Showing papers by "University of Vermont published in 2015"
University of Washington1, Stanford University2, University of Minnesota3, Oregon State University4, Royal Swedish Academy of Sciences5, University of East Anglia6, Stockholm University7, World Wide Fund for Nature8, The Nature Conservancy9, Philippine Institute for Development Studies10, Chinese Academy of Sciences11, Council for Scientific and Industrial Research12, University of Vermont13, University of Cambridge14
TL;DR: Why ecosystem service information has yet to fundamentally change decision-making is explored and a path forward is suggested that emphasizes developing solid evidence linking decisions to impacts on natural capital and ecosystem services, and then to human well-being.
Abstract: The central challenge of the 21st century is to develop economic, social, and governance systems capable of ending poverty and achieving sustainable levels of population and consumption while securing the life-support systems underpinning current and future human well-being. Essential to meeting this challenge is the incorporation of natural capital and the ecosystem services it provides into decision-making. We explore progress and crucial gaps at this frontier, reflecting upon the 10 y since the Millennium Ecosystem Assessment. We focus on three key dimensions of progress and ongoing challenges: raising awareness of the interdependence of ecosystems and human well-being, advancing the fundamental interdisciplinary science of ecosystem services, and implementing this science in decisions to restore natural capital and use it sustainably. Awareness of human dependence on nature is at an all-time high, the science of ecosystem services is rapidly advancing, and talk of natural capital is now common from governments to corporate boardrooms. However, successful implementation is still in early stages. We explore why ecosystem service information has yet to fundamentally change decision-making and suggest a path forward that emphasizes: (i) developing solid evidence linking decisions to impacts on natural capital and ecosystem services, and then to human well-being; (ii) working closely with leaders in government, business, and civil society to develop the knowledge, tools, and practices necessary to integrate natural capital and ecosystem services into everyday decision-making; and (iii) reforming institutions to change policy and practices to better align private short-term goals with societal long-term goals.
720 citations
Wageningen University and Research Centre1, Rutgers University2, Spanish National Research Council3, University of Leeds4, Naturalis5, Institut national de la recherche agronomique6, Michigan State University7, University of Freiburg8, University of California, Berkeley9, University of New England (United States)10, University of Vermont11, University of California, Davis12, National University of Singapore13, Hungarian Academy of Sciences14, University of Göttingen15, Cornell University16, Swedish University of Agricultural Sciences17, Stellenbosch University18, Centre national de la recherche scientifique19, Simon Fraser University20, University of Reading21, University of Würzburg22, Plant & Food Research23, University of Giessen24, University of Texas at Austin25, University of Bern26, Hebrew University of Jerusalem27, Lund University28, Federal University of Bahia29
TL;DR: It is shown that, while the contribution of wild bees to crop production is significant, service delivery is restricted to a limited subset of all known bee species, suggesting that cost-effective management strategies to promote crop pollination should target a different set of species than management Strategies to promote threatened bees.
Abstract: There is compelling evidence that more diverse ecosystems deliver greater benefits to people, and these ecosystem services have become a key argument for biodiversity conservation. However, it is unclear how much biodiversity is needed to deliver ecosystem services in a cost-effective way. Here we show that, while the contribution of wild bees to crop production is significant, service delivery is restricted to a limited subset of all known bee species. Across crops, years and biogeographical regions, crop-visiting wild bee communities are dominated by a small number of common species, and threatened species are rarely observed on crops. Dominant crop pollinators persist under agricultural expansion and many are easily enhanced by simple conservation measures, suggesting that cost-effective management strategies to promote crop pollination should target a different set of species than management strategies to promote threatened bees. Conserving the biological diversity of bees therefore requires more than just ecosystem-service-based arguments.
698 citations
Harvard University1, University of South Florida2, University of Washington3, University of British Columbia4, University of Ottawa5, Boston Children's Hospital6, Christiana Care Health System7, University of Minnesota8, University of Vermont9, Washington University in St. Louis10, Food and Drug Administration11, Wayne State University12, University of Pennsylvania13, Englewood Hospital and Medical Center14, Yale University15, Canadian Blood Services16, University of Massachusetts Medical School17, University of Texas Southwestern Medical Center18, Johns Hopkins University19, Children's National Medical Center20
TL;DR: These guidelines were designed to provide pragmatic recommendations, based on the best available published evidence, about when platelet transfusion may be appropriate in adult patients, and provide advice for adult patients who are candidates for platelets transfusion.
Abstract: Platelet transfusions are administered to prevent or treat bleeding in patients with quantitative or qualitative platelet disorders The AABB (formerly, the American Association of Blood Banks) dev
684 citations
Johns Hopkins University1, National Institutes of Health2, University of Texas Medical Branch3, Centers for Disease Control and Prevention4, Creighton University5, United States Department of Agriculture6, Tufts University7, University of Virginia8, Brandeis University9, University of Vermont10, University of Maryland, Baltimore11, Christian Medical College & Hospital12, Veterans Health Administration13, Emory University14, University of Pennsylvania15, University of Georgia16, Murdoch University17, Tufts Medical Center18, University of Washington19, Texas A&M University20
TL;DR: Use of cryptosporidium genomes has helped to identify promising therapeutic targets, and drugs are in development, but methods to assess the efficacy in vitro and in animals are not well standardised.
