Family group conferencing for children and families: Evaluation of implementation, context and effectiveness (Family VOICE). Study protocol.

BACKGROUND: Family group conferences (FGCs) in child welfare bring immediate and wider family members together to decide on the best way to meet a child's needs. Unlike professionally led meetings, the aim is for decisions to be made by or with family members. Qualitative and mixed-method research with FGC participants tends to show positive experiences: most participants feel their voices are heard; FGCs facilitate family-driven solutions and closer relationships-within families and with social workers. Although there is existing literature on FGCs, there is a paucity of robust comparative UK evaluations, i.e., randomised controlled trials or quasi-experimental studies. Comparative studies internationally have focused on a narrow range of outcomes, not recognised the importance of context, and paid little attention to the quality of delivery. Some qualitative studies have considered process and context but there is scant measurement of these. The aims of this study are, firstly, to establish how FGCs improve outcomes for families and what factors vary their quality, and, secondly, to assess longer-term outcomes in terms of service use and associated costs. METHODS: Given the importance of process and context, evaluation informed by realist and complex systems approaches is needed. This multi-method evaluation includes a survey of FGC services in all UK local authorities (n = 212) to map service provision; co-design of programme theory and evaluation measures with family members who have experienced an FGC (n = 16-24) and practitioners (n = 16-24) in two sites; a prospective single-arm study of FGC variability and outcomes after six months; and comparison of service use and costs in FGC participants (n≥300 families) and a control group (n≥1000) after two years using a quasi-experiment. DISCUSSION: This is a pragmatic evaluation of an existing intervention, to identify what mechanisms and contexts influence effective process and longer-term outcomes. The study is registered with Research Registry (ref. 7432).

Protein Intake and Physical Activity Levels as Determinants of Sarcopenia Risk in Community-Dwelling Older Adults.

Community screening for sarcopenia is complex, with barriers including access to specialized equipment and trained staff to conduct body composition, strength and function assessment. In the current study, self-reported dietary protein intake and physical activity (PA) in adults ≥65 years was assessed relative to sarcopenia risk, as determined by body composition, strength and physical function assessments, consistent with the European Working Group on Sarcopenia in Older People (EWGSOP) definition. Of those screened (n = 632), 92 participants (77% female) were assessed as being at high risk of developing sarcopenia on the basis of dietary protein intake ≤1 g∙kg-1∙day-1 [0.9 (0.7-0.9) g∙kg-1∙day-1] and moderate intensity physical activity <150 min.week-1. A further 31 participants (65% female) were defined as being at low risk, with both protein intake [1.2 (1.1-1.5) g∙kg-1∙day-1] and PA greater than the cut-off values. High-risk participants had reduced % lean mass [53.5 (7.8)% versus 54.8 (6.1)%, p < 0.001] and impaired strength and physical function. Notably, high-risk females exhibited greater deficits in lean mass and strength, with minimal differences between groups for males. In community-dwelling older adults, self-reported low protein intake and low weekly PA is associated with heightened risk for sarcopenia, particularly in older women. Future research should determine whether early intervention in older adults with low protein intake and PA attenuates functional decline.

FOXL2 interaction with different binding partners regulates the dynamics of ovarian development.

The transcription factor FOXL2 is required in ovarian somatic cells for female fertility. Differential timing of Foxl2 deletion, in embryonic versus adult mouse ovary, leads to distinctive outcomes, suggesting different roles across development. Here, we comprehensively investigated FOXL2's role through a multi-omics approach to characterize gene expression dynamics and chromatin accessibility changes, coupled with genome-wide identification of FOXL2 targets and on-chromatin interacting partners in somatic cells across ovarian development. We found that FOXL2 regulates more targets postnatally, through interaction with factors regulating primordial follicle formation and steroidogenesis. Deletion of one interactor, ubiquitin-specific protease 7 (Usp7), results in impairment of somatic cell differentiation, germ cell nest breakdown, and ovarian development, leading to sterility. Our datasets constitute a comprehensive resource for exploration of the molecular mechanisms of ovarian development and causes of female infertility.

Validation and clinical usefulness of the Hamilton Program for Schizophrenia Voices Questionnaire (HPSVQ) among French-speaking voice-hearers.

