A Microsoft-Excel-based tool for running and critically appraising network meta-analyses--an overview and application of NetMetaXL.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.BACKGROUND: The use of network meta-analysis has increased dramatically in recent years. WinBUGS, a freely available Bayesian software package, has been the most widely used software package to conduct network meta-analyses. However, the learning curve for WinBUGS can be daunting, especially for new users. Furthermore, critical appraisal of network meta-analyses conducted in WinBUGS can be challenging given its limited data manipulation capabilities and the fact that generation of graphical output from network meta-analyses often relies on different software packages than the analyses themselves. METHODS: We developed a freely available Microsoft-Excel-based tool called NetMetaXL, programmed in Visual Basic for Applications, which provides an interface for conducting a Bayesian network meta-analysis using WinBUGS from within Microsoft Excel. . This tool allows the user to easily prepare and enter data, set model assumptions, and run the network meta-analysis, with results being automatically displayed in an Excel spreadsheet. It also contains macros that use NetMetaXL's interface to generate evidence network diagrams, forest plots, league tables of pairwise comparisons, probability plots (rankograms), and inconsistency plots within Microsoft Excel. All figures generated are publication quality, thereby increasing the efficiency of knowledge transfer and manuscript preparation. RESULTS: We demonstrate the application of NetMetaXL using data from a network meta-analysis published previously which compares combined resynchronization and implantable defibrillator therapy in left ventricular dysfunction. We replicate results from the previous publication while demonstrating result summaries generated by the software. CONCLUSIONS: Use of the freely available NetMetaXL successfully demonstrated its ability to make running network meta-analyses more accessible to novice WinBUGS users by allowing analyses to be conducted entirely within Microsoft Excel. NetMetaXL also allows for more efficient and transparent critical appraisal of network meta-analyses, enhanced standardization of reporting, and integration with health economic evaluations which are frequently Excel-based.CC is a recipient of a Vanier Canada Graduate Scholarship from the Canadian Institutes of Health Research (funding reference number—CGV 121171) and is a trainee on the Canadian Institutes of Health Research Drug Safety and Effectiveness Network team grant (funding reference number—116573). BH is funded by a New Investigator award from the Canadian Institutes of Health Research and the Drug Safety and Effectiveness Network. This research was partly supported by funding from CADTH as part of a project to develop Excel-based tools to support the conduct of health technology assessments. This research was also supported by Cornerstone Research Group

Past dynamics of HIV transmission among men who have sex with men in Montréal, Canada: a mathematical modeling study

BACKGROUND: Gay, bisexual, and other men who have sex with men (gbMSM) experience disproportionate risks of HIV acquisition and transmission. In 2017, Montréal became the first Canadian Fast-Track City, setting the 2030 goal of zero new HIV infections. To inform local elimination efforts, we estimate the evolving role of prevention and sexual behaviours on HIV transmission dynamics among gbMSM in Montréal between 1975 and 2019. METHODS: Data from local bio-behavioural surveys were analyzed to develop, parameterize, and calibrate an agent-based model of sexual HIV transmission. Partnership dynamics, HIV's natural history, and treatment and prevention strategies were considered. The model simulations were analyzed to estimate the fraction of HIV acquisitions and transmissions attributable to specific groups, with a focus on age, sexual partnering level, and gaps in the HIV care-continuum. RESULTS: The model-estimated HIV incidence peaked in 1985 (2.3 per 100 person years (PY); 90% CrI: 1.4-2.9 per 100 PY) and decreased to 0.1 per 100 PY (90% CrI: 0.04-0.3 per 100 PY) in 2019. Between 2000-2017, the majority of HIV acquisitions and transmissions occurred among men aged 25-44 years, and men aged 35-44 thereafter. The unmet prevention needs of men with > 10 annual anal sex partners contributed 90-93% of transmissions and 67-73% of acquisitions annually. The primary stage of HIV played an increasing role over time, contributing to 11-22% of annual transmissions over 2000-2019. In 2019, approximately 70% of transmission events occurred from men who had discontinued, or never initiated antiretroviral therapy. CONCLUSIONS: The evolving HIV landscape has contributed to the declining HIV incidence among gbMSM in Montréal. The shifting dynamics identified in this study highlight the need for continued population-level surveillance to identify gaps in the HIV care continuum and core groups on which to prioritize elimination efforts

