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Dynamic antigen expression and cytotoxic T cell resistance in HIV reservoir clones

Clonally expanded CD4+ T-cells harboring rebound-competent HIV persist lifelong during ART1-5. Latency is considered the principal barrier to viral eradication and has resisted pharmacological reversal6,7, yet sustained immune pressure appears to …

Predicting Imminent Conversion to Exudative Age-Related Macular Degeneration Using Multimodal Data and Ensemble Machine Learning

OBJECTIVE. Exudative age-related macular degeneration (eAMD) is a major cause of central vision loss. Identifying patients at high risk of imminent eAMD could enable timely treatment and improve outcomes. Our goal was to develop and compare classical …

The trouble with triples: Examining the impact of measurement error in mediation analysis

Mediation analysis is used in genetic mapping studies to identify candidate gene mediators of quantitative trait loci (QTL). We consider genetic mediation analysis of triplets—sets of three variables consisting of a target trait, the genotype at a …

A Bayesian model selection approach to mediation analysis

Mediation analysis is a powerful tool for discovery of causal relationships. We describe a Bayesian model selection approach to mediation analysis that is implemented in our bmediatR software. Using simulations, we show that bmediatR performs as well …

Quantification of the Impact of Partition Coefficient Prediction Methods on Physiologically Based Pharmacokinetic Model Output Using a Standardized Tissue Composition

Tissue:plasma partition coefficients are key parameters in physiologically based pharmacokinetic (PBPK) models, yet the coefficients are challenging to measure in vivo. Several mechanistic-based equations have been developed to predict partition …

Midazolam Dose Optimization in Critically Ill Pediatric Patients With Acute Respiratory Failure

OBJECTIVES: To develop a pharmacokinetic-pharmacogenomic population model of midazolam in critically ill children with primary respiratory failure. DESIGN: Prospective pharmacokinetic-pharmacogenomic observational study. SETTING: Thirteen PICUs …

Morphine Dose Optimization in Critically Ill Pediatric Patients With Acute Respiratory Failure

OBJECTIVE: To develop a pharmacokinetic-pharmacogenomic population model of morphine in critically ill children with acute respiratory failure. DESIGN: Prospective pharmacokinetic-pharmacogenomic observational study. SETTING: Thirteen PICUs across …