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Showing papers by "Queen's University published in 2021"


Journal ArticleDOI
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

1,129 citations


Journal ArticleDOI
04 Mar 2021-Nature
TL;DR: The GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2244 critically ill Covid-19 patients from 208 UK intensive care units is reported, finding evidence in support of a causal link from low expression of IFNAR2, and high expression of TYK2, to life-threatening disease.
Abstract: Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10−8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10−8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10−12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10−8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte–macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice. A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

941 citations


Journal ArticleDOI
TL;DR: It is found that more than 40% of persons worldwide have FGIDs, which affect quality of life and healthcare use, and similar trends and relative distributions were found in people who completed internet vs personal interviews.

763 citations


Journal ArticleDOI
TL;DR: In this paper, the authors review recent advances in integrated photonic neuromorphic systems, discuss current and future challenges, and outline the advances in science and technology needed to meet those challenges.
Abstract: Research in photonic computing has flourished due to the proliferation of optoelectronic components on photonic integration platforms. Photonic integrated circuits have enabled ultrafast artificial neural networks, providing a framework for a new class of information processing machines. Algorithms running on such hardware have the potential to address the growing demand for machine learning and artificial intelligence in areas such as medical diagnosis, telecommunications, and high-performance and scientific computing. In parallel, the development of neuromorphic electronics has highlighted challenges in that domain, particularly related to processor latency. Neuromorphic photonics offers sub-nanosecond latencies, providing a complementary opportunity to extend the domain of artificial intelligence. Here, we review recent advances in integrated photonic neuromorphic systems, discuss current and future challenges, and outline the advances in science and technology needed to meet those challenges. Photonics offers an attractive platform for implementing neuromorphic computing due to its low latency, multiplexing capabilities and integrated on-chip technology.

480 citations


Posted ContentDOI
27 Aug 2021-medRxiv
TL;DR: In this article, the authors investigated the persistence of BNT162b2 (Pfizer-BioNTech) vaccine effectiveness against infection and disease in Qatar, where the Beta and Delta variants have dominated incidence and PCR testing is done at a mass scale.
Abstract: BACKGROUND Waning of vaccine protection against SARS-CoV-2 infection or COVID-19 disease is a concern. This study investigated persistence of BNT162b2 (Pfizer-BioNTech) vaccine effectiveness against infection and disease in Qatar, where the Beta and Delta variants have dominated incidence and PCR testing is done at a mass scale. METHODS A matched test-negative, case-control study design was used to estimate vaccine effectiveness against SARS-CoV-2 infection and against any severe, critical, or fatal COVID-19 disease, between January 1, 2021 to August 15, 2021. RESULTS Estimated BNT162b2 effectiveness against any infection, asymptomatic or symptomatic, was negligible for the first two weeks after the first dose, increased to 36.5% (95% CI: 33.1-39.8) in the third week after the first dose, and reached its peak at 72.1% (95% CI: 70.9-73.2) in the first five weeks after the second dose. Effectiveness declined gradually thereafter, with the decline accelerating ≥15 weeks after the second dose, reaching diminished levels of protection by the 20th week. Effectiveness against symptomatic infection was higher than against asymptomatic infection, but still waned in the same fashion. Effectiveness against any severe, critical, or fatal disease increased rapidly to 67.7% (95% CI: 59.1-74.7) by the third week after the first dose, and reached 95.4% (95% CI: 93.4-96.9) in the first five weeks after the second dose, where it persisted at about this level for six months. CONCLUSIONS BNT162b2-induced protection against infection appears to wane rapidly after its peak right after the second dose, but it persists at a robust level against hospitalization and death for at least six months following the second dose.

