A new multitest correction (SGoF) that increases its statistical power when increasing the number of tests

<p>Abstract</p> <p>Background</p> <p>The detection of true significant cases under multiple testing is becoming a fundamental issue when analyzing high-dimensional biological data. Unfortunately, known multitest adjustments reduce their statistical power as the number of tests increase. We propose a new multitest adjustment, based on a sequential goodness of fit metatest (SGoF), which increases its statistical power with the number of tests. The method is compared with Bonferroni and FDR-based alternatives by simulating a multitest context via two different kinds of tests: 1) one-sample t-test, and 2) homogeneity G-test.</p> <p>Results</p> <p>It is shown that SGoF behaves especially well with small sample sizes when 1) the alternative hypothesis is weakly to moderately deviated from the null model, 2) there are widespread effects through the family of tests, and 3) the number of tests is large.</p> <p>Conclusion</p> <p>Therefore, SGoF should become an important tool for multitest adjustment when working with high-dimensional biological data.</p

Understanding discrepancies in parent-child reporting of emotional and behavioural problems: Effects of relational and socio-demographic factors

<p>Abstract</p> <p>Background</p> <p>Discrepancies between parents and children in their assessment of children's mental health affect the evaluation of need for services and must be taken seriously. This article presents the differences between parents' and children's reports of the children's symptoms and social impairment, based on the results of the Strengths and Difficulties Questionnaire (SDQ). The interrelationship between relational aspects and socio-demographic factors with patterns of disagreement are explored.</p> <p>Methods</p> <p>Differences in the prevalence and means of SDQ symptom and impact scores were obtained from 8,154 primary school children, aged between 10 and 13 years, and their parents. Agreement between matched pairs was measured using Pearson's and Spearman's rho correlations. Socio-demographic variables, communication patterns and parental engagement were analysed as possible correlates of informant discrepancies using bivariate and multivariate logistic regression models.</p> <p>Results</p> <p>In general, although children reported more symptoms, they reported less impact of perceived difficulties than parents. The parents were more consistent in their evaluation of symptoms and impact than were the children. Exploration of highly discrepant subgroups showed that, when children reported the most symptoms and impact, qualitative aspects of the parent-child relationship and family structure seemed to be more powerful predictors of disagreement than were gender of the child and socio-demographic variables. When parents reported the most symptoms and impact, low parental educational level, low income and male gender of the child played an additional role.</p> <p>Conclusions</p> <p>Our findings underline the importance of paying attention to child reports of emotional-behavioural difficulties, particularly when parents do not identify these problems. Considerations on what meaning parent-child discrepancy might have in the context of the parent-child relationship or the family's psychosocial status should be integrated in the overall understanding of the child's situation and subsequent recommendations.</p

Neural networks for modeling gene-gene interactions in association studies

<p>Abstract</p> <p>Background</p> <p>Our aim is to investigate the ability of neural networks to model different two-locus disease models. We conduct a simulation study to compare neural networks with two standard methods, namely logistic regression models and multifactor dimensionality reduction. One hundred data sets are generated for each of six two-locus disease models, which are considered in a low and in a high risk scenario. Two models represent independence, one is a multiplicative model, and three models are epistatic. For each data set, six neural networks (with up to five hidden neurons) and five logistic regression models (the null model, three main effect models, and the full model) with two different codings for the genotype information are fitted. Additionally, the multifactor dimensionality reduction approach is applied.</p> <p>Results</p> <p>The results show that neural networks are more successful in modeling the structure of the underlying disease model than logistic regression models in most of the investigated situations. In our simulation study, neither logistic regression nor multifactor dimensionality reduction are able to correctly identify biological interaction.</p> <p>Conclusions</p> <p>Neural networks are a promising tool to handle complex data situations. However, further research is necessary concerning the interpretation of their parameters.</p

Functional treatment versus plaster for simple elbow dislocations (FuncSiE): a randomized trial

Background. Elbow dislocations can be classified as simple or complex. Simple dislocations are characterized by the absence of fractures, while complex dislocations are associated with fractures. After reduction of a simple dislocation, treatment options include immobilization in a static plaster for different periods of time or so-called functional treatment. Functional treatment is characterized by early active motion within the limits of pain with or without the use of a sling or hinged brace. Theoretically, functional treatment should prevent stiffness without introducing increased joint instability. The primary aim of this randomized controlled trial is to compare early functional treatment versus plaster immobilization following simple dislocations of the elbow. Methods/Design. The design of the study will be a multicenter randomized controlled trial of 100 patients who have sustained a simple elbow dislocation. After reduction of the dislocation, patients are randomized between a pressure bandage for 5-7 days and early functional treatment or a plaster in 90 degrees flexion, neutral position for pro-supination for a period of three weeks. In the functional group, treatment is started with early active motion within the limits of pain. Function, pain, and radiographic recovery will be evaluated at regular intervals over the subsequent 12 months. The primary outcome measure is the Quick Disabilities of the Arm, Shoulder, and Hand score. The secondary outcome measures are the Mayo Elbow Performance Index, Oxford elbow score, pain level at both sides, range of motion of the elbow joint at both sides, rate of secondary interventions and complication rates in both groups (secondary dislocation, instability, relaxation), health-related quality of life (Short-Form 36 and EuroQol-5D), radiographic appearance of the elbow joint (degenerative changes and heterotopic ossifications), costs, and cost-effectiveness. Discussion. The successful completion of this trial will provide evidence on the effectiveness of a functional treatment for the management of simple elbow dislocations. Trial Registration. The trial is registered at the Netherlands Trial Register (NTR2025)

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Virtual Reality Simulation and Ergonomics Assessment in Aviation Maintainability

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