Validity assumptions for a multiple-choice test of medical knowledge with open-books and web access. A known groups comparison study.

Relatively little evidence about the validity threats in open-book multiple-choice tests exist. The aim of this study was to examine validity aspects relating to gener-alization, extrapolation and decision of a multiple-choice test of medical knowledge with aids (open-book and internet access). The theoretical framework was modern validity theory, and the study was designed as a ‘known groups com-parison’ study. Test performances of three known groups of test takers hypothe-sized to have different knowledge levels of the test content were compared, and analysis of pass/fail decisions was used to examine implications of decisions based on test scores. Results indicated that it was possible to discriminate between expert and non-expert test taker groups even with the access to aids. In contrast, an inde-fensible passing score was found to be the largest potential threat to test validity. Relatively little evidence about the validity threats in open-book multiple-choice tests exist. The aim of this study was to examine validity aspects relating to gener-alization, extrapolation and decision of a multiple-choice test of medical knowledge with aids (open-book and internet access). The theoretical framework was modern validity theory, and the study was designed as a ‘known groups com-parison’ study. Test performances of three known groups of test takers hypothe-sized to have different knowledge levels of the test content were compared, and analysis of pass/fail decisions was used to examine implications of decisions based on test scores. Results indicated that it was possible to discriminate between expert and non-expert test taker groups even with the access to aids. In contrast, an inde-fensible passing score was found to be the largest potential threat to test validity.&nbsp

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes