Showing papers by "University of Calgary published in 2020"
TL;DR: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates, and there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries.
5,802 citations
Christopher J L Murray1, Christopher J L Murray2, Christopher J L Murray3, Aleksandr Y. Aravkin3 +2269 more•Institutions (286)
TL;DR: The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure.
3,059 citations
TL;DR: The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.
1,600 citations
TL;DR: This Consensus Statement outlines the definition and scope of the term ‘synbiotics’ as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in May 2019 and explores the levels of evidence, safety, effects upon targets and implications for stakeholders of the synbiotic concept.
Abstract: In May 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of nutritionists, physiologists and microbiologists to review the definition and scope of synbiotics. The panel updated the definition of a synbiotic to “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host”. The panel concluded that defining synbiotics as simply a mixture of probiotics and prebiotics could suppress the innovation of synbiotics that are designed to function cooperatively. Requiring that each component must meet the evidence and dose requirements for probiotics and prebiotics individually could also present an obstacle. Rather, the panel clarified that a complementary synbiotic, which has not been designed so that its component parts function cooperatively, must be composed of a probiotic plus a prebiotic, whereas a synergistic synbiotic does not need to be so. A synergistic synbiotic is a synbiotic for which the substrate is designed to be selectively utilized by the co-administered microorganisms. This Consensus Statement further explores the levels of evidence (existing and required), safety, effects upon targets and implications for stakeholders of the synbiotic concept. Gut microbiota can be manipulated to benefit host health, including the use of probiotics, prebiotics and synbiotics. This Consensus Statement outlines the definition and scope of the term ‘synbiotics’ as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in May 2019.
953 citations
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
Joan B. Soriano1, Parkes J Kendrick2, Katherine R. Paulson2, Vinay Gupta2 +311 more•Institutions (178)
TL;DR: It is shown that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.
829 citations
University of North Carolina at Chapel Hill1, Icahn School of Medicine at Mount Sinai2, University of Otago3, University of Calgary4, Mount Sinai Hospital5, University of Pennsylvania6, The Chinese University of Hong Kong7, Université catholique de Louvain8, Medical University of Vienna9, Necker-Enfants Malades Hospital10, University of São Paulo11
TL;DR: Increasing age, comorbidities, and corticosteroids are associated with severe COVID-19 among IBD patients, although a causal relationship cannot be definitively established.
576 citations
TL;DR: Higher symptoms of depression and anxiety were associated with more concern about threats of COVID-19 to the life of the mother and baby, as well as concerns about not getting the necessary prenatal care, relationship strain, and social isolation due to the CO VID-19 pandemic.
576 citations
Stavanger University Hospital1, University of Bergen2, University of Toronto3, University of Chicago4, Goethe University Frankfurt5, University of Oslo6, Oslo University Hospital7, The Chinese University of Hong Kong8, Hospital Clínico San Carlos9, City of Hope National Medical Center10, University of Melbourne11, University of Calgary12, Harvard University13, Boston Children's Hospital14, Lund University15, Agostino Gemelli University Polyclinic16
TL;DR: The ongoing pandemic is having a collateral health effect on delivery of surgical care to millions of patients, and little is known about pandemic management and effects on other services, including delivery of surgery.
Abstract: BACKGROUND: The ongoing pandemic is having a collateral health effect on delivery of surgical care to millions of patients. Very little is known about pandemic management and effects on other services, including delivery of surgery. METHODS: This was a scoping review of all available literature pertaining to COVID-19 and surgery, using electronic databases, society websites, webinars and preprint repositories. RESULTS: Several perioperative guidelines have been issued within a short time. Many suggestions are contradictory and based on anecdotal data at best. As regions with the highest volume of operations per capita are being hit, an unprecedented number of operations are being cancelled or deferred. No major stakeholder seems to have considered how a pandemic deprives patients with a surgical condition of resources, with patients disproportionally affected owing to the nature of treatment (use of anaesthesia, operating rooms, protective equipment, physical invasion and need for perioperative care). No recommendations exist regarding how to reopen surgical delivery. The postpandemic evaluation and future planning should involve surgical services as an essential part to maintain appropriate surgical care for the population during an outbreak. Surgical delivery, owing to its cross-cutting nature and synergistic effects on health systems at large, needs to be built into the WHO agenda for national health planning. CONCLUSION: Patients are being deprived of surgical access, with uncertain loss of function and risk of adverse prognosis as a collateral effect of the pandemic. Surgical services need a contingency plan for maintaining surgical care in an ongoing or postpandemic phase.
