The explosion of genetic information over the last decade presents an analytical challenge for genetic association studies. As the number of genetic variables examined per individual increases, both variable selection and statistical modeling tasks must be performed during analysis. While these tasks could be performed separately, coupling them is necessary to select meaningful variables that effectively model the data. This challenge is heightened due to the complex nature of the phenotypes under study and the complex underlying genetic etiologies. To address this problem, a number of novel methods have been developed. In the current study, we compare the performance of six analytical approaches to detect both main effects and gene-gene interactions in a range of genetic models. Multifactor dimensionality reduction, grammatical evolution neural networks, random forests, focused interaction testing framework, step-wise logistic regression, and explicit logistic regression were compared. As one might expect, the relative success of each method is context dependent. This study demonstrates the strengths and weaknesses of each method and illustrates the importance of continued methods development.

Objective Food insecurity is emerging as an important barrier to antiretroviral therapy (ART) adherence. The objective of this study was to determine if food insecurity is associated with poor ART adherence among HIV-positive adults in a resource-limited setting that utilizes the public health model of delivery. Design A cross-sectional study using a one-time questionnaire and routinely collected pharmacy data. Methods Participants were HIV-infected adults on ART at the public ART clinics in Windhoek, Namibia: Katutura State Hospital, Katutura Health Centre, and Windhoek Central Hospital. Food insecurity was measured by the Household Food Insecurity Access Scale (HFIAS). Adherence was assessed by the pharmacy adherence measure medication possession ratio (MPR). Multivariate regression was used to assess whether food insecurity was associated with ART adherence. Results Among 390 participants, 7% were food secure, 25% were mildly or moderately food insecure and 67% were severely food insecure. In adjusted analyses, severe household food insecurity was associated with MPR <80% (OR 3.84, 1.65 to 8.95). Higher household healthcare spending (OR 1.92, 1.02 to 3.57) and longer duration of ART (OR 0.82, 0.70 to 0.97) were also associated with <80% MPR. Conclusion Severe household food insecurity is present in more than half of the HIV-positive adults attending a public ART clinic in Windhoek, Namibia, and is associated with poor ART adherence as measured by MPR. Ensuring reliable access to food should be an important component of ART delivery in resource-limited settings using the public health model of care.

No abstract

Background In the Women’s Health Initiative Hormone Trials (WHI-HT), breast cancer risk was increased with estrogen plus progestin (E+P) but not with unopposed estrogen (E-alone). We hypothesized that E+P would preferentially metabolize to 16α-hydroxyestrone (16α-OHE1) rather than 2-hydroxyestrone (2-OHE1), and that breast cancer risk would be associated with baseline and 1 year changes in estrogen metabolites: positively for 16α-OHE1 levels and negatively for levels of 2-OHE-1 and the 2:16 ratio. Methods In a prospective case-control study nested in the WHI-HT, 845 confirmed breast cancer cases were matched to 1690 controls by age and ethnicity. Using stored serum, 2-OHE1 and 16α-OHE1 levels were measured by EIA at baseline, and for those randomized to active treatment (n=1259), at 1 year. Results The 1 year increase in 16α-OHE1 was greater with E+P than E-alone (median 55.5 vs. 43.5 pg/ml, p<0.001), but both increased 2-OHE1 by ~300 pg/ml. Breast cancer risk was modestly associated with higher baseline levels of 2-OHE1 and the 2:16 ratio, and. for estrogen receptor+/progesterone+ cases only, higher baseline 16α-OHE1 levels. For those randomized to active treatment, breast cancer risk was associated with greater increase in 2-OHE-1 and the 2:16 ratio, but associations were not significant. Conclusions Although E+P modestly increased 16α-OHE1 more than E-alone, increase in 16α-OHE1 was not associated with breast cancer. Impact Study results do not explain differences between the WHI E+P and WHI E-alone breast cancer results but metabolism of oral HT which may explain smaller than expected increase in breast cancer compared with endogenous estrogens.