28 research outputs found
Variation of mortality after coronary artery bypass surgery in relation to hour, day and month of the procedure
Impact of supplementary private health insurance on stomach cancer care in Korea: a cross-sectional study
Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors
Chronic exposure to drugs of abuse or stress regulates transcription factors, chromatin-modifying enzymes and histone post-translational modifications in discrete brain regions. Given the promiscuity of the enzymes involved, it has not yet been possible to obtain direct causal evidence to implicate the regulation of transcription and consequent behavioral plasticity by chromatin remodeling that occurs at a single gene. We investigated the mechanism linking chromatin dynamics to neurobiological phenomena by applying engineered transcription factors to selectively modify chromatin at a specific mouse gene in vivo. We found that histone methylation or acetylation at the Fosb locus in nucleus accumbens, a brain reward region, was sufficient to control drug- and stress-evoked transcriptional and behavioral responses via interactions with the endogenous transcriptional machinery. This approach allowed us to relate the epigenetic landscape at a given gene directly to regulation of its expression and to its subsequent effects on reward behavior
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Optimal Tradeoffs in Matched Designs Comparing US-Trained and Internationally Trained Surgeons
Does receiving a medical education outside the United States impact a surgeon’s performance? We study this question by matching operations performed by internationally trained surgeons to those performed by US-trained surgeons in reanalysis of a large health outcomes study. An effective matched design must achieve several goals, including balancing covariate distributions marginally, ensuring units within individual pairs have similar values on key covariates, and using a sufficiently large sample from the raw data. Yet in our study, optimizing some of these goals forces less desirable results on others. We address such tradeoffs from a multi-objective optimization perspective by creating matched designs that are Pareto optimal with respect to two goals. We provide general tools for generating representative subsets of Pareto optimal solution sets and articulate how they can be used to improve decision-making in observational study design. In the motivating surgical outcomes study, formulating a multi-objective version of the problem helps us balance an important variable without sacrificing two other design goals, average closeness of matched pairs on a multivariate distance and size of the final matched sample. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement
Recommended from our members
Optimal Tradeoffs in Matched Designs Comparing US-Trained and Internationally Trained Surgeons
Does receiving a medical education outside the United States impact a surgeon’s performance? We study this question by matching operations performed by internationally trained surgeons to those performed by US-trained surgeons in reanalysis of a large health outcomes study. An effective matched design must achieve several goals, including balancing covariate distributions marginally, ensuring units within individual pairs have similar values on key covariates, and using a sufficiently large sample from the raw data. Yet in our study, optimizing some of these goals forces less desirable results on others. We address such tradeoffs from a multi-objective optimization perspective by creating matched designs that are Pareto optimal with respect to two goals. We provide general tools for generating representative subsets of Pareto optimal solution sets and articulate how they can be used to improve decision-making in observational study design. In the motivating surgical outcomes study, formulating a multi-objective version of the problem helps us balance an important variable without sacrificing two other design goals, average closeness of matched pairs on a multivariate distance and size of the final matched sample. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement