Showing papers by "Laval University published in 2020"
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TL;DR: In this paper, the authors proposed a method to solve the problem of homonymity in the context of cancer diagnosis.http://www.thelancet.com Vol 395 March 28, 202
1,185 citations
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National Institutes of Health1, Delft University of Technology2, Humboldt University of Berlin3, DuPont4, Laval University5, University of Alicante6, University of Copenhagen7, Vilnius University8, University of Georgia9, University of St Andrews10, Bangor University11, University of Toronto12, University of Freiburg13, Wageningen University and Research Centre14, North Carolina State University15
TL;DR: An updated evolutionary classification of CRISPR–Cas systems and cas genes is provided, with an emphasis on the major developments that have occurred since the publication of the latest classification, in 2015, which includes 2 classes, 6 types and 33 subtypes.
Abstract: The number and diversity of known CRISPR-Cas systems have substantially increased in recent years. Here, we provide an updated evolutionary classification of CRISPR-Cas systems and cas genes, with an emphasis on the major developments that have occurred since the publication of the latest classification, in 2015. The new classification includes 2 classes, 6 types and 33 subtypes, compared with 5 types and 16 subtypes in 2015. A key development is the ongoing discovery of multiple, novel class 2 CRISPR-Cas systems, which now include 3 types and 17 subtypes. A second major novelty is the discovery of numerous derived CRISPR-Cas variants, often associated with mobile genetic elements that lack the nucleases required for interference. Some of these variants are involved in RNA-guided transposition, whereas others are predicted to perform functions distinct from adaptive immunity that remain to be characterized experimentally. The third highlight is the discovery of numerous families of ancillary CRISPR-linked genes, often implicated in signal transduction. Together, these findings substantially clarify the functional diversity and evolutionary history of CRISPR-Cas.
1,153 citations
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TL;DR: The extent of the trait data compiled in TRY is evaluated and emerging patterns of data coverage and representativeness are analyzed to conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements.
Abstract: Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
882 citations
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Population Health Research Institute1, Oregon State University2, University of British Columbia3, University of Ottawa4, King Saud University5, University of the Philippines6, University of La Frontera7, Istanbul Medeniyet University8, North-West University9, Universiti Teknologi MARA10, UCSI University11, St. John's Medical College12, College of Health Sciences, Bahrain13, Queen's University14, Isfahan University of Medical Sciences15, Dubai Health Authority16, Birzeit University17, Independence University18, Wrocław Medical University19, Aga Khan University20, Cardiovascular Institute of the South21, Sahlgrenska University Hospital22, Post Graduate Institute of Medical Education and Research23, Simon Fraser University24, National University of Ireland, Galway25, University of London26, Laval University27
TL;DR: The prevalence, hazard ratios, and population-attributable fractions (PAFs) for cardiovascular disease and mortality associated with a cluster of behavioural factors, metabolic factors, socioeconomic and psychosocial factors, and household and ambient pollution are described.
772 citations
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TL;DR: The FLUXNET2015 dataset provides ecosystem-scale data on CO 2 , water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe, and is detailed in this paper.
Abstract: The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.
681 citations
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Queen's University1, University of Texas Southwestern Medical Center2, Osaka University3, Ben-Gurion University of the Negev4, VU University Amsterdam5, University of Milan6, University of São Paulo7, Laval University8, Harvard University9, University of Surrey10, University of Padua11, University of New South Wales12, University of Colorado Denver13
TL;DR: The evidence is summarized that waist circumference and BMI together can provide improved assessments of cardiometabolic risk compared with either measurement alone, and it is recommended that health professionals are trained to properly perform this simple measurement in clinical practice.
Abstract: Despite decades of unequivocal evidence that waist circumference provides both independent and additive information to BMI for predicting morbidity and risk of death, this measurement is not routinely obtained in clinical practice. This Consensus Statement proposes that measurements of waist circumference afford practitioners with an important opportunity to improve the management and health of patients. We argue that BMI alone is not sufficient to properly assess or manage the cardiometabolic risk associated with increased adiposity in adults and provide a thorough review of the evidence that will empower health practitioners and professional societies to routinely include waist circumference in the evaluation and management of patients with overweight or obesity. We recommend that decreases in waist circumference are a critically important treatment target for reducing adverse health risks for both men and women. Moreover, we describe evidence that clinically relevant reductions in waist circumference can be achieved by routine, moderate-intensity exercise and/or dietary interventions. We identify gaps in the knowledge, including the refinement of waist circumference threshold values for a given BMI category, to optimize obesity risk stratification across age, sex and ethnicity. We recommend that health professionals are trained to properly perform this simple measurement and consider it as an important 'vital sign' in clinical practice.
