Showing papers by "University of Vermont published in 2011"
TL;DR: Among patients with acute decompensated heart failure, there were no significant differences in patients' global assessment of symptoms or in the change in renal function when diuretic therapy was administered by bolus as compared with continuous infusion or at a high dose asCompared with a low dose.
Abstract: Among patients with acute decompensated heart failure, there were no significant differences in patients’ global assessment of symptoms or in the change in renal function when diuretic therapy was administered by bolus as compared with continuous infusion or at a high dose as compared with a low dose. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00577135.)
1,261 citations
Université de Sherbrooke1, University of Alberta2, University of Lapland3, University of Victoria4, Wageningen University and Research Centre5, University of Alaska Fairbanks6, University of Oxford7, Université du Québec à Trois-Rivières8, Laval University9, St. John's University10, University of Amsterdam11, University of Vermont12, Aarhus University13, University of Zurich14, Swiss Federal Institute for Forest, Snow and Landscape Research15, University of Edinburgh16, La Trobe University17, Woods Hole Oceanographic Institution18, Lamont–Doherty Earth Observatory19, University of British Columbia20, University of Tromsø21, University of Alaska Anchorage22, Queen's University23, University of Virginia24
TL;DR: This article used repeat photography, long-term ecological monitoring and dendrochronology to document shrub expansion in arctic, high-latitude and alpine tundra.
Abstract: Recent research using repeat photography, long-term ecological monitoring and dendrochronology has documented shrub expansion in arctic, high-latitude and alpine tundra
1,153 citations
TL;DR: The standard of care (SOC) therapy for patients with chronic hepatitis C virus (HCV) infection has been the use of both peginterferon (PegIFN) and ribavirin (RBV) as mentioned in this paper.
1,117 citations
Institute of Ecosystem Studies1, University of California, Davis2, United States Forest Service3, Arizona State University4, Ohio State University5, Chesapeake Biological Laboratory6, The New School7, University of Missouri8, Johns Hopkins University9, University of Vermont10, University of Massachusetts Amherst11
TL;DR: The state factor approach is used to highlight the role of important aspects of climate, substrate, organisms, relief, and time in differentiating urban from non-urban areas, and for determining heterogeneity within spatially extensive metropolitan areas.
903 citations
TL;DR: Examination of expressions made on the online, global microblog and social networking service Twitter is examined, uncovering and explaining temporal variations in happiness and information levels over timescales ranging from hours to years.
Abstract: Individual happiness is a fundamental societal metric. Normally measured through self-report, happiness has often been indirectly characterized and overshadowed by more readily quantifiable economic indicators such as gross domestic product. Here, we examine expressions made on the online, global microblog and social networking service Twitter, uncovering and explaining temporal variations in happiness and information levels over timescales ranging from hours to years. Our data set comprises over 46 billion words contained in nearly 4.6 billion expressions posted over a 33 month span by over 63 million unique users. In measuring happiness, we construct a tunable, real-time, remote-sensing, and non-invasive, text-based hedonometer. In building our metric, made available with this paper, we conducted a survey to obtain happiness evaluations of over 10,000 individual words, representing a tenfold size improvement over similar existing word sets. Rather than being ad hoc, our word list is chosen solely by frequency of usage, and we show how a highly robust and tunable metric can be constructed and defended.
761 citations
TL;DR: Data suggest that perturbations in the PACAP–PAC1 pathway are involved in abnormal stress responses underlying PTSD, and sex-specific effects may occur via oestrogen regulation of ADCYAP1R1.
Abstract: Pituitary adenylate cyclase-activating polypeptide (PACAP) is known to broadly regulate the cellular stress response. In contrast, it is unclear if the PACAP-PAC1 receptor pathway has a role in human psychological stress responses, such as post-traumatic stress disorder (PTSD). Here we find, in heavily traumatized subjects, a sex-specific association of PACAP blood levels with fear physiology, PTSD diagnosis and symptoms in females. We examined 44 single nucleotide polymorphisms (SNPs) spanning the PACAP (encoded by ADCYAP1) and PAC1 (encoded by ADCYAP1R1) genes, demonstrating a sex-specific association with PTSD. A single SNP in a putative oestrogen response element within ADCYAP1R1, rs2267735, predicts PTSD diagnosis and symptoms in females only. This SNP also associates with fear discrimination and with ADCYAP1R1 messenger RNA expression in human brain. Methylation of ADCYAP1R1 in peripheral blood is also associated with PTSD. Complementing these human data, ADCYAP1R1 mRNA is induced with fear conditioning or oestrogen replacement in rodent models. These data suggest that perturbations in the PACAP-PAC1 pathway are involved in abnormal stress responses underlying PTSD. These sex-specific effects may occur via oestrogen regulation of ADCYAP1R1. PACAP levels and ADCYAP1R1 SNPs may serve as useful biomarkers to further our mechanistic understanding of PTSD.
