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Abstract Background Research consistently finds poorer health and educational outcomes for children who have experienced out-of-home care relative to the general population. Few studies have explored differences between those in care and those in receipt of intervention from social services but not in care. Children receiving social services interventions often experience Adverse Childhood Experiences (ACEs), and deprivation, which are known to negatively impact outcomes. We aimed to estimate the association of different social services interventions with educational outcomes and hospital admissions, while adjusting for ACEs and deprivation. Methods We linked retrospective, routinely collected administrative records from health, education, and social care to create a cohort via the Secure Anonymised Information Linkage (SAIL) databank in Wales, UK. We analysed data for children and household members (N = 30,439) across four different groups: (1) no social care intervention; (2) children in need but not in care (CIN); (3) children on the Child Protection Register but not in care (CPR); (4) children in care - i.e. removed from the family home and looked after by the local authority (CLA). Our primary outcome was education outcomes at age 16 years. Secondary outcomes were all cause emergency hospital admissions, and emergency admissions for external causes/injuries. Results Children in receipt of social services intervention were more likely to not attain the expected level upon leaving statutory education at age 16 after adjusting for ACEs and other characteristics (for children who had been in out-of-home care (conditional OR: 1·76, (95%CI) 1·25 − 2·48), in need (2·51, 2·00–3·15) and those at risk (i.e., on the child protection register) (4·04, 2·44 − 6·68). For all-cause emergency admissions, all social care groups were at greater risk compared to children in the general population (children in care (conditional HR: 1·31, 1·01–1·68), children in need (1·62, 1·38 − 1·90), and children at risk (1·51, 1·11 − 2·04). Conclusions All groups receiving social service intervention experience poorer educational and health outcomes than peers in the general population. Children who remain with their home parents or caregivers but are identified as ‘in need’ or ‘at risk’ by social care practitioners require further research. Integrated support is needed from multiple sectors, including health, educational and social care.

Abstract Background Reducing health inequities for children from a disadvantaged background is an important task in public health. While intersectoral partnerships are a promising way to achieve this, few studies have examined the factors influencing the success of these interventions. In this study, we conducted a process evaluation of the integrated community-based intervention Präventionskette Freiham that the city of Munich, Germany, has implemented in a new residential development area. The aim was to investigate the implementation process as well as barriers and facilitators. Methods Following a mixed methods approach, we collected data from different core groups making up Präventionskette Freiham from April 2020 to August 2022, exploring their perspective on the implementation process. We conducted repeated qualitative interviews with the network coordinators and eleven local professionals from institutions engaged with or relevant for the intervention. We also undertook a focus group with four members of the advisory group representing the three municipal departments guiding the intervention. Ego-centered network maps were drawn by the network coordinators to chart the development of the network. Subsequently, we also conducted an online survey with local network members. Results At the early stage of the implementation process, the intervention was able to integrate actors from different sectors, serving as a platform for mutual exchange. However, the network produced limited output. According to the interviews, this may be mainly attributable to the early development status of the area. We identified seven topics that may act as facilitators or barriers to implementation of Präventionskette Freiham: (1) availability of resources, (2) political and administrative support, (3) the network coordinators, (4) network-internal processes, (5) trans-institutional cooperation, (6) perceived benefits of engagement, and (7) the output of the network. Conclusions The early development status of the area was a challenge for the intervention. This emphasizes the need to carefully consider context when planning and implementing integrated community-based public health interventions in new residential development areas.

Introduction: Adolescence is a critical time for mental health promotion and prevention and establishing healthy behaviours. Implementing universal, school-based psychosocial interventions can improve short- and long-term health trajectories for adolescents. While these interventions may offer important opportunities for fostering skills and relationships, few school-based interventions have been developed for and tested in low- and middle-income countries (LMICs) where adolescent mental health needs may be significant and under-served. This manuscript details the development of a multi-component, universal school-based intervention, Health Action in ScHools for a Thriving Adolescent Generation (HASHTAG), for adolescents aged 12–15 years in Nepal and South Africa. Methods and results: We describe HASHTAG's development over four phases, combining methods and results as each phase was iteratively conducted between 2018 and 2021. Phase 1 included a systematic review and components analysis, building from WHO guidelines for adolescent mental health. Seven components were strongly supported by the evidence: emotional regulation, stress management, mindfulness, problem-solving, interpersonal skills, assertiveness training, and alcohol and drug education. Phase 2 encompassed site selection, theory of change development, and formative research engagements; research teams in each site engaged adolescents and key adult stakeholders to identify priorities for intervention. Stakeholders voiced preferences for external facilitators and key content and delivery for intervention sessions. These findings informed Phase 3, a draft manual of HASHTAG, including a whole-school component, called Thriving Environment in Schools, and a classroom-based, six-session component, Thrive Together. In Phase 4, participants engaged in consultative workshops to review and contextualise content by country, preparing HASHTAG for implementation in a feasibility trial. Minor adaptations were made in Nepal, including using school nurses and adjusting take-home materials; both country's workshops identified practical considerations for implementing activities. Conclusions: HASHTAG was designed around core evidence-based components to increase translatability across LMICs, while enabling country-specific tailoring to enhance feasibility. Future research will test whether this multi-component, whole-school approach can improve adolescent mental health.

Abstract Background Role models have been identified as a potential means to tackle the persisting low levels of physical activity among young girls. The aim of this research was to explore the involvement of community- and peer role models within the CHARMING (CHoosing Active Role Models to INspire Girls) intervention, an intervention which aims to increase and sustain physical activity among 9–10-year-old girls. The research questions were, is it feasible and acceptable to recruit role models? and what are the perceived barriers and facilitators to the inclusion of peer role models within the intervention? Methods A mixed methods process evaluation was embedded within a larger feasibility study, involving three secondary schools and four adjoining primary schools in South Wales, United Kingdom. One-to-one interviews were conducted with teachers (N = 10) across the seven schools and community role models (N = 10). Focus groups were conducted with 18 peer role models (older girls from adjoining secondary schools) and 18 girls aged 9–10-years who had participated in the intervention. Primary school teachers kept observation logs of each intervention session. A researcher completed observation logs of two random sessions per school. Qualitative data were analysed using thematic analysis with a combined deductive and inductive coding approach. Observation data were analysed using descriptive statistics. Data were triangulated and comparative analyses conducted across schools. Results Twenty-three peer role models (aged 12–16-years) and 16 community role models participated in intervention delivery. Overall, the inclusion of both types of role models was shown as acceptable and feasible within the CHARMING intervention. Observation data highlighted key areas (i.e., intervention components delivered inconsistently) for further qualitative exploration. Six themes were identified during analyses; reach and access, communication, logistics, existing systems, interpersonal relationships, and perceived impacts. Themes were intertwined across the barriers and facilitators of recruitment and implementation. Areas for future improvement were highlighted. Conclusions Findings can be used to optimise the CHARMING intervention and inform wider interventions or policies employing several role models across settings to promote physical activity among children.

Background: Alcohol and smoking brief interventions (BIs) in general practice have been shown to be effective in lowering alcohol and smoking-related harm. Aim: To assess prevalence of self-reported BI receipt among increasing or higher-risk drinkers and past-year smokers in England, Scotland, and Wales, and associations between intervention receipt and socioeconomic position. Design & setting: Cross-sectional study using data from a monthly population-based survey in England, Scotland, and Wales. Method: The study comprised 47 799 participants (15 573 increasing or higher-risk drinkers [alcohol use disorders identification test consumption score ≥5] and 7791 past-year smokers) surveyed via telephone in 2020–2022 (during the COVID-19 pandemic). All data were self-reported. Prevalence of self-reported BI receipt was assessed descriptively; associations between receipt and socioeconomic position were analysed using logistic regression. Results: Among adults in England, Scotland, and Wales, 32.2% (95% confidence interval [CI] = 31.8 to 32.7) reported increasing or higher-risk drinking and 17.7% (95% CI = 17.3 to 18.1) past-year smoking. Among increasing or higher-risk drinkers, 58.0% (95% CI = 57.1 to 58.9) consulted with a GP in the past year, and of these, 4.1% (95% CI = 3.6 to 4.6) reported receiving BIs. Among past-year smokers, 55.8% (95% CI = 54.5 to 57.1) attended general practice in the past year; of these, 41.0% (95% CI = 39.4 to 42.7) stated receiving BIs. There was a tendency for patients from socioeconomically disadvantaged backgrounds to receive more alcohol (adjusted odds ratio [aOR] 1.38, 95% CI = 1.10 to 1.73) or smoking BIs (aOR 1.11, 95% CI = 0.98 to 1.26), but for the latter the results were statistically non-significant. Results did not differ notably by nation within Great Britain. Conclusion: BIs in general practice are more common for smoking than for alcohol. A greater proportion of BIs for alcohol were found to be delivered to people who were from socioeconomically disadvantaged backgrounds and who were increasing or higher-risk drinkers.

Introduction Family-Focused Adolescent & Lifelong Health Promotion (FLOURISH) project will adapt, implement and evaluate a programme to support adolescent mental health and well-being through strategies, such as strengthening parenting practices, adolescent-caregiver relationships, adolescent and parent socioemotional skills, and social support.Methods and analysis The project will focus on adolescents aged 10–14 years and their caregivers in North Macedonia and Moldova. The countries were selected based on implementation readiness of two organisations and a need for accessible evidence-informed services to help mitigate health risks due to economic, social and political challenges. Parenting for Lifelong Health (PLH) for Parents and Teens is a family-based programme developed for low-resource settings. PLH has been adapted with input from advisory groups. The programme includes additional components to strengthen impacts on adolescents: adolescent mental health tools, based on UNICEF’s Helping Adolescents Thrive, adolescent peer support and participation booster. This pilot is first of three study phases. The pilot will be a feasibility testing of the adapted intervention and the assessment and implementation procedures to determine further refinements. The pilot will examine if the adapted programme is acceptable for adolescents, their families and providers, explore contextual factors relevant to embedding this programme into longer-term scale-up and investigate whether the programme can be delivered with fidelity and participation; whether the participants report changes in adolescent emotional and behavioural problems, well-being and other outcomes; and whether the study tools are feasible and appropriate. Pre-post adolescent and caregiver questionnaires will provide outcome data. Process evaluation will include attendance and fidelity data, and focus groups. We will examine delivery cost and resource requirements.Ethics and dissemination The study was approved at the University of Klagenfurt (Austria), Medical Faculty at St. Cyril and Methodius University (North Macedonia) and National Committee of Ethical Expertise for Clinical Trials (Moldova). Through stakeholder engagement and dissemination, FLOURISH will advance scale-up of open-source family interventions.Trial registration number Trial registration: ID101095528; project page: https://www.flourish-study.org/about.html; https://www.linkedin.com/company/flourish-study/

Effective chromosome synapsis and crossover formation during meiosis are essential for fertility, especially in grain crops such as wheat. These processes function most efficiently in wheat at temperatures between 17-23 °C, although the genetic mechanisms for such temperature dependence are unknown. In a previously identified mutant of the hexaploid wheat reference variety ‘Chinese Spring’ lacking the long arm of chromosome 5D, exposure to low temperatures during meiosis resulted in asynapsis and crossover failure. In a second mutant (ttmei1), containing a 4 Mb deletion in chromosome 5DL, exposure to 13 °C led to similarly high levels of asynapsis and univalence. Moreover, exposure to 30 °C led to a significant, but less extreme effect on crossovers. Previously, we proposed that, of 41 genes deleted in this 4 Mb region, the major meiotic gene TaDMC1-D1 was the most likely candidate for preservation of synapsis and crossovers at low (and possibly high) temperatures. In the current study, using RNA-guided Cas9, we developed a new Chinese Spring CRISPR mutant, containing a 39 bp deletion in the 5D copy of DMC1, representing the first reported CRISPR-Cas9 targeted mutagenesis in Chinese Spring, and the first CRISPR mutant for DMC1 in wheat. In controlled environment experiments, wild-type Chinese Spring, CRISPR dmc1-D1 and backcrossed ttmei1 mutants were exposed to either high or low temperatures during the temperature-sensitive period from premeiotic interphase to early meiosis I. After 6-7 days at 13 °C, crossovers decreased by over 95% in the dmc1-D1 mutants, when compared with wild-type plants grown under the same conditions. After 24 hours at 30 °C, dmc1-D1 mutants exhibited a reduced number of crossovers and increased univalence, although these differences were less marked than at 13 °C. Similar results were obtained for ttmei1 mutants, although their scores were more variable, possibly reflecting higher levels of background mutation. These experiments confirm our previous hypothesis that DMC1-D1 is responsible for preservation of normal crossover formation at low and, to a certain extent, high temperatures. Given that reductions in crossovers have significant effects on grain yield, these results have important implications for wheat breeding, particularly in the face of climate change.

Abstract Background COVID-19 related lockdowns may have affected engagement in health behaviours among the UK adult population. This prospective observational study assessed socio-demographic patterning in attempts to change and maintain a range of health behaviours and changes between two time points during the pandemic. Methods Adults aged 18 years and over (n = 4,978) were recruited using Dynata (an online market research platform) and the HealthWise Wales platform, supplemented through social media advertising. Online surveys were conducted in August/September 2020 when lockdown restrictions eased in the UK following the first major UK lockdown (survey phase 1) and in February/March 2021 during a further national lockdown (survey phase 2). Measures derived from the Cancer Awareness Measure included self-reported attempts to reduce alcohol consumption, increase fruit/vegetable consumption, increase physical activity, lose weight and reduce/stop smoking. Multivariable logistic regressions were used to assess individual health behaviour change attempts over time, adjusted for age, sex, ethnicity, employment and education. Results Around half of participants in survey phase 1 reported trying to increase physical activity (n = 2607, 52.4%), increase fruit/vegetables (n = 2445, 49.1%) and lose weight (n = 2413, 48.5%), with 19.0% (n = 948) trying to reduce alcohol consumption among people who drink. Among the 738 participants who smoked, 51.5% (n = 380) were trying to reduce and 27.4% (n = 202) to stop smoking completely. Most behaviour change attempts were more common among women, younger adults and minority ethnic group participants. Efforts to reduce smoking (aOR: 0.98, 95% CI: 0.82–1.17) and stop smoking (aOR: 0.98, 95% CI: 0.80–1.20) did not differ significantly in phase 2 compared to phase 1. Similarly, changes over time in attempts to improve other health behaviours were not statistically significant: physical activity (aOR: 1.07; 95% CI: 0.99–1.16); weight loss (aOR: 0.95; 95% CI: 0.90–1.00); fruit/vegetable intake (aOR: 0.98, 95% CI: 0.91–1.06) and alcohol use (aOR: 1.32, 95% CI: 0.92–1.91). Conclusion A substantial proportion of participants reported attempts to change health behaviours in the initial survey phase. However, the lack of change observed over time indicated that overall motivation to engage in healthy behaviours was sustained among the UK adult population, from a period shortly after the first lockdown toward the end of the second prolonged lockdown.

Tetraploid (AABB) and hexaploid (AABBDD) wheat have multiple sets of similar chromosomes, with successful meiosis and preservation of fertility relying on synapsis and crossover (CO) formation only taking place between homologous chromosomes. In hexaploid wheat, the major meiotic gene TaZIP4-B2 (Ph1) on chromosome 5B, promotes CO formation between homologous chromosomes, whilst suppressing COs between homeologous (related) chromosomes. In other species, ZIP4 mutations eliminate approximately 85% of COs, consistent with loss of the class I CO pathway. Tetraploid wheat has three ZIP4 copies: TtZIP4-A1 on chromosome 3A, TtZIP4-B1 on 3B and TtZIP4-B2 on 5B. Here, we have developed single, double and triple zip4 TILLING mutants and a CRISPR Ttzip4-B2 mutant, to determine the effect of ZIP4 genes on synapsis and CO formation in the tetraploid wheat cultivar ‘Kronos’. We show that disruption of two ZIP4 gene copies in Ttzip4-A1B1 double mutants, results in a 76-78% reduction in COs when compared to wild-type plants. Moreover, when all three copies are disrupted in Ttzip4-A1B1B2 triple mutants, COs are reduced by over 95%, suggesting that the TtZIP4-B2 copy may also affect class II COs. If this is the case, the class I and class II CO pathways may be interlinked in wheat. When ZIP4 duplicated and diverged from chromosome 3B on wheat polyploidization, the new 5B copy, TaZIP4-B2, could have acquired an additional function to stabilize both CO pathways. In tetraploid plants deficient in all three ZIP4 copies, synapsis is delayed and does not complete, consistent with our previous studies in hexaploid wheat, when a similar delay in synapsis was observed in a 59.3 Mb deletion mutant, ph1b, encompassing the TaZIP4-B2 gene on chromosome 5B. These findings confirm the requirement of ZIP4-B2 for efficient synapsis, and suggest that TtZIP4 genes have a stronger effect on synapsis than previously described in Arabidopsis and rice. Thus, ZIP4-B2 in wheat accounts for the two major phenotypes reported for Ph1, promotion of homologous synapsis and suppression of homeologous COs.

Abstract Background This meta-ethnography investigates how young adults describe their tobacco use, smoking identities and pathways into and out of regular smoking, to inform future smoking prevention and harm reduction interventions. Methods Eight databases were systematically searched using keywords and indexed terms. Studies were included if they presented qualitative data from young adults aged 16–25 reporting smoking histories and/or smoking identities from countries culturally similar to the UK. A systematic and rigorous meta-ethnographic approach was employed, consistent with Noblit and Hare’s methodology. Results Thirty papers were included. Reasons stated for taking up smoking and becoming a smoker included alleviating stress, transforming one’s identity, and coping with the transition to further education, employment or leaving home. Many used smoking to aid acceptance within new peer groups, particularly when alcohol was present. Smoking was also perceived as an act of resistance and a coping mechanism for those with marginalised identities. Barriers to quitting smoking included young adults’ minimisation or denial of the health risks of smoking and not identifying with “being a smoker”. Conclusions This meta-ethnography may provide a blueprint to inform the development of health and wellbeing interventions designed specifically for young adults. Smoking cessation interventions should be co-designed with young adults based on their perceived needs, resonant with their desire to quit in the future at key milestones. Harm reduction interventions should address the social aspect of addiction, without reinforcing stigma, particularly for those with marginalised identities.

