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Showing papers by "Monash University published in 2021"


Journal ArticleDOI
29 Mar 2021-BMJ
TL;DR: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement as discussed by the authors was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found.
Abstract: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.

16,613 citations


Journal ArticleDOI
TL;DR: It is shown that neutralization level is highly predictive of immune protection, and an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic is provided.
Abstract: Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using data from seven current vaccines and from convalescent cohorts. We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4–28.4%). The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level; 95% CI = 0.7–13%, P = 0.0004). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic. Estimates of the levels of neutralizing antibodies necessary for protection against symptomatic SARS-CoV-2 or severe COVID-19 are a fraction of the mean level in convalescent serum and will be useful in guiding vaccine rollouts.

2,705 citations


Journal ArticleDOI
29 Mar 2021-BMJ
TL;DR: The preferred reporting items for systematic reviews and meta-analyses (PRISMA 2020) as mentioned in this paper was developed to facilitate transparent and complete reporting of systematic reviews, and has been updated to reflect recent advances in systematic review methodology and terminology.
Abstract: The methods and results of systematic reviews should be reported in sufficient detail to allow users to assess the trustworthiness and applicability of the review findings. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was developed to facilitate transparent and complete reporting of systematic reviews and has been updated (to PRISMA 2020) to reflect recent advances in systematic review methodology and terminology. Here, we present the explanation and elaboration paper for PRISMA 2020, where we explain why reporting of each item is recommended, present bullet points that detail the reporting recommendations, and present examples from published reviews. We hope that changes to the content and structure of PRISMA 2020 will facilitate uptake of the guideline and lead to more transparent, complete, and accurate reporting of systematic reviews.

2,217 citations


Journal ArticleDOI
TL;DR: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement as discussed by the authors was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found.
Abstract: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.

2,192 citations



Journal ArticleDOI
TL;DR: The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa guidelines summarise the most recent findings and advice for their use in clinical practice and include a strong recommendation to consider moderate hypofractionation in intermediate-risk patients.

1,369 citations


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: The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications as discussed by the authors, which are either strong or weak, or in the form of best practice statements.
Abstract: Background Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications. Methods We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements. Results The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care. Conclusion The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.

893 citations


Journal ArticleDOI
TL;DR: The PRISMA 2020, an updated reporting guideline for systematic reviews and meta-analyses, was proposed by Page and colleagues as discussed by the authors, who describe the guidelines as "an updated reporting guidelines for systematic review and meta analysis".
Abstract: Matthew Page and co-authors describe PRISMA 2020, an updated reporting guideline for systematic reviews and meta-analyses.

824 citations


Proceedings ArticleDOI
04 Feb 2021
TL;DR: MPRNet as discussed by the authors proposes a multi-stage architecture that progressively learns restoration functions for the degraded inputs, thereby breaking down the overall recovery process into more manageable steps, and introduces a novel per-pixel adaptive design that leverages in-situ supervised attention to reweight the local features.
Abstract: Image restoration tasks demand a complex balance between spatial details and high-level contextualized information while recovering images. In this paper, we propose a novel synergistic design that can optimally balance these competing goals. Our main proposal is a multi-stage architecture, that progressively learns restoration functions for the degraded inputs, thereby breaking down the overall recovery process into more manageable steps. Specifically, our model first learns the contextualized features using encoder-decoder architectures and later combines them with a high-resolution branch that retains local information. At each stage, we introduce a novel per-pixel adaptive design that leverages in-situ supervised attention to reweight the local features. A key ingredient in such a multi-stage architecture is the information exchange between different stages. To this end, we propose a two-faceted approach where the information is not only exchanged sequentially from early to late stages, but lateral connections between feature processing blocks also exist to avoid any loss of information. The resulting tightly interlinked multi-stage architecture, named as MPRNet, delivers strong performance gains on ten datasets across a range of tasks including image deraining, deblurring, and denoising. The source code and pre-trained models are available at https://github.com/swz30/MPRNet.

Journal ArticleDOI
TL;DR: The PRISMA 2020 statement consists of updated reporting guidance for systematic reviews as discussed by the authors, which includes a survey conducted to inform the update, summarise decisions made at the PRISCMA update meeting, and describe and justify changes made to the guideline.

Journal ArticleDOI
TL;DR: The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications as mentioned in this paper, which are either strong or weak, or in the form of best practice statements.
Abstract: Background Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications. Methods We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements. Results The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care. Conclusion The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.


