Publications

Using respondent-driven sampling (RDS), we gathered data from 128 HIV surveillance studies conducted outside the United States through October 1, 2007. We examined predictors of poor study outcomes, reviewed operational, design and analytical challenges associated with conducting RDS in international settings and offer recommendations to improve HIV surveillance. We explored factors for poor study outcomes using differences in mean sample size ratios (recruited/calculated sample size) as the outcome variable. Ninety-two percent of studies reported both calculated and recruited sample sizes. Studies of injecting drug users had a higher sample size ratio compared with other risk groups. Study challenges included appropriately defining eligibility criteria, structuring social network size questions, selecting design effects and conducting statistical analysis. As RDS is increasingly used for HIV surveillance, it is important to learn from past practical, theoretical and analytical challenges to maximize the utility of this method.

A highly heritable and reproducible measure of asthma severity is baseline pulmonary function. Pulmonary function is largely determined by airway smooth muscle (ASM) tone and contractility. The large conductance, voltage and calcium-activated potassium (BK) channel negatively regulates smooth muscle tone and contraction in ASM. The modulatory subunit of BK channels, the beta1-subunit, is critical for proper activation of BK channels in smooth muscle and has shown sex hormone specific regulation. We hypothesized that KCNMB1 genetic variants in African Americans may underlie differences in bronchial smooth muscle tone and thus pulmonary function, possibly in a sex-specific manner. Through resequencing of the KCNMB1 gene we identified several common variants including a novel African-specific coding polymorphism (C818T, R140W). The C818T SNP and four other KCNMB1 variants were genotyped in two independent groups of African American asthmatics (n = 509) and tested for association with the pulmonary function measure--forced expiratory volume (FEV(1)) % of predicted value. The 818T allele is associated with a clinically significant decline (-13%) in FEV(1) in both cohorts of asthmatics among males but not females (P(combined) = 0.0003). Patch clamp electrophysiology studies of the BK channel expressed with the 140Trp variant of the beta1-subunit demonstrated significantly reduced channel openings, predicted by the loss of pulmonary function observed. African American male asthmatics carrying the 818T allele (10% of population) are potentially at risk for greater airway obstruction and increased asthma morbidity. Female asthmatics may be insulated from the deleterious effects of the 818T allele by estrogen-mediated upregulation in BK channel activity.