Evaluation of the Effectiveness of a Whole-System Intervention to Increase the Physical Activity of Children Aged 5 to 11 Years (Join Us: Move Play, JU:MP): Protocol for a Quasiexperimental Trial.

YesDaily physical activity is vital for the health and development of children. However, many children are inactive. Previous attempts to achieve sustained increases in daily physical activity in children have been ineffective. Join Us: Move Play (JU:MP) is a whole-system, complex, community-based intervention aiming to increase the physical activity levels of children aged 7 to 11 years who live in areas of Bradford, England, which are multicultural and have high levels of deprivation. The purpose of this quasiexperimental controlled trial is to assess whether the JU:MP program increases primary school children's physical activity. The study has a 2-arm, quasiexperimental, nonblinded, nonequivalent group design and will be conducted with primary school children aged 5 to 11 years at 3 timepoints, including baseline (before intervention), 24 months (during intervention), and 36 months (after intervention). Children attending primary schools within the intervention area will be invited to participate. Children attending similar schools within similar neighborhoods based on school and community census demographics (deprivation, free school meals, and ethnicity) outside of the JU:MP geographical area will be invited to participate in the control condition. At each timepoint, consenting participants will wear an accelerometer for 7 consecutive days (24 hours a day) to measure the primary outcome (average daily moderate-to-vigorous physical activity). Multivariable mixed effects linear regression will be applied to estimate differences in the primary outcome between the 2 arms at 24 months and 36 months on an intention-to-treat basis. The secondary outcome analysis will explore changes in socioemotional well-being (teacher reported), quality of life (parental/carer reported), and other contextual factors (parents/carer reported), as well as segments of the day activity, sleep, sedentary screen time, frequency of places to be active, parent practices (nondirective support and autonomy support), social cohesion, and neighborhood walking/exercise environment. Recruitment occurred from July 2021 to March 2022, and baseline data were collected from September 2021 to March 2022. As of March 2022 (end of baseline data collection), a total of 1454 children from 37 schools (17 intervention schools and 20 control schools) have been recruited. The first follow-up data collection will occur from September 2023 to March 2024, and the second and final follow-up data collection will occur from September 2024 to March 2025. Data analysis has not begun, and the final results will be published in December 2025. This article describes the protocol for a quasiexperimental controlled trial examining a novel whole-system intervention. ISRCTN ISRCTN14332797; https://www.isrctn.com/ISRCTN14332797. DERR1-10.2196/43619

Initial insights into the impact and implementation of Creating Active Schools in Bradford, UK

YesFew whole-school physical activity programmes integrate implementation science frameworks within the design, delivery, and evaluation. As a result, knowledge of the key factors that support implementation at scale is lacking. The Creating Active Schools (CAS) programme was co-designed and is underpinned by the Capability, Opportunity, Motivation and Behaviour (COM-B) model and the Consolidated Framework for Implementation Research (CFIR). The study aims to understand the initial impact and implementation of CAS in Bradford over 9 months using McKay's et al.'s (2019) implementation evaluation roadmap. Focus groups and interviews were conducted with school staff (n = 30, schools = 25), CAS Champions (n = 9), and the CAS strategic lead (n = 1). Qualitative data were analysed both inductively and deductively. The deductive analysis involved coding data into a priori themes based on McKay et al's implementation evaluation roadmap, using a codebook approach to thematic analysis. The inductive analysis included producing initial codes and reviewing themes before finalising. Identified themes aligned into three categories: (i) key ingredients for successful adoption and implementation of CAS, (ii) CAS implementation: challenges and solutions, and (iv) the perceived effectiveness of CAS at the school level. This included the willingness of schools to adopt and implement whole-school approaches when they are perceived as high quality and aligned with current school values. The programme implementation processes were seen as supportive; schools identified and valued the step-change approach to implementing CAS long-term. Formal and informal communities of practice provided "safe spaces" for cross-school support. Conversely, challenges persisted with gaining broader reach within schools, school staff's self-competence and shifting school culture around physical activity. This resulted in varied uptake between and within schools. This study provides novel insights into the implementation of CAS, with outcomes aligning to the adoption, reach, and sustainability. Successful implementation of CAS was underpinned by determinants including acceptability, intervention complexity, school culture and school stakeholders' perceived self-efficacy. The combination of McKay's evaluation roadmap and CFIR establishes a rigorous approach for evaluating activity promotion programmes underpinned by behavioural and implementation science. Resultantly this study offers originality and progression in understanding the implementation and effectiveness of whole-school approaches to physical activity.Higher Education Innovation Fund (UKRI), Sport England’s Local Delivery Pilot in Bradford, Bradford District Metropolitan Council via the Living Well Programm