Abstract: Summary Cryptosporidium spp are well recognised as causes of diarrhoeal disease during waterborne epidemics and in immunocompromised hosts. Studies have also drawn attention to an underestimated global burden and suggest major gaps in optimum diagnosis, treatment, and immunisation. Cryptosporidiosis is increasingly identified as an important cause of morbidity and mortality worldwide. Studies in low-resource settings and high-income countries have confirmed the importance of cryptosporidium as a cause of diarrhoea and childhood malnutrition. Diagnostic tests for cryptosporidium infection are suboptimum, necessitating specialised tests that are often insensitive. Antigen-detection and PCR improve sensitivity, and multiplexed antigen detection and molecular assays are underused. Therapy has some effect in healthy hosts and no proven efficacy in patients with AIDS. Use of cryptosporidium genomes has helped to identify promising therapeutic targets, and drugs are in development, but methods to assess the efficacy in vitro and in animals are not well standardised. Partial immunity after exposure suggests the potential for successful vaccines, and several are in development; however, surrogates of protection are not well defined. Improved methods for propagation and genetic manipulation of the organism would be significant advances.
676 citations
TL;DR: In this paper, the authors discuss how energy justice can serve as a conceptual tool for philosophers and ethicists that better integrates usually distinct distributive and procedural justice concerns, and present a useful decision-making tool that can assist energy planners and consumers in making more informed energy choices.
592 citations
University of Pennsylvania1, University College London2, University of Warwick3, University of Bristol4, McMaster University5, Glenfield Hospital6, University of London7, University of Glasgow8, Utrecht University9, University of Amsterdam10, University of Edinburgh11, University of Leeds12, University of North Carolina at Chapel Hill13, Baylor College of Medicine14, University of Vermont15, University of Texas Health Science Center at Houston16, Harvard University17, University of Washington18, University of Minnesota19, Stanford University20, University of Groningen21, Lund University22, University of Ulm23, University of Oxford24, University of Mississippi25, University of Virginia26, Fred Hutchinson Cancer Research Center27
TL;DR: The genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain.
Abstract: AIMS: To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization. METHODS AND RESULTS: We developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholesterol (LDL-C). For each trait, we constructed two scores. The first was unrestricted, including all independent SNPs associated with the lipid trait identified from a prior meta-analysis (threshold P < 2 × 10(-6)); and the second a restricted score, filtered to remove any SNPs also associated with either of the other two lipid traits at P ≤ 0.01. Mendelian randomization meta-analyses were conducted in 17 studies including 62,199 participants and 12,099 CHD events. Both the unrestricted and restricted allele scores for LDL-C (42 and 19 SNPs, respectively) associated with CHD. For HDL-C, the unrestricted allele score (48 SNPs) was associated with CHD (OR: 0.53; 95% CI: 0.40, 0.70), per 1 mmol/L higher HDL-C, but neither the restricted allele score (19 SNPs; OR: 0.91; 95% CI: 0.42, 1.98) nor the unrestricted HDL-C allele score adjusted for triglycerides, LDL-C, or statin use (OR: 0.81; 95% CI: 0.44, 1.46) showed a robust association. For triglycerides, the unrestricted allele score (67 SNPs) and the restricted allele score (27 SNPs) were both associated with CHD (OR: 1.62; 95% CI: 1.24, 2.11 and 1.61; 95% CI: 1.00, 2.59, respectively) per 1-log unit increment. However, the unrestricted triglyceride score adjusted for HDL-C, LDL-C, and statin use gave an OR for CHD of 1.01 (95% CI: 0.59, 1.75). CONCLUSION: The genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain.
579 citations
University of Ottawa1, University of Calgary2, York University3, University of Reading4, University of Mons5, Helmholtz Centre for Environmental Research - UFZ6, Wildlife Preservation Canada7, University of Vermont8, University of Connecticut9, American Museum of Natural History10, University of Alaska Fairbanks11, United States Department of Agriculture12
TL;DR: Using long-term observations across Europe and North America over 110 years, testing for climate change–related range shifts in bumblebee species across the full extents of their latitudinal and thermal limits and movements along elevation gradients found cross-continentally consistent trends in failures to track warming through time at species’ northern range limits.
Abstract: For many species, geographical ranges are expanding toward the poles in response to climate change, while remaining stable along range edges nearest the equator. Using long-term observations across Europe and North America over 110 years, we tested for climate change–related range shifts in bumblebee species across the full extents of their latitudinal and thermal limits and movements along elevation gradients. We found cross-continentally consistent trends in failures to track warming through time at species’ northern range limits, range losses from southern range limits, and shifts to higher elevations among southern species. These effects are independent of changing land uses or pesticide applications and underscore the need to test for climate impacts at both leading and trailing latitudinal and thermal limits for species.
559 citations
University College London1, University of Glasgow2, University of Cambridge3, Utrecht University4, University of Groningen5, University of Pennsylvania6, University of London7, University of Edinburgh8, Imperial College London9, Jackson State University10, Lithuanian University of Health Sciences11, Jagiellonian University12, Russian Academy13, University of Milan14, Karolinska Institutet15, Translational Genomics Research Institute16, Leiden University17, Memorial Hospital of Rhode Island18, University of Iowa19, University of Oslo20, University of Texas at San Antonio21, Veterans Health Administration22, Cornell University23, University of Sydney24, University of Paris25, Harvard University26, St George's, University of London27, University of Minnesota28, University of Texas Health Science Center at Houston29, University of Washington30, University of Vermont31, GlaxoSmithKline32, Broad Institute33, Children's Hospital Oakland Research Institute34, University of North Carolina at Chapel Hill35, University of Bristol36, Johns Hopkins University37, Cardiff University38, University of Mississippi39, Fred Hutchinson Cancer Research Center40
TL;DR: The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition.