Auditory verbal hallucinations (AVH), also called voices, are often distressing to individuals experiencing them. Valid and reliable instruments are necessary to document the hearing voices experience across cultures. The Hamilton Program for Schizophrenia Voices Questionnaire (HPSVQ) is becoming a widely used self-administered instrument for assessing characteristics, content and subjective effect of AVH. This study investigates the psychometric characteristics of the HPSVQ French version (HPSVQ FV) in a clinical sample of voice-hearers. The results showed that the HPSVQ yields a global score (HPSVQ-Global) as well as a distress (HPSVQ-Distress) and a severity (HPSVQ-Severity) sub-score having good, acceptable and questionable internal consistency respectively. Significant correlations were found between hallucination severity (BPRS 4.0), distress (PSYRATS-AH), voices acceptance (VAAS-9), anxiety and depression (HADS). However, no significant associations were observed between Suspicion and Unusual Thoughts (BPRS 4.0). At a one-week interval, the temporal stability of the three indices was excellent. Moreover, after a brief cognitive intervention, a significant reduction was observed in all indices. Taken together, the HPSVQ FV demonstrated good construct validity, reliability and sensitivity to change. These findings support the use of the HPSVQ in francophone clinical and research settings. However, the bi-factorial solution of the HPSVQ FV should be further examined in larger samples.

The role of the healthcare assistant on a stroke unit: A scoping review.

OBJECTIVE: This scoping review explores the role of a healthcare assistant on a stroke unit, potential barriers to role fulfilment and whether stroke-specific training could enhance rehabilitative practice. DATA SOURCES: Searches were conducted on CINAHL, MEDLINE and APA PsycInfo in May 2021 and repeated in September 2022. METHODS: This scoping review was guided by Arksey and O'Malley's framework. Article selection and data extraction were conducted by one researcher using a structured proforma. A narrative approach to data synthesis was undertaken following the research questions. RESULTS: From a combined total of 533 articles, sixty-six full-text articles were assessed for eligibility. Sixteen full articles were included in this review. A healthcare assistants' role was viewed as caring directly for patients - some individuals felt they contributed to rehabilitation during these tasks, and that they could be undervalued by multidisciplinary team members, patients and their families. The barriers identified to healthcare assistants' role fulfilment were lack of time, training and staffing shortages. Training was perceived to improve healthcare assistants' communication, confidence and knowledge but training needed to be flexible, ward based and accommodate staffing shortages. However, it is unclear whether training has any clinical benefit for patients. CONCLUSION: Healthcare assistants are well placed to enhance rehabilitative practice with patients; however, there are clear perceived barriers to this occurring. Future research should aim to define the role of healthcare assistants and explore whether further stroke-specific training could cause clinical benefits for patients.

A scoping review of system-level mechanisms to prevent children being in out-of-home care.

Identifying which approaches can effectively reduce the need for out-of-home care for children is critically important. Despite the proliferation of different interventions and approaches globally, evidence summaries on this topic are limited. This study is a scoping review using a realist framework to explore what research evidence exists about reducing the number of children and young people in care. Searches of databases and websites were used to identify studies evaluating intervention effect on at least one of the following outcomes: reduction in initial entry to care; increase in family reunification post care. Data extracted from papers included type of study, outcome, type and level of intervention, effect, mechanism and moderator, implementation issues and economic (EMMIE) considerations. Data were coded by: primary outcome; level of intervention (community, policy, organisation, family or child); and type of evidence, using the realist EMMIE framework. This is the first example of a scoping review on any topic using this framework. Evaluated interventions were grouped and analysed according to system-level mechanism. We present the spread of evidence across system-level mechanisms and an overview of how each system-level mechanism might reduce the number of children in care. Implications and gaps are identified.

Improving the quality of hospital care provided to people aged 11-25 years with a mental health condition.

The National Confidential Enquiry into Patient Outcome and Death undertook a detailed analysis of data from 1269 patients aged 11-25 years, admitted to hospital with intentional injury, affective disorder, or eating disorders, to assess the quality of physical and mental healthcare provided. This article summarises the findings and associated recommendations relevant for the general hospital setting.

Developing a standardised approach to the aggregation of inpatient episodes into person-based spells in all specialties and psychiatric specialties.

