Health and lifestyle advisors in support of primary care: An evaluation of an innovative pilot service in a region of high health inequality.

INTRODUCTION: A health and lifestyle advisor service embedded within primary care was piloted in Kingston-upon-Hull from January 2021. We aimed to evaluate the first two years of service delivery by identifying patient demographics referred to the service, reason for referral, determine uptake and retention rates, and monitor individual lifestyle-related risk factor changes following discharge. METHODS: Anonymised data were extracted from the SystmOne database for all patients referred to the service between January 2021 and January 2023. RESULTS: In the initial two years of the service, 705 unique patients were referred at a mean rate of ∼29 per month. Each unique patient received a median (robust median absolute deviation; [MAD]) of 3 (Steel N, et al 2018) planned consultations prior to discharge over this period. The majority of referrals were for symptom management and health promotion purposes (95%). Of those referred, 69% attended their appointments, and 14% did not attend. The majority of referrals were white British (55%), however, the service did receive a substantial number of referrals from minority ethnic groups, with only 67% of referrals speaking English as their main language. Eighteen distinct languages were spoken. Most referrals were classified as class I obese (59.4%). Across initial and final appointments, median (robust MAD) systolic blood pressure was 130 (15) mmHg and 130 (15) mmHg, and median (robust MAD) waist circumference was 103.0 (13.3) cm and 101.0 (13.3) cm. CONCLUSION: The evaluation highlighted the demand for this service embedded within primary care settings in Kingston-upon-Hull. Service engagement was evident, and a large proportion of those who engaged were from minority ethnic groups. A high proportion of referrals presented with obesity and/or hypertension which requires further investigation.

Proxies of Trustworthiness: A Novel Framework to Support the Performance of Trust in Human Health Research.

Without trust there is no credible human health research (HHR). This article accepts this truism and addresses a crucial question that arises: how can trust continually be promoted in an ever-changing and uncertain HHR environment? The article analyses long-standing mechanisms that are designed to elicit trust-such as consent, anonymization, and transparency-and argues that these are best understood as trust represented by proxies of trustworthiness, i.e., regulatory attempts to convey the trustworthiness of the HHR system and/or its actors. Often, such proxies are assumed to operate as markers that trust exists or, at least, has not been lost. But, since trust can neither be "built" nor "secured," this is a precarious assumption. Worryingly, there is no existing theoretical account of how to understand and evaluate these proxies of trustworthiness as part of a trusted HHR ecosystem. To remedy this, the paper argues for a radical reimagining of trust and trustworthiness as performative acts that ought to be understood in relation to each other and by reference to the common values at stake. It is shown that proxies of trustworthiness are the operational tools used to perform trustworthiness. It advocates for a values-based approach to understanding the relationship between trust and trustworthiness. This establishes a strong basis for an evaluative framework for proxies of trustworthiness, i.e., to determine how to perform trustworthiness well. Five common proxies in HHR are scrutinized from a values perspective. The contribution is to provide a far-reaching normative and practical framework by which existing and future proxies of trustworthiness can be identified, assessed, maintained, or replaced in rapidly changing HHR regulatory ecosystems where trust itself is crucial to the success of the entire HHR enterprise.

Detailed DNA methylation characterisation of phyllodes tumours identifies a signature of malignancy and distinguishes phyllodes from metaplastic breast carcinoma.

Phyllodes tumours (PTs) are rare fibroepithelial lesions of the breast that are classified as benign, borderline, or malignant. As little is known about the molecular underpinnings of PTs, current diagnosis relies on histological examination. However, accurate classification is often difficult, particularly for distinguishing borderline from malignant PTs. Furthermore, PTs can be misdiagnosed as other tumour types with shared histological features, such as fibroadenoma and metaplastic breast cancers. As DNA methylation is a recognised hallmark of many cancers, we hypothesised that DNA methylation could provide novel biomarkers for diagnosis and tumour stratification in PTs, whilst also allowing insight into the molecular aetiology of this otherwise understudied tumour. We generated whole-genome methylation data using the Illumina EPIC microarray in a novel PT cohort (n = 33) and curated methylation microarray data from published datasets including PTs and other potentially histopathologically similar tumours (total n = 817 samples). Analyses revealed that PTs have a unique methylome compared to normal breast tissue and to potentially histopathologically similar tumours (metaplastic breast cancer, fibroadenoma and sarcomas), with PT-specific methylation changes enriched in gene sets involved in KRAS signalling and epithelial-mesenchymal transition. Next, we identified 53 differentially methylated regions (DMRs) (false discovery rate < 0.05) that specifically delineated malignant from non-malignant PTs. The top DMR in both discovery and validation cohorts was hypermethylation at the HSD17B8 CpG island promoter. Matched PT single-cell expression data showed that HSD17B8 had minimal expression in fibroblast (putative tumour) cells. Finally, we created a methylation classifier to distinguish PTs from metaplastic breast cancer samples, where we revealed a likely misdiagnosis for two TCGA metaplastic breast cancer samples. In conclusion, DNA methylation alterations are associated with PT histopathology and hold the potential to improve our understanding of PT molecular aetiology, diagnostics, and risk stratification. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Living in food insecurity: A qualitative study exploring parents' food parenting practices and their perceptions of the impact of food insecurity on their children's eating.

