Improving estimation and prediction in linear regression incorporating external information from an established reduced model

We consider a situation where there is rich historical data available for the coefficients and their standard errors in a linear regression model describing the association between a continuous outcome variable Y and a set of predicting factors X , from a large study. We would like to use this summary information for improving inference in an expanded model of interest, Y given X , B . The additional variable B is a new biomarker, measured on a small number of subjects in a new dataset. We formulate the problem in an inferential framework where the historical information is translated in terms of nonlinear constraints on the parameter space and propose both frequentist and Bayes solutions to this problem. We show that a Bayesian transformation approach proposed by Gunn and Dunson is a simple and effective computational method to conduct approximate Bayesian inference for this constrained parameter problem. The simulation results comparing these methods indicate that historical information on E( Y | X ) can improve the efficiency of estimation and enhance the predictive power in the regression model of interest E( Y | X , B ). We illustrate our methodology by enhancing a published prediction model for bone lead levels in terms of blood lead and other covariates, with a new biomarker defined through a genetic risk score.     

Contribution of the CmeABC efflux pump to macrolide and tetracycline resistance in Campylobacter jejuni

We investigated the involvement of the CmeABC efflux pump in acquired resistance of Campylobacter jejuni to macrolides and tetracycline. Inactivation of the cmeB gene had no effect on macrolide resistance when all copies of the target gene carried an A2074C mutation. In contrast, the CmeABC pump significantly contributed to macrolide resistance when two or three copies of the 23S rRNA had an A2075G transition. Inactivation of the cmeB gene led to restoration of tetracycline susceptibility in the isolates examined. Complete susceptibility to tetracycline or macrolides, however, was not restored when phenylalanine-arginine beta-naphthylamide was used. These data confirm contribution of the CmeABC efflux pump to acquired resistance of Campylobacter jejuni to tetracycline and macrolides.     

Pre-B-cell colony-enhancing factor gene polymorphisms and risk of acute respiratory distress syndrome

OBJECTIVE: Pre-B-cell colony-enhancing factor (PBEF) levels are elevated in bronchoalveolar lavage fluid and serum of patients with acute lung injury. There are several suspected functional polymorphisms of the corresponding PBEF gene. We hypothesized that variations in PBEF gene polymorphisms alter the risk of developing acute respiratory distress syndrome (ARDS). DESIGN: Nested case-control study. SETTING: Tertiary academic medical center. PATIENTS: We studied 375 patients with ARDS and 787 at-risk controls genotyped for the PBEF T-1001G and C-1543T polymorphisms. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with the -1001G (variant) allele had significantly greater odds of developing ARDS than wild-type homozygotes (odds ratio, 1.35; 95% confidence interval, 1.02-1.78). Patients with the -1543T (variant) allele did not have significantly different odds of developing ARDS than wild-type homozygotes (odds ratio, 0.86; 95% confidence interval, 0.65-1.13). When analysis was stratified by ARDS risk factor, -1543T was associated with decreased odds of developing ARDS in septic shock patients (odds ratio, 0.66; 95% confidence interval, 0.45-0.97). Also, -1001G was associated with increased hazard of intensive care unit mortality, whereas -1543T was associated with decreased hazard of 28-day and 60-day ARDS mortality, as well as shorter duration of mechanical ventilation. Similar results were found in analyses of the related GC (-1001G:-1543C) and TT (-1001T:-1543T) haplotypes. CONCLUSIONS: The PBEFT-1001G variant allele and related haplotype are associated with increased odds of developing ARDS and increased hazard of intensive care unit mortality among at-risk patients, whereas the C-1543T variant allele and related haplotype are associated with decreased odds of ARDS among patients with septic shock and better outcomes among patients with ARDS.     

Eye on religion: considering the influence of Buddhist and Shinto thought on contemporary Japanese bioethics

Religious traditions can play a significant role in the shaping of bioethical thought. In Japan, traditional Buddhist and Shinto thought continue to influence contemporary bioethical perspectives. To better define this relationship, this paper examines the correlation between Japanese bioethical perspectives and Buddhist and Shinto thought. An in-depth discussion explores how Buddhist and Shinto scholars have used fundamental concepts with each religious tradition to agree and disagree with the disclosure of an incurable disease to a patient, brain death, and brain-dead organ transplantation.