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Abstract Background Housing insecurity can be understood as experiencing or being at risk of multiple house moves that are not through choice and related to poverty. Many aspects of housing have all been shown to impact children/young people’s health and wellbeing. However, the pathways linking housing and childhood health and wellbeing are complex and poorly understood. Methods We undertook a systematic review synthesising qualitative data on the perspectives of children/young people and those close to them, from the United Kingdom (UK). We searched databases, reference lists, and UK grey literature. We extracted and tabulated key data from the included papers, and appraised study quality. We used best fit framework synthesis combined with thematic synthesis, and generated diagrams to illustrate hypothesised causal pathways. Results We included 59 studies and identified four populations: those experiencing housing insecurity in general (40 papers); associated with domestic violence (nine papers); associated with migration status (13 papers); and due to demolition-related forced relocation (two papers). Housing insecurity took many forms and resulted from several interrelated situations, including eviction or a forced move, temporary accommodation, exposure to problematic behaviour, overcrowded/poor-condition/unsuitable property, and making multiple moves. Impacts included school-related, psychological, financial and family wellbeing impacts, daily long-distance travel, and poor living conditions, all of which could further exacerbate housing insecurity. People perceived that these experiences led to mental and physical health problems, tiredness and delayed development. The impact of housing insecurity was lessened by friendship and support, staying at the same school, having hope for the future, and parenting practices. The negative impacts of housing insecurity on child/adolescent health and wellbeing may be compounded by specific life circumstances, such as escaping domestic violence, migration status, or demolition-related relocation. Conclusion Housing insecurity has a profound impact on children and young people. Policies should focus on reducing housing insecurity among families, particularly in relation to reducing eviction; improving, and reducing the need for, temporary accommodation; minimum requirements for property condition; and support to reduce multiple and long-distance moves. Those working with children/young people and families experiencing housing insecurity should prioritise giving them optimal choice and control over situations that affect them.

ABSTRACT: The global food animal industry faces a growing concern regarding antimicrobial resistance (AMR), primarily driven by the use of antimicrobials (AM) for the treatment, control, and prevention of diseases. Addressing this challenge requires promoting responsible antimicrobial use (AMU) practices. In 2019, the province of Québec, Canada, took a significant step by implementing a regulation that limits the use of AM of very high importance for human medicine (category I AM as defined by Health Canada) in the food animal industry. However, the implementation of such regulation can significantly influence behavioral shifts among producers, contributing to the wider effort against AMR. Therefore, the objective of this observational study was to describe the perceived changes in dairy producers' knowledge and on-farm practices following the implementation of this regulation, using a cohort design. Data collection involved administering questionnaires to 87 dairy producers from 3 regions of the province of Québec (Estrie, Montérégie, Centre-Du-Québec) before (2017–2018) and after (2020–2021) the implementation of the regulation. The questionnaires explored the descriptive characteristics of farms, the knowledge of producers about the categorization of AM, the on-farm treatment practices, and the perceived effects of the regulation. Statistical analysis included t-tests and McNemar tests to compare the paired data obtained using the 2 questionnaires. The results indicated an increase in the knowledge score (the number of AM correctly categorized by the producers by their importance for human medicine) after the implementation of the regulation, suggesting an improved understanding of the categorization of AM based on their importance for human medicine. Trends in AMU practices for treating clinical mastitis and reproductive diseases suggested that category I AM were less likely to be reported as the primary treatment after the regulation, whereas category II AM were more often reported as primary treatment. Adoption of the selective dry cow therapy method significantly increased, whereas the use of teat sealants remained unchanged. Moreover, producers had divergent perceptions regarding the effect of the regulation on the cure rates and disease frequencies. This disparity emphasizes the need for comprehensive data collection to discern the risks associated with such regulatory shifts. The study acknowledges several limitations, including the potential for recall bias, confirmation bias, and desirability bias. Despite these limitations, this study shows that implementing regulations to encourage responsible AMU drives positive transformations in producers' knowledge and on-farm practices. This underscores the pivotal effect of proactive interventions in combating the escalating threat of AMR within the global food animal industry.

Abstract Background Improving the public’s understanding of how regional and socioeconomic inequalities create and perpetuate inequalities in health, is argued to be necessary for building support for policies geared towards creating a more equal society. However, research exploring public perceptions of health inequalities, and how they are generated, is limited. This is particularly so for young people. Our study sought to explore young people’s lived experiences and understandings of health inequalities. Methods We carried out focus group discussions (n = 18) with 42 young people, aged 13–21, recruited from six youth organisations in England in 2021. The organisations were located in areas of high deprivation in South Yorkshire, the North East and London. Young people from each organisation took part in three interlinked focus group discussions designed to explore their (i) perceptions of factors impacting their health in their local area, (ii) understandings of health inequalities and (iii) priorities for change. Due to the Covid-19 pandemic, most discussions took place online (n = 15). However, with one group in the North East, we carried out discussions face-to-face (n = 3). Data were analysed thematically and we used NVivo-12 software to facilitate data management. Results Young people from all groups demonstrated an awareness of a North-South divide in England, UK. They described how disparities in local economies and employment landscapes between the North and the South led to tangible differences in everyday living and working conditions. They clearly articulated how these differences ultimately led to inequalities in people’s health and wellbeing, such as linking poverty and employment precarity to chronic stress. Young people did not believe these inequalities were inevitable. They described the Conservative government as prioritising the South and thus perpetuating inequalities through uneven investment. Conclusions Our study affords important insights into young people’s perceptions of how wider determinants can help explain the North-South health divide in England. It demonstrates young people’s contextualised understandings of the interplay between spatial, social and health inequalities. Our findings support calls for pro-equity policies to address the structural causes of regional divides in health. Further research, engaging young people in deliberative policy analysis, could build on this work.

