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Showing papers by "University of Alberta published in 2018"


Journal ArticleDOI
TL;DR: A PRISMA extension for scoping reviews was needed to provide reporting guidance for this specific type of knowledge synthesis and was developed according to published guidance by the EQUATOR (Enhancing the QUAlity and Transparency of health Research) Network for the development of reporting guidelines.
Abstract: Scoping reviews, a type of knowledge synthesis, follow a systematic approach to map evidence on a topic and identify main concepts, theories, sources, and knowledge gaps. Although more scoping reviews are being done, their methodological and reporting quality need improvement. This document presents the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) checklist and explanation. The checklist was developed by a 24-member expert panel and 2 research leads following published guidance from the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network. The final checklist contains 20 essential reporting items and 2 optional items. The authors provide a rationale and an example of good reporting for each item. The intent of the PRISMA-ScR is to help readers (including researchers, publishers, commissioners, policymakers, health care providers, guideline developers, and patients or consumers) develop a greater understanding of relevant terminology, core concepts, and key items to report for scoping reviews.

11,709 citations


Journal ArticleDOI
Gregory A. Roth1, Gregory A. Roth2, Degu Abate3, Kalkidan Hassen Abate4  +1025 moreInstitutions (333)
TL;DR: Non-communicable diseases comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2).

5,211 citations


Journal ArticleDOI
TL;DR: This year’s update, DrugBank 5.0, represents the most significant upgrade to the database in more than 10 years and significant improvements have been made to the quantity, quality and consistency of drug indications, drug binding data as well as drug-drug and drug-food interactions.
Abstract: DrugBank (www.drugbank.ca) is a web-enabled database containing comprehensive molecular information about drugs, their mechanisms, their interactions and their targets. First described in 2006, DrugBank has continued to evolve over the past 12 years in response to marked improvements to web standards and changing needs for drug research and development. This year's update, DrugBank 5.0, represents the most significant upgrade to the database in more than 10 years. In many cases, existing data content has grown by 100% or more over the last update. For instance, the total number of investigational drugs in the database has grown by almost 300%, the number of drug-drug interactions has grown by nearly 600% and the number of SNP-associated drug effects has grown more than 3000%. Significant improvements have been made to the quantity, quality and consistency of drug indications, drug binding data as well as drug-drug and drug-food interactions. A great deal of brand new data have also been added to DrugBank 5.0. This includes information on the influence of hundreds of drugs on metabolite levels (pharmacometabolomics), gene expression levels (pharmacotranscriptomics) and protein expression levels (pharmacoprotoemics). New data have also been added on the status of hundreds of new drug clinical trials and existing drug repurposing trials. Many other important improvements in the content, interface and performance of the DrugBank website have been made and these should greatly enhance its ease of use, utility and potential applications in many areas of pharmacological research, pharmaceutical science and drug education.

4,797 citations


Journal ArticleDOI
Jeffrey D. Stanaway1, Ashkan Afshin1, Emmanuela Gakidou1, Stephen S Lim1  +1050 moreInstitutions (346)
TL;DR: This study estimated levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs) by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017 and explored the relationship between development and risk exposure.

2,910 citations


Journal ArticleDOI
TL;DR: The user interface of MetaboAnalyst 4.0 has been reengineered to provide a more modern look and feel, as well as to give more space and flexibility to introduce new functions.
Abstract: We present a new update to MetaboAnalyst (version 4.0) for comprehensive metabolomic data analysis, interpretation, and integration with other omics data. Since the last major update in 2015, MetaboAnalyst has continued to evolve based on user feedback and technological advancements in the field. For this year's update, four new key features have been added to MetaboAnalyst 4.0, including: (1) real-time R command tracking and display coupled with the release of a companion MetaboAnalystR package; (2) a MS Peaks to Pathways module for prediction of pathway activity from untargeted mass spectral data using the mummichog algorithm; (3) a Biomarker Meta-analysis module for robust biomarker identification through the combination of multiple metabolomic datasets and (4) a Network Explorer module for integrative analysis of metabolomics, metagenomics, and/or transcriptomics data. The user interface of MetaboAnalyst 4.0 has been reengineered to provide a more modern look and feel, as well as to give more space and flexibility to introduce new functions. The underlying knowledgebases (compound libraries, metabolite sets, and metabolic pathways) have also been updated based on the latest data from the Human Metabolome Database (HMDB). A Docker image of MetaboAnalyst is also available to facilitate download and local installation of MetaboAnalyst. MetaboAnalyst 4.0 is freely available at http://metaboanalyst.ca.