545 citations
Stanford University1, University of Geneva2, VA Palo Alto Healthcare System3, National Institutes of Health4, Douglas Mental Health University Institute5, McGill University6, Heidelberg University7, King's College London8, Trinity College, Dublin9, Université de Montréal10, Commissariat à l'énergie atomique et aux énergies alternatives11, Charité12, University of Vermont13, University of Nottingham14, French Institute of Health and Medical Research15, Paris Descartes University16, University of Toronto17, University of Cambridge18, Dresden University of Technology19, Medical Research Council20, Allen Institute for Brain Science21, Helen Wills Neuroscience Institute22
TL;DR: It is shown that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set.
Abstract: During rest, brain activity is synchronized between different regions widely distributed throughout the brain, forming functional networks. However, the molecular mechanisms supporting functional connectivity remain undefined. We show that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set. The set of 136 genes we identify is significantly enriched for ion channels. Polymorphisms in this set of genes significantly affect resting-state functional connectivity in a large sample of healthy adolescents. Expression levels of these genes are also significantly associated with axonal connectivity in the mouse. The results provide convergent, multimodal evidence that resting-state functional networks correlate with the orchestrated activity of dozens of genes linked to ion channel activity and synaptic function.
536 citations
TL;DR: It is argued that the understanding of biodiversity trends in the Anthropocene is impeded by a failure to consider different types of biodiversity measured at different spatial scales, and it is proposed that ecologists should recognize and assess 15 distinct categories of biodiversity trend.
Abstract: Humans are transforming the biosphere in unprecedented ways, raising the important question of how these impacts are changing biodiversity. Here we argue that our understanding of biodiversity trends in the Anthropocene, and our ability to protect the natural world, is impeded by a failure to consider different types of biodiversity measured at different spatial scales. We propose that ecologists should recognize and assess 15 distinct categories of biodiversity trend. We summarize what is known about each of these 15 categories, identify major gaps in our current knowledge, and recommend the next steps required for better understanding of trends in biodiversity.
526 citations
Harvard University1, Broad Institute2, Washington University in St. Louis3, University of Copenhagen4, University of Milan5, University of Oxford6, University of North Carolina at Chapel Hill7, Fred Hutchinson Cancer Research Center8, University of Verona9, University of Ottawa10, University of Cambridge11, Memorial Hospital of South Bend12, University of Amsterdam13, University of Leicester14, Technische Universität München15, University of Lübeck16, Duke University17, University of Western Ontario18, Heidelberg University19, Medical University of Graz20, Synlab Group21, National Institutes of Health22, University of Pennsylvania23, University of Alabama at Birmingham24, University of Minnesota25, Wake Forest University26, Stanford University27, University of Mississippi28, Karolinska Institutet29, Merck & Co.30, University of Washington31, Group Health Cooperative32, University of Virginia33, University of Vermont34, Boston University35, University of Missouri–Kansas City36, University of Southern California37, Cleveland Clinic38, Ohio State University39, University of Texas Health Science Center at Houston40, University of Michigan41
TL;DR: Kathiresan et al. as mentioned in this paper used exome sequencing of nearly 10,000 people to identify alleles associated with early-onset myocardial infarction; mutations in low-density lipoprotein receptor (LDLR) or apolipoprotein A-V (APOA5) were associated with disease risk.
Abstract: Exome sequence analysis of nearly 10,000 people was carried out to identify alleles associated with early-onset myocardial infarction; mutations in low-density lipoprotein receptor (LDLR) or apolipoprotein A-V (APOA5) were associated with disease risk, identifying the key roles of low-density lipoprotein cholesterol and metabolism of triglyceride-rich lipoproteins. Sekar Kathiresan and colleagues use exome sequencing of nearly 10,000 people to probe the contribution of multiple rare mutations within a gene to risk for myocardial infarction at a population level. They find that mutations in low-density lipoprotein receptor (LDLR) or apolipoprotein A-V (APOA5) are associated with disease risk. When compared with non-carriers, LDLR mutation carriers had higher plasma levels of LDL cholesterol, whereas APOA5 mutation carriers had higher plasma levels of triglycerides. As well as confirming that APOA5 is a myocardial infarction gene, this work informs the design and conduct of rare-variant association studies for complex diseases. Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance1,2. When MI occurs early in life, genetic inheritance is a major component to risk1. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families3,4,5,6,7,8, whereas common variants at more than 45 loci have been associated with MI risk in the population9,10,11,12,13,14,15. Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (≤50 years in males and ≤60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol16. Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol > 190 mg dl−1. At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase15,17 and apolipoprotein C-III (refs 18, 19). Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk.
University of Washington1, Fred Hutchinson Cancer Research Center2, Oregon Health & Science University3, University of Vermont4, The Dartmouth Institute for Health Policy and Clinical Practice5, Dartmouth College6, Providence Health & Services7, Stanford University8, Beth Israel Deaconess Medical Center9, Harvard University10, University of Toronto11
TL;DR: In this study of pathologists, in which diagnostic interpretation was based on a single breast biopsy slide, overall agreement between the individual pathologists' interpretations and the expert consensus-derived reference diagnoses was 75.3%, with the highest level of concordance for invasive carcinoma and lower levels of concords for DCIS and atypia.
