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Showing papers by "University of Ottawa published in 2016"


Journal ArticleDOI
Monkol Lek, Konrad J. Karczewski1, Konrad J. Karczewski2, Eric Vallabh Minikel2, Eric Vallabh Minikel1, Kaitlin E. Samocha, Eric Banks2, Timothy Fennell2, Anne H. O’Donnell-Luria3, Anne H. O’Donnell-Luria1, Anne H. O’Donnell-Luria2, James S. Ware, Andrew J. Hill1, Andrew J. Hill4, Andrew J. Hill2, Beryl B. Cummings1, Beryl B. Cummings2, Taru Tukiainen2, Taru Tukiainen1, Daniel P. Birnbaum2, Jack A. Kosmicki, Laramie E. Duncan2, Laramie E. Duncan1, Karol Estrada2, Karol Estrada1, Fengmei Zhao1, Fengmei Zhao2, James Zou2, Emma Pierce-Hoffman2, Emma Pierce-Hoffman1, Joanne Berghout5, David Neil Cooper6, Nicole A. Deflaux7, Mark A. DePristo2, Ron Do, Jason Flannick2, Jason Flannick1, Menachem Fromer, Laura D. Gauthier2, Jackie Goldstein1, Jackie Goldstein2, Namrata Gupta2, Daniel P. Howrigan2, Daniel P. Howrigan1, Adam Kiezun2, Mitja I. Kurki1, Mitja I. Kurki2, Ami Levy Moonshine2, Pradeep Natarajan, Lorena Orozco, Gina M. Peloso2, Gina M. Peloso1, Ryan Poplin2, Manuel A. Rivas2, Valentin Ruano-Rubio2, Samuel A. Rose2, Douglas M. Ruderfer8, Khalid Shakir2, Peter D. Stenson6, Christine Stevens2, Brett Thomas2, Brett Thomas1, Grace Tiao2, María Teresa Tusié-Luna, Ben Weisburd2, Hong-Hee Won9, Dongmei Yu, David Altshuler2, David Altshuler10, Diego Ardissino, Michael Boehnke11, John Danesh12, Stacey Donnelly2, Roberto Elosua, Jose C. Florez2, Jose C. Florez1, Stacey Gabriel2, Gad Getz2, Gad Getz1, Stephen J. Glatt13, Christina M. Hultman14, Sekar Kathiresan, Markku Laakso15, Steven A. McCarroll1, Steven A. McCarroll2, Mark I. McCarthy16, Mark I. McCarthy17, Dermot P.B. McGovern18, Ruth McPherson19, Benjamin M. Neale1, Benjamin M. Neale2, Aarno Palotie, Shaun Purcell8, Danish Saleheen20, Jeremiah M. Scharf, Pamela Sklar, Patrick F. Sullivan14, Patrick F. Sullivan21, Jaakko Tuomilehto22, Ming T. Tsuang23, Hugh Watkins17, Hugh Watkins16, James G. Wilson24, Mark J. Daly2, Mark J. Daly1, Daniel G. MacArthur2, Daniel G. MacArthur1 
18 Aug 2016-Nature
TL;DR: The aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC) provides direct evidence for the presence of widespread mutational recurrence.
Abstract: Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes.

8,758 citations


Journal ArticleDOI
12 Oct 2016-BMJ
TL;DR: Risk of Bias In Non-randomised Studies - of Interventions is developed, a new tool for evaluating risk of bias in estimates of the comparative effectiveness of interventions from studies that did not use randomisation to allocate units or clusters of individuals to comparison groups.
Abstract: Non-randomised studies of the effects of interventions are critical to many areas of healthcare evaluation, but their results may be biased. It is therefore important to understand and appraise their strengths and weaknesses. We developed ROBINS-I (“Risk Of Bias In Non-randomised Studies - of Interventions”), a new tool for evaluating risk of bias in estimates of the comparative effectiveness (harm or benefit) of interventions from studies that did not use randomisation to allocate units (individuals or clusters of individuals) to comparison groups. The tool will be particularly useful to those undertaking systematic reviews that include non-randomised studies.

8,028 citations


Journal ArticleDOI
Daniel J. Klionsky1, Kotb Abdelmohsen2, Akihisa Abe3, Joynal Abedin4  +2519 moreInstitutions (695)
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

5,187 citations


Journal ArticleDOI
Theo Vos1, Christine Allen1, Megha Arora1, Ryan M Barber1  +696 moreInstitutions (260)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) as discussed by the authors was used to estimate the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.

5,050 citations


Journal ArticleDOI
TL;DR: The PRESS 2015 Guideline Statement should help to guide and improve the peer review of electronic literature search strategies and suggested that structured PRESS could identify search errors and improved the selection of search terms.

2,051 citations


Journal ArticleDOI
Nicholas J Kassebaum1, Megha Arora1, Ryan M Barber1, Zulfiqar A Bhutta2  +679 moreInstitutions (268)
TL;DR: In this paper, the authors used the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015.

1,533 citations


Journal ArticleDOI
TL;DR: The Canadian 24-Hour Movement Guidelines for Children and Youth: An Integration of Physical Activity, Sedentary Behaviour, and Sleep provide evidence-informed recommendations for a healthy day (24 h), comprising a combination of sleep, sedentary behaviours, light-, moderate-, and vigorous-intensity physical activity.
Abstract: Leaders from the Canadian Society for Exercise Physiology convened representatives of national organizations, content experts, methodologists, stakeholders, and end-users who followed rigorous and transparent guideline development procedures to create the Canadian 24-Hour Movement Guidelines for Children and Youth: An Integration of Physical Activity, Sedentary Behaviour, and Sleep. These novel guidelines for children and youth aged 5-17 years respect the natural and intuitive integration of movement behaviours across the whole day (24-h period). The development process was guided by the Appraisal of Guidelines for Research Evaluation (AGREE) II instrument and systematic reviews of evidence informing the guidelines were assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Four systematic reviews (physical activity, sedentary behaviour, sleep, integrated behaviours) examining the relationships between and among movement behaviours and several health indicators were completed and interpreted by expert consensus. Complementary compositional analyses were performed using Canadian Health Measures Survey data to examine the relationships between movement behaviours and health indicators. A stakeholder survey was employed (n = 590) and 28 focus groups/stakeholder interviews (n = 104) were completed to gather feedback on draft guidelines. Following an introductory preamble, the guidelines provide evidence-informed recommendations for a healthy day (24 h), comprising a combination of sleep, sedentary behaviours, light-, moderate-, and vigorous-intensity physical activity. Proactive dissemination, promotion, implementation, and evaluation plans have been prepared in an effort to optimize uptake and activation of the new guidelines. Future research should consider the integrated relationships among movement behaviours, and similar integrated guidelines for other age groups should be developed.

1,114 citations


Journal ArticleDOI
TL;DR: It is demonstrated that zygomycetes comprise two major clades that form a paraphyletic grade, and the phyla Mucoromycota and ZoopagomyCota are circumscribed.
Abstract: Zygomycete fungi were classified as a single phylum, Zygomycota, based on sexual reproduction by zygospores, frequent asexual reproduction by sporangia, absence of multicellular sporocarps, and production of coenocytic hyphae, all with some exceptions. Molecular phylogenies based on one or a few genes did not support the monophyly of the phylum, however, and the phylum was subsequently abandoned. Here we present phylogenetic analyses of a genome-scale data set for 46 taxa, including 25 zygomycetes and 192 proteins, and we demonstrate that zygomycetes comprise two major clades that form a paraphyletic grade. A formal phylogenetic classification is proposed herein and includes two phyla, six subphyla, four classes and 16 orders. On the basis of these results, the phyla Mucoromycota and Zoopagomycota are circumscribed. Zoopagomycota comprises Entomophtoromycotina, Kickxellomycotina and Zoopagomycotina; it constitutes the earliest diverging lineage of zygomycetes and contains species that are primarily parasites and pathogens of small animals (e.g. amoeba, insects, etc.) and other fungi, i.e. mycoparasites. Mucoromycota comprises Glomeromycotina, Mortierellomycotina, and Mucoromycotina and is sister to Dikarya. It is the more derived clade of zygomycetes and mainly consists of mycorrhizal fungi, root endophytes, and decomposers of plant material. Evolution of trophic modes, morphology, and analysis of genome-scale data are discussed.

872 citations


Journal ArticleDOI
TL;DR: In this article, the authors conducted a scoping review to identify papers that utilized and/or described Scoping review methods; guidelines for reporting Scoping reviews; and studies that assessed the quality of reporting of scoping reviews.
Abstract: Scoping reviews are used to identify knowledge gaps, set research agendas, and identify implications for decision-making. The conduct and reporting of scoping reviews is inconsistent in the literature. We conducted a scoping review to identify: papers that utilized and/or described scoping review methods; guidelines for reporting scoping reviews; and studies that assessed the quality of reporting of scoping reviews. We searched nine electronic databases for published and unpublished literature scoping review papers, scoping review methodology, and reporting guidance for scoping reviews. Two independent reviewers screened citations for inclusion. Data abstraction was performed by one reviewer and verified by a second reviewer. Quantitative (e.g. frequencies of methods) and qualitative (i.e. content analysis of the methods) syntheses were conducted. After searching 1525 citations and 874 full-text papers, 516 articles were included, of which 494 were scoping reviews. The 494 scoping reviews were disseminated between 1999 and 2014, with 45 % published after 2012. Most of the scoping reviews were conducted in North America (53 %) or Europe (38 %), and reported a public source of funding (64 %). The number of studies included in the scoping reviews ranged from 1 to 2600 (mean of 118). Using the Joanna Briggs Institute methodology guidance for scoping reviews, only 13 % of the scoping reviews reported the use of a protocol, 36 % used two reviewers for selecting citations for inclusion, 29 % used two reviewers for full-text screening, 30 % used two reviewers for data charting, and 43 % used a pre-defined charting form. In most cases, the results of the scoping review were used to identify evidence gaps (85 %), provide recommendations for future research (84 %), or identify strengths and limitations (69 %). We did not identify any guidelines for reporting scoping reviews or studies that assessed the quality of scoping review reporting. The number of scoping reviews conducted per year has steadily increased since 2012. Scoping reviews are used to inform research agendas and identify implications for policy or practice. As such, improvements in reporting and conduct are imperative. Further research on scoping review methodology is warranted, and in particular, there is need for a guideline to standardize reporting.