694 citations
TL;DR: In this community-based sample, few adults in 1987 to 1989 had ideal cardiovascular health by the new American Heart Association definition, indicating that nationwide primordial prevention efforts at the population and individual levels will need to redouble.
647 citations
TL;DR: Evidence is presented that suggests M can adopt two conformations and that membrane curvature is regulated by one M conformer, providing insight into how M protein functions to promote virus assembly.
617 citations
University of Cambridge1, University College London2, McGill University3, University of Leicester4, University of Bristol5, University of Copenhagen6, University of London7, Copenhagen University Hospital8, University of Queensland9, University of Washington10, University of Vermont11, Sir Charles Gairdner Hospital12, University of Western Australia13, Ontario Institute for Cancer Research14, University of Würzburg15, ETH Zurich16, University of Edinburgh17, University of Warwick18, Utrecht University19, National Heart Foundation of Australia20, Boston University21, University of Kiel22, University of Lübeck23, University Hospital Regensburg24, King's College London25, Mario Negri Institute for Pharmacological Research26, Wake Forest University27, Karolinska Institutet28, University of Leeds29, Harvard University30, Group Health Cooperative31, McMaster University32, University of Oxford33, University of Glasgow34, Imperial College London35, Medical University of Graz36, University of Ulm37, Goethe University Frankfurt38, Lund University39, Helmholtz Zentrum München40, Robert Koch Institute41, Ludwig Maximilian University of Munich42, Umeå University43, University of Pennsylvania44, Johns Hopkins University45, Clinical Trial Service Unit46, Aga Khan University Hospital47, Robertson Centre for Biostatistics48, Tufts University49, University of Bonn50, Erasmus University Rotterdam51, Karolinska University Hospital52, University of Groningen53, Northwestern University54, University of California, Los Angeles55, Glasgow Royal Infirmary56, Glasgow Clinical Research Facility57
TL;DR: Human genetic data indicate that C reactive protein concentration itself is unlikely to be even a modest causal factor in coronary heart disease.
Abstract: Objective To use genetic variants as unconfounded proxies of C reactive protein concentration to study its causal role in coronary heart disease. Design Mendelian randomisation meta-analysis of ind ...
583 citations
TL;DR: Platelets provide a procoagulant surface facilitating amplification of cancer‐related coagulation, and can be recruited to shroud tumor cells, thereby shielding them from immune responses, and facilitate cancer growth and dissemination.
568 citations
TL;DR: Intraoperative blood transfusions is associated with a higher risk of mortality and morbidity in surgical patients with severe anemia, and it is unknown whether this association is due to the adverse effects of blood transfusion or is, instead, the result of increased blood loss in the patients receiving blood.
Abstract: Background: The impact of intraoperative erythrocyte transfusiononoutcomesofanemicpatientsundergoingnoncardiacsurgeryhasnotbeenwellcharacterized.Theobjective of this study was to examine the association between blood transfusion and mortality and morbidity in patients with severeanemia(hematocritlessthan30%)whoareexposedto one or two units of erythrocytes intraoperatively. Methods: Thiswasaretrospectiveanalysisoftheassociationof blood transfusion and 30-day mortality and 30-day morbidity in 10,100 patients undergoing general, vascular, or orthopedic surgery. We estimated separate multivariate logistic regression models for 30-day mortality and for 30-day complications. Results: Intraoperative blood transfusion was associated with an increased risk of death (odds ratio [OR], 1.29; 95% CI, 1.03–1.62). Patients receiving an intraoperative transfusion were more likely to have pulmonary, septic, wound, or thromboembolic complications, compared with patients not receiving an intraoperative transfusion. Compared with patients who were not transfused, patients receiving one or two units of erythrocytes were more likely to have pulmonary complications (OR, 1.76; 95% CI, 1.48–2.09), sepsis (OR, 1.43; 95% CI, 1.21–1.68), thromboembolic complications (OR, 1.77; 95% CI, 1.32–2.38), and wound complications (OR, 1.87; 95% CI, 1.47–2.37). Conclusions: Intraoperative blood transfusion is associated with a higher risk of mortality and morbidity in surgical patients with severe anemia. It is unknown whether this association is due to the adverse effects of blood transfusion or is, instead, the result of increased blood loss in the patients receiving blood.
