Objectives:To describe training loads and injury incidences, and explore their relationship in senior schoolboy rugby players in Leinster, Ireland. Methods:Prospective cohort study conducted during the 2019-2020 season. Methods aligned with consensus statements for rugby injury surveillance research. Injuries were coded using the Orchard Sports Injury Classification System (OSICS) version 10.1 and recorded using the World Rugby Injury Surveillance System. Training load measures (session type, duration and rate of perceived exertion) were recorded by the players using The Sports Office smartphone application. Results:In total, 463 participants (mean age 17, (SD=0.9 years)) in 16 schools provided data over 20 weeks. Injury incidence per 1000 player hours was 19.9 (95% CI: 15.2 to 25.6) match injuries and 0.7 (95% CI: 0.4 to 1.0) training injuries. Median injury severity was 22 days (95% CI: 17 to 28) lost for match injuries and 14 days (95% CI: 5 to 41) lost for training injuries. Frequent injury sites included shoulder (n=23, 27%), head (n=22, 26%), wrist/hand (n=9, 11%), ankle (n=8, 10%) and knee (n=5, 6%). Tackle accounted for 49% of injuries. Players' recording of individual training load showed 11.5% compliance. Exposure was calculated as 31 141 training hours and 3063 match hours. Training sessions included conditioning weights (31%), rugby skills: non-contact (28%) and semicontact (24%), with variation in proportion of sessions across schools. Conclusion:Match activity and tackle events accounted for most injuries. Training exposure and type varied widely across schools. Low compliance in recorded individual training load limited analysis of association with injury risk, highlighting the challenge in identifying injury risk factors in an adolescent cohort.

Objective: To determine the accuracy of formulas for estimation of fetal weight in twin pregnancy. Methods: Inclusion criteria from the ESPRiT twin cohort were twin pregnancies that resulted in live-born twins without congenital anomalies or twin-twin transfusion syndrome, ultrasound examination within 3 days of delivery, birth weight (BW) > 500 g and gestational age > 24 weeks. A total of 63 formulas using various combinations of abdominal circumference (AC), femur length (FL), biparietal diameter (BPD) and head circumference (HC) for the estimation of fetal weight (EFW), were compared to BW for accuracy in 226 twin pregnancies/452 fetuses. Results: Using median percentage error (MPE), the most accurate formulas were the Hadlock formulas (1984, 1985 with MPE < 1%) incorporating AC, HC, and FL. The INTERGROWTH-21st formula, which incorporates AC and HC, marginally underestimated BW (MPE -3.7%). The Hadlock formulas were more likely to overestimate BW than underestimate it. Using small-for-gestational (SGA, EFW < 5th centile), the sensitivity for detection of low BW (BW < 5th centile) was 92%, 81% and 89% for the Hadlock 1984, Hadlock 1985 and INTERGROWTH-21st formulas, respectively. SGA prevalence was noted to be higher for the INTERGROWTH-21st formula for fetal factors. Conclusion: Among 63 proposed formulas for EFW, the Hadlock formulas incorporating HC, AC and FL were the most accurate in twins. However, the INTERGROWTH-21st standard, which incorporates AC and HC, did not show lower detection rates for LBW. The frequency and intensity of twin ultrasound surveillance is such that restriction of ultrasound examination to two parameters in ultrasound could be recommended without diminution of accuracy.