856 citations



Journal ArticleDOI
13 May 2016-Science
TL;DR: It is reported that indium tin oxide can acquire an ultrafast and large intensity-dependent refractive index in the region of the spectrum where the real part of its permittivity vanishes, and offers the possibility of designing material structures with large ultrafast nonlinearity for applications in nanophotonics.
Abstract: Nonlinear optical phenomena are crucial for a broad range of applications, such as microscopy, all-optical data processing, and quantum information. However, materials usually exhibit a weak optical nonlinearity even under intense coherent illumination. We report that indium tin oxide can acquire an ultrafast and large intensity-dependent refractive index in the region of the spectrum where the real part of its permittivity vanishes. We observe a change in the real part of the refractive index of 0.72 ± 0.025, corresponding to 170% of the linear refractive index. This change in refractive index is reversible with a recovery time of about 360 femtoseconds. Our results offer the possibility of designing material structures with large ultrafast nonlinearity for applications in nanophotonics.

Book ChapterDOI
Matej Kristan1, Ales Leonardis2, Jiří Matas3, Michael Felsberg4, Roman Pflugfelder5, Luka Cehovin1, Tomas Vojir3, Gustav Häger4, Alan Lukežič1, Gustavo Fernandez5, Abhinav Gupta6, Alfredo Petrosino7, Alireza Memarmoghadam8, Alvaro Garcia-Martin9, Andres Solis Montero10, Andrea Vedaldi11, Andreas Robinson4, Andy J. Ma12, Anton Varfolomieiev13, A. Aydin Alatan14, Aykut Erdem15, Bernard Ghanem16, Bin Liu, Bohyung Han17, Brais Martinez18, Chang-Ming Chang19, Changsheng Xu20, Chong Sun21, Daijin Kim17, Dapeng Chen22, Dawei Du20, Deepak Mishra23, Dit-Yan Yeung24, Erhan Gundogdu25, Erkut Erdem15, Fahad Shahbaz Khan4, Fatih Porikli26, Fatih Porikli27, Fei Zhao20, Filiz Bunyak28, Francesco Battistone7, Gao Zhu27, Giorgio Roffo29, Gorthi R. K. Sai Subrahmanyam23, Guilherme Sousa Bastos30, Guna Seetharaman31, Henry Medeiros32, Hongdong Li27, Honggang Qi20, Horst Bischof33, Horst Possegger33, Huchuan Lu21, Hyemin Lee17, Hyeonseob Nam34, Hyung Jin Chang35, Isabela Drummond30, Jack Valmadre11, Jae-chan Jeong36, Jaeil Cho36, Jae-Yeong Lee36, Jianke Zhu37, Jiayi Feng20, Jin Gao20, Jin-Young Choi, Jingjing Xiao2, Ji-Wan Kim36, Jiyeoup Jeong, João F. Henriques11, Jochen Lang10, Jongwon Choi, José M. Martínez9, Junliang Xing20, Junyu Gao20, Kannappan Palaniappan28, Karel Lebeda38, Ke Gao28, Krystian Mikolajczyk35, Lei Qin20, Lijun Wang21, Longyin Wen19, Luca Bertinetto11, Madan Kumar Rapuru23, Mahdieh Poostchi28, Mario Edoardo Maresca7, Martin Danelljan4, Matthias Mueller16, Mengdan Zhang20, Michael Arens, Michel Valstar18, Ming Tang20, Mooyeol Baek17, Muhammad Haris Khan18, Naiyan Wang24, Nana Fan39, Noor M. Al-Shakarji28, Ondrej Miksik11, Osman Akin15, Payman Moallem8, Pedro Senna30, Philip H. S. Torr11, Pong C. Yuen12, Qingming Huang39, Qingming Huang20, Rafael Martin-Nieto9, Rengarajan Pelapur28, Richard Bowden38, Robert Laganiere10, Rustam Stolkin2, Ryan Walsh32, Sebastian B. Krah, Shengkun Li19, Shengping Zhang39, Shizeng Yao28, Simon Hadfield38, Simone Melzi29, Siwei Lyu19, Siyi Li24, Stefan Becker, Stuart Golodetz11, Sumithra Kakanuru23, Sunglok Choi36, Tao Hu20, Thomas Mauthner33, Tianzhu Zhang20, Tony P. Pridmore18, Vincenzo Santopietro7, Weiming Hu20, Wenbo Li40, Wolfgang Hübner, Xiangyuan Lan12, Xiaomeng Wang18, Xin Li39, Yang Li37, Yiannis Demiris35, Yifan Wang21, Yuankai Qi39, Zejian Yuan22, Zexiong Cai12, Zhan Xu37, Zhenyu He39, Zhizhen Chi21 
08 Oct 2016
TL;DR: The Visual Object Tracking challenge VOT2016 goes beyond its predecessors by introducing a new semi-automatic ground truth bounding box annotation methodology and extending the evaluation system with the no-reset experiment.
Abstract: The Visual Object Tracking challenge VOT2016 aims at comparing short-term single-object visual trackers that do not apply pre-learned models of object appearance. Results of 70 trackers are presented, with a large number of trackers being published at major computer vision conferences and journals in the recent years. The number of tested state-of-the-art trackers makes the VOT 2016 the largest and most challenging benchmark on short-term tracking to date. For each participating tracker, a short description is provided in the Appendix. The VOT2016 goes beyond its predecessors by (i) introducing a new semi-automatic ground truth bounding box annotation methodology and (ii) extending the evaluation system with the no-reset experiment. The dataset, the evaluation kit as well as the results are publicly available at the challenge website (http://votchallenge.net).