521 citations
TL;DR: Garnet-type electrolyte has been considered one of the most promising and important solid-state electrolytes for batteries with potential benefits in energy density, electrochemical stability, high temperature stability, and safety, and this Review will survey recent development of garnet- type LLZO electrolytes.
Abstract: Solid-state batteries with desirable advantages, including high-energy density, wide temperature tolerance, and fewer safety-concerns, have been considered as a promising energy storage technology to replace organic liquid electrolyte-dominated Li-ion batteries. Solid-state electrolytes (SSEs) as the most critical component in solid-state batteries largely lead the future battery development. Among different types of solid-state electrolytes, garnet-type Li7La3Zr2O12 (LLZO) solid-state electrolytes have particularly high ionic conductivity (10-3 to 10-4 S/cm) and good chemical stability against Li metal, offering a great opportunity for solid-state Li-metal batteries. Since the discovery of garnet-type LLZO in 2007, there has been an increasing interest in the development of garnet-type solid-state electrolytes and all solid-state batteries. Garnet-type electrolyte has been considered one of the most promising and important solid-state electrolytes for batteries with potential benefits in energy density, electrochemical stability, high temperature stability, and safety. In this Review, we will survey recent development of garnet-type LLZO electrolytes with discussions of experimental studies and theoretical results in parallel, LLZO electrolyte synthesis strategies and modifications, stability of garnet solid electrolytes/electrodes, emerging nanostructure designs, degradation mechanisms and mitigations, and battery architectures and integrations. We will also provide a target-oriented research overview of garnet-type LLZO electrolyte and its application in various types of solid-state battery concepts (e.g., Li-ion, Li-S, and Li-air), and we will show opportunities and perspectives as guides for future development of solid electrolytes and solid-state batteries.
511 citations
Eötvös Loránd University1, Yale University2, University of Cape Town3, Flinders University4, University of Calgary5, University of Queensland6, Nottingham Trent University7, Macedonian Academy of Sciences and Arts8, University of Lausanne9, University of Duisburg-Essen10, Auckland University of Technology11, University of Cambridge12, Sapienza University of Rome13, Lithuanian University of Health Sciences14, University of Porto15, University of Ulm16, Stellenbosch University17, University of Zurich18, University of Chieti-Pescara19, Catholic University of Korea20, University of Lübeck21, University of Valencia22, Tehran University of Medical Sciences23, Bellvitge University Hospital24, Tel Aviv University25, Hertfordshire Partnership University NHS Foundation Trust26
TL;DR: Although for the vast majority ICT use is adaptive and should not be pathologized, a subgroup of vulnerable individuals are at risk of developing problematic usage patterns and the present consensus guidance discusses these risks and makes some practical recommendations that may help diminish them.
TL;DR: This study isolated three bacterial species—Bifidobacterium pseudolongum, Lactobacillus johnsonii, and Olsenella species—that significantly enhanced efficacy of immune checkpoint inhibitors in four mouse models of cancer, and identifies a previously unknown microbial metabolite immune pathway activated by immunotherapy that may be exploited to develop microbial-based adjuvant therapies.
Abstract: Several species of intestinal bacteria have been associated with enhanced efficacy of checkpoint blockade immunotherapy, but the underlying mechanisms by which the microbiome enhances antitumor immunity are unclear. In this study, we isolated three bacterial species-Bifidobacterium pseudolongum, Lactobacillus johnsonii, and Olsenella species-that significantly enhanced efficacy of immune checkpoint inhibitors in four mouse models of cancer. We found that intestinal B. pseudolongum modulated enhanced immunotherapy response through production of the metabolite inosine. Decreased gut barrier function induced by immunotherapy increased systemic translocation of inosine and activated antitumor T cells. The effect of inosine was dependent on T cell expression of the adenosine A2A receptor and required costimulation. Collectively, our study identifies a previously unknown microbial metabolite immune pathway activated by immunotherapy that may be exploited to develop microbial-based adjuvant therapies.