BackgroundSelf-stigma among people who have tuberculosis (TB) can contribute to non-adherence to medication and disengagement from care. It can manifest in feelings of worthlessness, shame, and guilt, leading to social withdrawal and disengagement from life opportunities. Self-stigma may also affect families of those who have TB, or healthcare workers who treat them. However, few interventions addressing TB self-stigma exist to date.MethodsWe piloted the delivery of a toolkit of psychosocial interventions using a "training-of-trainers" approach with six staff members of a TB-focused NGO (Non-Governmental Organisation) and partner organisations in Jakarta, Indonesia. These trainers could then disseminate the toolkit among community partner organisations. Local staff involvement throughout the study supported translation and adaptation to enhance cultural and language appropriateness. Over a 2-day training-of-trainers workshop, the NGO staff were familiarised with the mode of delivery of the toolkit, which they then delivered via a four-day participatory workshop with 22 people who have TB/TB survivors, who were representatives of partner organisations working among communities affected by TB.ResultsThe newly-trained local facilitators delivered the toolkit to the participants, who self-reported significant increases in knowledge and efficacy around TB self-stigma post-intervention compared to baseline (Z = 1.991, p = 0.047, Wilcoxon signed-rank test). The participants' levels of self-compassion were also significantly higher post-workshop (Z = 2.096, p = 0.036, Wilcoxon signed-rank test); however, these effects were not maintained at 3-month timepoint. There was also a significant increase post-workshop in one of the participants' Ryff dimensions of psychological wellbeing, that of positive relationships with others (Z = 2.509, p = 0.012, Wilcoxon signed-rank test) but this was also not maintained at the 3-month timepoint.ConclusionsThe observed changes in recipients' self-reported levels of knowledge and efficacy, self-compassion, and psychological wellbeing may warrant further investigation into the best modalities for toolkit delivery (frequency, dose, duration) and support for individuals as they progress through the TB treatment journey.

Despite the extensive use of community-based participatory research (CBPR) in health-related projects, there is limited work on how CBPR processes result in outcomes, especially in household and ambient air pollution (HAAP) research. This study explores the reflections of key informants on factors that shape the implementation and outcomes of CBPR in HAAP projects. We conducted semi-structured interviews with 13 key stakeholders, including academic researchers, non-governmental organisation administrators, a policymaker, and community members. All interviewees have experience in CBPR projects. Interviews were analysed using framework analysis, and findings were mapped to Wallerstein et al.’s CBPR conceptual model, which consists of four constructs: context, partnership processes, intervention and research, and outcomes. The findings are described under two main categories: ‘barriers to participation’ and ‘good practices for effective CBPR design and implementation’. Relevant sub-categories were barriers at the structural, research, community, and individual levels. Suggestions for good practices included respect, cultural humility, trust, effective communication, suitable and affordable interventions such as improved cookstoves, appropriate participatory research tools, and gratuity for the community’s time. Key informants’ perspectives identified factors supported by the CBPR model to inform the design and implementation of the CBPR approach. The add-ons to some of the model’s factors, such as intra-community dynamics, give value to the informants’ knowledge to support community-research partnerships and improve outcomes in HAAP intervention projects. Addressing these factors at the design stage and reporting CBPR evaluation could deepen the understanding of community-research partnerships.

PDF file, 55KB, Supplementary table 2: Rate of incidence of disease recurrence according to AIB1, HER2, tumour grade, tumour size and nodal status in breast cancer patients treated with first-line AI.

Aim Globally, household and ambient air pollution (HAAP) accounts for almost 7 million premature deaths each year. Over half of these are from incomplete biomass fuel combustion in open fires and inefficient cookstoves. Solutions to the problem remain challenging due to cost, people’s perception of pollution and unsuitability to meet user needs. Subject and methods We used mixed methods and participatory approaches to measure and understand practices and beliefs relating to HAAP in a low-resource community in Malawi. Eighty-six households were randomly sampled for the survey, fine particulate matter (PM 2.5 ) levels were measured in 46 kitchens and four ambient locations, and 38 households were engaged during participatory transect walks. We analysed the data using descriptive and thematic analysis. Results Kitchen PM 2.5 levels far exceeded the World Health Organization’s recommended safe levels. Open-burning practices further contributed to ambient air pollution in the community. While there was high awareness of smoke in cooking areas, participants did not associate it with adverse health outcomes. Availability and affordability of cleaner alternatives influenced household energy choices. Integrating participatory methods alongside quantitative data allowed an in-depth understanding of the community’s practices and relationship with HAAP. Conclusion The findings demonstrate that energy poverty is a key factor in access to clean energy sources and highlight the importance of engaging communities to design HAAP interventions that meet their physical, socioeconomic and cultural needs.

BackgroundThe Covid-19 pandemic has resulted in many student populations learning online in lockdown. While the mental health consequences of lockdown are increasingly understood, the core features of 'cabin fever' - the experience of lockdown - are poorly described.MethodsWe conducted a questionnaire survey of 649 undergraduate medicine and health sciences students. Item content was developed based on current literature and input from student representatives.ResultsMokken scaling identified seven questions that together formed a strongly unidimensional scale which comprised two domains: social isolation/cabin fever and demotivation / demoralisation. Scale scores were significantly associated with depression, self-rated mental health, impaired study efficacy and doomscrolling.ConclusionsThe adverse effects of lockdown on student wellbeing appear to be driven to an important extent by an experience of isolation and demotivation that corresponds to narrative descriptions of cabin fever. In the foreseeable event of future pandemics, these experiences are a promising target for health promotion in students studying in lockdown.

Introduction:Self-stigma-negative self-judgements or core beliefs-can result in feelings of shame, worthlessness and self-blame, and impacts social interaction, mental health and health service utilization among people living with HIV (PLHIV). Few interventions target self-stigma among PLHIV and, to our knowledge, none until now for adolescents and young people LHIV (AYPLHIV) in sub-Saharan Africa. We present qualitative findings on the perceived impact of a self-stigma intervention (Wakakosha, "You are Worth it").Methods:The Wakakosha intervention adopted inquiry-based stress reduction (IBSR) at its core-a unique way of identifying and questioning deeply rooted self-stigma, combined with mindfulness, meditation and creativity. The intervention consisted of 16 × 3 hour group sessions. Supporting the intervention was a 156-page activity journal. We utilized a qualitative enquiry to explore the perceived impact of the intervention at various time points between November 2021 and November 2022, with 62 participants (n = 32 female). Discussions explored experiences of being involved in the intervention and any reports on changes in relation to self-stigma and shame. Additionally, we reviewed intervention documentation and creative elements. A thematic analysis guided generation of themes across all data sources.Results:Both intervention participants and coaches described the transformative effect of the intervention, detailing their experiences before and after. Main themes that emerged were positive changes around: self-confidence, self-agency, sense of purpose/meaning, body positivity, improved communication and personal/family relationships and, forgiveness. The intervention also transferred a set of practical skills on self-inquiry, mindfulness, meditation and creativity that continued to be used in participants' daily lives.Conclusion:The Wakakosha intervention, using IBSR supported by music, creativity, writing and mindfulness techniques, showed potential for reducing self-stigma and improving self-worth among AYPLHIV. It also transferred practical skills to intervention participants and peer coaches, building their capacity to support others and deal with life challenges beyond HIV. The next phase is to continue supporting the young people to ensure fidelity as the peer coaches deliver the intervention to others. Study results indicate that culturally and practically, interventions to reduce self-stigma and/or improve self-worth operate at various levels and need to be designed and assessed at each level.

PDF file, 213KB, Supplementary Table 3b ER/AIB1 overlap genelist - partial ERE.

PDF file, 320KB, Supplementary Figures 1-9 Supplementary Figure 1: Expression levels of aromatase in our cell lines and aromatase activity assay Supplementary Figure 2: Proliferation of Aro and LetR in response to treatment Supplementary Figure 3: Kaplan Meier estimates of disease free survival in the entire ER positive population Supplementary Figure 4:Interactions between ERalpha and AIB1 in letrozole sensitive Aro cells Supplementary Figure 5: Analysis of protein levels in Anastrozole resistant cell line (ANAR) Supplementary Figure 6: ChiP showing recruitment of ERalpha and AIB1 to distal region promoters Supplementary Figure 7: Basal protein levels of Myc and cyclinD1 protein and basal mRNA levels of pS2 Supplementary Figure 8:Effect of Lapatinib treatment on pS2 and Myc mRNA levels Supplementary Figure 9: Pathway analysis of ERalpha-AIB1 target genes.