Proceedings ArticleDOI
01 Jun 2016
TL;DR: A shared task on detecting stance from tweets: given a tweet and a target entity (person, organization, etc.), automatic natural language systems must determine whether the tweeter is in favor of the given target, against thegiven target, or whether neither inference is likely.
Abstract: Here for the first time we present a shared task on detecting stance from tweets: given a tweet and a target entity (person, organization, etc.), automatic natural language systems must determine whether the tweeter is in favor of the given target, against the given target, or whether neither inference is likely. The target of interest may or may not be referred to in the tweet, and it may or may not be the target of opinion. Two tasks are proposed. Task A is a traditional supervised classification task where 70% of the annotated data for a target is used as training and the rest for testing. For Task B, we use as test data all of the instances for a new target (not used in task A) and no training data is provided. Our shared task received submissions from 19 teams for Task A and from 9 teams for Task B. The highest classification F-score obtained was 67.82 for Task A and 56.28 for Task B. However, systems found it markedly more difficult to infer stance towards the target of interest from tweets that express opinion towards another entity.

Journal ArticleDOI
TL;DR: It is found that numerous long-term studies of lake ecosystems in Europe and North America show that controlling algal blooms and other symptoms of eutrophication depends on reducing inputs of a single nutrient: phosphorus.
Abstract: As human populations increase and land-use intensifies, toxic and unsightly nuisance blooms of algae are becoming larger and more frequent in freshwater lakes. In most cases, the blooms are predominantly blue-green algae (Cyanobacteria), which are favored by low ratios of nitrogen to phosphorus. In the past half century, aquatic scientists have devoted much effort to understanding the causes of such blooms and how they can be prevented or reduced. Here we review the evidence, finding that numerous long-term studies of lake ecosystems in Europe and North America show that controlling algal blooms and other symptoms of eutrophication depends on reducing inputs of a single nutrient: phosphorus. In contrast, small-scale experiments of short duration, where nutrients are added rather than removed, often give spurious and confusing results that bear little relevance to solving the problem of cyanobacteria blooms in lakes.

Journal ArticleDOI
TL;DR: Evidence-based pharmacological treatments are available for first-line treatment of major depressive disorder and for management of inadequate response, however, given the limitations of the evidence base, pharmacological management of MDD still depends on tailoring treatments to the patient.
Abstract: Background:The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines r...


Journal ArticleDOI
TL;DR: In an analysis of participants with serial lipid measurements over many years, FH mutation carriers had higher cumulative exposure to LDL cholesterol than noncarriers and within any stratum of observed LDL cholesterol, risk of CAD was higher among FH mutations carriers than non carriers.

Journal ArticleDOI
TL;DR: A comprehensive, flexible, and computable, purely structure-based chemical taxonomy (ChemOnt) is developed along with a computer program (ClassyFire) that uses only chemical structures and structural features to automatically assign all known chemical compounds to a taxonomy consisting of >4800 different categories.
Abstract: Scientists have long been driven by the desire to describe, organize, classify, and compare objects using taxonomies and/or ontologies. In contrast to biology, geology, and many other scientific disciplines, the world of chemistry still lacks a standardized chemical ontology or taxonomy. Several attempts at chemical classification have been made; but they have mostly been limited to either manual, or semi-automated proof-of-principle applications. This is regrettable as comprehensive chemical classification and description tools could not only improve our understanding of chemistry but also improve the linkage between chemistry and many other fields. For instance, the chemical classification of a compound could help predict its metabolic fate in humans, its druggability or potential hazards associated with it, among others. However, the sheer number (tens of millions of compounds) and complexity of chemical structures is such that any manual classification effort would prove to be near impossible. We have developed a comprehensive, flexible, and computable, purely structure-based chemical taxonomy (ChemOnt), along with a computer program (ClassyFire) that uses only chemical structures and structural features to automatically assign all known chemical compounds to a taxonomy consisting of >4800 different categories. This new chemical taxonomy consists of up to 11 different levels (Kingdom, SuperClass, Class, SubClass, etc.) with each of the categories defined by unambiguous, computable structural rules. Furthermore each category is named using a consensus-based nomenclature and described (in English) based on the characteristic common structural properties of the compounds it contains. The ClassyFire webserver is freely accessible at http://classyfire.wishartlab.com/ . Moreover, a Ruby API version is available at https://bitbucket.org/wishartlab/classyfire_api , which provides programmatic access to the ClassyFire server and database. ClassyFire has been used to annotate over 77 million compounds and has already been integrated into other software packages to automatically generate textual descriptions for, and/or infer biological properties of over 100,000 compounds. Additional examples and applications are provided in this paper. ClassyFire, in combination with ChemOnt (ClassyFire’s comprehensive chemical taxonomy), now allows chemists and cheminformaticians to perform large-scale, rapid and automated chemical classification. Moreover, a freely accessible API allows easy access to more than 77 million “ClassyFire” classified compounds. The results can be used to help annotate well studied, as well as lesser-known compounds. In addition, these chemical classifications can be used as input for data integration, and many other cheminformatics-related tasks.

Journal ArticleDOI
TL;DR: In this article, the authors quantified maternal mortality throughout the world by underlying cause and age from 1990 to 2015 for ages 10-54 years by systematically compiling and processing all available data sources from 186 of 195 countries and territories.

Journal ArticleDOI
TL;DR: This updated review found that key context (presage) and process factors reported in the previous review continue to have resonance on the delivery of IPE.
Abstract: Background: Interprofessional education (IPE) aims to bring together different professionals to learn with, from, and about one another in order to collaborate more effectively in the delivery of safe, high-quality care for patients/clients. Given its potential for improving collaboration and care delivery, there have been repeated calls for the wider-scale implementation of IPE across education and clinical settings. Increasingly, a range of IPE initiatives are being implemented and evaluated which are adding to the growth of evidence for this form of education.Aim: The overall aim of this review is to update a previous BEME review published in 2007. In doing so, this update sought to synthesize the evolving nature of the IPE evidence.Methods: Medline, CINAHL, BEI, and ASSIA were searched from May 2005 to June 2014. Also, journal hand searches were undertaken. All potential abstracts and papers were screened by pairs of reviewers to determine inclusion. All included papers were assessed for metho...

Journal ArticleDOI
13 Sep 2016-Trials
TL;DR: This study resulted in a consensus-based guideline on the methods for selecting outcome measurement instruments for outcomes included in a COS, which can be used by COS developers in defining how to measure core outcomes.
Abstract: In cooperation with the Core Outcome Measures in Effectiveness Trials (COMET) initiative, the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) initiative aimed to develop a guideline on how to select outcome measurement instruments for outcomes (i.e., constructs or domains) included in a “Core Outcome Set” (COS). A COS is an agreed minimum set of outcomes that should be measured and reported in all clinical trials of a specific disease or trial population. Informed by a literature review to identify potentially relevant tasks on outcome measurement instrument selection, a Delphi study was performed among a panel of international experts, representing diverse stakeholders. In three consecutive rounds, panelists were asked to rate the importance of different tasks in the selection of outcome measurement instruments, to justify their choices, and to add other relevant tasks. Consensus was defined as being achieved when 70 % or more of the panelists agreed and when fewer than 15 % of the panelists disagreed. Of the 481 invited experts, 120 agreed to participate of whom 95 (79 %) completed the first Delphi questionnaire. We reached consensus on four main steps in the selection of outcome measurement instruments for COS: Step 1, conceptual considerations; Step 2, finding existing outcome measurement instruments, by means of a systematic review and/or a literature search; Step 3, quality assessment of outcome measurement instruments, by means of the evaluation of the measurement properties and feasibility aspects of outcome measurement instruments; and Step 4, generic recommendations on the selection of outcome measurement instruments for outcomes included in a COS (consensus ranged from 70 to 99 %). This study resulted in a consensus-based guideline on the methods for selecting outcome measurement instruments for outcomes included in a COS. This guideline can be used by COS developers in defining how to measure core outcomes.

Journal ArticleDOI
Haidong Wang1, Zulfiqar A Bhutta2, Zulfiqar A Bhutta3, Matthew M Coates1  +610 moreInstitutions (263)
TL;DR: The Global Burden of Disease 2015 Study provides an analytical framework to comprehensively assess trends for under-5 mortality, age-specific and cause-specific mortality among children under 5 years, and stillbirths by geography over time and decomposed the changes in under- 5 mortality to changes in SDI at the global level.

Journal ArticleDOI
08 Mar 2016-JAMA
TL;DR: A clinical risk score developed among children presenting to the emergency department with concussion and head injury within the previous 48 hours had modest discrimination to stratify PPCS risk at 28 days.
Abstract: Importance Approximately one-third of children experiencing acute concussion experience ongoing somatic, cognitive, and psychological or behavioral symptoms, referred to as persistent postconcussion symptoms (PPCS). However, validated and pragmatic tools enabling clinicians to identify patients at risk for PPCS do not exist. Objective To derive and validate a clinical risk score for PPCS among children presenting to the emergency department. Design, Setting, and Participants Prospective, multicenter cohort study (Predicting and Preventing Postconcussive Problems in Pediatrics [5P]) enrolled young patients (aged 5- Exposures All eligible patients had concussions consistent with the Zurich consensus diagnostic criteria. Main Outcomes and Measures The primary outcome was PPCS risk score at 28 days, which was defined as 3 or more new or worsening symptoms using the patient-reported Postconcussion Symptom Inventory compared with recalled state of being prior to the injury. Results In total, 3063 patients (median age, 12.0 years [interquartile range, 9.2-14.6 years]; 1205 [39.3%] girls) were enrolled (n = 2006 in the derivation cohort; n = 1057 in the validation cohort) and 2584 of whom (n = 1701 [85%] in the derivation cohort; n = 883 [84%] in the validation cohort) completed follow-up at 28 days after the injury. Persistent postconcussion symptoms were present in 801 patients (31.0%) (n = 510 [30.0%] in the derivation cohort and n = 291 [33.0%] in the validation cohort). The 12-point PPCS risk score model for the derivation cohort included the variables of female sex, age of 13 years or older, physician-diagnosed migraine history, prior concussion with symptoms lasting longer than 1 week, headache, sensitivity to noise, fatigue, answering questions slowly, and 4 or more errors on the Balance Error Scoring System tandem stance. The area under the curve was 0.71 (95% CI, 0.69-0.74) for the derivation cohort and 0.68 (95% CI, 0.65-0.72) for the validation cohort. Conclusions and Relevance A clinical risk score developed among children presenting to the emergency department with concussion and head injury within the previous 48 hours had modest discrimination to stratify PPCS risk at 28 days. Before this score is adopted in clinical practice, further research is needed for external validation, assessment of accuracy in an office setting, and determination of clinical utility.

Journal ArticleDOI
TL;DR: The gender differences in health care-seeking behaviour advances previous research by exploring in detail the variables predicting differences inhealth care- seeking behaviour for men and women.
Abstract: Canadians’ health care-seeking behaviour for physical and mental health issues was examined using the international Quality and Cost of Primary Care (QUALICOPC) survey that was conducted in 2013 in Canada. This study used the cross-sectional Patient Experiences Survey collected from 7260 patients in 759 practices across 10 Canadian provinces as part of the QUALICOPC study. A Responsive Care Scale (RCS) was constructed to reflect the degree of health care-seeking behaviour across 11 health conditions. Using several patient characteristics as independent variables, four multiple regression analyses were conducted. Patients’ self-reports indicated that there were gender differences in health care-seeking behaviour, with women reporting they visited their primary care provider to a greater extent than did men for both physical and mental health concerns. Overall, patients were less likely to seek care for mental health concerns in comparison to physical health concerns. For both women and men, the results of the regressions indicated that age, illness prevention, trust in physicians and chronic conditions were important factors when explaining health care-seeking behaviours for mental health concerns. This study confirms the gender differences in health care-seeking behaviour advances previous research by exploring in detail the variables predicting differences in health care-seeking behaviour for men and women. The variables were better predictors of health care-seeking behaviour in response to mental health concerns than physical health concerns, likely reflecting greater variation among those seeking mental health care. This study has implications for those working to improve barriers to health care access by identifying those more likely to engage in health care-seeking behaviours and the variables predicting health care-seeking. Consequently, those who are not accessing primary care can be targeted and policies can be developed and put in place to promote their health care-seeking behavior.

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Haidong Wang1, Timothy M. Wolock1, Austin Carter1, Grant Nguyen1  +497 moreInstitutions (214)
TL;DR: This report provides national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.