Food insecurity in rich countries is a growing problem with far reaching consequences but how it impacts parents, particularly their food parenting practices, is under researched. Food parenting practices play a critical role in the development of children's eating and may be a mechanism in the link between food insecurity and children's health outcomes; this study aims to illuminate their potential role. Twenty-one parents participated in a qualitative interview study. Their household food security was very low (18/21) or low (3/21). Reflexive Thematic Analysis generated three themes. Challenges of food insecurity: parents shielded children from hunger by eating less themselves, relying on free school meals and turning to family and food banks when in crisis. They perceived a conflict between giving children food of high nutritional quality and its cost. Practical impact of food insecurity: although motivated to provide children with healthy food, finances meant parents struggled to achieve this goal. Parents used a range of food parenting practices but their use of some that are known to be effective may have been compromised by their food insecurity. Emotional impact of food insecurity: parents described feelings of failure, despair, helplessness and shame. Food insecurity adversely effects both children and parents, and non-stigmatising services that mitigate its impact and facilitate children's exposure to food parenting practices known to be effective are needed.

Therapist guided, parent-led cognitive behavioural therapy (CBT) for pre-adolescent children with obsessive compulsive disorder (OCD): a non-concurrent multiple baseline case series.

BACKGROUND: Cognitive behavioural therapy (CBT) including exposure and response prevention (ERP) is an effective treatment for preadolescent children with obsessive compulsive disorder (OCD); however, there is a need to increase access to this treatment for affected children. AIMS: This study is a preliminary evaluation of the efficacy and acceptability of a brief therapist-guided, parent-led CBT intervention for pre-adolescent children (5-12 years old) with OCD using a non-concurrent multiple baseline approach. METHOD: Parents of 10 children with OCD were randomly allocated to no-treatment baselines of 3, 4 or 5 weeks before receiving six to eight individual treatment sessions with a Psychological Wellbeing Practitioner. Diagnostic measures were completed prior to the baseline, 1-week post-treatment, and at a 1-month follow-up, and parents completed weekly measures of children's OCD symptoms/impairment. RESULTS: Seventy percent of children were 'responders' and/or 'remitters' on diagnostic measures at post-treatment, and 60% at the 1-month follow-up. At least 50% of children showed reliable improvements on parent-reported OCD symptoms/impairment from pre- to post-treatment, and from pre-treatment to 1-month follow-up. Crucially, the intervention was acceptable to parents. CONCLUSIONS: Brief therapist-guided, parent-led CBT has the potential to be an effective, acceptable and accessible first-line treatment for pre-adolescent children with OCD, subject to the findings of further evaluations.

Consumer Liking of Turnip Cooked by Different Methods: The Influence of Sensory Profile and Consumer Bitter Taste Genotype.

Brassica vegetables are bitter, predominantly because they contain bitter-tasting glucosinolates. Individuals with high bitter taste sensitivity are reported to have lower consumption of bitter vegetables. Studies reported that cooking methods can alter the sensory characteristics of vegetables, increasing acceptability. This study investigated consumer liking of turnip cooked by four methods (boiled-pureed, roasted, steamed-pureed and stir-fried) and related this to sensory characteristics. Additionally, this study examined the effect of the bitter taste genotype on taste perception and liking of the cooked turnip samples. Participants (n = 74) were recruited and the TAS2R38 genotype was measured. Liking, consumption intent, perception of bitterness and sweetness of turnip were evaluated. A sensory profile of the cooked turnip variants was also determined by a trained sensory panel. There were significant differences in the overall (p = 0.001) and taste (p = 0.002) liking between cooking methods. Turnip liking was increased when preparation led to sweeter taste profiles. The TAS2R38 genotype had a significant effect on bitter perception (p = 0.02) but did not significantly affect taste liking. In conclusion, the cooking method affected turnip liking, and the bitter perception in turnip was influenced by the TAS2R38 genotype. However, taste sensitivity did not predict turnip liking in this UK adult cohort.