Abstract Background In many countries, including in the United Kingdom (UK), COVID-19 social distancing measures placed substantial restrictions on children’s lives in 2020 and 2021, including closure of schools and limitations on play. Many children faced milestones such as transition to secondary school having missed several months of face-to-face schooling in the previous academic years. Methods This paper examines change in mental health difficulties, life satisfaction, school connectedness, and feelings about transition to secondary school among 10–11-year-olds in Wales, UK, using data from repeat cross-sectional surveys before and after the onset of the COVID-19 pandemic. Participants were 4032 10–11-year-old schoolchildren. The first cohort completed a school-based survey in 2019 (prior to introduction of social distancing measures), and the second in 2021 (following full return to school after two rounds of school closure). Results The percentage of children reporting elevated emotional difficulties rose from 17% in 2019 to 27% in 2021 (Odds Ratio = 1.65; 95%CI = 1.23 to 2.20). There was no evidence of increased behavioural difficulties (OR = 1.04; 95%CI = 0.73 to 1.46). There was a tendency toward declines in life satisfaction in all analyses, but this intersected the null (OR = 0.86; 95%CI = 0.70 to 1.07). Children reported a high degree of school connectedness before and after the pandemic, with no evidence of change in ratings of teacher relationships, pupil relationships or pupil involvement in school life. There was no evidence of impacts of the pandemic on children’s feelings about the transition to secondary school, with feelings becoming more positive as transition neared. Most findings were robust to a range of sensitivity analyses. Conclusions Supporting children’s emotional recovery from the COVID-19 pandemic is a public health priority requiring urgent and effective action at multiple levels of society. Maintaining connectedness to school through the pandemic may have played a role in preventing a steeper increase in child mental health difficulties.

Abstract Background In the UK, there is evidence that girls’ physical activity tends to decline to a greater extent than boys as they enter adolescence. ‘Role models’ could play a vital role in inspiring girls to become or remain physically active. The CHARMING Programme is a primary school-based community linked role-model programme, co-developed in 2016, with children, parents, schools and wider stakeholders. It involves different types of physical activity delivered for 1-h each week by a community provider and peer role models (e.g. older girls from secondary schools) joining in with the sessions. The programme ultimately aims to increase and sustain physical activity levels among 9–10-year-old girls. This study aims to assess the feasibility and acceptability of the CHARMING Programme and of evaluating it using a randomised trial. Methods This study is a feasibility cluster randomised controlled trial, with embedded process evaluation and health economic evaluation. Approximately 90 Year 5 (i.e. 9–10-year-old) girls will be recruited across six primary schools in Mid-South Wales. Participating schools will be allocated to the programme: control on a 2:1 basis; four intervention schools will run the CHARMING Programme and two will continue with usual practice. A survey and accelerometer will be administered at baseline and repeated at 12 months. Interviews and focus groups will be conducted post-intervention delivery. The primary aim is to assess feasibility of a future randomised trial via the recruitment of schools, participants and role models; randomisation; retention; reach; data collection completion rates; programme adherence; and programme fidelity, views on intervention acceptability and programme barriers and facilitators. Secondary aims are to evaluate established physical activity outcome measures for children plus additional health economic outcomes for inclusion in a future full-scale trial. Discussion The results of this study will inform decisions on whether and how to proceed to a full-scale evaluation of the effectiveness and cost-effectiveness of the CHARMING Programme to improve or sustain physical activity. Trial registration ClinicalTrials.gov ISRCTN36223327. Registered March 29, 2021

BackgroundAddressing violence related harm is a global public health priority. While violence is primarily managed in the criminal justice system, healthcare supports and manages those injured by violence. Emergency Departments (EDs), the primary destination for those seriously injured, have emerged as a candidate location for violence prevention initiatives. There is limited evaluation of ED-based violence prevention, and a lack of guidance for the implementation and delivery of them. Nurse-led Violence Prevention Teams (VPTs) have been developed and implemented in two EDs in Wales, UK. This protocol describes methods used in the process evaluation of these VPTs.AimTo understand how VPTs function, how they were implemented, and mechanisms of impact, as well as the exploration of wider contextual factors influencing their function.MethodsAdopting a critical realist approach and informed by the Medical Research Council (MRC) guidance for process evaluations, the process evaluation will employ qualitative methods to collect and analyse data: a scoping review of evidence of effectiveness that considers the causal mechanisms underpinning violence; a documentary analysis to determine operational considerations concerning the development, implementation and delivery of the VPTs; a descriptive analysis of routine ED data to characterise the prevalence of violence-related attendances in each ED; interviews with professional stakeholders (N = 60) from the violence prevention ecologies in which the VPTs are embedded.DiscussionThis protocol outlines a process evaluation of a novel, nurse led violence prevention intervention. Findings will be used to inform policy makers' decision making on whether and how VPTs should be used in practice in other EDs across the UK, and the extent that a single operational model should be adjusted to address the local characteristic of violence. To the authors knowledge, this is the first process evaluation of a UK-based, nurse led Emergency Department Violence Prevention Team.Trial registrationProtocol registration ISRCTN: 15286575. Registered 13th March, 2023.

Abstract Background Over ten years on from a randomised controlled trial and subsequent national roll-out, the National Exercise Referral Scheme (NERS) continues to be routinely delivered in primary care across Wales, UK. Few studies have revisited effective interventions years into their delivery in routine practice to understand how implementation, and perceived effects, have been maintained over time. This study explores perceptions and experiences of referral to NERS among referrers, scheme deliverers and patients. Methods Individual, semi-structured interviews were conducted with 50 stakeholders: scheme referrers (n = 9); scheme deliverers (n = 22); and referred patients (n = 19). Convenience sampling techniques were used to recruit scheme referrers and purposive sampling to recruit scheme deliverers and patients. Thematic analysis was employed. Results Analyses resulted in five key themes; referrer characteristics, geographical disparities in referral and scheme access, reinforcements for awareness of the scheme, patient characteristics and processes and context underpinning a referral. Overall there was a high concordance of views between all three stakeholder groups and barriers and facilitators were found to be entwined within and across themes. Referral barriers persisting since the earlier trial included a lack of consultation time and a lack of referral feedback. Newly identified barriers included a lack of scheme awareness and a referral system perceived to be time intensive and disjointed. Key referral facilitators included patient self-referrals, a growing scheme reputation and promotional activities of scheme deliverers. Conclusions Findings provide evidence that could inform the further development of NERS and wider exercise referral schemes to ensure the referral process is timely, efficient and equitable.

Abstract Many species, including most flowering plants, are polyploid, possessing multiple genomes. During polyploidisation, fertility is preserved via the evolution of mechanisms to control the behaviour of these multiple genomes during meiosis. On the polyploidisation of wheat, the major meiotic gene ZIP4 duplicated and diverged, with the resulting new gene TaZIP4-B2 being inserted into chromosome 5B. Previous studies showed that this TaZIP4-B2 promotes pairing and synapsis between wheat homologous chromosomes, whilst suppressing crossover between related (homoeologous) chromosomes. Moreover, in wheat, the presence of TaZIP4-B2 preserves up to 50% of grain number. The present study exploits a ‘separation-of-function’ wheat Tazip4-B2 mutant named zip4-ph1d, in which the Tazip4-B2 copy still promotes correct pairing and synapsis between homologues (resulting in the same pollen profile and fertility normally found in wild type wheat), but which also allows crossover between the related chromosomes in wheat haploids of this mutant. This suggests an improved utility for the new zip4-ph1d mutant line during wheat breeding, compared to the previously described CRISPR Tazip4-B2 and ph1 mutant lines. The results also reveal that loss of suppression of homoeologous crossover between wheat chromosomes does not in itself reduce wheat fertility when promotion of homologous pairing and synapsis by TaZIP4-B2 is preserved.

Abstract Background Today’s primary school children have grown up in a climate of strong smoking restrictions, decreasing tobacco use, and the emergence of e-cigarettes. Children’s exposure to tobacco declined substantially in years following the introduction of smoke-free legislation, with smoking uptake and perceived smoking norms declining. There is debate regarding whether emergence of e-cigarettes may interrupt trends in children’s smoking perceptions, or offer a means for adults to limit children’s exposure to tobacco. This study examines change in children’s tobacco and e-cigarettes experimentation (ever use), exposure to secondhand smoking and vaping, and perceived smoking norms. Methods Data from four, repeat cross-sectional surveys of Year 6 primary school pupils (age 10–11 years) in Wales in 2007, 2008, 2014 and 2019 (n = 6741) were combined. E-cigarette use and perceptions were included in 2014 and 2019 surveys. Analyses used binary logistic regression analyses, adjusted for school-level clustering. Results Child tobacco experimentation and most indicators of exposure to tobacco smoke indicated a graded decreasing trend over time from 2007 to 2019. Exposure to e-cigarettes increased from 2014 to 2019, as did pupil awareness of e-cigarettes (OR = 2.56, 95%CI = 2.12–3.10), and parental use (OR = 1.26, 95%CI = 1.00–1.57). A decrease in child e-cigarette experimentation was not significant (OR = 0.80, 95%CI = 0.57–1.13). Children’s normative perceptions for smoking by adults and children indicated a graded decrease over time (OR = 0.66, 95%CI = 0.54–0.80; OR = 0.69, 95%CI = 0.55–0.86; respectively from 2014 to 2019). However, fewer reported disapproval of people smoking around them in 2019 relative to 2014 (OR = 0.68, 95%CI = 0.53–0.88). Higher exposure to tobacco cigarettes and e-cigarettes in public places, cars and households were associated with favourable normative perceptions for tobacco smoking; however in models adjusted for exposure to both associations of e-cigarette exposure were attenuated. Conclusion Children’s experimentation with and exposure to tobacco, and their perceptions of smoking as a normative behaviour, have continued to decline alongside growth in exposure to e-cigarettes. Although a large majority of pupils reported they minded people smoking around them, there was some evidence of diminishing disapproval of secondhand smoke since 2007. Further research is needed to understand whether use of e-cigarettes in cars and homes is displacing prior smoking or being introduced into environments where smoking had been eliminated.