619 citations
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TL;DR: The reciprocal impacts of the COVID-19 crisis and digital inequalities are explored, and a set of multi-layered strategies focusing on actionability that can be implemented at multiple structural levels, ranging from governmental to corporate and community levels are proposed.
593 citations
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TL;DR: It is proposed that obesity can no longer be evaluated solely by the body mass index (expressed in kg/m2) because it represents a heterogeneous entity and should be referred to obesities rather than obesity.
Abstract: This review addresses the interplay between obesity, type 2 diabetes mellitus, and cardiovascular diseases. It is proposed that obesity, generally defined by an excess of body fat causing prejudice to health, can no longer be evaluated solely by the body mass index (expressed in kg/m2) because it represents a heterogeneous entity. For instance, several cardiometabolic imaging studies have shown that some individuals who have a normal weight or who are overweight are at high risk if they have an excess of visceral adipose tissue-a condition often accompanied by accumulation of fat in normally lean tissues (ectopic fat deposition in liver, heart, skeletal muscle, etc). On the other hand, individuals who are overweight or obese can nevertheless be at much lower risk than expected when faced with excess energy intake if they have the ability to expand their subcutaneous adipose tissue mass, particularly in the gluteal-femoral area. Hence, excessive amounts of visceral adipose tissue and of ectopic fat largely define the cardiovascular disease risk of overweight and moderate obesity. There is also a rapidly expanding subgroup of patients characterized by a high accumulation of body fat (severe obesity). Severe obesity is characterized by specific additional cardiovascular health issues that should receive attention. Because of the difficulties of normalizing body fat content in patients with severe obesity, more aggressive treatments have been studied in this subgroup of individuals such as obesity surgery, also referred to as metabolic surgery. On the basis of the above, we propose that we should refer to obesities rather than obesity.
496 citations
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TL;DR: Inhibition of IL‐6 may be a novel target for therapeutics for the management of dysregulated host responses in patients with Covid‐19 and high‐quality studies of intervention in this field are urgently required.
Abstract: Coronaviruses may activate dysregulated host immune responses. As exploratory studies have suggested that interleukin-6 (IL-6) levels are elevated in cases of complicated Covid-19, we undertook a systematic review and meta-analysis to assess the evidence in this field. We systematically searched MEDLINE and EMBASE for studies investigating the immunological response in Covid-19; additional grey literature searches were undertaken. Study selection and data abstraction was undertaken independently by two authors. Meta-analysis was undertaken using random effects models to compute ratios of means with 95% confidence intervals (95%CIs). Eight published studies and two preprints (n = 1798) were eligible for inclusion. Meta-analysis of mean IL-6 concentrations demonstrated 2.9-fold higher levels in patients with complicated Covid-19 compared with patients with noncomplicated disease (six studies; n = 1302; 95%CI, 1.17-7.19; I2 = 100%). Consistent results were found in sensitivity analyses exclusively restricted to studies comparing patients requiring ICU admission vs no ICU admission (two studies; n = 540; ratio of means = 3.24; 95%CI, 2.54-4.14; P < .001; I2 = 87%). Nine of ten studies were assessed to have at least moderate risk of bias. In patients with Covid-19, IL-6 levels are significantly elevated and associated with adverse clinical outcomes. Inhibition of IL-6 may be a novel target for therapeutics for the management of dysregulated host responses in patients with Covid-19 and high-quality studies of intervention in this field are urgently required.
487 citations
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TL;DR: The biology of cannabinoids, the endocannabinoid system and the expanded endoc cannabinoidoid system are outlined and the involvement in and clinical relevance of these systems and the therapeutic potential of cannabinoids across the spectrum of neurological disease are discussed.