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
Katrina L. Grasby1, Neda Jahanshad2, Jodie N. Painter1, Lucía Colodro-Conde3 +356 more•Institutions (115)
TL;DR: Results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness and find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function.
Abstract: The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
McMaster University1, University of Pennsylvania2, University of Adelaide3, University of Copenhagen4, Population Health Research Institute5, University of Miyazaki6, University of Queensland7, University of Birmingham8, University of Toronto9, University of Calgary10, University of British Columbia11, University of Brescia12, University of Western Ontario13, Charles University in Prague14, Kyoto Prefectural University of Medicine15, Kyoto University16, Imperial College London17, University of Cambridge18
TL;DR: Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD, and a reduced-dose regimen of glucocorticoids was noninferior to a standard- dose regimen with respect to death orESKD.
Abstract: Background More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. Methods We conducted a randomized trial with a 2-by-2 factor...
TL;DR: This paper showed that stocks with higher ES ratings have significantly higher returns, lower return volatility, and higher operating profit margins during the COVID-19 pandemic and the subsequent lockdown brought about an exogenous and unparalleled stock market crash The crisis thus provides a unique opportunity to test theories of environmental and social policies.
Abstract: The COVID-19 pandemic and the subsequent lockdown brought about an exogenous and unparalleled stock market crash The crisis thus provides a unique opportunity to test theories of environmental and social (ES) policies This paper shows that stocks with higher ES ratings have significantly higher returns, lower return volatility, and higher operating profit margins during the first quarter of 2020 ES firms with higher advertising expenditures experience higher stock returns, and stocks held by more ES-oriented investors experience less return volatility during the crash This paper highlights the importance of customer and investor loyalty to the resiliency of ES stocks
Norwegian School of Sport Sciences1, Stellenbosch University2, University of Calgary3, Edith Cowan University4, Linköping University5, University of British Columbia6, University of North Carolina at Chapel Hill7, McMaster University8, University of Sydney9, Wellington Management Company10, University of Chicago11, University of Pretoria12, International Olympic Committee13, University of Bath14
TL;DR: The objective was to further strengthen consistency in data collection, injury definitions and research reporting through an updated set of recommendations for sports injury and illness studies, including a new Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist extension.
Abstract: Injury and illness surveillance, and epidemiological studies, are fundamental elements of concerted efforts to protect the health of the athlete. To encourage consistency in the definitions and methodology used, and to enable data across studies to be compared, research groups have published 11 sport-specific or setting-specific consensus statements on sports injury (and, eventually, illness) epidemiology to date. Our objective was to further strengthen consistency in data collection, injury definitions and research reporting through an updated set of recommendations for sports injury and illness studies, including a new Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist extension. The IOC invited a working group of international experts to review relevant literature and provide recommendations. The procedure included an open online survey, several stages of text drafting and consultation by working groups and a 3-day consensus meeting in October 2019. This statement includes recommendations for data collection and research reporting covering key components: defining and classifying health problems; severity of health problems; capturing and reporting athlete exposure; expressing risk; burden of health problems; study population characteristics and data collection methods. Based on these, we also developed a new reporting guideline as a STROBE Extension-the STROBE Sports Injury and Illness Surveillance (STROBE-SIIS). The IOC encourages ongoing in- and out-of-competition surveillance programmes and studies to describe injury and illness trends and patterns, understand their causes and develop measures to protect the health of the athlete. Implementation of the methods outlined in this statement will advance consistency in data collection and research reporting.
Tufts Medical Center1, Charité2, American Medical Association3, Erasmus University Rotterdam4, Harvard University5, University of British Columbia6, University of Washington7, University of Pittsburgh8, Yale University9, Veterans Health Administration10, Children's Hospital at Westmead11, Great Ormond Street Hospital for Children NHS Foundation Trust12, American Society of Nephrology13, University of Maryland, Baltimore14, Royal Free London NHS Foundation Trust15, University of Pennsylvania16, University Medical Center Groningen17, Mayo Clinic18, University of Calgary19, University of Michigan20, Keele University21, University of Oklahoma Health Sciences Center22, St Thomas' Hospital23, French Institute of Health and Medical Research24, University of Paris25, Heidelberg University26, National Kidney Foundation27, University College London28, Cliniques Universitaires Saint-Luc29, Baylor College of Medicine30
TL;DR: Recommendations to use "kidney" rather than "renal" or "nephro-" when referring to kidney disease and kidney function and to use the KDIGO definition and classification of chronic kidney disease rather than alternative descriptions to define and classify severity of CKD.
TL;DR: The relevance of extant international business (IB) research, and more specifically work on international human resources management (IHRM), to address COVID-19 pandemic challenges is shown.
Abstract: We show the relevance of extant international business (IB) research, and more specifically work on international human resources management (IHRM), to address COVID-19 pandemic challenges. Decision-makers in multinational enterprises have undertaken various types of actions to alleviate the impacts of the pandemic. In most cases these actions relate in some way to managing distance and to rethinking boundaries, whether at the macro- or firm-levels. Managing distance and rethinking boundaries have been the primary focus of much IB research since the IB field was established as a legitimate area of academic inquiry. The pandemic has led to increased cross-border distance problems (e.g., as the result of travel bans and reduced international mobility), and often also to new intra-firm distancing challenges imposed upon previously co-located employees. Prior IHRM research has highlighted the difficulties presented by distance, in terms of employee selection, training, support, health and safety, as well as leadership and virtual collaboration. Much of this thinking is applicable to solve pandemic-related distance challenges. The present, extreme cases of requisite physical distancing need not imply equivalent increases in psychological distance, and also offer firms some insight into the unanticipated benefits of a virtual workforce - a type of workforce that, quite possibly, will influence the 'new normal' of the post-COVID world. Extant IHRM research does offer actionable insight for today, but outstanding knowledge gaps remain. Looking ahead, we offer three domains for future IHRM research: managing under uncertainty, facilitating international and even global work, and redefining organizational performance.
TL;DR: This review discusses leukocytes in the context of sterile inflammation, a process caused by sterile molecules, comprising damage-associated molecular patterns (DAMPs), which bind specific receptors to activate inflammation and start a highly optimized sequence of immune cell recruitment of neutrophils and monocytes to initiate effective tissue repair.
Abstract: Recognizing the importance of leukocyte trafficking in inflammation led to some therapeutic breakthroughs. However, many inflammatory pathologies remain without specific therapy. This review discusses leukocytes in the context of sterile inflammation, a process caused by sterile (non-microbial) molecules, comprising damage-associated molecular patterns (DAMPs). DAMPs bind specific receptors to activate inflammation and start a highly optimized sequence of immune cell recruitment of neutrophils and monocytes to initiate effective tissue repair. When DAMPs are cleared, the recruited leukocytes change from a proinflammatory to a reparative program, a switch that is locally supervised by invariant natural killer T cells. In addition, neutrophils exit the inflammatory site and reverse transmigrate back to the bloodstream. Inflammation persists when the program switch or reverse transmigration fails, or when the coordinated leukocyte effort cannot clear the immunostimulatory molecules. The latter causes inappropriate leukocyte activation, a driver of many pathologies associated with poor lifestyle choices. We discuss lifestyle-associated inflammatory diseases and their corresponding immunostimulatory lifestyle-associated molecular patterns (LAMPs) and distinguish them from DAMPs.
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.
TL;DR: This review focuses on the discussion of the latest progress and remaining challenges in selected metal-free photocatalysts for hydrogen production and the potential strategies that are deemed necessary to attain high quantum efficiency and high solar-to-hydrogen (STH) conversion efficiency.
