Showing papers by "Queen's University published in 2018"
University of Toronto1, St. Michael's Hospital2, Northeastern University3, Ottawa Hospital Research Institute4, University of South Australia5, Royal College of Physicians and Surgeons of Canada6, Canadian Agency for Drugs and Technologies in Health7, RAND Corporation8, American University of Beirut9, Agency for Healthcare Research and Quality10, University of Ottawa11, University of York12, University of Alberta13, McMaster University14, South African Medical Research Council15, Queen's University16, Dalhousie University17, World Health Organization18, Cochrane Collaboration19, King's College London20
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
University of Minnesota1, University of Colorado Boulder2, VU University Amsterdam3, Harvard University4, University of Southern California5, University of Tartu6, University of Queensland7, Erasmus University Rotterdam8, Hospital for Special Surgery9, University of Copenhagen10, Statens Serum Institut11, Broad Institute12, University of Essex13, University of Edinburgh14, University of Cambridge15, University Hospital of Lausanne16, Geisinger Health System17, Wenzhou Medical College18, Stanford University19, University of North Carolina at Chapel Hill20, University of Wisconsin-Madison21, The Feinstein Institute for Medical Research22, Hofstra University23, University of Dundee24, University of Toronto25, Princeton University26, Queen's University27, National Bureau of Economic Research28, New York University Shanghai29, Karolinska Institutet30, Uppsala University31, University of Lausanne32, New York University33, Stockholm School of Economics34
TL;DR: A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11–13% of the variance ineducational attainment and 7–10% ofthe variance in cognitive performance, which substantially increases the utility ofpolygenic scores as tools in research.
Abstract: Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.
1,658 citations
University of British Columbia1, University of Toronto2, University of Michigan3, University of Minnesota4, McMaster University5, University of Western Ontario6, McGill University7, Dalhousie University8, University of Calgary9, Queen's University10, Kyushu University11, University of São Paulo12, Stanford University13, Case Western Reserve University14, University of Barcelona15, University of Sydney16, George Washington University17, Deakin University18
TL;DR: These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments.
Abstract: The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third- line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment-emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second- line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence-based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first-line treatments for acute mania. First-line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first-line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.
950 citations
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.
534 citations
TL;DR: Patients with PAH have dyspnea, reduced exercise capacity, exertional syncope, and premature death from right ventricular failure, and targeted therapies, used alone or in combination, improve functional capacity and hemodynamics and reduce hospital admissions.
Abstract: Pulmonary hypertension is defined as a resting mean pulmonary artery pressure of 25 mm Hg or above. This review deals with pulmonary arterial hypertension (PAH), a type of pulmonary hypertension that primarily affects the pulmonary vasculature. In PAH, the pulmonary vasculature is dynamically obstructed by vasoconstriction, structurally obstructed by adverse vascular remodeling, and pathologically non-compliant as a result of vascular fibrosis and stiffening. Many cell types are abnormal in PAH, including vascular cells (endothelial cells, smooth muscle cells, and fibroblasts) and inflammatory cells. Progress has been made in identifying the causes of PAH and approving new drug therapies. A cancer-like increase in cell proliferation and resistance to apoptosis reflects acquired abnormalities of mitochondrial metabolism and dynamics. Mutations in the type II bone morphogenetic protein receptor (BMPR2) gene dramatically increase the risk of developing heritable PAH. Epigenetic dysregulation of DNA methylation, histone acetylation, and microRNAs also contributes to disease pathogenesis. Aberrant bone morphogenetic protein signaling and epigenetic dysregulation in PAH promote cell proliferation in part through induction of a Warburg mitochondrial-metabolic state of uncoupled glycolysis. Complex changes in cytokines (interleukins and tumor necrosis factor), cellular immunity (T lymphocytes, natural killer cells, macrophages), and autoantibodies suggest that PAH is, in part, an autoimmune, inflammatory disease. Obstructive pulmonary vascular remodeling in PAH increases right ventricular afterload causing right ventricular hypertrophy. In some patients, maladaptive changes in the right ventricle, including ischemia and fibrosis, reduce right ventricular function and cause right ventricular failure. Patients with PAH have dyspnea, reduced exercise capacity, exertional syncope, and premature death from right ventricular failure. PAH targeted therapies (prostaglandins, phosphodiesterase-5 inhibitors, endothelin receptor antagonists, and soluble guanylate cyclase stimulators), used alone or in combination, improve functional capacity and hemodynamics and reduce hospital admissions. However, these vasodilators do not target key features of PAH pathogenesis and have not been shown to reduce mortality, which remains about 50% at five years. This review summarizes the epidemiology, pathogenesis, diagnosis, and treatment of PAH.
516 citations
Haramaya University1, Université de Moncton2, Université de Montréal3, University of Ibadan4, National Heart Foundation of Australia5, University of La Frontera6, University of Cuenca7, University of Waterloo8, University of the Republic9, Ghent University10, National Taiwan University11, University of Ottawa12, Karolinska Institutet13, Technische Universität München14, University of the Witwatersrand15, University of Cape Town16, Swansea University17, Lithuanian Sports University18, Emory University19, University of Los Andes20, Central University of Venezuela21, Hong Kong Baptist University22, Qatar Airways23, University of Tartu24, University of Regina25, Mahidol University26, The Chinese University of Hong Kong27, Pennington Biomedical Research Center28, University of Queensland29, Seoul National University30, Queen's University31, Linköping University32, University of Medicine and Health Sciences33, University of Guadalajara34, Shanghai University of Sport35, National University of Science and Technology36, University of Primorska37, University of Porto38, University of Ghana39, University of Strathclyde40, Carlos III Health Institute41, University of Girona42, Universidade Federal de Santa Catarina43, Katholieke Universiteit Leuven44, University of South Australia45, University of Southern Denmark46, University of Auckland47, Bath Spa University48, University of Ljubljana49, Tribhuvan University50, Utrecht University51, J. F. Oberlin University52, University of Botswana53, Stamford University Bangladesh54, National Chung Hsing University55, University of Warsaw56
TL;DR: The present study provides rich new evidence showing that the situation regarding the physical activity of children and youth is a concern worldwide and strategic public investments to implement effective interventions to increase physical activity opportunities are needed.