Abstract: Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Δ9-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, especially in relation to the unwanted central effects that result from activation of cannabinoid receptor 1 (CB1), which have limited the therapeutic use of drugs that activate or inactivate this receptor. The discovery of CB2 and of endogenous cannabinoid receptor ligands (endocannabinoids) raised new possibilities for safe targeting of this endocannabinoid system. However, clinical success has been limited, complicated by the discovery of an expanded endocannabinoid system — known as the endocannabinoidome — that includes several mediators that are biochemically related to the endocannabinoids, and their receptors and metabolic enzymes. The approvals of nabiximols, a mixture of THC and the non-psychotropic cannabinoid cannabidiol, for the treatment of spasticity and neuropathic pain in multiple sclerosis, and of purified botanical cannabidiol for the treatment of otherwise untreatable forms of paediatric epilepsy, have brought the therapeutic use of cannabinoids and endocannabinoids in neurological diseases into the limelight. In this Review, we provide an overview of the endocannabinoid system and the endocannabinoidome before discussing their involvement in and clinical relevance to a variety of neurological disorders, including Parkinson disease, Alzheimer disease, Huntington disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, stroke, epilepsy and glioblastoma. In this Review, Cristino, Bisogno and Di Marzo outline the biology of cannabinoids, the endocannabinoid system and the expanded endocannabinoid system and discuss the involvement of these systems and the therapeutic potential of cannabinoids across the spectrum of neurological disease.
480 citations
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McMaster University1, University of Pennsylvania2, University of Calgary3, Libin Cardiovascular Institute of Alberta4, Dalhousie University5, University of Alberta6, Alexandra Hospital7, Laval University8, University of Ottawa9, Concordia University10, Ottawa Hospital11, University of British Columbia12, Heart and Stroke Foundation of Canada13, Florida International University14, Queen's University15, University of Toronto16, Alberta Health Services17, Centre for Addiction and Mental Health18, University Health Network19, University of Minnesota20, York University21, Université de Sherbrooke22, Centre Hospitalier Universitaire de Sherbrooke23, Simon Fraser University24, Vancouver Island Health Authority25, Foothills Medical Centre26, University of Saskatchewan27, Population Health Research Institute28, St. Michael's Hospital29, St. John's University30, Memorial University of Newfoundland31
TL;DR: Obesity is a complex chronic disease in which abnormal or excess body fat (adiposity) impairs health, increases the risk of long-term medical complications and reduces lifespan.
Abstract: KEY POINTS
Obesity is a complex chronic disease in which abnormal or excess body fat (adiposity) impairs health, increases the risk of long-term medical complications and reduces lifespan.[1][1] Epidemiologic studies define obesity using the body mass index (BMI; weight/height2), which can stratify
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Cedars-Sinai Medical Center1, Emory University2, Medical City Dallas Hospital3, Columbia University Medical Center4, Cleveland Clinic5, Laval University6, University of Pennsylvania7, MedStar Washington Hospital Center8, University of Missouri–Kansas City9, Washington University in St. Louis10, Mayo Clinic11, Intermountain Medical Center12, Providence St. Vincent Medical Center13, Rutgers University14, New York University15, Primary Children's Hospital16, Scott & White Hospital17, Stanford University18, Columbia University19, Edwards Lifesciences Corporation20
TL;DR: There was no significant difference in the incidence of death or disabling stroke at 5 years after TAVR as compared with surgical aortic-valve replacement among patients with severe, symptomaticAortic stenosis who were at intermediate surgical risk.
Abstract: Background There are scant data on long-term clinical outcomes and bioprosthetic-valve function after transcatheter aortic-valve replacement (TAVR) as compared with surgical aortic-valve r...
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TL;DR: With extended study follow-up, results from KEYNOTE-426 show that pembrolizumab plus axitinib continues to have superior clinical outcomes over sunit inib, and these results continue to support the first-line treatment with pembroizumAB plus ax itinib as the standard of care of advanced renal cell carcinoma.