TL;DR: Preterm neonates initially managed with either n CPAP or PS with rapid extubation to nCPAP had similar clinical outcomes to those treated with PS followed by a period of mechanical ventilation, suggesting an approach that uses early nCP AP leads to a reduction in the number of infants who are intubated and given surfactant.
Abstract: OBJECTIVE: We designed a multicenter randomized trial to compare 3 approaches to the initial respiratory management of preterm neonates: prophylactic surfactant followed by a period of mechanical ventilation (prophylactic surfactant [PS]); prophylactic surfactant with rapid extubation to bubble nasal continuous positive airway pressure (intubate-surfactant-extubate [ISX]) or initial management with bubble continuous positive airway pressure and selective surfactant treatment (nCPAP). DESIGN/METHODS: Neonates born at 26 0 7 to 29 6 7 weeks9 gestation were enrolled at participating Vermont Oxford Network centers and randomly assigned to PS, ISX, or nCPAP groups before delivery. Primary outcome was the incidence of death or bronchopulmonary dysplasia (BPD) at 36 weeks9 postmenstrual age. RESULTS: 648 infants enrolled at 27 centers. The study was halted before the desired sample size was reached because of declining enrollment. When compared with the PS group, the relative risk of BPD or death was 0.78 (95% confidence interval: 0.59–1.03) for the ISX group and 0.83 (95% confidence interval: 0.64–1.09) for the nCPAP group. There were no statistically significant differences in mortality or other complications of prematurity. In the nCPAP group, 48% were managed without intubation and ventilation, and 54% without surfactant treatment. CONCLUSIONS: Preterm neonates were initially managed with either nCPAP or PS with rapid extubation to nCPAP had similar clinical outcomes to those treated with PS followed by a period of mechanical ventilation. An approach that uses early nCPAP leads to a reduction in the number of infants who are intubated and given surfactant.
TL;DR: This work provides national estimates of stroke incidence by race and region, contrasting these to publicly available stroke mortality data.
Abstract: Stroke mortality rates declined dramatically in the 20th century, yielding 1 of the top 10 public health achievements of that era.1 Despite this, rates have remained consistently higher among blacks than any other race/ethnic group in the United States.2–5 This disparity in stroke mortality is largest at younger ages; at age 45 years, the mortality rate is 3 times higher for blacks than whites, with a decreasing racial disparity with increasing age: by age 85 years the difference is no longer apparent.2–4,6 There are also substantial geographic disparities in stroke mortality with higher rates in the southeastern United States, termed the “stroke belt.” First identified in 1965, excess stroke mortality rates in this region have existed since at least 1940 and have persisted.6–8 A 153-county region including the coastal plain of North Carolina, South Carolina, and Georgia is referred to as the “stroke buckle” due to even higher stroke mortality than the rest of the stroke belt.9 Because the stroke belt and buckle contain counties with very high stroke mortality rates and counties with average or even low stroke mortality, the overall stroke mortality is approximately 20% higher in the stroke belt than rest of the nation, with rates in the stroke buckle approximately 40% higher than rest of the nation.6–9
In the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS), the black-white disparity in stroke mortality was primarily due to higher stroke incidence among blacks, with little contribution of case fatality, the other potential contributor to disparities in stroke mortality.10 National racial and geographic disparities in stroke mortality are documented based on death certificates through the national vital statistics system. National data on stroke incidence based on validated stroke events are not available. The goal of this report was to describe black-white and geographic differences in stroke incidence in a national population-based cohort and assess if the pattern and magnitude of stroke incidence rates mirror the disparities in stroke mortality.
TL;DR: Occult metastases were an independent prognostic variable in patients with sentinel nodes that were negative on initial examination; however, the magnitude of the difference in outcome at 5 years was small, and these data do not indicate a clinical benefit of additional evaluation, including immunohistochemical analysis, of initially negative sentinel node in Patients with breast cancer.
Abstract: BackgroundRetrospective and observational analyses suggest that occult lymph-node metastases are an important prognostic factor for disease recurrence or survival among patients with breast cancer. Prospective data on clinical outcomes from randomized trials according to sentinel-node involvement have been lacking. MethodsWe randomly assigned women with breast cancer to sentinel-lymph-node biopsy plus axillary dissection or sentinel-lymph-node biopsy alone. Paraffin-embedded tissue blocks of sentinel lymph nodes obtained from patients with pathologically negative sentinel lymph nodes were centrally evaluated for occult metastases deeper in the blocks. Both routine staining and immunohistochemical staining for cytokeratin were used at two widely spaced additional tissue levels. Treating physicians were unaware of the findings, which were not used for clinical treatment decisions. The initial evaluation at participating sites was designed to detect all macrometastases larger than 2 mm in the greatest dimens...