473 citations


Journal ArticleDOI
01 Mar 2021
TL;DR: The JBI Scoping Review Methodology Group developed guidance for conducting a JBI scoping review, with a focus on new updates to the approach and development of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (the PRISMA-ScR) as mentioned in this paper.
Abstract: OBJECTIVE The objective of this paper is to describe the updated methodological guidance for conducting a JBI scoping review, with a focus on new updates to the approach and development of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (the PRISMA-ScR) INTRODUCTION Scoping reviews are an increasingly common approach to informing decision-making and research based on the identification and examination of the literature on a given topic or issue Scoping reviews draw on evidence from any research methodology and may also include evidence from non-research sources, such as policy In this manner, scoping reviews provide a comprehensive overview to address broader review questions than traditionally more specific systematic reviews of effectiveness or qualitative evidence The increasing popularity of scoping reviews has been accompanied by the development of a reporting guideline: the PRISMA-ScR In 2014, the JBI Scoping Review Methodology Group developed guidance for scoping reviews that received minor updates in 2017 and was most recently updated in 2020 The updates reflect ongoing and substantial developments in approaches to scoping review conduct and reporting As such, the JBI Scoping Review Methodology Group recognized the need to revise the guidance to align with the current state of knowledge and reporting standards in evidence synthesis METHODS Between 2015 and 2020, the JBI Scoping Review Methodology Group expanded its membership; extensively reviewed the literature; engaged via annual face-to-face meetings, regular teleconferences, and email correspondence; sought advice from methodological experts; facilitated workshops; and presented at scientific conferences This process led to updated guidance for scoping reviews published in the JBI Manual for Evidence Synthesis The updated chapter was endorsed by JBI's International Scientific Committee in 2020 RESULTS The updated JBI guidance for scoping reviews includes additional guidance on several methodological issues, such as when a scoping review is (or is not) appropriate, and how to extract, analyze, and present results, and provides clarification for implications for practice and research Furthermore, it is aligned with the PRISMA-ScR to ensure consistent reporting CONCLUSIONS The latest JBI guidance for scoping reviews provides up-to-date guidance that can be used by authors when conducting a scoping review Furthermore, it aligns with the PRISMA-ScR, which can be used to report the conduct of a scoping review A series of ongoing and future methodological projects identified by the JBI Scoping Review Methodology Group to further refine the methodology are planned

271 citations


Journal ArticleDOI
TL;DR: The default mode network (DMN) as mentioned in this paper is a set of widely distributed brain regions in the parietal, temporal and frontal cortex, and it has been shown that these regions often show reductions in activity during attention-demanding tasks but increase their activity across multiple forms of complex cognition.
Abstract: The default mode network (DMN) is a set of widely distributed brain regions in the parietal, temporal and frontal cortex. These regions often show reductions in activity during attention-demanding tasks but increase their activity across multiple forms of complex cognition, many of which are linked to memory or abstract thought. Within the cortex, the DMN has been shown to be located in regions furthest away from those contributing to sensory and motor systems. Here, we consider how our knowledge of the topographic characteristics of the DMN can be leveraged to better understand how this network contributes to cognition and behaviour. Regions of the default mode network (DMN) are distributed across the brain and show patterns of activity that have linked them to various different functional domains. In this Perspective, Smallwood and colleagues consider how an examination of the topographic characteristics of the DMN can shed light on its contribution to cognition.