Abstract: This review focuses on the discussion of the latest progress and remaining challenges in selected metal-free photocatalysts for hydrogen production. The scope of this review is limited to the metal-free elemental photocatalysts (i.e. B, C, P, S, Si, Se etc.), binary photocatalysts (i.e. BC3, B4C, CxNy, h-BN etc.) and their heterojunction, ternary photocatalysts (i.e. BCN) and their heterojunction, and different types of organic photocatalysts (i.e. linear, covalent organic frameworks, microporous polymer, covalent triazine frameworks etc.) and their heterostructures. Following a succinct depiction of the latest progress in hydrogen evolution on these photocatalysts, discussion has been extended to the potential strategies that are deemed necessary to attain high quantum efficiency and high solar-to-hydrogen (STH) conversion efficiency. Issues with reproducibility and the disputes in reporting the hydrogen evolution rate have been also discussed with recommendations to overcome them. A few key factors are highlighted that may facilitate the scalability of the photocatalyst from microscale to macroscale production in meeting the targeted 10% STH. This review is concluded with additional perspectives regarding future research in fundamental materials aspects of high efficiency photocatalysts followed by six open questions that may need to be resolved by forming a global hydrogen taskforce in order to translate bench-top research into large-scale production of hydrogen.
TL;DR: Evidence of a rising burden of both premenopausal and postmenopausal breast cancer worldwide is provided, although early diagnosis and access to treatment remain crucial in low-income and middle-income countries.
TL;DR: To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—the authors estimated additional population equivalents with UHC effective coverage from 2018 to 2023, and quantified frontiers of U HC effective coverage performance on the basis of pooled health spending per capita.
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02 Apr 2020
TL;DR: Earlier, more aggressive treatment with biologic therapies or novel small molecules could profoundly change the natural history of the disease and decrease complications and the need for hospitalization and surgery in Crohn’s disease.
Abstract: Crohn’s disease is an inflammatory bowel disease that is characterized by chronic inflammation of any part of the gastrointestinal tract, has a progressive and destructive course and is increasing in incidence worldwide. Several factors have been implicated in the cause of Crohn’s disease, including a dysregulated immune system, an altered microbiota, genetic susceptibility and environmental factors, but the cause of the disease remains unknown. The onset of the disease at a young age in most cases necessitates prompt but long-term treatment to prevent disease flares and disease progression with intestinal complications. Thus, earlier, more aggressive treatment with biologic therapies or novel small molecules could profoundly change the natural history of the disease and decrease complications and the need for hospitalization and surgery. Although less invasive biomarkers are in development, diagnosis still relies on endoscopy and histological assessment of biopsy specimens. Crohn’s disease is a complex disease, and treatment should be personalized to address the underlying pathogenetic mechanism. In the future, disease management might rely on severity scores that incorporate prognostic factors, bowel damage assessment and non-invasive close monitoring of disease activity to reduce the severity of complications. Crohn’s disease is a progressive, destructive inflammatory bowel disease of unclear cause and involves chronic inflammation of any part of the gastrointestinal tract. This Primer reviews the epidemiology, pathophysiology, diagnosis and management of this disease.
British Heart Foundation1, University of Toronto2, Yale University3, University of Minnesota4, First Faculty of Medicine, Charles University in Prague5, Saarland University6, National Yang-Ming University7, Taipei Veterans General Hospital8, University Medical Center Groningen9, Brigham and Women's Hospital10, Medical University of Łódź11, Comenius University in Bratislava12, Fudan University13, University of Calgary14, University of Gothenburg15, Semmelweis University16, University of São Paulo17, Montreal Heart Institute18, Copenhagen University Hospital19, University of Missouri–Kansas City20, AstraZeneca21, National University of Cordoba22, Wrocław Medical University23
TL;DR: In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status.
