Showing papers by "McGill University published in 2009"
TL;DR: This 5-year evaluation provides strong evidence that the classification of complications is valid and applicable worldwide in many fields of surgery, and subjective, inaccurate, or confusing terms such as “minor or major” should be removed from the surgical literature.
Abstract: Background and Aims:The lack of consensus on how to define and grade adverse postoperative events has greatly hampered the evaluation of surgical procedures. A new classification of complications, initiated in 1992, was updated 5 years ago. It is based on the type of therapy needed to correct the co
7,537 citations
TL;DR: Findings translate previous results from rat to humans and suggest a common effect of parental care on the epigenetic regulation of hippocampal glucocorticoid receptor expression.
Abstract: Maternal care influences hypothalamic-pituitary-adrenal (HPA) function in the rat through epigenetic programming of glucocorticoid receptor expression. In humans, childhood abuse alters HPA stress responses and increases the risk of suicide. We examined epigenetic differences in a neuron-specific glucocorticoid receptor (NR3C1) promoter between postmortem hippocampus obtained from suicide victims with a history of childhood abuse and those from either suicide victims with no childhood abuse or controls. We found decreased levels of glucocorticoid receptor mRNA, as well as mRNA transcripts bearing the glucocorticoid receptor 1F splice variant and increased cytosine methylation of an NR3C1 promoter. Patch-methylated NR3C1 promoter constructs that mimicked the methylation state in samples from abused suicide victims showed decreased NGFI-A transcription factor binding and NGFI-A–inducible gene transcription. These findings translate previous results from rat to humans and suggest a common effect of parental care on the epigenetic regulation of hippocampal glucocorticoid receptor expression.
3,087 citations
TL;DR: Recent advances in understanding of the molecular structures and biochemical functions of the translation initiation machinery are described and key strategies that mediate general or gene-specific translational control are summarized, particularly in mammalian systems.
2,899 citations
TL;DR: This work over the past several years to form carbon-carbon bonds directly from two different C-H bonds under oxidative conditions, cross-dehydrogenative coupling (CDC) is described, which provides an alternative to the separate steps of prefunctionalization and defunctionsalization that have traditionally been part of synthetic design.
Abstract: Synthetic chemists aspire both to develop novel chemical reactions and to improve reaction conditions to maximize resource efficiency, energy efficiency, product selectivity, operational simplicity, and environmental health and safety. Carbon−carbon bond formation is a central part of many chemical syntheses, and innovations in these types of reactions will profoundly improve overall synthetic efficiency. This Account describes our work over the past several years to form carbon−carbon bonds directly from two different C−H bonds under oxidative conditions, cross-dehydrogenative coupling (CDC). We have focused most of our efforts on carbon−carbon bonds formed via the functionalization of sp3 C−H bonds with other C−H bonds. In the presence of simple and cheap catalysts such as copper and iron salts and oxidants such as hydrogen peroxide, dioxygen, tert-butylhydroperoxide, and 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), we can directly functionalize various sp3 C−H bonds by other C−H bonds without requiring ...
2,308 citations
Columbia University1, University of Oxford2, Nathan Kline Institute for Psychiatric Research3, New York University4, University College London5, University of Pennsylvania6, University of California, Los Angeles7, University of Iowa8, McGill University9, French Institute of Health and Medical Research10, French Institute for Research in Computer Science and Automation11, John Radcliffe Hospital12, Imperial College London13, Mauna Kea Technologies14
TL;DR: This study is the largest evaluation of nonlinear deformation algorithms applied to brain image registration ever conducted and suggests that the findings are generalizable to new subject populations that are labeled or evaluated using different labeling protocols.
2,214 citations
TL;DR: A typology of relationships between ecosystem services based on the role of drivers and the interactions between services is proposed to help drive ecological science towards a better understanding of the relationships among multiple ecosystem services.
Abstract: Ecosystem management that attempts to maximize the production of one ecosystem service often results in substantial declines in the provision of other ecosystem services. For this reason, recent studies have called for increased attention to development of a theoretical understanding behind the relationships among ecosystem services. Here, we review the literature on ecosystem services and propose a typology of relationships between ecosystem services based on the role of drivers and the interactions between services. We use this typology to develop three propositions to help drive ecological science towards a better understanding of the relationships among multiple ecosystem services. Research which aims to understand the relationships among multiple ecosystem services and the mechanisms behind these relationships will improve our ability to sustainably manage landscapes to provide multiple ecosystem services.
