieve high-quantity and high-quality survey response by minimizing 4 sources of survey error (coverage, sampling, nonresponse, andmeasurement) and motivating respondents using features informed by scientiÞc evidence. This new edition updates the previous edition by articulating the current climate of survey research and integrating Web-based survey design throughout the book alongside the discussion of longstanding traditional mail, in-person, and telephone modes of data collection. After a brief history of survey research, the second chapter explores tailored design as a conceptual framework for survey design based on the unique situation and target population and focused on improving accuracy and completion rates of respondents. Coverage and sampling considerations and processes are reviewed in Chapter 3. The next 3 chapters introduce evidence-based guidelines for (1) writing highquality questions with tips ranging from word choice to visual presentation, (2) constructing openand closed-ended
2,747 citations
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Virginia Commonwealth University1, Indiana University – Purdue University Indianapolis2, Virginia Mason Medical Center3, Case Western Reserve University4, Duke University5, University of California, San Francisco6, Saint Louis University7, University of California, San Diego8, Johns Hopkins University9, Washington University in St. Louis10, National Institutes of Health11
TL;DR: Vitamin E was superior to placebo for the treatment of nonalcoholic steatohepatitis in adults without diabetes, and significant benefits of pioglitazone were observed for some of the secondary outcomes.
Abstract: Background Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrho sis. Currently, there is no established treatment for this disease. Methods We randomly assigned 247 adults with nonalcoholic steatohepatitis and without dia betes to receive pioglitazone at a dose of 30 mg daily (80 subjects), vitamin E at a dose of 800 IU daily (84 subjects), or placebo (83 subjects), for 96 weeks. The pri mary outcome was an improvement in histologic features of nonalcoholic steato hepatitis, as assessed with the use of a composite of standardized scores for steato sis, lobular inflammation, hepatocellular ballooning, and fibrosis. Given the two planned primary comparisons, P values of less than 0.025 were considered to indi cate statistical significance. Results Vitamin E therapy, as compared with placebo, was associated with a significantly higher rate of improvement in nonalcoholic steatohepatitis (43% vs. 19%, P = 0. 001), but the difference in the rate of improvement with pioglitazone as compared with placebo was not significant (34% and 19%, respectively; P = 0. 04). Serum alanine and aspartate aminotransferase levels were reduced with vitamin E and with pio glitazone, as compared with placebo (P<0.001 for both comparisons), and both agents were associated with reductions in hepatic steatosis (P = 0. 005 for vitamin E and P<0.001 for pioglitazone) and lobular inflammation (P = 0. 02 for vitamin E and P = 0. 004 for pioglitazone) but not with improvement in fibrosis scores (P = 0. 24 for vitamin E and P = 0. 12 for pioglitazone). Subjects who received pioglitazone gained more weight than did those who received vitamin E or placebo; the rates of other side effects were similar among the three groups. Conclusions Vitamin E was superior to placebo for the treatment of nonalcoholic steatohepatitis in adults without diabetes. There was no benefit of pioglitazone over placebo for the primary outcome; however, significant benefits of pioglitazone were observed for some of the secondary outcomes. (ClinicalTrials.gov number, NCT000 63622.)
2,632 citations
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TL;DR: It is demonstrated that insufficient sleep and irregular sleep-wake patterns, which have been extensively documented in younger adolescents, are also present at alarming levels in the college student population.
1,360 citations
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University of North Carolina at Chapel Hill1, University of Texas Health Science Center at Houston2, University of Cambridge3, University of Pavia4, University of Milan5, Stanford University6, Kaiser Permanente7, National Institutes of Health8, University of Washington9, Wake Forest University10, Cedars-Sinai Medical Center11, Group Health Cooperative12, Lund University13, University of Michigan14, University of Helsinki15, National Institute for Health and Welfare16, Boston University17, University of Chicago18, International Agency for Research on Cancer19, Charles University in Prague20, French Institute of Health and Medical Research21, Institut Gustave Roussy22, University of Padua23, University of Glasgow24, Palacký University, Olomouc25, Trinity College, Dublin26, National and Kapodistrian University of Athens27, Newcastle University28, University of Aberdeen29, University of Turin30, Nofer Institute of Occupational Medicine31, Russian Academy32, University of Exeter33, Massachusetts Institute of Technology34, Harvard University35, Broad Institute36, VU University Amsterdam37, Erasmus University Rotterdam38, University of Virginia39, Virginia Commonwealth University40, University of Pennsylvania41, Duke University42, Tufts University43, University of Ioannina44
TL;DR: A meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium found the strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3, and three loci associated with number of cigarettes smoked per day were identified.