Vanderbilt University1, Shizuoka University2, Arizona State University3, University of Oxford4, University of Gothenburg5, Pierre-and-Marie-Curie University6, Imperial College London7, McMaster University8, Institute of Science and Technology Austria9, University of Groningen10, Aarhus University11, University of Maryland, College Park12, University of Colorado Boulder13, University of California, Irvine14, University of Exeter15, University of Lausanne16, University of New Mexico17, University of Cambridge18, Australian National University19, University of Houston20, University of Edinburgh21, University of California, Santa Barbara22, Princeton University23, University of Chicago24, Montana State University25, Simon Fraser University26, Villanova University27, Queen's University28, Cornell University29, University of Louisville30, United States Department of Agriculture31, École Normale Supérieure32, University of Sussex33, Ludwig Maximilian University of Munich34, University of Kentucky35, Flinders University36, Michigan State University37, Georgia Institute of Technology38, University of California, Davis39, Pennsylvania State University40, University of Toronto41, University of Sheffield42, University of Regensburg43, University of Helsinki44, University of Vermont45, VU University Amsterdam46, University of Osnabrück47, Harvard University48, Swiss Federal Institute of Aquatic Science and Technology49, University of Copenhagen50, Royal Holloway, University of London51, University of California, Santa Cruz52, University of Arizona53, University of Oklahoma54, University of Texas at Austin55, University of Strasbourg56, University of Bristol57, University of Liverpool58, University of North Carolina at Chapel Hill59, Rice University60, University of Zurich61, University College London62, Newcastle University63, James Cook University64, University of Montpellier65, University of North Carolina at Greensboro66, University of California, Riverside67, ETH Zurich68, University of St Andrews69, William Paterson University70, University of Michigan71, University of Illinois at Urbana–Champaign72, University of Bern73, University of Western Ontario74, University of California, Berkeley75, University of the Ryukyus76, University of Florence77, University of Tennessee78, North Carolina State University79, Humboldt University of Berlin80, Katholieke Universiteit Leuven81, Smithsonian Institution82, University of Nevada, Reno83, San Francisco State University84
TL;DR: It is argued that inclusive fitness theory has been of little value in explained the natural world, and that it has led to negligible progress in explaining the evolution of eusociality, but these arguments are based upon a misunderstanding of evolutionary theory and a misrepresentation of the empirical literature.
Abstract: Arising from M. A. Nowak, C. E. Tarnita & E. O. Wilson 466, 1057-1062 (2010); Nowak et al. reply. Nowak et al. argue that inclusive fitness theory has been of little value in explaining the natural world, and that it has led to negligible progress in explaining the evolution of eusociality. However, we believe that their arguments are based upon a misunderstanding of evolutionary theory and a misrepresentation of the empirical literature. We will focus our comments on three general issues.
TL;DR: Weight loss has dichotomous effects on airway physiology and T-cell function typically involved in the pathogenesis of asthma, suggesting that obesity produces a unique phenotype of asthma that will require a distinct therapeutic approach.
Abstract: Background Asthma in obese subjects is poorly understood, and these patients are often refractory to standard therapy. Objectives We sought to gain insights into the pathogenesis and treatment of asthma in obese subjects by determining how obesity and bariatric surgery affect asthma control, airway hyperresponsiveness (AHR), and markers of asthmatic inflammation. Methods We performed a prospective study of (1) asthmatic and nonasthmatic patients undergoing bariatric surgery compared at baseline and (2) asthmatic patients followed for 12 months after bariatric surgery. Results We studied 23 asthmatic and 21 nonasthmatic patients undergoing bariatric surgery. At baseline, asthmatic patients had lower FEV 1 and forced vital capacity and lower numbers of lymphocytes in bronchoalveolar lavage fluid. After surgery, asthmatic participants experienced significant improvements in asthma control (asthma control score, 1.55 to 0.74; P P 20 , 3.9 to 7.28, P = .03). There was a statistically significant interaction between IgE status and change in airways responsiveness ( P for interaction = .01). The proportion of lymphocytes in bronchoalveolar lavage fluid and the production of cytokines from activated peripheral blood CD4 + T cells increased significantly. Conclusions Bariatric surgery improves AHR in obese asthmatic patients with normal serum IgE levels. Weight loss has dichotomous effects on airway physiology and T-cell function typically involved in the pathogenesis of asthma, suggesting that obesity produces a unique phenotype of asthma that will require a distinct therapeutic approach.
TL;DR: This work estimates that the life cycle effects of coal and the waste stream generated are costing the U.S. public a third to over one‐half of a trillion dollars annually, and conservatively doubles to triples the price of electricity from coal per kWh generated, making wind, solar, and other forms of nonfossil fuel power generation, along with investments in efficiency and electricity conservation methods, economically competitive.
Abstract: Each stage in the life cycle of coal-extraction, transport, processing, and combustion-generates a waste stream and carries multiple hazards for health and the environment. These costs are external to the coal industry and are thus often considered "externalities." We estimate that the life cycle effects of coal and the waste stream generated are costing the U.S. public a third to over one-half of a trillion dollars annually. Many of these so-called externalities are, moreover, cumulative. Accounting for the damages conservatively doubles to triples the price of electricity from coal per kWh generated, making wind, solar, and other forms of nonfossil fuel power generation, along with investments in efficiency and electricity conservation methods, economically competitive. We focus on Appalachia, though coal is mined in other regions of the United States and is burned throughout the world.
TL;DR: In this article, β-catenin levels control tumor differentiation and regulate both MAPK/Erk and PI3K/Akt signaling in melanoma, which is a central mediator of melanoma metastasis to lymph nodes and lungs.
TL;DR: It is suggested that key methodologic and contextual issues have contributed to this state of affairs and a major shift is proposed to produce research with more rapid clinical, public health, and policy impact.
Université de Montréal1, Harvard University2, Broad Institute3, University of Southern California4, Boston University5, University of the West Indies6, Wake Forest University7, Johns Hopkins University8, University of Mississippi9, University of Minnesota10, University of Texas Health Science Center at Houston11, National Institutes of Health12, Cleveland Clinic13, University of Washington14, Group Health Cooperative15, University of Pennsylvania16, Case Western Reserve University17, University of Pittsburgh18, University of Virginia19, Cedars-Sinai Medical Center20, Tougaloo College21, Jackson State University22, University of Vermont23, Veterans Health Administration24
TL;DR: It is suggested that no major loci uniquely explain the high prevalence of CHD in African Americans, and resources and methods that address both admixture- and SNP-association to maximize power for genetic discovery in even larger African-American consortia are developed.
Abstract: Coronary heart disease (CHD) is the leading cause of mortality in African Americans. To identify common genetic polymorphisms associated with CHD and its risk factors (LDL- and HDL-cholesterol (LDL-C and HDL-C), hypertension, smoking, and type-2 diabetes) in individuals of African ancestry, we performed a genome-wide association study (GWAS) in 8,090 African Americans from five population-based cohorts. We replicated 17 loci previously associated with CHD or its risk factors in Caucasians. For five of these regions (CHD: CDKN2A/CDKN2B; HDL-C: FADS1-3, PLTP, LPL, and ABCA1), we could leverage the distinct linkage disequilibrium (LD) patterns in African Americans to identify DNA polymorphisms more strongly associated with the phenotypes than the previously reported index SNPs found in Caucasian populations. We also developed a new approach for association testing in admixed populations that uses allelic and local ancestry variation. Using this method, we discovered several loci that would have been missed using the basic allelic and global ancestry information only. Our conclusions suggest that no major loci uniquely explain the high prevalence of CHD in African Americans. Our project has developed resources and methods that address both admixture- and SNP-association to maximize power for genetic discovery in even larger African-American consortia.
TL;DR: In this article, a spatially explicit agent-based vehicle consumer choice model is developed to explore sensitivities and nonlinear interactions between various potential influences on plug-in hybrid vehicle (PHEV) market penetration.
TL;DR: The most significant association with adult asthma is observed at rs404860 in the major histocompatiblity complex region, which is close to rs2070600, a SNP previously reported for association with FEV1/FVC in genome-wide association studies for lung function.
Abstract: Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors. Through a genome-wide association study and a replication study consisting of a total of 7,171 individuals with adult asthma (cases) and 27,912 controls in the Japanese population, we identified five loci associated with susceptibility to adult asthma. In addition to the major histocompatibility complex and TSLP-WDR36 loci previously reported, we identified three additional loci: a USP38-GAB1 locus on chromosome 4q31 (combined P = 1.87 × 10(-12)), a locus on chromosome 10p14 (P = 1.79 × 10(-15)) and a gene-rich region on chromosome 12q13 (P = 2.33 × 10(-13)). We observed the most significant association with adult asthma at rs404860 in the major histocompatiblity complex region (P = 4.07 × 10(-23)), which is close to rs2070600, a SNP previously reported for association with FEV(1)/FVC in genome-wide association studies for lung function. Our findings offer a better understanding of the genetic contribution to asthma susceptibility.