1,836 citations
TL;DR: The results suggest that viral eradication might be achieved through the combined use of strategic interventions targeting viral replication and drugs that interfere with the self renewal and persistence of proliferating memory T cells.
Abstract: HIV persists in a reservoir of latently infected CD4+ T cells in individuals treated with highly active antiretroviral therapy (HAART). Here we identify central memory (TCM) and transitional memory (TTM) CD4+ T cells as the major cellular reservoirs for HIV and find that viral persistence is ensured by two different mechanisms. HIV primarily persists in TCM cells in subjects showing reconstitution of the CD4+ compartment upon HAART. This reservoir is maintained through T cell survival and low-level antigen-driven proliferation and is slowly depleted with time. In contrast, proviral DNA is preferentially detected in TTM cells from aviremic individuals with low CD4+ counts and higher amounts of interleukin-7–mediated homeostatic proliferation, a mechanism that ensures the persistence of these cells. Our results suggest that viral eradication might be achieved through the combined use of strategic interventions targeting viral replication and, as in cancer, drugs that interfere with the self renewal and persistence of proliferating memory T cells.
1,517 citations
TL;DR: This work uses causal diagrams and an empirical example (the effect of maternal smoking on neonatal mortality) to illustrate and clarify the definition of overadjustment bias, and to distinguish over adjustment bias from unnecessary adjustment.
Abstract: Overadjustment is defined inconsistently. This term is meant to describe control (eg, by regression adjustment, stratification, or restriction) for a variable that either increases net bias or decreases precision without affecting bias. We define overadjustment bias as control for an intermediate variable (or a descending proxy for an intermediate variable) on a causal path from exposure to outcome. We define unnecessary adjustment as control for a variable that does not affect bias of the causal relation between exposure and outcome but may affect its precision. We use causal diagrams and an empirical example (the effect of maternal smoking on neonatal mortality) to illustrate and clarify the definition of overadjustment bias, and to distinguish overadjustment bias from unnecessary adjustment. Using simulations, we quantify the amount of bias associated with overadjustment. Moreover, we show that this bias is based on a different causal structure from confounding or selection biases. Overadjustment bias is not a finite sample bias, while inefficiencies due to control for unnecessary variables are a function of sample size.
1,480 citations
University of Louisville1, University of Pittsburgh2, Royal Brisbane and Women's Hospital3, Carolinas Medical Center4, Beaumont Hospital5, University of Cincinnati6, Seoul National University7, Iwate Medical University8, Toho University9, Kaohsiung Medical University10, University of Paris11, University of Texas MD Anderson Cancer Center12, McGill University13, University of California, Los Angeles14, Memorial Sloan Kettering Cancer Center15, Mayo Clinic16, University of Chicago17, Icahn School of Medicine at Mount Sinai18, University of Hong Kong19, Duke University20, Vanderbilt University21, Roger Williams Medical Center22, Northwestern University23, University of Duisburg-Essen24, Washington University in St. Louis25
TL;DR: Laparoscopic liver surgery is a safe and effective approach to the management of surgical liver disease in the hands of trained surgeons with experience in hepatobiliary and laparoscopic surgery, and national and international societies should become involved in the goal of establishing training standards and credentialing.
Abstract: Objective:To summarize the current world position on laparoscopic liver surgery.Summary Background Data:Multiple series have reported on the safety and efficacy of laparoscopic liver surgery. Small and medium sized procedures have become commonplace in many centers, while major laparoscopic liver re
1,366 citations
TL;DR: It is shown that tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6), an adaptor protein in the TNF-receptor and interleukin-1R/Toll-like receptor superfamily, regulates CD8 TM-cell development after infection by modulating fatty acid metabolism.
Abstract: CD8 T cells, which have a crucial role in immunity to infection and cancer, are maintained in constant numbers, but on antigen stimulation undergo a developmental program characterized by distinct phases encompassing the expansion and then contraction of antigen-specific effector (T(E)) populations, followed by the persistence of long-lived memory (T(M)) cells. Although this predictable pattern of CD8 T-cell responses is well established, the underlying cellular mechanisms regulating the transition to T(M) cells remain undefined. Here we show that tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6), an adaptor protein in the TNF-receptor and interleukin-1R/Toll-like receptor superfamily, regulates CD8 T(M)-cell development after infection by modulating fatty acid metabolism. We show that mice with a T-cell-specific deletion of TRAF6 mount robust CD8 T(E)-cell responses, but have a profound defect in their ability to generate T(M) cells that is characterized by the disappearance of antigen-specific cells in the weeks after primary immunization. Microarray analyses revealed that TRAF6-deficient CD8 T cells exhibit altered expression of genes that regulate fatty acid metabolism. Consistent with this, activated CD8 T cells lacking TRAF6 display defective AMP-activated kinase activation and mitochondrial fatty acid oxidation (FAO) in response to growth factor withdrawal. Administration of the anti-diabetic drug metformin restored FAO and CD8 T(M)-cell generation in the absence of TRAF6. This treatment also increased CD8 T(M) cells in wild-type mice, and consequently was able to considerably improve the efficacy of an experimental anti-cancer vaccine.
1,325 citations
TL;DR: A geometric-flow-based algorithm for computing a dense oversegmentation of an image, often referred to as superpixels, which yields less undersegmentation than algorithms that lack a compactness constraint while offering a significant speedup over N-cuts, which does enforce compactness.
Abstract: We describe a geometric-flow-based algorithm for computing a dense oversegmentation of an image, often referred to as superpixels. It produces segments that, on one hand, respect local image boundaries, while, on the other hand, limiting undersegmentation through a compactness constraint. It is very fast, with complexity that is approximately linear in image size, and can be applied to megapixel sized images with high superpixel densities in a matter of minutes. We show qualitative demonstrations of high-quality results on several complex images. The Berkeley database is used to quantitatively compare its performance to a number of oversegmentation algorithms, showing that it yields less undersegmentation than algorithms that lack a compactness constraint while offering a significant speedup over N-cuts, which does enforce compactness.
University of Washington1, Johns Hopkins University2, University of Alabama at Birmingham3, Yale University4, Simon Fraser University5, University of California, San Francisco6, University of North Carolina at Chapel Hill7, Centers for Disease Control and Prevention8, University of Toronto9, University of Calgary10, Harvard University11, McGill University12, Case Western Reserve University13, Vanderbilt University14, Kaiser Permanente15, National Institutes of Health16, University of California, San Diego17
TL;DR: The early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy.
Abstract: BACKGROUND The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain. METHODS We conducted two parallel analyses involving a total of 17,517 asymptomatic patients with HIV infection in the United States and Canada who received medical care during the period from 1996 through 2005. None of the patients had undergone previous antiretroviral therapy. In each group, we stratified the patients according to the CD4+ count (351 to 500 cells per cubic millimeter or >500 cells per cubic millimeter) at the initiation of antiretroviral therapy. In each group, we compared the relative risk of death for patients who initiated therapy when the CD4+ count was above each of the two thresholds of interest (early-therapy group) with that of patients who deferred therapy until the CD4+ count fell below these thresholds (deferred-therapy group). RESULTS In the first analysis, which involved 8362 patients, 2084 (25%) initiated therapy at a CD4+ count of 351 to 500 cells per cubic millimeter, and 6278 (75%) deferred therapy. After adjustment for calendar year, cohort of patients, and demographic and clinical characteristics, among patients in the deferred-therapy group there was an increase in the risk of death of 69%, as compared with that in the early-therapy group (relative risk in the deferred-therapy group, 1.69; 95% confidence interval [CI], 1.26 to 2.26; P<0.001). In the second analysis involving 9155 patients, 2220 (24%) initiated therapy at a CD4+ count of more than 500 cells per cubic millimeter and 6935 (76%) deferred therapy. Among patients in the deferred-therapy group, there was an increase in the risk of death of 94% (relative risk, 1.94; 95% CI, 1.37 to 2.79; P<0.001). CONCLUSIONS The early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy.
Harvard University1, Broad Institute2, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico3, McMaster University4, McGill University5, University of Leicester6, University of Lübeck7, University of Pennsylvania8, Vanderbilt University9, University of Missouri–Kansas City10, University of Münster11, University of Verona12, Queen's University Belfast13, University of Washington14, Boston University15, University of Helsinki16, National Institute for Health and Welfare17, Lund University18, University of Cambridge19, Vita-Salute San Raffaele University20, University of Ferrara21, University of Turin22, Hebrew University of Jerusalem23, University of Girona24, University of Milan25, University of Leeds26, University of Regensburg27, Ludwig Maximilian University of Munich28, University of Kiel29, Wellcome Trust Sanger Institute30, University of Paris31, MedStar Washington Hospital Center32, deCODE genetics33, University of Iceland34
TL;DR: SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with my Cardiovascular Infarction risk.