Family Mealtimes: A Systematic Umbrella Review of Characteristics, Correlates, Outcomes and Interventions.

Systematic reviews have examined the multitude of studies investigating family mealtimes and their importance to child/adolescent health and psychosocial outcomes, but the focus of each is limited to specific aspects of family meals (e.g., frequency) and/or specific outcomes (e.g., nutrition). Their findings require synthesis and so a systematic umbrella review was undertaken. Databases were searched to identify systematic reviews (with or without meta-analysis/meta-synthesis) addressing at least one of the following questions: what are the characteristics and/or correlates of family mealtimes; what outcomes are associated with family mealtimes; are interventions aimed at promoting family mealtimes effective? Forty-one eligible reviews were retrieved. Their findings demonstrate that families with children/adolescents typically eat together at least a few days each week. More frequent family meals are predicted by a more positive mealtime environment, more positive attitudes towards family meals, the presence of younger children, and families having more time. Greater family meal frequency protects children/adolescents against a poorer diet, obesity, risk behaviours, poorer mental health and wellbeing, and poorer academic outcomes. Findings from interventions seeking to promote family mealtimes are mixed. This umbrella review provides a comprehensive and integrated understanding of research into family mealtimes, establishing where evidence is sound and where further research is needed.

Adventurous play for a healthy childhood: Facilitators and barriers identified by parents in Britain.

RATIONALE: Adventurous play, where children take age-appropriate risks involving uncertainty, fear, and thrill, is positively associated with children's physical health, mental health, and development. There is growing concern that children's access to and engagement with adventurous play opportunities are declining in Westernised countries, which may have negative implications for children's health. OBJECTIVE: The current study aimed to ascertain the facilitators of and barriers to children's adventurous play most identified by parents in Britain and to determine whether these differ across socio-demographic and geographic groups. METHODS: This study analysed the responses of a nationally representative sample of 1919 parents who took part in the British Children's Play Survey. Two open-ended questions asked parents to identify what they perceive to be the facilitators of and barriers to their child's adventurous play. A quantitative coding scheme, developed using the qualitative framework identified by Oliver et al. (2022), was applied to parents' responses. RESULTS: A diversity in the most identified facilitators and barriers was found, including concerns about the risk of injury from adventurous play and the safety of society, positive attitudes about the benefits of adventurous play, as well as factors related to child attributes. In general, these were consistently identified across different socio-demographic and geographic groups, although some differences were found in barriers. CONCLUSIONS: The findings of this research support the identification of key targets for those working with parents to improve children's adventurous play opportunities and ultimately their physical and mental health. Future research should seek to design and tailor interventions by asking parents about the support they would value.

Reversal of Lactate and PD-1-mediated Macrophage Immunosuppression Controls Growth of PTEN/p53-deficient Prostate Cancer.

