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"Interaction Studies"
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Testing for Gene–Environment Interaction Under Exposure Misspecification
Complex interplay between genetic and environmental factors characterizes the etiology of many diseases. Modeling gene-environment (GxE) interactions is often challenged by the unknown functional form of the environment term in the true data-generating mechanism. We study the impact of misspecification of the environmental exposure effect on inference for the GxE interaction term in linear and logistic regression models. We first examine the asymptotic bias of the GxE interaction regression coefficient, allowing for confounders as well as arbitrary misspecification of the exposure and confounder effects. For linear regression, we show that under gene-environment independence and some confounder-dependent conditions, when the environment effect is misspecified, the regression coefficient of the GxE interaction can be unbiased. However, inference on the GxE interaction is still often incorrect. In logistic regression, we show that the regression coefficient is generally biased if the genetic factor is associated with the outcome directly or indirectly. Further, we show that the standard robust sandwich variance estimator for the GxE interaction does not perform well in practical GxE studies, and we provide an alternative testing procedure that has better finite sample properties.
Journal Article
A unified set-based test with adaptive filtering for gene-environment interaction analyses
In genome-wide gene–environment interaction (GxE) studies, a common strategy to improve power is to first conduct a filtering test and retain only the SNPs that pass the filtering in the subsequent GxE analyses. Inspired by two-stage tests and gene-based tests in GxE analysis, we consider the general problem of jointly testing a set of parameters when only a few are truly from the alternative hypothesis and when filtering information is available. We propose a unified set-based test that simultaneously considers filtering on individual parameters and testing on the set. We derive the exact distribution and approximate the power function of the proposed unified statistic in simplified settings, and use them to adaptively calculate the optimal filtering threshold for each set. In the context of gene-based GxE analysis, we show that although the empirical power function may be affected by many factors, the optimal filtering threshold corresponding to the peak of the power curve primarily depends on the size of the gene. We further propose a resampling algorithm to calculate P-values for each gene given the estimated optimal filtering threshold. The performance of the method is evaluated in simulation studies and illustrated via a genome-wide gene–gender interaction analysis using pancreatic cancer genome-wide association data.
Journal Article
Brain, mind and Internet : a deep history and future
\"The 'architecture of the mind' consists of both the biological brain coupled with the technologies that we have developed to extend our cognition. From the moment that we started storing our thoughts in permanent symbolic form outside of our bodies via Venus figures, body paint markings and cave paintings, humans have 'offloaded' cognition onto symbols outside of the brain. These external, materialized symbols have allowed us to extend our cognitive abilities beyond the limits of our biological brains. Far from 'making us stupid', the Internet represents merely the next great extension of this 'external symbolic storage system'. For all the dramatic and disruptive change that the Internet surely represents, placing it in this long term historical context renders this change more familiar, perhaps even less jarring. Understanding that there has been a deep history of intimacy between humans and their cognitive tools provides a framework for thinking about the possible futures of the brain-Internet interface: the future of the architecture of the mind. \"-- Provided by publisher.
Book
Researching Language Teacher Cognition and Practice
This book presents a wide range of methodological perspectives on researching what teachers think and do in language teaching. It contains chapters by the editors and a leading expert in teacher cognition, as well as eight case studies by new researchers, accompanied by commentaries by internationally known researchers.
eBook
The lost boys : inside Muzafer Sherif's Robbers Cave experiment
\"Competition. Prejudice. Discrimination. Conflict. In 1954, a group of American boys attended a remote summer camp where they were split into two groups, and encouraged to bully, harass, and demonize each other. The results would make history as one of social psychology's classic studies, and most controversial, studies: the Robbers Cave experiment. Conducted at the height of the Cold War, officially the experiment had a happy ending: the boys reconciled, and psychologist Muzafer Sherif demonstrated that while hatred and violence are powerful forces, so too are cooperation and harmony. Today it is proffered as proof that under the right conditions warring groups can make peace. Yet the true story of the experiments is far more complex, and more chilling. In The Lost Boys, Gina Perry explores the experiment and its consequences, tracing the story of Sherif, a troubled outsider who struggled to craft an experiment that would vanquish his personal demons. Drawing on archival material and new interviews, Perry pieces together a story of drama, mutiny, and intrigue that has never been told before\"-- Provided by publisher.
Book
The hidden life of girls
Winner of the Best Book of 2008 from The International Gender and Language Association In this ground-breaking ethnography of girls on a playground, Goodwin offers a window into their complex social worlds. - Combats stereotypes that have dominated theories on female moral development by challenging the notion that girls are inherently supportive of each other - Examines the stances that girls on a playground in a multicultural school setting assume and shows how they position themselves in their peer groups - Documents the language practices and degradation rituals used to sanction friends and to bully others - Part of the Blackwell Studies in Discourse and Culture Series
eBook
Migration, diversity, and education : beyond third culture kids
\"The existing literature and numerous webpages dealing with Third Culture Kids often appear to be overenthusiastic about the concept. TCKs have spent their childhood on the move, living in many different countries and languages. Researchers, practitioners and TCKs themselves have created an essentialized image of TCKs, even though, in essence, these individuals are just migrants in special circumstances. This book proposes to think otherwise and to review the ideologies and myths behind this construct. With contributors from different parts of the world and from various disciplines, the origins of the term TCKs, its development and the current debates around it are discussed, beyond the current and somewhat stagnant discourses about these individuals. The key concepts associated with Third Culture Kids are also revisited. This volume represents a timely, authoritative and alternative way of rethinking and reimagining the impact of mobility\"-- Provided by publisher.
Book
Drug–Drug Interaction Studies: Regulatory Guidance and An Industry Perspective
Recently, the US Food and Drug Administration and European Medicines Agency have issued new guidance for industry on drug interaction studies, which outline comprehensive recommendations on a broad range of in vitro and in vivo studies to evaluate drug–drug interaction (DDI) potential. This paper aims to provide an overview of these new recommendations and an in-depth scientifically based perspective on issues surrounding some of the recommended approaches in emerging areas, particularly, transporters and complex DDIs. We present a number of theoretical considerations and several case examples to demonstrate complexities in applying (1) the proposed transporter decision trees and associated criteria for studying a broad spectrum of transporters to derive actionable information and (2) the recommended model-based approaches at an early stage of drug development to prospectively predict DDIs involving time-dependent inhibition and mixed inhibition/induction of drug metabolizing enzymes. We hope to convey the need for conducting DDI studies on a case-by-case basis using a holistic scientifically based interrogative approach and to communicate the need for additional research to fill in knowledge gaps in these areas where the science is rapidly evolving to better ensure the safety and efficacy of new therapeutic agents.
Journal Article