Abstract: We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls We carried out replication in an independent sample with an effective sample size of up to 19,492 SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations1, 2, 3, 4 (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9) We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10-3) We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk
TL;DR: This review considers the potential role of tumor suppressors as metabolic regulators and a number of well-established tumor suppressers play critical roles in suppressing growth and/or proliferation when intracellular supplies of essential metabolites become reduced.
Abstract: Growing tumors face two major metabolic challenges-how to meet the bioenergetic and biosynthetic demands of increased cell proliferation, and how to survive environmental fluctuations in external nutrient and oxygen availability when tumor growth outpaces the delivery capabilities of the existing vasculature. Cancer cells display dramatically altered metabolic circuitry that appears to directly result from the oncogenic mutations selected during the tumorigenic process. An emerging theme in cancer biology is that many of the genes that can initiate tumorigenesis are intricately linked to metabolic regulation. In turn, it appears that a number of well-established tumor suppressors play critical roles in suppressing growth and/or proliferation when intracellular supplies of essential metabolites become reduced. In this review, we consider the potential role of tumor suppressors as metabolic regulators.
TL;DR: Pain researchers now have at their disposal a much wider range of mutant animals to study, assays that more closely resemble clinical pain states, and dependent measures beyond simple reflexive withdrawal, however, the complexity of the phenomenon of pain has made it difficult to assess the true value of these advances.
Abstract: Many are frustrated with the lack of translational progress in the pain field, in which huge gains in basic science knowledge obtained using animal models have not led to the development of many new clinically effective compounds. A careful re-examination of animal models of pain is therefore warranted. Pain researchers now have at their disposal a much wider range of mutant animals to study, assays that more closely resemble clinical pain states, and dependent measures beyond simple reflexive withdrawal. However, the complexity of the phenomenon of pain has made it difficult to assess the true value of these advances. In addition, pain studies are importantly affected by a wide range of modulatory factors, including sex, genotype and social communication, all of which must be taken into account when using an animal model.
TL;DR: In this article, a comprehensive review of the status of the contemporary carbon cycle of the Arctic and its response to climate change is presented to clarify key uncertainties and vulnerabilities in the response of the carbon cycle in the Arctic to ongoing climatic change.
Abstract: The recent warming in the Arctic is affecting a broad spectrum of physical, ecological, and human/cultural systems that may be irreversible on century time scales and have the potential to cause rapid changes in the earth system. The response of the carbon cycle of the Arctic to changes in climate is a major issue of global concern, yet there has not been a comprehensive review of the status of the contemporary carbon cycle of the Arctic and its response to climate change. This review is designed to clarify key uncertainties and vulnerabilities in the response of the carbon cycle of the Arctic to ongoing climatic change. While it is clear that there are substantial stocks of carbon in the Arctic, there are also significant uncertainties associated with the magnitude of organic matter stocks contained in permafrost and the storage of methane hydrates beneath both subterranean and submerged permafrost of the Arctic. In the context of the global carbon cycle, this review demonstrates that the Arctic plays an important role in the global dynamics of both CO2 and CH4. Studies suggest that the Arctic has been a sink for atmospheric CO2 of between 0 and 0.8 Pg C/yr in recent decades, which is between 0% and 25% of the global net land/ocean flux during the 1990s. The Arctic is a substantial source of CH4 to the atmosphere (between 32 and 112 Tg CH4/yr), primarily because of the large area of wetlands throughout the region. Analyses to date indicate that the sensitivity of the carbon cycle of the Arctic during the remainder of the 21st century is highly uncertain. To improve the capability to assess the sensitivity of the carbon cycle of the Arctic to projected climate change, we recommend that (1) integrated regional studies be conducted to link observations of carbon dynamics to the processes that are likely to influence those dynamics, and (2) the understanding gained from these integrated studies be incorporated into both uncoupled and fully coupled carbon-climate modeling efforts. (Less)
TL;DR: For people choosing to start pharmacological prophylaxis, reduction in both LDL cholesterol and hsCRP are indicators of successful treatment with rosuvastatin, and these reductions were predictive of event rates irrespective of the lipid endpoint used.