Abstract: Importance Additional treatments are needed for heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors may be an effective treatment for patients with HFrEF, even those without diabetes. Objective To evaluate the effects of dapagliflozin in patients with HFrEF with and without diabetes. Design, Setting, and Participants Exploratory analysis of a phase 3 randomized trial conducted at 410 sites in 20 countries. Patients with New York Heart Association classification II to IV with an ejection fraction less than or equal to 40% and elevated plasma N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Interventions Addition of once-daily 10 mg of dapagliflozin or placebo to recommended therapy. Main Outcomes and Measures The primary outcome was the composite of an episode of worsening heart failure or cardiovascular death. This outcome was analyzed by baseline diabetes status and, in patients without diabetes, by glycated hemoglobin level less than 5.7% vs greater than or equal to 5.7%. Results Among 4744 patients randomized (mean age, 66 years; 1109 [23%] women; 2605 [55%] without diabetes), 4742 completed the trial. Among participants without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) in the dapagliflozin group and 231 of 1307 (17.7%) in the placebo group (hazard ratio, 0.73 [95% CI, 0.60-0.88]). In patients with diabetes, the primary outcome occurred in 215 of 1075 (20.0%) in the dapagliflozin group and 271 of 1064 (25.5%) in the placebo group (hazard ratio, 0.75 [95% CI, 0.63-0.90]) (Pvalue for interaction = .80). Among patients without diabetes and a glycated hemoglobin level less than 5.7%, the primary outcome occurred in 53 of 438 patients (12.1%) in the dapagliflozin group and 71 of 419 (16.9%) in the placebo group (hazard ratio, 0.67 [95% CI, 0.47-0.96]). In patients with a glycated hemoglobin of at least 5.7%, the primary outcome occurred in 118 of 860 patients (13.7%) in the dapagliflozin group and 160 of 888 (18.0%) in the placebo group (hazard ratio, 0.74 [95% CI, 0.59-0.94]) (Pvalue for interaction = .72). Volume depletion was reported as an adverse event in 7.3% of patients in the dapagliflozin group and 6.1% in the placebo group among patients without diabetes and in 7.8% of patients in the dapagliflozin group and 7.8% in the placebo group among patients with diabetes. A kidney adverse event was reported in 4.8% of patients in the dapagliflozin group and 6.0% in the placebo group among patients without diabetes and in 8.5% of patients in the dapagliflozin group and 8.7% in the placebo group among patients with diabetes. Conclusions and Relevance In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status. Trial Registration ClinicalTrials.gov Identifier:NCT03036124
University of Chicago1, American Heart Association2, University of Missouri–Kansas City3, University of Iowa4, University of Alberta5, Hofstra University6, University of Pennsylvania7, Queen's University8, University of Calgary9, University of Oklahoma10, American Academy of Pediatrics11, Stanford University12, University of Texas at Arlington13, Ohio State University14, Virginia Commonwealth University15, Boston Children's Hospital16, Liberty University17, Columbia University18, New York University19
TL;DR: The importance of including appropriate variables, following the proper steps, and adopting the proper methods when selecting variables for prediction models is focused on.
Abstract: Clinical prediction models are used frequently in clinical practice to identify patients who are at risk of developing an adverse outcome so that preventive measures can be initiated. A prediction model can be developed in a number of ways; however, an appropriate variable selection strategy needs to be followed in all cases. Our purpose is to introduce readers to the concept of variable selection in prediction modelling, including the importance of variable selection and variable reduction strategies. We will discuss the various variable selection techniques that can be applied during prediction model building (backward elimination, forward selection, stepwise selection and all possible subset selection), and the stopping rule/selection criteria in variable selection (p values, Akaike information criterion, Bayesian information criterion and Mallows’ Cp statistic). This paper focuses on the importance of including appropriate variables, following the proper steps, and adopting the proper methods when selecting variables for prediction models.
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.
TL;DR: A conserved neural tri-lineage cancer hierarchy centered around glial progenitor-like cells is found, and this hierarchal map can be used to identify therapeutic targets specific to progenitors cancer stem cells.
Abstract: Cancer stem cells are critical for cancer initiation, development, and treatment resistance. Our understanding of these processes, and how they relate to glioblastoma heterogeneity, is limited. To overcome these limitations, we performed single-cell RNA sequencing on 53586 adult glioblastoma cells and 22637 normal human fetal brain cells, and compared the lineage hierarchy of the developing human brain to the transcriptome of cancer cells. We find a conserved neural tri-lineage cancer hierarchy centered around glial progenitor-like cells. We also find that this progenitor population contains the majority of the cancer’s cycling cells, and, using RNA velocity, is often the originator of the other cell types. Finally, we show that this hierarchal map can be used to identify therapeutic targets specific to progenitor cancer stem cells. Our analyses show that normal brain development reconciles glioblastoma development, suggests a possible origin for glioblastoma hierarchy, and helps to identify cancer stem cell-specific targets. Glioblastoma is thought to arise from neural stem cells. Here, to investigate this, the authors use single-cell RNA-sequencing to compare glioblastoma to the fetal human brain, and find a similarity between glial progenitor cells and a subpopulation of glioblastoma cells.