Abstract: Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
1,104 citations
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TL;DR: Over a 6-month period, treatment with rifaximin maintained remission from hepatic encephalopathy more effectively than did placebo, and also significantly reduced the risk of hospitalization involving hepaticEncephalopathy.
Abstract: Background Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrhosis. The efficacy of rifaximin, a minimally absorbed antibiotic, is well documented in the treatment of acute hepatic encephalopathy, but its efficacy for prevention of the disease has not been established. Methods In this randomized, double-blind, placebo-controlled trial, we randomly assigned 299 patients who were in remission from recurrent hepatic encephalopathy resulting from chronic liver disease to receive either rifaximin, at a dose of 550 mg twice daily (140 patients), or placebo (159 patients) for 6 months. The primary efficacy end point was the time to the first breakthrough episode of hepatic encephalopathy. The key secondary end point was the time to the first hospitalization involving hepatic encephalopathy. Results Rifaximin significantly reduced the risk of an episode of hepatic encephalopathy, as compared with placebo, over a 6-month period (hazard ratio with rifaximin, 0.42; 95% confidence interval [CI], 0.28 to 0.64; P<0.001). A breakthrough episode of hepatic encephalopathy occurred in 22.1% of patients in the rifaximin group, as compared with 45.9% of patients in the placebo group. A total of 13.6% of the patients in the rifaximin group had a hospitalization involving hepatic encephalopathy, as compared with 22.6% of patients in the placebo group, for a hazard ratio of 0.50 (95% CI, 0.29 to 0.87; P = 0.01). More than 90% of patients received concomitant lactulose therapy. The incidence of adverse events reported during the study was similar in the two groups, as was the incidence of serious adverse events. Conclusions Over a 6-month period, treatment with rifaximin maintained remission from hepatic encephalopathy more effectively than did placebo. Rifaximin treatment also significantly reduced the risk of hospitalization involving hepatic encephalopathy. (ClinicalTrials.gov number, NCT00298038.)
968 citations
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St. Michael's Hospital1, Southampton General Hospital2, Royal Melbourne Hospital3, University of Melbourne4, University of Pittsburgh5, University of Iowa6, Denver Health Medical Center7, University of Michigan8, University of Arizona9, University of New South Wales10, University of Oslo11, Virginia Commonwealth University12, Weil, Gotshal & Manges13, University of Cologne14, Singapore General Hospital15, Royal United Hospital16
TL;DR: Part 8 : Advanced life support : 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations with treatment Recommendations.
Abstract: Part 8 : Advanced life support : 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations
851 citations
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TL;DR: The mechanisms of neurotoxicity associated with chronic microglia activation are reviewed and the role of neuronal death and microglial ROS driving the chronic and toxic microglian phenotype is discussed.
771 citations
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TL;DR: The data show that TRAF2 is a novel intracellular target of S1p, and that S1P is the missing cofactor for TRAF 2 E3 ubiquitin ligase activity, indicating a new paradigm for the regulation of lysine-63-linked polyubiquitination.
Abstract: Tumour-necrosis factor (TNF) receptor-associated factor 2 (TRAF2) is a key component in NF-kappaB signalling triggered by TNF-alpha. Genetic evidence indicates that TRAF2 is necessary for the polyubiquitination of receptor interacting protein 1 (RIP1) that then serves as a platform for recruitment and stimulation of IkappaB kinase, leading to activation of the transcription factor NF-kappaB. Although TRAF2 is a RING domain ubiquitin ligase, direct evidence that TRAF2 catalyses the ubiquitination of RIP1 is lacking. TRAF2 binds to sphingosine kinase 1 (SphK1), one of the isoenzymes that generates the pro-survival lipid mediator sphingosine-1-phosphate (S1P) inside cells. Here we show that SphK1 and the production of S1P is necessary for lysine-63-linked polyubiquitination of RIP1, phosphorylation of IkappaB kinase and IkappaBalpha, and IkappaBalpha degradation, leading to NF-kappaB activation. These responses were mediated by intracellular S1P independently of its cell surface G-protein-coupled receptors. S1P specifically binds to TRAF2 at the amino-terminal RING domain and stimulates its E3 ligase activity. S1P, but not dihydro-S1P, markedly increased recombinant TRAF2-catalysed lysine-63-linked, but not lysine-48-linked, polyubiquitination of RIP1 in vitro in the presence of the ubiquitin conjugating enzymes (E2) UbcH13 or UbcH5a. Our data show that TRAF2 is a novel intracellular target of S1P, and that S1P is the missing cofactor for TRAF2 E3 ubiquitin ligase activity, indicating a new paradigm for the regulation of lysine-63-linked polyubiquitination. These results also highlight the key role of SphK1 and its product S1P in TNF-alpha signalling and the canonical NF-kappaB activation pathway important in inflammatory, antiapoptotic and immune processes.