Abstract: Background: Accumulating sufficient moderate to vigorous physical activity is recognized as a key determinant of physical, physiological, developmental, mental, cognitive, and social health among children and youth (aged 5–17 y). The Global Matrix 3.0ofReportCardgradesonphysicalactivitywasdevelopedtoachieveabetterunderstandingoftheglobalvariationinchildand youth physical activity and associated supports. Methods: Work groups from 49 countries followed harmonized procedures to develop their Report Cards by grading 10 common indicators using the best available data. The participating countries were divided into 3 categories using the United Nations’ human development index (HDI) classification (low or medium, high, and very high HDI). Results: A total of 490 grades, including 369 letter grades and 121 incomplete grades, were assigned by the 49 work groups. Overall, an average grade of “C−,”“D+,” and “C−” was obtained for the low and medium HDI countries, high HDI countries, and very high HDI countries, respectively. Conclusions: The present study provides rich new evidence showing that the situation regarding the physical activity of children and youth is a concern worldwide. Strategic public investments to implement effective interventions to increase physical activity opportunities are needed.
502 citations
University of Birmingham1, University of Sydney2, University of Toronto3, Medicines and Healthcare Products Regulatory Agency4, University of Washington5, University of Oxford6, University of North Carolina at Chapel Hill7, University of Leeds8, University of Warwick9, University of Bristol10, Johnson & Johnson11, Merck & Co.12, Food and Drug Administration13, Patient-Centered Outcomes Research Institute14, Queen's University15, National Cancer Research Institute16
TL;DR: The SPIRIT-PRO guidelines provide recommendations for items that should be addressed and included in clinical trial protocols in which PROs are a primary or key secondary outcome and improved design of clinical trials including PROs could help ensure high-quality data that may inform patient-centered care.
Abstract: Importance Patient-reported outcome (PRO) data from clinical trials can provide valuable evidence to inform shared decision making, labeling claims, clinical guidelines, and health policy; however, the PRO content of clinical trial protocols is often suboptimal. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was published in 2013 and aims to improve the completeness of trial protocols by providing evidence-based recommendations for the minimum set of items to be addressed, but it does not provide PRO-specific guidance. Objective To develop international, consensus-based, PRO-specific protocol guidance (the SPIRIT-PRO Extension). Design, Setting, and Participants The SPIRIT-PRO Extension was developed following the Enhancing Quality and Transparency of Health Research (EQUATOR) Network’s methodological framework for guideline development. This included (1) a systematic review of existing PRO-specific protocol guidance to generate a list of potential PRO-specific protocol items (published in 2014); (2) refinements to the list and removal of duplicate items by the International Society for Quality of Life Research (ISOQOL) Protocol Checklist Taskforce; (3) an international stakeholder survey of clinical trial research personnel, PRO methodologists, health economists, psychometricians, patient advocates, funders, industry representatives, journal editors, policy makers, ethicists, and researchers responsible for evidence synthesis (distributed by 38 international partner organizations in October 2016); (4) an international Delphi exercise (n = 137 invited; October 2016 to February 2017); and (5) consensus meeting (n = 30 invited; May 2017). Prior to voting, consensus meeting participants were informed of the results of the Delphi exercise and given data from structured reviews evaluating the PRO protocol content of 3 defined samples of trial protocols. Results The systematic review identified 162 PRO-specific protocol recommendations from 54 sources. The ISOQOL Taskforce (n = 21) reduced this to 56 items, which were considered by 138 international stakeholder survey participants and 99 Delphi panelists. The final wording of the SPIRIT-PRO Extension was agreed on at a consensus meeting (n = 29 participants) and reviewed by external group of experts during a consultation period. Eleven extensions and 5 elaborations to the SPIRIT 2013 checklist were recommended for inclusion in clinical trial protocols in which PROs are a primary or key secondary outcome. Extension items focused on PRO-specific issues relating to the trial rationale, objectives, eligibility criteria, concepts used to evaluate the intervention, time points for assessment, PRO instrument selection and measurement properties, data collection plan, translation to other languages, proxy completion, strategies to minimize missing data, and whether PRO data will be monitored during the study to inform clinical care. Conclusions and Relevance The SPIRIT-PRO guidelines provide recommendations for items that should be addressed and included in clinical trial protocols in which PROs are a primary or key secondary outcome. Improved design of clinical trials including PROs could help ensure high-quality data that may inform patient-centered care.
