A Systems Genetics Approach Implicates USF1, FADS3, and Other Causal Candidate Genes for Familial Combined Hyperlipidemia

We hypothesized that a common SNP in the 3' untranslated region of the upstream transcription factor 1 (USF1), rs3737787, may affect lipid traits by influencing gene expression levels, and we investigated this possibility utilizing the Mexican population, which has a high predisposition to dyslipidemia. We first associated rs3737787 genotypes in Mexican Familial Combined Hyperlipidemia (FCHL) case/control fat biopsies, with global expression patterns. To identify sets of co-expressed genes co-regulated by similar factors such as transcription factors, genetic variants, or environmental effects, we utilized weighted gene co-expression network analysis (WGCNA). Through WGCNA in the Mexican FCHL fat biopsies we identified two significant Triglyceride (TG)-associated co-expression modules. One of these modules was also associated with FCHL, the other FCHL component traits, and rs3737787 genotypes. This USF1-regulated FCHL-associated (URFA) module was enriched for genes involved in lipid metabolic processes. Using systems genetics procedures we identified 18 causal candidate genes in the URFA module. The FCHL causal candidate gene fatty acid desaturase 3 (FADS3) was associated with TGs in a recent Caucasian genome-wide significant association study and we replicated this association in Mexican FCHL families. Based on a USF1-regulated FCHL-associated co-expression module and SNP rs3737787, we identify a set of causal candidate genes for FCHL-related traits. We then provide evidence from two independent datasets supporting FADS3 as a causal gene for FCHL and elevated TGs in Mexicans

Growth of medical knowledge

Background Knowledge is an essential component of medical competence and a major objective of medical education. Thus, the degree of acquisition of knowledge by students is one of the measures of the effectiveness of a medical curriculum. We studied the growth in student knowledge over the course of Maastricht Medical School's 6-year problem-based curriculum. Methods We analysed 60 491 progress test (PT) scores of 3226 undergraduate students at Maastricht Medical School. During the 6-year curriculum a student sits 24 PTs (i.e. four PTs in each year), intended to assess knowledge at graduation level. On each test occasion all students are given the same PT, which means that in year 1 a student is expected to score considerably lower than in year 6. The PT is therefore a longitudinal, objective assessment instrument. Mean scores for overall knowledge and for clinical, basic, and behavioural/social sciences knowledge were calculated and used to estimate growth curves. Findings Overall medical knowledge and clinical sciences knowledge demonstrated a steady upward growth curve. However, the curves for behavioural/social sciences and basic sciences started to level off in years 4 and 5, respectively. The increase in knowledge was greatest for clinical sciences (43%), whereas it was32% and 25% for basic and behavioural/social sciences, respectively. Interpretation Maastricht Medical School claims to offer a problem-based, student-centred, horizontally and vertically integrated curriculum in the first 4 years, followed by clerkships in years 5 and 6. Students learn by analysing patient problems and exploring pathophysiological explanations. Originally, it was intended that students' knowledge of behavioural/social sciences would continue to increase during their clerkships. However, the results for years 5 and 6 show diminishing growth in basic and behavioural/social sciences knowledge compared to overall and clinical sciences knowledge, which appears to suggest there are discrepancies between the actual and the planned curricula. Further research is needed to explain this

Panel expertise for an Angoff standard setting procedure in progress testing: item writers compared to recently graduated students

Introduction An earlier study showed that an Angoff procedure with greater than or equal to 10 recently graduated students as judges can be used to estimate the passing score of a progress test. As the acceptability and feasibility of this approach are questionable, we conducted an Angoff procedure with test item writers as judges. This paper reports on thereliability and credibility of this procedure and compares the standards set by the two different panels. Methods Fourteen item writers judged 146 test items. Recently graduated students had assessed these items in a previous study. Generalizability was investigated as a function of the number of items and judges. Credibility was judged by comparing the pass/fail rates associated with the Angoff standard, a relative standard and a fixed standard. The Angoff standards obtained by item writers and graduates were compared. Results The variance associated with consistent variability of item writers across items was 1.5% and for graduate students it was 0.4%. An acceptable error score required 39 judges. Item-Angoff estimates of the two panels and item P -values correlated highly. Failure rates of 57%, 55% and 7% were associated with the item writers' standard, the fixed standard and the graduates' standard, respectively. Conclusion The graduates' and the item writers' standards differed substantially, as did the associated failure rates. A panel of 39 item writers is not feasible. The item writers' passing score appears to be less credible. The credibility of the graduates' standard needs further evaluation. The acceptability and feasibility of a panel consisting of both students and item writers may be worth investigating

Objective structured clinical examinations (OSCEs), psychiatry and the clinical assessment of skills and competencies (CASC) : same evidence, different judgement

Background: The Objective Structured Clinical Examination (OSCE), originally developed in the 1970’s, has been hailed as the "gold standard" of clinical assessments for medical students and is used within medical schools throughout the world. The Clinical assessment of Skills and Competencies (CASC) is an OSCE used as a clinical examination gateway, granting access to becoming a senior Psychiatrist in the UK. Discussion: Van der Vleuten’s utility model is used to examine the CASC from the viewpoint of a senior psychiatrist. Reliability may be equivalent to more traditional examinations. Whilst the CASC is likely to have content validity, other forms of validity are untested and authenticity is poor. Educational impact has the potential to change facets of psychiatric professionalism and influence future patient care. There are doubts about acceptability from candidates and more senior psychiatrists. Summary: Whilst OSCEs may be the best choice for medical student examinations, their use in post graduate psychiatric examination in the UK is subject to challenge on the grounds of validity, authenticity and educational impact

Gait and calf muscle endurance in patients with chronic venous insufficiency.

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