Book•
04 Nov 2009TL;DR: The 2006 second edition of this book as mentioned in this paper develops the basic formalism and theoretical techniques for studying relativistic quantum field theory at high temperature and density, including functional integral representation of the partition function, diagrammatic expansions, linear response theory, screening and plasma oscillations, spontaneous symmetry breaking, Goldstone theorem, resummation and hard thermal loops, lattice gauge theory, phase transitions, nucleation theory, quark-gluon plasma, and color superconductivity.
Abstract: The 2006 second edition of this book develops the basic formalism and theoretical techniques for studying relativistic quantum field theory at high temperature and density. Specific physical theories treated include QED, QCD, electroweak theory, and effective nuclear field theories of hadronic and nuclear matter. Topics include: functional integral representation of the partition function, diagrammatic expansions, linear response theory, screening and plasma oscillations, spontaneous symmetry breaking, Goldstone theorem, resummation and hard thermal loops, lattice gauge theory, phase transitions, nucleation theory, quark-gluon plasma, and color superconductivity. Applications to astrophysics and cosmology cover white dwarf and neutron stars, neutrino emissivity, baryon number violation in the early universe, and cosmological phase transitions. Applications to relativistic nucleus-nucleus collisions are also included. The book is written for theorists in elementary particle physics, nuclear physics, astrophysics, and cosmology. Problems are given at the end of each chapter, and numerous references to the literature are included.
TL;DR: The prognostic factors for BM patients varied by diagnosis, and two new DS-GPA indexes were designed for breast/gastrointestinal cancer and melanoma/renal cell carcinoma.
Abstract: Purpose Controversy endures regarding the optimal treatment of patients with brain metastases (BMs). Debate persists, despite many randomized trials, perhaps because BM patients are a heterogeneous population. The purpose of the present study was to identify significant diagnosis-specific prognostic factors and indexes (Diagnosis-Specific Graded Prognostic Assessment [DS-GPA]). Methods and Materials A retrospective database of 5,067 patients treated for BMs between 1985 and 2007 was generated from 11 institutions. After exclusion of the patients with recurrent BMs or incomplete data, 4,259 patients with newly diagnosed BMs remained eligible for analysis. Univariate and multivariate analyses of the prognostic factors and outcomes by primary site and treatment were performed. The significant prognostic factors were determined and used to define the DS-GPA prognostic indexes. The DS-GPA scores were calculated and correlated with the outcomes, stratified by diagnosis and treatment. Results The significant prognostic factors varied by diagnosis. For non–small-cell lung cancer and small-cell lung cancer, the significant prognostic factors were Karnofsky performance status, age, presence of extracranial metastases, and number of BMs, confirming the original GPA for these diagnoses. For melanoma and renal cell cancer, the significant prognostic factors were Karnofsky performance status and the number of BMs. For breast and gastrointestinal cancer, the only significant prognostic factor was the Karnofsky performance status. Two new DS-GPA indexes were thus designed for breast/gastrointestinal cancer and melanoma/renal cell carcinoma. The median survival by GPA score, diagnosis, and treatment were determined. Conclusion The prognostic factors for BM patients varied by diagnosis. The original GPA was confirmed for non–small-cell lung cancer and small-cell lung cancer. New DS-GPA indexes were determined for other histologic types and correlated with the outcome, and statistical separation between the groups was confirmed. These data should be considered in the design of future randomized trials and in clinical decision-making.
TL;DR: In this review, a summary and discussion of recent progress in the field is discussed and the prospects for better understanding of long-lasting changes in synaptic strength, learning, and memory and implications for neurological diseases are highlighted.
TL;DR: A scoring system is proposed for concomitantly appraising the methodological quality of qualitative, quantitative and mixed methods studies for SMSRs and this scoring system may also be used to appraise the quantitative and qualitative quality of mixed methods research.
TL;DR: Rituximab, a monoclonal antibody selectively depleting CD20+ B cells, has demonstrated efficacy in reducing disease activity in relapsing‐remitting multiple sclerosis (MS).
Abstract: Objective
Rituximab, a monoclonal antibody selectively depleting CD20+ B cells, has demonstrated efficacy in reducing disease activity in relapsing-remitting multiple sclerosis (MS). We evaluated rituximab in adults with primary progressive MS (PPMS) through 96 weeks and safety through 122 weeks.