Abstract The majority of genic transcription is intronic. Introns are removed by splicing as branched lariat RNAs which require rapid recycling. The branch site is recognized during splicing catalysis and later debranched by Dbr1 in the rate-limiting step of lariat turnover. Through generation of a viable DBR1 knockout cell line, we find the predominantly nuclear Dbr1 enzyme to encode the sole debranching activity in human cells. Dbr1 preferentially debranches substrates that contain canonical U2 binding motifs, suggesting that branchsites discovered through sequencing do not necessarily represent those favored by the spliceosome. We find that Dbr1 also exhibits specificity for particular 5’ splice site sequences. We identify Dbr1 interactors through co-immunoprecipitation mass spectrometry. We present a mechanistic model for Dbr1 recruitment to the branchpoint through the intron-binding protein AQR. In addition to a 20-fold increase in lariats, Dbr1 depletion increases exon skipping. Using ADAR fusions to timestamp lariats, we demonstrate a defect in spliceosome recycling. In the absence of Dbr1, spliceosomal components remain associated with the lariat for a longer period of time. As splicing is co-transcriptional, slower recycling increases the likelihood that downstream exons will be available for exon skipping.

Abstract Microplastics and nanoplastics (collectively, MNPs) are increasingly entering soils, with potential adverse impacts to agriculture and groundwater. Environmental detection, characterization, and quantification of MNPs is difficult and subject to artifacts, often requiring labor-intensive separation from environmental matrices. These analytical challenges make it difficult to conduct experiments investigating specific MNP characteristics influencing their transport and fate, particularly when examining multiple plastic types at low concentrations. By synthesizing a suite of metal-tagged polymers, which are cryomilled to create polydisperse fragmented particle suspensions, single particle ICP-MS (spICP-MS) can be used to quantify MNP particle size and concentration in controlled fate and transport studies. Use of unique metal-polymer pairs enables accurate, simultaneous analysis of multiple MNP types which can be used to track total particle transport and retention within a variety of environmental matrices. This was demonstrated using saturated sand column transport experiments to quantify the movement of two plastics having different properties: tin-tagged polystyrene (Sn-PS) and tantalum-tagged polyvinylpyrrolidone (Ta-PVP). The behavior of these polydisperse, fragmented MNPs was compared to that of fluorescent, carboxylated monodisperse PS spherical microspheres (Fl-PS). Mobility of all MNP types increased with decreasing particle size, and hydrophilic Ta-PVP particles migrated more effectively than the hydrophobic Sn-PS particles. Furthermore, the addition of humic acid (HA) to the carrier solution increased the colloidal stability of both metal-tagged MNP suspensions, resulting in much greater elution from the column than in HA-free deionized water or moderately- hard water (ionic strength = 5mM). This combination of particle synthesis and spICP-MS analysis provides insights into the transport of MNP having physical properties that are representative of environmental MNPs and opens up a broad range of applications for study of MNP environmental fate and transport.

The pre-mRNA life cycle requires intron processing; yet, how intron-processing defects influence splicing and gene expression is unclear. Here, we find that TTDN1/MPLKIP, which is encoded by a gene implicated in non-photosensitive trichothiodystrophy (NP-TTD), functionally links intron lariat processing to spliceosomal function. The conserved TTDN1 C-terminal region directly binds lariat debranching enzyme DBR1, whereas its N-terminal intrinsically disordered region (IDR) binds the intron-binding complex (IBC). TTDN1 loss, or a mutated IDR, causes significant intron lariat accumulation, as well as splicing and gene expression defects, mirroring phenotypes observed in NP-TTD patient cells. A Ttdn1-deficient mouse model recapitulates intron-processing defects and certain neurodevelopmental phenotypes seen in NP-TTD. Fusing DBR1 to the TTDN1 IDR is sufficient to recruit DBR1 to the IBC and circumvents the functional requirement for TTDN1. Collectively, our findings link RNA lariat processing with splicing outcomes by revealing the molecular function of TTDN1.

Abstract Background Intersecting socioeconomic and demographic reasons for physical activity (PA) inequalities are not well understood for young people at risk of experiencing marginalisation and living with disadvantage. This study explored young people’s experiences of PA in their local area, and the associated impacts on opportunities for good physical and emotional health and wellbeing. Methods Seven local youth groups were purposefully sampled from disadvantaged areas across urban, rural and coastal areas of England, including two that were specifically for LGBTQ + young people. Each group engaged in three interlinked focus groups which explored young people’s perceptions and lived experience of PA inequalities. Data were analysed using an inductive, reflexive thematic approach to allow for flexibility in coding. Results Fifty five young people aged 12–21 years of different sexualities, gender and ethnicity took part. Analysis yielded four themes: PA experiences across spaces; resigned to a lack of inclusivity and ‘belonging’; safety first; complexities in access and accessibility. Young people felt more comfortable to be active in spaces that were simpler to navigate, particularly outdoor locations largely based in nature. In contrast, local gyms and sports clubs, and the school environment in general, were spoken about often in negative terms and as spaces where they experienced insecurity, unsafety or discomfort. It was common for these young people to feel excluded from PA, often linked to their gender and sexuality. Lived experiences or fears of being bullied and harassed in many activity spaces was a powerful message, but in contrast, young people perceived their local youth club as a safe space. Intersecting barriers related to deprivation, gender and sexuality, accessibility, disability, Covid-19, affordability, ethnicity, and proximity of social networks. A need emerged for safe spaces in which young people can come together, within the local community and choose to be active. Conclusions The overarching concept of ‘physical activity insecurity’ emerged as a significant concern for the young people in this study. We posit that PA insecurity in this context can be described as a limited or restricted ability to be active, reinforced by worries and lived experiences of feeling uncomfortable, insecure, or unsafe.

Abstract Background The anxiety and their related disorders (AD) are the most common of all mental health conditions, and affect approximately 20% of pregnant and postpartum people. They are associated with significant distress and life interference for sufferers, as well as negative consequences for fetal and infant development. At present, little if any routine screening for prenatal AD is being conducted and data regarding the most effective tools to screen for these disorders is lacking. The majority of screening studies suffer from methodological difficulties which undermine the confidence needed to recommend measures for population distribution. The primary purpose of this research is to identify the most accurate self-report tool(s) to screen for perinatal AD. Methods A large, prospective cohort of pregnant people (N = 1,000) is being recruited proportionally across health service delivery regions in British Columbia (BC). The screening accuracy of a broad range of perinatal AD self-report measures are being assessed using gold standard methodology. Consenting individuals are administered online questionnaires followed by a semi-structured diagnostic interview between 16- and 36-weeks’ gestation, and again between 6 and 20 weeks postpartum. Questionnaires include all screening measures, measures of sleep and unpaid family work, and questions pertaining to demographic and reproductive history, COVID-19, gender role burden, and mental health treatment utilization. Interviews assess all current anxiety disorders, as well as obsessive–compulsive disorder, and posttraumatic stress disorder. Discussion This research is in response to an urgent demand for accurate perinatal AD screening tools based on high quality evidence. AD among perinatal people often go unidentified and untreated, resulting in continued suffering and life impairment. Findings from this research will inform healthcare providers, policymakers, and scientists, about the most effective approach to screening for anxiety and related disorders in pregnancy in the postpartum period.

Abstract Background The removal of introns occurs through the splicing of a 5′ splice site (5′ss) with a 3′ splice site (3′ss). These two elements are recognized by distinct components of the spliceosome. However, introns in higher eukaryotes contain many matches to the 5′ and 3′ splice-site motifs that are presumed not to be used. Results Here, we find that many of these sites can be used. We also find occurrences of the AGGT motif that can function as either a 5′ss or a 3′ss—previously referred to as dual-specific splice sites (DSSs)—within introns. Analysis of the Sequence Read Archive reveals a 3.1-fold enrichment of DSSs relative to expectation, implying synergy between the ability to function as a 5′ss and 3′ss. Despite this suggested mechanistic advantage, DSSs are 2.7- and 4.7-fold underrepresented in annotated 5′ and 3′ splice sites. A curious exception is the polyubiquitin gene UBC, which contains a tandem array of DSSs that precisely delimit the boundary of each ubiquitin monomer. The resulting isoforms splice stochastically to include a variable number of ubiquitin monomers. We found no evidence of tissue-specific or feedback regulation but note the 8.4-fold enrichment of DSS-spliced introns in tandem repeat genes suggests a driving role in the evolution of genes like UBC. Conclusions We find an excess of unannotated splice sites and the utilization of DSSs in tandem repeats supports the role of splicing in gene evolution. These findings enhance our understanding of the diverse and complex nature of the splicing process.

This study aimed to identify contamination sources in raw milk and cheese on small farms in Brazil by isolating Escherichia coli at various stages of milk production and cheese manufacturing. The study targeted EAEC, EIEC, ETEC, EPEC, STEC, and ExPEC pathotypes, characterizing isolates for the presence of virulence genes, phylogroups, antimicrobial susceptibility, and phylogenetic relationships using PFGE and MLST. The presence of antimicrobial resistance genes and serogroups was also determined. Three categories of E. coli were identified: pathogenic, commensal, and ceftriaxone-resistant (ESBL) strains. Pathogenic EPEC, STEC, and ExPEC isolates were detected in milk and cheese samples. Most isolates belonged to phylogroups A and B1 and were resistant to antimicrobials such as nalidixic acid, ampicillin, kanamycin, streptomycin, sulfisoxazole, and tetracycline. Genetic analysis revealed that E. coli with identical virulence genes were present at different stages within the same farm. The most frequently identified serogroup was O18, and MLST identified ST131 associated with pathogenic isolates. The study concluded that E. coli was present at multiple points in milk collection and cheese production, with significant phylogroups and high antimicrobial resistance. These findings highlight the public health risk posed by contamination in raw milk and fresh cheese, emphasizing the need to adopt hygienic practices to control these microorganisms.

Abstract Background The LOw RISk DCIS (LORIS) study was set up to compare conventional surgical treatment with active monitoring in women with ductal carcinoma in situ (DCIS). Recruitment to trials with a surveillance arm is known to be challenging, so strategies to maximise patient recruitment, aimed at both patients and recruiting centres, were implemented. Methods Women aged ≥ 46 years with a histologically confirmed diagnosis of non-high-grade DCIS were eligible for 1:1 randomisation to either surgery or active monitoring. Prior to randomisation, all eligible women were invited to complete: (1) the Clinical Trials Questionnaire (CTQ) examining reasons for or against participation, and (2) interviews exploring in depth opinions about the study information sheets and film. Women agreeing to randomisation completed validated questionnaires assessing health status, physical and mental health, and anxiety levels. Hospital site staff were invited to communication workshops and refresher site initiation visits to support recruitment. Their perspectives on LORIS recruitment were collected via surveys and interviews. Results Eighty percent (181/227) of eligible women agreed to be randomised. Over 40% of participants had high anxiety levels at baseline. On the CTQ, the most frequent most important reasons for accepting randomisation were altruism and belief that the trial offered the best treatment, whilst worries about randomisation and the influences of others were the most frequent most important reasons for declining. Most women found the study information provided clear and useful. Communication workshops for site staff improved knowledge and confidence but only about half said they themselves would join LORIS if eligible. The most common recruitment barriers identified by staff were low numbers of eligible patients and patient preference. Conclusions Recruitment to LORIS was challenging despite strategies aimed at both patients and site staff. Ensuring that recruiting staff support the study could improve recruitment in similar future trials. Trial registration ISRCTN27544579, prospectively registered on 22 May 2014

Nurse leaders manage complex workplace demands. Coaching skills are a core leadership competency which can assist them in their roles. However, training alone may not always effect positive leadership change. This randomised trial sought to compare outcomes of leadership coaching training, with and without follow-up support, against waitlist control. Psychometric and professional achievement outcomes for 86 Australian nurse leaders were tracked for six months. Trial results provide empirical support for the hypothesis that leadership coaching training, paired with coaching follow-up, yields superior outcomes to a training only approach and, versus control, in terms of leadership and communication-related outcomes.

