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Social learning through friendships is important in child development. Autistic children often initiate and engage in social interactions differently than neurotypical peers. LEGO® based therapy is a group intervention which facilitates social interactions with peers using collaborative LEGO® play. A 1:1 cluster randomised controlled trial with autistic children aged 7-15 comparing 12 weeks' LEGO® based therapy and usual support to usual support alone in 98 mainstream schools (2017-2019) was carried out. The primary outcome was social skills (Social Skills Improvement System) completed by unblinded teachers (not intervention deliverers) at 20 weeks. Analysis used intention-to-treat. Fifty intervention schools (127 participants) and 48 control schools (123 participants) were allocated. Primary analysis included 45 intervention schools (116 participants) and 42 control schools (101 participants). The between-arms difference was 3.74 (p = 0.06, 95% confidence interval: -0.16, 7.63) and 1.68 (p = 0.43, 95% confidence interval: -2.51, 5.87) at 20 and 52 weeks (0.18 and 0.08 standardised effect sizes). Twenty-week outcomes for those receiving per protocol intervention were 4.23 (95% confidence interval 0.27, 8.19) with a standardised effect size of 0.21. Sensitivity estimates were between 3.10 and 4.37 (0.15-0.21 standardised effect sizes). Three unrelated serious adverse events were reported. LEGO® based therapy has a small positive non-significant benefit for social skills at 20 weeks but not 52 weeks.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 300,000 people worldwide. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease. As therapies that slow or prevent symptoms continue to develop, such as antisense oligonucleotides, it is important to discover novel genes that could be targets for treatment. Additionally, as cohorts continue to grow, performing analyses in ALS subtypes, such as primary lateral sclerosis (PLS), becomes possible due to an increase in power. These analyses could highlight novel pathways in disease manifestation. Methods: Building on our previous discoveries using rare variant association analyses, we conducted rare variant burden testing on a substantially larger multi-ethnic cohort of 6,970 ALS patients, 166 PLS patients, and 22,524 controls. We used intolerant domain percentiles based on sub-region Residual Variation Intolerance Score (subRVIS) that have been described previously in conjunction with gene based collapsing approaches to conduct burden testing to identify genes that associate with ALS and PLS. Results: A gene based collapsing model showed significant associations with SOD1, TARDBP, and TBK1 (OR = 19.18, p = 3.67 × 10–39; OR = 4.73, p = 2 × 10–10; OR = 2.3, p = 7.49 × 10–9, respectively). These genes have been previously associated with ALS. Additionally, a significant novel control enriched gene, ALKBH3 (p = 4.88 × 10–7), was protective for ALS in this model. An intolerant domain-based collapsing model showed a significant improvement in identifying regions in TARDBP that associated with ALS (OR = 10.08, p = 3.62 × 10–16). Our PLS protein truncating variant collapsing analysis demonstrated significant case enrichment in ANTXR2 (p = 8.38 × 10–6). Conclusions: In a large multi-ethnic cohort of 6,970 ALS patients, collapsing analyses validated known ALS genes and identified a novel potentially protective gene, ALKBH3. A first-ever analysis in 166 patients with PLS found a candidate association with loss-of-function mutations in ANTXR2. [ABSTRACT FROM AUTHOR]

Background and Aim: Drinking alcohol may cause harm to an individual's health and social relationships, while a drinking culture may harm societies as it may increase crime rates and make an area feel less safe. Local councils in Greater Manchester, UK, developed the Communities in Charge of Alcohol (CICA) intervention, in which volunteers were trained to give alcohol‐related advice to the public and taught how to influence policies to restrict when, where and how alcohol is sold. As part of a larger study, the aim of the current project is to measure the impact of CICA on health and crime outcomes at the lower super output (LSOA) geographical aggregation. Design: Quantitative evaluation using four time series analytic methods (stepped‐wedge design, and comparisons to local controls, national controls and synthetic controls) with findings triangulated across these methods. A cost–benefit analysis was carried out alongside the effectiveness analysis. Setting and Participants: The general public in Greater Manchester, UK, between 2010 and 2020. Measurements: The primary outcome of interest was alcohol‐related hospital admissions. Secondary outcomes were accident and emergency (A&E) attendances, ambulance callouts, recorded crimes and anti‐social behaviour incidents. Findings Triangulation of the results did not indicate any consistent effect on area‐level alcohol‐related hospital admissions, A&E attendances, ambulance callouts, reported crimes or anti‐social behaviour associated with the implementation of CICA. The primary stepped‐wedge analysis indicated an increase in alcohol‐related hospital admissions following the implementation of CICA of 13.4% (95% confidence interval −3.3%, +30.1%), which was consistent with analyses based on other methods with point estimates ranging from +3.4% to 16.4%. Conclusion: There is no evidence of a measurable impact of the Communities in Charge of Alcohol (CICA) programme on area‐level health and crime outcomes in Greater Manchester, UK, within 3 years of the programme start. The increase in alcohol‐related hospital admissions was likely the result of other temporal trends rather than the CICA programme. Possible explanations include insufficient follow‐up time, too few volunteers trained, volunteers being unwilling to get involved in licensing decisions or that the intervention has no direct impact on the selected outcomes. [ABSTRACT FROM AUTHOR]

Social learning through friendships is important in child development. Autistic children often initiate and engage in social interactions differently than neurotypical peers. LEGO® based therapy is a group intervention which facilitates social interactions with peers using collaborative LEGO® play. A 1:1 cluster randomised controlled trial with autistic children aged 7–15 comparing 12 weeks' LEGO® based therapy and usual support to usual support alone in 98 mainstream schools (2017–2019) was carried out. The primary outcome was social skills (Social Skills Improvement System) completed by unblinded teachers (not intervention deliverers) at 20 weeks. Analysis used intention-to-treat. Fifty intervention schools (127 participants) and 48 control schools (123 participants) were allocated. Primary analysis included 45 intervention schools (116 participants) and 42 control schools (101 participants). The between-arms difference was 3.74 (p = 0.06, 95% confidence interval: −0.16, 7.63) and 1.68 (p = 0.43, 95% confidence interval: −2.51, 5.87) at 20 and 52 weeks (0.18 and 0.08 standardised effect sizes). Twenty-week outcomes for those receiving per protocol intervention were 4.23 (95% confidence interval 0.27, 8.19) with a standardised effect size of 0.21. Sensitivity estimates were between 3.10 and 4.37 (0.15–0.21 standardised effect sizes). Three unrelated serious adverse events were reported. LEGO® based therapy has a small positive non-significant benefit for social skills at 20 weeks but not 52 weeks. Autism is characterised by keen interests and differences in social interactions and communication. Activities that help autistic children and young people with social skills are commonly used in UK schools. LEGO® based therapy is a new activity that provides interesting and fun social opportunities for children and young people and involves building LEGO® models together. This study looked at LEGO® based therapy for the social skills of autistic children and young people in schools. It was a randomised controlled trial, meaning each school was randomly chosen (like flipping a coin) to either run LEGO® based therapy groups in school over 12 weeks and have usual support from school or other professionals, or only have usual support from school or other professionals. The effect of the LEGO® based therapy groups was measured by asking children and young people, their parents/guardians, and a teacher at school in both arms of the study to complete some questionnaires. The main objective was to see if the teacher's questionnaire answers about the children and young people's social skills changed between their first and second completions. The social skills of participants in the LEGO® based therapy groups were found to have improved in a small way when compared to usual support only. The study also found that LEGO® based therapy was not very costly for schools to run and parents/guardians and teachers said they thought it was good for their children and young people. We suggest further research into different potential benefits of LEGO® based therapy. [ABSTRACT FROM AUTHOR]