445 citations
University of Edinburgh1, Aarhus University2, University of Colorado Boulder3, Institute of Arctic and Alpine Research4, National Ecological Observatory Network5, Smithsonian Institution6, Lund University7, VU University Amsterdam8, University of Lapland9, Northern Arizona University10, Bigelow Laboratory For Ocean Sciences11, University of British Columbia12, University of Washington13, Grand Valley State University14, Swiss Federal Institute for Forest, Snow and Landscape Research15, Max Planck Society16, University of Zurich17, Université de Sherbrooke18, University of Greifswald19, University of Parma20, Memorial University of Newfoundland21, Université du Québec à Trois-Rivières22, University of Gothenburg23, Leiden University24, University of California, Riverside25, Qatar University26, Mississippi State University27, University of Barcelona28, Umeå University29, Utrecht University30, University of Alaska Anchorage31, Adam Mickiewicz University in Poznań32, Wageningen University and Research Centre33, Alaska Department of Fish and Game34, University of Tromsø35, University of Vienna36, University of Copenhagen37, Helmholtz Centre for Environmental Research - UFZ38, University of Oulu39, Spanish National Research Council40, Queen's University41, Saint Mary's University42, Oak Ridge National Laboratory43, University of Aberdeen44, University of Saskatchewan45, Vrije Universiteit Brussel46, University of Victoria47, Swiss Federal Institute of Aquatic Science and Technology48, Norwegian University of Science and Technology49, Research Institute for Nature and Forest50, Florida International University51, Moscow State University52, University of Alaska Fairbanks53, University of Waterloo54, Laval University55, Deakin University56, University of Bonn57, United States Forest Service58, Simon Fraser University59, University of Iceland60, University Centre in Svalbard61, United States Fish and Wildlife Service62, Colorado State University63, University of Texas at El Paso64, University of Stirling65, University of Innsbruck66, Rocky Mountain Biological Laboratory67, University of Oxford68, Pacific Northwest National Laboratory69, University of Camerino70, University of Insubria71, University of New South Wales72, University of Manchester73, National University of Cordoba74, Santa Fe Institute75, University of Arizona76, Harvard University77, King Juan Carlos University78, Estonian University of Life Sciences79, Kyoto University80, World Agroforestry Centre81, Radboud University Nijmegen82, Macquarie University83, Forschungszentrum Jülich84, University of Regensburg85, University of Minnesota86, University of Sydney87, Santa Clara University88, Algoma University89, Komarov Botanical Institute90, University of Wisconsin–Eau Claire91
TL;DR: Biome-wide relationships between temperature, moisture and seven key plant functional traits across the tundra and over time show that community height increased with warming across all sites, whereas other traits lagged behind predicted rates of change.
Abstract: The tundra is warming more rapidly than any other biome on Earth, and the potential ramifications are far-reaching because of global feedback effects between vegetation and climate. A better understanding of how environmental factors shape plant structure and function is crucial for predicting the consequences of environmental change for ecosystem functioning. Here we explore the biome-wide relationships between temperature, moisture and seven key plant functional traits both across space and over three decades of warming at 117 tundra locations. Spatial temperature-trait relationships were generally strong but soil moisture had a marked influence on the strength and direction of these relationships, highlighting the potentially important influence of changes in water availability on future trait shifts in tundra plant communities. Community height increased with warming across all sites over the past three decades, but other traits lagged far behind predicted rates of change. Our findings highlight the challenge of using space-for-time substitution to predict the functional consequences of future warming and suggest that functions that are tied closely to plant height will experience the most rapid change. They also reveal the strength with which environmental factors shape biotic communities at the coldest extremes of the planet and will help to improve projections of functional changes in tundra ecosystems with climate warming.
425 citations
TL;DR: Analysis of analytically validated assays in tumour tissue has shown a robust correlation between loss of PTEN and its protein as well as a strong association between PTEN loss and adverse pathological features and oncological outcomes, and assessing PTEN status in liquid biopsies shows promise in predicting response to targeted therapy.
Abstract: Genomic aberrations of the PTEN tumour suppressor gene are among the most common in prostate cancer. Inactivation of PTEN by deletion or mutation is identified in ∼20% of primary prostate tumour samples at radical prostatectomy and in as many as 50% of castration-resistant tumours. Loss of phosphatase and tensin homologue (PTEN) function leads to activation of the PI3K-AKT (phosphoinositide 3-kinase-RAC-alpha serine/threonine-protein kinase) pathway and is strongly associated with adverse oncological outcomes, making PTEN a potentially useful genomic marker to distinguish indolent from aggressive disease in patients with clinically localized tumours. At the other end of the disease spectrum, therapeutic compounds targeting nodes in the PI3K-AKT-mTOR (mechanistic target of rapamycin) signalling pathway are being tested in clinical trials for patients with metastatic castration-resistant prostate cancer. Knowledge of PTEN status might be helpful to identify patients who are more likely to benefit from these therapies. To enable the use of PTEN status as a prognostic and predictive biomarker, analytically validated assays have been developed for reliable and reproducible detection of PTEN loss in tumour tissue and in blood liquid biopsies. The use of clinical-grade assays in tumour tissue has shown a robust correlation between loss of PTEN and its protein as well as a strong association between PTEN loss and adverse pathological features and oncological outcomes. In advanced disease, assessing PTEN status in liquid biopsies shows promise in predicting response to targeted therapy. Finally, studies have shown that PTEN might have additional functions that are independent of the PI3K-AKT pathway, including those affecting tumour growth through modulation of the immune response and tumour microenvironment.
373 citations
University of Western Ontario1, University of Alberta2, Université du Québec à Trois-Rivières3, Queen's University4, Children's Hospital of Eastern Ontario5, University of Ottawa6, Technical University of Madrid7, University of Saskatchewan8, Sunnybrook Health Sciences Centre9, University of Toronto10, Camosun College11
TL;DR: These guidelines provided guidance for pregnant women and obstetric care and exercise professionals on prenatal physical activity and the majority of stakeholders and end users indicated that following these recommendations would be feasible, acceptable and equitable.
Abstract: The objective is to provide guidance for pregnant women and obstetric care and exercise professionals on prenatal physical activity. The outcomes evaluated were maternal, fetal or neonatal morbidity, or fetal mortality during and following pregnancy. Literature was retrieved through searches of MEDLINE, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Scopus and Web of Science Core Collection, CINAHL Plus with Full Text, Child Development & Adolescent Studies, Education Resources Information Center, SPORTDiscus, ClinicalTrials.gov and the Trip Database from inception up to 6 January 2017. Primary studies of any design were eligible, except case studies. Results were limited to English-language, Spanish-language or French-language materials. Articles related to maternal physical activity during pregnancy reporting on maternal, fetal or neonatal morbidity, or fetal mortality were eligible for inclusion. The quality of evidence was rated using the Grading of Recommendations Assessment, Development and Evaluation methodology. The Guidelines Consensus Panel solicited feedback from end users (obstetric care providers, exercise professionals, researchers, policy organisations, and pregnant and postpartum women). The development of these guidelines followed the Appraisal of Guidelines for Research and Evaluation II instrument. The benefits of prenatal physical activity are moderate and no harms were identified; therefore, the difference between desirable and undesirable consequences (net benefit) is expected to be moderate. The majority of stakeholders and end users indicated that following these recommendations would be feasible, acceptable and equitable. Following these recommendations is likely to require minimal resources from both individual and health systems perspectives.