699 citations
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10 May 2010TL;DR: There are still a number of important issues that need to be resolved before ZnO can be transitioned to commercial use, not to mention the stiff competition it is facing with GaN, which is much more mature in terms of devices.
Abstract: ZnO is an attractive material for applications in electronics, photonics, acoustics, and sensing In optical emitters, its high exciton binding energy (60 meV) gives ZnO an edge over other semiconductors such as GaN if reproducible and reliable p-type doping in ZnO were to be achieved, which currently remains to be the main obstacle for realization of bipolar devices On the electronic side, ZnO holds some potential in transparent thin film transistors (TFTs) owing to its high optical transmittivity and high conductivity Among the other promising areas of application for ZnO are acoustic wave devices, due to large electromechanical coupling in ZnO, and devices utilizing nanowires/nanorods such as biosensors and gas sensors and solar cells, since it is relatively easy to produce such forms of ZnO nanostructures, which have good charge carrier transport properties and high crystalline quality Despite the significant progress made, there is still a number of important issues that need to be resolved before ZnO can be transitioned to commercial use, not to mention the stiff competition it is facing with GaN, which is much more mature in terms of devices In this paper, recent progress in device applications of ZnO is discussed and a review of critical issues for realization of ZnO-based devices is given
684 citations
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TL;DR: Evidence that the construct of impulsivity may be better studied in the context of more meaningful subfacets is provided, and recommendations for how research in this direction may provide for better consilience between human and animal studies of the connection between impulsivity and alcohol use are provided.
Abstract: There are well-established links between impulsivity and alcohol use in humans and other model organisms; however, the etiological nature of these associations remains unclear. This is likely due, in part, to the heterogeneous nature of the construct of impulsivity. Many different measures of impulsivity have been employed in human studies, using both questionnaire and laboratory-based tasks. Animal studies also use multiple tasks to assess the construct of impulsivity. In both human and animal studies, different measures of impulsivity often show little correlation and are differentially related to outcome, suggesting that the impulsivity construct may actually consist of a number of more homogeneous (and potentially more meaningful) subfacets. Here, we provide an overview of the different measures of impulsivity used across human and animal studies, evidence that the construct of impulsivity may be better studied in the context of more meaningful subfacets, and recommendations for how research in this direction may provide for better consilience between human and animal studies of the connection between impulsivity and alcohol use.
604 citations
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TL;DR: It is hypothesized that patterns of community similarity and evolution might explain the variation in novelty advantage that can underlie variation in invasion outcomes, including suggestions for managing invasive predators, predator reintroductions and biological control.
Abstract: We present a framework for explaining variation in predator invasion success and predator impacts on native prey that integrates information about predator–prey naivete, predator and prey behavioral responses to each other, consumptive and non-consumptive eff ects of predators on prey, and interacting eff ects of multiple species interactions. We begin with the ‘naive prey’ hypothesis that posits that naive, native prey that lack evolutionary history with non-native predators suff er heavy predation because they exhibit ineff ective antipredator responses to novel predators. Not all naive prey, however, show ineff ective antipredator responses to novel predators. To explain variation in prey response to novel predators, we focus on the interaction between prey use of general versus specifi c cues and responses, and the functional similarity of non-native and native predators. Eff ective antipredator responses reduce predation rates (reduce consumptive eff ects of predators, CEs), but often also carry costs that result in non-consumptive eff ects (NCEs) of predators. We contrast expected CEs versus NCEs for non-native versus native predators, and discuss how diff erences in the relative magnitudes of CEs and NCEs might infl uence invasion dynamics. Going beyond the eff ects of naive prey, we discuss how the ‘naive prey’, ‘enemy release’ and ‘evolution of increased competitive ability’ (EICA) hypotheses are inter-related, and how the importance of all three might be mediated by prey and predator naivete. Th ese ideas hinge on the notion that non-native predators enjoy a ‘novelty advantage’ associated with the naivete of native prey and top predators. However, non-native predators could instead suff er from a novelty disadvantage because they are also naive to their new prey and potential predators. We hypothesize that patterns of community similarity and evolution might explain the variation in novelty advantage that can underlie variation in invasion outcomes. Finally, we discuss management implications of our framework, including suggestions for managing invasive predators, predator reintroductions and biological control.
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TL;DR: Individual endocannabinoids generate distinct analgesic profiles that are either sustained or transitory and associated with agonism and functional antagonism of the brain cannabinoid system, respectively.
Abstract: Prolonged exposure to drugs of abuse, such as cannabinoids and opioids, leads to pharmacological tolerance and receptor desensitization in the nervous system. We found that a similar form of functional antagonism was produced by sustained inactivation of monoacylglycerol lipase (MAGL), the principal degradative enzyme for the endocannabinoid 2-arachidonoylglycerol. After repeated administration, the MAGL inhibitor JZL184 lost its analgesic activity and produced cross-tolerance to cannabinoid receptor (CB1) agonists in mice, effects that were phenocopied by genetic disruption of Mgll (encoding MAGL). Chronic MAGL blockade also caused physical dependence, impaired endocannabinoid-dependent synaptic plasticity and desensitized brain CB1 receptors. These data contrast with blockade of fatty acid amide hydrolase, an enzyme that degrades the other major endocannabinoid anandamide, which produced sustained analgesia without impairing CB1 receptors. Thus, individual endocannabinoids generate distinct analgesic profiles that are either sustained or transitory and associated with agonism and functional antagonism of the brain cannabinoid system, respectively.
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TL;DR: Macrolides have diverse biological activities and an ability to modulate inflammation and immunity in eukaryotes without affecting homeostatic immunity, which led to their long-term use in treating neutrophil-dominated inflammation in diffuse panbronchiolitis, bronchiectasis, rhinosinusitis, and cystic fibrosis.
Abstract: Summary: Macrolides have diverse biological activities and an ability to modulate inflammation and immunity in eukaryotes without affecting homeostatic immunity. These properties have led to their long-term use in treating neutrophil-dominated inflammation in diffuse panbronchiolitis, bronchiectasis, rhinosinusitis, and cystic fibrosis. These immunomodulatory activities appear to be polymodal, but evidence suggests that many of these effects are due to inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and nuclear factor kappa B (NF-κB) activation. Macrolides accumulate within cells, suggesting that they may associate with receptors or carriers responsible for the regulation of cell cycle and immunity. A concern is that long-term use of macrolides increases the emergence of antimicrobial resistance. Nonantimicrobial macrolides are now in development as potential immunomodulatory therapies.
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TL;DR: In this paper, the authors review the latest developments in and properties of transparent conducting oxides (TCO), particularly in relation to thin film transparent electrode applications for LEDs and solar cells.
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Washington University in St. Louis1, Johns Hopkins University2, University of Washington3, Texas Biomedical Research Institute4, Michigan State University5, Virginia Commonwealth University6, Indiana University7, University of Minnesota8, University of Connecticut9, RTI International10, University of Iowa11, University of Bonn12, University at Albany, SUNY13, University of Regensburg14, University of California, San Diego15, Rutgers University16
TL;DR: The dissection of the alcoholism phenotype, to disentangle the influence of comorbid substance-use disorders, will be a next step in identifying genetic variants associated with alcohol dependence.
