Replication in Genome-Wide Association Studies

Replication helps ensure that a genotype-phenotype association observed in a genome-wide association (GWA) study represents a credible association and is not a chance finding or an artifact due to uncontrolled biases. We discuss prerequisites for exact replication, issues of heterogeneity, advantages and disadvantages of different methods of data synthesis across multiple studies, frequentist vs. Bayesian inferences for replication, and challenges that arise from multi-team collaborations. While consistent replication can greatly improve the credibility of a genotype-phenotype association, it may not eliminate spurious associations due to biases shared by many studies. Conversely, lack of replication in well-powered follow-up studies usually invalidates the initially proposed association, although occasionally it may point to differences in linkage disequilibrium or effect modifiers across studies.Comment: Published in at http://dx.doi.org/10.1214/09-STS290 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

The Ideal Free Distribution of Group Choice: A social psychology of human behavior

This dissertation presents an experimental analysis of social behavior. The behavior is called Group Choice (Baum & Kraft, 1998) and the analysis is a social foraging model called the Ideal Free Distribution (IFD; Fretwell & Lucas, 1970). The IFD is a social foraging model that describes the distribution of a group of foragers in a patchy environment. Group Choice describes group members engaging in two behaviors. The IFD suggests that group members engage in two behaviors in the same relative relation to the consequences obtained from those behaviors. The IFD of Group Choice is analogous to the Matching Law analysis of individual choice (Baum, 1974; Herrnstein, 1961, 1970; Kennedy & Gray, 1993). The results showed consistent IFD matching of the groups\u27 choices to the point distributions when unequal amounts of points were shared among subgroup members (Experiments 1, 2, 7a, and 7b). In contrast, the groups undermatched point distributions when the points were allocated probabilistically. Groups tended to match to the same degree regardless of the type of behavior alternative (i.e., sitting in chairs or choosing cards). Not being able to ideally distribute (imperfect solutions) tended to reduce group sensitivity to the distribution of points. Assigning different competitive weights to participants did not have an impact on group choice. Overall, the groups\u27 choices before knowing what others chose were more variable, but similar to the choices made after knowing what others chose. Analyses of individuals\u27 consistency in preferences and obtained points from block-to-block of trials failed to reveal order on the individual level that could explain the group level results. A promising analysis of individuals\u27 choices between alternatives and obtained points from those alternatives also did not reveal a satisfactory explanation for group level results. The analogy between an IFD analysis of Group Choice and a Matching Law analysis of individual choice may be far reaching. Whereas an individual\u27s responses match the relative consequences, group members\u27 behavior match the relative resources. Basic equations for both relations can be expressed in ratio form and generalized to account for deviations as a power function. Undermatching is the common result for both lines of research. Whereas the Matching Law describing individual choice became the foundation for the quantification of the Law of Effect and decades of fruitful research, it remains to be seen if the IFD of Group Choice stimulates similar progress. If the analogy between the Matching Law analysis of individual choice and the IFD of Group Choice is thoroughgoing, this research may provide the foundation for the quantification of a social level Law of Effect. (Abstract shortened by UMI.)

Alternative Approach for Assessment of Hydraulic Design Basis for Pressure Pipe Liners

New product development requires stringent testing to ensure that strength and safety standards are met by the innovative materials. When developing a new pipe material, several factors have to be tested for. In addition to normal material characteristics such as elastic modulus of pipe materials, long-term hydrostatic strength (LTHS) and hydrostatic design basis (HDB) are needed. Tests for typical material characteristics are commonplace and can certainly be conducted in most lab facilities. In contrast, LTHS and HDB as described in ASTM D2992 are two tests that can prove very challenging to conduct. The current method requires a minimum of 18 full pipe specimen be placed under hydrostatic test at various stress levels to produce required failures. Successfully generating these failures can be very hard to achieve with a relatively unfamiliar material. This work suggests a modified method drawing from years of successful ASTM D2990 testing. This method will combine the loading apparatus used for ASTM D2990 creep testing, strain gauges and a new relationship between strain and the typical ductile failures seen in D2992 testing. It is also possible, with existing long-term data, to model the material behavior and reduce time further. The goal of this approach is to increase the volume of testing in order to ensure a higher level of confidence for designers and owners and save clients research funding as well

Brain Mechanisms Supporting the Modulation of Pain by Mindfulness Meditation

The subjective experience of one’s environment is constructed by interactions among sensory, cognitive, and affective processes. For centuries, meditation has been thought to influence such processes by enabling a nonevaluative representation of sensory events. To better understand how meditation influences the sensory experience, we used arterial spin labeling functional magnetic resonance imaging to assess the neural mechanisms by which mindfulness meditation influences pain in healthy human participants. After 4 d of mindfulness meditation training, meditating in the presence of noxious stimulation significantly reduced pain unpleasantness by 57% and pain intensity ratings by 40% when compared to rest. A two-factor repeated-measures ANOVA was used to identify interactions between meditation and pain-related brain activation. Meditation reduced pain-related activation of the contralateral primary somatosensory cortex. Multiple regression analysis was used to identify brain regions associated with individual differences in the magnitude of meditation-related pain reductions. Meditation-induced reductions in pain intensity ratings were associated with increased activity in the anterior cingulate cortex and anterior insula, areas involved in the cognitive regulation of nociceptive processing. Reductions in pain unpleasantness ratings were associated with orbitofrontal cortex activation, an area implicated in reframing the contextual evaluation of sensory events. Moreover, reductions in pain unpleasantness also were associated with thalamic deactivation, which may reflect a limbic gating mechanism involved in modifying interactions between afferent input and executive-order brain areas. Together, these data indicate that meditation engages multiple brain mechanisms that alter the construction of the subjectively available pain experience from afferent information