Showing papers by "University of Alberta published in 2013"
TL;DR: Lipidic nanoparticles are the first nanomedicine delivery system to make the transition from concept to clinical application, and they are now an established technology platform with considerable clinical acceptance.
3,497 citations
TL;DR: Yin this paper explains that case study research is a linear, but iterative process and that each chapter contains one step in the linear process of case design (planning, designing, preparing, collecting, analyzing, and sharing) and highlights how each step requires the researcher to review and re-examine former decisions.
Abstract: Yin begins the fourth edition of his 6 chapter book by explaining that case study research is a “linear, but iterative process.” This statement is supported by a visual which is displayed on the first page of each chapter. Each chapter contains one step in the linear process of case design (planning, designing, preparing, collecting, analyzing, and sharing) as well as it highlights how each step requires the researcher to review and re-examine former decisions. As Yin points out, each chapter can stand alone, yet it is linked to the other stages of the research process.
3,221 citations
TL;DR: The Arcade Learning Environment (ALE) as discussed by the authors is a platform for evaluating the development of general, domain-independent AI technology, which provides an interface to hundreds of Atari 2600 game environments, each one different, interesting, and designed to be a challenge for human players.
Abstract: In this article we introduce the Arcade Learning Environment (ALE): both a challenge problem and a platform and methodology for evaluating the development of general, domain-independent AI technology. ALE provides an interface to hundreds of Atari 2600 game environments, each one different, interesting, and designed to be a challenge for human players. ALE presents significant research challenges for reinforcement learning, model learning, model-based planning, imitation learning, transfer learning, and intrinsic motivation. Most importantly, it provides a rigorous testbed for evaluating and comparing approaches to these problems. We illustrate the promise of ALE by developing and benchmarking domain-independent agents designed using well-established AI techniques for both reinforcement learning and planning. In doing so, we also propose an evaluation methodology made possible by ALE, reporting empirical results on over 55 different games. All of the software, including the benchmark agents, is publicly available.
2,429 citations
University of California, San Diego1, University of Western Ontario2, Katholieke Universiteit Leuven3, University of Chicago4, Icahn School of Medicine at Mount Sinai5, Lille University of Science and Technology6, Charles University in Prague7, University of Alberta8, University of Washington9, University of British Columbia10, Millennium Pharmaceuticals11
TL;DR: Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive vedolIZumab (rather than switching to placebo) were morelikely to be in remission at week 52.
Abstract: BackgroundUstekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. MethodsWe randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 w...
2,059 citations
TL;DR: Patients with cancer who are cachexic by the conventional criterion and by two additional criteria (muscle depletion and low muscle attenuation) share a poor prognosis, regardless of overall body weight.
Abstract: Purpose Emerging evidence suggests muscle depletion predicts survival of patients with cancer. Patients and Methods At a cancer center in Alberta, Canada, consecutive patients with cancer (lung or GI; N 1,473) were assessed at presentation for weight loss history, lumbar skeletal muscle index, and mean muscle attenuation (Hounsfield units) by computed tomography (CT). Univariate and multivariate analyses were conducted. Concordance (c) statistics were used to test predictive accuracy of survival models. Results Body mass index (BMI) distribution was 17% obese, 35% overweight, 36% normal weight, and 12% underweight. Patients in all BMI categories varied widely in weight loss, muscle index, and muscle attenuation. Thresholds defining associations between these three variables and survival were determined using optimal stratification. High weight loss, low muscle index, and low muscle attenuation were independently prognostic of survival. A survival model containing conventional covariates (cancer diagnosis, stage, age, performance status) gave a c statistic of 0.73 (95% CI, 0.67 to 0.79), whereas a model ignoring conventional variables and including only BMI, weight loss, muscle index, and muscle attenuation gave a c statistic of 0.92 (95% CI, 0.88 to 0.95; P .001). Patients who possessed all three of these poor prognostic variables survived 8.4 months (95% CI, 6.5 to 10.3), regardless of whether they presented as obese, overweight, normal weight, or underweight, in contrast to patients who had none of these features, who survived 28.4 months (95% CI, 24.2 to 32.6; P .001).
1,813 citations
Alternatives1, John Innes Centre2, University of Bonn3, University of North Carolina at Chapel Hill4, University of Wisconsin-Madison5, University of Utah6, University of Southern California7, University of Edinburgh8, University of Warwick9, Harvard University10, University College Cork11, University of Queensland12, University of Hertfordshire13, University of Potsdam14, University of California, San Diego15, Goethe University Frankfurt16, University of California, San Francisco17, University of Delaware18, Uppsala University19, Medical University of Vienna20, J. Craig Venter Institute21, University of Hawaii at Manoa22, Leibniz Association23, University of Iowa24, University of Aberdeen25, Georgia Institute of Technology26, University of California, Berkeley27, University of Groningen28, Princeton University29, University of Marburg30, University of Illinois at Urbana–Champaign31, Saarland University32, Norwegian University of Life Sciences33, Massey University34, Toyama Prefectural University35, ETH Zurich36, University of Saskatchewan37, Rutgers University38, Scripps Research Institute39, University of Helsinki40, Texas A&M University41, National Institutes of Health42, Technical University of Berlin43, University of Otago44, University of Cambridge45, University of Alberta46, Michigan State University47, Hofstra University48
TL;DR: This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products.
1,560 citations
University of Adelaide1, University of Wisconsin-Madison2, Ghent University3, University of Canterbury4, University of Geneva5, Humboldt University of Berlin6, University of California, Irvine7, University of Mainz8, University of California, Berkeley9, Ohio State University10, Université libre de Bruxelles11, Ruhr University Bochum12, University of Wuppertal13, University of Maryland, College Park14, University of Kansas15, Lawrence Berkeley National Laboratory16, RWTH Aachen University17, Uppsala University18, University of Alberta19, Stockholm University20, Vrije Universiteit Brussel21, University of Bonn22, École Polytechnique Fédérale de Lausanne23, Georgia Institute of Technology24, Pennsylvania State University25, Technical University of Dortmund26, Southern University and A&M College27
TL;DR: The presence of a high-energy neutrino flux containing the most energetic neutrinos ever observed is revealed, including 28 events at energies between 30 and 1200 TeV, although the origin of this flux is unknown and the findings are consistent with expectations for a neutRino population with origins outside the solar system.
Abstract: We report on results of an all-sky search for high-energy neutrino events interacting within the IceCube neutrino detector conducted between May 2010 and May 2012. The search follows up on the previous detection of two PeV neutrino events, with improved sensitivity and extended energy coverage down to about 30 TeV. Twenty-six additional events were observed, substantially more than expected from atmospheric backgrounds. Combined, both searches reject a purely atmospheric origin for the 28 events at the 4 sigma level. These 28 events, which include the highest energy neutrinos ever observed, have flavors, directions, and energies inconsistent with those expected from the atmospheric muon and neutrino backgrounds. These properties are, however, consistent with generic predictions for an additional component of extraterrestrial origin.
1,490 citations
TL;DR: This paper attempts to survey and summarize the recent research and development of EMD in fault diagnosis of rotating machinery, providing comprehensive references for researchers concerning with this topic and helping them identify further research topics.
1,410 citations
14 Apr 2013
TL;DR: This work proposes a theoretically and practically improved density-based, hierarchical clustering method, providing a clustering hierarchy from which a simplified tree of significant clusters can be constructed, and proposes a novel cluster stability measure.
Abstract: We propose a theoretically and practically improved density-based, hierarchical clustering method, providing a clustering hierarchy from which a simplified tree of significant clusters can be constructed For obtaining a “flat” partition consisting of only the most significant clusters (possibly corresponding to different density thresholds), we propose a novel cluster stability measure, formalize the problem of maximizing the overall stability of selected clusters, and formulate an algorithm that computes an optimal solution to this problem We demonstrate that our approach outperforms the current, state-of-the-art, density-based clustering methods on a wide variety of real world data
1,132 citations
TL;DR: A comprehensive, quantitative, metabolome-wide characterization of human urine and the identification and annotation of several previously unknown urine metabolites and to substantially enhance the level of metabolome coverage are undertaken.
