A Rank-Based Nonparametric Method for Mapping Quantitative Trait Loci in Outbred Half-Sib Pedigrees: Application to Milk Production in a Granddaughter Design

We describe the development of a multipoint nonparametric quantitative trait loci mapping method based on the Wilcoxon rank-sum test applicable to outbred half-sib pedigrees. The method has been evaluated on a simulated dataset and its efficiency compared with interval mapping by using regression. It was shown that the rank-based approach is slightly inferior to regression when the residual variance is homoscedastic normal; however, in three out of four other scenarios envisaged, i.e., residual variance heteroscedastic normal, homoscedastic skewed, and homoscedastic positively kurtosed, the latter outperforms the former one. Both methods were applied to a real data set analyzing the effect of bovine chromosome 6 on milk yield and composition by using a 125-cM map comprising 15 microsatellites and a granddaughter design counting 1158 Holstein-Friesian sires

Adverse Drug Reactions in Hospital In-Patients: A Prospective Analysis of 3695 Patient-Episodes

Adverse drug reactions (ADRs) are a major cause of hospital admissions, but recent data on the incidence and clinical characteristics of ADRs which occur following hospital admission, are lacking. Patients admitted to twelve wards over a six-month period in 2005 were assessed for ADRs throughout their admission. Suspected ADRs were recorded and analysed for causality, severity and avoidability and whether they increased the length of stay. Multivariable analysis was undertaken to identify the risk factors for ADRs. The 5% significance level was used when assessing factors for inclusion in multivariable models. Out of the 3695 patient episodes assessed for ADRs, 545 (14.7%, 95% CI 13.6–15.9%) experienced one or more ADRs. Half of ADRs were definitely or possibly avoidable. The patients experiencing ADRs were more likely to be older, female, taking a larger number of medicines, and had a longer length of stay than those without ADRs. However, the only significant predictor of ADRs, from the multivariable analysis of a representative sample of patients, was the number of medicines taken by the patient with each additional medication multiplying the hazard of an ADR episode by 1.14 (95% CI 1.09, 1.20). ADRs directly increased length of stay in 147 (26.8%) patients. The drugs most frequently associated with ADRs were diuretics, opioid analgesics, and anticoagulants. In conclusion, approximately one in seven hospital in-patients experience an ADR, which is a significant cause of morbidity, increasing the length of stay of patients by an average of 0.25 days/patient admission episode. The overall burden of ADRs on hospitals is high, and effective intervention strategies are urgently needed to reduce this burden

Explaining Scientific Progress. Lakatos's Methodological Account of Kuhnian Patterns of Theory Change

Carrier M. Explaining Scientific Progress. Lakatos's Methodological Account of Kuhnian Patterns of Theory Change. In: Kampis G, Kvasz L, Stöltzner M, eds. Appraising Lakatos: Mathematics, Meth­od­ology, and the Man. Vienna Circle Institute library. Vol 1. Dordrecht [u.a.]: Kluwer Academic Publishers; 2002: 53-71

Delayed initiation of subcutaneous insulin therapy after failure of oral glucose-lowering agents in patients with Type 2 diabetes: a population-based analysis in the UK.

AIMS: The aim of this retrospective cohort study was to estimate the time to insulin initiation in patients with Type 2 diabetes inadequately controlled on oral glucose-lowering agents (OGLAs). METHODS: Insulin-naïve patients failing on OGLAs were identified from The Health Improvement Network database, which collects records from general practices throughout the UK. Patients were included if they were aged > or = 40 years, had concomitant prescriptions for > or = 2 OGLAs, and > or = 1 year of available records prior to the first occurrence of HbA(1c) > or = 8.0% after > or = 90 days of OGLA polytherapy at > or = 50% of maximum recommended dosages. RESULTS: A total of 2501 eligible patients with Type 2 diabetes who had an HbA(1c) above the OGLA failure threshold of > or = 8.0% were identified (54.0% male; 30.9% aged 60-69 years). It was estimated that if all the eligible patients were followed for 5 years, 25% would initiate insulin within 1.8 years of OGLA failure (95% CI 1.6-2.0), and 50% within 4.9 years (95% CI 4.6-5.8). The presence of diabetes-related complications had no substantial impact on the time to insulin initiation. CONCLUSIONS: This study found that 25% of patients with Type 2 diabetes had insulin initiation delayed for at least 1.8 years, and 50% of patients delayed starting insulin for almost 5 years after failure of glycaemic control with OGLA polytherapy, even in the presence of diabetes-related complications. Interventions that reduce this delay to insulin initiation are required to help achieve and maintain recommended glycaemic targets in patients with Type 2 diabetes

Inquiry based mathematics education and the development of learning trajectories

This article is based on the panel on inquiry based mathematics education and the development of learning trajectories held at the VARGA 100 Conference. After an introduction presenting the theme and organization of the panel, this article focuses on the diversity of conceptualizations of inquiry based education existing today in mathematics education and their influence on the vision and development of learning trajectories. More precisely, it considers the conceptualizations respectively associated with Realistic Mathematics Education, Genetic Constructivism, Tamás Varga’s educational approach and the Anthropological Theory of the Didactic, presented by the panellists, and also shows the efforts undertaken in European projects to reach consensusal visions