Effect of under-reinforcement on the flexural strength of corroded beams

Reinforced concrete beams are normally designed as under-reinforced to provide ductile behaviour i.e. the tensile moment of resistance, Mt(0) is less than the moment of resistance of the compressive zone, Mc. The degree of under-reinforcement (Mt(0)/Mc ratio) can depend upon the preferences of the designer in complying with design and construction constraints, codes and availability of steel reinforcement diameters and length. Mt(0)/Mc is further influenced during service life by corrosion which decreases Mt(0). The paper investigates the influence of Mt(0)/Mc on the residual flexural strength of corroded beams and determines detailing parameters (e.g. size and percentage of steel reinforcement, cover) on Mt(0)/Mc. Corroded reinforced concrete beams (100 mm · 150 mm deep) with varying Mt(0)/Mc ratios were tested in flexure. The results of the investigation were combined with the results of similar work by other researchers and show that beams with lower Mt(0)/Mc ratios suffer lower flexural strength loss when subjected to tensile reinforcement corrosion. Cover to the main steel does not directly influence Mt(0)/Mc and, thus, the residual flexural strength of corroded beams is not normally affected by increased cover. A simplified expression for estimating the residual strength of corroded beams is also given

Common variants in FOXP1 are associated with generalized vitiligo

In a recent genome-wide association study of generalized vitiligo, we identified ten confirmed susceptibility loci. By testing additional loci that showed suggestive association in the genome-wide study, using two replication cohorts of European descent, we observed replicated association of generalized vitiligo with variants at 3p13 encompassing FOXP1 (rs17008723, combined P = 1.04 × 10−8) and with variants at 6q27 encompassing CCR6 (rs6902119, combined P = 3.94 × 10−7)

Do self-reported intentions predict clinicians behaviour: a systematic review.

Background: Implementation research is the scientific study of methods to promote the systematic uptake of clinical research findings into routine clinical practice. Several interventions have been shown to be effective in changing health care professionals' behaviour, but heterogeneity within interventions, targeted behaviours, and study settings make generalisation difficult. Therefore, it is necessary to identify the 'active ingredients' in professional behaviour change strategies. Theories of human behaviour that feature an individual's "intention" to do something as the most immediate predictor of their behaviour have proved to be useful in non-clinical populations. As clinical practice is a form of human behaviour such theories may offer a basis for developing a scientific rationale for the choice of intervention to use in the implementation of new practice. The aim of this review was to explore the relationship between intention and behaviour in clinicians and how this compares to the intention-behaviour relationship in studies of non-clinicians. Methods: We searched: PsycINFO, MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Science/Social science citation index, Current contents (social & behavioural med/clinical med), ISI conference proceedings, and Index to Theses. The reference lists of all included papers were checked manually. Studies were eligible for inclusion if they had: examined a clinical behaviour within a clinical context, included measures of both intention and behaviour, measured behaviour after intention, and explored this relationship quantitatively. All titles and abstracts retrieved by electronic searching were screened independently by two reviewers, with disagreements resolved by discussion. Discussion: Ten studies were found that examined the relationship between intention and clinical behaviours in 1623 health professionals. The proportion of variance in behaviour explained by intention was of a similar magnitude to that found in the literature relating to non-health professionals. This was more consistently the case for studies in which intention-behaviour correspondence was good and behaviour was self-reported. Though firm conclusions are limited by a smaller literature, our findings are consistent with that of the non-health professional literature. This review, viewed in the context of the larger populations of studies, provides encouragement for the contention that there is a predictable relationship between the intentions of a health professional and their subsequent behaviour. However, there remain significant methodological challenges

Global Diversity of Ascidiacea

The class Ascidiacea presents fundamental opportunities for research in the fields of development, evolution, ecology, natural products and more. This review provides a comprehensive overview of the current knowledge regarding the global biodiversity of the class Ascidiacea, focusing in their taxonomy, main regions of biodiversity, and distribution patterns. Based on analysis of the literature and the species registered in the online World Register of Marine Species, we assembled a list of 2815 described species. The highest number of species and families is found in the order Aplousobranchia. Didemnidae and Styelidae families have the highest number of species with more than 500 within each group. Sixty percent of described species are colonial. Species richness is highest in tropical regions, where colonial species predominate. In higher latitudes solitary species gradually contribute more to the total species richness. We emphasize the strong association between species richness and sampling efforts, and discuss the risks of invasive species. Our inventory is certainly incomplete as the ascidian fauna in many areas around the world is relatively poorly known, and many new species continue to be discovered and described each year

Bayesian Hierarchical Models Combining Different Study Types and Adjusting for Covariate Imbalances: A Simulation Study to Assess Model Performance

BACKGROUND: Bayesian hierarchical models have been proposed to combine evidence from different types of study designs. However, when combining evidence from randomised and non-randomised controlled studies, imbalances in patient characteristics between study arms may bias the results. The objective of this study was to assess the performance of a proposed Bayesian approach to adjust for imbalances in patient level covariates when combining evidence from both types of study designs. METHODOLOGY/PRINCIPAL FINDINGS: Simulation techniques, in which the truth is known, were used to generate sets of data for randomised and non-randomised studies. Covariate imbalances between study arms were introduced in the non-randomised studies. The performance of the Bayesian hierarchical model adjusted for imbalances was assessed in terms of bias. The data were also modelled using three other Bayesian approaches for synthesising evidence from randomised and non-randomised studies. The simulations considered six scenarios aimed at assessing the sensitivity of the results to changes in the impact of the imbalances and the relative number and size of studies of each type. For all six scenarios considered, the Bayesian hierarchical model adjusted for differences within studies gave results that were unbiased and closest to the true value compared to the other models. CONCLUSIONS/SIGNIFICANCE: Where informed health care decision making requires the synthesis of evidence from randomised and non-randomised study designs, the proposed hierarchical Bayesian method adjusted for differences in patient characteristics between study arms may facilitate the optimal use of all available evidence leading to unbiased results compared to unadjusted analyses

Interaction and engagement with an anxiety management app: Analysis using large-Scale behavioral data

© Paul Matthews, Phil Topham, Praminda Caleb-Solly. Background: SAM (Self-help for Anxiety Management) is a mobile phone app that provides self-help for anxiety management. Launched in 2013, the app has achieved over one million downloads on the iOS and Android platform app stores. Key features of the app are anxiety monitoring, self-help techniques, and social support via a mobile forum (“the Social Cloud”). This paper presents unique insights into eMental health app usage patterns and explores user behaviors and usage of self-help techniques. Objective: The objective of our study was to investigate behavioral engagement and to establish discernible usage patterns of the app linked to the features of anxiety monitoring, ratings of self-help techniques, and social participation. Methods: We use data mining techniques on aggregate data obtained from 105,380 registered users of the app’s cloud services. Results: Engagement generally conformed to common mobile participation patterns with an inverted pyramid or “funnel” of engagement of increasing intensity. We further identified 4 distinct groups of behavioral engagement differentiated by levels of activity in anxiety monitoring and social feature usage. Anxiety levels among all monitoring users were markedly reduced in the first few days of usage with some bounce back effect thereafter. A small group of users demonstrated long-term anxiety reduction (using a robust measure), typically monitored for 12-110 days, with 10-30 discrete updates and showed low levels of social participation. Conclusions: The data supported our expectation of different usage patterns, given flexible user journeys, and varying commitment in an unstructured mobile phone usage setting. We nevertheless show an aggregate trend of reduction in self-reported anxiety across all minimally-engaged users, while noting that due to the anonymized dataset, we did not have information on users also enrolled in therapy or other intervention while using the app. We find several commonalities between these app-based behavioral patterns and traditional therapy engagement

Polymerase δ replicates both strands after homologous recombination-dependent fork restart

To maintain genetic stability DNA must be replicated only once and replication completed even when individual replication forks are inactivated. Because fork inactivation is common, the passive convergence of an adjacent fork is insufficient to rescue all inactive forks. Thus, eukaryotic cells have evolved homologous recombination-dependent mechanisms to restart persistent inactive forks. Completing DNA synthesis via Homologous Recombination Restarted Replication (HoRReR) ensures cell survival, but at a cost. One such cost is increased mutagenesis caused by HoRReR being more error prone than canonical replication. This increased error rate implies that the HoRReR mechanism is distinct from that of a canonical fork. Here we exploit the fission yeast Schizosaccharomyces pombe to demonstrate that a DNA sequence duplicated by HoRReR during S phase is replicated semi-conservatively, but that both the leading and lagging strands are synthesised by DNA polymerase delta