2,857 citations


Journal ArticleDOI
TL;DR: This year's update to the HMDB, HMDB 4.0, represents the most significant upgrade to the database in its history and should greatly enhance its ease of use and its potential applications in nutrition, biochemistry, clinical chemistry, clinical genetics, medicine, and metabolomics science.
Abstract: The Human Metabolome Database or HMDB (www.hmdb.ca) is a web-enabled metabolomic database containing comprehensive information about human metabolites along with their biological roles, physiological concentrations, disease associations, chemical reactions, metabolic pathways, and reference spectra. First described in 2007, the HMDB is now considered the standard metabolomic resource for human metabolic studies. Over the past decade the HMDB has continued to grow and evolve in response to emerging needs for metabolomics researchers and continuing changes in web standards. This year's update, HMDB 4.0, represents the most significant upgrade to the database in its history. For instance, the number of fully annotated metabolites has increased by nearly threefold, the number of experimental spectra has grown by almost fourfold and the number of illustrated metabolic pathways has grown by a factor of almost 60. Significant improvements have also been made to the HMDB's chemical taxonomy, chemical ontology, spectral viewing, and spectral/text searching tools. A great deal of brand new data has also been added to HMDB 4.0. This includes large quantities of predicted MS/MS and GC-MS reference spectral data as well as predicted (physiologically feasible) metabolite structures to facilitate novel metabolite identification. Additional information on metabolite-SNP interactions and the influence of drugs on metabolite levels (pharmacometabolomics) has also been added. Many other important improvements in the content, the interface, and the performance of the HMDB website have been made and these should greatly enhance its ease of use and its potential applications in nutrition, biochemistry, clinical chemistry, clinical genetics, medicine, and metabolomics science.

2,608 citations


Journal ArticleDOI
TL;DR: Indirect comparisons suggest combination therapy provides improved efficacy relative to anti-programmed death-1 monotherapy and has a favorable benefit-risk profile.
Abstract: PurposeNivolumab provides clinical benefit (objective response rate [ORR], 31%; 95% CI, 20.8 to 42.9; disease control rate, 69%; 12-month overall survival [OS], 73%) in previously treated patients with DNA mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) metastatic colorectal cancer (mCRC); nivolumab plus ipilimumab may improve these outcomes. Efficacy and safety results for the nivolumab plus ipilimumab cohort of CheckMate-142, the largest single-study report of an immunotherapy combination in dMMR/MSI-H mCRC, are reported.Patients and MethodsPatients received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks. Primary end point was investigator-assessed ORR.ResultsOf 119 patients, 76% had received ≥ two prior systemic therapies. At median follow-up of 13.4 months, investigator-assessed ORR was 55% (95% CI, 45.2 to 63.8), and disease control rate for ≥ 12 weeks was 80%. Median duration of response was not reac...

1,339 citations


Journal ArticleDOI
TL;DR: This review will focus on dietary fibers, which interact directly with gut microbes and lead to the production of key metabolites such as short-chain fatty acids, and discuss how dietary fiber impacts gut microbial ecology, host physiology, and health.

1,216 citations



Journal ArticleDOI
13 Jun 2018-BMJ
TL;DR: Ana M Valdes and colleagues discuss strategies for modulating the gut microbiota through diet and probiotics and suggest that a Mediterranean diet supplemented with probiotics can be a viable alternative to a probiotic regime.
Abstract: Ana M Valdes and colleagues discuss strategies for modulating the gut microbiota through diet and probiotics

1,019 citations


Journal ArticleDOI
18 Jan 2018
TL;DR: Cachexia is a disorder characterized by loss of body weight with specific losses of skeletal muscle and adipose tissue as mentioned in this paper, which is associated with cancers of the pancreas, oesophagus, stomach, lung, liver and bowel.
Abstract: Cancer-associated cachexia is a disorder characterized by loss of body weight with specific losses of skeletal muscle and adipose tissue. Cachexia is driven by a variable combination of reduced food intake and metabolic changes, including elevated energy expenditure, excess catabolism and inflammation. Cachexia is highly associated with cancers of the pancreas, oesophagus, stomach, lung, liver and bowel; this group of malignancies is responsible for half of all cancer deaths worldwide. Cachexia involves diverse mediators derived from the cancer cells and cells within the tumour microenvironment, including inflammatory and immune cells. In addition, endocrine, metabolic and central nervous system perturbations combine with these mediators to elicit catabolic changes in skeletal and cardiac muscle and adipose tissue. At the tissue level, mechanisms include activation of inflammation, proteolysis, autophagy and lipolysis. Cachexia associates with a multitude of morbidities encompassing functional, metabolic and immune disorders as well as aggravated toxicity and complications of cancer therapy. Patients experience impaired quality of life, reduced physical, emotional and social well-being and increased use of healthcare resources. To date, no effective medical intervention completely reverses cachexia and there are no approved drug therapies. Adequate nutritional support remains a mainstay of cachexia therapy, whereas drugs that target overactivation of catabolic processes, cell injury and inflammation are currently under investigation.