Methods
Using 2:1 randomization, 439 PPMS patients received two 1,000mg intravenous rituximab or placebo infusions every 24 weeks, through 96 weeks (4 courses). The primary endpoint was time to confirmed disease progression (CDP), a prespecified increase in Expanded Disability Status Scale sustained for 12 weeks. Secondary endpoints were change from baseline to week 96 in T2 lesion volume and total brain volume on magnetic resonance imaging scans.
Results
Differences in time to CDP between rituximab and placebo did not reach significance (96-week rates: 38.5% placebo, 30.2% rituximab; p = 0.14). From baseline to week 96, rituximab patients had less (p < 0.001) increase in T2 lesion volume; brain volume change was similar (p = 0.62) to placebo. Subgroup analysis showed time to CDP was delayed in rituximab-treated patients aged <51 years (hazard ratio [HR] = 0.52; p = 0.010), those with gadolinium-enhancing lesions (HR = 0.41; p = 0.007), and those aged <51 years with gadolinium-enhancing lesions (HR = 0.33; p = 0.009) compared with placebo. Adverse events were comparable between groups; 16.1% of rituximab and 13.6% of placebo patients reported serious events. Serious infections occurred in 4.5% of rituximab and <1.0% of placebo patients. Infusion-related events, predominantly mild to moderate, were more common with rituximab during the first course, and decreased to rates comparable to placebo on successive courses.
Interpretation
Although time to CDP between groups was not significant, overall subgroup analyses suggest selective B-cell depletion may affect disease progression in younger patients, particularly those with inflammatory lesions. Ann Neurol 2009;66:460–471
McGill University Health Centre1, University of Ottawa2, St. Paul's Hospital3, Libin Cardiovascular Institute of Alberta4, Centre Hospitalier Universitaire de Sherbrooke5, McMaster University6, Robarts Research Institute7, University of Calgary8, University of Toronto9, Population Health Research Institute10, University of British Columbia11, University of Alberta12, McGill University13
TL;DR: The present article represents the 2009 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult.
University of Ottawa1, University of Ioannina2, University of Bern3, Centers for Disease Control and Prevention4, PLOS5, University of Bristol6, Ottawa Hospital Research Institute7, University of Texas Health Science Center at Houston8, University of Western Ontario9, Erasmus University Rotterdam10, Cancer Care Ontario11, McGill University12, Harvard University13
TL;DR: The STREGA recommendations are presented, which are aimed at improving the reporting of genetic association studies and are designed to improve the quality of studies.
Abstract: Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.
TL;DR: Evidence is presented that autoimmunity has a role in the development of COPD and how pulmonary damage caused by cigarette smoke and other environmental toxins can incite inflammatory and immunologic reactions that culminate in COPD.
Abstract: This review is an account of how pulmonary damage caused by cigarette smoke and other environmental toxins can incite inflammatory and immunologic reactions that culminate in chronic obstructive pulmonary disease (COPD). The authors present evidence that autoimmunity has a role in the development of COPD.
Posted Content•
TL;DR: In this article, the influence of the structure and composition of a firm's alliance network on its exploratory innovation was examined and the benefits of network closure and access to diverse information can coexist in a firm’s alliance network.
Abstract: This study examines the influence of the structure and composition of a firm’s alliance network on its exploratory innovation. In a longitudinal investigation of 77 telecommunications equipment manufacturers, I find the technological diversity of a firm’s alliance partners increases its exploratory innovation. I also find that network density among a firm’s alliance partners strengthens the influence of diversity. These results suggest the benefits of network closure and access to diverse information can coexist in a firm’s alliance network and the combination of the two increases exploratory innovation.
TL;DR: In this paper, the authors highlight the problematic nature of academic ranking systems and question if such assessments are drawing scholarship away from its fundamental purpose, and call for an immediate examination of existing ranking systems, not only as a legitimate scholarly question vis-a-vis performance, but also because the very health and vibrancy of the field are at stake.
Abstract: “Not everything that can be counted counts, and not everything that counts can be counted”—Albert Einstein Has university scholarship gone astray? Do our academic assessment systems reward scholarship that addresses the questions that matter most to society? Using international business as an example, we highlight the problematic nature of academic ranking systems and question if such assessments are drawing scholarship away from its fundamental purpose We call for an immediate examination of existing ranking systems, not only as a legitimate scholarly question vis-a`-vis performance—a conceptual lens with deep roots in management research—but also because the very health and vibrancy of the field are at stake Indeed, in light of the data presented here, which suggest that current systems are dysfunctional and potentially cause more harm than good, a temporary moratorium on rankings may be appropriate until more valid and reliable ways to assess scholarly contributions can be developed The worldwide community of scholars, along with the global network of institutions interacting with and supporting management scholarship (such as the Academy of Management, AACSB, and Thomson Reuters Scientific) are invited to innovate and design more reliable and valid ways to assess scholarly contributions that truly promote the advancement of relevant 21st century knowledge, and likewise recognize those individuals and institutions that best fulfill the university’s fundamental purpose
TL;DR: It is established that the same operational definitions and types of evidence underpin the deduction of both reconsolidation and consolidation, thus validating the extrapolation that post-retrieval memory plasticity reflects processes akin to those that stabilized the memory following acquisition.
Abstract: Consolidated memories can re-enter states of transient instability following reactivation, from which they must again stabilize in order to persist, contradicting the previously dominant view that memory and its associated plasticity mechanisms progressively and irreversibly decline with time. We witness exciting times, as neuroscience begins embracing a position, long-held in cognitive psychology, that recognizes memory as a principally dynamic process. In light of remaining controversy, we here establish that the same operational definitions and types of evidence underpin the deduction of both reconsolidation and consolidation, thus validating the extrapolation that post-retrieval memory plasticity reflects processes akin to those that stabilized the memory following acquisition.
TL;DR: The many SNPs associated with BMD map to genes in signaling pathways with relevance to bone metabolism and highlight the complex genetic architecture that underlies osteoporosis and variation in BMD.
Abstract: Bone mineral density (BMD) is a heritable complex trait used in the clinical diagnosis of osteoporosis and the assessment of fracture risk. We performed meta-analysis of five genome-wide association studies of femoral neck and lumbar spine BMD in 19,195 subjects of Northern European descent. We identified 20 BMD loci that reached genome-wide significance (GWS; P < 5 x 10(-8)), of which 13 map to regions not previously associated with this trait: 1p31.3 (GPR177), 2p21 (SPTBN1), 3p22 (CTNNB1), 4q21.1 (MEPE), 5q14 (MEF2C), 7p14 (STARD3NL), 7q21.3 (FLJ42280), 11p11.2 (LRP4, ARHGAP1, F2), 11p14.1 (DCDC5), 11p15 (SOX6), 16q24 (FOXL1), 17q21 (HDAC5) and 17q12 (CRHR1). The meta-analysis also confirmed at GWS level seven known BMD loci on 1p36 (ZBTB40), 6q25 (ESR1), 8q24 (TNFRSF11B), 11q13.4 (LRP5), 12q13 (SP7), 13q14 (TNFSF11) and 18q21 (TNFRSF11A). The many SNPs associated with BMD map to genes in signaling pathways with relevance to bone metabolism and highlight the complex genetic architecture that underlies osteoporosis and variation in BMD.
University of Leicester1, Pennsylvania State University2, University of Warwick3, Harvard University4, University of Copenhagen5, Max Planck Society6, Goddard Space Flight Center7, University of California, Berkeley8, University of Amsterdam9, University of Iceland10, University of Exeter11, University of Bristol12, Spanish National Research Council13, European Southern Observatory14, Australian National University15, Special Astrophysical Observatory16, Space Telescope Science Institute17, Universities Space Research Association18, California Institute of Technology19, Liverpool John Moores University20, Pomona College21, University of Oxford22, McGill University23, University College London24, Stockholm University25, George Washington University26
TL;DR: In this paper, the authors reported that GRB 090423 lies at a redshift of z approximate to 8.2, implying that massive stars were being produced and dying as GRBs similar to 630 Myr after the Big Bang.
Abstract: Long-duration gamma-ray bursts (GRBs) are thought to result from the explosions of certain massive stars(1), and some are bright enough that they should be observable out to redshifts of z > 20 using current technology(2-4). Hitherto, the highest redshift measured for any object was z = 6.96, for a Lyman-alpha emitting galaxy(5). Here we report that GRB 090423 lies at a redshift of z approximate to 8.2, implying that massive stars were being produced and dying as GRBs similar to 630 Myr after the Big Bang. The burst also pinpoints the location of its host galaxy.