Rare high branching pattern from the first part of the right axillary artery

A 77-year-old female cadaver was observed to have a rare branching pattern of the right axillary artery (AA)  The first part of the AA typically gives off only a superior thoracic artery (STA) but was observed to give off three branches in the case: a lateral thoracic artery (LTA), a thoracoacromial trunk (TAT), and a large common trunk (CT). The LTA traveled to provide a variant STA to the 1st and 2nd intercostal spaces. The CT provided an accessory lateral thoracic artery (aLTA) and accessory thoracodorsal artery (aTDA) before bifurcating into a subscapular artery (SA) and posterior humeral circumflex artery (PHCA). As expected, the SA further divided into the circumflex scapular artery (CSA) and thoracodorsal artery (TDA). A pectoral artery and the anterior humeral circumflex artery (AHCA) originated directly from the second and third parts of the AA, respectively. Knowledge of AA branching variations is of great clinical significance to anatomists, radiologists, and surgeons due to the high rate of injury to this artery

‘You just have to work with what you’ve got’ Practitioner research with precarious migrant families

This is an accepted manuscript of an article published by Taylor and Francis in Practice on 09/10/2017, available online: https://doi.org/10.1080/09503153.2017.1385756 The accepted version of the publication may differ from the final published version.Undocumented migrant families experience high levels of food poverty, exclusion from mainstream benefits, and sometimes from social work services. This is an under-researched area for social work in the UK, and there is no statutory guidance for social workers on supporting undocumented migrants. Practitioner research is one way of ‘visibilising’ their experiences. Six migrant families accessing a voluntary sector stay and play project were interviewed using a practitioner research model of semi-structured interviews on the themes of food, access to services and children. The research found that families responded to their situation with a seemingly contradictory strategy of resignation and resilience. The implications for practitioners working with this user group are considered, and suggestions for support services for this group of families are offered

Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial

Importance: The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive. Objective: To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. Design, Setting, and Participants: The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. Interventions: The immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). Main Outcomes and Measures: The primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, -1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. Results: Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (O

The self-reported oral health status and dental attendance of smokers and non-smokers in England

Smoking has been identified as the second greatest risk factor for global death and disability and has impacts on the oral cavity from aesthetic changes to fatal diseases such as oral cancer. The paper presents a secondary analysis of the National Adult Dental Health Survey (2009). The analysis used descriptive statistics, bivariate analyses and logistic regression models to report the self-reported oral health status and dental attendance of smokers and non-smokers in England. Of the 9,657 participants, 21% reported they were currently smoking. When compared with smokers; non-smokers were more likely to report ‘good oral health’ (75% versus 57% respectively, p<0.05). Smokers were twice as likely to attend the dentist symptomatically (OR = 2.27, CI = 2.02–2.55) compared with non-smoker regardless the deprivation status. Smokers were more likely to attend symptomatically in the most deprived quintiles (OR = 1.99, CI = 1.57–2.52) and perceive they had poorer oral health (OR = 1.77, CI = 1.42–2.20). The present research is consistent with earlier sub-national research and should be considered when planning early diagnosis and management strategies for smoking-related conditions, considering the potential impact dental teams might have on smoking rates

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers

The risk of germline copy number variants (CNVs) in BRCA1 and BRCA2 pathogenic variant carriers in breast cancer is assessed, with CNVs overlapping SULT1A1 decreasing breast cancer risk in BRCA1 carriers.The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.Peer reviewe

Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

Purpose We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks forBRCA1andBRCA2pathogenic variant carriers. Methods Retrospective cohort data on 18,935BRCA1and 12,339BRCA2female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Results The ER-negative PRS showed the strongest association with BC risk forBRCA1carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33],P = 3x10(-72)). ForBRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36],P = 7x10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk forBRCA1(HR = 1.32 [95% CI 1.25-1.40],P = 3x10(-22)) andBRCA2(HR = 1.44 [95% CI 1.30-1.60],P = 4x10(-12)) carriers. The associations in the prospective cohort were similar. Conclusion Population-based PRS are strongly associated with BC and EOC risks forBRCA1/2carriers and predict substantial absolute risk differences for women at PRS distribution extremes.Peer reviewe

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10-8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care