Global, local and focused geographic clustering for case-control data with residential histories

BACKGROUND: This paper introduces a new approach for evaluating clustering in case-control data that accounts for residential histories. Although many statistics have been proposed for assessing local, focused and global clustering in health outcomes, few, if any, exist for evaluating clusters when individuals are mobile. METHODS: Local, global and focused tests for residential histories are developed based on sets of matrices of nearest neighbor relationships that reflect the changing topology of cases and controls. Exposure traces are defined that account for the latency between exposure and disease manifestation, and that use exposure windows whose duration may vary. Several of the methods so derived are applied to evaluate clustering of residential histories in a case-control study of bladder cancer in south eastern Michigan. These data are still being collected and the analysis is conducted for demonstration purposes only. RESULTS: Statistically significant clustering of residential histories of cases was found but is likely due to delayed reporting of cases by one of the hospitals participating in the study. CONCLUSION: Data with residential histories are preferable when causative exposures and disease latencies occur on a long enough time span that human mobility matters. To analyze such data, methods are needed that take residential histories into account

The Ets Transcription Factor EHF as a Regulator of Cornea Epithelial Cell Identity

The cornea is the clear, outermost portion of the eye composed of three layers: an epithelium that provides a protective barrier while allowing transmission of light into the eye, a collagen-rich stroma, and an endothelium monolayer. How cornea development and aging is controlled is poorly understood. Here we characterize the mouse cornea transcriptome from early embryogenesis through aging and compare it with transcriptomes of other epithelial tissues, identifying cornea-enriched genes, pathways, and transcriptional regulators. Additionally, we profiled cornea epithelium and stroma, defining genes enriched in these layers. Over 10,000 genes are differentially regulated in the mouse cornea across the time course, showing dynamic expression during development and modest expression changes in fewer genes during aging. A striking transition time point for gene expression between postnatal days 14 and 28 corresponds with completion of cornea development at the transcriptional level. Clustering classifies co-expressed, and potentially co-regulated, genes into biologically informative categories, including groups that exhibit epithelial or stromal enriched expression. Based on these findings, and through loss of function studies and ChIP-seq, we show that the Ets transcription factor EHF promotes cornea epithelial fate through complementary gene activating and repressing activities. Furthermore, we identify potential interactions between EHF, KLF4, and KLF5 in promoting cornea epithelial differentiation. These data provide insights into the mechanisms underlying epithelial development and aging, identifying EHF as a regulator of cornea epithelial identity and pointing to interactions between Ets and KLF factors in promoting epithelial fate. Furthermore, this comprehensive gene expression data set for the cornea is a powerful tool for discovery of novel cornea regulators and pathways

A typological approach to testing the evolutionary functions of human female orgasm

Building on previous work that identified different types of orgasm in women (King, Belsky, Mah, & Binik, 2011), the goal of the present study was to extend such typological work and determine whether female orgasmic variability tracked potentially evolutionarily salient sexual partner characteristics (e.g., those displaying possible immune-system compatibility). A total of 265 females completed an Internet survey about their orgasmic experience—achieved either with partners or alone. For partnered orgasms, they also provided details of partner characteristics and sexual behaviors. Latent class analysis revealed two orgasm types which were meaningfully distinguishable in terms of sensations and location—either centered on the surface of genitalia or deep inside. Deep orgasms were associated with internal sensations consistent with proposed functions of female orgasm in terms of differential sperm insuck. Such orgasms were associated with partners who were perceived as considerate, dominant, with a noticeably attractive smell, and as providing firm penetration. However, some hypothesized reproductively significant partner characteristics were not differentially associated with deep orgasms (i.e., muscularity, aggression, masculinity). Results were discussed and future research directions outlined. In particular, it is suggested that sexual passion between partners is a non-accidental component of sexual functioning and that this has too frequently been missing in sex research involving humans. Direct physiological measures of the results of female orgasm need to be undertaken. Additionally, the intriguing phenomenon of female ejaculation deserves scientific attention