Abstract: Importance A breast pathology diagnosis provides the basis for clinical treatment and management decisions; however, its accuracy is inadequately understood. Objectives To quantify the magnitude of diagnostic disagreement among pathologists compared with a consensus panel reference diagnosis and to evaluate associated patient and pathologist characteristics. Design, Setting, and Participants Study of pathologists who interpret breast biopsies in clinical practices in 8 US states. Exposures Participants independently interpreted slides between November 2011 and May 2014 from test sets of 60 breast biopsies (240 total cases, 1 slide per case), including 23 cases of invasive breast cancer, 73 ductal carcinoma in situ (DCIS), 72 with atypical hyperplasia (atypia), and 72 benign cases without atypia. Participants were blinded to the interpretations of other study pathologists and consensus panel members. Among the 3 consensus panel members, unanimous agreement of their independent diagnoses was 75%, and concordance with the consensus-derived reference diagnoses was 90.3%. Main Outcomes and Measures The proportions of diagnoses overinterpreted and underinterpreted relative to the consensus-derived reference diagnoses were assessed. Results Sixty-five percent of invited, responding pathologists were eligible and consented to participate. Of these, 91% (N = 115) completed the study, providing 6900 individual case diagnoses. Compared with the consensus-derived reference diagnosis, the overall concordance rate of diagnostic interpretations of participating pathologists was 75.3% (95% CI, 73.4%-77.0%; 5194 of 6900 interpretations). Among invasive carcinoma cases (663 interpretations), 96% (95% CI, 94%-97%) were concordant, and 4% (95% CI, 3%-6%) were underinterpreted; among DCIS cases (2097 interpretations), 84% (95% CI, 82%-86%) were concordant, 3% (95% CI, 2%-4%) were overinterpreted, and 13% (95% CI, 12%-15%) were underinterpreted; among atypia cases (2070 interpretations), 48% (95% CI, 44%-52%) were concordant, 17% (95% CI, 15%-21%) were overinterpreted, and 35% (95% CI, 31%-39%) were underinterpreted; and among benign cases without atypia (2070 interpretations), 87% (95% CI, 85%-89%) were concordant and 13% (95% CI, 11%-15%) were overinterpreted. Disagreement with the reference diagnosis was statistically significantly higher among biopsies from women with higher (n = 122) vs lower (n = 118) breast density on prior mammograms (overall concordance rate, 73% [95% CI, 71%-75%] for higher vs 77% [95% CI, 75%-80%] for lower,P Conclusions and Relevance In this study of pathologists, in which diagnostic interpretation was based on a single breast biopsy slide, overall agreement between the individual pathologists’ interpretations and the expert consensus–derived reference diagnoses was 75.3%, with the highest level of concordance for invasive carcinoma and lower levels of concordance for DCIS and atypia. Further research is needed to understand the relationship of these findings with patient management.
Marjolein J. Peters1, Roby Joehanes2, Luke C. Pilling3, Claudia Schurmann4 +155 more•Institutions (46)
TL;DR: Differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index and the transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models.
Abstract: Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.
TL;DR: In this article, the authors apply new approaches and tools for quantifying biodiversity and ecosystem services (BES) in 20 pilot demonstrations and find that applying a BES approach is most effective in leading to policy change as part of an iterative science-policy process.
Memorial Sloan Kettering Cancer Center1, City of Hope National Medical Center2, University of South Florida3, University of Vermont4, University of California, San Francisco5, MedStar Washington Hospital Center6, St. Joseph Hospital7, Washington University in St. Louis8, University of California, Irvine9, University of Nebraska Medical Center10, Oregon Health & Science University11, University of Chicago12, Cleveland Clinic13
TL;DR: Delivery of mFOLFOX6 after chemoradiation and before total mesorectal excision has the potential to increase the proportion of patients eligible for less invasive treatment strategies; this strategy is being tested in phase 3 clinical trials.
Abstract: Summary Background Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiation have an improved prognosis. The need for surgery in these patients has been questioned, but the proportion of patients achieving a pathological complete response is small. We aimed to assess whether adding cycles of mFOLFOX6 between chemoradiation and surgery increased the proportion of patients achieving a pathological complete response. Methods We did a phase 2, non-randomised trial consisting of four sequential study groups of patients with stage II–III locally advanced rectal cancer at 17 institutions in the USA and Canada. All patients received chemoradiation (fluorouracil 225 mg/m 2 per day by continuous infusion throughout radiotherapy, and 45·0 Gy in 25 fractions, 5 days per week for 5 weeks, followed by a minimum boost of 5·4 Gy). Patients in group 1 had total mesorectal excision 6–8 weeks after chemoradiation. Patients in groups 2–4 received two, four, or six cycles of mFOLFOX6, respectively, between chemoradiation and total mesorectal excision. Each cycle of mFOLFOX6 consisted of racemic leucovorin 200 mg/m 2 or 400 mg/m 2 , according to the discretion of the treating investigator, oxaliplatin 85 mg/m 2 in a 2-h infusion, bolus fluorouracil 400 mg/m 2 on day 1, and a 46-h infusion of fluorouracil 2400 mg/m 2 . The primary endpoint was the proportion of patients who achieved a pathological complete response, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00335816. Findings Between March 24, 2004, and Nov 16, 2012, 292 patients were registered, 259 of whom (60 in group 1, 67 in group 2, 67 in group 3, and 65 in group 4) met criteria for analysis. 11 (18%, 95% CI 10–30) of 60 patients in group 1, 17 (25%, 16–37) of 67 in group 2, 20 (30%, 19–42) of 67 in group 3, and 25 (38%, 27–51) of 65 in group 4 achieved a pathological complete response (p=0·0036). Study group was independently associated with pathological complete response (group 4 compared with group 1 odds ratio 3·49, 95% CI 1·39–8·75; p=0·011). In group 2, two (3%) of 67 patients had grade 3 adverse events associated with the neoadjuvant administration of mFOLFOX6 and one (1%) had a grade 4 adverse event; in group 3, 12 (18%) of 67 patients had grade 3 adverse events; in group 4, 18 (28%) of 65 patients had grade 3 adverse events and five (8%) had grade 4 adverse events. The most common grade 3 or higher adverse events associated with the neoadjuvant administration of mFOLFOX6 across groups 2–4 were neutropenia (five in group 3 and six in group 4) and lymphopenia (three in group 3 and four in group 4). Across all study groups, 25 grade 3 or worse surgery-related complications occurred (ten in group 1, five in group 2, three in group 3, and seven in group 4); the most common were pelvic abscesses (seven patients) and anastomotic leaks (seven patients). Interpretation Delivery of mFOLFOX6 after chemoradiation and before total mesorectal excision has the potential to increase the proportion of patients eligible for less invasive treatment strategies; this strategy is being tested in phase 3 clinical trials. Funding National Institutes of Health National Cancer Institute.