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TL;DR: Osimertinib showed clinical activity with manageable side-effects in patients with EGFR Thr790Met-positive non-small-cell lung cancer and could be a suitable treatment for patients who have progressed on an EGFR tyrosine-kinase inhibitor.
Abstract: Summary Background Osimertinib (AZD9291) is an oral, potent, irreversible EGFR tyrosine-kinase inhibitor selective for EGFR tyrosine-kinase inhibitor sensitising mutations, and the EGFR Thr790Met resistance mutation. We assessed the efficacy and safety of osimertinib in patients with EGFR Thr790Met-positive non-small-cell lung cancer (NSCLC), who had progressed after previous therapy with an approved EGFR tyrosine-kinase inhibitor. Methods In this phase 2, open-label, single-arm study (AURA2), patients aged at least 18 years with centrally confirmed EGFR Thr790Met-positive mutations, locally advanced or metastatic (stage IIIB/IV) NSCLC who progressed on previous EGFR tyrosine-kinase inhibitor therapy received osimertinib 80 mg orally once daily; treatment could continue beyond progression if the investigator observed a clinical benefit. Patients with asymptomatic, stable CNS metastases not requiring steroids were allowed to enrol. The primary endpoint was the proportion of patients achieving an objective response by blinded independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1. Response endpoints were assessed in the evaluable for response analysis set (ie, all patients who received at least one dose of osimertinib and had measurable disease at baseline according to blinded independent central review). Other endpoints and safety were assessed in all patients receiving at least one osimertinib dose (full analysis set). The study is ongoing and patients are still receiving treatment. This study is registered with ClinicalTrials.gov, number NCT02094261. Findings Between May 20, 2014, and Sept 12, 2014, 472 patients were screened, of whom 210 started osimertinib treatment between June 13, 2014, and Oct 27, 2014; 11 patients were excluded from the evaluable for response analysis set (n=199) due to absence of measurable disease at baseline by blinded independent central review. At data cutoff (Nov 1, 2015), 122 (58%) patients remained on treatment. The median duration of follow-up was 13·0 months (IQR 7·6–14·2). 140 (70%; 95% CI 64–77) of 199 patients achieved an objective response by blinded independent central review: confirmed complete responses were achieved in six (3%) patients and partial responses were achieved in 134 (67%) patients. The most common all-causality grade 3 and 4 adverse events were pulmonary embolism (seven [3%]), prolonged electrocardiogram QT (five [2%]), decreased neutrophil count (four [2%]), anaemia, dyspnoea, hyponatraemia, increased alanine aminotransferase, and thrombocytopenia (three [1%] each). Serious adverse events were reported in 52 (25%) patients, of which 11 (5%) were investigator assessed as possibly treatment-related to osimertinib. Seven deaths were due to adverse events; these were pneumonia (n=2), pneumonia aspiration (n=1), rectal haemorrhage (n=1), dyspnoea (n=1), failure to thrive (n=1), and interstitial lung disease (n=1). The only fatal event assessed as possibly treatment-related by the investigator was due to interstitial lung disease. Interpretation Osimertinib showed clinical activity with manageable side-effects in patients with EGFR Thr790Met-positive NSCLC. Therefore, osimertinib could be a suitable treatment for patients with EGFR Thr790Met-positive disease who have progressed on an EGFR tyrosine-kinase inhibitor. Funding AstraZeneca.

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TL;DR: Machine learning combining clinical and CCTA data was found to predict 5-year all-cause mortality significantly better than existing clinical or C CTA metrics alone.
Abstract: Aims Traditional prognostic risk assessment in patients undergoing non-invasive imaging is based upon a limited selection of clinical and imaging findings Machine learning (ML) can consider a greater number and complexity of variables Therefore, we investigated the feasibility and accuracy of ML to predict 5-year all-cause mortality (ACM) in patients undergoing coronary computed tomographic angiography (CCTA), and compared the performance to existing clinical or CCTA metrics Methods and results The analysis included 10 030 patients with suspected coronary artery disease and 5-year follow-up from the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry All patients underwent CCTA as their standard of care Twenty-five clinical and 44 CCTA parameters were evaluated, including segment stenosis score (SSS), segment involvement score (SIS), modified Duke index (DI), number of segments with non-calcified, mixed or calcified plaques, age, sex, gender, standard cardiovascular risk factors, and Framingham risk score (FRS) Machine learning involved automated feature selection by information gain ranking, model building with a boosted ensemble algorithm, and 10-fold stratified cross-validation Seven hundred and forty-five patients died during 5-year follow-up Machine learning exhibited a higher area-under-curve compared with the FRS or CCTA severity scores alone (SSS, SIS, DI) for predicting all-cause mortality (ML: 079 vs FRS: 061, SSS: 064, SIS: 064, DI: 062; P < 0001) Conclusions Machine learning combining clinical and CCTA data was found to predict 5-year ACM significantly better than existing clinical or CCTA metrics alone

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TL;DR: Investigation of the epidemiological and reporting characteristics of a more recent cross-section of SRs suggests that more than 8,000 SRs are being indexed in MEDLINE annually, corresponding to a 3-fold increase over the last decade.
Abstract: Background Systematic reviews (SRs) can help decision makers interpret the deluge of published biomedical literature. However, a SR may be of limited use if the methods used to conduct the SR are flawed, and reporting of the SR is incomplete. To our knowledge, since 2004 there has been no cross-sectional study of the prevalence, focus, and completeness of reporting of SRs across different specialties. Therefore, the aim of our study was to investigate the epidemiological and reporting characteristics of a more recent cross-section of SRs. Methods and Findings We searched MEDLINE to identify potentially eligible SRs indexed during the month of February 2014. Citations were screened using prespecified eligibility criteria. Epidemiological and reporting characteristics of a random sample of 300 SRs were extracted by one reviewer, with a 10% sample extracted in duplicate. We compared characteristics of Cochrane versus non-Cochrane reviews, and the 2014 sample of SRs versus a 2004 sample of SRs. We identified 682 SRs, suggesting that more than 8,000 SRs are being indexed in MEDLINE annually, corresponding to a 3-fold increase over the last decade. The majority of SRs addressed a therapeutic question and were conducted by authors based in China, the UK, or the US; they included a median of 15 studies involving 2,072 participants. Meta-analysis was performed in 63% of SRs, mostly using standard pairwise methods. Study risk of bias/quality assessment was performed in 70% of SRs but was rarely incorporated into the analysis (16%). Few SRs (7%) searched sources of unpublished data, and the risk of publication bias was considered in less than half of SRs. Reporting quality was highly variable; at least a third of SRs did not report use of a SR protocol, eligibility criteria relating to publication status, years of coverage of the search, a full Boolean search logic for at least one database, methods for data extraction, methods for study risk of bias assessment, a primary outcome, an abstract conclusion that incorporated study limitations, or the funding source of the SR. Cochrane SRs, which accounted for 15% of the sample, had more complete reporting than all other types of SRs. Reporting has generally improved since 2004, but remains suboptimal for many characteristics. Conclusions An increasing number of SRs are being published, and many are poorly conducted and reported. Strategies are needed to help reduce this avoidable waste in research.

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TL;DR: Single-molecule magnets that contain one spin centre (so-called single-ion magnets) theoretically represent the smallest possible unit for spin-based electronic devices.
Abstract: Single-molecule magnets (SMMs) that contain one spin centre (so-called single-ion magnets) theoretically represent the smallest possible unit for spin-based electronic devices. The realisation of this and related technologies, depends on first being able to design systems with sufficiently large energy barriers to magnetisation reversal, Ueff, and secondly, on being able to organise these molecules into addressable arrays. In recent years, significant progress has been made towards the former goal - principally as a result of efforts which have been directed towards studying complexes based on highly anisotropic lanthanide ions, such as Tb(iii) and Dy(iii). Since 2013 however, and the remarkable report by Long and co-workers of a linear Fe(i) system exhibiting Ueff = 325 K, single-ion systems of transition metals have undergone something of a renaissance in the literature. Not only do they have important lessons to teach us about anisotropy and relaxation dynamics in the quest to enhance Ueff, the ability to create strongly coupled spin systems potentially offers access to a whole of host of 1, 2 and 3-dimensional materials with interesting structural and physical properties. This perspective summarises recent progress in this rapidly expanding sub-genre of molecular magnetism from the viewpoint of the synthetic chemist, with a particular focus on the lessons that have so far been learned from single-ion magnets of the d-block, and, the future research directions which we feel are likely to emerge in the coming years.

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TL;DR: The 2015 update of the Canadian Stroke Best Practice Recommendations: Stroke Rehabilitation Practice Guidelines is a comprehensive summary of current evidence-based recommendations for all members of multidisciplinary teams working in a range of settings, who provide care to patients following stroke.
Abstract: Stroke rehabilitation is a progressive, dynamic, goal-orientated process aimed at enabling a person with impairment to reach their optimal physical, cognitive, emotional, communicative, social and/or functional activity level. After a stroke, patients often continue to require rehabilitation for persistent deficits related to spasticity, upper and lower extremity dysfunction, shoulder and central pain, mobility/gait, dysphagia, vision, and communication. Each year in Canada 62,000 people experience a stroke. Among stroke survivors, over 6500 individuals access in-patient stroke rehabilitation and stay a median of 30 days (inter-quartile range 19 to 45 days). The 2015 update of the Canadian Stroke Best Practice Recommendations: Stroke Rehabilitation Practice Guidelines is a comprehensive summary of current evidence-based recommendations for all members of multidisciplinary teams working in a range of settings, who provide care to patients following stroke. These recommendations have been developed to address both the organization of stroke rehabilitation within a system of care (i.e., Initial Rehabilitation Assessment; Stroke Rehabilitation Units; Stroke Rehabilitation Teams; Delivery; Outpatient and Community-Based Rehabilitation), and specific interventions and management in stroke recovery and direct clinical care (i.e., Upper Extremity Dysfunction; Lower Extremity Dysfunction; Dysphagia and Malnutrition; Visual-Perceptual Deficits; Central Pain; Communication; Life Roles). In addition, stroke happens at any age, and therefore a new section has been added to the 2015 update to highlight components of stroke rehabilitation for children who have experienced a stroke, either prenatally, as a newborn, or during childhood. All recommendations have been assigned a level of evidence which reflects the strength and quality of current research evidence available to support the recommendation. The updated Rehabilitation Clinical Practice Guidelines feature several additions that reflect new research areas and stronger evidence for already existing recommendations. It is anticipated that these guidelines will provide direction and standardization for patients, families/caregiver(s), and clinicians within Canada and internationally.