Objectives Research on the adaptation of population health interventions for implementation in new contexts is rapidly expanding. This has been accompanied by a recent increase in the number of frameworks and guidance to support adaptation processes. Nevertheless, there remains limited exploration of the real-world experiences of undertaking intervention adaptation, notably the challenges encountered by different groups of stakeholders, and how these are managed. Understanding experiences is imperative in ensuring that guidance to support adaptation has practical utility. This qualitative study examines researcher and stakeholder experiences of funding, conducting and reporting adaptation research.Setting Adaptation studies.Participants Participants/cases were purposefully sampled to represent a range of adapted interventions, types of evaluations, expertise and countries. Semistructured interviews were conducted with a sample of researchers (n=23), representatives from research funding panels (n=6), journal editors (n=5) and practitioners (n=3).Measures A case study research design was used. Data were analysed using the framework approach. Overarching themes were discussed within the study team, with further iterative refinement of subthemes.Results The results generated four central themes. The first three relate to the experience of intervention adaptation (1) involving stakeholders throughout the adaptation process and how to integrate the evidence base with experience; (2) selecting the intervention and negotiating the mismatch between the original and the new context; and (3) the complexity and uncertainty when deciding the re-evaluation process. The final theme (4) reflects on participants’ experiences of using adaptation frameworks in practice, considering recommendations for future guidance development and refinement.Conclusion This study highlights the range of complexities and challenges experienced in funding, conducting and reporting research on intervention adaptation. Moving forward, guidance can be helpful in systematising processes, provided that it remains responsive to local contexts and encourage innovative practice.

Abstract Background The use of process evaluations is a growing area of interest in research groups working on complex interventions. This methodology tries to understand how the intervention was implemented to inform policy and practice. A recent systematic review by Liu et al. on process evaluations of complex interventions addressing non-communicable diseases found few studies in low- and middle- income countries (LMIC) because it was restricted to randomized controlled trials, primary healthcare level and non-communicable diseases. Yet, LMICs face different barriers to implement interventions in comparison to high-income countries such as limited human resources, access to health care and skills of health workers to treat chronic conditions especially at primary health care level. Therefore, understanding the challenges of interventions for non-communicable diseases and neglected tropical diseases (diseases that affect poor populations and have chronic sequelae) will be important to improve how process evaluation is designed, conducted and used in research projects in LMICs. For these reasons, in comparison to the study of Liu et al., the current study will expand the search strategy to include different study designs, languages and settings. Objective Map research using process evaluation in the areas of non-communicable diseases and neglected tropical diseases to inform the gaps in the design and conduct of this type of research in LMICs. Methods Scoping review of process evaluation studies of randomized controlled trials (RCTs) and non-RCTs of complex interventions implemented in LMICs including participants with non-communicable diseases or neglected tropical diseases and their health care providers (physicians, nurses, technicians and others) related to achieve better health for all through reforms in universal coverage, public policy, service delivery and leadership. The aspects that will be evaluated are as follows: (i) available evidence of process evaluation in the areas of non-communicable diseases and neglected tropical diseases such as frameworks and theories, (ii) methods applied to conduct process evaluations and (iii) gaps between the design of the intervention and its implementation that were identified through the process evaluation. Studies published from January 2008. Exclusion criteria are as follows: not peer reviewed articles, not a report based on empirical research, not reported in English or Spanish or Portuguese or French, reviews and non-human research. Discussion This scoping review will map the evidence of process evaluations conducted in LMICs. It will also identify the methods they used to collect and interpret data, how different theories and frameworks were used and lessons from the implementation of complex interventions. This information will allow researchers to conduct better process evaluations considering special characteristics from countries with limited human resources, scarce data available and limited access to health care.

Objectives The aim of this review is to map out the use of process evaluation (PE) in complex interventions that address non-communicable diseases (NCDs) and neglected tropical diseases (NTDs) to identify gaps in the design and conduct, as well as strengths, limitations and implications, of this type of research in low- and middle-income countries (LMICs).Design Scoping review of PE studies of complex interventions implemented in LMICs. Six databases were searched focused on studies published since 2008.Data sources Embase, PubMed, EbscoHost, Web of Science (WOS), Virtual Health Library (VHL) Regional Portal and Global Index Medicus: Regional Indexes AIM (AFRO), LILACS (AMRO/PAHO), IMEMR (EMRO), IMSEAR (SEARO), WPRIM (WPRO) Global Index Regional Indexes, MEDLINE, SciELO.Eligibility criteria Studies conducted in LMICs on PEs of randomised controlled trials (RCTs) and non-RCTs published between January 2008 and January 2020. Other criteria were studies of interventions for people at risk or having physical and mental NCDs, and/or NTDs, and/or their healthcare providers and/or others related to achieve better health for these two disease groups. Studies were excluded if they were not reported in English or Spanish or Portuguese or French, not peer-reviewed articles, not empirical research and not human research.Data extraction and synthesis Data extracted to be evaluated were: available evidence in the utilisation of PE in the areas of NCDs and NTDs, including frameworks and theories used; methods applied to conduct PEs; and in a subsample, the barriers and facilitators to implement complex interventions identified through the PE. Variables were extracted and categorised. The information was synthesised through quantitative analysis by reporting frequencies and percentages. Qualitative analysis was also performed to understand facilitators and barriers presented in these studies. The implications for PEs, and how the information from the PE was used by researchers or other stakeholders were also assessed in this approach.Results 303 studies were identified, 79% were for NCDs, 12% used the label ‘PE’, 27% described a theory or framework for the PE, and 42% used mixed methods to analyse their findings. Acceptability, barriers and facilitators to implement the interventions, experiences and perceptions, and feasibility were the outcomes most frequently evaluated as part of the PEs. Barriers and facilitators themes identified were contextual factors, health system factors, human resources, attitudes and policy factors.Conclusions PEs in NCDs and NTDs are used in LMICs with a wide variety of methods. This review identified many PEs that were not labelled by the authors as such, as well as a limited application of PE-related theories and frameworks, and heterogeneous reporting of this type of study.

The genomic organization and origin of the avenacin biosynthetic gene cluster remain unknown. Here, the authors assemble the genome of diploid oat Avena strigosa, reveal the structure and organization of the consecutive genes, characterize the last two missing pathway steps, and investigate the origin of the pathway in cereals.

Abstract Background Linking survey data to administrative records requires informed participant consent. When linkage includes child data, this includes parental and child consent. Little is known of the potential impacts of introducing consent to data linkage on response rates and biases in school-based surveys. This paper assessed: i) the impact on overall parental consent rates and sample representativeness when consent for linkage was introduced and ii) the quality of identifiable data provided to facilitate linkage. Methods Including an option for data linkage was piloted in a sub-sample of schools participating in the Student Health and Wellbeing survey, a national survey of adolescents in Wales, UK. Schools agreeing to participate were randomized 2:1 to receive versus not receive the data linkage question. Survey responses from consenting students were anonymised and linked to routine datasets (e.g. general practice, inpatient, and outpatient records). Parental withdrawal rates were calculated for linkage and non-linkage samples. Multilevel logistic regression models were used to compare characteristics between: i) consenters and non-consenters; ii) successfully and unsuccessfully linked students; and iii) the linked cohort and peers within the general population, with additional comparisons of mental health diagnoses and health service contacts. Results The sub-sample comprised 64 eligible schools (out of 193), with data linkage piloted in 39. Parental consent was comparable across linkage and non-linkage schools. 48.7% (n = 9232) of students consented to data linkage. Modelling showed these students were more likely to be younger, more affluent, have higher positive mental wellbeing, and report fewer risk-related behaviours compared to non-consenters. Overall, 69.8% of consenting students were successfully linked, with higher rates of success among younger students. The linked cohort had lower rates of mental health diagnoses (5.8% vs. 8.8%) and specialist contacts (5.2% vs. 7.7%) than general population peers. Conclusions Introducing data linkage within a national survey of adolescents had no impact on study completion rates. However, students consenting to data linkage, and those successfully linked, differed from non-consenting students on several key characteristics, raising questions concerning the representativeness of linked cohorts. Further research is needed to better understand decision-making processes around providing consent to data linkage in adolescent populations.