University of Edinburgh1, University of Colorado Boulder2, National Ecological Observatory Network3, Woods Hole Oceanographic Institution4, University of Greifswald5, University of Copenhagen6, University of Alaska Fairbanks7, University of Vermont8, University of Oxford9, Norwegian University of Science and Technology10, Université du Québec11, Aarhus University12, St. John's University13, University of Victoria14, University of Bonn15, Adam Mickiewicz University in Poznań16, Texas A&M University17, Norwegian Polar Institute18, University of Zurich19, University of Basel20, University of Alberta21, Université de Sherbrooke22
TL;DR: In this article, the authors analyzed circumpolar data from 37 Arctic and alpine sites in 9 countries, including 25 species, and ∼42,000 annual growth records from 1,821 individuals, and demonstrated that the sensitivity of shrub growth to climate was heterogeneous, with European sites showing greater summer temperature sensitivity than North American sites, and higher at sites with greater soil moisture and for taller shrubs (for example, alders and willows) growing at their northern or upper elevational range edges.
Abstract: Rapid climate warming has been linked to increasing shrub dominance in the Arctic tundra. Research now shows that climate–shrub growth relationships vary spatially and according to site characteristics such as soil moisture and shrub height. Rapid climate warming in the tundra biome has been linked to increasing shrub dominance1,2,3,4. Shrub expansion can modify climate by altering surface albedo, energy and water balance, and permafrost2,5,6,7,8, yet the drivers of shrub growth remain poorly understood. Dendroecological data consisting of multi-decadal time series of annual shrub growth provide an underused resource to explore climate–growth relationships. Here, we analyse circumpolar data from 37 Arctic and alpine sites in 9 countries, including 25 species, and ∼42,000 annual growth records from 1,821 individuals. Our analyses demonstrate that the sensitivity of shrub growth to climate was: (1) heterogeneous, with European sites showing greater summer temperature sensitivity than North American sites, and (2) higher at sites with greater soil moisture and for taller shrubs (for example, alders and willows) growing at their northern or upper elevational range edges. Across latitude, climate sensitivity of growth was greatest at the boundary between the Low and High Arctic, where permafrost is thawing4 and most of the global permafrost soil carbon pool is stored9. The observed variation in climate–shrub growth relationships should be incorporated into Earth system models to improve future projections of climate change impacts across the tundra biome.
TL;DR: In this article, the authors determined whether patients with heart failure and a preserved ejection fraction (HFpEF) have an increase in passive myocardial stiffness and the extent to which discovered changes depend on changes in extracellular matrix fibrillar collagen and cardiomyocyte titin.
Abstract: Background—The purpose of this study was to determine whether patients with heart failure and a preserved ejection fraction (HFpEF) have an increase in passive myocardial stiffness and the extent to which discovered changes depend on changes in extracellular matrix fibrillar collagen and cardiomyocyte titin. Methods and Results—Seventy patients undergoing coronary artery bypass grafting underwent an echocardiogram, plasma biomarker determination, and intraoperative left ventricular epicardial anterior wall biopsy. Patients were divided into 3 groups: referent control (n=17, no hypertension or diabetes mellitus), hypertension (HTN) without (–) HFpEF (n=31), and HTN with (+) HFpEF (n=22). One or more of the following studies were performed on the biopsies: passive stiffness measurements to determine total, collagen-dependent and titin-dependent stiffness (differential extraction assay), collagen assays (biochemistry or histology), or titin isoform and phosphorylation assays. In comparison with controls, pat...
The Chinese University of Hong Kong1, Utrecht University2, Sahlgrenska University Hospital3, University of Gothenburg4, Washington University in St. Louis5, University of Hong Kong6, Université de Montréal7, University of California, San Diego8, Boston Children's Hospital9, University of Vermont10, University of Iowa11, Nottingham University Hospitals NHS Trust12
TL;DR: Both the prevention of AIS and the treatment of its direct underlying cause are not possible, because the definite aetiology and aetiopathogenetic mechanisms that underlie AIS are still unclear.
Abstract: Adolescent idiopathic scoliosis (AIS) is the most common form of structural spinal deformities that have a radiological lateral Cobb angle - a measure of spinal curvature - of ≥10(°). AIS affects between 1% and 4% of adolescents in the early stages of puberty and is more common in young women than in young men. The condition occurs in otherwise healthy individuals and currently has no recognizable cause. In the past few decades, considerable progress has been made towards understanding the clinical patterns and the three-dimensional pathoanatomy of AIS. Advances in biomechanics and technology and their clinical application, supported by limited evidence-based research, have led to improvements in the safety and outcomes of surgical and non-surgical treatments. However, the definite aetiology and aetiopathogenetic mechanisms that underlie AIS are still unclear. Thus, at present, both the prevention of AIS and the treatment of its direct underlying cause are not possible.