TL;DR: CMV (and/or other herpesvirus) replication is a significant cause of immune activation in HIV-infected individuals with incomplete antiretroviral therapy-mediated CD4(+) T cell recovery, and trends were significant even among those with undetectable plasma HIV RNA levels.
Abstract: Background. Elevated immune activation persists during treated human immunodeficiency virus (HIV) infection and is associated with blunted CD4 recovery and premature mortality, but its causes remain incompletely characterized. We hypothesized that asymptomatic cytomegalovirus (CMV) replication might contribute to immune activation in this setting. Methods. Thirty antiretroviral therapy‐treated HIV-infected CMV-seropositive participants with CD4 counts ,350 cells/mm 3 were randomized to receive valganciclovir 900 mg daily or placebo for 8 weeks, followed by an additional 4-week observation period. The primary outcome was the week 8 change in percentage of activated (CD38 1 HLA-DR 1 ) CD8 1 T cells. Results. Fourteen participants were randomized to valganciclovir and 16 to placebo. Most participants (21 [70%] of 30) had plasma HIV RNA levels ,75 copies/mL. The median CD4 count was 190 (IQR: 134‐232) cells/ mm 3 , and 12 (40%) of 30 had detectable CMV DNA in saliva, plasma, or semen at baseline. CMV DNA continued to be detectable at weeks 4‐12 in 7 (44%) of 16 placebo-treated participants, but in none of the valganciclovir-treated participants (P 5 .007). Valganciclovir-treated participants had significantly greater reductions in CD8 activation at weeks 8 (P 5 .03) and 12 (P 5 .02) than did placebo-treated participants. These trends were significant even among those with undetectable plasma HIV RNA levels. Conclusions. CMV (and/or other herpesvirus) replication is a significant cause of immune activation in HIVinfected individuals with incomplete antiretroviral therapy‐mediated CD4 1 T cell recovery.
TL;DR: This review highlights recent targeted approaches towards improving microbial tolerance to next-generation biofuels with a particular emphasis on strategies that will improve production.
Abstract: A major challenge when using microorganisms to produce bulk chemicals such as biofuels is that the production targets are often toxic to cells. Many biofuels are known to reduce cell viability through damage to the cell membrane and interference with essential physiological processes. Therefore, cells must trade off biofuel production and survival, reducing potential yields. Recently, there have been several efforts towards engineering strains for biofuel tolerance. Promising methods include engineering biofuel export systems, heat shock proteins, membrane modifications, more general stress responses, and approaches that integrate multiple tolerance strategies. In addition, in situ recovery methods and media supplements can help to ease the burden of end-product toxicity and may be used in combination with genetic approaches. Recent advances in systems and synthetic biology provide a framework for tolerance engineering. This review highlights recent targeted approaches towards improving microbial tolerance to next-generation biofuels with a particular emphasis on strategies that will improve production.
TL;DR: Overall, cancer detection with digital or film-screen mammography is similar in U.S. women aged 50 to 79 years undergoing screening mammography; women aged 40 to 49 years are more likely to have extremely dense breasts and estrogen receptor-negative tumors; if they are offered mammography screening, they may choose to undergo digital mammography to optimize cancer detection.
Abstract: Few studies have examined the comparative effectiveness of digital versus film-screen mammography in U.S. community practice. In a large sample of women screened in community settings, digital and ...
TL;DR: These data weakly corroborate prior findings of associations between LTL and mortality in the elderly and suggest increased age and male gender were associated with shorter LTLs, and African Americans had significantly longer L TLs independent of age and sex.
Abstract: TELOMERE shortening has been intrinsically linked to cell division and is a key determinant of replicative senescence of cultured somatic cells (1,2). Leukocyte telomere length (LTL) and its age-dependent shortening, that is LTL dynamics, have been the focus of intense investigations. LTL has been reported to be associated with age (3,4), gender (5,6), and many age-related diseases (7–14) as well as measures of general health (15,16). Several studies have evaluated associations between LTL and mortality with conflicting results; some observing that LTL was inversely related to mortality (17,18,20–24), whereas others have not (16,19,25,26). In addition, the mechanistic connection between LTL and mortality is an enigma and a number of problems have been cited in epidemiological studies (27,28). The question remains whether LTL is an index of aging and longevity or if its dynamics, which may mirror the kinetics of the hematopoietic stem cells (29), are actively engaged in determining end-of-life or age-related pathology (27,30).