Abstract Background Polyploidy is ubiquitous in eukaryotic plant and fungal lineages, and it leads to the co-existence of several copies of similar or related genomes in one nucleus. In plants, polyploidy is considered a major factor in successful domestication. However, polyploidy challenges chromosome folding architecture in the nucleus to establish functional structures. Results We examine the hexaploid wheat nuclear architecture by integrating RNA-seq, ChIP-seq, ATAC-seq, Hi-C, and Hi-ChIP data. Our results highlight the presence of three levels of large-scale spatial organization: the arrangement into genome territories, the diametrical separation between facultative and constitutive heterochromatin, and the organization of RNA polymerase II around transcription factories. We demonstrate the micro-compartmentalization of transcriptionally active genes determined by physical interactions between genes with specific euchromatic histone modifications. Both intra- and interchromosomal RNA polymerase-associated contacts involve multiple genes displaying similar expression levels. Conclusions Our results provide new insights into the physical chromosome organization of a polyploid genome, as well as on the relationship between epigenetic marks and chromosome conformation to determine a 3D spatial organization of gene expression, a key factor governing gene transcription in polyploids.

Background, Aims, Methods, Results, Conclusions: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global challenge due to its ability to mutate into variants that spread more rapidly than the wild-type virus. The molecular biology of this virus has been extensively studied and computational methods applied are an example paradigm for novel antiviral drug therapies. The rapid evolution of SARS-CoV-2 in the human population is driven, in part, by mutations in the receptor-binding domain (RBD) of the spike (S-) protein, some of which enable tighter binding to angiotensin-converting enzyme (ACE2). More stable RBD-ACE2 association is coupled with accelerated hydrolysis by proteases, such as furin, trypsin, and the Transmembrane Serine Protease 2 (TMPRSS2) that augment infection rates, while inhibition of the 3-chymotrypsin-like protease (3CLpro) can prevent the viral replication. Additionally, non-RBD and non-interfacial mutations may assist the S-protein in adopting thermodynamically favorable conformations for stronger binding. This study aimed to report variant distribution of SARS-CoV-2 across European Union (EU)/European Economic Area (EEA) countries and relate mutations with the driving forces that trigger infections. Variants’ distribution data for SARS-CoV-2 across EU/EEA countries were mined from the European Centre for Disease Prevention and Control (ECDC) based on the sequence or genotyping data that are deposited in the Global Science Initiative for providing genomic data (GISAID) and The European Surveillance System (TESSy) databases. Docking studies performed with AutoDock VINA revealed stabilizing interactions of putative antiviral drugs, e.g., selected anionic imidazole biphenyl tetrazoles, with the ACE2 receptor in the RBD-ACE2 complex. The driving forces of key mutations for Alpha, Beta, Gamma, Delta, Epsilon, Kappa, Lambda, and Omicron variants, which stabilize the RBD-ACE2 complex, were investigated by computational approaches. Arginine is the critical amino acid in the polybasic furin cleavage sites S1/S2 (681-PRRARS-686) S2′ (814-KRS-816). Critical mutations into arginine residues that were found in the delta variant (L452R, P681R) and may be responsible for the increased transmissibility and morbidity are also present in two widely spreading omicron variants, named BA.4.6 and BQ.1, where mutation R346T in the S-protein potentially contributes to neutralization escape. Arginine binders, such as Angiotensin Receptor Blockers (ARBs), could be a class of novel drugs for treating COVID-19.

Changes in the prevalence of psychological distress among smokers during the COVID-19 pandemic in England may exacerbate existing health inequalities. This study examined the prevalence of psychological distress among smokers following the onset of the pandemic compared with previous years. Cross-sectional data came from a representative survey of smokers (18+) in England (n = 2,927) between April–July in 2016, 2017 and 2020. Logistic regressions estimated the associations between past-month distress across 2016/2017 and 2020, and age. Weighted proportions, chi-squared statistics and stratified logistic regression models were used to compare the distributions of moderate and severe distress, respectively, within socio-demographic and smoking characteristics in 2016/2017 and 2020. Between the combined April–July 2016 and 2017 sample and April–July 2020 the prevalence of moderate and severe distress among past-year smokers increased (2016/2017: moderate 20.66%, 19.02–22.43; severe 8.23%, 7.16–9.47; 2020: moderate 28.79%, 95%CI 26.11–31.60; OR = 2.08, 95%CI 1.34–3.25; severe 11.04%, 9.30–13.12; OR = 2.16, 1.13–4.07). While there was no overall evidence of an interaction between time period and age, young (16–24 years) and middle-age groups (45–54 years) may have experienced greater increases in moderate distress and older age groups (65+ years) increases in severe distress. There were increases of moderate distress among more disadvantaged social grades and both moderate and severe distress among women and those with low cigarette addiction. Between April–July 2016/2017 and April–July 2020 in England there were increases in both moderate and severe distress among smokers. The distribution of distress among smokers differed between 2016/2017 and 2020 and represents a widening of inequalities.

Objectives To understand self-reported potential cancer symptom help-seeking behaviours and attitudes during the first 6 months (March–August 2020) of the UK COVID-19 pandemic.Design UK population-based survey conducted during August and September 2020. Correlates of help-seeking behaviour were modelled using logistic regression in participants reporting potential cancer symptoms during the previous 6 months. Qualitative telephone interviews with a purposeful subsample of participants, analysed thematically.Setting Online UK wide survey.Participants 7543 adults recruited via Cancer Research UK online panel provider (Dynata) and HealthWise Wales (a national register of ‘research ready’ participants) supplemented with social media (Facebook and Twitter) recruitment. 30 participants were also interviewed.Main outcome measures Survey measures included experiences of 15 potential cancer symptoms, help-seeking behaviour, barriers and prompts to help-seeking.Results Of 3025 (40.1%) participants who experienced a potential cancer symptom, 44.8% (1355/3025) had not contacted their general practitioner (GP). Odds of help-seeking were higher among participants with disability (adjusted OR (aOR)=1.38, 95% CI 1.11 to 1.71) and who experienced more symptoms (aOR=1.68, 95% CI 1.56 to 1.82), and lower among those who perceived COVID-19 as the cause of symptom(s) (aOR=0.36, 95% CI 0.25 to 0.52). Barriers included worries about wasting the doctor’s time (1158/7543, 15.4%), putting strain on healthcare services (945, 12.6%) and not wanting to make a fuss (907, 12.0%). Interviewees reported reluctance to contact the GP due to concerns about COVID-19 and fear of attending hospitals, and described putting their health concerns on hold.Conclusions Many people avoided healthcare services despite experiencing potential cancer symptoms during the COVID-19 pandemic. Alongside current help-seeking campaigns, well-timed and appropriate nationally coordinated campaigns should signal that services are open safely for those with unusual or persistent symptoms.Trial registration number ISRCTN17782018.

Abstract Purpose The study of mental wellbeing requires reliable, valid, and practical measurement tools. One of the most widely used measures of mental wellbeing is the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS). Our aim was to examine the psychometric properties of SWEMWBS (a brief seven-item version) in a ‘real-world’ population sample of young people. Methods We used data from the 2017 School Health Research Network Student Health and Wellbeing Survey, completed by 103,971 students in years 7 to 11 from 193 secondary schools in Wales. We first estimated polychoric correlation matrices for the whole sample and by school year, and undertook a principal components analysis to check for configural invariance. Subsequently, we used a multiple-groups structural equation model with successively greater constraints to test measurement invariance. To examine external construct validity, we calculated correlations between the SWEMWBS score and four covariates: life satisfaction, somatisation, school pressure and bullying victimisation. Results Parallel analysis suggested that extraction of one factor was appropriate both overall and in each year group. Inspection of standardised loadings suggested that four items had progressively stronger correlations with the factor as students are older, but change in fit indices between models suggested that loadings and thresholds, but not residual variances, were invariant by age group. SWEMWBS scores were moderately correlated with measures of life satisfaction and somatisation, and weakly to moderately correlated with school pressure and bullying victimisation. Conclusions This study adds to the growing evidence that SWEMWBS is appropriate for measuring mental wellbeing in young people and suggests that SWEMWBS is appropriate for tracking the development of wellbeing across adolescence.

Abstract Background An international workshop on population health intervention research (PHIR) was organized to foster exchanges between experts from different disciplines and different fields. This paper aims to summarize the discussions around some of the issues addressed: (1) the place of theories in PHIR, (2) why theories can be useful, and (3) how to choose and use the most relevant of them in evaluating PHIR. Methods The workshop included formal presentations by participants and moderated discussions. An oral synthesis was produced by a rapporteur to validate, through an expert consensus, the key points of the discussion and the recommendations. All discussions were recorded and have been fully transcribed. Results The following recommendations were generated through a consensus in the workshop discussions: (i) The evaluation of interventions, like their development, could be improved through better use of theory. (ii) The referenced theory and framework must be clarified. (iii) An intervention theory should be developed by a partnership of researchers and practitioners. (iv) More use of social theory is recommended. (v) Frameworks and a common language are helpful in selecting and communicating a theory. (vi) Better reporting of interventions and theories is needed. Conclusion Theory-driven interventions and evaluations are key in PHIR as they facilitate the understanding of mechanisms of change. There are many challenges in developing the most appropriate theories for interventions and evaluations. With the wealth of information now being generated, this subject is of increasing importance at many levels, including for public health policy. It is, therefore, timely to consider how to build on the experiences of many different disciplines to enable the development of better theories and facilitate evidence-based decisions.