222 citations



Journal ArticleDOI
14 Oct 2021-BMJ
TL;DR: In this paper, the authors evaluated the effects of therapeutic heparin compared with prophylactic hepharmin among moderately ill patients with covid-19 admitted to hospital wards.
Abstract: Objective To evaluate the effects of therapeutic heparin compared with prophylactic heparin among moderately ill patients with covid-19 admitted to hospital wards. Design Randomised controlled, adaptive, open label clinical trial. Setting 28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and US. Participants 465 adults admitted to hospital wards with covid-19 and increased D-dimer levels were recruited between 29 May 2020 and 12 April 2021 and were randomly assigned to therapeutic dose heparin (n=228) or prophylactic dose heparin (n=237). Interventions Therapeutic dose or prophylactic dose heparin (low molecular weight or unfractionated heparin), to be continued until hospital discharge, day 28, or death. Main outcome measures The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation, or admission to an intensive care unit, assessed up to 28 days. The secondary outcomes included all cause death, the composite of all cause death or any mechanical ventilation, and venous thromboembolism. Safety outcomes included major bleeding. Outcomes were blindly adjudicated. Results The mean age of participants was 60 years; 264 (56.8%) were men and the mean body mass index was 30.3 kg/m2. At 28 days, the primary composite outcome had occurred in 37/228 patients (16.2%) assigned to therapeutic heparin and 52/237 (21.9%) assigned to prophylactic heparin (odds ratio 0.69, 95% confidence interval 0.43 to 1.10; P=0.12). Deaths occurred in four patients (1.8%) assigned to therapeutic heparin and 18 patients (7.6%) assigned to prophylactic heparin (0.22, 0.07 to 0.65; P=0.006). The composite of all cause death or any mechanical ventilation occurred in 23 patients (10.1%) assigned to therapeutic heparin and 38 (16.0%) assigned to prophylactic heparin (0.59, 0.34 to 1.02; P=0.06). Venous thromboembolism occurred in two patients (0.9%) assigned to therapeutic heparin and six (2.5%) assigned to prophylactic heparin (0.34, 0.07 to 1.71; P=0.19). Major bleeding occurred in two patients (0.9%) assigned to therapeutic heparin and four (1.7%) assigned to prophylactic heparin (0.52, 0.09 to 2.85; P=0.69). Conclusions In moderately ill patients with covid-19 and increased D-dimer levels admitted to hospital wards, therapeutic heparin was not significantly associated with a reduction in the primary outcome but the odds of death at 28 days was decreased. The risk of major bleeding appeared low in this trial. Trial registration ClinicalTrials.gov NCT04362085.

210 citations


Journal ArticleDOI
TL;DR: In this article, a large cross-sectional study examined the impact of COVID-19 emergency measures on child/adolescent mental health for children/adolescents with and without pre-existing psychiatric diagnoses.
Abstract: This large cross-sectional study examined the impact of COVID-19 emergency measures on child/adolescent mental health for children/adolescents with and without pre-existing psychiatric diagnoses. Using adapted measures from the CRISIS questionnaire, parents of children aged 6–18 (N = 1013; 56% male; 62% pre-existing psychiatric diagnosis) and self-reporting children/adolescents aged 10–18 (N = 385) indicated changes in mental health across six domains: depression, anxiety, irritability, attention, hyperactivity, and obsessions/compulsions. Changes in anxiety, irritability, and hyperactivity were calculated for children aged 2–5 years using the Strengths and Difficulties Questionnaire. COVID-19 exposure, compliance with emergency measures, COVID-19 economic concerns, and stress from social isolation were measured with the CRISIS questionnaire. Prevalence of change in mental health status was estimated for each domain; multinomial logistic regression was used to determine variables associated with mental health status change in each domain. Depending on the age group, 67–70% of children/adolescents experienced deterioration in at least one mental health domain; however, 19–31% of children/adolescents experienced improvement in at least one domain. Children/adolescents without and with psychiatric diagnoses tended to experience deterioration during the first wave of COVID-19. Rates of deterioration were higher in those with a pre-exiting diagnosis. The rate of deterioration was variable across different age groups and pre-existing psychiatric diagnostic groups: depression 37–56%, anxiety 31–50%, irritability 40–66%, attention 40–56%, hyperactivity 23–56%, obsessions/compulsions 13–30%. Greater stress from social isolation was associated with deterioration in all mental health domains (all ORs 11.12–55.24). The impact of pre-existing psychiatric diagnosis was heterogenous, associated with deterioration in depression, irritability, hyperactivity, obsession/compulsions for some children (ORs 1.96–2.23) but also with improvement in depression, anxiety, and irritability for other children (ORs 2.13–3.12). Economic concerns were associated with improvement in anxiety, attention, and obsessions/compulsions (ORs 3.97–5.57). Children/adolescents with and without pre-existing psychiatric diagnoses reported deterioration. Deterioration was associated with increased stress from social isolation. Enhancing social interactions for children/adolescents will be an important mitigation strategy for current and future COVID-19 waves.