Abstract: Excessive alcohol consumption is one of the leading causes of preventable death in the United States. Approximately 14% of those who use alcohol meet criteria during their lifetime for alcohol dependence, which is characterized by tolerance, withdrawal, inability to stop drinking, and continued drinking despite serious psychological or physiological problems. We explored genetic influences on alcohol dependence among 1,897 European-American and African-American subjects with alcohol dependence compared with 1,932 unrelated, alcohol-exposed, nondependent controls. Constitutional DNA of each subject was genotyped using the Illumina 1M beadchip. Fifteen SNPs yielded P < 10−5, but in two independent replication series, no SNP passed a replication threshold of P < 0.05. Candidate gene GABRA2, which encodes the GABA receptor α2 subunit, was evaluated independently. Five SNPs at GABRA2 yielded nominal (uncorrected) P < 0.05, with odds ratios between 1.11 and 1.16. Further dissection of the alcoholism phenotype, to disentangle the influence of comorbid substance-use disorders, will be a next step in identifying genetic variants associated with alcohol dependence.
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TL;DR: Lead extraction employing laser sheaths is highly successful with a low procedural complication rate, particularly in the setting of diabetes, renal insufficiency, or body mass index <25 kg/m(2).
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TL;DR: The process of electrospinning is presented and the use of natural polymers in the creation of bioactive ECM analogues in tissue engineering is described, due in part to the enhanced bioactivity afforded by materials normally found within the human body.
Abstract: Natural polymers such as collagens, elastin, and fibrinogen make up much of the body’s native extracellular matrix (ECM). This ECM provides structure and mechanical integrity to tissues, as well as communicating with the cellular components it supports to help facilitate and regulate daily cellular processes and wound healing. An ideal tissue engineering scaffold would not only replicate the structure of this ECM, but would also replicate the many functions that the ECM performs. In the past decade, the process of electrospinning has proven effective in creating non-woven ECM analogue scaffolds of micro to nanoscale diameter fibers from an array of synthetic and natural polymers. The ability of this fabrication technique to utilize the aforementioned natural polymers to create tissue engineering scaffolds has yielded promising results, both in vitro and in vivo , due in part to the enhanced bioactivity afforded by materials normally found within the human body. This review will present the process of electrospinning and describe the use of natural polymers in the creation of bioactive ECM analogues in tissue engineering.
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University of California, San Diego1, University of Basel2, Henry Ford Health System3, Cleveland Clinic4, Wrocław Medical University5, Charité6, Virginia Commonwealth University7, University of California, San Francisco8, University of Otago9, Veterans Health Administration10, National and Kapodistrian University of Athens11, University of Leicester12, University of Maryland, Baltimore13
TL;DR: MR-proANP is as useful as BNP for AHF diagnosis in dyspneic patients and may provide additional clinical utility when BNP is difficult to interpret, and MR-proADM identifies patients with high 90-day mortality risk and adds prognostic value to BNP.
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TL;DR: A review of evi-dence-based research related to employment for individuals with autism spectrum disorder (ASD) can be found in this article, where the authors provide an in depth review of supports needed for success, focusing on job tasks and interpersonal skills needed to foster a positive work experience.
Abstract: Individuals with autism spectrum disorder (ASD) have the ability and desire to work, but there are still several obstructions. Research overwhelmingly demonstrates disappointing employment outcomes for this group. The vast majority is unemployed and for those who do have gainful employment, underemployment is common. The increased prevalence of ASD coupled with unique social, communication, and behavioral characteristics translate into the need for services to help them achieve employment success. Consideration of individual characteristics including strengths, needs, as well as specific interests, coupled with implementation of proper supports can result in successful and ongoing employment. This paper provides a review of evi- dence based research related to employment for individuals with ASD. Specific areas addressed include benefits of employment, state of employment, obstacles to employment, current service options, and an in depth review of supports needed for success. These supports focus not only on job tasks, but also the interpersonal skills needed to foster a positive work experience.
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Veterans Health Administration1, University of California, Irvine2, National Institutes of Health3, Virginia Commonwealth University4, University of Colorado Denver5, University of Texas Southwestern Medical Center6, Saint Louis University7, Carolinas Medical Center8, University of Connecticut9, Harvard University10, University of Washington11, University of Southern California12, University of Michigan13
TL;DR: Patients with advanced chronic hepatitis C who achieved SVR had a marked reduction in death/liver transplantation, and in liver‐related morbidity/mortality, although they remain at risk for HCC.
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TL;DR: In this article, the effects of being outdoors on subjective vitality were investigated using survey, experimental, and diary methods, and it was found that being outdoors was associated with greater vitality, a relation mediated by the presence of natural elements.