Abstract: Summary Background The first interim analysis of the KEYNOTE-426 study showed superior efficacy of pembrolizumab plus axitinib over sunitinib monotherapy in treatment-naive, advanced renal cell carcinoma. The exploratory analysis with extended follow-up reported here aims to assess long-term efficacy and safety of pembrolizumab plus axitinib versus sunitinib monotherapy in patients with advanced renal cell carcinoma. Methods In the ongoing, randomised, open-label, phase 3 KEYNOTE-426 study, adults (≥18 years old) with treatment-naive, advanced renal cell carcinoma with clear cell histology were enrolled in 129 sites (hospitals and cancer centres) across 16 countries. Patients were randomly assigned (1:1) to receive 200 mg pembrolizumab intravenously every 3 weeks for up to 35 cycles plus 5 mg axitinib orally twice daily or 50 mg sunitinib monotherapy orally once daily for 4 weeks per 6-week cycle. Randomisation was done using an interactive voice response system or integrated web response system, and was stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk status and geographical region. Primary endpoints were overall survival and progression-free survival in the intention-to-treat population. Since the primary endpoints were met at the first interim analysis, updated data are reported with nominal p values. This study is registered with ClinicalTrials.gov, NCT02853331. Findings Between Oct 24, 2016, and Jan 24, 2018, 861 patients were randomly assigned to receive pembrolizumab plus axitinib (n=432) or sunitinib monotherapy (n=429). With a median follow-up of 30·6 months (IQR 27·2–34·2), continued clinical benefit was observed with pembrolizumab plus axitinib over sunitinib in terms of overall survival (median not reached with pembrolizumab and axitinib vs 35·7 months [95% CI 33·3–not reached] with sunitinib); hazard ratio [HR] 0·68 [95% CI 0·55–0·85], p=0·0003) and progression-free survival (median 15·4 months [12·7–18·9] vs 11·1 months [9·1–12·5]; 0·71 [0·60–0·84], p Interpretation With extended study follow-up, results from KEYNOTE-426 show that pembrolizumab plus axitinib continues to have superior clinical outcomes over sunitinib. These results continue to support the first-line treatment with pembrolizumab plus axitinib as the standard of care of advanced renal cell carcinoma. Funding Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc.
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Laval University1, Population Health Research Institute2, University of La Frontera3, Rajasthan University of Health Sciences4, University of Ottawa5, St. John's Medical College6, King Saud University7, National University of Malaysia8, College of Health Sciences, Bahrain9, Queen's University10, Birzeit University11, Independence University12, Wrocław Medical University13, Aga Khan University14, Peking Union Medical College15, Cardiovascular Institute of the South16, Sahlgrenska University Hospital17, Amrita Institute of Medical Sciences and Research Centre18, Post Graduate Institute of Medical Education and Research19, Dubai Health Authority20, Isfahan University of Medical Sciences21
TL;DR: This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, finding a pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels.
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University of Colorado Denver1, University of South Florida2, National Institutes of Health3, University of Leicester4, Monash University5, Federal University of Paraná6, Emory University7, University of Rochester8, University of Newcastle9, McMaster University10, Wake Forest University11, Cochrane Collaboration12, University of Bern13, University of Arizona14, Laval University15, University of California, San Francisco16, Washington University in St. Louis17, University of Southampton18, Boston Children's Hospital19, University of Wisconsin-Madison20, Hokkaido University21, Zhejiang University22, University of Pittsburgh23
TL;DR: Clinical recommendations for the management of severe asthma are provided and the use of novel therapies for severe asthma, specifically biologicals for type 2 high asthma, and antimuscarinic agents and macrolides, as well as on biomarkers for predicting treatment response are made.
Abstract: This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the European Respiratory Society/American Thoracic Society Task Force9s questions. The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on six specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: 1) suggest using anti-interleukin (IL)-5 and anti-IL-5 receptor α for severe uncontrolled adult eosinophilic asthma phenotypes; 2) suggest using a blood eosinophil cut-point ≥150 μL−1 to guide anti-IL-5 initiation in adult patients with severe asthma; 3) suggest considering specific eosinophil (≥260 μL−1) and exhaled nitric oxide fraction (≥19.5 ppb) cut-offs to identify adolescents or adults with the greatest likelihood of response to anti-IgE therapy; 4) suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite Global Initiative for Asthma (GINA) step 4–5 or National Asthma Education and Prevention Program (NAEPP) step 5 therapies; 5) suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype; and 6) suggest using anti-IL-4/13 for adult patients with severe eosinophilic asthma and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.
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Imperial College London1, Laval University2, Harvard University3, University of Sydney4, Cancer Council New South Wales5, University of New South Wales6, University of Oslo7, University of Hong Kong8, Public Health England9, University of London10, International Agency for Research on Cancer11, World Health Organization12
TL;DR: It is suggested that high HPV vaccination coverage of girls can lead to cervical cancer elimination in most LMICs by the end of the century, and elimination could occur between 2059 and 2102, depending on the threshold and region.
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TL;DR: This Review explores phage diversity at the structural, genomic and community levels as well as the complex evolutionary relationships between phages, moulded by the mosaicity of their genomes.
