Schoolcompositie en kenmerken van docentkwaliteit op VO-scholen. Resultaten van secundaire analyses op de Nederlandse data in het OESO-TALIS 2013 bestand.

In deze studie worden de resultaten gerapporteerd van secundaire analyses op de Nederlandse data van het Teaching and Learning International Survey (TALIS) onderzoek van de OESO. Onderzocht werd of schoolcompositie en ervaring een verband hadden met werktevredenheid, kenmerken van docentkwaliteit en behoefte aan professionalisering op het gebied van diversiteit. Uit de resultaten blijkt dat docenten op scholen met relatief veel leerlingen met een lage sociaaleconomische achtergrond, minder tevreden zijn met hun beroep, minder vertrouwen i

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.

Congenital heart defects (CHDs) have a neonatal incidence of 0.8-1% (refs. 1,2). Despite abundant examples of monogenic CHD in humans and mice, CHD has a low absolute sibling recurrence risk (∼2.7%), suggesting a considerable role for de novo mutations (DNMs) and/or incomplete penetrance. De novo protein-truncating variants (PTVs) have been shown to be enriched among the 10% of 'syndromic' patients with extra-cardiac manifestations. We exome sequenced 1,891 probands, including both syndromic CHD (S-CHD, n = 610) and nonsyndromic CHD (NS-CHD, n = 1,281). In S-CHD, we confirmed a significant enrichment of de novo PTVs but not inherited PTVs in known CHD-associated genes, consistent with recent findings. Conversely, in NS-CHD we observed significant enrichment of PTVs inherited from unaffected parents in CHD-associated genes. We identified three genome-wide significant S-CHD disorders caused by DNMs in CHD4, CDK13 and PRKD1. Our study finds evidence for distinct genetic architectures underlying the low sibling recurrence risk in S-CHD and NS-CHD

Age at First Alcohol Use as a Possible Risk Factor for Adolescent Acute Alcohol Intoxication Hospital Admission in the Netherlands

Background: The primary objective of this study is to determine whether age at first alcohol use is a determinant for adolescent acute alcohol intoxication characteristics, such as age at first acute alcohol intoxication and blood alcohol concentration (BAC) at hospital admission. Around the world, as in the Netherlands, a key aim of alcohol policy is to postpone the age at first alcohol use. This is based on cohort studies that indicate a relationship between a younger age at first alcohol use and subsequent adult alcohol use disorders. Methods: This study was conducted using a cohort of data comprising individuals under 18 years of age. Data were collected between 2007 and 2017 by the Dutch Pediatric Surveillance System (NSCK) in order to monitor trends in admissions for acute alcohol intoxication. Multivariate linear regression analyses were used to determine the association between age at first alcohol use and acute alcohol intoxication characteristics, such as age at first acute alcohol intoxication and BAC at admission. Results: This study indicates that among adolescents admitted for acute alcohol intoxication, adolescents who started drinking at ≤ 14 years of age are significantly more often female, lower educated, and raised in nontraditional family structures than adolescents who started drinking between 15 and 18 years of age. Multiple linear regression analyses indicated that age at first alcohol use, corrected for covariates, significantly predicted the age at acute alcohol intoxication and BAC at admission. The association between age at first alcohol use and age at intoxication was also found to be clinically relevant. Conclusions: Although causation cannot be implied based on the results of these analyses, the results of this study suggest that interventions delaying the age at first alcohol use could be successful in increasing the average age that adolescents are admitted to the hospital for acute alcohol intoxication