PURPOSE: Phosphatase and tensin homolog (PTEN) loss of function occurs in approximately 50% of patients with metastatic castrate-resistant prostate cancer (mCRPC), and is associated with poor prognosis and responsiveness to standard-of-care therapies and immune checkpoint inhibitors. While PTEN loss of function hyperactivates PI3K signaling, combinatorial PI3K/AKT pathway and androgen deprivation therapy (ADT) has demonstrated limited anticancer efficacy in clinical trials. Here, we aimed to elucidate mechanism(s) of resistance to ADT/PI3K-AKT axis blockade, and to develop rational combinatorial strategies to effectively treat this molecular subset of mCRPC. EXPERIMENTAL DESIGN: Prostate-specific PTEN/p53-deficient genetically engineered mice (GEM) with established 150-200 mm3 tumors, as assessed by ultrasound, were treated with either ADT (degarelix), PI3K inhibitor (copanlisib), or anti-PD-1 antibody (aPD-1), as single agents or their combinations, and tumors were monitored by MRI and harvested for immune, transcriptomic, and proteomic profiling, or ex vivo co-culture studies. Single-cell RNA sequencing on human mCRPC samples was performed using 10X Genomics platform. RESULTS: Coclinical trials in PTEN/p53-deficient GEM revealed that recruitment of PD-1-expressing tumor-associated macrophages (TAM) thwarts ADT/PI3Ki combination-induced tumor control. The addition of aPD-1 to ADT/PI3Ki combination led to TAM-dependent approximately 3-fold increase in anticancer responses. Mechanistically, decreased lactate production from PI3Ki-treated tumor cells suppressed histone lactylation within TAM, resulting in their anticancer phagocytic activation, which was augmented by ADT/aPD-1 treatment and abrogated by feedback activation of Wnt/ß-catenin pathway. Single-cell RNA-sequencing analysis in mCRPC patient biopsy samples revealed a direct correlation between high glycolytic activity and TAM phagocytosis suppression. CONCLUSIONS: Immunometabolic strategies that reverse lactate and PD-1-mediated TAM immunosuppression, in combination with ADT, warrant further investigation in patients with PTEN-deficient mCRPC.

See and Eat! The impact of repeated exposure to vegetable ebooks on young children's vegetable acceptance.

Vegetable consumption in young children in the UK is well below the recommended five child-sized portions per day. Effective and practical strategies are therefore needed to encourage vegetable consumption in young children. In this exploratory study, we examine the effects of visual familiarization to foods via See & Eat ebooks, which show vegetables on their journey from 'field to fork'. As part of a larger study, in which 242 British families completed a range of measures about their family's eating habits, child's food preferences and potential parent and child predictors of these (Masento et al., 2022), parents were invited to download a See & Eat ebook about a vegetable their child did not eat. Thirty-six families participated in the intervention, looking at the ebook with their child for two weeks and reporting on their child's willingness to taste, intake and liking of the vegetable targeted by the ebook and a matched control vegetable before and after the intervention period. Results showed significant increases in parental ratings of children's acceptance of the target vegetable. Willingness to taste and intake ratings improved for the target vegetable, but not the control vegetable, while liking was reported to increase for both vegetables. These results corroborate previous research demonstrating the benefits of familiarising children with vegetables before they are offered at mealtimes and suggest that ebooks can be added to the set of tools parents can use to support children's vegetable consumption.

The acceptability of a therapist-assisted internet-delivered cognitive behaviour therapy program for the treatment of anxiety disorders in adolescents: a qualitative study.

Computerized treatments have been shown to be effective in young people with anxiety disorders. However, there has been limited investigation into the experiences of adolescents in undertaking this treatment. This qualitative study explored adolescents' experiences of being treated for an anxiety disorder, using an online intervention with therapist support, as part of a randomised controlled trial. Individual semi-structured interviews were conducted with thirteen adolescents aged between 13 and 17 years, who had received the online intervention. Data were analysed using reflexive thematic analysis. Two cross-cutting themes were identified: (i) Usability of the program, and (ii) Putting techniques into practice. Although the convenience of online sessions was recognised as positive, many of the adolescents expressed a preference for face-to-face sessions. The length of sessions and the large amount of reading involved was highlighted by most participants. The transdiagnostic nature of the content meant some elements of the programme were seen as less relevant. While many participants appreciated the 'fun' aspect of the program, others felt that certain aspects of the program were not suitable for their age group. Exposure, psychoeducation and cognitive restructuring were generally received positively, whereas responses to the use of relaxation and rewards were much more mixed. Our findings highlight the potential utility for online treatments delivered with therapist support. However, they also highlight how issues with both the format and treatment components can impact the acceptability of a program. As such, further work is warranted to improve the acceptability of online treatments for adolescents with anxiety disorders.

In the moment social experiences and perceptions of children with social anxiety disorder: A qualitative study.