340 citations
TL;DR: The estimated proportion of PSP reporting current symptom clusters consistent with 1 or more mental disorders appears higher than previously published estimates for the general population; however, direct comparisons are impossible because of methodological differences.
Abstract: Background:Canadian public safety personnel (PSP; e.g., correctional workers, dispatchers, firefighters, paramedics, police officers) are exposed to potentially traumatic events as a function of their work. Such exposures contribute to the risk of developing clinically significant symptoms related to mental disorders. The current study was designed to provide estimates of mental disorder symptom frequencies and severities for Canadian PSP.Methods:An online survey was made available in English or French from September 2016 to January 2017. The survey assessed current symptoms, and participation was solicited from national PSP agencies and advocacy groups. Estimates were derived using well-validated screening measures.Results:There were 5813 participants (32.5% women) who were grouped into 6 categories (i.e., call center operators/dispatchers, correctional workers, firefighters, municipal/provincial police, paramedics, Royal Canadian Mounted Police). Substantial proportions of participants reported current ...
TL;DR: In conclusion, exercise-only interventions were effective at lowering the odds of developing GDM, GH and PE.
Abstract: Objective Gestational diabetes mellitus (GDM), gestational hypertension (GH) and pre-eclampsia (PE) are associated with short and long-term health issues for mother and child; prevention of these complications is critically important. This study aimed to perform a systematic review and meta-analysis of the relationships between prenatal exercise and GDM, GH and PE. Design Systematic review with random effects meta-analysis and meta-regression. Data sources Online databases were searched up to 6 January 2017. Study eligibility criteria Studies of all designs were included (except case studies) if published in English, Spanish or French, and contained information on the Population (pregnant women without contraindication to exercise), Intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone [“exercise-only”] or in combination with other intervention components [e.g., dietary; “exercise + co-intervention”]), Comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and Outcomes (GDM, GH, PE). Results A total of 106 studies (n=273 182) were included. ‘Moderate’ to ‘high’-quality evidence from randomised controlled trials revealed that exercise-only interventions, but not exercise+cointerventions, reduced odds of GDM (n=6934; OR 0.62, 95% CI 0.52 to 0.75), GH (n=5316; OR 0.61, 95% CI 0.43 to 0.85) and PE (n=3322; OR 0.59, 95% CI 0.37 to 0.9) compared with no exercise. To achieve at least a 25% reduction in the odds of developing GDM, PE and GH, pregnant women need to accumulate at least 600 MET-min/week of moderate-intensity exercise (eg, 140 min of brisk walking, water aerobics, stationary cycling or resistance training). Summary/conclusions In conclusion, exercise-only interventions were effective at lowering the odds of developing GDM, GH and PE.
Population Health Research Institute1, McMaster University2, Aga Khan University3, Simon Fraser University4, North-West University5, St. John's Medical College6, Post Graduate Institute of Medical Education and Research7, College of Health Sciences, Bahrain8, King Saud University9, Isfahan University of Medical Sciences10, Istanbul Medeniyet University11, University of La Frontera12, Wrocław Medical University13, University of Gothenburg14, UCSI University15, Universiti Teknologi MARA16, University of the Western Cape17, University of the Philippines Manila18, Dubai Health Authority19, Laval University20, Northwestern University21, Peking Union Medical College22, Centers for Disease Control and Prevention23, Queen's University24, University Kebangsaan Malaysia Medical Centre25, Tufts University26, Independence University27
TL;DR: Dairy consumption was associated with lower risk of mortality and major cardiovascular disease events in a diverse multinational cohort study of individuals aged 35-70 years.
University of British Columbia1, Loughborough University2, Queen's University3, Sapienza University of Rome4, Brock University5, University of Groningen6, McMaster University7, Lund University8, University of Western Ontario9, University of Alberta10, Rick Hansen Institute11, University of Alabama at Birmingham12, University of Birmingham13, Stoke Mandeville Hospital14, Lawson Health Research Institute15
TL;DR: These guidelines represent an important step toward international harmonization of exercise guidelines for adults withSCI, and a foundation for developing exercise policies and programs for people with SCI around the world.
Abstract: To describe the process and outcomes of using a new evidence base to develop scientific guidelines that specify the type and minimum dose of exercise necessary to improve fitness and cardiometabolic health in adults with spinal cord injury (SCI). International. Using Appraisal of Guidelines, Research and Evaluation (AGREE) II reporting criteria, steps included (a) determining the guidelines’ scope; (b) conducting a systematic review of relevant literature; (c) holding three consensus panel meetings (European, Canadian and International) to formulate the guidelines; (d) obtaining stakeholder feedback; and (e) process evaluation by an AGREE II consultant. Stakeholders were actively involved in steps (c) and (d). For cardiorespiratory fitness and muscle strength benefits, adults with a SCI should engage in at least 20 min of moderate to vigorous intensity aerobic exercise 2 times per week AND 3 sets of strength exercises for each major functioning muscle group, at a moderate to vigorous intensity, 2 times per week (strong recommendation). For cardiometabolic health benefits, adults with a SCI are suggested to engage in at least 30 min of moderate to vigorous intensity aerobic exercise 3 times per week (conditional recommendation). Through a systematic, rigorous, and participatory process involving international scientists and stakeholders, a new exercise guideline was formulated for cardiometabolic health benefits. A previously published SCI guideline was endorsed for achieving fitness benefits. These guidelines represent an important step toward international harmonization of exercise guidelines for adults with SCI, and a foundation for developing exercise policies and programs for people with SCI around the world.
University of Florida1, California Institute of Technology2, SLAC National Accelerator Laboratory3, Pacific Northwest National Laboratory4, Texas A&M University5, National Institute of Science Education and Research6, University of Minnesota7, Fermilab8, University of South Dakota9, South Dakota School of Mines and Technology10, Stanford University11, Southern Methodist University12, Durham University13, Autonomous University of Madrid14, Queen's University15, University of California, Berkeley16, Northwestern University17, University of Colorado Denver18, Santa Clara University19, University of British Columbia20, TRIUMF21, University of Evansville22, Université de Montréal23, Lawrence Berkeley National Laboratory24, University of Toronto25
TL;DR: These first limits on inelastic electron-scattering dark matter and dark photon absorption are presented using a prototype SuperCDMS detector having a charge resolution of 0.1 electron-hole pairs and demonstrated a sensitivity to dark photons competitive with other leading approaches but using substantially less exposure.
Abstract: We present the first limits on inelastic electron-scattering dark matter and dark photon absorption using a prototype SuperCDMS detector having a charge resolution of 0.1 electron-hole pairs (CDMS HVeV, a 0.93 g CDMS high-voltage device). These electron-recoil limits significantly improve experimental constraints on dark matter particles with masses as low as 1 MeV/c^{2}. We demonstrate a sensitivity to dark photons competitive with other leading approaches but using substantially less exposure (0.49 g d). These results demonstrate the scientific potential of phonon-mediated semiconductor detectors that are sensitive to single electronic excitations.
TL;DR: Selective inhibition of TYK2 with the oral agent BMS‐986165 at doses of 3 mg daily and higher resulted in greater clearing of psoriasis than did placebo over a period of 12 weeks.
Abstract: Background Tyrosine kinase 2 (TYK2) signaling pathways, which mediate cytokine signaling, are implicated in the pathophysiology of psoriasis. Selective inhibitors of TYK2 may be effective in treating psoriasis. Methods We conducted a phase 2, double-blind trial of a TYK2 inhibitor, BMS-986165, in adults with moderate-to-severe psoriasis, excluding patients with a previous lack of response to agents targeting cytokine signaling through the same tyrosine kinase pathway. Patients were randomly assigned to receive the drug orally at a dose of 3 mg every other day, 3 mg daily, 3 mg twice daily, 6 mg twice daily, or 12 mg daily or to receive placebo. The primary end point was a 75% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 12 (higher scores indicate greater severity of psoriasis). Results A total of 267 patients received at least one dose in an intervention group of the trial. At week 12, the percentage of patients with a 75% or greater reduction i...
McMaster University1, Population Health Research Institute2, National University of Ireland, Galway3, Laval University4, University of Ottawa5, Simon Fraser University6, The Chinese University of Hong Kong7, Peking Union Medical College8, University of La Frontera9, St. John's Medical College10, Wrocław Medical University11, Aga Khan University12, Independent University, Bangladesh13, Isfahan University of Medical Sciences14, Northwestern University15, Universiti Teknologi MARA16, UCSI University17, University Kebangsaan Malaysia Medical Centre18, Ankara University19, Sahlgrenska University Hospital20, Dubai Health Authority21, North-West University22, University of the Western Cape23, College of Health Sciences, Bahrain24, University of the Philippines25, King Saud University26, Queen's University27
TL;DR: Sodium intake was associated with cardiovascular disease and strokes only in communities where mean intake was greater than 5 g/day, and all major cardiovascular outcomes decreased with increasing potassium intake in all countries.
TL;DR: In-depth insights are provided into the current understanding of the immunopathophysiology of endometriosis and challenges and opportunities for future research are highlighted.
TL;DR: A resource theory for continuous-variable systems grounded on operations routinely available within current quantum technologies, which lends itself to quantify both quantum non-Gaussianity and Wigner negativity as resources, depending on the choice of the free-state set.
Abstract: We develop a resource theory for continuous-variable systems grounded on operations routinely available within current quantum technologies. In particular, the set of free operations is convex and includes quadratic transformations and conditional coarse-grained measurements. The present theory lends itself to quantify both quantum non-Gaussianity and Wigner negativity as resources, depending on the choice of the free-state set---i.e., the convex hull of Gaussian states or the states with positive Wigner function, respectively. After showing that the theory admits no maximally resourceful state, we define a computable resource monotone---the Wigner logarithmic negativity. We use the latter to assess the resource content of experimentally relevant states---e.g., photon-added, photon-subtracted, cubic-phase, and cat states---and to find optimal working points of some resource concentration protocols. We envisage applications of this framework to subuniversal and universal quantum information processing over continuous variables.
TL;DR: Serum 25-hydroxyvitamin D [25(OH)D] concentrations higher than 150 ng/ml (375 nmol/l) are the hallmark of VDT due to vitamin D overdosing, and Laboratory testing during routine clinical examinations may reveal asymptomatic hypercalcemia caused by the intake of vitamin D even in doses recommended for the general population and considered safe.
Abstract: Confusion, apathy, recurrent vomiting, abdominal pain, polyuria, polydipsia, and dehydration are the most often noted clinical symptoms of vitamin D toxicity (VDT; also called vitamin D intoxication or hypervitaminosis D). VDT and its clinical manifestation, severe hypercalcemia, are related to excessive long-term intake of vitamin D, malfunctions of the vitamin D metabolic pathway, or the existence of coincident disease that produces the active vitamin D metabolite locally. Although VDT is rare, the health effects can be serious if it is not promptly identified. Many forms of exogenous (iatrogenic) and endogenous VDT exist. Exogenous VDT is usually caused by the inadvertent or improper intake of extremely high doses of pharmacological preparations of vitamin D and is associated with hypercalcemia. Serum 25-hydroxyvitamin D [25(OH)D] concentrations higher than 150 ng/ml (375 nmol/l) are the hallmark of VDT due to vitamin D overdosing. Endogenous VDT may develop from excessive production of an active vitamin D metabolite - 1,25(OH)2D in granulomatous disorders and in some lymphomas or from the reduced degradation of that metabolite in idiopathic infantile hypercalcemia. Endogenous VDT may also develop from an excessive production of 25(OH)D and 1,25(OH)2D in congenital disorders, such as Williams-Beuren syndrome. Laboratory testing during routine clinical examinations may reveal asymptomatic hypercalcemia caused by the intake of vitamin D even in doses recommended for the general population and considered safe. That phenomenon, called hypersensitivity to vitamin D, reflects dysregulated vitamin D metabolism. Researchers have proposed many processes to explain VDT. Those processes include elevated activity of 1α-hydroxylase or inhibited activity of 24-hydroxylase, both leading to increased concentration of 1,25(OH)D; increased number of vitamin D receptors; and saturation of the capacity of vitamin D binding protein. Increased public awareness of vitamin D-related health benefits might increase the risk of VDT due to self-administration of vitamin D in doses higher then recommended for age and body weight or even higher than the established upper limit intake values. Consequently, the incidence of hypercalcemia due to hypervitaminosis D might increase.
TL;DR: In this article, the authors review Mode 2 UTT from a quadruple helix perspective to identify key themes to develop a research agenda which reflects progression from a triple into quadruple-helix ecosystem.
Abstract: Within recent years, there has been a rapid expansion of the University's role in economic development. This has resulted in University Technology Transfer (UTT) taking place within an increasingly complex network of regional stakeholders. This complexity has resulted in quadruple helix models where the triple helix model of academia, industry and regional government now includes societal based innovation users as a fourth helix. Despite this development, extant research is fragmented and lacks coherent frameworks and conceptualisations which fully depict the dynamic and evolving nature of UTT. Accordingly, this article reviews Mode 2 UTT from a quadruple helix perspective to identify key themes to develop a research agenda which reflects progression from a triple into a quadruple helix ecosystem.
TL;DR: Clinical trials have shown that adults with moderate‐to‐severe AD who receive weekly or biweekly dupilumab injections have significantly improved clinical and patient‐reported outcomes, including Eczema Area Severity Index, SCORing Atopic Dermatitis, Dermatology Life Quality Index, and itch Numeric Rating Scale scores.
Abstract: Atopic dermatitis (AD) is a chronic, pruritic immune-mediated inflammatory dermatosis characterized by a T helper 2 (Th2) immune response phenotype and may be associated with systemic inflammation. Dupilumab is an interleukin 4 (IL-4) receptor α-antagonist that inhibits IL-4 and IL-13 signaling through blockade of the shared IL-4α subunit. Blockade of IL-4/13 is effective in reducing Th2 response. Dupilumab has recently been approved in the United States and Europe for the treatment of adult patients with moderate-to-severe AD. Clinical trials have shown that adults with moderate-to-severe AD who receive weekly or biweekly dupilumab injections have significantly improved clinical and patient-reported outcomes, including Eczema Area Severity Index, SCORing Atopic Dermatitis, Dermatology Life Quality Index, and itch Numeric Rating Scale scores. Concomitant use of topical corticosteroids along with dupilumab results in a greater improvement in signs and symptoms of AD than with use of dupilumab alone. Biomarker analyses show that dupilumab modulates the AD molecular signature and other Th2-associated biomarkers. Common adverse events reported in the clinical trials were nasopharyngitis, upper respiratory tract infection, injection site reactions, skin infections, and conjunctivitis. These were mild-to-moderate in nature, and overall rates of adverse events occurred with similar frequency between the treatment and placebo groups. There were no significant serious safety concerns identified in phase III clinical trials. Dupilumab, as monotherapy or with concomitant use of topical corticosteroids, can significantly improve clinical outcomes and quality of life in patients suffering from moderate-to-severe AD. Ongoing studies of dupilumab will help determine the clinical efficacy and safety profile of its long-term use.
TL;DR: This paper extends the ActivitySpace framework to collect and analyze Human-Computer Interaction data across many applications (not just the IDEs), and finds that on average developers spend on average 58 percent of their time on program comprehension activities, and that they frequently use web browsers and document editors to performprogram comprehension activities.
Abstract: During software development and maintenance, developers spend a considerable amount of time on program comprehension activities. Previous studies show that program comprehension takes up as much as half of a developer’s time. However, most of these studies are performed in a controlled setting, or with a small number of participants, and investigate the program comprehension activities only within the IDEs. However, developers’ program comprehension activities go well beyond their IDE interactions. In this paper, we extend our ActivitySpace framework to collect and analyze Human-Computer Interaction (HCI) data across many applications (not just the IDEs). We follow Minelli et al.’s approach to assign developers’ activities into four categories: navigation, editing, comprehension, and other. We then measure the comprehension time by calculating the time that developers spend on program comprehension, e.g., inspecting console and breakpoints in IDE, or reading and understanding tutorials in web browsers. Using this approach, we can perform a more realistic investigation of program comprehension activities, through a field study of program comprehension in practice across a total of seven real projects, on 78 professional developers, and amounting to 3,148 working hours. Our study leverages interaction data that is collected across many applications by the developers. Our study finds that on average developers spend $\sim$ 58 percent of their time on program comprehension activities, and that they frequently use web browsers and document editors to perform program comprehension activities. We also investigate the impact of programming language, developers’ experience, and project phase on the time that is spent on program comprehension, and we find senior developers spend significantly less percentages of time on program comprehension than junior developers. Our study also highlights the importance of several research directions needed to reduce program comprehension time, e.g., building automatic detection and improvement of low quality code and documentation, construction of software-engineering-specific search engines, designing better IDEs that help developers navigate code and browse information more efficiently, etc.
01 Jul 2018
TL;DR: This paper enrich the state-of-the-art neural natural language inference models with external knowledge and demonstrate that the proposed models improve neural NLI models to achieve the state of the art performance on the SNLI and MultiNLI datasets.