Abstract: Recent advances in viral metagenomics have enabled the rapid discovery of an unprecedented catalogue of phages in numerous environments, from the human gut to the deep ocean. Although these advances have expanded our understanding of phage genomic diversity, they also revealed that we have only scratched the surface in the discovery of novel viruses. Yet, despite the remarkable diversity of phages at the nucleotide sequence level, the structural proteins that form viral particles show strong similarities and conservation. Phages are uniquely interconnected from an evolutionary perspective and undergo multiple events of genetic exchange in response to the selective pressure of their hosts, which drives their diversity. In this Review, we explore phage diversity at the structural, genomic and community levels as well as the complex evolutionary relationships between phages, moulded by the mosaicity of their genomes. Phages are tremendously abundant and are found in every environment where bacteria exist. In this Review, Dion, Oechslin and Moineau explore the diversity of phages at the structural, genomic and community levels as well as their complex evolutionary relationships.
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TL;DR: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo, and this trial is registered with ClinicalTrials.gov, NCT02930018.
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TL;DR: This paper conducted a literature review with the following objectives: 1) explore which individual green behaviors were studied through the lens of the TPB, 2) understand how scholars have used the theory and what variance the theory has helped to explain, and 3) formulate recommendations, if necessary, for improving the use of the theory.
Abstract: The theory of planned behavior (TPB) allows researchers to identify the determinants of environmental behavior and subsequently target these factors in interventions. Multiple studies on conservation behaviors have recently applied this theoretical framework in both organizational and domestic settings. To shed more light on how the TPB was used in these studies, we conducted a literature review with the following objectives: 1) explore which individual green behaviors were studied though the lens of the TPB, 2) understand how scholars have used the theory and what variance the theory has helped to explain, and 3) formulate recommendations, if necessary, for improving the use of the theory. The review of the results from 126 publications demonstrated that the majority of scholars tend to overlook the importance of identifying and evaluating indirect variables (beliefs) that affect behaviors. More than half of the analyzed articles did not report the amount of explained variance, which undermines the principal strength of the theory. Scholars could obtain more substantial and consistent results if the guidelines regarding the application of the theory are consistently respected. More specifically, four aspects should be considered in the application of the theory: choice of framework, decision to extend the original model, methodology, and results. To help scholars overcome these commonly encountered problems, this article suggests a roadmap with several guiding questions and possible answers.
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TL;DR: The impact of achieving the 90–70–90 triple-intervention targets on cervical cancer mortality and deaths averted over the next century is assessed and the potential for the elimination initiative to support target 3.4 of the UN Sustainable Development Goals is assessed.
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Thomas Powles1, Michiel S. van der Heijden2, Daniel Castellano, Matthew D. Galsky3 +203 more•Institutions (20)
TL;DR: The overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab ( a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carcinoma was assessed.
Abstract: Background: Survival outcomes are poor for patients with metastatic urothelial carcinoma who receive standard, first-line, platinum-based chemotherapy. We assessed the overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab (a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carcinoma. Methods: DANUBE is an open-label, randomised, controlled, phase 3 trial in patients with untreated, unresectable, locally advanced or metastatic urothelial carcinoma, conducted at 224 academic research centres, hospitals, and oncology clinics in 23 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned patients (1:1:1) to receive durvalumab monotherapy (1500 mg) administered intravenously every 4 weeks; durvalumab (1500 mg) plus tremelimumab (75 mg) administered intravenously every 4 weeks for up to four doses, followed by durvalumab maintenance (1500 mg) every 4 weeks; or standard-of-care chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin, depending on cisplatin eligibility) administered intravenously for up to six cycles. Randomisation was done through an interactive voice–web response system, with stratification by cisplatin eligibility, PD-L1 status, and presence or absence of liver metastases, lung metastases, or both. The coprimary endpoints were overall survival compared between the durvalumab monotherapy versus chemotherapy groups in the population of patients with high PD-L1 expression (the high PD-L1 population) and between the durvalumab plus tremelimumab versus chemotherapy groups in the intention-to-treat population (all randomly assigned patients). The study has completed enrolment and the