Abstract: Urine has long been a “favored” biofluid among metabolomics researchers. It is sterile, easy-to-obtain in large volumes, largely free from interfering proteins or lipids and chemically complex. However, this chemical complexity has also made urine a particularly difficult substrate to fully understand. As a biological waste material, urine typically contains metabolic breakdown products from a wide range of foods, drinks, drugs, environmental contaminants, endogenous waste metabolites and bacterial by-products. Many of these compounds are poorly characterized and poorly understood. In an effort to improve our understanding of this biofluid we have undertaken a comprehensive, quantitative, metabolome-wide characterization of human urine. This involved both computer-aided literature mining and comprehensive, quantitative experimental assessment/validation. The experimental portion employed NMR spectroscopy, gas chromatography mass spectrometry (GC-MS), direct flow injection mass spectrometry (DFI/LC-MS/MS), inductively coupled plasma mass spectrometry (ICP-MS) and high performance liquid chromatography (HPLC) experiments performed on multiple human urine samples. This multi-platform metabolomic analysis allowed us to identify 445 and quantify 378 unique urine metabolites or metabolite species. The different analytical platforms were able to identify (quantify) a total of: 209 (209) by NMR, 179 (85) by GC-MS, 127 (127) by DFI/LC-MS/MS, 40 (40) by ICP-MS and 10 (10) by HPLC. Our use of multiple metabolomics platforms and technologies allowed us to identify several previously unknown urine metabolites and to substantially enhance the level of metabolome coverage. It also allowed us to critically assess the relative strengths and weaknesses of different platforms or technologies. The literature review led to the identification and annotation of another 2206 urinary compounds and was used to help guide the subsequent experimental studies. An online database containing the complete set of 2651 confirmed human urine metabolite species, their structures (3079 in total), concentrations, related literature references and links to their known disease associations are freely available at http://www.urinemetabolome.ca.
1,118 citations
Clark University1, University of Michigan2, Scripps Institution of Oceanography3, Trent University4, University of Colorado Boulder5, University of Bristol6, University of Alaska Fairbanks7, Cooperative Institute for Research in Environmental Sciences8, Centre national de la recherche scientifique9, Uppsala University10, Institute of Arctic and Alpine Research11, University of Innsbruck12, Utrecht University13, Dresden University of Technology14, University of Zurich15, University of Alberta16, University of Oslo17
TL;DR: It is found that glaciers in the Arctic, Canada, Alaska, coastal Greenland, the southern Andes, and high-mountain Asia contribute approximately as much melt water as the ice sheets themselves: 260 billion tons per year between 2003 and 2009, accounting for about 30% of the observed sea-level rise during that period.
Abstract: Glaciers distinct from the Greenland and Antarctic Ice Sheets are losing large amounts of water to the world's oceans. However, estimates of their contribution to sea level rise disagree. We provide a consensus estimate by standardizing existing, and creating new, mass-budget estimates from satellite gravimetry and altimetry and from local glaciological records. In many regions, local measurements are more negative than satellite-based estimates. All regions lost mass during 2003-2009, with the largest losses from Arctic Canada, Alaska, coastal Greenland, the southern Andes, and high-mountain Asia, but there was little loss from glaciers in Antarctica. Over this period, the global mass budget was -259 ± 28 gigatons per year, equivalent to the combined loss from both ice sheets and accounting for 29 ± 13% of the observed sea level rise.
TL;DR: Comparisons between families of children of ASD and families with other disabilities also generated a large effect size however, this result should be interpreted with caution as it may be associated with the specific experience of parenting a child with DS.
Abstract: Researchers commonly report that families of children with autism spectrum disorder (ASD) experience more parenting stress than families of typically developing (TD) children or those diagnosed with other disabilities [e.g., Down syndrome (DS), cerebral palsy, intellectual disability]. The authors reexamined the research using comparison groups to investigate parenting stress and conducted a meta-analysis to pool results across studies. The experience of stress in families of children with ASD versus families of TD children resulted in a large effect size. Comparisons between families of children of ASD and families with other disabilities also generated a large effect size however, this result should be interpreted with caution as it may be associated with the specific experience of parenting a child with DS.
University of Florida1, University of Bonn2, Goddard Institute for Space Studies3, Commonwealth Scientific and Industrial Research Organisation4, Institut national de la recherche agronomique5, Agro ParisTech6, Michigan State University7, Blaise Pascal University8, International Water Management Institute9, University of Leeds10, CGIAR11, Counterintelligence Field Activity12, University of Tübingen13, University of Alberta14, International Atomic Energy Agency15, University of Reading16, University of Guelph17, University of Hohenheim18, Joint Global Change Research Institute19, Potsdam Institute for Climate Impact Research20, Indian Agricultural Research Institute21, Aarhus University22, Rothamsted Research23, Washington State University24, Wageningen University and Research Centre25, Chinese Academy of Sciences26, International Trademark Association27, Texas A&M University28
TL;DR: In this article, the authors present the largest standardized model intercomparison for climate change impacts so far, finding that individual crop models are able to simulate measured wheat grain yields accurately under a range of environments, particularly if the input information is sufficient.