BACKGROUND: Electronic health record (EHR) data are available for research in all UK nations and cross-nation comparative studies are becoming more common. All UK inpatient EHRs are based around episodes, but episode-based analysis may not sufficiently capture the patient journey. There is no UK-wide method for aggregating episodes into standardised person-based spells. This study identifies two data quality issues affecting the creation of person-based spells, and tests four methods to create these spells, for implementation across all UK nations. METHODS: Welsh inpatient EHRs from 2013 to 2017 were analysed. Phase one described two data quality issues; transfers of care and episode sequencing. Phase two compared four methods for creating person spells. Measures were mean length of stay (LOS, expressed in days) and number of episodes per person spell for each method. RESULTS: 3.5% of total admissions were transfers-in and 3.1% of total discharges were transfers-out. 68.7% of total transfers-in and 48.7% of psychiatric transfers-in had an identifiable preceding transfer-out, and 78.2% of total transfers-out and 59.0% of psychiatric transfers-out had an identifiable subsequent transfer-in. 0.2% of total episodes and 4.0% of psychiatric episodes overlapped with at least one other episode of any specialty. Method one (no evidence of transfer required; overlapping episodes grouped together) resulted in the longest mean LOS (4.0 days for all specialties; 48.5 days for psychiatric specialties) and the fewest single episode person spells (82.4% of all specialties; 69.7% for psychiatric specialties). Method three (evidence of transfer required; overlapping episodes separated) resulted in the shortest mean LOS (3.7 days for all specialties; 45.8 days for psychiatric specialties) and the most single episode person spells; (86.9% for all specialties; 86.3% for psychiatric specialties). CONCLUSIONS: Transfers-in appear better recorded than transfers-out. Transfer coding is incomplete, particularly for psychiatric specialties. The proportion of episodes that overlap is small but psychiatric episodes are disproportionately affected. The most successful method for grouping episodes into person spells aggregated overlapping episodes and required no evidence of transfer from admission source/method or discharge destination codes. The least successful method treated overlapping episodes as distinct and required transfer coding. The impact of all four methods was greater for psychiatric specialties.

Epidemiology of eating disorders in primary care in children and young people: a Clinical Practice Research Datalink study in England.

OBJECTIVES: Examination of current temporal trends and clinical management patterns of eating disorders (ED) in primary care is lacking. We aimed to calculate annual incidence rates of EDs in primary care by age, sex and deprivation. We also explored the care received through referrals, psychotropic prescriptions and associated secondary care service use. PARTICIPANTS AND SETTINGS: A retrospective electronic cohort study was conducted using the Clinical Practice Research Datalink in those aged 11-24 years between 2004 and 2014 in England (n=1 135 038). RESULTS: A total of 4775 individuals with a first ever recorded ED diagnosis were identified. The crude incidence rate was 100.1 per 100 000 person years at risk (95% CI 97.2 to 102.9). Incidence rates were highest in females (189.3 per 100 000 person years, 95% CI 183.7 to 195.0, n=4336), 16-20 years of age (141.0 per 100 000 person years, 95% CI 135.4 to 146.9, n=2348) and individuals from the least deprived areas (115.8 per 100 000 person years (95% CI 109.3 to 122.5, n=1203). Incidence rates decreased across the study period (incidence rate ratio (IRR) 0.6, 95% CI 0.5 to 0.8), particularly for individuals with bulimia nervosa (IRR 0.5, 95% CI 0.3 to 0.7) and from the most deprived areas (IRR 0.5, 95% CI 0.4 to 0.7). A total of 17.4% (95% CI 16.3 to 18.5, n=831) of first ever recorded ED cases were referred from primary to secondary care. 27.1% (95% CI 25.9 to 28.4, n=1294) of individuals had an inpatient admission 6 months before or 12 months after an incident ED diagnosis and 53.4% (95% CI 52.0 to 54.9, n=2550) had an outpatient attendance. Antidepressants were the most commonly prescribed psychotropic medication. CONCLUSIONS: New ED presentations in primary care are reducing. Understanding the cause of this decrease (coding behaviours, changes in help-seeking or a genuine reduction in new cases) is important to plan services, allocate resources and deliver effective care.

Furin, a transcriptional target of NKX2-5, has an essential role in heart development and function.

The homeodomain transcription factor NKX2-5 is known to be essential for both normal heart development and for heart function. But little is yet known about the identities of its downstream effectors or their function during differentiation of cardiac progenitor cells (CPCs). We have used transgenic analysis and CRISPR-mediated ablation to identify a cardiac enhancer of the Furin gene. The Furin gene, encoding a proprotein convertase, is directly repressed by NKX2-5. Deletion of Furin in CPCs is embryonic lethal, with mutant hearts showing a range of abnormalities in the outflow tract. Those defects are associated with a reduction in proliferation and premature differentiation of the CPCs. Deletion of Furin in differentiated cardiomyocytes results in viable adult mutant mice showing an elongation of the PR interval, a phenotype that is consistent with the phenotype of mice and human mutant for Nkx2-5. Our results show that Furin mediate some aspects of Nkx2-5 function in the heart.

Sex reversal following deletion of a single distal enhancer of Sox9.

Cell fate decisions require appropriate regulation of key genes. Sox9, a direct target of SRY, is pivotal in mammalian sex determination. In vivo high-throughput chromatin accessibility techniques, transgenic assays, and genome editing revealed several novel gonadal regulatory elements in the 2-megabase gene desert upstream of Sox9 Although others are redundant, enhancer 13 (Enh13), a 557-base pair element located 565 kilobases 5' from the transcriptional start site, is essential to initiate mouse testis development; its deletion results in XY females with Sox9 transcript levels equivalent to those in XX gonads. Our data are consistent with the time-sensitive activity of SRY and indicate a strict order of enhancer usage. Enh13 is conserved and embedded within a 32.5-kilobase region whose deletion in humans is associated with XY sex reversal, suggesting that it is also critical in humans.

Self-Harm, Suicidal Behaviours, and Cyberbullying in Children and Young People: Systematic Review.

BACKGROUND: Given the concerns about bullying via electronic communication in children and young people and its possible contribution to self-harm, we have reviewed the evidence for associations between cyberbullying involvement and self-harm or suicidal behaviors (such as suicidal ideation, suicide plans, and suicide attempts) in children and young people. OBJECTIVE: The aim of this study was to systematically review the current evidence examining the association between cyberbullying involvement as victim or perpetrator and self-harm and suicidal behaviors in children and young people (younger than 25 years), and where possible, to meta-analyze data on the associations. METHODS: An electronic literature search was conducted for all studies published between January 1, 1996, and February 3, 2017, across sources, including MEDLINE, Cochrane, and PsycINFO. Articles were included if the study examined any association between cyberbullying involvement and self-harm or suicidal behaviors and reported empirical data in a sample aged under 25 years. Quality of included papers was assessed and data were extracted. Meta-analyses of data were conducted. RESULTS: A total of 33 eligible articles from 26 independent studies were included, covering a population of 156,384 children and young people. A total of 25 articles (20 independent studies, n=115,056) identified associations (negative influences) between cybervictimization and self-harm or suicidal behaviors or between perpetrating cyberbullying and suicidal behaviors. Three additional studies, in which the cyberbullying, self-harm, or suicidal behaviors measures had been combined with other measures (such as traditional bullying and mental health problems), also showed negative influences (n=44,526). A total of 5 studies showed no significant associations (n=5646). Meta-analyses, producing odds ratios (ORs) as a summary measure of effect size (eg, ratio of the odds of cyber victims who have experienced SH vs nonvictims who have experienced SH), showed that, compared with nonvictims, those who have experienced cybervictimization were OR 2.35 (95% CI 1.65-3.34) times as likely to self-harm, OR 2.10 (95% CI 1.73-2.55) times as likely to exhibit suicidal behaviors, OR 2.57 (95% CI 1.69-3.90) times more likely to attempt suicide, and OR 2.15 (95% CI 1.70-2.71) times more likely to have suicidal thoughts. Cyberbullying perpetrators were OR 1.21 (95% CI 1.02-1.44) times more likely to exhibit suicidal behaviors and OR 1.23 (95% CI 1.10-1.37) times more likely to experience suicidal ideation than nonperpetrators. CONCLUSIONS: Victims of cyberbullying are at a greater risk than nonvictims of both self-harm and suicidal behaviors. To a lesser extent, perpetrators of cyberbullying are at risk of suicidal behaviors and suicidal ideation when compared with nonperpetrators. Policy makers and schools should prioritize the inclusion of cyberbullying involvement in programs to prevent traditional bullying. Type of cyberbullying involvement, frequency, and gender should be assessed in future studies.

Exploring the relationship between childhood obesity and proximity to the coast: A rural/urban perspective.

Childhood obesity is one of the 21st century's most serious global health challenges. Research suggests that better access to 'greenspace' (e.g. parks) may encourage physical activity and reduce the risk of obesity amongst children. We extend earlier work by considering childhood obesity in relation to proximity to the coast, using data from England's National Child Measurement Programme. Results suggest that although the overall prevalence of childhood obesity is slightly lower at the coast (-0.68% points comparing <1km to >20km, p<0.001), the relationship depends on area type. Specifically, although a coastal proximity gradient (lower obesity rates nearer the coast) was found for rural areas and smaller cities and towns, it was not present among large urban conurbations (interaction p-value<0.001). Coastal environments and access to them are changing in many areas, and research to explore potential impacts on child health is warranted.

Sequential Binding of MEIS1 and NKX2-5 on the Popdc2 Gene: A Mechanism for Spatiotemporal Regulation of Enhancers during Cardiogenesis.

The homeobox transcription factors NKX2-5 and MEIS1 are essential for vertebrate heart development and normal physiology of the adult heart. We show that, during cardiac differentiation, the two transcription factors have partially overlapping expression patterns, with the result that as cardiac progenitors from the anterior heart field differentiate and migrate into the cardiac outflow tract, they sequentially experience high levels of MEIS1 and then increasing levels of NKX2-5. Using the Popdc2 gene as an example, we also show that a significant proportion of target genes for NKX2-5 contain a binding motif recognized by NKX2-5, which overlaps with a binding site for MEIS1. Binding of the two factors to such overlapping sites is mutually exclusive, and this provides a simple regulatory mechanism for spatial and temporal synchronization of a common pool of targets between NKX2-5 and MEIS1.

RA Acts in a Coherent Feed-Forward Mechanism with Tbx5 to Control Limb Bud Induction and Initiation.

The retinoic acid (RA)- and ß-catenin-signaling pathways regulate limb bud induction and initiation; however, their mechanisms of action are not understood and have been disputed. We demonstrate that both pathways are essential and that RA and ß-catenin/TCF/LEF signaling act cooperatively with Hox gene inputs to directly regulate Tbx5 expression. Furthermore, in contrast to previous models, we show that Tbx5 and Tbx4 expression in forelimb and hindlimb, respectively, are not sufficient for limb outgrowth and that input from RA is required. Collectively, our data indicate that RA signaling and Tbx genes act in a coherent feed-forward loop to regulate Fgf10 expression and, as a result, establish a positive feedback loop of FGF signaling between the limb mesenchyme and ectoderm. Our results incorporate RA-, ß-catenin/TCF/LEF-, and FGF-signaling pathways into a regulatory network acting to recruit cells of the embryo flank to become limb precursors.

A combination of activation and repression by a colinear Hox code controls forelimb-restricted expression of Tbx5 and reveals Hox protein specificity.

Tight control over gene expression is essential for precision in embryonic development and acquisition of the regulatory elements responsible is the predominant driver for evolution of new structures. Tbx5 and Tbx4, two genes expressed in forelimb and hindlimb-forming regions respectively, play crucial roles in the initiation of limb outgrowth. Evolution of regulatory elements that activate Tbx5 in rostral LPM was essential for the acquisition of forelimbs in vertebrates. We identified such a regulatory element for Tbx5 and demonstrated Hox genes are essential, direct regulators. While the importance of Hox genes in regulating embryonic development is clear, Hox targets and the ways in which each protein executes its specific function are not known. We reveal how nested Hox expression along the rostro-caudal axis restricts Tbx5 expression to forelimb. We demonstrate that Hoxc9, which is expressed in caudal LPM where Tbx5 is not expressed, can form a repressive complex on the Tbx5 forelimb regulatory element. This repressive capacity is limited to Hox proteins expressed in caudal LPM and carried out by two separate protein domains in Hoxc9. Forelimb-restricted expression of Tbx5 and ultimately forelimb formation is therefore achieved through co-option of two characteristics of Hox genes; their colinear expression along the body axis and the functional specificity of different paralogs. Active complexes can be formed by Hox PG proteins present throughout the rostral-caudal LPM while restriction of Tbx5 expression is achieved by superimposing a dominant repressive (Hoxc9) complex that determines the caudal boundary of Tbx5 expression. Our results reveal the regulatory mechanism that ensures emergence of the forelimbs at the correct position along the body. Acquisition of this regulatory element would have been critical for the evolution of limbs in vertebrates and modulation of the factors we have identified can be molecular drivers of the diversity in limb morphology.