final analysis of overall survival is reported. The trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24. Findings: Between Nov 24, 2015, and March 21, 2017, we randomly assigned 1032 patients to receive durvalumab (n=346), durvalumab plus tremelimumab (n=342), or chemotherapy (n=344). At data cutoff (Jan 27, 2020), median follow-up for survival was 41·2 months (IQR 37·9–43·2) for all patients. In the high PD-L1 population, median overall survival was 14·4 months (95% CI 10·4–17·3) in the durvalumab monotherapy group (n=209) versus 12·1 months (10·4–15·0) in the chemotherapy group (n=207; hazard ratio 0·89, 95% CI 0·71–1·11; p=0·30). In the intention-to-treat population, median overall survival was 15·1 months (13·1–18·0) in the durvalumab plus tremelimumab group versus 12·1 months (10·9–14·0) in the chemotherapy group (0·85, 95% CI 0·72–1·02; p=0·075). In the safety population, grade 3 or 4 treatment-related adverse events occurred in 47 (14%) of 345 patients in the durvalumab group, 93 (27%) of 340 patients in the durvalumab plus tremelimumab group, and in 188 (60%) of 313 patients in the chemotherapy group. The most common grade 3 or 4 treatment-related adverse event was increased lipase in the durvalumab group (seven [2%] of 345 patients) and in the durvalumab plus tremelimumab group (16 [5%] of 340 patients), and neutropenia in the chemotherapy group (66 [21%] of 313 patients). Serious treatment-related adverse events occurred in 30 (9%) of 345 patients in the durvalumab group, 78 (23%) of 340 patients in the durvalumab plus tremelimumab group, and 50 (16%) of 313 patients in the chemotherapy group. Deaths due to study drug toxicity were reported in two (1%) patients in the durvalumab group (acute hepatic failure and hepatitis), two (1%) patients in the durvalumab plus tremelimumab group (septic shock and pneumonitis), and one (<1%) patient in the chemotherapy group (acute kidney injury). Interpretation: This study did not meet either of its coprimary endpoints. Further research to identify the patients with previously untreated metastatic urothelial carcinoma who benefit from treatment with immune checkpoint inhibitors, either alone or in combination regimens, is warranted. Funding: AstraZeneca.
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TL;DR: A meta-analysis of 251 peer-reviewed journal papers relevant to remote sensing image classification and a comparative analysis regarding the performances of RF and SVM classification against various parameters is applied.
Abstract: Several machine-learning algorithms have been proposed for remote sensing image classification during the past two decades. Among these machine learning algorithms, Random Forest (RF) and Support Vector Machines (SVM) have drawn attention to image classification in several remote sensing applications. This article reviews RF and SVM concepts relevant to remote sensing image classification and applies a meta-analysis of 251 peer-reviewed journal papers. A database with more than 40 quantitative and qualitative fields was constructed from these reviewed papers. The meta-analysis mainly focuses on 1) the analysis regarding the general characteristics of the studies, such as geographical distribution, frequency of the papers considering time, journals, application domains, and remote sensing software packages used in the case studies, and 2) a comparative analysis regarding the performances of RF and SVM classification against various parameters, such as data type, RS applications, spatial resolution, and the number of extracted features in the feature engineering step. The challenges, recommendations, and potential directions for future research are also discussed in detail. Moreover, a summary of the results is provided to aid researchers to customize their efforts in order to achieve the most accurate results based on their thematic applications.
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University of Calgary1, McGill University Health Centre2, Libin Cardiovascular Institute of Alberta3, Cardiovascular Institute of the South4, University of British Columbia5, Université du Québec à Trois-Rivières6, University of Ottawa7, Ottawa Hospital Research Institute8, Winnipeg Regional Health Authority9, Northern Ontario School of Medicine10, Concordia University Wisconsin11, University of Western Ontario12, Centre Hospitalier Universitaire Sainte-Justine13, Heart and Stroke Foundation of Canada14, McMaster University15, McGill University16, Université de Montréal17, University of Ontario Institute of Technology18, Université de Sherbrooke19, Brown University20, St. Michael's Hospital21, Montreal Heart Institute22, National Institutes of Health23, Université du Québec à Montréal24, University of Toronto25, University of Alberta26, University Health Network27, St Thomas' Hospital28, Alberta Health Services29, Laval University30, University of Manitoba31, Centre for Addiction and Mental Health32, Population Health Research Institute33, University of Saskatchewan34, University of Pennsylvania35, Hôpital Maisonneuve-Rosemont36
TL;DR: The 2020 guidelines include new guidance on themanagement of resistant hypertension and the management of hypertension in women planning pregnancy.
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TL;DR: The development of applications like lidR are of fundamental importance for developing transparent, flexible and open ALS tools to ensure not only reproducible workflows, but also to offer researchers the creative space required for the progress and development of the discipline.