202 citations


Journal ArticleDOI
TL;DR: It is argued that the authorities and healthcare executives must show strong leadership and support for doctors and their families during the COVID-19 outbreak and call for efforts to reduce mental health stigma in clinical workplaces.
Abstract: Doctors experience high levels of work stress even under normal circumstances, but many would be reluctant to disclose mental health difficulties or seek help for them, with stigma an often-cited reason. The coronavirus disease 2019 (COVID-19) crisis places additional pressure on doctors and on the healthcare system in general and research shows that such pressure brings a greater risk of psychological distress for doctors. For this reason, we argue that the authorities and healthcare executives must show strong leadership and support for doctors and their families during the COVID-19 outbreak and call for efforts to reduce mental health stigma in clinical workplaces. This can be facilitated by deliberately adding ‘healthcare staff mental health support process’ as an ongoing agenda item to high-level management planning meetings.

Journal ArticleDOI
TL;DR: One year into the global COVID-19 pandemic, the focus of attention has shifted to the emergence and spread of SARS-CoV-2 variants of concern (VOCs) as discussed by the authors.

Journal ArticleDOI
TL;DR: Tissue-specific immunopathology occurs in COVID-19, implicating a significant component of the immune-mediated, virus-independent immunopathologic process as a primary mechanism in severe disease.
Abstract: Rationale: In life-threatening coronavirus disease (COVID-19), corticosteroids reduce mortality, suggesting that immune responses have a causal role in death. Whether this deleterious inflammation is primarily a direct reaction to the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or an independent immunopathologic process is unknown.Objectives: To determine SARS-CoV-2 organotropism and organ-specific inflammatory responses and the relationships among viral presence, inflammation, and organ injury.Methods: Tissue was acquired from 11 detailed postmortem examinations. SARS-CoV-2 organotropism was mapped by using multiplex PCR and sequencing, with cellular resolution achieved by in situ viral S (spike) protein detection. Histologic evidence of inflammation was quantified from 37 anatomic sites, and the pulmonary immune response was characterized by using multiplex immunofluorescence.Measurements and Main Results: Multiple aberrant immune responses in fatal COVID-19 were found, principally involving the lung and reticuloendothelial system, and these were not clearly topologically associated with the virus. Inflammation and organ dysfunction did not map to the tissue and cellular distribution of SARS-CoV-2 RNA and protein between or within tissues. An arteritis was identified in the lung, which was further characterized as a monocyte/myeloid-rich vasculitis, and occurred together with an influx of macrophage/monocyte-lineage cells into the pulmonary parenchyma. In addition, stereotyped abnormal reticuloendothelial responses, including excessive reactive plasmacytosis and iron-laden macrophages, were present and dissociated from viral presence in lymphoid tissues.Conclusions: Tissue-specific immunopathology occurs in COVID-19, implicating a significant component of the immune-mediated, virus-independent immunopathologic process as a primary mechanism in severe disease. Our data highlight novel immunopathologic mechanisms and validate ongoing and future efforts to therapeutically target aberrant macrophage and plasma-cell responses as well as promote pathogen tolerance in COVID-19.