Abstract: Modeling natural language inference is a very challenging task. With the availability of large annotated data, it has recently become feasible to train complex models such as neural-network-based inference models, which have shown to achieve the state-of-the-art performance. Although there exist relatively large annotated data, can machines learn all knowledge needed to perform natural language inference (NLI) from these data? If not, how can neural-network-based NLI models benefit from external knowledge and how to build NLI models to leverage it? In this paper, we enrich the state-of-the-art neural natural language inference models with external knowledge. We demonstrate that the proposed models improve neural NLI models to achieve the state-of-the-art performance on the SNLI and MultiNLI datasets.
TL;DR: A comprehensive screen for immune-related genes regulated by TAZ and its paralog YAP using NanoString gene expression profiling identifies the immune checkpoint molecule PD-L1 as a target of Hippo signaling and provides evidence implicating TAZ in human cancer immune evasion.
Abstract: The Hippo pathway component WW domain-containing transcription regulator 1 (TAZ) is a transcriptional coactivator and an oncogene in breast and lung cancer. Transcriptional targets of TAZ that modulate immune cell function in the tumor microenvironment are poorly understood. Here, we perform a comprehensive screen for immune-related genes regulated by TAZ and its paralog YAP using NanoString gene expression profiling. We identify the immune checkpoint molecule PD-L1 as a target of Hippo signaling. The upstream kinases of the Hippo pathway, mammalian STE20-like kinase 1 and 2 (MST1/2), and large tumor suppressor 1 and 2 (LATS1/2), suppress PD-L1 expression while TAZ and YAP enhance PD-L1 levels in breast and lung cancer cell lines. PD-L1 expression in cancer cell lines is determined by TAZ activity and TAZ/YAP/TEAD increase PD-L1 promoter activity. Critically, TAZ-induced PD-L1 upregulation in human cancer cells is sufficient to inhibit T-cell function. The relationship between TAZ and PD-L1 is not conserved in multiple mouse cell lines, likely due to differences between the human and mouse PD-L1 promoters. To explore the extent of divergence in TAZ immune-related targets between human and mouse cells, we performed a second NanoString screen using mouse cell lines. We show that many targets of TAZ may be differentially regulated between these species. These findings highlight the role of Hippo signaling in modifying human/murine physiologic/pathologic immune responses and provide evidence implicating TAZ in human cancer immune evasion.Significance: Human-specific activation of PD-L1 by a novel Hippo signaling pathway in cancer immune evasion may have a significant impact on research in immunotherapy. Cancer Res; 78(6); 1457-70. ©2018 AACR.
VU University Medical Center1, University of California, San Francisco2, Oslo University Hospital3, University of Oslo4, Katholieke Universiteit Leuven5, Cornell University6, University of Wisconsin-Madison7, Queen's University8, Children's Hospital at Westmead9, Columbia University10, Università telematica San Raffaele11
TL;DR: In an effort to bridge knowledge gaps in defining hypovitaminosis D, an international study on rickets as a multifactorial disease is proposed and standardizing 25(OH)D measurement in research is recommended.
Abstract: The First International Conference on Controversies in Vitamin D was held in Pisa, Italy, 14–16 June 2017. The meeting's purpose was to address controversies in vitamin D research, review the data available, to help resolve them, and suggest a research agenda to clarify areas of uncertainty. The serum 25-hydroxyvitamin D [25(OH)D] concentration [i.e. the sum of 25(OH)D3 and 25(OH)D2] remains the critical measurement for defining vitamin D status. Assay variation for 25(OH)D has contributed to the current chaos surrounding efforts to define hypovitaminosis D. An essential requirement to develop a consensus on vitamin D status is that measurement of 25(OH)D and, in the future, other potential vitamin D biomarkers [e.g. 1α,25(OH)2D3, 3-epi-25(OH)D, 24,25(OH)2D3, vitamin D-binding protein, free/bioavailable 25(OH)D and parathyroid hormone] be standardized/harmonized, to allow pooling of research data. Vitamin D Standardization Program tools are described and recommended for standardizing 25(OH)D measurement in research. In the future, similar methodology, based on National Institute for Standards and Technology standard reference materials, must be developed for other candidate markers of vitamin D status. Failure to standardize/harmonize vitamin D metabolite measurements is destined to promulgate continued chaos. At this time, 25(OH)D values below 12 ng ml–1 (30 nmol l–1) should be considered to be associated with an increased risk of rickets/osteomalacia, whereas 25(OH)D concentrations between 20 ng ml–1 and 50 ng ml–1 (50–125 nmol l–1) appear to be safe and sufficient in the general population for skeletal health. In an effort to bridge knowledge gaps in defining hypovitaminosis D, an international study on rickets as a multifactorial disease is proposed.
TL;DR: High nonsynonymous TMB was associated with a better prognosis in patients with resected NSCLC, and the benefit of adjuvant chemotherapy on LCSS was more pronounced in Patients with low nonsynonym TMBs.
Abstract: PurposeThe survival benefit with adjuvant chemotherapy for patients with resected stage II-III non–small-cell lung cancer (NSCLC) is modest. Efforts to develop prognostic or predictive biomarkers i...
Pacific Northwest National Laboratory1, Lawrence Berkeley National Laboratory2, University of Washington3, University of South Carolina4, North Carolina State University5, Kurchatov Institute6, University of Chicago7, University of South Dakota8, Oak Ridge National Laboratory9, Max Planck Society10, South Dakota School of Mines and Technology11, Durham University12, Joint Institute for Nuclear Research13, Los Alamos National Laboratory14, University of Tennessee15, Osaka University16, University of Alberta17, Black Hills State University18, Queen's University19
TL;DR: The Majorana Demonstrator as discussed by the authors achieved an energy resolution of 2.5 keV FWHM at Qββ and a very low background with no observed candidate events in 9.95 kg yr of enriched Ge exposure, resulting in a lower limit on the half-life of 1.9×10−25−25 −1.