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University of Duisburg-Essen1, University of Stirling2, Aarhus University3, Middle East Technical University4, University of Lisbon5, Norwegian Institute for Water Research6, Laval University7, Estonian University of Life Sciences8, Lancaster University9, Leibniz Association10, Technical University of Berlin11, University of Ljubljana12, Helmholtz Centre for Environmental Research - UFZ13, University of Natural Resources and Life Sciences, Vienna14, University of Barcelona15, Cardiff University16, Finnish Environment Institute17, DHI Water & Environment18, National Technical University of Athens19, Radboud University Nijmegen20, Free University of Berlin21, University of Koblenz and Landau22
TL;DR: A cross-scale analysis of paired-stressor effects on biological variables of European freshwater ecosystems shows that in 39% of cases, significant effects were limited to single stressors, with nutrient enrichment being the most important of these in lakes.
Abstract: Climate and land-use change drive a suite of stressors that shape ecosystems and interact to yield complex ecological responses (that is, additive, antagonistic and synergistic effects). We know little about the spatial scales relevant for the outcomes of such interactions and little about effect sizes. These knowledge gaps need to be filled to underpin future land management decisions or climate mitigation interventions for protecting and restoring freshwater ecosystems. This study combines data across scales from 33 mesocosm experiments with those from 14 river basins and 22 cross-basin studies in Europe, producing 174 combinations of paired-stressor effects on a biological response variable. Generalized linear models showed that only one of the two stressors had a significant effect in 39% of the analysed cases, 28% of the paired-stressor combinations resulted in additive effects and 33% resulted in interactive (antagonistic, synergistic, opposing or reversal) effects. For lakes, the frequencies of additive and interactive effects were similar for all spatial scales addressed, while for rivers these frequencies increased with scale. Nutrient enrichment was the overriding stressor for lakes, with effects generally exceeding those of secondary stressors. For rivers, the effects of nutrient enrichment were dependent on the specific stressor combination and biological response variable. These results vindicate the traditional focus of lake restoration and management on nutrient stress, while highlighting that river management requires more bespoke management solutions.
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TL;DR: The study aimed to determine the extent to which the coronavirus disease 2019 (COVID‐19) pandemic may aggravate the prenatal distress and psychiatric symptomatology of pregnant women.
Abstract: Introduction Prenatal maternal distress has a negative impact on the course of pregnancy, fetal development, offspring development, and later psychopathologies. The study aimed to determine the extent to which the coronavirus disease 2019 (COVID-19) pandemic may aggravate the prenatal distress and psychiatric symptomatology of pregnant women. Material and methods Two cohorts of pregnant volunteer women were evaluated, one that was recruited before the COVID-19 pandemic (n = 496) through advertisements in prenatal clinics in Quebec, Canada, from April 2018 to March 2020; the other (n = 1258) was recruited online during the pandemic from 2 April to 13 April 2020. Prenatal distress and psychiatric symptomatology were measured with the Kessler Distress Scale (K10), Post-traumatic Checklist for DSM-5 (PCL-5), Dissociative Experiences Scale (DES-II), and Positive and Negative Affect Schedule (PANAS). Results The 1754 pregnant women (Mage = 29.27, SD = 4.23) were between 4 and 41 gestational weeks (M = 24.80, SD = 9.42), were generally educated (91.3% had post-high-school training), and financially well-resourced (85.3% were above the low-income cut-off). A multivariate analysis of covariance controlling for age, gestational age, household income, education, and lifetime psychiatric disorders showed a large effect size (ES) in the difference between the two cohorts on psychiatric symptoms (Wilks' λ = 0.68, F6,1400 = 108.50, P Conclusions Pregnant women assessed during the COVID-19 pandemic reported more distress and psychiatric symptoms than pregnant women assessed before the pandemic, mainly in the form of depression and anxiety symptoms. Given the harmful consequences of prenatal distress on mothers and offspring, the presently observed upsurge of symptoms in pregnant women calls for special means of clinical surveillance.
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University of British Columbia1, Montreal Heart Institute2, University of Toronto3, Dalhousie University4, McMaster University5, University of Alberta6, University of Calgary7, University of Ottawa8, McGill University9, Laval University10, Population Health Research Institute11, University of Western Ontario12
TL;DR: The 2020 iteration of the CCS AF guidelines represents a comprehensive renewal that integrates, updates, and replaces the past decade of guidelines, recommendations, and practical tips.