Journal ArticleDOI
TL;DR: The Banff ABMR criteria are updated and paves the way for the Banff scheme to be part of an integrative approach for defining surrogate endpoints in next‐generation clinical trials.

Journal ArticleDOI
TL;DR: The human genome encodes 538 protein kinases that transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues, which are the second most targeted group of drug targets, after the G-protein-coupled receptors.
Abstract: The human genome encodes 538 protein kinases that transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are associated with human cancer initiation and progression. The recent development of small-molecule kinase inhibitors for the treatment of diverse types of cancer has proven successful in clinical therapy. Significantly, protein kinases are the second most targeted group of drug targets, after the G-protein-coupled receptors. Since the development of the first protein kinase inhibitor, in the early 1980s, 37 kinase inhibitors have received FDA approval for treatment of malignancies such as breast and lung cancer. Furthermore, about 150 kinase-targeted drugs are in clinical phase trials, and many kinase-specific inhibitors are in the preclinical stage of drug development. Nevertheless, many factors confound the clinical efficacy of these molecules. Specific tumor genetics, tumor microenvironment, drug resistance, and pharmacogenomics determine how useful a compound will be in the treatment of a given cancer. This review provides an overview of kinase-targeted drug discovery and development in relation to oncology and highlights the challenges and future potential for kinase-targeted cancer therapies.