TL;DR: Patients with heart failure and a preserved ejection fraction who received isosorbide mononitrate were less active and did not have better quality of life or submaximal exercise capacity than did patients who received placebo.
Abstract: BackgroundNitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients. MethodsIn this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks. The primary end point was the daily activity level, quantified as the average daily accelerometer units during the 120-mg phase, as assessed by patient-worn accelerometers. Secondary end points included hours of activity per day during the 120-mg phase, daily accelerometer units during all three dose regimens, quality-of-life scores, 6-minute walk distance, and levels of N-terminal pro–brain natriuretic peptide (NT-proBNP). ResultsIn the group receiving the ...
National Institutes of Health1, University of Vermont2, University of North Carolina at Chapel Hill3, Cincinnati Children's Hospital Medical Center4, New York University5, Michigan State University6, University of California, San Francisco7, University of Wisconsin-Madison8, Baylor College of Medicine9, Yale University10, University of Missouri11, University of Kansas12, Washington State University13, Harvard University14
TL;DR: Leaders gathered at the US National Institutes of Health in November 2014 to discuss recent advances and emerging research areas in aspects of maternal-fetal immunity that may affect fetal development and pregnancy success.
Abstract: Leaders gathered at the US National Institutes of Health in November 2014 to discuss recent advances and emerging research areas in aspects of maternal-fetal immunity that may affect fetal development and pregnancy success.
Northern Kentucky University1, Boise State University2, Arizona State University3, Chinese Academy of Sciences4, North Carolina State University5, United States Forest Service6, University of Vermont7, University of California, Santa Barbara8, Ohio University9, Florida International University10, University of California, Los Angeles11, University of Utah12, University of Washington13, University of California, Davis14
TL;DR: It is suggested that a suite of variables, including income, contribute to the distribution of UTC cover, and can help target simultaneous strategies for UTC goals and environmental justice concerns.
Abstract: This study examines the distributional equity of urban tree canopy (UTC) cover for Baltimore, MD, Los Angeles, CA, New York, NY, Philadelphia, PA, Raleigh, NC, Sacramento, CA, and Washington, D.C. using high spatial resolution land cover data and census data. Data are analyzed at the Census Block Group levels using Spearman’s correlation, ordinary least squares regression (OLS), and a spatial autoregressive model (SAR). Across all cities there is a strong positive correlation between UTC cover and median household income. Negative correlations between race and UTC cover exist in bivariate models for some cities, but they are generally not observed using multivariate regressions that include additional variables on income, education, and housing age. SAR models result in higher r-square values compared to the OLS models across all cities, suggesting that spatial autocorrelation is an important feature of our data. Similarities among cities can be found based on shared characteristics of climate, race/ethnicity, and size. Our findings suggest that a suite of variables, including income, contribute to the distribution of UTC cover. These findings can help target simultaneous strategies for UTC goals and environmental justice concerns.
Utrecht University1, University of Alberta2, University of Vermont3, Institut national de la recherche scientifique4, Laval University5, University of Helsinki6, Université de Montréal7, University of Stirling8, Instituto Superior Técnico9, University of Michigan10, University of Copenhagen11, Umeå University12, Université du Québec à Chicoutimi13, University of Alaska Fairbanks14, United States Geological Survey15
TL;DR: In this article, the effects of permafrost thaw on lakes and streams in the Arctic were explored, where the authors explored the effect of both thermokarst (thawing and collapse of ice-rich permaculture) and deepening of the active layer (the surface soil layer that thaws and refreezes each year).
Abstract: . The Arctic is a water-rich region, with freshwater systems covering about 16 % of the northern permafrost landscape. Permafrost thaw creates new freshwater ecosystems, while at the same time modifying the existing lakes, streams, and rivers that are impacted by thaw. Here, we describe the current state of knowledge regarding how permafrost thaw affects lentic (still) and lotic (moving) systems, exploring the effects of both thermokarst (thawing and collapse of ice-rich permafrost) and deepening of the active layer (the surface soil layer that thaws and refreezes each year). Within thermokarst, we further differentiate between the effects of thermokarst in lowland areas vs. that on hillslopes. For almost all of the processes that we explore, the effects of thaw vary regionally, and between lake and stream systems. Much of this regional variation is caused by differences in ground ice content, topography, soil type, and permafrost coverage. Together, these modifying factors determine (i) the degree to which permafrost thaw manifests as thermokarst, (ii) whether thermokarst leads to slumping or the formation of thermokarst lakes, and (iii) the manner in which constituent delivery to freshwater systems is altered by thaw. Differences in thaw-enabled constituent delivery can be considerable, with these modifying factors determining, for example, the balance between delivery of particulate vs. dissolved constituents, and inorganic vs. organic materials. Changes in the composition of thaw-impacted waters, coupled with changes in lake morphology, can strongly affect the physical and optical properties of thermokarst lakes. The ecology of thaw-impacted lakes and streams is also likely to change; these systems have unique microbiological communities, and show differences in respiration, primary production, and food web structure that are largely driven by differences in sediment, dissolved organic matter, and nutrient delivery. The degree to which thaw enables the delivery of dissolved vs. particulate organic matter, coupled with the composition of that organic matter and the morphology and stratification characteristics of recipient systems will play an important role in determining the balance between the release of organic matter as greenhouse gases (CO2 and CH4), its burial in sediments, and its loss downstream. The magnitude of thaw impacts on northern aquatic ecosystems is increasing, as is the prevalence of thaw-impacted lakes and streams. There is therefore an urgent need to quantify how permafrost thaw is affecting aquatic ecosystems across diverse Arctic landscapes, and the implications of this change for further climate warming.
TL;DR: PARN and RTEL1 genes explain ∼7% of familial pulmonary fibrosis and strengthen the link between lung Fibrosis and telomere dysfunction.
Abstract: Idiopathic pulmonary fibrosis (IPF) is an age-related disease featuring progressive lung scarring. To elucidate the molecular basis of IPF, we performed exome sequencing of familial kindreds with pulmonary fibrosis. Gene burden analysis comparing 78 European cases and 2,816 controls implicated PARN, an exoribonuclease with no previous connection to telomere biology or disease, with five new heterozygous damaging mutations in unrelated cases and none in controls (P = 1.3 × 10(-8)); mutations were shared by all affected relatives (odds in favor of linkage = 4,096:1). RTEL1, an established locus for dyskeratosis congenita, harbored significantly more new damaging and missense variants at conserved residues in cases than in controls (P = 1.6 × 10(-6)). PARN and RTEL1 mutation carriers had shortened leukocyte telomere lengths, and we observed epigenetic inheritance of short telomeres in family members. Together, these genes explain ~7% of familial pulmonary fibrosis and strengthen the link between lung fibrosis and telomere dysfunction.
TL;DR: The mammalian genome encodes 28 distinct members of the transient receptor potential (TRP) superfamily of cation channels, which exhibit varying degrees of selectivity for different ionic species, including sensory perception and signal transduction.
Abstract: The mammalian genome encodes 28 distinct members of the transient receptor potential (TRP) superfamily of cation channels, which exhibit varying degrees of selectivity for different ionic species. Multiple TRP channels are present in all cells and are involved in diverse aspects of cellular function, including sensory perception and signal transduction. Notably, TRP channels are involved in regulating vascular function and pathophysiology, the focus of this review. TRP channels in vascular smooth muscle cells participate in regulating contractility and proliferation, whereas endothelial TRP channel activity is an important contributor to endothelium-dependent vasodilation, vascular wall permeability, and angiogenesis. TRP channels are also present in perivascular sensory neurons and astrocytic endfeet proximal to cerebral arterioles, where they participate in the regulation of vascular tone. Almost all of these functions are mediated by changes in global intracellular Ca2+ levels or subcellular Ca2+ signaling events. In addition to directly mediating Ca2+ entry, TRP channels influence intracellular Ca2+ dynamics through membrane depolarization associated with the influx of cations or through receptor- or store-operated mechanisms. Dysregulation of TRP channels is associated with vascular-related pathologies, including hypertension, neointimal injury, ischemia-reperfusion injury, pulmonary edema, and neurogenic inflammation. In this review, we briefly consider general aspects of TRP channel biology and provide an in-depth discussion of the functions of TRP channels in vascular smooth muscle cells, endothelial cells, and perivascular cells under normal and pathophysiological conditions.
TL;DR: In this crossover comparison between HBP and BiVP, HBP was found to effect an equivalent CRT response, suggesting this approach may be feasible in more patients with left bundle branch block than previously assumed.
Northwestern University1, University of Chicago2, University of Oxford3, University of Warwick4, Hammersmith Hospital5, Broad Institute6, University of Utah7, National and Kapodistrian University of Athens8, Aristotle University of Thessaloniki9, Cedars-Sinai Medical Center10, Georgia Regents University11, Medical College of Wisconsin12, Texas Biomedical Research Institute13, Karolinska Institutet14, Pennsylvania State University15, University of Colorado Denver16, Duke University17, Stanford University18, University of Pennsylvania19, University of Alabama20, University of Texas Health Science Center at San Antonio21, University of Texas Southwestern Medical Center22, Baylor College of Medicine23, University of Vermont24, University of Michigan25, Wayne State University26, National Institutes of Health27, University of Pittsburgh28, University of California, San Francisco29, University of Virginia30, Yale University31, Virginia Commonwealth University32, Rutgers University33, State University of New York Upstate Medical University34, Carolinas Medical Center35
TL;DR: Common genetic susceptibility loci in European ancestry women for the National Institutes of Health PCOS phenotype are identified, which confers the highest risk for metabolic morbidities, as well as reproductive hormone levels, and implicate neuroendocrine changes in disease pathogenesis.
Abstract: Polycystic ovary syndrome (PCOS) is a common, highly heritable complex disorder of unknown aetiology characterized by hyperandrogenism, chronic anovulation and defects in glucose homeostasis. Increased luteinizing hormone relative to follicle-stimulating hormone secretion, insulin resistance and developmental exposure to androgens are hypothesized to play a causal role in PCOS. Here we map common genetic susceptibility loci in European ancestry women for the National Institutes of Health PCOS phenotype, which confers the highest risk for metabolic morbidities, as well as reproductive hormone levels. Three loci reach genome-wide significance in the case–control meta-analysis, two novel loci mapping to chr 8p32.1 and chr 11p14.1, and a chr 9q22.32 locus previously found in Chinese PCOS. The same chr 11p14.1 SNP, rs11031006, in the region of the follicle-stimulating hormone B polypeptide (FSHB) gene strongly associates with PCOS diagnosis and luteinizing hormone levels. These findings implicate neuroendocrine changes in disease pathogenesis.
College of American Pathologists1, Harvard University2, University of Central Florida3, University of California, Los Angeles4, Emory University5, Cleveland Clinic6, University of Vermont7, Stanford University8, Washington University in St. Louis9, Mayo Clinic10, University of North Carolina at Chapel Hill11, University of Utah12
TL;DR: This report describes the important issues considered by the CAP committee during the development of the new checklist requirements, which address documentation, validation, quality assurance, confirmatory testing, exception logs, monitoring of upgrades, variant interpretation and reporting, incidental findings, data storage, version traceability and data transfer confidentiality.
Abstract: Context.— The higher throughput and lower per-base cost of next-generation sequencing (NGS) as compared to Sanger sequencing has led to its rapid adoption in clinical testing. The number of laborat...
TL;DR: Using human evaluation of 100,000 words spread across 24 corpora in 10 languages diverse in origin and culture, evidence of a deep imprint of human sociality in language is presented, observing that the words of natural human language possess a universal positivity bias.
Abstract: Using human evaluation of 100,000 words spread across 24 corpora in 10 languages diverse in origin and culture, we present evidence of a deep imprint of human sociality in language, observing that (i) the words of natural human language possess a universal positivity bias, (ii) the estimated emotional content of words is consistent between languages under translation, and (iii) this positivity bias is strongly independent of frequency of word use. Alongside these general regularities, we describe interlanguage variations in the emotional spectrum of languages that allow us to rank corpora. We also show how our word evaluations can be used to construct physical-like instruments for both real-time and offline measurement of the emotional content of large-scale texts.
TL;DR: More studies are needed to understand how changes in morphology and resistance-related traits arising from domestication may interact with environmental variation to affect species interactions across multiple scales in agroecosystems and natural ecosystems.
Abstract: Crop domestication is the process of artificially selecting plants to increase their suitability to human requirements: taste, yield, storage, and cultivation practices. There is increasing evidence that crop domestication can profoundly alter interactions among plants, herbivores, and their natural enemies. Overall, little is known about how these interactions are affected by domestication in the geographical ranges where these crops originate, where they are sympatric with the ancestral plant and share the associated arthropod community. In general, domestication consistently has reduced chemical resistance against herbivorous insects, improving herbivore and natural enemy performance on crop plants. More studies are needed to understand how changes in morphology and resistance-related traits arising from domestication may interact with environmental variation to affect species interactions across multiple scales in agroecosystems and natural ecosystems.
Memorial Sloan Kettering Cancer Center1, Mayo Clinic2, Oregon Health & Science University3, Vanderbilt University Medical Center4, University of Vermont5, Tampa General Hospital6, University of Pittsburgh7, John Muir Health8, University of California, Irvine9, Holy Family Hospital10, Brigham and Women's Hospital11
TL;DR: The data suggest that nCRT followed by LE may be considered as an organ-preserving alternative in carefully selected patients with clinically-staged T2N0 tumours who refuse, or are not candidates for, transabdominal resection.
Abstract: Summary Background Local excision is an organ-preserving treatment alternative to transabdominal resection for patients with stage I rectal cancer. However, local excision alone is associated with a high risk of local recurrence and inferior survival compared with transabdominal rectal resection. We investigated the oncological and functional outcomes of neoadjuvant chemoradiotherapy and local excision for patients with stage T2N0 rectal cancer. Methods We did a multi-institutional, single-arm, open-label, non-randomised, phase 2 trial of patients with clinically staged T2N0 distal rectal cancer treated with neoadjuvant chemoradiotherapy at 26 American College of Surgeons Oncology Group institutions. Patients with clinical T2N0 rectal adenocarcinoma staged by endorectal ultrasound or endorectal coil MRI, measuring less than 4 cm in greatest diameter, involving less than 40% of the circumference of the rectum, located within 8 cm of the anal verge, and with an Eastern Cooperative Oncology Group performance status of at least 2 were included in the study. Neoadjuvant chemoradiotherapy consisted of capecitabine (original dose 825 mg/m 2 twice daily on days 1–14 and 22–35), oxaliplatin (50 mg/m 2 on weeks 1, 2, 4, and 5), and radiation (5 days a week at 1·8 Gy per day for 5 weeks to a dose of 45 Gy, followed by a boost of 9 Gy, for a total dose of 54 Gy) followed by local excision. Because of adverse events during chemoradiotherapy, the dose of capecitabine was reduced to 725 mg/m 2 twice-daily, 5 days per week, for 5 weeks, and the boost of radiation was reduced to 5·4 Gy, for a total dose of 50·4 Gy. The primary endpoint was 3-year disease-free survival for all eligible patients (intention-to-treat population) and for patients who completed chemotherapy and radiation, and had ypT0, ypT1, or ypT2 tumours, and negative resection margins (per-protocol group). This study is registered with ClinicalTrials.gov, number NCT00114231. Findings Between May 25, 2006, and Oct 22, 2009, 79 eligible patients were recruited to the trial and started neoadjuvant chemoradiotherapy. Two patients had no surgery and one had a total mesorectal excision. Four additional patients completed protocol treatment, but one had a positive margin and three had ypT3 tumours. Thus, the per-protocol population consisted of 72 patients. Median follow-up was 56 months (IQR 46–63) for all patients. The estimated 3-year disease-free survival for the intention-to-treat group was 88·2% (95% CI 81·3–95·8), and for the per-protocol group was 86·9% (79·3–95·3). Of 79 eligible patients, 23 (29%) had grade 3 gastrointestinal adverse events, 12 (15%) had grade 3–4 pain, and 12 (15%) had grade 3–4 haematological adverse events during chemoradiation. Of the 77 patients who had surgery, six (8%) had grade 3 pain, three (4%) had grade 3–4 haemorrhage, and three (4%) had gastrointestinal adverse events. Interpretation Although the observed 3-year disease free survival was not as high as anticipated, our data suggest that neoadjuvant chemoradiotherapy followed by local excision might be considered as an organ-preserving alternative in carefully selected patients with clinically staged T2N0 tumours who refuse, or are not candidates for, transabdominal resection. Funding National Cancer Institute and Sanofi-Aventis.