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Johns Hopkins University1, University of Washington2, Virginia Commonwealth University3, Medical College of Wisconsin4, University of California, San Diego5, University of Western Ontario6, Mayo Clinic7, Oregon Health & Science University8, University of Ottawa9, National Institutes of Health10, University of Toronto11
TL;DR: Application of an AED in communities is associated with nearly a doubling of survival after out-of-hospital cardiac arrest, and these results reinforce the importance of strategically expanding community-based AED programs.
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TL;DR: Severe, sustained pulmonary hypertension in a very late stage of the Sugen 5416/hypoxia/normoxia-exposed rat is accompanied by the formation of lesions that are indistinguishable from the pulmonary arteriopathy of human pulmonary arterial hypertension.
Abstract: Background— The plexiform lesion is the hallmark of severe pulmonary arterial hypertension. However, its genesis and hemodynamic effects are largely unknown because of the limited availability of lung tissue samples from patients with pulmonary arterial hypertension and the lack of appropriate animal models. This study investigated whether rats with severe progressive pulmonary hypertension developed plexiform lesions. Methods and Results— After a single subcutaneous injection of the vascular endothelial growth factor receptor blocker Sugen 5416, rats were exposed to hypoxia for 3 weeks. They were then returned to normoxia for an additional 10 to 11 weeks. Hemodynamic and histological examinations were performed at 13 to 14 weeks after the Sugen 5416 injection. All rats developed pulmonary hypertension (right ventricular systolic pressure ≈100 mm Hg) and severe pulmonary arteriopathy, including concentric neointimal and complex plexiform-like lesions. There were 2 patterns of complex lesion formation: a l...
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TL;DR: Enhanced visual performance in the deaf is caused by cross-modal reorganization of deaf auditory cortex and it is possible to localize individual visual functions in discrete portions of reorganized auditory cortex.
Abstract: When the brain is deprived of input from one sensory modality, it often compensates with supranormal performance in one or more of the intact sensory systems. In the absence of acoustic input, it has been proposed that cross-modal reorganization of deaf auditory cortex may provide the neural substrate mediating compensatory visual function. We tested this hypothesis using a battery of visual psychophysical tasks and found that congenitally deaf cats, compared with hearing cats, have superior localization in the peripheral field and lower visual movement detection thresholds. In the deaf cats, reversible deactivation of posterior auditory cortex selectively eliminated superior visual localization abilities, whereas deactivation of the dorsal auditory cortex eliminated superior visual motion detection. Our results indicate that enhanced visual performance in the deaf is caused by cross-modal reorganization of deaf auditory cortex and it is possible to localize individual visual functions in discrete portions of reorganized auditory cortex.
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TL;DR: This work developed methods to isolate and characterize short RNAs derived from stalled RNA polymerase II in Drosophila cells, indicating that promoter-proximal stalling is a general feature of early polymerase elongation.
Abstract: Emerging evidence indicates that gene expression in higher organisms is regulated by RNA polymerase II stalling during early transcription elongation. To probe the mechanisms responsible for this regulation, we developed methods to isolate and characterize short RNAs derived from stalled RNA polymerase II in Drosophila cells. Significant levels of these short RNAs were generated from more than one-third of all genes, indicating that promoter-proximal stalling is a general feature of early polymerase elongation. Nucleotide composition of the initially transcribed sequence played an important role in promoting transcriptional stalling by rendering polymerase elongation complexes highly susceptible to backtracking and arrest. These results indicate that the intrinsic efficiency of early elongation can greatly affect gene expression.
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Saint Louis University1, Johns Hopkins University2, University of California, San Francisco3, Cleveland Clinic4, Washington University in St. Louis5, National Institutes of Health6, Virginia Commonwealth University7, Duke University8, Columbia University9, Indiana University – Purdue University Indianapolis10, Virginia Mason Medical Center11
TL;DR: Readily available clinical and laboratory variables can predict advanced fibrosis in adults with NAFLD, but additional information is needed to reliably predict the presence and severity of NASH.
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TL;DR: The International Society on Hypertension in Blacks consensus statement on hypertension management in African American was updated in 2003 as mentioned in this paper, which emphasized effective multidrug regimens and de-emphasized monotherapy.