BackgroundDNA sequencing is increasingly incorporated into the routine care of cancer patients, many of whom also carry inherited, moderate/high-penetrance variants associated with other diseases. Yet, the prevalence and consequence of such variants remain unclear.MethodsWe analyzed the germline genomes of 10,389 adult cancer cases in the TCGA cohort, identifying pathogenic/likely pathogenic variants in autosomal-dominant genes, autosomal-recessive genes, and 59 medically actionable genes curated by the American College of Molecular Genetics (i.e., the ACMG 59 genes). We also analyzed variant- and gene-level expression consequences in carriers.ResultsThe affected genes exhibited varying pan-ancestry and population-specific patterns, and overall, the European population showed the highest frequency of pathogenic/likely pathogenic variants. We further identified genes showing expression consequence supporting variant functionality, including altered gene expression, allelic specific expression, and mis-splicing determined by a massively parallel splicing assay.ConclusionsOur results demonstrate that expression-altering variants are found in a substantial fraction of cases and illustrate the yield of genomic risk assessments for a wide range of diseases across diverse populations.

Abstract Background Improving the health and well-being of young people is a public health priority. Schools present an ideal setting to implement strategies to improve young people’s health and well-being. A key strategy involves conducting surveys to assess student health needs, inform interventions, and monitor health over time. Conducting research in schools is, however, challenging. Schools can find it difficult to participate and adhere to research processes, even when they are keen to be involved in research, because of competing priorities (e.g., attendance and educational achievement), as well as time and resource constraints. There is a lack of literature on the perspectives of school staff and other key stakeholders working in young people’s health on how best to work with schools to conduct health research, and in particular, health surveys. Methods Participants (n = 26) included members of staff from 11 secondary schools (covering students aged 11–16 years), 5 local authority professionals, and 10 wider key stakeholders in young people's health and well-being (e.g., a school governor, a national government member), based in South West England. Participants took part in semi-structured interviews that were conducted either over the phone or via an online platform. Data were analysed using the Framework Method. Results Three main themes were identified: Recruitment and Retention, Practicalities of Data Collection in Schools, and Collaboration from Design to Dissemination. It is important to acknowledge the role of local authorities and academy trusts in the English education system, and work closely with these when conducting school-based health surveys. School staff prefer to be contacted about research via email and in the summer term, following exams. Researchers should contact a member of staff involved in student health/well-being, as well as senior leadership, during recruitment. Data collection during the start and end of the school year is undesirable. Research should be collaborative with school staff and young people, consistent with school priorities and values, and flexible and tailored to school timetables and resources. Conclusions Overall the findings demonstrate that survey-based research methods should be school-led and tailored to each school.

BackgroundSince the early 2000s, there have been marked trends in adolescent health and wellbeing indicators across Europe, North America and Australia. In particular, there have been substantial declines in youth drinking. We know little about how these trends are underpinned by co-occurring indicators within individuals. This paper aims to analyse change over time in how indicators cluster within individuals and differences in these patterns between five countries with different trends in youth drinking.MethodsWe analysed four waves of repeat cross-sectional survey data from 15-year-olds in England (n = 5942), Italy (n = 5234), the Netherlands (n = 5408), Hungary (n = 5274), and Finland (n = 7446), which were included in the Health Behaviours in School-aged Children (HBSC) study between 2001/02 and 2013/14. We defined clusters of individuals using multigroup latent class analyses which accounts for change over time. The class indicators included health behaviours, attitudes, wellbeing and relationships. We modelled associations between class membership, sex, and family affluence over time.ResultsWe identified four classes in all countries: Overall unhealthy, Overall healthy, Moderately healthy and Substance abstainers with behaviour risk indicators. The proportion of adolescents in the Overall unhealthy class declined between 2001/02 and 2013/14 by between 22.8 percentage points (pp) in England and 3.2pp in Italy. The extent to which indicators of health and wellbeing changed as linked clusters differed across countries, but changes in alcohol consumption, smoking, drug use and sexual activity were typically concurrent. Adolescents with low family affluence were more likely to be in the Overall unhealthy class in all years.ConclusionsImprovements in indicators of adolescent health and well-being are due mainly to concurrent declines in drinking, smoking, sexual activity, and cannabis use, but these declines are not consistently associated with improvements in other domains. They have also not led to reductions in inequalities in indicators of health and well-being.

Background. Ictal arrhythmia is a rare condition that causes arrhythmic manifestations induced by epileptic seizures, including asystole or bradycardia. Ictal asystole (IA) is a very rare condition found in patients undergoing video-encephalography (EEG) monitoring. It is often related to temporal lobe epilepsy and can cause syncope, which can lead to injury or even death. Case Presentation. Two patients with epilepsy showed symptoms of syncope. Both patients underwent 4-day ambulatory EEG tests and were diagnosed with IA. Following the tests, the patients were implanted with a permanent pacemaker, and one of them underwent a temporal lobectomy. As a result of these procedures, the patients experienced a reduction in episodes of symptomatic syncope. Conclusion. Patients with ictal asystole and symptomatic ictal bradycardia are at increased risk of falls due to seizures. Although there are no specific guidelines for managing this condition, antiseizure medications, epilepsy surgery, and cardiac pacemaker implantation have been effective treatments.