Journal ArticleDOI
Marlee A. Tucker1, Katrin Böhning-Gaese1, William F. Fagan2, John M. Fryxell3, Bram Van Moorter, Susan C. Alberts4, Abdullahi H. Ali, Andrew M. Allen5, Andrew M. Allen6, Nina Attias7, Tal Avgar8, Hattie L. A. Bartlam-Brooks9, Buuveibaatar Bayarbaatar10, Jerrold L. Belant11, Alessandra Bertassoni12, Dean E. Beyer13, Laura R. Bidner14, Floris M. van Beest15, Stephen Blake10, Stephen Blake16, Niels Blaum17, Chloe Bracis1, Danielle D. Brown18, P J Nico de Bruyn19, Francesca Cagnacci20, Francesca Cagnacci21, Justin M. Calabrese2, Justin M. Calabrese22, Constança Camilo-Alves23, Simon Chamaillé-Jammes24, André Chiaradia25, André Chiaradia26, Sarah C. Davidson16, Sarah C. Davidson27, Todd E. Dennis28, Stephen DeStefano29, Duane R. Diefenbach30, Iain Douglas-Hamilton31, Iain Douglas-Hamilton32, Julian Fennessy, Claudia Fichtel33, Wolfgang Fiedler16, Christina Fischer34, Ilya R. Fischhoff35, Christen H. Fleming2, Christen H. Fleming22, Adam T. Ford36, Susanne A. Fritz1, Benedikt Gehr37, Jacob R. Goheen38, Eliezer Gurarie2, Eliezer Gurarie39, Mark Hebblewhite40, Marco Heurich41, Marco Heurich42, A. J. Mark Hewison43, Christian Hof, Edward Hurme2, Lynne A. Isbell14, René Janssen, Florian Jeltsch17, Petra Kaczensky44, Adam Kane45, Peter M. Kappeler33, Matthew J. Kauffman38, Roland Kays46, Roland Kays47, Duncan M. Kimuyu48, Flávia Koch33, Flávia Koch49, Bart Kranstauber37, Scott D. LaPoint50, Scott D. LaPoint16, Peter Leimgruber22, John D. C. Linnell, Pascual López-López51, A. Catherine Markham52, Jenny Mattisson, Emília Patrícia Medici53, Ugo Mellone54, Evelyn H. Merrill8, Guilherme Miranda de Mourão55, Ronaldo Gonçalves Morato, Nicolas Morellet43, Thomas A. Morrison56, Samuel L. Díaz-Muñoz57, Samuel L. Díaz-Muñoz14, Atle Mysterud58, Dejid Nandintsetseg1, Ran Nathan59, Aidin Niamir, John Odden, Robert B. O'Hara60, Luiz Gustavo R. Oliveira-Santos7, Kirk A. Olson10, Bruce D. Patterson61, Rogério Cunha de Paula, Luca Pedrotti, Björn Reineking62, Björn Reineking63, Martin Rimmler, Tracey L. Rogers64, Christer Moe Rolandsen, Christopher S. Rosenberry65, Daniel I. Rubenstein66, Kamran Safi16, Kamran Safi67, Sonia Saïd, Nir Sapir68, Hall Sawyer, Niels Martin Schmidt15, Nuria Selva69, Agnieszka Sergiel69, Enkhtuvshin Shiilegdamba10, João P. Silva70, João P. Silva71, João P. Silva72, Navinder J. Singh6, Erling Johan Solberg, Orr Spiegel14, Olav Strand, Siva R. Sundaresan, Wiebke Ullmann17, Ulrich Voigt44, Jake Wall32, David W. Wattles29, Martin Wikelski16, Martin Wikelski67, Christopher C. Wilmers73, John W. Wilson74, George Wittemyer32, George Wittemyer75, Filip Zięba, Tomasz Zwijacz-Kozica, Thomas Mueller1, Thomas Mueller22 
Goethe University Frankfurt1, University of Maryland, College Park2, University of Guelph3, Duke University4, Radboud University Nijmegen5, Swedish University of Agricultural Sciences6, Federal University of Mato Grosso do Sul7, University of Alberta8, Royal Veterinary College9, Wildlife Conservation Society10, Mississippi State University11, Sao Paulo State University12, Michigan Department of Natural Resources13, University of California, Davis14, Aarhus University15, Max Planck Society16, University of Potsdam17, Middle Tennessee State University18, Mammal Research Institute19, Edmund Mach Foundation20, Harvard University21, Smithsonian Conservation Biology Institute22, University of Évora23, University of Montpellier24, Monash University25, Parks Victoria26, Ohio State University27, Fiji National University28, University of Massachusetts Amherst29, United States Geological Survey30, University of Oxford31, Save the Elephants32, German Primate Center33, Technische Universität München34, Institute of Ecosystem Studies35, University of British Columbia36, University of Zurich37, University of Wyoming38, University of Washington39, University of Montana40, University of Freiburg41, Bavarian Forest National Park42, University of Toulouse43, University of Veterinary Medicine Vienna44, University College Cork45, North Carolina State University46, North Carolina Museum of Natural Sciences47, Karatina University48, University of Lethbridge49, Lamont–Doherty Earth Observatory50, University of Valencia51, Stony Brook University52, International Union for Conservation of Nature and Natural Resources53, University of Alicante54, Empresa Brasileira de Pesquisa Agropecuária55, University of Glasgow56, New York University57, University of Oslo58, Hebrew University of Jerusalem59, Norwegian University of Science and Technology60, Field Museum of Natural History61, University of Bayreuth62, University of Grenoble63, University of New South Wales64, Pennsylvania Game Commission65, Princeton University66, University of Konstanz67, University of Haifa68, Polish Academy of Sciences69, Instituto Superior de Agronomia70, University of Lisbon71, University of Porto72, University of California, Santa Cruz73, University of Pretoria74, Colorado State University75
26 Jan 2018-Science
TL;DR: Using a unique GPS-tracking database of 803 individuals across 57 species, it is found that movements of mammals in areas with a comparatively high human footprint were on average one-half to one-third the extent of their movements in area with a low human footprint.
Abstract: Animal movement is fundamental for ecosystem functioning and species survival, yet the effects of the anthropogenic footprint on animal movements have not been estimated across species. Using a unique GPS-tracking database of 803 individuals across 57 species, we found that movements of mammals in areas with a comparatively high human footprint were on average one-half to one-third the extent of their movements in areas with a low human footprint. We attribute this reduction to behavioral changes of individual animals and to the exclusion of species with long-range movements from areas with higher human impact. Global loss of vagility alters a key ecological trait of animals that affects not only population persistence but also ecosystem processes such as predator-prey interactions, nutrient cycling, and disease transmission.

Journal ArticleDOI
TL;DR: This paper aims to provide a contemporary and comprehensive literature review on fundamentals, applications, challenges, and research efforts/progress of ambient backscatter communications.
Abstract: Recently, ambient backscatter communication has been introduced as a cutting-edge technology which enables smart devices to communicate by utilizing ambient radio frequency (RF) signals without requiring active RF transmission. This technology is especially effective in addressing communication and energy efficiency problems for low-power communications systems such as sensor networks, and thus it is expected to realize numerous Internet-of-Things applications. Therefore, this paper aims to provide a contemporary and comprehensive literature review on fundamentals, applications, challenges, and research efforts/progress of ambient backscatter communications. In particular, we first present fundamentals of backscatter communications and briefly review bistatic backscatter communications systems. Then, the general architecture, advantages, and solutions to address existing issues and limitations of ambient backscatter communications systems are discussed. Additionally, emerging applications of ambient backscatter communications are highlighted. Finally, we outline some open issues and future research directions.

Journal ArticleDOI
TL;DR: Inspired by the phototaxis and Lévy flights of the moths, a new kind of metaheuristic algorithm, called moth search (MS) algorithm, is developed in the present work and significantly outperforms five other methods on most test functions and engineering cases.
Abstract: Phototaxis, signifying movement of an organism towards or away from a source of light, is one of the most representative features for moths. It has recently been shown that one of the characteristics of moths has been the propensity to follow Levy flights. Inspired by the phototaxis and Levy flights of the moths, a new kind of metaheuristic algorithm, called moth search (MS) algorithm, is developed in the present work. In nature, moths are a family insects associated with butterflies belonging to the order Lepidoptera. In MS method, the best moth individual is viewed as the light source. Some moths that are close to the fittest one always display an inclination to fly around their own positions in the form of Levy flights. On the contrary, due to phototaxis, the moths that are comparatively far from the fittest one will tend to fly towards the best one directly in a big step. These two features correspond to the processes of exploitation and exploration of any metaheuristic optimization method. The phototaxis and Levy flights of the moths can be used to build up a general-purpose optimization method. In order to demonstrate the superiority of its performance, the MS method is further compared with five other state-of-the-art metaheuristic optimization algorithms through an array of experiments on fourteen basic benchmarks, eleven IEEE CEC 2005 complicated benchmarks and seven IEEE CEC 2011 real world problems. The results clearly demonstrate that MS significantly outperforms five other methods on most test functions and engineering cases.

Journal ArticleDOI
TL;DR: A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology of PrCa1.
Abstract: Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10−9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55–2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04–6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1. A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology.

Journal ArticleDOI
TL;DR: Questioning the disruptive talk associated with digital transformation, it is suggested that the institutional perspective is a prolific lens to study digital innovation and transformation and that existing institutional arrangements are pivotal arbiters in deciding whether and how novel arrangements gain acceptance.

Journal ArticleDOI
TL;DR: The global epidemiology of acute kidney injury is described and the influence of modifiable and non-modifiable AKI risk factors, delayed diagnosis, variation in diagnostic criteria and disparities in access to health care are also discussed.
Abstract: Acute kidney injury (AKI) is a commonly encountered syndrome associated with various aetiologies and pathophysiological processes leading to decreased kidney function. In addition to retention of waste products, impaired electrolyte homeostasis and altered drug concentrations, AKI induces a generalized inflammatory response that affects distant organs. Full recovery of kidney function is uncommon, which leaves these patients at risk of long-term morbidity and death. Estimates of AKI prevalence range from <1% to 66%. These variations can be explained by not only population differences but also inconsistent use of standardized AKI classification criteria. The aetiology and incidence of AKI also differ between high-income and low-to-middle-income countries. High-income countries show a lower incidence of AKI than do low-to-middle-income countries, where contaminated water and endemic diseases such as malaria contribute to a high burden of AKI. Outcomes of AKI are similar to or more severe than those of patients in high-income countries. In all resource settings, suboptimal early recognition and care of patients with AKI impede their recovery and lead to high mortality, which highlights unmet needs for improved detection and diagnosis of AKI and for efforts to improve care for these patients.

Journal ArticleDOI
TL;DR: Single‐dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superiorto both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza.
Abstract: Background Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infection...

Journal ArticleDOI
Craig E. Aalseth1, Fabio Acerbi2, P. Agnes3, Ivone F. M. Albuquerque4  +297 moreInstitutions (48)
TL;DR: The DarkSide-20k detector as discussed by the authors is a direct WIMP search detector using a two-phase Liquid Argon Time Projection Chamber (LAr TPC) with an active mass of 23 t (20 t).
Abstract: Building on the successful experience in operating the DarkSide-50 detector, the DarkSide Collaboration is going to construct DarkSide-20k, a direct WIMP search detector using a two-phase Liquid Argon Time Projection Chamber (LAr TPC) with an active (fiducial) mass of 23 t (20 t). This paper describes a preliminary design for the experiment, in which the DarkSide-20k LAr TPC is deployed within a shield/veto with a spherical Liquid Scintillator Veto (LSV) inside a cylindrical Water Cherenkov Veto (WCV). This preliminary design provides a baseline for the experiment to achieve its physics goals, while further development work will lead to the final optimization of the detector parameters and an eventual technical design. Operation of DarkSide-50 demonstrated a major reduction in the dominant 39Ar background when using argon extracted from an underground source, before applying pulse shape analysis. Data from DarkSide-50, in combination with MC simulation and analytical modeling, shows that a rejection factor for discrimination between electron and nuclear recoils of $>3 \times 10^{9}$ is achievable. This, along with the use of the veto system and utilizing silicon photomultipliers in the LAr TPC, are the keys to unlocking the path to large LAr TPC detector masses, while maintaining an experiment in which less than $< 0.1$ events (other than $ u$ -induced nuclear recoils) is expected to occur within the WIMP search region during the planned exposure. DarkSide-20k will have ultra-low backgrounds than can be measured in situ, giving sensitivity to WIMP-nucleon cross sections of $1.2 \times 10^{-47}$ cm2 ( $1.1 \times 10^{-46}$ cm2) for WIMPs of 1 TeV/c2 (10 TeV/c2) mass, to be achieved during a 5 yr run producing an exposure of 100 t yr free from any instrumental background.

Journal ArticleDOI
TL;DR: This article provided a synthesized summary of a Showcase Symposium held at the 2016 Academy of Management Annual Meeting in which prominent scholars such as Denny Gioia, Domenico et al. participated.
Abstract: This article, together with a companion video, provides a synthesized summary of a Showcase Symposium held at the 2016 Academy of Management Annual Meeting in which prominent scholars—Denny Gioia, ...

Journal ArticleDOI
TL;DR: New approaches being taken by analytical chemists, engineers, toxicologists and epidemiologists to characterize theDBP classes driving disinfected water toxicity are discussed, and it is suggested that DBP exposure should be measured using other DBP classes in addition to THMs.
Abstract: While drinking water disinfection has effectively prevented waterborne diseases, an unintended consequence is the generation of disinfection byproducts (DBPs). Epidemiological studies have consistently observed an association between consumption of chlorinated drinking water with an increased risk of bladder cancer. Out of the >600 DBPs identified, regulations focus on a few classes, such as trihalomethanes (THMs), whose concentrations were hypothesized to correlate with the DBPs driving the toxicity of disinfected waters. However, the DBPs responsible for the bladder cancer association remain unclear. Utilities are switching away from a reliance on chlorination of pristine drinking water supplies to the application of new disinfectant combinations to waters impaired by wastewater effluents and algal blooms. In light of these changes in disinfection practice, this article discusses new approaches being taken by analytical chemists, engineers, toxicologists and epidemiologists to characterize the DBP classes driving disinfected water toxicity, and suggests that DBP exposure should be measured using other DBP classes in addition to THMs.

Journal ArticleDOI
Carolina Roselli1, Mark Chaffin1, Lu-Chen Weng1, Lu-Chen Weng2  +257 moreInstitutions (82)
TL;DR: This large, multi-ethnic genome-wide association study identifies 97 loci significantly associated with atrial fibrillation that are enriched for genes involved in cardiac development, electrophysiology, structure and contractile function.
Abstract: Atrial fibrillation (AF) affects more than 33 million individuals worldwide1 and has a complex heritability2. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.

Journal ArticleDOI
TL;DR: The IOC RED-S consensus authors have reconvened to provide an update summary of the interim scientific progress in the field of relative energy deficiency with the ultimate goal of stimulating advances inRED-S awareness, clinical application and scientific research to address current gaps in knowledge.
Abstract: In 2014, the IOC published a consensus statement entitled ‘Beyond the Female Athlete Triad: Relative Energy Deficiency in Sport (RED-S)’. The syndrome of RED-S refers to ‘impaired physiological functioning caused by relative energy deficiency and includes, but is not limited to, impairments of metabolic rate, menstrual function, bone health, immunity, protein synthesis and cardiovascular health’. The aetiological factor of this syndrome is low energy availability (LEA).1 The publication of the RED-S consensus statement stimulated activity in the field of Female Athlete Triad science, including some initial controversy2 3 followed by numerous scientific publications addressing: 1. The health parameters identified in the RED-S conceptual model (figure 1).1 4 2. Relative energy deficiency in male athletes. 3. The measurement of LEA. 4. The performance parameters identified in the RED-S conceptual model (figure 2).1 4 The IOC RED-S consensus authors have reconvened to provide an update summary of the interim scientific progress in the field of relative energy deficiency with the ultimate goal of stimulating advances in RED-S awareness, clinical application and scientific research to address current gaps in knowledge. Figure 1 Health consequences of Relative Energy Deficiency in Sport (RED-S) showing an expanded concept of the Female Athlete Triad to acknowledge a wider range of outcomes and the application to male athletes (*Psychological consequences can either precede RED-S or be the result of RED-S).1 4 Figure 2 Potential Performance consequences of Relative Energy Deficiency in Sport (*Aerobic and anerobic performance).1 4 ### Low energy availability LEA, which underpins the concept of RED-S, is a mismatch between an athlete’s energy intake (diet) and the energy expended in exercise, leaving inadequate energy to support the functions required by the body to maintain optimal health and performance. Operationally, energy availability (EA) is defined as: ![Formula][1] where exercise energy expenditure (EEE) is calculated as the additional energy expended above that of … [1]: /embed/mml-math-1.gif

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Kara Nerenberg1, Kelly B. Zarnke1, Alexander A. Leung1, Kaberi Dasgupta2, Sonia Butalia3, Kerry McBrien1, Kevin C. Harris4, Meranda Nakhla2, Lyne Cloutier5, Mark Gelfer4, Maxime Lamarre-Cliche6, Alain Milot7, Peter Bolli8, Guy Tremblay, Donna McLean9, Raj Padwal10, Karen C. Tran4, Steven A. Grover11, Simon W. Rabkin4, Gordon W. Moe12, Jonathan G. Howlett1, Patrice Lindsay13, Michael D. Hill1, Mike Sharma14, Thalia S. Field4, Theodore Wein15, Ashkan Shoamanesh14, George K. Dresser16, Pavel Hamet6, Robert J. Herman1, Ellen Burgess1, Steven E. Gryn16, Jean Grégoire17, Richard Lewanczuk10, Luc Poirier, Tavis S. Campbell1, Ross D. Feldman18, Kim L. Lavoie19, Ross T. Tsuyuki10, George Honos6, Ally P.H. Prebtani8, Gregory A. Kline1, Ernesto L. Schiffrin11, Andrew C. Don-Wauchope8, Sheldon W. Tobe20, Richard E. Gilbert21, Lawrence A. Leiter21, Charlotte Jones, Vincent Woo22, Robert A. Hegele16, Peter Selby23, Andrew L. Pipe24, Philip A. McFarlane12, Paul Oh25, Milan Gupta8, Simon L. Bacon26, Janusz Kaczorowski6, Luc Trudeau11, Norman R.C. Campbell1, Swapnil Hiremath27, Michael Roerecke23, JoAnne Arcand28, Marcel Ruzicka24, G. V. Ramesh Prasad12, Michel Vallée29, Cedric Edwards24, Praveena Sivapalan30, S. Brian Penner22, Anne Fournier31, Geneviève Benoit31, Janusz Feber32, Janis M. Dionne4, Laura A. Magee33, Alexander G. Logan34, Anne-Marie Côté35, Evelyne Rey6, Tabassum Firoz36, Laura M. Kuyper4, Jonathan Y. Gabor37, Raymond R. Townsend38, Doreen M. Rabi1, Doreen M. Rabi3, Stella S. Daskalopoulou11 
TL;DR: All individuals with hypertension should have an assessment of global cardiovascular risk to promote health behaviours that lower blood pressure, and an angiotensin receptor-neprilysin inhibitor combination should be used in place of either an ang Elliotensin-converting enzyme inhibitor or angiotENSin receptor blocker in individuals with heart failure.