Abstract: Projections of climate change impacts on crop yields are inherently uncertain(1). Uncertainty is often quantified when projecting future greenhouse gas emissions and their influence on climate(2). However, multi-model uncertainty analysis of crop responses to climate change is rare because systematic and objective comparisons among process-based crop simulation models(1,3) are difficult(4). Here we present the largest standardized model intercomparison for climate change impacts so far. We found that individual crop models are able to simulate measured wheat grain yields accurately under a range of environments, particularly if the input information is sufficient. However, simulated climate change impacts vary across models owing to differences in model structures and parameter values. A greater proportion of the uncertainty in climate change impact projections was due to variations among crop models than to variations among downscaled general circulation models. Uncertainties in simulated impacts increased with CO2 concentrations and associated warming. These impact uncertainties can be reduced by improving temperature and CO2 relationships in models and better quantified through use of multi-model ensembles. Less uncertainty in describing how climate change may affect agricultural productivity will aid adaptation strategy development and policymaking.
Mayo Clinic1, University of Pittsburgh2, Autonomous University of Barcelona3, University of Alberta4, Karolinska University Hospital5, University of Florida6, New York Methodist Hospital7, United States Department of Veterans Affairs8, George Washington University9, University of Duisburg-Essen10, Albert Einstein College of Medicine11, Virginia Commonwealth University12, Otto-von-Guericke University Magdeburg13, Vrije Universiteit Brussel14, Ghent University Hospital15, Hospital of the University of Pennsylvania16, University of Chicago17, Duke University18, University of Maryland, Baltimore19, RWTH Aachen University20, St. John Providence Health System21, University of California, San Diego22, St Thomas' Hospital23, Beth Israel Deaconess Medical Center24, Medical University of Vienna25, Tampa General Hospital26, Goethe University Frankfurt27
TL;DR: Two novel markers for AKI have been identified and validated in independent multicenter cohorts and are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI.
Abstract: Introduction: Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods: We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results: Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P 0.72. Furthermore, [TIMP2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method.
27 May 2013
TL;DR: This paper reviews recent progress in the area, including design of approximate arithmetic blocks, pertinent error and quality measures, and algorithm-level techniques for approximate computing.
Abstract: Approximate computing has recently emerged as a promising approach to energy-efficient design of digital systems. Approximate computing relies on the ability of many systems and applications to tolerate some loss of quality or optimality in the computed result. By relaxing the need for fully precise or completely deterministic operations, approximate computing techniques allow substantially improved energy efficiency. This paper reviews recent progress in the area, including design of approximate arithmetic blocks, pertinent error and quality measures, and algorithm-level techniques for approximate computing.
TL;DR: In this article, the structure of mesoporous cellular foam with egg white-derived proteins was used to obtain hierarchically mesophorous (pores centered at ∼4 nm and at 20-30 nm) partially graphitized carbons with a surface area of 805.7 m2 g−1 and a bulk N content of 10.1 wt%.
Abstract: In this work we demonstrate that biomass-derived proteins serve as an ideal precursor for synthesizing carbon materials for energy applications. The unique composition and structure of the carbons resulted in very promising electrochemical energy storage performance. We obtained a reversible lithium storage capacity of 1780 mA h g−1, which is among the highest ever reported for any carbon-based electrode. Tested as a supercapacitor, the carbons exhibited a capacitance of 390 F g−1, with an excellent cycle life (7% loss after 10 000 cycles). Such exquisite properties may be attributed to a unique combination of a high specific surface area, partial graphitization and very high bulk nitrogen content. It is a major challenge to derive carbons possessing all three attributes. By templating the structure of mesoporous cellular foam with egg white-derived proteins, we were able to obtain hierarchically mesoporous (pores centered at ∼4 nm and at 20–30 nm) partially graphitized carbons with a surface area of 805.7 m2 g−1 and a bulk N-content of 10.1 wt%. When the best performing sample was heated in Ar to eliminate most of the nitrogen, the Li storage capacity and the specific capacitance dropped to 716 mA h g−1 and 80 F g−1, respectively.
