Integration of academic and health education for the prevention of physical aggression and violence in young people: systematic review, narrative synthesis and intervention components analysis.

OBJECTIVES: To systematically review evidence on the effectiveness of interventions including integration of academic and health education for reducing physical aggression and violence, and describe the content of these interventions. DATA SOURCES: Between November and December 2015, we searched 19 databases and 32 websites and consulted key experts in the field. We updated our search in February 2018. ELIGIBILITY CRITERIA: We included randomised trials of school-based interventions integrating academic and health education in students aged 4-18 and not targeted at health-related subpopulations (eg, learning or developmental difficulties). We included evaluations reporting a measure of interpersonal violence or aggression. DATA EXTRACTION AND ANALYSIS: Data were extracted independently in duplicate, interventions were analysed to understand similarities and differences and outcomes were narratively synthesised by key stage (KS). RESULTS: We included 13 evaluations of 10 interventions reported in 20 papers. Interventions included either full or partial integration, incorporated a variety of domains beyond the classroom, and used literature, local development or linking of study skills and health promoting skills. Evidence was concentrated in KS2, with few evaluations in KS3 or KS4, and evaluations had few consistent effects; evaluations in KS3 and KS4 did not suggest effectiveness. DISCUSSION: Integration of academic and health education may be a promising approach, but more evidence is needed. Future research should consider the 'lifecourse' aspects of these interventions; that is, do they have a longitudinal effect? Evaluations did not shed light on the value of different approaches to integration

TRIM5α requires Ube2W to anchor Lys63-linked ubiquitin chains and restrict reverse transcription

TRIM5α is an antiviral, cytoplasmic, E3 ubiquitin (Ub) ligase that assembles on incoming retroviral capsids and induces their premature dissociation. It inhibits reverse transcription of the viral genome and can also synthesize unanchored polyubiquitin (polyUb) chains to stimulate innate immune responses. Here, we show that TRIM5α employs the E2 Ub-conjugating enzyme Ube2W to anchor the Lys63-linked polyUb chains in a process of TRIM5α auto-ubiquitination. Chain anchoring is initiated, in cells and in vitro, through Ube2W-catalyzed monoubiquitination of TRIM5α. This modification serves as a substrate for the elongation of anchored Lys63-linked polyUb chains, catalyzed by the heterodimeric E2 enzyme Ube2N/Ube2V2. Ube2W targets multiple TRIM5α internal lysines with Ub especially lysines 45 and 50, rather than modifying the N-terminal amino group, which is instead αN-acetylated in cells. E2 depletion or Ub mutation inhibits TRIM5α ubiquitination in cells and restores restricted viral reverse transcription, but not infection. Our data indicate that the stepwise formation of anchored Lys63-linked polyUb is a critical early step in the TRIM5α restriction mechanism and identify the E2 Ub-conjugating cofactors involved

Systematic review and meta-analysis of effects of community-delivered positive youth development interventions on violence outcomes

Background We systematically reviewed and meta-analysed evaluations testing the effectiveness of positive youth development (PYD) interventions for reducing violence in young people. Methods Two reviewers working independently screened records, assessed full-text studies for inclusion and extracted data. Outcomes were transformed to Cohen's d. Quality assessment of included evaluations was undertaken using the Cochrane risk of bias tool. Effect sizes were combined using multilevel meta-analysis. We searched 21 databases, including MEDLINE, PsycINFO, CINAHL and CENTRAL, and hand-searched key journals and websites. We included studies where the majority of participants were aged 11–18 years and where interventions were delivered in community (not clinical or judicial) settings outside of normal school hours. We excluded studies targeting predefined physical and mental health conditions or parents/carers alongside young people. We defined violence as perpetration or victimisation of physical violence including violent crime. Results Three randomised trials were included in this systematic review. Included evaluations each had design flaws. Meta-analyses suggested that PYD interventions did not have a statistically significant effect on violence outcomes across all time points (d=0.021, 95% CI −0.050 to 0.093), though interventions did have a statistically significant short-term effect (d=0.076, 95% CI 0.013 to 0.140). Conclusions Our meta-analyses do not offer evidence of PYD interventions in general having effects of public health significance in reducing violence among young people. Evaluations did not consistently report theories of change or implementation fidelity, so it is unclear if our meta-analyses provide evidence that the PYD theory of change is ineffective in reducing violence among young people

How Do Contextual Factors Influence Implementation and Receipt of Positive Youth Development Programs Addressing Substance Use and Violence? A Qualitative Meta-Synthesis of Process Evaluations

Objective:Positive youth development (PYD) often aims to prevent tobacco, alcohol, and drugs use and violence. We systematically reviewed PYD interventions, synthesizing process, and outcomes evidence. Synthesis of outcomes, published elsewhere, found no overall evidence of reducing substance use or violence but notable variability of fidelity. Our synthesis of process evaluations examined how implementation varied and was influenced by context.Data Source:Process evaluations of PYD aiming to reduce substance use and violence.Study Inclusion Criteria:Overall review published since 1985; written in English; focused on youth aged 11 to 18 years; focused on interventions addressing multiple positive assets; reported on theory, process, or outcomes; and concerned with reducing substance use or violence. Synthesis of process evaluations examined how implementation varies with or is influenced by context.Data Extraction:Two reviewers in parallel.Data Synthesis:Thematic synthesis.Results:We identified 12 reports. Community engagement enhanced program appeal. Collaboration with other agencies could broaden the activities offered. Calm but authoritative staff increased acceptability. Staff continuity underpinned diverse activities and durable relationships. Empowering participants were sometimes in tension with requiring them to engage in diverse activities.Conclusion:Our systematic review identified factors that might help improve the fidelity and acceptability of PYD interventions. Addressing these might enable PYD to fulfill its potential as a means of promoting health

The effects of Positive Youth Development interventions on substance use, violence and inequalities: systematic review of theories of change, processes and outcomes

BackgroundPositive Youth Development (PYD) delivered outside school aims to enable young people to develop positive assets such as relationships and confidence, rather than to merely address risk. Existing reviews of PYD effects on substance use or violence are old and unsystematic.ObjectivesTo systematically review evidence to answer the following questions: what theories of change inform PYD interventions addressing substance use and violence? What characteristics of participants and contexts are identified as barriers to and facilitators of implementation and receipt in process evaluations of PYD? What is the effectiveness and cost-effectiveness of PYD in reducing substance use and violence? What characteristics of participants and contexts appear to moderate, or are necessary and sufficient for, PYD effectiveness?Data sourcesA total of 21 bibliographic databases; 35 websites and contacting authors.Review methodsWe included reports published in English since 1985 and reporting on theories of change, as well as process, outcome and economic evaluations of PYD targeting 11- to 18-year-olds and addressing substance use or violence. References were screened on title/abstract and, where appropriate, on full report. Data extraction and quality assessment used Critical Appraisal Skills Programme, Evidence for Policy and Practice Information and Co-ordinating Centre and Cochrane tools. Theories of change and process evaluations were qualitatively metasynthesised. Outcome evaluations were synthesised narratively and meta-analytically.Results32,394 unique references were identified and 48 were included. A total of 16 reports described theories, 13 (10 studies) evaluated processes and 25 (10 studies) evaluated outcomes.Theories of changePYD interventions aim to offer opportunities for young people to develop positive ‘assets’ such as skills and confidence. These are theorised to promote and be promoted by young people’s ‘intentional self-regulation’, which involves reflecting on behaviour; determining goals; using existing resources to pursue these; and redirecting effort when thwarted. This enables ‘developmental regulation’, namely individuals capitalising on other opportunities to promote personal development. Positive assets thus accrued reduce health risks by reducing the impact on individuals of environmental risk or by ameliorating the impact of such risks. The literature offers limited insights beyond these general ideas.Process evaluationsCommunity engagement ensured that programmes were accessible and appealing. Staff capacity and continuity were crucial factors but often challenging when programmes could not offer full-time jobs. Tensions arose between a desire to empower participants to choose activities and a requirement for them to undertake a breadth of activities.Outcome evaluationsMeta-analyses of all combined outcomes and of short-term alcohol use, illicit drug use and smoking found no significant effects. There were small, statistically significant, short-term effects for an omnibus measure of substance use and for violence. We could not undertake metaregression to assess sociodemographic moderators but narrative synthesis suggested no clear pattern of effects by sex. We found no economic evaluations.LimitationsInsufficient studies precluded qualitative comparative analyses.ConclusionsHow PYD might promote health is currently undertheorised. Implementation can be challenging. We found little evidence that current PYD interventions delivered outside school reduce substance use or violence. However, these may not constitute a test of the effectiveness of the PYD model, as some included interventions that, although meeting our inclusion criteria, were not exemplars of PYD.Future workFurther evaluations should assess interventions employing PYD theory of change.Study registrationThis study is registered as PROSPERO CRD42013005439.FundingThe National Institute for Health Research Public Health Research programme.</jats:sec

Optimisation of Bioluminescent Reporters for Use with Mycobacteria

BACKGROUND: Mycobacterium tuberculosis, the causative agent of tuberculosis, still represents a major public health threat in many countries. Bioluminescence, the production of light by luciferase-catalyzed reactions, is a versatile reporter technology with multiple applications both in vitro and in vivo. In vivo bioluminescence imaging (BLI) represents one of its most outstanding uses by allowing the non-invasive localization of luciferase-expressing cells within a live animal. Despite the extensive use of luminescent reporters in mycobacteria, the resultant luminescent strains have not been fully applied to BLI. METHODOLOGY/PRINCIPAL FINDINGS: One of the main obstacles to the use of bioluminescence for in vivo imaging is the achievement of reporter protein expression levels high enough to obtain a signal that can be detected externally. Therefore, as a first step in the application of this technology to the study of mycobacterial infection in vivo, we have optimised the use of firefly, Gaussia and bacterial luciferases in mycobacteria using a combination of vectors, promoters, and codon-optimised genes. We report for the first time the functional expression of the whole bacterial lux operon in Mycobacterium tuberculosis and M. smegmatis thus allowing the development of auto-luminescent mycobacteria. We demonstrate that the Gaussia luciferase is secreted from bacterial cells and that this secretion does not require a signal sequence. Finally we prove that the signal produced by recombinant mycobacteria expressing either the firefly or bacterial luciferases can be non-invasively detected in the lungs of infected mice by bioluminescence imaging. CONCLUSIONS/SIGNIFICANCE: While much work remains to be done, the finding that both firefly and bacterial luciferases can be detected non-invasively in live mice is an important first step to using these reporters to study the pathogenesis of M. tuberculosis and other mycobacterial species in vivo. Furthermore, the development of auto-luminescent mycobacteria has enormous ramifications for high throughput mycobacterial drug screening assays which are currently carried out either in a destructive manner using LuxAB or the firefly luciferase

Straight-sided beer and cider glasses to reduce alcohol sales for on-site consumption: A randomised crossover trial in bars.

BACKGROUND: Straight-sided glasses can slow the rate of lager consumption in a laboratory setting compared with curved glasses. Slower drinking rates may lower overall alcohol consumption. Glass shape is therefore a potential target for intervention. The aim of this randomised crossover trial was to estimate the impact of serving draught beer and cider in straight-sided glasses, compared with usual, predominantly curved glasses, on alcohol sales for on-site consumption in bars. METHODS: Twenty-four bars in England completed two intervention periods (A) and two control periods (B) in a randomised order: 1) BABA; 2) BAAB; 3) ABBA; or 4) ABAB. Each period lasted two weeks and involved serving draught beer and cider in either straight-sided glasses (A) or the venue's usual glasses (≥75% curved; B). The primary outcome was the mean volume (in litres) of draught beer and cider sold weekly, compared between A and B periods using a paired-samples t-test on aggregate data. A regression model adjusted for season, order, special events, and busyness. FINDINGS: Mean weekly volume sales of draught beer and cider was 690·9 L (SD 491·3 L) across A periods and 732·5 L (SD 501·0 L) across B periods. The adjusted mean difference (A minus B) was 8·9 L per week (95% CI -45·5 to 63·3; p = 0·737). INTERPRETATION: This study provides no clear evidence that using straight-sided glasses, compared with usual, predominantly curved glasses, reduces the volume of draught beer and cider sold for on-site consumption in bars

Four patients with a history of acute exacerbations of COPD: implementing the CHEST/Canadian Thoracic Society guidelines for preventing exacerbations

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