OBJECTIVES: Childhood social anxiety disorder (SAD) is a common and disabling condition. General forms of cognitive behavioural treatments have demonstrated poorer efficacy for childhood SAD when compared to other childhood anxiety disorders and further understanding of the psychological factors that contribute to the maintenance of childhood SAD is warranted. Examining the social experiences of children with SAD may help to identify relevant psychological factors and increase our understanding of what keeps childhood SAD going. METHODS: The current study used reflexive thematic analysis to analyse the transcripts of interviews with 12 children aged 8-12 years with SAD who had been interviewed about their 'in the moment' social experiences during a social stress induction task. The interview topic guide included factors hypothesized to maintain SAD in adult cognitive models of the disorder. RESULTS: The interviews revealed both variety and commonalities in the experiences and interpretations of social events in children with SAD, captured in three related main themes: (i) Discomfort being the centre of attention, (ii) (Lack of) awareness of cognitions and (iii) Managing social fears. Findings indicated likely developmental influences on which maintenance mechanisms apply at which point in time. CONCLUSIONS: There is variation in the psychological mechanisms that children with SAD endorse and developmental factors are likely to influence when specific mechanisms are relevant. We now need further studies that take a developmentally informed approach to understand the nature of the association between the factors identified in this study and social anxiety in childhood to inform the development of more effective interventions for childhood SAD.

Mitigating inequalities at a large COVID-19 vaccination centre.

Introduction: The COVID-19 vaccination service is a key component in the UK approach to reducing disease morbidity and mortality. Groups within the population at increased risk of severe outcomes from COVID-19 overlap with groups that are less likely to take up the offer of vaccination. This article outlines some learning from approaches within a large vaccination centre in the UK to reduce inequalities. Solution: Continuous quality improvement processes were used to operationalise the mitigations to inequalities with vaccination uptake that were identified by a systematic equality impact assessment framework and continuous service feedback. Outcome: Quality improvement processes and community engagement enabled tailored mitigations to vaccination uptake. Engagement with community ambassadors strengthened community relationships and the co-creation of bespoke sessions encouraged vaccination uptake within specific groups. Conclusion: Recommendations for strengthening approaches to inequality reduction include having a systematic framework for assessment and mitigation of inequalities, embedding quality improvement, identifying resources, and taking a collaborative and co-design approach to services with underserved groups.

Parent, child, and environmental predictors of vegetable consumption in Italian, Polish, and British preschoolers.

This study compared the vegetable intake of preschool children from three European countries [Italy, Poland, and the United Kingdom (UK)] and explored the parent, child, and environmental factors that predicted intake in each country. A total of 408 parents of preschoolers (Italy: N = 61, Poland: N = 124, and UK: N = 225; child mean age = 32.2 months, SD = 9.47) completed an online survey comprising a set of standardised questionnaires. For all three countries, the questionnaires included measures of children's vegetable intake (VegFFQ), child eating behaviour (CEBQ-FF), parents' mealtime goals (FMGs), and sociodemographic questions about family background and environment. In the UK and Italy, additional questionnaires were used to assess child temperament (EAS-T) and parents' feeding practices (CFPQ). The results showed that the number of child-sized portions of vegetables consumed per day varied significantly across countries; Polish children consumed the most (∼3 portions) and Italian children the least (∼1.5 portions). Between-country differences were seen in parents' goals for family mealtimes; compared to Italian parents, Polish and UK parents were more motivated to minimise mealtime stress, increase family involvement in meal preparation, and share the same foods with family members. British and Italian parents also adopted different feeding practices; parents in the UK reported more use of healthy modelling behaviours and more use of foods to support their child's emotion regulation. In terms of child factors, Italian children were reported to be more emotional and more sociable than British children. Analyses of the relationships between the parent, child, and environmental factors and children's vegetable intake revealed both similarities and differences between countries. Negative predictors of vegetable intake included child food fussiness in the UK and Poland, child temperament (especially, shyness) in Italy, and the use of food as a reward and child emotionality in the UK. Positive predictors included the parental mealtime goal of 'family involvement' in the UK. These results highlight differences in the extent to which European preschoolers achieve recommended levels of vegetable intake, and in the factors that influence whether they do. The results suggest a need to develop healthy eating interventions that are adopted to meet the specific needs of the countries in which they are implemented.

Deep whole genome sequencing identifies recurrent genomic alterations in commonly used breast cancer cell lines and patient-derived xenograft models.

BACKGROUND: Breast cancer cell lines (BCCLs) and patient-derived xenografts (PDXs) are the most frequently used models in breast cancer research. Despite their widespread usage, genome sequencing of these models is incomplete, with previous studies only focusing on targeted gene panels, whole exome or shallow whole genome sequencing. Deep whole genome sequencing is the most sensitive and accurate method to detect single nucleotide variants and indels, gene copy number and structural events such as gene fusions. RESULTS: Here we describe deep whole genome sequencing (WGS) of commonly used BCCL and PDX models using the Illumina X10 platform with an average ~ 60 × coverage. We identify novel genomic alterations, including point mutations and genomic rearrangements at base-pair resolution, compared to previously available sequencing data. Through integrative analysis with publicly available functional screening data, we annotate new genomic features likely to be of biological significance. CSMD1, previously identified as a tumor suppressor gene in various cancer types, including head and neck, lung and breast cancers, has been identified with deletion in 50% of our PDX models, suggesting an important role in aggressive breast cancers. CONCLUSIONS: Our WGS data provides a comprehensive genome sequencing resource of these models.

Controlling feeding practices moderate the relationship between emotionality and food fussiness in young children.

Emotional child temperament has consistently been found to be related to food fussiness. One factor that may exacerbate or reduce the risk conferred by children's emotionality is parent feeding practices during mealtimes. Specifically, the use of controlling feeding practices aimed at increasing food consumption may particularly affect children with an emotional temperament. The primary aim of this study was to investigate whether the association between child food fussiness and higher emotionality found in previous studies is moderated by maternal use of controlling feeding practices, namely verbal pressure, physical prompts and food rewards. Sixty-seven mother-child dyads were video-recorded during a meal in their home and mothers' use of controlling feeding practices during this meal were coded. Mothers completed a questionnaire assessing child temperament. Moderation analyses revealed that maternal use of verbal pressure and physical prompts moderated the relationship between higher emotionality and food fussiness, but maternal use of food rewards did not. These results indicate that the use of verbal pressure and physical prompts may have a particularly negative influence on fussy eating for children higher in emotionality.

Short-term safety outcomes of mastectomy and immediate prepectoral implant-based breast reconstruction: Pre-BRA prospective multicentre cohort study.

BACKGROUND: Prepectoral breast reconstruction (PPBR) has recently been introduced to reduce postoperative pain and improve cosmetic outcomes in women having implant-based procedures. High-quality evidence to support the practice of PPBR, however, is lacking. Pre-BRA is an IDEAL stage 2a/2b study that aimed to establish the safety, effectiveness, and stability of PPBR before definitive evaluation in an RCT. The short-term safety endpoints at 3 months after surgery are reported here. METHODS: Consecutive patients electing to undergo immediate PPBR at participating UK centres between July 2019 and December 2020 were invited to participate. Demographic, operative, oncology, and complication data were collected. The primary outcome was implant loss at 3 months. Other outcomes of interest included readmission, reoperation, and infection. RESULTS: Some 347 women underwent 424 immediate implant-based reconstructions at 40 centres. Most were single-stage direct-to-implant (357, 84.2 per cent) biological mesh-assisted (341, 80.4 per cent) procedures. Conversion to subpectoral reconstruction was necessary in four patients (0.9 per cent) owing to poor skin-flap quality. Of the 343 women who underwent PPBR, 144 (42.0 per cent) experienced at least one postoperative complication. Implant loss occurred in 28 women (8.2 per cent), 67 (19.5 per cent) experienced an infection, 60 (17.5 per cent) were readmitted for a complication, and 55 (16.0 per cent) required reoperation within 3 months of reconstruction. CONCLUSION: Complication rates following PPBR are high and implant loss is comparable to that associated with subpectoral mesh-assisted implant-based techniques. These findings support the need for a well-designed RCT comparing prepectoral and subpectoral reconstruction to establish best practice for implant-based breast reconstruction.

Parent perceived barriers and facilitators of children's adventurous play in Britain: a framework analysis.

