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1.  Differential effects of enalapril and losartan on body composition and indices of muscle quality in aged male Fischer 344 × Brown Norway rats 
Age  2010;33(2):167-183.
The primary purpose of the present set of studies was to provide a direct comparison of the effects of the angiotensin-converting enzyme inhibitor enalapril and the angiotensin receptor blocker losartan on body composition, physical performance, and muscle quality when administered late in life to aged rats. Overall, enalapril treatment consistently attenuated age-related increases in adiposity relative to both placebo and losartan. The maximal effect was achieved after 3 months of treatment (between 24 and 27 months of age), at a dose of 40 mg/kg and was observed in the absence of any changes in physical activity, body temperature, or food intake. In addition, the reduction in fat mass was not due to changes in pathology given that enalapril attenuated age-related increases in tumor development relative to placebo- and losartan-treated animals. Both enalapril and losartan attenuated age-related decreases in grip strength, suggesting that changes in body composition appear dissociated from improvements in physical function and may reflect a differential impact of enalapril and losartan on muscle quality. To link changes in adiposity to improvements in skeletal muscle quality, we performed gene array analyses to generate hypotheses regarding cell signaling pathways altered with enalapril treatment. Based on these results, our primary follow-up pathway was mitochondria-mediated apoptosis of myocytes. Relative to losartan- and placebo-treated rats, only enalapril decreased DNA fragmentation and caspase-dependent apoptotic signaling. These data suggest that attenuation of the severity of skeletal muscle apoptosis promoted by enalapril may represent a distinct mechanism through which this compound improves muscle strength/quality.
PMCID: PMC3127467  PMID: 21153712
Age-related adiposity; Body composition; Sarcopenia; Renin–angiotensin system; Physical function; Muscle quality
In longitudinal clinical trials, when outcome variables at later time points are only defined for patients who survive to those times, the evaluation of the causal effect of treatment is complicated. In this paper, we describe an approach that can be used to obtain the causal effect of three treatment arms with ordinal outcomes in the presence of death using a principal stratification approach. We introduce a set of flexible assumptions to identify the causal effect and implement a sensitivity analysis for non-identifiable assumptions which we parameterize parsimoniously. Methods are illustrated on quality of life data from a recent colorectal cancer clinical trial.
PMCID: PMC3035160  PMID: 21318119
Principal stratification; QOL; Ordinal data; Sensitivity analysis
3.  Modeling Competing Infectious Pathogens from a Bayesian Perspective: Application to Influenza Studies with Incomplete Laboratory Results 
In seasonal influenza epidemics, pathogens such as respiratory syncytial virus (RSV) often co-circulate with influenza and cause influenza-like illness (ILI) in human hosts. However, it is often impractical to test for each potential pathogen or to collect specimens for each observed ILI episode, making inference about influenza transmission difficult. In the setting of infectious diseases, missing outcomes impose a particular challenge because of the dependence among individuals. We propose a Bayesian competing-risk model for multiple co-circulating pathogens for inference on transmissibility and intervention efficacies under the assumption that missingness in the biological confirmation of the pathogen is ignorable. Simulation studies indicate a reasonable performance of the proposed model even if the number of potential pathogens is misspecified. They also show that a moderate amount of missing laboratory test results has only a small impact on inference about key parameters in the setting of close contact groups. Using the proposed model, we found that a non-pharmaceutical intervention is marginally protective against transmission of influenza A in a study conducted in elementary schools.
PMCID: PMC3070363  PMID: 21472041
Missing data; MCMC; Infectious disease; Competing risks; Intervention efficacy

Results 1-3 (3)