Journal ArticleDOI
TL;DR: In this article, a population-based study compared comprehensive, linked primary care physician billing data from Jan 1 to July 28, 2020, with the same period in 2019 to understand the degree to which office and virtual primary care changed, and for which patients and physicians, during the initial months of the pandemic in Ontario, Canada.
Abstract: BACKGROUND: Globally, primary care changed dramatically as a result of the coronavirus disease 2019 (COVID-19) pandemic We aimed to understand the degree to which office and virtual primary care changed, and for which patients and physicians, during the initial months of the pandemic in Ontario, Canada METHODS: This population-based study compared comprehensive, linked primary care physician billing data from Jan 1 to July 28, 2020, with the same period in 2019 We identified Ontario residents with at least 1 office or virtual (telephone or video) visit during the study period We compared trends in total physician visits, office visits and virtual visits before COVID-19 with trends after pandemic-related public health measures changed the delivery of care, according to various patient and physician characteristics We used interrupted time series analysis to compare trends in the early and later halves of the COVID-19 period RESULTS: Compared with 2019, total primary care visits between March and July 2020 decreased by 280%, from 766 to 551 per 1000 people/day The smallest declines were among patients with the highest expected health care use (83%), those who could not be attributed to a primary care physician (102%), and older adults (191%) In contrast, total visits in rural areas increased by 64% Office visits declined by 791% and virtual care increased 56-fold, comprising 711% of primary care physician visits The lowest uptake of virtual care was among children (576%), rural residents (606%) and physicians with panels of ≥ 2500 patients (660%) INTERPRETATION: Primary care in Ontario saw large shifts from office to virtual care over the first 4 months of the COVID-19 pandemic Total visits declined least among those with higher health care needs The determinants and consequences of these major shifts in care require further study

Journal ArticleDOI
TL;DR: In this article, the authors present evidence-based guidelines of the American Society of Hematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Hemophilia Foundation (NHF), and the World Federation of Hemopathilia (WFH) for von Willebrand disease (VWD) diagnosis.

Journal ArticleDOI
TL;DR: Intravenous ketamine appears to be more efficacious than intranasal esketamine for the treatment of depression.

Journal ArticleDOI
TL;DR: This work considers NN-based approaches to build PESs in the sums-of-product form important for quantum dynamics, ways to treat symmetry, and issues related to sampling data distributions and the relation between PES errors and errors in observables.
Abstract: We review progress in neural network (NN)-based methods for the construction of interatomic potentials from discrete samples (such as ab initio energies) for applications in classical and quantum dynamics including reaction dynamics and computational spectroscopy. The main focus is on methods for building molecular potential energy surfaces (PES) in internal coordinates that explicitly include all many-body contributions, even though some of the methods we review limit the degree of coupling, due either to a desire to limit computational cost or to limited data. Explicit and direct treatment of all many-body contributions is only practical for sufficiently small molecules, which are therefore our primary focus. This includes small molecules on surfaces. We consider direct, single NN PES fitting as well as more complex methods that impose structure (such as a multibody representation) on the PES function, either through the architecture of one NN or by using multiple NNs. We show how NNs are effective in building representations with low-dimensional functions including dimensionality reduction. We consider NN-based approaches to build PESs in the sums-of-product form important for quantum dynamics, ways to treat symmetry, and issues related to sampling data distributions and the relation between PES errors and errors in observables. We highlight combinations of NNs with other ideas such as permutationally invariant polynomials or sums of environment-dependent atomic contributions, which have recently emerged as powerful tools for building highly accurate PESs for relatively large molecular and reactive systems.

Journal ArticleDOI
07 Jan 2021-Eye
TL;DR: An updated review on infectious keratitis is provided, encompassing the epidemiology, causative microorganisms, major risk factors and the impact of antimicrobial resistance.
Abstract: Corneal opacity is the 5th leading cause of blindness and visual impairment globally, affecting ~6 million of the world population. In addition, it is responsible for 1.5–2.0 million new cases of monocular blindness per year, highlighting an ongoing uncurbed burden on human health. Among all aetiologies such as infection, trauma, inflammation, degeneration and nutritional deficiency, infectious keratitis (IK) represents the leading cause of corneal blindness in both developed and developing countries, with an estimated incidence ranging from 2.5 to 799 per 100,000 population-year. IK can be caused by a wide range of microorganisms, including bacteria, fungi, virus, parasites and polymicrobial infection. Subject to the geographical and temporal variations, bacteria and fungi have been shown to be the most common causative microorganisms for corneal infection. Although viral and Acanthamoeba keratitis are less common, they represent important causes for corneal blindness in the developed countries. Contact lens wear, trauma, ocular surface diseases, lid diseases, and post-ocular surgery have been shown to be the major risk factors for IK. Broad-spectrum topical antimicrobial treatment is the current mainstay of treatment for IK, though its effectiveness is being challenged by the emergence of antimicrobial resistance, including multidrug resistance, in some parts of the world. In this review, we aim to provide an updated review on IK, encompassing the epidemiology, causative microorganisms, major risk factors and the impact of antimicrobial resistance.