Abstract: The Majorana Collaboration is operating an array of high purity Ge detectors to search for neutrinoless double-β decay in ^{76}Ge. The Majorana Demonstrator comprises 44.1 kg of Ge detectors (29.7 kg enriched in ^{76}Ge) split between two modules contained in a low background shield at the Sanford Underground Research Facility in Lead, South Dakota. Here we present results from data taken during construction, commissioning, and the start of full operations. We achieve unprecedented energy resolution of 2.5 keV FWHM at Q_{ββ} and a very low background with no observed candidate events in 9.95 kg yr of enriched Ge exposure, resulting in a lower limit on the half-life of 1.9×10^{25} yr (90% C.L.). This result constrains the effective Majorana neutrino mass to below 240-520 meV, depending on the matrix elements used. In our experimental configuration with the lowest background, the background is 4.0_{-2.5}^{+3.1} counts/(FWHM t yr).
TL;DR: In patients with acute ischemic stroke, more distal throm bus location, greater thrombus permeability, and longer time to recanalization assessment were associated with recanAlization of arterial occlusion after administration of intravenous alteplase.
Abstract: Importance Recanalization of intracranial thrombus is associated with improved clinical outcome in patients with acute ischemic stroke. The association of intravenous alteplase treatment and thrombus characteristics with recanalization over time is important for stroke triage and future trial design. Objective To examine recanalization over time across a range of intracranial thrombus occlusion sites and clinical and imaging characteristics in patients with ischemic stroke treated with intravenous alteplase or not treated with alteplase. Design, Setting, and Participants Multicenter prospective cohort study of 575 patients from 12 centers (in Canada, Spain, South Korea, the Czech Republic, and Turkey) with acute ischemic stroke and intracranial arterial occlusion demonstrated on computed tomographic angiography (CTA). Exposures Demographics, clinical characteristics, time from alteplase to recanalization, and intracranial thrombus characteristics (location and permeability) defined on CTA. Main Outcomes and Measures Recanalization on repeat CTA or on first angiographic acquisition of affected intracranial circulation obtained within 6 hours of baseline CTA, defined using the revised arterial occlusion scale (rAOL) (scores from 0 [primary occlusive lesion remains the same] to 3 [complete revascularization of primary occlusion]). Results Among 575 patients (median age, 72 years [IQR, 63-80]; 51.5% men; median time from patient last known well to baseline CTA of 114 minutes [IQR, 74-180]), 275 patients (47.8%) received intravenous alteplase only, 195 (33.9%) received intravenous alteplase plus endovascular thrombectomy, 48 (8.3%) received endovascular thrombectomy alone, and 57 (9.9%) received conservative treatment. Median time from baseline CTA to recanalization assessment was 158 minutes (IQR, 79-268); median time from intravenous alteplase start to recanalization assessment was 132.5 minutes (IQR, 62-238). Successful recanalization occurred at an unadjusted rate of 27.3% (157/575) overall, including in 30.4% (143/470) of patients who received intravenous alteplase and 13.3% (14/105) who did not (difference, 17.1% [95% CI, 10.2%-25.8%]). Among patients receiving alteplase, the following factors were associated with recanalization: time from treatment start to recanalization assessment (OR, 1.28 for every 30-minute increase in time [95% CI, 1.18-1.38]), more distal thrombus location, eg, distal M1 middle cerebral artery (39/84 [46.4%]) vs internal carotid artery (10/92 [10.9%]) (OR, 5.61 [95% CI, 2.38-13.26]), and higher residual flow (thrombus permeability) grade, eg, hairline streak (30/45 [66.7%]) vs none (91/377 [24.1%]) (OR, 7.03 [95% CI, 3.32-14.87]). Conclusions and Relevance In patients with acute ischemic stroke, more distal thrombus location, greater thrombus permeability, and longer time to recanalization assessment were associated with recanalization of arterial occlusion after administration of intravenous alteplase; among patients who did not receive alteplase, rates of arterial recanalization were low. These findings may help inform treatment and triage decisions in patients with acute ischemic stroke.
TL;DR: The authors in this paper identified an emerging epidemic of pulmonary hypertension (PH) that likely has substantial adverse health and economic implications, which is a relatively rare complication of these common diseases.
Abstract: Background: The World Health Organization recognizes 5 groups of pulmonary hypertension (PH), categorized by pathogenesis or comorbidity: 1-pulmonary arterial hypertension 2-left-heart disease, 3-lung disease and hypoxia 4-chronic thromboembolic disease, and 5-miscellaneous. The epidemiology of PH, apart from group 1, is largely unknown. Methods and Results: We describe incidence, prevalence, comorbidities, mortality and prescribing patterns for groups 1 to 4 PH from 1993 to 2012. Case definitions are based on hospitalizations and emergency department visits, using the Institute for Clinical Evaluative Sciences data, which comprises linked databases of universal coverage health service records for Ontario residents. This cohort included 50 529 patients with PH. The annual incidence of adult PH increased from 2003 to 2012 from 24.1 to 28.7 cases/100 000 population and the annual prevalence from 1993 to 2012 from 99.8 to 127.3 cases/100 000 population, respectively. The most common form of adult PH was group 2, alone (34.2%) or combined with group 3 PH (29.3%). A diagnosis of PH increased the 1-year standardized mortality ratio 7.2-fold. Mortality in adults with PH was 13.0%, 36.4%, and 62.4%, at 30 days, 1 year, and 5 years, respectively. Mortality was highest in groups 2 and 3 and lowest in group 1. PH was present in only 3.6% of people with left heart disease, 0.7% with lung disease, and 1.4% with thromboembolic disease, suggesting that PH is a relatively rare complication of these common diseases. Children (age Conclusions: The incidence and prevalence of adult PH are increasing. Groups 2 and 3 are the most common and lethal forms of PH. This study identifies an emerging epidemic of PH that likely has substantial adverse health and economic implications.