Household air pollution (HAP), primarily from biomass fuels used for cooking, is associated with adverse health outcomes and premature mortality. It affects almost half of the world's population, especially in low-income and low-resourced communities. However, many of the 'improved' biomass cookstoves (ICS) aimed at reducing HAP lack empirical evidence of pollutant reduction and reliability in the field. A scoping review guided by the Joanna Briggs Institute framework was systematically conducted to explore and analyse the characteristics of cookstoves to assess the ICS available to meet the socio-economic and health needs of households in sub-Sahara Africa (sSA). The review searched Scopus, PubMed, Web of Science, EMBASE, Global Health Database on OVID, BASE, and conducted a grey literature search from 2014 to 2022 for all field-based ICS studies. In addition, user perspectives were explored for cookstoves analysed as available, affordable, and effective in reducing harmful biomass emissions. The search returned 1984 records. Thirty-three references containing 23 ICS brands were included. The cookstoves were analysed into seven categories: (1) efficiency in HAP reduction, (2) availability, (3) affordability, (4) sustainability, (5) safety, (6) health outcomes, and (7) user experience. Most (86.9%) of the improved cookstoves showed a reduction in harmful emission levels compared to the traditional three-stone fire. However, the levels were higher than the WHO-recommended safe levels. Only nine were priced below 40 USD. Users placed emphasis on cookstoves' suitability for cooking, fuel and time savings, safety, and price. Equality in cooking-related gender roles and psychosocial benefits were also reported. The review demonstrated limited field testing, a lack of evidence of ICS emissions in real-life settings in sSA, heterogeneity in emission measurements, and incomplete descriptions of ICS and kitchen features. Gender differences in exposure and psychosocial benefits were also reported. The review recommends improved cookstove promotion alongside additional measures to reduce HAP at a cost affordable to low-resource households. Future research should focus on detailed reporting of study parameters to facilitate effective comparison of ICS performance in different social settings with different local foods and fuel types. Finally, a more community-based approach is needed to assess and ensure user voices are represented in HAP intervention studies, including designing the cookstoves.

PDF file, 14KB, Supplementary Table 1: Demographics of patients according to AIB1 status.

Background Rapid access to thrombectomy for patients with large vessel occlusion (LVO) acute ischemic stroke (AIS) is critical for improving outcome. A major challenge for the ‘drip and ship’ model is reducing the door-in-door-out time (DIDO). We propose a new protocol with the aim of reducing DIDO, without adversely affecting emergency service usage time. Methods Consecutive patients with suspected LVO AIS admitted to a Primary Stroke Center (PSC) from October 2018 to January 2021 were included. On arrival, the ambulance crew remained with the patient. Following immediate clinical and radiological evaluation, patients were transferred to the Comprehensive Stroke Center (CSC) by the same waiting crew. Key time metrics were collected and compared with historical data prior to the new protocol. Results 27 patients had an LVO amenable for mechanical thrombectomy during the time period. There was a significant reduction in the DIDO times compared with the historical group (median 45 min vs 96 min; p<0.0001). There was no significant difference in ambulance usage time between the two time periods (median 53 min vs 45 min; p=0.530). There was an increase in ambulance usage time in FAST-positive patients not for transfer in the pilot group compared with FAST-positive patients not for transfer in the historical group (27 min vs 58 min; p<0.001). In addition, door-to-needle times (24 min vs 40 min; p=0.018) and door-to-CT times (11 min vs 25 min; p<0.0001) improved between the two groups. Conclusion Our data show a significant reduction in the DIDO for patients transferred for thrombectomy, with no adverse effects on ambulance usage time.