Antimicrobial resistance can be effectively limited by improving the judicious use of antimicrobials in food production. However, its effect on the spread of AMR genes in animal populations is not well described. In the province of Québec, Canada, a new legislation implemented in 2019 has led to an unprecedented reduction in the use of critical antimicrobials in dairy production. We aimed to investigate the potential link between ESBL/AmpC E. coli isolated before and after legislation and to determine the presence of plasmids carrying genes responsible for critical AMR. We collected fecal samples from calves, cows, and manure pit from 87 Québec dairy farms approximately 2 years before and 2 years after the legislation came into effect. The whole genomes of 183 presumptive ESBL/AmpC E. coli isolated after cefotaxime enrichment were sequenced. Their phylogenetic characteristics (MLST, serogroup, cgMLST) and the presence of virulence and resistance genes and replicons were examined. A maximum likelihood phylogenetic tree was constructed based on single nucleotide polymorphism (SNPs). We identified 10 clonal lineages (same cgMLST) and 7 clones (SNPs ≤ 52). Isolates belonging to these clones could be found on different farms before and after the legislation, strongly suggesting a clonal spread of AMR genes in the population during this 4-year period. All isolates were multidrug resistant (MDR), with clone 2 being notable for the presence of macrolide, fluoroquinolone, and third-generation cephalosporin resistance genes. We also identified clinically relevant ExPEC (ST10) and APEC-like lineages (ST117, ST58, ST88) associated with the presence of ExPEC and APEC virulence genes, respectively. Our data also suggests the presence of one epidemic plasmid belonging to the IncY incompatibility group and carrying qnrs1 and blaCTX–M–15. We demonstrated that AMR genes spread through farms and can persist over a 4-year period in the dairy cattle population through both plasmids and E. coli clones, despite the restriction of critical antimicrobial use. MDR ExPEC and APEC-like STs are present in the normal microbiota of cattle (more frequently in calves). These data increase our knowledge on gene dissemination dynamics and highlight the fact that biosecurity measures should be enhanced in this industry to limit such dissemination.

IntroductionSupporting adolescents with their health and wellbeing is an international public health priority. Schools are well placed to universally detect unmet health needs and support pupils. This study aimed to evaluate the effectiveness of a digital health and wellbeing screening tool, called the 'Digital Health Contact' (DHC) implemented in schools in the East Midlands of England. The DHC, delivered by Public Health Nurses (School Nurses) (PHN(SN)), aims to identify pupils with unmet health needs (via a 'red flag' system) and provide appropriate support.Materials and methodsUsing data from 22 schools which took part in the DHC and 14 schools which did not take part, across three academic years (2018-2020), we conducted a controlled interrupted timeseries analysis with negative binomial regression to explore the effect of the DHC on the number of annual referrals to PHN(SN). Using DHC data from 164 pupils, we further conducted a Difference-in-Difference analysis to explore the impact of 'red flag' and referral via the DHC in Year 9 (age 13-14) on the number of red flags in Year 11 (age 15-16).ResultsAcross all schools, the mean annual number of referrals increased over the three year follow-up period. In the adjusted model, the number of referrals was comparable between schools taking part in the DHC and non-participating schools (0.15 referrals [95% CI -0.21, 0.50]). Red flag score was not significantly different among Year 11 pupils, after being referred via the DHC in Year 9 (-0.36 red flags [95% CI -0.97, 0.24]).DiscussionThe DHC, and similar screening tools, have the potential to raise awareness of the health and wellbeing support in schools and provide an additional pathway of referral to this support for pupils with unmet health needs, without replacing the traditional pathway where pupils refer themselves or are referred by teachers.

Background Housing insecurity can be understood as experiencing or being at risk of multiple house moves that are (1) not through choice and (2) related to poverty. For example, due to short-term private rental tenancies, temporary or emergency housing, and homelessness. Housing insecurity has grown due to recent trends in the cost and availability of housing. The quality, affordability and stability of housing have all been shown to impact children’s health and well-being. However, the pathways linking housing and child health and well-being are complex and poorly understood. Objectives To identify, appraise and synthesise research evidence that explores the relationship between housing insecurity and the health and well-being of children and young people. Data sources MEDLINE via Ovid (searched 8 April 2022), EMBASE via Ovid (searched 8 April 2022), PsycINFO via Ovid (searched 8 April 2022). Review methods We undertook a systematic review synthesising qualitative data. We searched databases, reference lists and United Kingdom grey literature. We extracted and tabulated key data from the included papers, and appraised study quality. We synthesised the data qualitatively into an a priori conceptual framework using best-fit framework synthesis combined with thematic synthesis, and generated logic models to highlight links between specific exposures, impacts and outcomes. Results We included 59 studies and identified four populations: those experiencing housing insecurity in general (40 papers); associated with domestic violence (nine papers); associated with migration status (13 papers) and those forced to relocate due to demolition (two papers). Most published studies had an overall assessment of moderate-high quality, and most grey literature originated from known and valued sources. Housing insecurity took many forms and resulted from several, often inter-related, situations, including being evicted or having a forced move, living in temporary accommodation, exposure to problematic behaviour, overcrowded/poor-condition/unsuitable property, and making multiple moves. The resultant housing insecurity had multiple impacts, including school-related, psychological, financial and family well-being impacts, long-distance travel to attend school and see friends, living in a poor-condition or unsuitable property, all of which could further exacerbate housing insecurity. These experiences impacted health and well-being, in terms of mental health problems (often manifesting physically/behaviourally) and physical health problems related to poor housing conditions. Some factors lessened the impact of housing insecurity, including friendship and support, staying at the same school, having hope for the future and protective parenting. The negative impacts of housing insecurity on health and well-being may be compounded by specific situations and life circumstances, such as escaping domestic violence, migration status, or a forced relocation due to housing demolition. Limitations Many accounts were from parents or other informants, and more data directly from children and young people may give a more nuanced picture. Likewise, there was little information relating to outcomes, and it is difficult to know whether the current evidence has captured all relevant outcomes, and the links from impacts to health and well-being outcomes are less well understood. The complexity and diversity of the data added additional challenges to the synthesis process. Conclusions Our findings suggest that policies should focus on reducing housing insecurity among families, particularly in relation to reducing eviction, improving and reducing the need for temporary accommodation, minimum requirements for property condition, and support to reduce multiple moves and moves far from families’ desired location. Those working with children and families experiencing housing insecurity should give them optimal choice and control over situations that affect them. Future work Future qualitative research should focus explicitly on the health and well-being of children and young people experiencing housing insecurity, and how it links with the impacts identified in the current review, foregrounding the accounts of children and young people themselves, including specific groups of young people who are likely to be marginalised. Qualitative research focusing on the impact of interventions to address housing insecurity among families in the United Kingdom is also needed. Study registration This study is registered as PROSPERO CRD42022327506. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (Award ref: NIHR135455) and is published in full in Public Health Research; Vol. 11, No. 13. See the NIHR Funding and Awards website for further award information. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Plain language summary Introduction Housing insecurity is being at risk of moving house many times, due to poverty and having no choice, for example, due to a short-term rental house/flat, emergency housing and homelessness. Children’s health and well-being are known to be affected by how suitable, affordable and stable their housing is. However, the reasons for this are poorly understood. Methods We looked for studies exploring how housing insecurity can affect the health and well-being of children and young people (aged 0–16) in the United Kingdom. We included the views of children, parents/close family members and professionals (e.g. teachers). We searched for studies published in academic journals, searched relevant websites and received suggestions from experts. Results We included 59 studies on the impact of housing insecurity on young people. We found that children are affected in many ways including their social life (e.g. being far from friends), schooling (e.g. joining a new school), health, financial and family well-being. This led to anxiety/stress, trouble eating and sleeping, wetting the bed and health problems, such as asthma, due to poor living conditions. Some things can help to protect children experiencing housing insecurity, including friendship and support, staying at the same school, and support from parents. The problems of housing insecurity may be made worse by life circumstances, including domestic violence, being a migrant/refugee/asylum seeker and a forced relocation. Most studies included parents/professionals, with few seeking the views of the children and young people themselves. Conclusions Our review suggests that it is important to reduce housing insecurity among families. All those working with children and families experiencing housing insecurity should give them as much choice and control over situations that affect them as possible. Future studies should gather the views of children and young people themselves. Scientific summary Introduction Housing insecurity can be understood as experiencing or being at risk of multiple house moves that are (1) not through choice and (2) related to poverty. This may include a range of precarious housing situations (e.g. private rental accommodation with short-term or insecure tenancy agreements; temporary or emergency housing and homelessness). Housing insecurity has grown as a result of a number of trends in the cost and availability of housing, reflecting in particular the rapid increase in the number of low-income families with children in the private rental sector. The evidence from cohort studies that show a relationship between housing insecurity, homelessness or frequent moves in childhood and health-related outcomes can usefully quantify the proportion of children and families at risk of poorer health associated with housing instability. Such evidence, however, cannot determine causal associations, and the complex pathways linking housing and child health and well-being have not been synthesised. Objectives The current review aimed to identify, appraise and synthesise research evidence that explores the relationship between housing insecurity and the health and well-being of children and young people (CYP). We aimed to highlight the relevant factors and causal mechanisms. Methods We undertook a systematic review synthesising qualitative data, employing elements of rapid review methodology. Database searches [of MEDLINE, EMBASE, PsycINFO, Applied Social Sciences Index and Abstracts (ASSIA), International Bibliography of the Social Sciences (IBSS) and the Social Sciences Citation Index] were accompanied by scrutiny of reference lists of included papers and relevant systematic reviews, and grey literature searching of key websites, including those identified by stakeholders. We extracted and tabulated key data from the included papers. Data extraction was performed by one reviewer, with a 10% sample checked by a second reviewer. We appraised study quality of the published literature using the Critical Appraisal Skills Programme (CASP) qualitative checklist, and the quality of grey literature sources using the authority, accuracy, coverage, objectivity, date, significance (AACODS) checklist. Before commencing the review, we developed an initial a priori conceptual framework in consultation with stakeholders and topic experts, to inform and guide the review and synthesis. The framework consisted of: the policy context, population, exposures, impacts (i.e. interim outcomes) and outcomes (health and well-being outcomes in childhood/youth). We synthesised the data qualitatively into the conceptual framework using best-fit framework synthesis combined with thematic synthesis, and generated logic models to highlight the links between specific exposures, impacts and outcomes by population. Inclusion criteria Population The population included families with children aged 0–16 experiencing or at risk of housing insecurity, living in a family unit, in the UK. This could include, but not be limited to, those on low incomes, lone parents and ethnic minority groups including migrants, refugees and asylum seekers. Informants could include the children themselves, parents/close family members (e.g. grandparents, if the children live with them), or other informants with insight into the child’s/children’s experiences (e.g. teachers, clinicians). Children outside a family unit (i.e. who had left home or who were being looked after by the local authority) and traveller families were excluded. Exposure We defined ‘housing insecurity’ according to the Children’s Society (3) definition: those experiencing and at risk of multiple moves that are (1) not through choice and (2) related to poverty. This included actual or perceived insecurity related to housing situations, which may include the following: private rental accommodation with short-term or insecure tenancy agreements; temporary emergency housing; homelessness (including ‘hidden’ homelessness). We also aimed to include research related to interventions that have the specific aim of reducing housing insecurity and/or mitigating the impact of housing insecurity on the health and well-being of children, where identified. Context The current UK policy context shows exacerbation of factors that can lead to housing insecurity. These include the following: trends in poverty and inequality exacerbated by the COVID pandemic; changes in the housing market (an increase in investment properties, loss of social housing); increased numbers of low-income families living in the private rental sector; insecure or short-term tenancies; increasing housing costs (and fuel/food costs) and lack of affordable properties (see Background). Outcomes Any reported immediate and short-term outcomes related to childhood mental and physical health and well-being (up to the age of 16) were included. Studies reporting on the long-term outcomes and impacts in adulthood of housing insecurity experienced in childhood were excluded, as were short-term outcomes reported by adults. Studies We included studies reporting qualitative data on the views of young people and/or parents with young children on how housing insecurity has impacted on their (or their children’s) well-being. Books (with the exception of searchable e-books) and dissertations were excluded. Conference abstracts were only included if they contained relevant data unavailable elsewhere. Results In total, 59 studies were included in the review, which included 16 from database searches, 37 from grey literature searches, and 6 from reference lists of included studies and relevant reviews. Most published studies had an overall assessment of moderate-high quality, although few reported reflexivity. Most of the grey literature included originated from known and valued sources, and although methodologies and methods were often poorly described, primary data in the form of quotations were usually available. We identified four distinct populations for which research evidence was available during the process of study selection and data extraction: general population (housing insecurity in general) (reported in 40 papers) domestic violence population (housing insecurity associated with domestic violence) (reported in nine papers) migrant, refugee and asylum seeker population (housing insecurity associated with migration status) (reported in 13 papers) relocation population (families forced to relocate due to planned demolition) (reported in two papers). We detected all elements of the conceptual framework in the data from the included studies and identified an additional element through thematic synthesis: protective factors. We included this new element in our logic models and constructed a separate logic model for each population. Although we anticipated potentially different experiences of housing insecurity and its impacts and outcomes across the four populations, the evidence reviewed suggests many similarities across all the populations in terms of impacts, exposures, outcomes and protective factors. Common exposures included being evicted or having a forced move, living in temporary accommodation, experiencing overcrowding, exposure to problematic behaviour, poor-condition/unsuitable property and making multiple moves. Common impacts included social, school-related, psychological, financial and family well-being impacts, having to travel long distances to attend school and see friends, having to live in a property that was unsuitable or in a poor state of repair, overcrowded and often noisy, all of which could then further exacerbate housing insecurity. Common outcomes reported were mental health problems (which could manifest in physical ways, e.g. trouble eating and sleeping, or wetting the bed) and physical health problems, such as skin complaints and asthma related to poor housing conditions. Protective factors common to several populations included friendship and support, staying at the same school, having hope for the future, and protective parenting. Pervasive throughout all populations and accounts was an overall lack of choice or control over the housing situation. In addition, some considerations specific to certain populations were identified. In the domestic violence population, there was an additional consideration of the family choosing to remain in the property or leave the property, but both options came with insecurity attached, as those who stayed were not sure if they would be evicted due to the perpetrator defaulting on the mortgage. Some positive results were reported in relation to an intervention that helped families to feel safe if they chose to stay in their property (the Sanctuary Scheme), which reduced fear related to the perpetrator returning. Housing insecurity negatively impacted on friendships in all populations, with CYP reporting greater difficulty in forming close bonds and a peer network in each new location. However, this could be potentially more challenging for those escaping domestic violence, due to the need to keep information about themselves confidential to keep the family safe. In the migrant, refugee and asylum seeker population, parents and children spoke of having very little notice before having to move out of a property, in some cases only 48 hours. This could lead to a housing emergency for the family, and in this population there were several accounts of families becoming homeless and having to sleep in unsuitable places, such as the accident and emergency (A&E) waiting room and on a night bus. In some families, parents had no recourse to public funds, so even in cases where a child or children were born in the UK, the family still ended up destitute and homeless. This situation caused significant worry for the parents, which in turn was perceived and experienced by the children. A key commonality across everyone in the relocation population was that they were forced to move by a particular date, as their property (a flat in a high-rise block) was scheduled for demolition. Many families desired a move, due to a lack of space, overcrowding and unsafe outdoor spaces; however, many did not want to leave behind social networks and schools in the community, and even some who wanted to move had difficulty finding a property that was suitable (e.g. for their family size). In synthesising the evidence, a key challenge was the complexity of the data, in particular of the relationships between exposures and impacts. Factors that were exposures in the first instance could then become impacts, and particular impacts could then drive housing insecurity. Another key challenge in synthesising the qualitative evidence was that many elements of the experience of housing insecurity have been separated out in the logic models, but are likely to have been experienced simultaneously by the CYP, such that the experience of these elements may have been conflated and difficult to separate out. It has been particularly challenging to highlight this complexity in our synthesis. Policy-makers and practitioners should consider that the logic models presented here may be somewhat simplified, and that conflation of the factors represented as well as complexity in relationships is likely to occur among families experiencing housing insecurity. Conclusions Housing insecurity among CYP in families in the UK can take many forms and result from several, often inter-related, situations including being evicted or having a forced move, living in temporary accommodation, experiencing overcrowding, exposure to problematic behaviour, poor-condition/unsuitable property, and making multiple moves. The resultant housing insecurity can have multiple (often simultaneous) impacts, including school-related, psychological, financial and family well-being impacts, having to travel long distances to attend school and see friends, having to live in a property that was unsuitable or in a poor state of repair, overcrowded and often noisy, all of which could then further exacerbate housing insecurity. These experiences can impact on health and well-being, in terms of mental health problems (which could manifest in physical ways) and physical health problems related to poor housing conditions. Some experiences and situations can lessen the impact of housing insecurity, including friendship and support, staying at the same school, having hope for the future and protective parenting; and in some groups, as the relocation population, influencing the decision was also a protective factor. The negative impacts of housing insecurity on health and well-being may be compounded by specific situations and life circumstances, such as escaping domestic violence, being a migrant, refugee or asylum seeker (or having a parent with that status), or a forced relocation due to housing demolition. Our review findings suggest that policies should focus on reducing housing insecurity among families, particularly in relation to reducing eviction, improving and reducing the need for temporary accommodation, minimum requirements for property condition, and support to reduce multiple moves and moves far from families’ desired location. All those working with children and families experiencing housing insecurity should give them optimal choice and control over situations that affect them, as far as possible. Study registration This study is registered as PROSPERO CRD42022327506. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: NIHR135455) and is published in full in Public Health Research; Vol. 11, No. 13. See the NIHR Funding and Awards website for further award information. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