Journal ArticleDOI
TL;DR: In this article, the authors provide guidance and advice for researchers and clinicians who are preparing to undertake an evidence synthesis and are considering a scoping review methodology in the field of nursing and midwifery.
Abstract: Aim The aim of this study is to discuss the available methodological resources and best-practice guidelines for the development and completion of scoping reviews relevant to nursing and midwifery policy, practice, and research. Design Discussion Paper. Data sources Scoping reviews that exemplify best practice are explored with reference to the recently updated JBI scoping review guide (2020) and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review extension (PRISMA-ScR). Implications for nursing and midwifery Scoping reviews are an increasingly common form of evidence synthesis. They are used to address broad research questions and to map evidence from a variety of sources. Scoping reviews are a useful form of evidence synthesis for those in nursing and midwifery and present opportunities for researchers to review a broad array of evidence and resources. However, scoping reviews still need to be conducted with rigour and transparency. Conclusion This study provides guidance and advice for researchers and clinicians who are preparing to undertake an evidence synthesis and are considering a scoping review methodology in the field of nursing and midwifery. Impact With the increasing popularity of scoping reviews, criticism of the rigour, transparency, and appropriateness of the methodology have been raised across multiple academic and clinical disciplines, including nursing and midwifery. This discussion paper provides a unique contribution by discussing each component of a scoping review, including: developing research questions and objectives; protocol development; developing eligibility criteria and the planned search approach; searching and selecting the evidence; extracting and analysing evidence; presenting results; and summarizing the evidence specifically for the fields of nursing and midwifery. Considerations for when to select this methodology and how to prepare a review for publication are also discussed. This approach is applied to the disciplines of nursing and midwifery to assist nursing and/or midwifery students, clinicians, researchers, and academics.

Journal ArticleDOI
TL;DR: Combined treatment with a polypill plus aspirin led to a lower incidence of cardiovascular events than did placebo among participants without cardiovascular disease who were at intermediate cardiovascular risk.
Abstract: Background A polypill comprising statins, multiple blood-pressure–lowering drugs, and aspirin has been proposed to reduce the risk of cardiovascular disease. Methods Using a 2-by-2-by-2 fa...

Journal ArticleDOI
TL;DR: In this article, Li-ion batteries are widely employed in portable electric devices, electric vehicles, and hybrid electric vehicles (HEVs), indicating a potential increasing demand for rechargeable lithium ion batteries.
Abstract: Rechargeable lithium-ion batteries (LIBs) are widely employed in portable electric devices, electric vehicles (EVs), and hybrid electric vehicles (HEVs), indicating a potential increasing demand fo...

Journal ArticleDOI
TL;DR: In this article, a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions.


Journal ArticleDOI
Katherine S. Ruth1, Felix R. Day2, Jazib Hussain3, Ana Martínez-Marchal4  +307 moreInstitutions (91)
04 Aug 2021-Nature
TL;DR: In this paper, the authors identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry.
Abstract: Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease. Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

Journal ArticleDOI
TL;DR: In this article, the authors evaluated the effect of government-imposed stringency and timeliness of response to the COVID-19 pandemic on the prevalence of depressive symptoms across 33 countries (k=114, N=640,037).

Journal ArticleDOI
TL;DR: In this article, the authors present evidence-based guidelines from the American Society of Hematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Hemophilia Foundation (NHF), and the World Federation of Hemopathilia (WFH) intended to support patients, clinicians, and health care professionals in their decisions about management of VWD.