University of Alberta1, Peking University2, Chinese Academy of Sciences3, Macquarie University4, Los Alamos National Laboratory5, Northwestern University6, Radboud University Nijmegen7, McMaster University8, Nanjing University9, Xinjiang University10, University of Warwick11, University of Oxford12, University of Cambridge13, Technion – Israel Institute of Technology14, Academia Sinica15, University of Bonn16, Max Planck Society17, University of Amsterdam18, University of Illinois at Urbana–Champaign19
TL;DR: In this paper, the authors present the current best physical understanding of common envelope evolution (CEE) and highlight areas of consensus and disagreement, and stress ideas which should point the way forward for progress in this important but long-standing and largely unconquered problem.
Abstract: This work aims to present our current best physical understanding of common-envelope evolution (CEE). We highlight areas of consensus and disagreement, and stress ideas which should point the way forward for progress in this important but long-standing and largely unconquered problem. Unusually for CEE-related work, we mostly try to avoid relying on results from population synthesis or observations, in order to avoid potentially being misled by previous misunderstandings. As far as possible we debate all the relevant issues starting from physics alone, all the way from the evolution of the binary system immediately before CEE begins to the processes which might occur just after the ejection of the envelope. In particular, we include extensive discussion about the energy sources and sinks operating in CEE, and hence examine the foundations of the standard energy formalism. Special attention is also given to comparing the results of hydrodynamic simulations from different groups and to discussing the potential effect of initial conditions on the differences in the outcomes. We compare current numerical techniques for the problem of CEE and also whether more appropriate tools could and should be produced (including new formulations of computational hydrodynamics, and attempts to include 3D processes within 1D codes). Finally we explore new ways to link CEE with observations. We compare previous simulations of CEE to the recent outburst from V1309 Sco, and discuss to what extent post-common-envelope binaries and nebulae can provide information, e.g. from binary eccentricities, which is not currently being fully exploited.
TL;DR: In this article, the authors document the development of the body of work known as women's entrepreneurship research and assess the contributions of this work, specifically vis-a-vis the broader entrepreneurship literature.
Abstract: This paper has three overarching objectives. The first is to document the development of the body of work known as women's entrepreneurship research. The second is to assess the contributions of this work, specifically vis-a-vis the broader entrepreneurship literature. The third is to discuss how this broader literature poses challenges (both difficulties as well as opportunities) for scholarship on female entrepreneurs. We approach these objectives from the standpoint of informed pluralism, seeking to explore whether and how women's entrepreneurship research offers extensions to—and can be extended by—general research on entrepreneurs and their ventures.
Book•
15 Apr 2013TL;DR: In this paper, D. Jean Clandininin, one of the pioneers in using narrative as research, updates her classic formulation on narrative inquiry (with F. Michael Connelly), clarifying, extending and refining the method based on an additional decade of work.
Abstract: Narrative inquiry examines human lives through the lens of a narrative, honouring lived experience as a source of important knowledge and understanding. In this concise volume, D. Jean Clandinin, one of the pioneers in using narrative as research, updates her classic formulation on narrative inquiry (with F. Michael Connelly), clarifying, extending and refining the method based on an additional decade of work. A valuable feature is the inclusion of several exemplary cases with the author's critique and analysis of the work. The rise of interest in narrative inquiry in recent years makes this is an essential guide for researchers and an excellent text for graduate courses in qualitative inquiry.
TL;DR: These exquisite carbons were able to be achieved by simple hydrothermal carbonization combined with activation by taking advantage of the complex multilayered structure of a hemp bast fiber precursor, providing among the best power-energy characteristics ever reported for an electrochemical capacitor.
Abstract: We created unique interconnected partially graphitic carbon nanosheets (10–30 nm in thickness) with high specific surface area (up to 2287 m2 g–1), significant volume fraction of mesoporosity (up to 58%), and good electrical conductivity (211–226 S m–1) from hemp bast fiber. The nanosheets are ideally suited for low (down to 0 °C) through high (100 °C) temperature ionic-liquid-based supercapacitor applications: At 0 °C and a current density of 10 A g–1, the electrode maintains a remarkable capacitance of 106 F g–1. At 20, 60, and 100 °C and an extreme current density of 100 A g–1, there is excellent capacitance retention (72–92%) with the specific capacitances being 113, 144, and 142 F g–1, respectively. These characteristics favorably place the materials on a Ragone chart providing among the best power–energy characteristics (on an active mass normalized basis) ever reported for an electrochemical capacitor: At a very high power density of 20 kW kg–1 and 20, 60, and 100 °C, the energy densities are 19, 3...