In England, the proportion of 13–15 year-olds who have ever drunk alcohol fell from 71% in 1999 to 35% in 2019. Despite substantial research literature studying this decline, we know little about connections with concurrent shifts in wider aspects of health and wellbeing. This paper aims to identify how indicators of health and wellbeing cluster within 15-year-olds in England, identify changes in clustering over time, and explore associations with sex and family affluence. We used latent class analysis of cross-sectional data from the Health Behaviours in School-aged Children study (n = 5,942; four waves 2001/02–2013/14). Classes were defined by indicators of substance use, sexual activity, diet, exercise, school-related measures, e-media use, parental relationships, and wellbeing. We identified three classes, which we labelled Overall unhealthy, Substance abstainers with behavioural risk indicators, and Overall healthy. The probability of being in the Overall unhealthy class fell (2001/02: 0.39; 2013/14: 0.18) while the probability of being in the Overall healthy class increased (0.21 to 0.41). The probability of weekly alcohol use fell in all classes (e.g. Overall unhealthy: 0.71 to 0.28). Females (female vs male OR: 1.74 95%CI: 1.30 – 2.34) and those with low family affluence (high vs low family affluence OR: 0.18 95%CI: 0.08 – 0.44) had significantly higher odds of being in the Overall unhealthy class. Overall, adolescents became more likely to have co-occurring indicators of good health and wellbeing, including reduced alcohol consumption, sexual activity and cigarette smoking. However, girls and those from poorer families remained more likely to have poor health and wellbeing.

