A gene variant near ATM is significantly associated with metformin treatment response In type 2 diabetes: A replication and meta-analysis of five cohorts

_Aims/hypothesis:_ In this study we aimed to replicate the previously reported association between the glycaemic response to metformin and the SNP rs11212617 at a locus that includes the ataxia telangiectasia mutated (ATM) gene in multiple additional populations. _Methods:_ Incident users of metformin selected from the Diabetes Care System West-Friesland (DCS, n=929) and the Rotterdam Study (n=182) from the Netherlands, and the CARDS Trial (n=254) from the UK were genotyped for rs11212617 and tested for an association with both HbA1c reduction and treatment success, defined as the ability to reach the treatment target of an HbA1c ≤7 % (53 mmol/mol). Finally, a meta-analysis including data from literature was performed. _Results:_ In the DCS cohort, we observed an association between rs11212617 genotype and treatment success on metformin (OR 1.27, 95% CI 1.03, 1.58, p=0.028); in the smaller Rotterdam Study cohort, a numerically similar but non-significant trend was observed (OR 1.45, 95% CI 0.87, 2.39, p=0.15); while in the CARDS cohort there was no significant association. In meta-analyses of these three cohorts separately or combined with the previously published cohorts, rs11212617 genotype is associated with metformin treatment success (OR 1.24, 95% CI 1.04, 1.49, p=0.016 and OR 1.25, 95% CI 1.33, 1.38, p=7.8×10-6, respectively). _ Conclusions/inte

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Utilising the ‘Getting to Outcomes^®’ Framework in Community Engagement for Development and Implementation of Sickle Cell Disease Newborn Screening in Kaduna State, Nigeria

Background: Sickle Cell Disease (SCD) has been designated by WHO as a public health problem in sub-Saharan Africa, and the development of newborn screening (NBS) is crucial to the reduction of high SCD morbidity and mortality. Strategies from the field of implementation science can be useful for supporting the translation of NBS evidence from high income countries to the unique cultural context of sub-Saharan Africa. One such strategy is community engagement at all levels of the healthcare system, and a widely-used implementation science framework, &#8220;Getting to Outcomes&#174;&#8222; (GTO), which incorporates continuous multilevel evaluation by stakeholders about the quality of the implementation. Objectives: (1) to obtain critical information on potential barriers to NBS in the disparate ethnic groups and settings (rural and urban) in the healthcare system of Kaduna State in Nigeria; and, (2) to assist in the readiness assessment of Kaduna in the implementation of a sustainable NBS programme for SCD. Methods: Needs assessment was conducted with stakeholder focus groups for two days in Kaduna state, Nigeria, in November 2017. Results: The two-day focus group workshop had a total of 52 participants. Asking and answering the 10 GTO accountability questions provided a structured format to understand strengths and weaknesses in implementation. For example, we found a major communication gap between policy-makers and user groups. Conclusion: In a two-day community engagement workshop, stakeholders worked successfully together to address SCD issues, to engage with each other, to share knowledge, and to prepare to build NBS for SCD in the existing healthcare system

Randomized Controlled Comparison of Two Cognitive Behavioral Therapies for Obese Children: Mother versus Mother-Child Cognitive Behavioral Therapy

BACKGROUND: Parent-child treatments have been shown to be superior to child-focused treatments of childhood obesity. Yet until now, the comparative effectiveness of parent-only and parent-child approaches has been little studied. METHOD: Fifty-six obese children and their families were randomly assigned to a 16-session cognitive behavioral therapy (CBT) for the parents only or for a combined treatment of parents and children. Children's percent overweight, the body mass index of their mothers, and behavioral and psychological problems of children and mothers were assessed. RESULTS: Both treatments reduced children's percent overweight significantly and equally by 6-month follow-up. Also both treatments provided similar results in reducing general behavior problems (externalizing and internalizing behavior problems), global and social anxiety, and depression. CONCLUSIONS: Our results point to a comparable efficacy of the two treatments. Further, psychological well-being of both mothers and children can be improved in a CBT for obese children and their parents. Future studies should focus on finding ways to improve the adherence of families to long-term treatment of obesity in childhood

Comparing TV ads and advergames targeting children: the impact of persuasion knowledge on behavioural response

Although thousands of advergames are directed at children, little is known about how advergames affect children and whether this persuasive process differs from traditional advertising formats. Investigating the underlying persuasive mechanism, Study 1 shows that, for TV advertising, persuasion knowledge drives the persuasive effects while, for advergames, persuasion is mainly driven by the attitude toward the game. Adding advertising cues to the advergame does not increase persuasion knowledge but does diminish the positive attitude toward the game effect, influencing behavior indirectly. Study 2 demonstrates that, for an advergame, the persuasive mechanism does not differ between a commercial versus a social persuasive message

Children's responses to advertising in social games

Contains fulltext : 116862.pdf (publisher's version ) (Closed access)This study explored children's (ages 9 through 12) level of persuasion knowledge and peer influence susceptibility concerning advertising in social games and investigated how these variables affect children's desire for the brands advertised in these games. Results showed that (1) children have a fairly good knowledge of the advertising in social games yet hold uncritical attitudes toward it and claim to be not very susceptible to peer influence; (2) the most important predictors of children's desire for the advertised brands are a low critical attitude and high peer influence susceptibility; and (3) recognition and understanding of advertising in social games is effective in reducing advertised brand desire only for children who are familiar with social games