Journal ArticleDOI
TL;DR: In this paper, a ternary oxide (Ru-O-Ir)-based catalysts were developed to achieve high anodic oxygen evolution reaction (OER) activity and stability in acidic electrolyte.
Abstract: In hydrogen production, the anodic oxygen evolution reaction (OER) limits the energy conversion efficiency and also impacts stability in proton-exchange membrane water electrolyzers. Widely used Ir-based catalysts suffer from insufficient activity, while more active Ru-based catalysts tend to dissolve under OER conditions. This has been associated with the participation of lattice oxygen (lattice oxygen oxidation mechanism (LOM)), which may lead to the collapse of the crystal structure and accelerate the leaching of active Ru species, leading to low operating stability. Here we develop Sr-Ru-Ir ternary oxide electrocatalysts that achieve high OER activity and stability in acidic electrolyte. The catalysts achieve an overpotential of 190 mV at 10 mA cm-2 and the overpotential remains below 225 mV following 1,500 h of operation. X-ray absorption spectroscopy and 18O isotope-labeled online mass spectroscopy studies reveal that the participation of lattice oxygen during OER was suppressed by interactions in the Ru-O-Ir local structure, offering a picture of how stability was improved. The electronic structure of active Ru sites was modulated by Sr and Ir, optimizing the binding energetics of OER oxo-intermediates.

Journal ArticleDOI
13 Jan 2021-Nature
TL;DR: In this article, the authors identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders.
Abstract: Up to 20% of people worldwide develop gastrointestinal symptoms following a meal1, leading to decreased quality of life, substantial morbidity and high medical costs. Although the interest of both the scientific and lay communities in this issue has increased markedly in recent years, with the worldwide introduction of gluten-free and other diets, the underlying mechanisms of food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response that leads to the production of dietary-antigen-specific IgE antibodies in mice, which are limited to the intestine. Following subsequent oral ingestion of the respective dietary antigen, an IgE- and mast-cell-dependent mechanism induced increased visceral pain. This aberrant pain signalling resulted from histamine receptor H1-mediated sensitization of visceral afferents. Moreover, injection of food antigens (gluten, wheat, soy and milk) into the rectosigmoid mucosa of patients with irritable bowel syndrome induced local oedema and mast cell activation. Our results identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders.

Journal ArticleDOI
TL;DR: It is shown that the expression of a nuclear long non-coding RNA (lncRNA), LINC00618, is reduced in human leukemia and strongly increased by vincristine (VCR) treatment, and VCR-induced ferroptosis and apoptosis are promoted by LINC0618, and Linc00618 accelerates ferroPTosis in a manner dependent upon apoptosis.

Journal ArticleDOI
TL;DR: In this article, a self-supervised deep multi-task learning framework for electrocardiogram (ECG)-based emotion recognition is proposed, which consists of two stages of learning a) learning ECG representations and b) learning to classify emotions.
Abstract: We exploit a self-supervised deep multi-task learning framework for electrocardiogram (ECG) -based emotion recognition. The proposed solution consists of two stages of learning a) learning ECG representations and b) learning to classify emotions. ECG representations are learned by a signal transformation recognition network. The network learns high-level abstract representations from unlabeled ECG data. Six different signal transformations are applied to the ECG signals, and transformation recognition is performed as pretext tasks. Training the model on pretext tasks helps the network learn spatiotemporal representations that generalize well across different datasets and different emotion categories. We transfer the weights of the self-supervised network to an emotion recognition network, where the convolutional layers are kept frozen and the dense layers are trained with labelled ECG data. We show that the proposed solution considerably improves the performance compared to a network trained using fully-supervised learning. New state-of-the-art results are set in classification of arousal, valence, affective states, and stress for the four utilized datasets. Extensive experiments are performed, providing interesting insights into the impact of using a multi-task self-supervised structure instead of a single-task model, as well as the optimum level of difficulty required for the pretext self-supervised tasks.