TL;DR: This project used multiple sources to develop and draw together evidence and expertise in realist synthesis, and synthesized expert input, evidence syntheses and real-time problem analysis into a definitive set of standards.
Abstract: There is growing interest in realist synthesis as an alternative systematic review method. This approach offers the potential to expand the knowledge base in policy-relevant areas -for example, by explaining the success, failure or mixed fortunes of complex interventions. No previous publication standards exist for reporting realist syntheses. This standard was developed as part of the RAMESES (Realist And MEta-narrative Evidence Syntheses: Evolving Standards) project. The project's aim is to produce preliminary publication standards for realist systematic reviews. We (a) collated and summarized existing literature on the principles of good practice in realist syntheses; (b) considered the extent to which these principles had been followed by published syntheses, thereby identifying how rigor may be lost and how existing methods could be improved; (c) used a three-round online Delphi method with an interdisciplinary panel of national and international experts in evidence synthesis, realist research, policy and/or publishing to produce and iteratively refine a draft set of methodological steps and publication standards; (d) provided real-time support to ongoing realist syntheses and the open-access RAMESES online discussion list so as to capture problems and questions as they arose; and (e) synthesized expert input, evidence syntheses and real-time problem analysis into a definitive set of standards. We identified 35 published realist syntheses, provided real-time support to 9 on-going syntheses and captured questions raised in the RAMESES discussion list. Through analysis and discussion within the project team, we summarized the published literature and common questions and challenges into briefing materials for the Delphi panel, comprising 37 members. Within three rounds this panel had reached consensus on 19 key publication standards, with an overall response rate of 91%. This project used multiple sources to develop and draw together evidence and expertise in realist synthesis. For each item we have included an explanation for why it is important and guidance on how it might be reported. Realist synthesis is a relatively new method for evidence synthesis and as experience and methodological developments occur, we anticipate that these standards will evolve to reflect further methodological developments. We hope that these standards will act as a resource that will contribute to improving the reporting of realist syntheses. To encourage dissemination of the RAMESES publication standards, this article is co-published in the Journal of Advanced Nursing and is freely accessible on Wiley Online Library (
http://www.wileyonlinelibrary.com/journal/jan
). Please see related article http://www.biomedcentral.com/1741-7015/11/20
and http://www.biomedcentral.com/1741-7015/11/22
TL;DR: These two neutrino-induced events could be a first indication of an astrophysical neutrinos flux; the moderate significance, however, does not permit a definitive conclusion at this time.
Abstract: We report on the observation of two neutrino-induced events which have an estimated deposited energy in the IceCube detector of 1.04 +/- 0.16 and 1.14 +/- 0.17 PeV, respectively, the highest neutrino energies observed so far. These events are consistent with fully contained particle showers induced by neutral-current nu(e,mu,tau) ((nu) over bar (e,mu,tau)) or charged-current nu(e) ((nu) over bar (e)) interactions within the IceCube detector. The events were discovered in a search for ultrahigh energy neutrinos using data corresponding to 615.9 days effective live time. The expected number of atmospheric background is 0.082 +/- 0.004(stat)(-0.057)(+0.041)(syst). The probability of observing two or more candidate events under the atmospheric background-only hypothesis is 2.9 x 10(-3) (2.8 sigma) taking into account the uncertainty on the expected number of background events. These two events could be a first indication of an astrophysical neutrino flux; the moderate significance, however, does not permit a definitive conclusion at this time.
TL;DR: It is demonstrated that peat moss, a wild plant that covers 3% of the earth's surface, serves as an ideal precursor to create sodium ion battery anodes with some of the most attractive electrochemical properties ever reported for carbonaceous materials.
Abstract: We demonstrate that peat moss, a wild plant that covers 3% of the earth’s surface, serves as an ideal precursor to create sodium ion battery (NIB) anodes with some of the most attractive electrochemical properties ever reported for carbonaceous materials. By inheriting the unique cellular structure of peat moss leaves, the resultant materials are composed of three-dimensional macroporous interconnected networks of carbon nanosheets (as thin as 60 nm). The peat moss tissue is highly cross-linked, being rich in lignin and hemicellulose, suppressing the nucleation of equilibrium graphite even at 1100 °C. Rather, the carbons form highly ordered pseudographitic arrays with substantially larger intergraphene spacing (0.388 nm) than graphite (c/2 = 0.3354 nm). XRD analysis demonstrates that this allows for significant Na intercalation to occur even below 0.2 V vs Na/Na+. By also incorporating a mild (300 °C) air activation step, we introduce hierarchical micro- and mesoporosity that tremendously improves the hig...