Abstract: Since the first International Society on Hypertension in Blacks consensus statement on the "Management of High Blood Pressure in African American" in 2003, data from additional clinical trials have become available. We reviewed hypertension and cardiovascular disease prevention and treatment guidelines, pharmacological hypertension clinical end point trials, and blood pressure-lowering trials in blacks. Selected trials without significant black representation were considered. In this update, blacks with hypertension are divided into 2 risk strata, primary prevention, where elevated blood pressure without target organ damage, preclinical cardiovascular disease, or overt cardiovascular disease for whom blood pressure consistently 15/10 mm Hg above target, 2-drug therapy is recommended, with either a calcium channel blocker plus a renin-angiotensin system blocker or, alternatively, in edematous and/or volume-overload states, with a thiazide diuretic plus a renin-angiotensin system blocker. Effective multidrug therapeutic combinations through 4 drugs are described. Comprehensive lifestyle modifications should be initiated in blacks when blood pressure is ≥115/75 mm Hg. The updated International Society on Hypertension in Blacks consensus statement on hypertension management in blacks lowers the minimum target blood pressure level for the lowest-risk blacks, emphasizes effective multidrug regimens, and de-emphasizes monotherapy.
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Hoffmann-La Roche1, Washington University in St. Louis2, University of Utah3, Virginia Commonwealth University4, University of Bonn5, Ludwig Maximilian University of Munich6, Yale University7, University of Texas MD Anderson Cancer Center8, University of Helsinki9, GlaxoSmithKline10, National Institutes of Health11, University of Virginia12, Brown University13, Harvard University14, University of Colorado Boulder15, American Cancer Society16, Wayne State University17, Michigan State University18, National Institute for Health and Welfare19, QIMR Berghofer Medical Research Institute20, University of Mississippi21, Boston University22
TL;DR: This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior, and is the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance.
Abstract: Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values < 10(-35) and < 10(-8) respectively). Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p < 10(-6)). In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p < 10(-20)) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance; these SNPs have previously been associated with mRNA levels of CHRNA5 in brain and lung tissue.
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Boston University1, Howard University2, Thomas Jefferson University3, University of Miami4, Virginia Commonwealth University5, University of North Carolina at Chapel Hill6, Wayne State University7, Georgia Regents University8, Duke University9, National Institutes of Health10, University of Mississippi11, University of California, San Francisco12, University of Illinois at Chicago13, University of Medicine and Dentistry of New Jersey14, Emory University15, Mount Sinai St. Luke's and Mount Sinai Roosevelt16, Children's Hospital Oakland Research Institute17, Case Western Reserve University18, University of Toronto19, Harvard University20, New York Methodist Hospital21, University of Alabama22, University of Pittsburgh23
TL;DR: It is suggested that long‐term use of hydroxyurea is safe and might decrease mortality, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment.
Abstract: A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at alpha = 0.05 level (P-value <0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for <5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality.
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TL;DR: New insights into DDR signaling pathways support the notion that Chk1 represents a core component central to the entire DDR, including direct involvement in DNA repair and apoptotic events in addition to checkpoint regulation.
Abstract: The DNA damage response (DDR) represents a complex network of multiple signaling pathways involving cell cycle checkpoints, DNA repair, transcriptional programs, and apoptosis, through which cells maintain genomic integrity following various endogenous (metabolic) or environmental stresses. In cancer treatment, the DDR occurs in response to various genotoxic insults by diverse cytotoxic agents and radiation, representing an important mechanism limiting chemotherapeutic and radiotherapeutic efficacy. This has prompted the development of agents targeting DDR signaling pathways, particularly checkpoint kinase 1 (Chk1), which contributes to all currently defined cell cycle checkpoints, including G1/S, intra-S-phase, G2/M, and the mitotic spindle checkpoint. Although numerous agents have been developed with the primary goal of enhancing the activity of DNA-damaging agents or radiation, the therapeutic outcome of this strategy remains to be determined. Recently, new insights into DDR signaling pathways support the notion that Chk1 represents a core component central to the entire DDR, including direct involvement in DNA repair and apoptotic events in addition to checkpoint regulation. Together, these new insights into the role of Chk1 in the DDR machinery could provide an opportunity for novel approaches to the development of Chk1 inhibitor strategies.