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Humboldt University of Berlin1, McMaster University2, National Institutes of Health3, Ghent University Hospital4, University of Amsterdam5, University of Marburg6, Nova Southeastern University7, Transylvania University8, Charité9, Woolcock Institute of Medical Research10, Laval University11, Humanitas University12, University of Cartagena13, University of South Florida14, University of Porto15, Federal University of Bahia16, University of Naples Federico II17, Université Paris-Saclay18, Saint Louis University19, Istanbul University20, Erasmus University Rotterdam21, University of Helsinki22, Odense University Hospital23, University of Crete24, Chiba University25, Wrocław Medical University26, Ukrainian Medical Stomatological Academy27, Hacettepe University28, Medical University of Łódź29, Vilnius University30, National Research Council31, University of Tennessee32, Oslo University Hospital33, University of Beira Interior34, Karolinska Institutet35, University of Cologne36, University of Barcelona37, Russian National Research Medical University38, Monash University39, Ajou University40, Charles University in Prague41, University of Genoa42, Pasteur Institute43, University of Southampton44, University of Edinburgh45, Medical University of Warsaw46, University College London47, Imperial College London48, University of Coimbra49, University of Turku50, University of Bari51, Celal Bayar University52
TL;DR: Next-generation guidelines for the pharmacologic treatment of allergic rhinitis were developed by using existing GRADE-based guidelines forThe disease, real-world evidence provided by mobile technology, and additive studies (allergen chamber studies) to refine the MACVIA algorithm.
Abstract: The selection of pharmacotherapy for patients with allergic rhinitis aims to control the disease and depends on many factors. Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines have considerably improved the treatment of allergic rhinitis. However, there is an increasing trend toward use of real-world evidence to inform clinical practice, especially because randomized controlled trials are often limited with regard to the applicability of results. The Contre les Maladies Chroniques pour un Vieillissement Actif (MACVIA) algorithm has proposed an allergic rhinitis treatment by a consensus group. This simple algorithm can be used to step up or step down allergic rhinitis treatment. Next-generation guidelines for the pharmacologic treatment of allergic rhinitis were developed by using existing GRADE-based guidelines for the disease, real-world evidence provided by mobile technology, and additive studies (allergen chamber studies) to refine the MACVIA algorithm.
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TL;DR: How older people are misrepresented and undervalued in the current public discourse surrounding the COVID-19 pandemic is discussed, including issues in documenting the deaths of older adults, the lack of preparation for such a crisis in long-term care homes, and how some ‘protective’ policies can be considered patronising.
Abstract: The goal of this commentary is to highlight the ageism that has emerged during the COVID-19 pandemic. Over 20 international researchers in the field of ageing have contributed to this document. This commentary discusses how older people are misrepresented and undervalued in the current public discourse surrounding the pandemic. It points to issues in documenting the deaths of older adults, the lack of preparation for such a crisis in long-term care homes, how some 'protective' policies can be considered patronising and how the initial perception of the public was that the virus was really an older adult problem. This commentary also calls attention to important intergenerational solidarity that has occurred during this crisis to ensure support and social-inclusion of older adults, even at a distance. Our hope is that with this commentary we can contribute to the discourse on older adults during this pandemic and diminish the ageist attitudes that have circulated.
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01 Jan 2020TL;DR: This article performed single-cell RNA sequencing of tissue specimen from obese individuals to characterize multiple immune cells, endothelial cells, fibroblasts, adipose and hematopoietic stem cell progenitors, showing depot-specific differences in the stromal vascual fraction of visceral and subcutaneous adipose tissue.
Abstract: The complex relationship between metabolic disease risk and body fat distribution in humans involves cellular characteristics which are specific to body fat compartments. Here we show depot-specific differences in the stromal vascual fraction of visceral and subcutaneous adipose tissue by performing single-cell RNA sequencing of tissue specimen from obese individuals. We characterize multiple immune cells, endothelial cells, fibroblasts, adipose and hematopoietic stem cell progenitors. Subpopulations of adipose-resident immune cells are metabolically active and associated with metabolic disease status and those include a population of potential dysfunctional CD8+ T cells expressing metallothioneins. We identify multiple types of adipocyte progenitors that are common across depots, including a subtype enriched in individuals with type 2 diabetes. Depot-specific analysis reveals a class of adipocyte progenitors unique to visceral adipose tissue, which shares common features with beige preadipocytes. Our human single-cell transcriptome atlas across fat depots provides a resource to dissect functional genomics of metabolic disease.