Diminazene aceturate (DIZE) is a putative angiotensin-converting enzyme 2 (ACE2) activator and angiotensin type 1 receptor antagonist (AT1R). Its simple chemical structure possesses a negatively charged triazene segment that is homologous to the tetrazole of angiotensin receptor blockers (ARB), which explains its AT1R antagonistic activity. Additionally, the activation of ACE2 by DIZE converts the toxic octapeptide angiotensin II (AngII) to the heptapeptides angiotensin 1–7 and alamandine, which promote vasodilation and maintains homeostatic balance. Due to DIZE’s protective cardiovascular and pulmonary effects and its ability to target ACE2 (the predominant receptor utilized by severe acute respiratory syndrome coronavirus 2 to enter host cells), it is a promising treatment for coronavirus 2019 (COVID-19). To determine DIZE’s ability to inhibit AngII constriction, in vitro isometric tension analysis was conducted on rabbit iliac arteries incubated with DIZE or candesartan and constricted with cumulative doses of AngII. In silico docking and ligand interaction studies were performed to investigate potential interactions between DIZE and other ARBs with AT1R and the spike protein/ACE2 complex. DIZE, similar to the other ARBs investigated, was able to abolish vasoconstriction in response to AngII and exhibited a binding affinity for the spike protein/ACE2 complex (PDB 6LZ6). These results support the potential of DIZE as a treatment for COVID-19.

Objectives To identify psychosocial determinants of quit motivation in older deprived smokers. The evidence may be used to optimise smoking cessation interventions for the target population.Design Cross-sectional survey using online recruitment methods including Facebook-targeted advertising.Setting UK, 2019.Participants Current smokers aged 50 years or older and from a socioeconomically deprived background.Main outcome measures Measures included motivation to stop smoking, smoking history, perceived social support, self-efficacy for quitting, self-exempting beliefs and lung cancer risk perception. Multivariable regression was used to analyse factors associated with quit motivation.Results Of a total 578 individuals who consented to take part, 278 (48.1%) did not meet the inclusion criteria. Of the 300 eligible participants, most were recruited using Facebook (94.0%), were aged 50–64 years (83.7%) and women (85.7%). Most participants were renting from a housing association (72.0%) and had low education (61.0%). Higher motivation to quit was statistically significantly associated with a higher intensity of previous quit attempts (p=0.03), higher quit confidence (p=0.01), higher smoking self-efficacy (p=0.01), a lower risk-minimising beliefs score (p=0.01) and using traditional nicotine replacement therapy (NRT) when trying to stop smoking or cut down (p

Background The Smoking and Alcohol Toolkit Study (STS/ATS) in England has delivered timely insights to inform and evaluate strategies aimed at reducing tobacco smoking- and alcohol-related harm. From the end of 2020 until at least 2024 the STS/ATS is expanding to Scotland and Wales to include all constituent nations in Great Britain. Expanding data collection to Scotland and Wales will permit the evaluation of how smoking and alcohol related behaviours respond to divergent policy scenarios across the devolved nations. Methods The STS/ATS consists of monthly cross-sectional household interviews (computer or telephone assisted) of representative samples of adults in Great Britain aged 16+ years. Commencing in October 2020 each month a new sample of approximately 1700 adults in England, 450 adults in Scotland and 300 adults in Wales complete the survey (~n = 29,400 per year). The expansion of the survey to Scotland and Wales has been funded for the collection of at least 48 waves of data across four years. The data collected cover a broad range of smoking and alcohol-related parameters (including but not limited to smoking status, cigarette/nicotine dependence, route to quit smoking, prevalence and frequency of hazardous drinking, attempts and motivation to reduce alcohol consumption, help sought and motives for attempts to reduce alcohol intake) and socio-demographic characteristics (including but not limited to age, gender, region, socio-economic position) and will be reviewed monthly and refined in response to evolving policy needs and public interests. All data analyses will be pre-specified and available on a free online platform. A dedicated website will publish descriptive data on important trends each month. Discussion The Smoking and Alcohol Toolkit Study will provide timely monitoring of smoking and alcohol related behaviours to inform and evaluate national policies across Great Britain.

The main causes of non-communicable diseases (NCDs), health inequalities and health inequity include consumption of unhealthy commodities such as tobacco, alcohol and/or foods high in fat, salt and/or sugar. These exposures are preventable, but the commodities involved are highly profitable. The economic interests of ‘Unhealthy Commodity Producers’ (UCPs) often conflict with health goals but their role in determining health has received insufficient attention. In order to address this gap, a new research consortium has been established. This open letter introduces the SPECTRUM (Shaping Public hEalth poliCies To Reduce ineqUalities and harM) Consortium: a multi-disciplinary group comprising researchers from 10 United Kingdom (UK) universities and overseas, and partner organisations including three national public health agencies in Great Britain (GB), five multi-agency alliances and two companies providing data and analytic support. Through eight integrated work packages, the Consortium seeks to provide an understanding of the nature of the complex systems underlying the consumption of unhealthy commodities, the role of UCPs in shaping these systems and influencing health and policy, the role of systems-level interventions, and the effectiveness of existing and emerging policies. Co-production is central to the Consortium’s approach to advance research and achieve meaningful impact and we will involve the public in the design and delivery of our research. We will also establish and sustain mutually beneficial relationships with policy makers, alongside our partners, to increase the visibility, credibility and impact of our evidence. The Consortium’s ultimate aim is to achieve meaningful health benefits for the UK population by reducing harm and inequalities from the consumption of unhealthy commodities over the next five years and beyond.

BackgroundThe adaptation of interventions for new contexts is a rapidly developing research area. To date there is no consensus-based guidance to support decision-making and recommend adaptation processes. The ADAPT study is developing such guidance. This aim of the qualitative component of the study was to explore stakeholders' understandings of adaptation, as to date there has limited consideration of how different concepts and meanings shape decision-making and practice.MethodsA case study research design was used. Participants/cases were purposefully sampled based on study outcome, study design, expertise, context and country. Semi-structured interviews were conducted with a sample of researchers (n = 23); representatives from research funding panels (n = 6); journal editors (n = 5) and practitioners (n = 3). Data were analysed using the Framework approach. Overarching themes were discussed with the ADAPT study team, with further iterative refinement of subthemes.ResultsThe results generated four central themes. Four themes related to stakeholders' understanding: 1) definitions of adaptation and related concepts; 2) rationales for undertaking adaptation; 3) the appropriate timing for adaptation; and 4) ensuring fidelity when implementing adapted interventions.ConclusionThe findings highlight the lack of clarity around key concepts and uncertainty about central decision-making processes, notably why interventions should be adapted, when and to what extent. This has informed the ADAPT study's guidance, shaping the scope and nature of recommendations to be included and surfacing key uncertainties that require future consideration.

To date no study has examined time trends in adolescent consumption of sugar-sweetened beverages and energy drinks, or modelled change in inequalities over time. The present study aimed to fill this gap by identifying historical trends among secondary school students in Wales, United Kingdom. The present study includes 11-16 year olds who completed the Health Behaviour in School-aged Children (HBSC) survey and the Welsh School Health Research Network (SHRN) survey between 1998 to 2017. Multinomial regression models were employed alongside tests for interaction effects. A total of 176,094 student responses were assessed. From 1998 to 2017, the prevalence of daily sugar-sweetened beverage consumption decreased (57% to 18%) while weekly consumption has remained constant since 2006 (49% to 52%). From 2013 to 2017, daily consumption of energy drinks remained stable (6%) while weekly consumption reports steadily decreased (23% to 15%). Boys, older children and those from a low socioeconomic group reported higher consumption rates of sugar-sweetened beverages and energy drinks. Consumption according to socioeconomic group was the only characteristic to show a statistically significant change over time, revealing a widening disparity between sugar-sweetened beverage consumption rates of those from low and high socioeconomic groups. Findings indicate a positive shift in overall consumption rates of both sugar-sweetened beverages and energy drinks. Adolescents from a low socioeconomic group however were consistently shown to report unfavourable sugar-sweetened beverages consumption when compared to peers from high socioeconomic group. Given the established longer term impacts of sugar-sweetened beverage and energy drink consumption on adolescent health outcomes, urgent policy action is required to reduce overall consumption rates, with close attention to equity of impact throughout policy design and evaluation plans.

The 1609 pamphlet The liues, apprehensions, arraignments, and executions of the 19 late pyrates tells the stories of nineteen pirates trialled in 1609. Historians of Jacobean piracy have used this pamphlet as evidence, finding value in its detailed, dramatic accounts of maritime depredation—yet it has often escaped close textual analysis. This article analyses the pamphlet’s content and context, in doing so illuminating the tensioned relationship between legal, state, and popular cultural narratives of what constituted a “pirate”. The pamphlet provides an opportunity to further discuss the ambiguous, developing cultural role of piracy (and its perpetrators) at this time. It allows us to approach such questions as: which elements of a pirate’s story were interesting to the seventeenth-century audience, and which elements marked out acts of depredation as truly being “piracy”? How does the source approach legal proceedings, and digest them for popular consumption? What place does this pamphlet have in the wider canon of piracy’s print culture? This article suggests that the figure of the pirate could be redeemed, where it was reconcilable with the sensibilities of the terrestrial community—however, tensions arose when different groups imposed their own ideologies and intentions upon the criminal. These tensions appear in the differences between representations of maritime depredation emanating from the state and from the public—differences visible in the transmission of information from law to literature.

