31 research outputs found

    The CD4+ T cell methylome contributes to a distinct CD4+ T cell transcriptional signature in Mycobacterium bovis-infected cattle

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    peer-reviewedWe hypothesised that epigenetic regulation of CD4+ T lymphocytes contributes to a shift toward a dysfunctional T cell phenotype which may impact on their ability to clear mycobacterial infection. Combined RNA-seq transcriptomic profiling and Reduced Representation Bisulfite Sequencing identified 193 significantly differentially expressed genes and 760 differentially methylated regions (DMRs), between CD4+ T cells from M. bovis infected and healthy cattle. 196 DMRs were located within 10 kb of annotated genes, including GATA3 and RORC, both of which encode transcription factors that promote TH2 and TH17 T helper cell subsets respectively. Gene-specific DNA methylation and gene expression levels for the TNFRSF4 and Interferon-γ genes were significantly negatively correlated suggesting a regulatory relationship. Pathway analysis of DMRs identified enrichment of genes involved in the anti-proliferative TGF-β signaling pathway and TGFB1 expression was significantly increased in peripheral blood leukocytes from TB-infected cattle. This first analysis of the bovine CD4+ T cell methylome suggests that DNA methylation directly contributes to a distinct gene expression signature in CD4+ T cells from cattle infected with M. bovis. Specific methylation changes proximal to key inflammatory gene loci may be critical to the emergence of a non-protective CD4+ T cell response during mycobacterial infection in cattle

    Does a video clip enhance recruitment into a parenting trial? Learnings from a study within a trial

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    Funder: NIHR Imperial Biomedical Research Centre; doi: http://dx.doi.org/10.13039/501100013342Abstract: Background: Reaching recruitment targets in randomised controlled trials is a challenge. Media tools are increasingly used to engage participants, yet there is a paucity of research into the use of video to optimise recruitment. We therefore tested whether adding a participant information video clip to a standard participant information sheet improved recruitment into a parenting trial. Methods: One hundred seven participants were randomised to receive either a participant information sheet (n = 51) or an informational video clip (n = 56) as part of an email contact following a screening phase. All participants went on to receive the information sheet as part of the existing consent procedure. Results: The video condition did not increase the odds of recruitment into the trial, such that those in the video condition were significantly less likely to participate in the main trial (OR = 0.253, CI = 0.104–0.618, p = 0.003). Conclusion: The introduction of a video clip into the recruitment stages of a parenting trial did not lead to an improvement in recruitment; however, the small sample size precludes definitive inferences. We offer reflections on challenges encountered in implementing the SWAT and suggestions for other researchers seeking to embed recruitment SWATs into similar trials. Trial registration: Current controlled trials ISRCTN 58327365. Registered on 19 March 2015. SWAT registration: SWAT 106; Effects of a video clip on recruitment into a randomised trial. Registered on 20 December 2016

    Can guidance during play enhance children’s learning and development in educational contexts? A systematic review and meta-analysis

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    This systematic review and meta-analysis considered evidence of guided play compared to direct instruction or free play to support children's learning and development. Interventions from 39 studies were reviewed (published 1977–2020); 17 were included in meta-analysis (Ntotal = 3893; Mchildage = 1–8 years; Mgirls 49.8%; Methnicity White 41%, African American/Black 28%, Hispanic 19%). Guided play had a greater positive effect than direct instruction on early maths skills (g = 0.24), shape knowledge (g = 0.63), and task switching (g = 0.40); and than free play on spatial vocabulary (g = 0.93). Differences were not identified for other key outcomes. Narrative synthesis highlighted heterogeneity in the conceptualization and implementation of guided play across studies

    Reconstructing readiness: Young children’s priorities for their early school adjustment

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    Young children in communities facing socioeconomic disadvantage are increasingly targeted by school readiness interventions. Interventions are stronger if they address stakeholders’ priorities, yet children’s priorities for early school adjustment are rarely accounted for in intervention design including selection of outcome measures. The Children’s Thoughts about School Study (CTSS) examined young children’s accounts of their early school experiences, and their descriptions of what a new school starter would need to know. Mixed-method interviews were conducted with 42 kindergarten children in a socioeconomically deprived suburb of Dublin, Ireland. First, inductive thematic analysis identified 25 priorities across four domains: feeling able and enthusiastic for school; navigating friendships and victimisation; supportive environments with opportunities to play; bridging school and family life. Second, deductive analysis compared children’s priorities at item level against a school readiness outcome battery. Children’s priorities were assigned to three groups: (1) assessed by outcome measures (core academic competencies, aspects of self regulation); (2) partially assessed (self-efficacy, social skills for friendship formation and avoiding victimisation, creative thinking, play); and (3) not assessed by outcome measures (school liking, school environment, family school involvement). This analysis derived from children’s own perspectives suggests that readiness interventions aiming to support early school adjustment would benefit from considering factors children consider salient. It offers recommendations for advancing conceptual frameworks, improving assessment, and identifying new targets for supporting children and schools. In doing so we provide a platform for children’s priorities to be integrated into the policies and practices that shape their early lives
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