Journal ArticleDOI
TL;DR: The PRISMA-S (Preferred Reporting Items for Systematic reviews and Meta-Analyses literature search extension) checklist as discussed by the authors was developed using a 3-stage Delphi survey process, followed by a consensus conference and public review process.
Abstract: Literature searches underlie the foundations of systematic reviews and related review types. Yet, the literature searching component of systematic reviews and related review types is often poorly reported. Guidance for literature search reporting has been diverse, and, in many cases, does not offer enough detail to authors who need more specific information about reporting search methods and information sources in a clear, reproducible way. This document presents the PRISMA-S (Preferred Reporting Items for Systematic reviews and Meta-Analyses literature search extension) checklist, and explanation and elaboration. The checklist was developed using a 3-stage Delphi survey process, followed by a consensus conference and public review process. The final checklist includes 16 reporting items, each of which is detailed with exemplar reporting and rationale. The intent of PRISMA-S is to complement the PRISMA Statement and its extensions by providing a checklist that could be used by interdisciplinary authors, editors, and peer reviewers to verify that each component of a search is completely reported and therefore reproducible.

Journal ArticleDOI
TL;DR: The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for use in clinical practice and guide the clinician in the discussion with the patient on the treatment decisions to be taken.

Journal ArticleDOI
TL;DR: It is concluded that RNNs are capable of modelling seasonality directly if the series in the dataset possess homogeneous seasonal patterns; otherwise, it is recommended to recommend a deseasonalisation step.


Journal ArticleDOI
Richard J. Abbott1, T. D. Abbott2, Sheelu Abraham3, Fausto Acernese4  +1692 moreInstitutions (195)
TL;DR: In this article, the authors reported the observation of gravitational waves from two compact binary coalescences in LIGO's and Virgo's third observing run with properties consistent with neutron star-black hole (NSBH) binaries.
Abstract: We report the observation of gravitational waves from two compact binary coalescences in LIGO’s and Virgo’s third observing run with properties consistent with neutron star–black hole (NSBH) binaries. The two events are named GW200105_162426 and GW200115_042309, abbreviated as GW200105 and GW200115; the first was observed by LIGO Livingston and Virgo and the second by all three LIGO–Virgo detectors. The source of GW200105 has component masses 8.9−1.5+1.2 and 1.9−0.2+0.3M⊙ , whereas the source of GW200115 has component masses 5.7−2.1+1.8 and 1.5−0.3+0.7M⊙ (all measurements quoted at the 90% credible level). The probability that the secondary’s mass is below the maximal mass of a neutron star is 89%–96% and 87%–98%, respectively, for GW200105 and GW200115, with the ranges arising from different astrophysical assumptions. The source luminosity distances are 280−110+110 and 300−100+150Mpc , respectively. The magnitude of the primary spin of GW200105 is less than 0.23 at the 90% credible level, and its orientation is unconstrained. For GW200115, the primary spin has a negative spin projection onto the orbital angular momentum at 88% probability. We are unable to constrain the spin or tidal deformation of the secondary component for either event. We infer an NSBH merger rate density of 45−33+75Gpc−3yr−1 when assuming that GW200105 and GW200115 are representative of the NSBH population or 130−69+112Gpc−3yr−1 under the assumption of a broader distribution of component masses.

Journal ArticleDOI
TL;DR: Age-based differences revealed that younger age-groups were more vulnerable to stress, depression and anxiety symptoms, and age-specific interventions for modifiable factors that mediate the psychological distress need to urgently deployed to address the global mental health pandemic.
Abstract: The COVID-19 pandemic has had far-ranging consequences for general physical and mental health. Country-specific research reveals a general reduction in mental and physical well-being, due to measures undertaken to stop the spread of COVID-19 disease. However, research is yet to examine the impact of the pandemic on global psychological distress and its effects upon vulnerable groups. Exploration of the factors that potentially mediate the relationship between stress and mental health during this period is needed, to assist in undertaking concrete measures to mitigate psychological distress and support vulnerable groups. Therefore, this study examined the impact of the COVID-19 pandemic on psychological distress globally, and identified factors that may exacerbate decline in mental health. N = 1653 participants (mean age 42.90 ± 13.63 years; 30.3% males) from 63 countries responded to the survey. Depression and anxiety were assessed using the Patient Health Questionnaire and State Trait Anxiety Inventory, respectively. Other measures included the Perceived Stress Scale, the Pittsburgh Sleep Quality Index, 3-item UCLA Loneliness Scale and the Brief Resilient Coping Scale. Globally, consistently high levels of stress, anxiety, depression and poor sleep were observed regardless of number of COVID-19 cases. Over 70% of the respondents had greater than moderate levels of stress, with 59% meeting the criteria for clinically significant anxiety and 39% reporting moderate depressive symptoms. People with a prior mental health diagnosis experienced greater psychological distress. Poor sleep, lower levels of resilience, younger age and loneliness significantly mediated the links between stress and depression, and stress and anxiety. Age-based differences revealed that younger age-groups were more vulnerable to stress, depression and anxiety symptoms. Results show that these vulnerable individuals need more support. Age-specific interventions for modifiable factors that mediate the psychological distress need to urgently deployed to address the global mental health pandemic.

Journal ArticleDOI
Richard J. Abbott1, T. D. Abbott2, Sheelu Abraham3, Fausto Acernese4  +1335 moreInstitutions (144)
TL;DR: The data recorded by these instruments during their first and second observing runs are described, including the gravitational-wave strain arrays, released as time series sampled at 16384 Hz.

Journal ArticleDOI
TL;DR: In this paper, the effect of COVID-19-related restrictions (i.e., stay at home orders, lockdown orders) on reported incidents of domestic violence was investigated.

Journal ArticleDOI
TL;DR: The Chicago Classification v4.4.0 as discussed by the authors is the most recent version of the Chicago Classification, which uses high-resolution manometry (HRM) for motility disorders.
Abstract: Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ.

Journal ArticleDOI
TL;DR: In this article, the authors summarize the latest insights into cellular uptake mechanisms and pathways and highlight limitations of current systems to study endocytosis, particularly problems with non-specific inhibitors.
Abstract: Endocytosis is a critical step in the process by which many therapeutic nanomedicines reach their intracellular targets. Our understanding of cellular uptake mechanisms has developed substantially in the past five years. However, these advances in cell biology have not fully translated to the nanoscience and therapeutics literature. Misconceptions surrounding the role of different endocytic pathways and how to study these pathways are hindering progress in developing improved nanoparticle therapies. Here, we summarize the latest insights into cellular uptake mechanisms and pathways. We highlight limitations of current systems to study endocytosis, particularly problems with non-specific inhibitors. We also summarize alternative genetic approaches to robustly probe these pathways and discuss the need to understand how cells endocytose particles in vivo. We hope that this critical assessment of the current methods used in studying nanoparticle uptake will guide future studies at the interface of cell biology and nanomedicine.

Journal ArticleDOI
14 Jan 2021-Nature
TL;DR: Using single-cell RNA sequencing, the transcriptomes of cells from the proximal and non-proximal tubules of healthy and fibrotic human kidneys are profiled to map the entire human kidney and identify distinct subpopulations of pericytes and fibroblasts as the main cellular sources of scar-forming myofibro Blasts during human kidney fibrosis.
Abstract: Kidney fibrosis is the hallmark of chronic kidney disease progression; however, at present no antifibrotic therapies exist1-3. The origin, functional heterogeneity and regulation of scar-forming cells that occur during human kidney fibrosis remain poorly understood1,2,4. Here, using single-cell RNA sequencing, we profiled the transcriptomes of cells from the proximal and non-proximal tubules of healthy and fibrotic human kidneys to map the entire human kidney. This analysis enabled us to map all matrix-producing cells at high resolution, and to identify distinct subpopulations of pericytes and fibroblasts as the main cellular sources of scar-forming myofibroblasts during human kidney fibrosis. We used genetic fate-tracing, time-course single-cell RNA sequencing and ATAC-seq (assay for transposase-accessible chromatin using sequencing) experiments in mice, and spatial transcriptomics in human kidney fibrosis, to shed light on the cellular origins and differentiation of human kidney myofibroblasts and their precursors at high resolution. Finally, we used this strategy to detect potential therapeutic targets, and identified NKD2 as a myofibroblast-specific target in human kidney fibrosis.

DOI
15 Nov 2021
TL;DR: In this paper, the authors explored whether in-vitro neutralization titres remain predictive of vaccine protection from infection with SARS-CoV-2 variants and used the model to predict the impact of booster vaccination on protection against SARS CoV2 variants.
Abstract: Summary Background Several SARS-CoV-2 variants of concern have been identified that partly escape serum neutralisation elicited by current vaccines. Studies have also shown that vaccines demonstrate reduced protection against symptomatic infection with SARS-CoV-2 variants. We explored whether in-vitro neutralisation titres remain predictive of vaccine protection from infection with SARS-CoV-2 variants. Methods In this meta-analysis, we analysed published data from 24 identified studies on in-vitro neutralisation and clinical protection to understand the loss of neutralisation to existing SARS-CoV-2 variants of concern. We integrated the results of this analysis into our existing statistical model relating in-vitro neutralisation to protection (parameterised on data from ancestral virus infection) to estimate vaccine efficacy against SARS-CoV-2 variants. We also analysed data on boosting of vaccine responses and use the model to predict the impact of booster vaccination on protection against SARS-CoV-2 variants. Findings The neutralising activity against the ancestral SARS-CoV-2 was highly predictive of neutralisation of variants of concern. Decreases in neutralisation titre to the alpha (1·6-fold), beta (8·8-fold), gamma (3·5-fold), and delta (3·9-fold) variants (compared to the ancestral virus) were not significantly different between different vaccines. Neutralisation remained strongly correlated with protection from symptomatic infection with SARS-CoV-2 variants of concern (rS=0·81, p=0·0005) and the existing model remained predictive of vaccine efficacy against variants of concern once decreases in neutralisation to the variants of concern were incorporated. Modelling of predicted vaccine efficacy against variants over time suggested that protection against symptomatic infection might decrease below 50% within the first year after vaccination for some vaccines. Boosting of previously infected individuals with existing vaccines (which target ancestral virus) is predicted to provide a higher degree of protection from infection with variants of concern than primary vaccination schedules alone. Interpretation In-vitro neutralisation titres remain a correlate of protection from SARS-CoV-2 variants and modelling of the effects of waning immunity predicts a loss of protection to the variants after vaccination. However, booster vaccination with current vaccines should enable higher neutralisation to SARS-CoV-2 variants than is achieved with primary vaccination, which is predicted to provide robust protection from severe infection outcomes with the current SARS-CoV-2 variants of concern, at least in the medium term. Funding The National Health and Medical Research Council (Australia), the Medical Research Future Fund (Australia), and the Victorian Government.


Journal ArticleDOI
TL;DR: The most common mechanisms of injury were traffic accidents and falls, and over time, the contribution of traffic accidents to total TBI events may be reducing.
Abstract: This systematic review provides a comprehensive, up-to-date summary of traumatic brain injury (TBI) epidemiology in Europe, describing incidence, mortality, age, and sex distribution, plus severity, mechanism of injury, and time trends. PubMed, CINAHL, EMBASE, and Web of Science were searched in January 2015 for observational, descriptive, English language studies reporting incidence, mortality, or case fatality of TBI in Europe. There were no limitations according to date, age, or TBI severity. Methodological quality was assessed using the Methodological Evaluation of Observational Research checklist. Data were presented narratively. Sixty-six studies were included in the review. Country-level data were provided in 22 studies, regional population or treatment center catchment area data were reported by 44 studies. Crude incidence rates varied widely. For all ages and TBI severities, crude incidence rates ranged from 47.3 per 100,000, to 694 per 100,000 population per year (country-level studies)...

Journal ArticleDOI
TL;DR: In this paper, the authors show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19.
Abstract: The durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.

Journal ArticleDOI
18 Nov 2021-BMJ
TL;DR: A systematic review and meta-analysis suggests that several personal protective and social measures, including handwashing, mask wearing, and physical distancing are associated with reductions in the incidence covid-19 as mentioned in this paper.
Abstract: Objective To review the evidence on the effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality. Design Systematic review and meta-analysis. Data sources Medline, Embase, CINAHL, Biosis, Joanna Briggs, Global Health, and World Health Organization COVID-19 database (preprints). Eligibility criteria for study selection Observational and interventional studies that assessed the effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality. Main outcome measures The main outcome measure was incidence of covid-19. Secondary outcomes included SARS-CoV-2 transmission and covid-19 mortality. Data synthesis DerSimonian Laird random effects meta-analysis was performed to investigate the effect of mask wearing, handwashing, and physical distancing measures on incidence of covid-19. Pooled effect estimates with corresponding 95% confidence intervals were computed, and heterogeneity among studies was assessed using Cochran’s Q test and the I2 metrics, with two tailed P values. Results 72 studies met the inclusion criteria, of which 35 evaluated individual public health measures and 37 assessed multiple public health measures as a “package of interventions.” Eight of 35 studies were included in the meta-analysis, which indicated a reduction in incidence of covid-19 associated with handwashing (relative risk 0.47, 95% confidence interval 0.19 to 1.12, I2=12%), mask wearing (0.47, 0.29 to 0.75, I2=84%), and physical distancing (0.75, 0.59 to 0.95, I2=87%). Owing to heterogeneity of the studies, meta-analysis was not possible for the outcomes of quarantine and isolation, universal lockdowns, and closures of borders, schools, and workplaces. The effects of these interventions were synthesised descriptively. Conclusions This systematic review and meta-analysis suggests that several personal protective and social measures, including handwashing, mask wearing, and physical distancing are associated with reductions in the incidence covid-19. Public health efforts to implement public health measures should consider community health and sociocultural needs, and future research is needed to better understand the effectiveness of public health measures in the context of covid-19 vaccination. Systematic review registration PROSPERO CRD42020178692.