The Cardiovascular Health Study (CHS) provides the opportunity to evaluate the association between survival and LTL using a large cohort of adults aged 65 years and older (31). In addition to providing a large sample size, the CHS has been well characterized in terms of health status and incident cardiovascular disease. All participants have been followed to ascertain death and classified by trained clinicians for specific cause of death (32). Over the last several years, LTL was measured in a subset of CHS participants. In this article, we have utilized mortality and other data collected in the CHS to answer the following questions: (a) Is LTL associated with total mortality in adults aged 65 years and older? (b) Do associations between LTL and mortality differ by cause of death? (c) Are associations modified by factors including age, sex, race, or other variables?
TL;DR: The aim of this study was to compare the efficacy and safety of once‐daily human glucagon‐like peptide‐1 analogue liraglutide with dipeptidyl peptidase‐4 inhibitor sitagliptin, each added to metformin, over 52 weeks in individuals with type 2 diabetes.
Abstract: Summary
Aim: The aim of this study was to compare the efficacy and safety of once-daily human glucagon-like peptide-1 analogue liraglutide with dipeptidyl peptidase-4 inhibitor sitagliptin, each added to metformin, over 52 weeks in individuals with type 2 diabetes.
Methods: In an open-label, parallel-group trial, metformin-treated participants were randomised to liraglutide 1.2 mg/day (n = 225), liraglutide 1.8 mg/day (n = 221) or sitagliptin 100 mg/day (n = 219) for 26 weeks (main phase). Participants continued the same treatment in a 26-week extension.
Results: Liraglutide (1.2 or 1.8 mg) was superior to sitagliptin for reducing HbA1c from baseline (8.4–8.5%) to 52 weeks: −1.29% and −1.51% vs. −0.88% respectively. Estimated mean treatment differences between liraglutide and sitagliptin were as follows: −0.40% (95% confidence interval −0.59 to −0.22) for 1.2 mg and −0.63% (−0.81 to −0.44) for 1.8 mg (both p < 0.0001). Weight loss was greater with liraglutide 1.2 mg (−2.78 kg) and 1.8 mg (−3.68 kg) than sitagliptin (−1.16 kg) (both p < 0.0001). Diabetes Treatment Satisfaction Questionnaire scores increased significantly more with liraglutide 1.8 mg than with sitagliptin (p = 0.03). Proportions of participants reporting adverse events were generally comparable; minor hypoglycaemia was 8.1%, 8.3% and 6.4% for liraglutide 1.2 mg, 1.8 mg and sitagliptin respectively. Gastrointestinal side effects, mainly nausea, initially occurred more frequently with liraglutide, but declined after several weeks.
Conclusion: Liraglutide provides greater sustained glycaemic control and body weight reduction over 52 weeks. Treatment satisfaction was significantly greater with 1.8 mg liraglutide, similar to 26-week results. The safety profiles of liraglutide and sitagliptin are consistent with previous reports.
TL;DR: Thoracolumbar fascia shear strain was reduced in the LBP group compared with the No-LBP group and this reduction of shear plane motion may be due to abnormal trunk movement patterns and/or intrinsic connective tissue pathology.
Abstract: The role played by the thoracolumbar fascia in chronic low back pain (LBP) is poorly understood. The thoracolumbar fascia is composed of dense connective tissue layers separated by layers of loose connective tissue that normally allow the dense layers to glide past one another during trunk motion. The goal of this study was to quantify shear plane motion within the thoracolumbar fascia using ultrasound elasticity imaging in human subjects with and without chronic low back pain (LBP). We tested 121 human subjects, 50 without LBP and 71 with LBP of greater than 12 months duration. In each subject, an ultrasound cine-recording was acquired on the right and left sides of the back during passive trunk flexion using a motorized articulated table with the hinge point of the table at L4-5 and the ultrasound probe located longitudinally 2 cm lateral to the midline at the level of the L2-3 interspace. Tissue displacement within the thoracolumbar fascia was calculated using cross correlation techniques and shear strain was derived from this displacement data. Additional measures included standard range of motion and physical performance evaluations as well as ultrasound measurement of perimuscular connective tissue thickness and echogenicity. Thoracolumbar fascia shear strain was reduced in the LBP group compared with the No-LBP group (56.4% ± 3.1% vs. 70.2% ± 3.6% respectively, p < .01). There was no evidence that this difference was sex-specific (group by sex interaction p = .09), although overall, males had significantly lower shear strain than females (p = .02). Significant correlations were found in male subjects between thoracolumbar fascia shear strain and the following variables: perimuscular connective tissue thickness (r = -0.45, p <.001), echogenicity (r = -0.28, p < .05), trunk flexion range of motion (r = 0.36, p < .01), trunk extension range of motion (r = 0.41, p < .01), repeated forward bend task duration (r = -0.54, p < .0001) and repeated sit-to-stand task duration (r = -0.45, p < .001). Thoracolumbar fascia shear strain was ~20% lower in human subjects with chronic low back pain. This reduction of shear plane motion may be due to abnormal trunk movement patterns and/or intrinsic connective tissue pathology. There appears to be some sex-related differences in thoracolumbar fascia shear strain that may also play a role in altered connective tissue function.