Tulane University1, University of Pittsburgh2, Aarhus University3, University of Alberta4, University of Leicester5, Princeton University6, Oregon Health & Science University7, Korea Institute of Science and Technology8, Nazarbayev University9, Troy University10, Universidade Federal do Rio Grande do Sul11, University of Toronto12, University of Southern Mississippi13, University of Zurich14, DePauw University15
TL;DR: A detailed catalog of zebrafish behaviors that covers both larval and adult models is developed, representing a beginning of creating a more comprehensive ethogram ofZebrafish behavior, which will improve interpretation of published findings, foster cross-species behavioral modeling, and encourage new groups to apply zebra fish neurobehavioral paradigms in their research.
Abstract: Zebrafish (Danio rerio) are rapidly gaining popularity in translational neuroscience and behavioral research. Physiological similarity to mammals, ease of genetic manipulations, sensitivity to pharmacological and genetic factors, robust behavior, low cost, and potential for high-throughput screening contribute to the growing utility of zebrafish models in this field. Understanding zebrafish behavioral phenotypes provides important insights into neural pathways, physiological biomarkers, and genetic underpinnings of normal and pathological brain function. Novel zebrafish paradigms continue to appear with an encouraging pace, thus necessitating a consistent terminology and improved understanding of the behavioral repertoire. What can zebrafish 'do', and how does their altered brain function translate into behavioral actions? To help address these questions, we have developed a detailed catalog of zebrafish behaviors (Zebrafish Behavior Catalog, ZBC) that covers both larval and adult models. Representing a beginning of creating a more comprehensive ethogram of zebrafish behavior, this effort will improve interpretation of published findings, foster cross-species behavioral modeling, and encourage new groups to apply zebrafish neurobehavioral paradigms in their research. In addition, this glossary creates a framework for developing a zebrafish neurobehavioral ontology, ultimately to become part of a unified animal neurobehavioral ontology, which collectively will contribute to better integration of biological data within and across species.
TL;DR: The gut microbiota of healthy Canadian infants is characterized and the effects of delivery mode and infant diet as determinants of this essential microbial community in early life are described and advance the understanding of the gut microbiota in healthy infants.
Abstract: Background: The gut microbiota is essential to human health throughout life, yet the acquisition and development of this microbial community during infancy remains poorly understood. Meanwhile, there is increasing concern over rising rates of cesarean delivery and insufficient exclusive breastfeeding of infants in developed countries. In this article, we characterize the gut microbiota of healthy Canadian infants and describe the influence of cesarean delivery and formula feeding. Methods: We included a subset of 24 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mode of delivery was obtained from medical records, and mothers were asked to report on infant diet and medication use. Fecal samples were collected at 4 months of age, and we characterized the microbiota composition using high-throughput DNA sequencing. Results: We observed high variability in the profiles of fecal microbiota among the infants. The profiles were generally dominated by Actinobacteria (mainly the genus Bifidobacterium ) and Firmicutes (with diverse representation from numerous genera). Compared with breastfed infants, formula-fed infants had increased richness of species, with overrepresentation of Clostridium difficile. Escherichia–Shigella and Bacteroides species were underrepresented in infants born by cesarean delivery. Infants born by elective cesarean delivery had particularly low bacterial richness and diversity. Interpretation: These findings advance our understanding of the gut microbiota in healthy infants. They also provide new evidence for the effects of delivery mode and infant diet as determinants of this essential microbial community in early life.
Libin Cardiovascular Institute of Alberta1, Montreal Heart Institute2, Robarts Research Institute3, University of British Columbia4, University of Ottawa5, Laval University6, McGill University7, Centre Hospitalier Universitaire de Sherbrooke8, McMaster University9, University of Calgary10, University of Toronto11, Population Health Research Institute12, University of Alberta13, Halifax14
TL;DR: An updated version of the CCS Dyslipidemia guidelines is presented, incorporating new recommendations based on recent findings and harmonizing CCS guidelines with those from other Societies, to increase the appropriate use of evidence-based cardiovascular disease event risk assessment in the management of dys Lipidemia.
TL;DR: The concept of ROC curves are introduced and their use in single biomarker analysis for clinical chemistry is described and the meaning of area under R OC curves under AUC and partial AUC is explained, as well as the calculation of confidence intervals.