Introduction Little is known of the potential impacts of introducing data linkage processes on response rates and biases in school-based surveys. Objectives and Approach This paper assessed: i) the impact on parental consent rates for student participation in a school survey; ii) sample representativeness; and iii) the quality of identifiable data provided to facilitate linkage. An option for data linkage was piloted in a sub-sample of schools participating in the Student Health and Wellbeing survey, a national survey of adolescents in Wales, UK. Schools agreeing to participate were randomized 2:1 to receive the data linkage question. Survey responses from consenting students were anonymised and linked to routine datasets (e.g. general practice, inpatient, and outpatient records). Parental withdrawal rates were calculated for linkage and non-linkage samples. Multilevel logistic regression models compared characteristics between: i) consenters and non-consenters; ii) successfully and unsuccessfully linked students; and iii) linked cohort and peers within the general population, with additional comparisons of mental health diagnoses and health service contacts. Results The sub-sample comprised 64 eligible schools (out of 193), with data linkage piloted in 39. Parental consent was comparable across linkage and non-linkage schools. 48.7% (n=9,232) of students consented to data linkage. Consenting students were more likely to be younger, more affluent, have higher positive mental wellbeing, and report fewer risk-related behaviours compared to non-consenters. Overall, 69.8% of consenting students were successfully linked, with higher rates of success among younger students. The linked cohort had lower rates of mental health diagnoses (5.8% vs. 8.8%) and specialist contacts (5.2% vs. 7.7%) than general population peers. Conclusion Introducing data linkage within a national survey of adolescents had no impact on study completion rates. Students consenting to data linkage, and those successfully linked, differed from non-consenting students on numerous key characteristics, raising questions concerning the representativeness of linked cohorts.

Experimentation with e-cigarettes has grown rapidly among UK adolescents. To date, this topic has been primarily researched in secondary schools, with less understanding of development of attitudes and behaviours at an earlier age. This research reports qualitative data from interviews with pupils, parents, and teachers at 4 case study schools in Wales (N = 42). It draws on Bronfenbrenner’s Ecological Systems Theory to consider how the intersection of systems surrounding primary school-age children and their interaction with these systems, shape knowledge, and attitudes towards e-cigarettes and tobacco. Findings indicate that consistent messaging on smoking from school and family was reflected in strong disapproval among pupils and clear understanding of harms. This was less evident for e-cigarettes, where messages were mixed and inconsistent between home and school, with concerns over what to tell children about e-cigarettes in light of mixed messages and absence of official guidance. Implications of findings for policy and teaching are discussed.

Introduction Complex population health interventions that are effective in one context may not be effective elsewhere, and may even be harmful. As such, an intervention may require adaptation to ensure it fits with a new context. To date, there is no overarching guidance to help researchers to adapt and evaluate interventions in new contexts, and no criteria to support research funders or journals assess proposed or reported adaptations or evaluation. There is limited assistance for policy-makers and practitioners to decide if evidence-informed interventions are appropriate to their context, or if adaptation and further evaluation is needed. This Delphi exercise will contribute to the development of guidance for these communities to support the adaptation, implementation and/or re-evaluation of complex population health interventions in new contexts.Methods We will conduct a Delphi consensus exercise to gather expert opinion from researchers, research funders, journal editors and policy-makers. Expert opinion will be sought on: appropriate definitions and concepts, identifying key methodological considerations and establishing adaptations and processes to be undertaken during adaptation of complex population health interventions in new contexts.Ethics and dissemination Ethics approval for the Delphi exercise has been obtained from the University of Glasgow and and the RAND institutional research board. Dissemination of the results of this study will be through peer-reviewed publications, workshops at national and international conferences, and a summary of the guidance developed for key organisations and stakeholders.

AbstractBackground:Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) is a multifunctional ubiquitin binding and editing enzyme that regulates inflammation. Genetic studies have implicated polymorphisms within the TNFAIP3 locus to the development of numerous immune-related diseases. This study evaluated the frequencies of single-nucleotide polymorphism (SNPs) within the exonic regions of the TNFAIP3 gene and an associated point mutation from the Illumina array among a predominantly Hispanic cohort.Methods:Genomic DNA was obtained from 721 participants and sequencing of all TNFAIP3 exons and an intergenic point mutation (rs6920220) was performed. In-vitro functional assessment was performed by transfecting mutated TNFAIP3 constructs into TNFAIP3 knockout cells containing the NF-kB luciferase reporter and stimulating with TNFα. Comparative statistics were performed with Student’s t-test for continuous variables and chi-squared test for categorical variables.Results:Sequencing revealed two missense SNPs, rs146534657:A>G and rs2230926:T>G, both within exon 3 of TNFAIP3, which encodes the protein’s deubiquitinating enzymatic domain. Frequencies of all three point mutations differed significantly across racial groups (χ2-test, P = 0.014 to P < 0.001). Compared to Caucasians, rs146534657:A>G was overrepresented among Hispanics (odds ratio (OR) [95% CI] 4.05 [1.24−13.18]), and rs2230926:T>G was more prevalent among African-Americans (OR [95% CI] 3.65 [1.58−8.43]). In-vitro assays confirm rs146534657:A>G and rs2230926:T>G decrease the ability of TNFAIP3 to abrogate NF-κB activation by 2-fold (P < 0.01) and 1.7-fold (P < 0.01), respectively.Conclusions:This study reports the frequency of rs146534657:A>G among Hispanics and is the first to evaluate its potential physiologic impact, establishing a basis for future research as a potential biomarker among this population.

Abstract Background Evaluations of complex interventions in public health are frequently undermined by problems that can be identified before the effectiveness study stage. Exploratory studies, often termed pilot and feasibility studies, are a key step in assessing the feasibility and value of progressing to an effectiveness study. Such studies can provide vital information to support more robust evaluations, thereby reducing costs and minimising potential harms of the intervention. This systematic review forms the first phase of a wider project to address the need for stand-alone guidance for public health researchers on designing and conducting exploratory studies. The review objectives were to identify and examine existing recommendations concerning when such studies should be undertaken, questions they should answer, suitable methods, criteria for deciding whether to progress to an effectiveness study and appropriate reporting. Methods We searched for published and unpublished guidance reported between January 2000 and November 2016 via bibliographic databases, websites, citation tracking and expert recommendations. Included papers were thematically synthesized. Results The search retrieved 4095 unique records. Thirty papers were included, representing 25 unique sources of guidance/recommendations. Eight themes were identified: pre-requisites for conducting an exploratory study, nomenclature, guidance for intervention assessment, guidance surrounding any future evaluation study design, flexible versus fixed design, progression criteria to a future evaluation study, stakeholder involvement and reporting of exploratory studies. Exploratory studies were described as being concerned with the intervention content, the future evaluation design or both. However, the nomenclature and endorsed methods underpinning these aims were inconsistent across papers. There was little guidance on what should precede or follow an exploratory study and decision-making surrounding this. Conclusions Existing recommendations are inconsistent concerning the aims, designs and conduct of exploratory studies, and guidance is lacking on the evidence needed to inform when to proceed to an effectiveness study. Trial registration PROSPERO 2016, CRD42016047843

Abstract Background We have previously proposed that trials of social interventions can be done within a “realist” research paradigm. Critics have countered that such trials are irredeemably positivist and asked us to explain our philosophical position. Methods We set out to explore what is meant by positivism and whether trials adhere to its tenets (of necessity or in practice) via a narrative literature review of social science and philosophical discussions of positivism, and of the trials literature and three case studies of trials. Results The philosophical literature described positivism as asserting: (1) the epistemic primacy of sensory information; (2) the requirement that theoretical terms equate with empirical terms; (3) the aim of developing universal laws; and (4) the unity of method between natural and social sciences. Regarding (1), it seems that rather than embodying the epistemic primacy of sensory data, randomised controlled trials (RCTs) of social interventions in health embrace an anti-positivist approach aiming to test hypotheses derived deductively from prior theory. Considering (2), while some RCTs of social interventions appear to limit theorisation to concepts with empirical analogues, others examine interventions underpinned by theories engaging with mechanisms and contextual contingencies not all of which can be measured. Regarding (3), while some trialists and reviewers in the health field do limit their role to estimating statistical trends as a mechanistic form of generalisation, this is not an inevitable feature of RCT-based research. Trials of social interventions can instead aim to generalise at the level of theory which specifies how mechanisms are contingent on context. In terms of (4), while RCTs are used to examine biomedical as well as social interventions in health, RCTs of social interventions are often distinctive in using qualitative analyses of data on participant accounts to examine questions of meaning and agency not pursued in the natural sciences. Conclusion We conclude that the most appropriate paradigm for RCTs of social interventions is realism not positivism.