BACKGROUND: From a public health perspective there is growing interest in children's play, including play involving risk and adventure, in relation to children's physical and mental health. Regarding mental health, it is theorised that adventurous play, where children experience thrilling, exciting emotions, offers important learning opportunities that prepare children for dealing with uncertainty and help prevent anxiety. Despite these benefits, adventurous play has decreased substantially within a generation. Parents have a key role in facilitating or limiting children's opportunities for adventurous play, but research identifying the barriers and facilitators parents perceive in relation to adventurous play is scarce. The present study therefore examined the barriers to and facilitators of adventurous play as perceived by parents of school-aged children in Britain. METHODS: This study analysed data from a subsample of parents in Britain (n = 377) who participated in the nationally representative British Children's Play Survey. Parents responded to two open-ended questions pertaining to the barriers to and facilitators of children's adventurous play. Responses were analysed using a qualitative Framework Analysis, an approach suitable for managing large datasets with specific research questions. RESULTS: Four framework categories were identified: Social Environment; Physical Environment; Risk of Injury; Child Factors. Social Environment included barriers and facilitators related to parents, family and peers, as well as community and society. Dominant themes within the Social Environment related to perceptions about the certainty of child safety, such as supervision and the safety of society. Beliefs about the benefits of adventurous play for development and well-being were also important in the Social Environment. Physical Environment factors focused on safety and practical issues. Risk of Injury captured concerns about children being injured during play. Child Factors included child attributes, such as play preference, developmental ability and trait-like characteristics. CONCLUSIONS: Improved understanding of what influences parent perceptions of adventurous play can inform public health interventions designed to improve children's opportunities for and engagement in adventurous play, with a view to promote children's physical and mental health.

The ASCEND study: protocol for a feasibility study to evaluate an early social communication intervention for young children with Down syndrome.

BACKGROUND: Down syndrome is the most common cause of learning disability, affecting approximately 1 in every 700 babies. Children with Down syndrome have particular difficulties with speech and language. This makes it challenging for them to participate fully in life, access healthcare services and educational opportunities. Improving the language skills of young children with Down syndrome is vital for their future social and emotional well-being and behaviour, and consequently contribution to society. As Down syndrome is detected before or at birth, we can provide support from early on. There are currently no standard interventions for improving the language skills of children with Down syndrome under the age of 36 months. Evidence suggests that early parent-based interventions may be effective in improving language outcomes. In partnership with parents and speech and language therapists, we have co-developed an intervention focusing on early social communication skills and our preliminary work shows that it can lead to better language in children with Down syndrome. Our aim is to carry out a feasibility study which will inform a future pilot/full trial to test whether the intervention is effective in improving language skills before children with Down syndrome start school. METHODS: This is a two-arm feasibility randomised controlled trial (RCT), with 1:1 randomisation stratified by trial site comparing the intervention (plus standard NHS speech and language therapy) with no intervention (standard NHS speech and language therapy only). We aim to recruit between 25 and 30 children with Down syndrome aged between 11 and 36 months. Sites are defined by the geographical boundaries of three National Health Service (NHS) Trusts. Recruitment is from NHS Speech and Language Therapist caseloads within the 3 Trusts, and self-referral. In the intervention arm, parents/guardians will receive brief training on the parent-based intervention and a manual to follow with their child for 10 weeks. The children's language and early communication skills and family health outcomes will be assessed by a blinded assessor at baseline, post-intervention and 6 month follow-up. Questionnaire and semi-structured interviews will explore the acceptability of the intervention to parents and SLTs. DISCUSSION: The feasibility study's outcomes will determine whether it would be viable to progress to a full-trial and whether adjustments need to made to the procedures, data collection methods, intervention delivery and the intensity of support needed. We want to assess whether our early intervention can be delivered and rolled out through NHS Speech and Language Therapy (SLT) Services. We anticipate that NHS SLT Services will need to make ongoing changes due to the COVID-19 pandemic, so it is likely that we will need to make adjustments for the definitive trial. We will also calculate descriptive statistics of the language outcome measure which we will use for any future sample size calculation. TRIAL REGISTRATION: ISRCTN13902755. Registered on 25 August 2020. http://www.isrctn.com/ISRCTN13902755.

Identification of DNA methylation biomarkers with potential to predict response to neoadjuvant chemotherapy in triple-negative breast cancer.

Neoadjuvant chemotherapy (NAC) is used to treat triple-negative breast cancer (TNBC) prior to resection. Biomarkers that accurately predict a patient's response to NAC are needed to individualise therapy and avoid chemotoxicity from unnecessary chemotherapy. We performed whole-genome DNA methylation profiling on diagnostic TNBC biopsy samples from the Sequential Evaluation of Tumours Undergoing Preoperative (SETUP) NAC study. We found 9 significantly differentially methylated regions (DMRs) at diagnosis which were associated with response to NAC. We show that 4 of these DMRs are associated with TNBC overall survival (P < 0.05). Our results highlight the potential of DNA methylation biomarkers for predicting NAC response in TNBC.