STATISTICAL INFERENCE OF TRANSMISSION FIDELITY OF DNA METHYLATION PATTERNS OVER SOMATIC CELL DIVISIONS IN MAMMALS

We develop Bayesian inference methods for a recently-emerging type of epigenetic data to study the transmission fidelity of DNA methylation patterns over cell divisions. The data consist of parent-daughter double-stranded DNA methylation patterns with each pattern coming from a single cell and represented as an unordered pair of binary strings. The data are technically difficult and time-consuming to collect, putting a premium on an efficient inference method. Our aim is to estimate rates for the maintenance and de novo methylation events that gave rise to the observed patterns, while accounting for measurement error. We model data at multiple sites jointly, thus using whole-strand information, and considerably reduce confounding between parameters. We also adopt a hierarchical structure that allows for variation in rates across sites without an explosion in the effective number of parameters. Our context-specific priors capture the expected stationarity, or near-stationarity, of the stochastic process that generated the data analyzed here. This expected stationarity is shown to greatly increase the precision of the estimation. Applying our model to a data set collected at the human FMR1 locus, we find that measurement errors, generally ignored in similar studies, occur at a non-trivial rate (inappropriate bisulfite conversion error: 1.6% with 80% CI: 0.9-2.3%). Accounting for these errors has a substantial impact on estimates of key biological parameters. The estimated average failure of maintenance rate and daughter de novo rate decline from 0.04 to 0.024 and from 0.14 to 0.07, respectively, when errors are accounted for. Our results also provide evidence that de novo events may occur on both parent and daughter strands: the median parent and daughter de novo rates are 0.08 (80% CI: 0.04-0.13) and 0.07 (80% CI: 0.04-0.11), respectively.     

Nonparametric density estimation from censored data

Nonparametric estimation of the probability density function f° of a lifetime distribution based on arbitrarily right-censor-ed observations from f° has been studied extensively in recent years. In this paper the density estimators from censored data that have been obtained to date are outlined. Histogram, kernel-type, maximum likelihood, series-type, and Bayesian nonparametric estimators are included. Since estimation of the hazard rate function can be considered as giving a density estimate, all known results concerning nonparametric hazard rate estimation from censored samples are also briefly mentioned.     

Sexual abuse and sexual functioning in a chronic pelvic pain sample

Sexual abuse, particularly childhood sexual abuse, has been linked to chronic pelvic pain and to sexual dysfunction, though the sexual functioning of survivors of sexual abuse has not been studied in a chronic pain population. Sixty-three women with chronic pelvic pain completed measures of sexual function, sexual abuse, and pain. Using an index of the extent of sexual abuse experiences in childhood and adolescence/adulthood, higher scores were related to lower rates of sexual activity, less satisfaction with orgasm and feelings of closeness with sexual partners, and greater severity of and interference from pain. Findings point to the importance of controlling for relationship status in analyses of long-term effects of sexual abuse and of assessing chronic pelvic pain patients for histories of sexual abuse using measures that address the extent or severity of abuse.     

The attitudes of socially marginalized men toward physician-assisted suicide

Bioethics and public policy literature suggests that socially marginalized populations may be at increased risk for overuse of physician-assisted suicide (PAS) were it to become more accepted. Yet the attitudes of socially marginalized populations toward PAS have not been widely studied. The present study surveyed a sample of men in a substance abuse recovery program. Participants completed a PAS attitude questionnaire and a religiosity measure. Support for PAS was fairly evenly split, with 52.2% indicating general opposition to PAS and 46.9% indicating general support. Greater religiosity was associated with more negative attitudes toward PAS. Higher educational level was associated with more acceptance. Overall attitudes toward PAS were considerably more negative than those of Dr. George Domino's (2003) general population sample.     

POLICY CHALLENGES OF THE CONTEMPORARY SOCIO-ECONOMIC STATUS OF INDIGENOUS AUSTRALIAN FAMILIES

The paper presents an analysis of the economic status of indigenous families relative to other Australian families. An innovative combination of economic analysis of current census data and ethnographic research is used in the paper, and reveals that indigenous families are experiencing substantial and multiple forms of economic burden in comparison to other Australian families, and display significantly different characteristics. They are more likely to be sole parent families and have on average, a larger number of children and larger households. The adults are younger, have lower levels of education and are less likely to be in employment than other Australians. The poor economic position of indigenous sole parents is highlighted, and the economic role of the aged, matrifocal families, young adults and children are consisdered. The paper concludes by examining the important policy and program implications raised by the research, and argues the need for an increased focus on the particular socio-economic and locational circumstances of indigenous families.     

Uncoupling

This article explores the process by which two individuals move from a coupled identity to separate, autonomous identities. Through the use of intensive interviews, the essentials of the process are abstracted and described as a series of stages through which the participants negotiate changing definitions of reality, both for themselves and for others. Berger and Kellner's conception of marriage as a socially constructed reality that is “nomos-building” is used as a starting point and is critiqued.     

Expert review of an approach to functional capacity evaluation

Functional capacity evaluation (FCE) is a widely used tool in work rehabilitation, despite the limited examination of the soundness of its measurement properties. This paper outlines the development of a new approach to FCE, the GAPP FCE, and reports on the findings of an expert review of aspects of its content validity and technical adequacy and how it meets established test criteria. Five expert occupational therapists reviewed the materials of the GAPP FCE then completed a questionnaire related to the content validity, technical adequacy and safety, reliability, validity, practicality and utility of the GAPP FCE. The experts gave support to most aspects of these criteria. The main issue identified by the review was related to interpretation and extrapolation of the FCE results for return to work. This and other issues are discussed in relation to recent developments in FCE and plans for future development of the GAPP FCE.