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TL;DR: The 2016 SOSORT guidelines were developed based on the current evidence on CTIS and include a total of 68 recommendations divided into following topics: bracing, PSSE to prevent scoliosis progression during growth, other conservative treatments, respiratory function and exercises and assessment.
Abstract: The International Scientific Society on Scoliosis Orthopaedic and Rehabilitation Treatment (SOSORT) produced its first guidelines in 2005 and renewed them in 2011. Recently published high-quality clinical trials on the effect of conservative treatment approaches (braces and exercises) for idiopathic scoliosis prompted us to update the last guidelines’ version. The objective was to align the guidelines with the new scientific evidence to assure faster knowledge transfer into clinical practice of conservative treatment for idiopathic scoliosis (CTIS). Physicians, researchers and allied health practitioners working in the area of CTIS were involved in the development of the 2016 guidelines. Multiple literature reviews reviewing the evidence on CTIS (assessment, bracing, physiotherapy, physiotherapeutic scoliosis-specific exercises (PSSE) and other CTIS) were conducted. Documents, recommendations and practical approach flow charts were developed using a Delphi procedure. The process was completed with the Consensus Session held during the first combined SOSORT/IRSSD Meeting held in Banff, Canada, in May 2016. The contents of the new 2016 guidelines include the following: background on idiopathic scoliosis, description of CTIS approaches for various populations with flow-charts for clinical practice, as well as literature reviews and recommendations on assessment, bracing, PSSE and other CTIS. The present guidelines include a total of 68 recommendations divided into following topics: bracing (n = 25), PSSE to prevent scoliosis progression during growth (n = 12), PSSE during brace treatment and surgical therapy (n = 6), other conservative treatments (n = 2), respiratory function and exercises (n = 3), general sport activities (n = 6); and assessment (n = 14). According to the agreed strength and level of evidence rating scale, there were 2 recommendations on bracing and 1 recommendation on PSSE that reached level of recommendation “I” and level of evidence “II”. Three recommendations reached strength of recommendation A based on the level of evidence I (2 for bracing and one for assessment); 39 recommendations reached strength of recommendation B (20 for bracing, 13 for PSSE, and 6 for assessment).The number of paper for each level of evidence for each treatment is shown in Table 8. The 2016 SOSORT guidelines were developed based on the current evidence on CTIS. Over the last 5 years, high-quality evidence has started to emerge, particularly in the areas of efficacy of bracing (one large multicentre trial) and PSSE (three single-centre randomized controlled trials). Several grade A recommendations were presented. Despite the growing high-quality evidence, the heterogeneity of the study protocols limits generalizability of the recommendations. There is a need for standardization of research methods of conservative treatment effectiveness, as recognized by SOSORT and the Scoliosis Research Society (SRS) non-operative management Committee.

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TL;DR: In this paper, the pyrolysis dependent properties of rapeseed stem biochar were investigated under various temperatures (200-700°C, in 50°C intervals), heating rates (1, 5, 10, 15, 20, 20°C/min), and residence times (10,20, 40, 60, 80, 100min).

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TL;DR: Deep stacked autoencoder (SAE) is introduced for soft sensor and shows that the proposed VW-SAE can give better prediction performance than the traditional multilayer neural networks and SAE.
Abstract: In modern industrial processes, soft sensors have played an important role for effective process control, optimization, and monitoring. Feature representation is one of the core factors to construct accurate soft sensors. Recently, deep learning techniques have been developed for high-level abstract feature extraction in pattern recognition areas, which also have great potential for soft sensing applications. Hence, deep stacked autoencoder (SAE) is introduced for soft sensor in this paper. As for output prediction purpose, traditional deep learning algorithms cannot extract high-level output-related features. Thus, a novel variable-wise weighted stacked autoencoder (VW-SAE) is proposed for hierarchical output-related feature representation layer by layer. By correlation analysis with the output variable, important variables are identified from other ones in the input layer of each autoencoder. The variables are assigned with different weights accordingly. Then, variable-wise weighted autoencoders are designed and stacked to form deep networks. An industrial application shows that the proposed VW-SAE can give better prediction performance than the traditional multilayer neural networks and SAE.

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TL;DR: This review shall provide a complete and simple illustrated reference guide of the Banff Classification of Kidney Allograft Pathology based on all publications including the 2017 update, intended as a concise desktop reference for pathologists and clinicians.
Abstract: The Banff Classification of Allograft Pathology is an international consensus classification for the reporting of biopsies from solid organ transplants. Since its initial conception in 1991 for renal transplants, it has undergone review every 2 years, with attendant updated publications. The rapid expansion of knowledge in the field has led to numerous revisions of the classification. The resultant dispersal of relevant content makes it difficult for novices and experienced pathologists to faithfully apply the classification in routine diagnostic work and in clinical trials. This review shall provide a complete and simple illustrated reference guide of the Banff Classification of Kidney Allograft Pathology based on all publications including the 2017 update. It is intended as a concise desktop reference for pathologists and clinicians, providing definitions, Banff Lesion Scores and Banff Diagnostic Categories. An online website reference guide hosted by the Banff Foundation for Allograft Pathology (www.banfffoundation.org) is being developed, which will be updated with future refinement of the Banff Classification from 2019 onward.