TL;DR: In patients with a first unprovoked venous thromboembolism, men have a 2.2-fold higher risk of recurrent venousThromboEmbolism than do women, and the risk of recurrence remains 1.8-foldHigher in men after adjustment for previous hormone associated venous Thrombo Embolism in women.
Abstract: Objective To determine the effect of sex on the risk of recurrent venous thromboembolism in all patients and in patients with venous thromboembolism that was unprovoked or provoked (by non-hormonal factors).
Data source Comprehensive search of electronic databases (Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials) until July 2010, supplemented by review of conference abstracts and contact with content experts.
Study selection Seven prospective studies investigating an association between D-dimer, measured after anticoagulation was stopped, and disease recurrence in patients with venous thromboembolism.
Data extraction Patient level databases were obtained, transferred to a central database, checked, and completed with further information provided by authors.
Data synthesis 2554 patients with a first venous thromboembolism had follow-up for a mean of 27.1 (SD 19.6) months. The one year incidence of recurrent venous thromboembolism was 5.3% (95% confidence interval 4.1% to 6.7%) in women and 9.5% (7.9% to 11.4%) in men, and the three year incidence of recurrence was 9.1% (7.3% to 11.3%) in women and 19.7% (16.5% to 23.4%) in men. Among patients with unprovoked venous thromboembolism, men had a higher risk of recurrence than did women (hazard ratio 2.2, 95% confidence interval 1.7 to 2.8). After adjustment for women with hormone associated initial venous thromboembolism, the risk of recurrence remained higher in men (hazard ratio 1.8, 1.4 to 2.5). In patients with provoked venous thromboembolism, occurring after exposure to a major risk factor, recurrence of disease did not differ between men and women (hazard ratio 1.2, 0.6 to 2.4). In women with hormone associated venous thromboembolism and no other risk factors, recurrence was lower than that in women with unprovoked venous thromboembolism and no previous hormone use (hazard ratio 0.5, 0.3 to 0.8).
Conclusion In patients with a first unprovoked venous thromboembolism, men have a 2.2-fold higher risk of recurrent venous thromboembolism than do women, which remained 1.8-fold higher in men after adjustment for previous hormone associated venous thromboembolism in women. In patients with a first provoked venous thromboembolism, risk of recurrence does not differ between men and women with or without hormone associated venous thromboembolism. Indefinite anticoagulation may be given greater consideration in men than in women after a first venous thromboembolism.
TL;DR: The experiments demonstrated a clear ABA renewal effect, a recovery of extinguished responding when conditioning, extinction, and testing occurred in contexts A, B, and A, respectively, and demonstrated ABC renewal and, for the first time in operant conditioning, AAB renewal, indicating that operant extinction is relatively specific to the context in which it is learned.
Abstract: Four experiments were performed to explore the role of context in operant extinction. In all experiments, leverpressing in rats was first reinforced with food pellets on a variable interval 30-s schedule, then extinguished, and finally tested in the same and a different physical context. The experiments demonstrated a clear ABA renewal effect, a recovery of extinguished responding when conditioning, extinction, and testing occurred in contexts A, B, and A, respectively. They also demonstrated ABC renewal (where conditioning extinction and testing occurred in contexts A, B, and C) and, for the first time in operant conditioning, AAB renewal (where conditioning, extinction, and testing occurred in contexts A, A, and B). The latter two phenomena indicate that tests outside the extinction context are sufficient to cause a recovery of extinguished operant behavior and, thus, that operant extinction, like Pavlovian extinction, is relatively specific to the context in which it is learned. AAB renewal was not weakened by tripling the amount of extinction training. ABA renewal was stronger than AAB, but not merely because of context A’s direct association with the reinforcer.