While transition from primary to secondary school is a positive experience for many young people, for others, it may be a difficult period of adjustment. Socioeconomic status (SES) may influence the likelihood of a positive or negative transition experience owing to differences in psychosocial (self-esteem, self-efficacy, social support) and flexible (cultural capital, financial support, power) resources to respond to the challenges presented by a new school environment. Welsh all-age schools do not have a typical primary to secondary school transition and offer an opportunity for comparative analysis to explore the impact of transition on young people. This analysis used multilevel and structural equation modelling to assess differences in mental health and bullying outcomes in year 7 (first year of secondary education) in young people in all-age schools compared with those in secondary schools. It also considered whether school connectedness might explain these differences. It found that school type did not significantly predict outcomes at a population level; however, there was evidence of an interaction between SES and school attended for some outcomes. Peer problems, conduct problems and bullying victimisation were lower for children with low SES when attending all-age schools. For children with high SES, the same outcomes tended to be more positive if the children attended secondary schools. There was no evidence that school connectedness mediated the relationship between school type and mental health or bullying outcomes. Findings provide tentative evidence that all-age schools may act to reduce health inequalities caused by SES.

Abstract Background Exercise referral schemes are recommended by the National Institute for Clinical Excellence (NICE) for physical activity promotion among inactive patients with health conditions or risk factors. Whilst there is evidence for the initial effectiveness and cost-effectiveness of such schemes for increasing physical activity, evidence of long-term effects is limited. Techniques such as goal setting, self-monitoring and personalised feedback may support motivation for physical activity. Technologies such as activity monitoring devices provide an opportunity to enhance delivery of motivational techniques. This paper describes the PACERS study protocol, which aims to assess the feasibility and acceptability of implementing an activity monitor within the existing Welsh National Exercise Referral Scheme (NERS) and proposed evaluation methodology for a full-scale randomised controlled trial. Methods/design The PACERS study consists of a pilot randomised controlled trial, process evaluation and exploratory economic analyses. Participants will be recruited from the generic pathway of the Welsh NERS and will be randomly assigned to receive the intervention or usual practice. Usual practice is a 16-week structured exercise programme; the intervention consists of an accelerometry-based activity monitor (MyWellnessKey) and an associated web platform (MyWellnessCloud). The primary outcomes are predefined progression criteria assessing the acceptability and feasibility of the intervention and feasibility of the proposed evaluation methodology. Postal questionnaires will be completed at baseline (time 0: T0), 16 weeks after T0 (T1) and 12 months after T0 (T2). Routinely collected data will also be accessed at the same time points. A sub-sample of intervention participants and exercise referral staff will be interviewed following initiation of intervention delivery and at the end of the study. Discussion The PACERS study seeks to assess the feasibility of adding a novel motivational component to an existing effective intervention in order to enhance effects on physical activity and support longer-term maintenance. The study will provide insight into the acceptability of activity-monitoring technologies to an exercise referral population and delivery staff. Data from this study will be used to determine whether and how to proceed to a full-scale trial of effectiveness of the intervention, including any necessary refinements to intervention implementation or the proposed evaluation methodology. Trial registration ISRCTN85785652

Abstract Background Multi-level, longer-term obesity prevention interventions that focus on inequalities are scarce. Fun ‘n healthy in Moreland! aimed to improve child adiposity, school policies and environments, parent engagement, health behaviours and child wellbeing. Methods All children from primary schools in an inner urban, culturally diverse and economically disadvantaged area in Victoria, Australia were eligible for participation. The intervention, fun ‘n healthy in Moreland!, used a Health Promoting Schools Framework and provided schools with evidence, school research data and part time support from a Community Development Worker to develop health promoting strategies. Comparison schools continued as normal. Participants were not blinded to intervention status. The primary outcome was change in adiposity. Repeated cross-sectional design with nested longitudinal subsample. Results Students from twenty-four primary schools (clusters) were randomised (aged 5–12 years at baseline). 1426 students from 12 intervention schools and 1539 students from 10 comparison schools consented to follow up measurements. Despite increased prevalence of healthy weight across all schools, after 3.5 years of intervention there was no statistically significant difference between trial arms in BMI z score post-intervention (Mean (sd): Intervention 0.68(1.16); Comparison: 0.72(1.12); Adjusted mean difference (AMD): -0.05, CI: -0.19 to 0.08, p = 0.44). Children from intervention schools consumed more daily fruit serves (AMD: 0.19, CI:0.00 to 0.37, p = 0.10), were more likely to have water (AOR: 1.71, CI:1.05 to 2.78, p = 0.03) and vegetables (AOR: 1.23, CI: 0.99 to 1.55, p = 0.07), and less likely to have fruit juice/cordial (AOR: 0.58, CI:0.36 to 0.93, p = 0.02) in school lunch compared to children in comparison schools. More intervention schools (8/11) had healthy eating and physical activity policies compared with comparison schools (2/9). Principals and schools highly valued the approach as a catalyst for broader positive school changes. The cost of the intervention per child was $65 per year. Conclusion The fun n healthy in Moreland! intervention did not result in statistically significant differences in BMI z score across trial arms but did result in greater policy implementation, increased parent engagement and resources, improved child self-rated health, increased fruit, vegetable and water consumption, and reduction in sweet drinks. A longer-term follow up evaluation may be needed to demonstrate whether these changes are sustainable and impact on childhood overweight and obesity. Clinical trial registration ACTRN12607000385448 (Date submitted 31/05/2007; Date registered 23/07/2007; Date last updated 15/12/2009).

Introduction The associations between smoking prevalence, socioeconomic group and lung cancer outcomes are well established. There is currently limited evidence for how inequalities could be addressed through specific smoking cessation interventions (SCIs) for a lung cancer screening eligible population. This systematic review aims to identify the behavioural elements of SCIs used in older adults from low socioeconomic groups, and to examine their impact on smoking abstinence and psychosocial variables.Method Systematic searches of Medline, EMBASE, PsychInfo and CINAHL up to November 2018 were conducted. Included studies examined the characteristics of SCIs and their impact on relevant outcomes including smoking abstinence, quit motivation, nicotine dependence, perceived social influence and quit determination. Included studies were restricted to socioeconomically deprived older adults who are at (or approaching) eligibility for lung cancer screening. Narrative data synthesis was conducted.Results Eleven studies met the inclusion criteria. Methodological quality was variable, with most studies using self-reported smoking cessation and varying length of follow-up. There were limited data to identify the optimal form of behavioural SCI for the target population. Intense multimodal behavioural counselling that uses incentives and peer facilitators, delivered in a community setting and tailored to individual needs indicated a positive impact on smoking outcomes.Conclusion Tailored, multimodal behavioural interventions embedded in local communities could potentially support cessation among older, deprived smokers. Further high-quality research is needed to understand the effectiveness of SCIs in the context of lung screening for the target population.PROSPERO registration number CRD42018088956.

It is common to undertake qualitative research alongside randomised controlled trials (RCTs) when evaluating complex interventions. Researchers tend to analyse these datasets one by one and then consider their findings separately within the discussion section of the final report, rarely integrating quantitative and qualitative data or findings, and missing opportunities to combine data in order to add rigour, enabling thorough and more complete analysis, provide credibility to results, and generate further important insights about the intervention under evaluation. This paper reports on a 2 day expert meeting funded by the United Kingdom Medical Research Council Hubs for Trials Methodology Research with the aims to identify current strengths and weaknesses in the integration of quantitative and qualitative methods in clinical trials, establish the next steps required to provide the trials community with guidance on the integration of mixed methods in RCTs and set-up a network of individuals, groups and organisations willing to collaborate on related methodological activity. We summarise integration techniques and go beyond previous publications by highlighting the potential value of integration using three examples that are specific to RCTs. We suggest that applying mixed methods integration techniques to data or findings from studies involving both RCTs and qualitative research can yield insights that might be useful for understanding variation in outcomes, the mechanism by which interventions have an impact, and identifying ways of tailoring therapy to patient preference and type. Given a general lack of examples and knowledge of these techniques, researchers and funders will need future guidance on how to undertake and appraise them.

Polyploidization has played an important role in plant evolution. However, upon polyploidization, the process of meiosis must adapt to ensure the proper segregation of increased numbers of chromosomes to produce balanced gametes. It has been suggested that meiotic gene (MG) duplicates return to a single copy following whole genome duplication to stabilize the polyploid genome. Therefore, upon the polyploidization of wheat, a hexaploid species with three related (homeologous) genomes, the stabilization process may have involved rapid changes in content and expression of MGs on homeologous chromosomes (homeologs). To examine this hypothesis, sets of candidate MGs were identified in wheat using co-expression network analysis and orthology informed approaches. In total, 130 RNA-Seq samples from a range of tissues including wheat meiotic anthers were used to define co-expressed modules of genes. Three modules were significantly correlated with meiotic tissue samples but not with other tissue types. These modules were enriched for GO terms related to cell cycle, DNA replication, and chromatin modification and contained orthologs of known MGs. Overall, 74.4% of genes within these meiosis-related modules had three homeologous copies which was similar to other tissue-related modules. Amongst wheat MGs identified by orthology, rather than co-expression, the majority (93.7%) were either retained in hexaploid wheat at the same number of copies (78.4%) or increased in copy number (15.3%) compared to ancestral wheat species. Furthermore, genes within meiosis-related modules showed more balanced expression levels between homeologs than genes in non-meiosis-related modules. Taken together, our results do not support extensive gene loss nor changes in homeolog expression of MGs upon wheat polyploidization. The construction of the MG co-expression network allowed identification of hub genes and provided key targets for future studies.