On the Analysis of Genome-Wide Association Studies in Family-Based Designs: A Universal, Robust Analysis Approach and an Application to Four Genome-Wide Association Studies

For genome-wide association studies in family-based designs, we propose a new, universally applicable approach. The new test statistic exploits all available information about the association, while, by virtue of its design, it maintains the same robustness against population admixture as traditional family-based approaches that are based exclusively on the within-family information. The approach is suitable for the analysis of almost any trait type, e.g. binary, continuous, time-to-onset, multivariate, etc., and combinations of those. We use simulation studies to verify all theoretically derived properties of the approach, estimate its power, and compare it with other standard approaches. We illustrate the practical implications of the new analysis method by an application to a lung-function phenotype, forced expiratory volume in one second (FEV1) in 4 genome-wide association studies

Validation of a method for identifying nursing home admissions using administrative claims

<p>Abstract</p> <p>Background</p> <p>Currently there is no standard algorithm to identify whether a subject is residing in a nursing home from administrative claims. Our objective was to develop and validate an algorithm that identifies nursing home admissions at the resident-month level using the MarketScan Medicare Supplemental and Coordination of Benefit (COB) database.</p> <p>Methods</p> <p>The computer algorithms for identifying nursing home admissions were created by using provider type, place of service, and procedure codes from the 2000 – 2002 MarketScan Medicare COB database. After the algorithms were reviewed and refined, they were compared with a detailed claims review by an expert reviewer. A random sample of 150 subjects from the claims was selected and used for the validity analysis of the algorithms. Contingency table analysis, comparison of mean differences, correlations, and t-test analyses were performed. Percentage agreement, sensitivity, specificity, and Kappa statistics were analyzed.</p> <p>Results</p> <p>The computer algorithm showed strong agreement with the expert review (99.9%) for identification of the first month of nursing home residence, with high sensitivity (96.7%), specificity (100%) and a Kappa statistic of 0.97. Weighted Pearson correlation coefficient between the algorithm and the expert review was 0.97 (<it>p </it>< 0.0001).</p> <p>Conclusion</p> <p>A reliable algorithm indicating evidence of nursing home admission was developed and validated from administrative claims data. Our algorithm can be a useful tool to identify patient transitions from and to nursing homes, as well as to screen and monitor for factors associated with nursing home admission and nursing home discharge.</p

Protein Pattern Formation

Protein pattern formation is essential for the spatial organization of many intracellular processes like cell division, flagellum positioning, and chemotaxis. A prominent example of intracellular patterns are the oscillatory pole-to-pole oscillations of Min proteins in \textit{E. coli} whose biological function is to ensure precise cell division. Cell polarization, a prerequisite for processes such as stem cell differentiation and cell polarity in yeast, is also mediated by a diffusion-reaction process. More generally, these functional modules of cells serve as model systems for self-organization, one of the core principles of life. Under which conditions spatio-temporal patterns emerge, and how these patterns are regulated by biochemical and geometrical factors are major aspects of current research. Here we review recent theoretical and experimental advances in the field of intracellular pattern formation, focusing on general design principles and fundamental physical mechanisms.Comment: 17 pages, 14 figures, review articl

Cosmogenic neutron production at the Sudbury Neutrino Observatory

Neutrons produced in nuclear interactions initiated by cosmic-ray muons present an irreducible background to many rare-event searches, even in detectors located deep underground. Models for the production of these neutrons have been tested against previous experimental data, but the extrapolation to deeper sites is not well understood. Here we report results from an analysis of cosmogenically produced neutrons at the Sudbury Neutrino Observatory. A specific set of observables are presented, which can be used to benchmark the validity of geant4 physics models. In addition, the cosmogenic neutron yield, in units of 10-4 cm2/(g·μ), is measured to be 7.28±0.09(stat)-1.12+1.59(syst) in pure heavy water and 7.30±0.07(stat)-1.02+1.40(syst) in NaCl-loaded heavy water. These results provide unique insights into this potential background source for experiments at SNOLAB

Spatial dependency of action simulation

In this study, we investigated the spatial dependency of action simulation. From previous research in the field of single-cell recordings, grasping studies and from crossmodal extinction tasks, it is known that our surrounding space can be divided into a peripersonal space and extrapersonal space. These two spaces are functionally different at both the behavioral and neuronal level. The peripersonal space can be seen as an action space which is limited to the area in which we can grasp objects without moving the object or ourselves. The extrapersonal space is the space beyond the peripersonal space. Objects situated within peripersonal space are mapped onto an egocentric reference frame. This mapping is thought to be accomplished by action simulation. To provide direct evidence of the embodied nature of this simulated motor act, we performed two experiments, in which we used two mental rotation tasks, one with stimuli of hands and one with stimuli of graspable objects. Stimuli were presented in both peri- and extrapersonal space. The results showed increased reaction times for biomechanically difficult to adopt postures compared to more easy to adopt postures for both hand and graspable object stimuli. Importantly, this difference was only present for stimuli presented in peripersonal space but not for the stimuli presented in extrapersonal space. These results extend previous behavioral findings on the functional distinction between peripersonal- and extrapersonal space by providing direct evidence for the spatial dependency of the use of action simulation. Furthermore, these results strengthen the hypothesis that objects situated within the peripersonal space are mapped onto an egocentric reference frame by action simulation

Training of attention functions in children with attention deficit hyperactivity disorder

Pharmacological treatment of children with ADHD has been shown to be successful; however, medication may not normalize attention functions. The present study was based on a neuropsychological model of attention and assessed the effect of an attention training program on attentional functioning of children with ADHD. Thirty-two children with ADHD and 16 healthy children participated in the study. Children with ADHD were randomly assigned to one of the two conditions, i.e., an attention training program which trained aspects of vigilance, selective attention and divided attention, or a visual perception training which trained perceptual skills, such as perception of figure and ground, form constancy and position in space. The training programs were applied in individual sessions, twice a week, for a period of four consecutive weeks. Healthy children did not receive any training. Alertness, vigilance, selective attention, divided attention, and flexibility were examined prior to and following the interventions. Children with ADHD were assessed and trained while on ADHD medications. Data analysis revealed that the attention training used in the present study led to significant improvements of various aspects of attention, including vigilance, divided attention, and flexibility, while the visual perception training had no specific effects. The findings indicate that attention training programs have the potential to facilitate attentional functioning in children with ADHD treated with ADHD drugs