Knowledge of genomic features specific to the human lineage may provide insights into brain-related diseases. We leverage high-depth whole genome sequencing data to generate a combined annotation identifying regions simultaneously depleted for genetic variation (constrained regions) and poorly conserved across primates. We propose that these constrained, non-conserved regions (CNCRs) have been subject to human-specific purifying selection and are enriched for brain-specific elements. We find that CNCRs are depleted from protein-coding genes but enriched within lncRNAs. We demonstrate that per-SNP heritability of a range of brain-relevant phenotypes are enriched within CNCRs. We find that genes implicated in neurological diseases have high CNCR density, including APOE, highlighting an unannotated intron-3 retention event. Using human brain RNA-sequencing data, we show the intron-3-retaining transcript to be more abundant in Alzheimer's disease with more severe tau and amyloid pathological burden. Thus, we demonstrate potential association of human-lineage-specific sequences in brain development and neurological disease.

Abstract Background There is an increased need for prevention and early intervention surrounding young people’s health and well-being. Schools offer a pivotal setting for this with evidence suggesting that focusing on health within schools improves educational attainment. One promising approach is the creation of School Health Research Networks which exist in Wales and Scotland, but are yet to be developed and evaluated in England. Methods This qualitative process evaluation aimed to identify the main barriers and facilitators to implementing a pilot School Health Research Network in the South West of England (SW-SHRN). Semi-structured interviews were conducted with school staff, local authority members, and other key stakeholders. Interview data were analysed using the 7-stage framework analysis approach. Results Four main themes were identified from the data: (1) ‘Key barriers to SW-SHRN’ (competing priorities of academic attainment and well-being, schools feeling overwhelmed with surveys and lack of school time and resource); (2) ‘Key facilitators to SW-SHRN: providing evidence-based support to schools’ (improved knowledge to facilitate change, feedback reports and benchmarking and data to inform interventions); (3) ‘Effective dissemination of findings’ (interpretation and implementation, embedding findings with existing evidence and policy, preferences for an online platform as well personalised communication and the importance of involving young people and families); and (4) ‘Longer-term facilitators: ensuring sustainability’ (keeping schools engaged, the use of repeat surveys to evaluate impact, informing school inspection frameworks and expanding reach of the network). Conclusion This study identifies several barriers to be addressed and facilitators to be enhanced in order to achieve successful implementation of School Health Research Networks in England which include providing a unique offering to schools that is not too burdensome, supporting schools to take meaningful action with their data and to work closely with existing organisations, services and providers to become meaningfully embedded in the system.

Abstract Background Youth alcohol consumption has fallen markedly over the last twenty years in England. This paper explores the drivers of the decline from the perspectives of young people. Methods The study used two methods in a convergent triangulation design. We undertook 38 individual or group qualitative interviews with 96 participants in various educational contexts in England. An online survey of 547 young people in England, was also conducted. Participants were aged between 12–19 years. For both data sources, participants were asked why they thought youth alcohol drinking might be in decline. Analysis of interview data was both deductive and inductive, guided by a thematic approach. Content analysis of survey responses further refined these themes and indicated their prevalence within a larger sample. Results The research identified eight key themes that young people used to explain the decline in youth drinking: The potential for alcohol-related harm; Contemporary youth cultures and places of socialisation; The affordability of alcohol; Displacement of alcohol by other substances; Access and the regulatory environment; Disputing the decline; Future Orientations; and Parenting and the home environment. Heterogeneity in the experiences and perspectives of different groups of young people was evident, particularly in relation to age, gender, and socio-economic position. Conclusions Young people’s explanations for the decline in youth drinking in England aligned well with those generated by researchers and commentators in prior literature. Our findings suggest that changing practices of socialisation, decreased alcohol affordability and changed attitudes toward risk and self-governance may be key explanations.