The lack of safe drinking water affects communities in low-to-medium-income countries most. This barrier can be overcome by using sustainable point-of-use water treatments. Solar energy has been used to disinfect water for decades, and several efforts have been made to optimise the standard procedure of solar water disinfection (SODIS process). However, the Health Impact Assessment of implementing advanced technologies in the field is also a critical step in evaluating the success of the optimisation. This work reports a sustainable scaling-up of SODIS from standard 2 L bottles to 25 L transparent jerrycans (TJC) and a 12-month field implementation in four sites of Tigray in Ethiopia, where 80.5% of the population lives without reliable access to safe drinking water and whose initial baseline average rate of diarrhoeal disease in children under 5 years was 13.5%. The UVA dose required for 3-log reduction of E. coli was always lower than the minimum UVA daily dose received in Tigray (9411 ± 55 Wh/m2). Results confirmed a similar decrease in cases of diarrhoea in children in the implementation (25 L PET TJC) and control (2 L PET bottles) groups, supporting the feasibility of increasing the volume of the SODIS water containers to produce safer drinking water with a sustainable and user-friendly process.

Angelman syndrome (AS) is a severe neurodevelopmental disorder featuring ataxia, cognitive impairment, and drug-resistant epilepsy. AS is caused by mutations or deletion of the maternal copy of the paternally imprinted UBE3A gene, with current precision therapy approaches focusing on re-expression of UBE3A. Certain phenotypes, however, are difficult to rescue beyond early development. Notably, a cluster of microRNA binding sites was reported in the untranslated Ube3a1 transcript, including for miR-134, suggesting that AS may be associated with microRNA dysregulation. Here, we report levels of miR-134 and key targets are normal in the hippocampus of mice carrying a maternal deletion of Ube3a (Ube3am /p+). Nevertheless, intracerebroventricular injection of an antimiR oligonucleotide inhibitor of miR-134 (Ant-134) reduced audiogenic seizure severity over multiple trials in 21- and 42-day-old AS mice. Interestingly, Ant-134 also improved distance traveled and center crossings of AS mice in the open-field test. Finally, we show that silencing miR-134 can upregulate targets of miR-134 in neurons differentiated from Angelman patient-derived induced pluripotent stem cells. These findings indicate that silencing miR-134 and possibly other microRNAs could be useful to treat clinically relevant phenotypes with a later developmental window in AS.

Abstract Introduction. Vaccination against SARS-CoV-2 infection has been shown to reduce the severity of infection; however, the overall reinfection rate in those unvaccinated, partially vaccinated and fully vaccinated remains unclear. Therefore, this study was undertaken to elucidate the rates and associated factors for such occurrences.Methods. This was a retrospective epidemiological report analysing 1362 COVID-19 reinfection cases in the Kingdom of Bahrain between April 2020 and July 2021. The differences in disease severity and characteristics of reinfection between various levels of vaccination statuses were determined among fully vaccinated, interrupted vaccination (positive test less than 14 days after receiving the second dose of vaccine), one dose of vaccination, post-reinfection vaccination and unvaccinated. Data were collected from the National COVID-19 Contact Tracing Team Database of individuals who tested positive for SARS-CoV-2.Results. During the study, reinfection cases increased from zero cases per month in April – June 2020 to a sharp peak of 579 reinfection cases in May 2021 followed by a rapid decline. Males constituted a significantly larger proportion of reinfections (n=821, 60.3%) than females (39.7%) (p<0.0001). Reinfection episodes were highest amongst the 30-39 years of age (n=405, 29.7%). The rate of reinfection increased with time from the initial infection with the lowest reinfection rate occurring at 3-6 months after the first infection (n=281, 20.6%) and the highest episodes occurring ≥9 months after initial infection (n=632, 46.4%). Comparison of the symptomatology between initial infection and reinfection episode for each individual showed that most individuals were asymptomatic during both episodes (n=486, 35.7%), while 265 (19.5%) individuals were symptomatic during both episodes. Reinfection disease severity was mild and differed across the cohort (X2 test p=0.003) with vaccinated patients less likely to have symptomatic reinfection (OR 0·71, p=0·004). Only 89 (6.6%) reinfection cases required hospitalization and there were no deaths (Poisson exact, 97.5% Cl 2.7 per 1000).Conclusion. Vaccine induced immunity and prior infection with or without vaccination were effective in reducing disease severity of reinfection episodes.