Abstract: Metabolomics is increasingly being applied towards the identification of biomarkers for disease diagnosis, prognosis and risk prediction. Unfortunately among the many published metabolomic studies focusing on biomarker discovery, there is very little consistency and relatively little rigor in how researchers select, assess or report their candidate biomarkers. In particular, few studies report any measure of sensitivity, specificity, or provide receiver operator characteristic (ROC) curves with associated confidence intervals. Even fewer studies explicitly describe or release the biomarker model used to generate their ROC curves. This is surprising given that for biomarker studies in most other biomedical fields, ROC curve analysis is generally considered the standard method for performance assessment. Because the ultimate goal of biomarker discovery is the translation of those biomarkers to clinical practice, it is clear that the metabolomics community needs to start “speaking the same language” in terms of biomarker analysis and reporting-especially if it wants to see metabolite markers being routinely used in the clinic. In this tutorial, we will first introduce the concept of ROC curves and describe their use in single biomarker analysis for clinical chemistry. This includes the construction of ROC curves, understanding the meaning of area under ROC curves (AUC) and partial AUC, as well as the calculation of confidence intervals. The second part of the tutorial focuses on biomarker analyses within the context of metabolomics. This section describes different statistical and machine learning strategies that can be used to create multi-metabolite biomarker models and explains how these models can be assessed using ROC curves. In the third part of the tutorial we discuss common issues and potential pitfalls associated with different analysis methods and provide readers with a list of nine recommendations for biomarker analysis and reporting. To help readers test, visualize and explore the concepts presented in this tutorial, we also introduce a web-based tool called ROCCET (ROC Curve Explorer & Tester, http://www.roccet.ca). ROCCET was originally developed as a teaching aid but it can also serve as a training and testing resource to assist metabolomics researchers build biomarker models and conduct a range of common ROC curve analyses for biomarker studies.
TL;DR: The goal is to not only conceptually review the results in this area but also to provide enough algorithmic details so that the advantages and disadvantages of the various approaches can become quite clear.
TL;DR: Developing or progression of chronic kidney disease after one or more episode of acute kidney injury could have striking socioeconomic and public health outcomes for all countries.
University of Copenhagen1, University of Alberta2, University of California, Santa Cruz3, Technical University of Denmark4, University of Chicago5, University of Bristol6, University of California, Berkeley7, Macau University of Science and Technology8, University of Texas at Austin9, University of Southampton10, Norwegian University of Life Sciences11, Centre national de la recherche scientifique12, Uppsala University13, Cornell University14, Copenhagen Zoo15, King Saud University16, University of York17
TL;DR: Thealyses suggest that the Equus lineage giving rise to all contemporary horses, zebras and donkeys originated 4.0–4.5 million years before present, twice the conventionally accepted time to the most recent common ancestor of the genus Equus, and supports the contention that Przewalski's horses represent the last surviving wild horse population.
Abstract: The rich fossil record of equids has made them a model for evolutionary processes. Here we present a 1.12-times coverage draft genome from a horse bone recovered from permafrost dated to approximately 560-780 thousand years before present (kyr BP). Our data represent the oldest full genome sequence determined so far by almost an order of magnitude. For comparison, we sequenced the genome of a Late Pleistocene horse (43 kyr BP), and modern genomes of five domestic horse breeds (Equus ferus caballus), a Przewalski's horse (E. f. przewalskii) and a donkey (E. asinus). Our analyses suggest that the Equus lineage giving rise to all contemporary horses, zebras and donkeys originated 4.0-4.5 million years before present (Myr BP), twice the conventionally accepted time to the most recent common ancestor of the genus Equus. We also find that horse population size fluctuated multiple times over the past 2 Myr, particularly during periods of severe climatic changes. We estimate that the Przewalski's and domestic horse populations diverged 38-72 kyr BP, and find no evidence of recent admixture between the domestic horse breeds and the Przewalski's horse investigated. This supports the contention that Przewalski's horses represent the last surviving wild horse population. We find similar levels of genetic variation among Przewalski's and domestic populations, indicating that the former are genetically viable and worthy of conservation efforts. We also find evidence for continuous selection on the immune system and olfaction throughout horse evolution. Finally, we identify 29 genomic regions among horse breeds that deviate from neutrality and show low levels of genetic variation compared to the Przewalski's horse. Such regions could correspond to loci selected early during domestication.