Rare variants create synthetic genome-wide associations.

Genome-wide association studies (GWAS) have now identified at least 2,000 common variants that appear associated with common diseases or related traits (http://www.genome.gov/gwastudies), hundreds of which have been convincingly replicated. It is generally thought that the associated markers reflect the effect of a nearby common (minor allele frequency >0.05) causal site, which is associated with the marker, leading to extensive resequencing efforts to find causal sites. We propose as an alternative explanation that variants much less common than the associated one may create "synthetic associations" by occurring, stochastically, more often in association with one of the alleles at the common site versus the other allele. Although synthetic associations are an obvious theoretical possibility, they have never been systematically explored as a possible explanation for GWAS findings. Here, we use simple computer simulations to show the conditions under which such synthetic associations will arise and how they may be recognized. We show that they are not only possible, but inevitable, and that under simple but reasonable genetic models, they are likely to account for or contribute to many of the recently identified signals reported in genome-wide association studies. We also illustrate the behavior of synthetic associations in real datasets by showing that rare causal mutations responsible for both hearing loss and sickle cell anemia create genome-wide significant synthetic associations, in the latter case extending over a 2.5-Mb interval encompassing scores of "blocks" of associated variants. In conclusion, uncommon or rare genetic variants can easily create synthetic associations that are credited to common variants, and this possibility requires careful consideration in the interpretation and follow up of GWAS signals.

How actions create--not just reveal--preferences.

The neo-classical economics view that behavior is driven by - and reflective of - hedonic utility is challenged by psychologists' demonstrations of cases in which actions do not merely reveal preferences but rather create them. In this view, preferences are frequently constructed in the moment and are susceptible to fleeting situational factors; problematically, individuals are insensitive to the impact of such factors on their behavior, misattributing utility caused by these irrelevant factors to stable underlying preferences. Consequently, subsequent behavior might reflect not hedonic utility but rather this erroneously imputed utility that lingers in memory. Here we review the roles of these streams of utility in shaping preferences, and discuss how neuroimaging offers unique possibilities for disentangling their independent contributions to behavior.

Research Question, Study Design and Continuous Research Education and Training Exercises (CREATE) Program.

The clinical research project starts with identifying the optimal research question, one that is ethical, impactful, feasible, scientifically sound, novel, relevant, and interesting. The project continues with the design of the study to answer the research question. Such design should be consistent with ethical and methodological principles, and make optimal use of resources in order to have the best chances of identifying a meaningful answer to the research question. Physicians and other healthcare providers are optimally positioned to identify meaningful research questions the answer to which could make significant impact on healthcare delivery. The typical medical education curriculum, however, lacks solid training in clinical research. We propose CREATE (Continuous Research Education And Training Exercises) as a peer- and group-based, interactive, analytical, customized, and accrediting program with didactic, training, mentoring, administrative, and professional support to enhance clinical research knowledge and skills among healthcare professionals, promote the generation of original research projects, increase the chances of their successful completion and potential for meaningful impact. The key features of the program are successive intra- and inter-group discussions and confrontational thematic challenges among participating peers aimed at capitalizing on the groups' collective knowledge, experience and skills, and combined intellectual processing capabilities to optimize choice of research project elements and stakeholder decision-making.

Politics and Poetics of the Novel: Using Domesticity to Create the Nation

This thesis examines how the depiction of the family during war reinforces or challenges societal values in three nineteenth-century novels. The primary focus lies in three novels by Sir Walter Scott, Leo Tolstoy, and Harriet Beecher Stowe that represent the perspectives of England, Russia, and the United States, respectively, and their evolving nationalism as the roots of the Napoleonic Wars and the American Civil War became visible. By investigating the interaction between economic classes, it can be concluded that the preservation of the family is inherently dependent on social status in some nations, while in others, it is integral to daily life regardless of class. The backdrop of impending war only serves to heighten national differences, overturn the organization of the family hierarchy, and redefine the idea of the modern household.