Objectives: SARS-CoV-2 vaccination has been shown to reduce infection severity; however, the reinfection frequency among unvaccinated, partially vaccinated, and fully vaccinated individuals remains unclear. This study aims to elucidate the rates of and factors associated with such occurrences. Methods: This retrospective epidemiological report included 1362 COVID-19 reinfection cases in Bahrain between April 2020 and July 2021. We analyzed differences in disease severity and reinfection characteristics among various vaccination statuses: fully vaccinated, interrupted vaccination, one-dose vaccination, postreinfection vaccination, and unvaccinated. Results: Reinfection cases increased from zero per month in April-June 2020 to a sharp peak of 579 in May 2021. A significantly larger proportion of reinfected individuals were male (60.3%, P <0.0001). Reinfection episodes were highest among those 30-39 years of age (29.7%). The fewest reinfection episodes occurred at 3-6 months after the first infection (20.6%) and most occurred ≥9 months after the initial infection (46.4%). Most individuals were asymptomatic during both episodes (35.7%). Reinfection disease severity was mild, with vaccinated patients less likely to have symptomatic reinfection (odds ratio 0.71, P = 0.004). Only 6.6% of reinfected patients required hospitalization. One death was recorded; the patient belonged to the unvaccinated group. Conclusion: Vaccine-induced immunity and previous infection with or without vaccination were effective in reducing reinfection disease severity.

Objective This study aimed to determine if the implementation of large-scale patient safety initiatives have been successful in reducing overall and preventable adverse event rates in hospital inpatients. Design The design used in this study was systematic review and meta-analysis. Data Resources We followed our published protocol (PROSPERO [CRD42019140058]) and searched the following databases: PubMed, CINAHL, PsycINFO, Cochrane Library, and Embase from inception to February 2020. The reference lists of eligible studies were also searched. Eligibility All longitudinal retrospective record review studies that examined adverse event rates before and after the introduction of patient safety initiatives in hospital inpatients were included. Data Extraction Data extraction, quality, and risk of bias assessment were carried out by 2 independent reviewers. Information on study design, setting, demographics, interventions, and safety outcome measures was extracted. Results A total of 3894 articles were screened, and 7 articles met the eligibility criteria for our systematic review with 5 of these providing sufficient information for inclusion in the meta-analysis. The degree of heterogeneity was high among studies. The meta-analysis demonstrated a minimal risk reduction in overall adverse event rates of 0.017 (95% confidence interval, 0.002-0.032) when the lower-quality studies were excluded, with one adverse event being prevented for every 59 hospital admissions. Conclusions These findings are significant when the large numbers of admissions to a hospital every year are considered. Given the low numbers of large-scale implementation studies, there is a need for more research on the effectiveness of patient safety initiatives to further assess the impact of such initiatives on adverse events.

Background: The Covid-19 pandemic has resulted in many student populations learning online in lockdown. While the mental health consequences of lockdown are increasingly understood, the core features of ‘cabin fever’ are poorly described. Methods: We conducted a questionnaire survey of 649 undergraduate medicine and health sciences students. Item content was developed based on current literature and input from student representatives. Results: Mokken scaling identified seven questions that together formed a strongly unidimensional scale which comprised two domains : social isolation/cabin fever and demotivation / demoralisation. Scale scores were significantly associated with depression, self-rated mental health, impaired study efficacy and doomscrolling. Conclusions: The adverse effects of lockdown on student wellbeing appear to be driven to an important extent by an experience of isolation and demotivation that correspond to narrative descriptions of cabin fever. In the foreseeable event of future pandemics, these experiences are a promising target for health promotion in students studying in lockdown.