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Roughly two-thirds of all breast cancers are ERα-positive and can be treated with the antiestrogen, Tamoxifen, however resistance occurs in 33% of women who take the drug for more than 5 y. Aberrant DNA methylation, an epigenetic mechanism that alters gene expression in cancer, is thought to play a role in this resistance. To develop an understanding of Tamoxifen-resistance and identify novel pathways and targets of aberrant methylation, DNA from MCF-7 breast cancer cells and Tamoxifen-resistant derivatives, TMX2-11 and TMX2-28, were analyzed using the Illumina HumanMethylation450 BeadChip. Normalizing against MCF-7 values, ERα-positive TMX2-11 had 4000 hypermethylated sites and ERα-negative TMX2-28 had over 33 000. Analysis of CpG sites altered in both TMX2-11 and TMX2-28 revealed that the Tamoxifen-resistant cell lines share 3000 hypermethylated and 200 hypomethylated CpGs. ZNF350 and MAGED1, two genes hypermethylated in both cell lines, were examined in greater detail. Treatment with 5-aza-2ꞌdeoxycitidine caused a significant reduction in promoter methylation of both ZNF350 and MAGED1 and a corresponding increase in expression in TMX2-28. A similar relationship between methylation and expression was not detected in TMX2-11. Our findings are indicative of the variable responses to methylation-targeted breast cancer therapy and highlight the need for biomarkers that accurately predict treatment outcome.

Accurately identifying women at increased risk of developing breast cancer will provide greater opportunity for early detection and prevention. DNA promoter methylation is a promising biomarker for assessing breast cancer risk. Breast milk contains large numbers of exfoliated epithelial cells that are ideal for methylation analyses. Exfoliated epithelial cells were isolated from the milk obtained from each breast of 134 women with a history of a non-proliferative benign breast biopsy (Biopsy Group). Promoter methylation of three tumor suppressor genes, RASSF1, SFRP1 and GSTP1, was assessed by pyrosequencing of bisulfite-modified DNA. Methylation scores from the milk of the 134 women in the Biopsy Group were compared to scores from 102 women for whom a breast biopsy was not a recruitment requirement (Reference Group). Mean methylation scores for RASSF1 and GSTP1 were significantly higher in the Biopsy than in the Reference Group. For all three genes the percentage of outlier scores was greater in the Biopsy than in the Reference Group but reached statistical significance only for GSTP1. A comparison between the biopsied and non-biopsied breasts of the Biopsy Group revealed higher mean methylation and a greater number of outlier scores in the biopsied breast for both SFRP1 and RASSF1, but not for GSTP1. This is the first evidence of CpG island methylation in tumor suppressor genes of women who may be at increased risk of developing breast cancer based on having had a prior breast biopsy.

In this study, we investigate the extent to which women and men differ in patterns of medication use, based on quantitative and qualitative data from a household survey in Western Massachusetts. Using a broad definition of medications, 96% of the sample reported taking one or more medications in the month preceding the survey (86% if vitamins, supplements, and alternative medications are excluded). Twenty-one percent of respondents reported taking five or more medications, and women were significantly more likely to report taking five or more medications in the month preceding the survey. For both sexes, analgesics and vitamins were the most commonly used medications, but women were more likely to report having taken hormones, supplements, and antihistamines. The likelihood of medicating reported health conditions did not differ by sex, but the frequency of reporting health conditions was higher among women, and the difference was significant for body aches and psychosomatic conditions. Analyses of qualitative data indicate that female networks of relatives and friends are an important source of advice on medications for both men and women. Responses to open-ended questions suggest that women's discourse about the effect of medications differs from men's in terms of the range and detail of descriptions of symptoms and side effects.

Many local agencies that provide services to the homeless have only limited data and resources to estimate the extent of need or the size of the local population at risk of requiring the services they provide. Methods exist, however, that are capable of providing reasonable estimates of underlying service populations with minimal record keeping. In this paper one group of such models, first‐capture models, is discussed as a resource‐efficient technique for estimating the underlying population consistently at risk ("residents") and those occasionally at risk ("transients") of requiring agency services.

This article presents an analysis of the effect that urban secularization of religious pronatalism had upon established birth spacing behavior over the course of the fertility transition in the population of 19th century Utah. A model of variance in birth intervals attributable to age at marriage age of childbearing termination and completed family size over the duration of childbearing thus defined is presented. The simple analytical model achieves a reasonable fit for birth interval data. In addition the model demonstrates the relative dependence of birth intervals upon the fertility achieved over the duration of childbearing rather than upon deliberate control over the beginning or ending of the childbearing interval. Variations in age at marriage become more important in explaining birth intervals than do variation in age at last birth. The model is elaborated by incorporating 5 specific hypotheses concerning the effects of urbanism secularization and their interaction upon interbirth intervals. 2 principal conclusions were derived. 1) Birth interval differentials among subcohorts defined by religiosity and urbanism are generally consistent with fertility effects of traditional urbanism and secularization perspectives. 2) There is however no consistent evidence that this frontier population was as heterogeneous in the secularization of traditional pronatalism as is often the case in either European or 3rd world settings. Although a pattern of urban secularization is found uniformity of social and behavioral changes suggestsa that relatively homogeneous demographic behavior was produced on the frontier by the largely external locus of secularizing influences in the mainstream eastern American community.

The intent was to highlight the practical methods and issues of contextual analysis rather than detail the statistical characteristics of any one contextual model. There is too much emphasis in the discussion of contextual effects on forcing theoretical hypotheses into the single-level linear regression model. Similarly there is too much dislike for basic contextual analyses that avoid indiscriminately collapsing reality into a single linear dimension. There is no one correct method for analyzing a contextual effect because there are clearly distinct theoretical and methodological notions of what a contextual effect is. The models reviewed differ primarily according to whether the context is environs characterized by differing types of individuals a characteristic membership of the individual a distinct identifiable environment with unique impact upon individual outcomes or a similar setting with identifiable effects upon causal relationships themselves. The basic question pertains to what a context is and whether it is possible to meaningfully incorporate contexts into explanations of human action. The force of the mechanistic principles embodied in methodologies often accommodate such influences through a forced decomposition of reality into characteristics of the individual rather than those of the environment. Five major linear models represent a general statement of relationship that might also be pursued with a variety of analytical methods other than linear modeling. The first two of these models (individual-effects and macro-effects) are confined to a single level of analysis. The third model is the simplest of those that can be considered a contextual-effect analysis in that both individual and contextual terms are included. The distinction between the simple conditional probability model (Model 3) and the contextual-effects model (Model 4) is the inclusion of both context and individual-level effects. With Model 5 it is possible to model individual-level relationships and contextual effects on the relations.

This paper [examines] the marital and fertility experience of women born between 1800 and 1899 who participated in the settlement colonization and development of a region that marked one of the last frontier settlements in [U.S.] history. The focus is on the effects of different marriage patterns particularly polygyny on fertility. "In conclusion cumulative fertility behavior within periods of exposure was found to be similar across substantial variations in both marital histories and arrangements." (EXCERPT)

In this article we summarize the methods and present the initial results from a linkage of [U.S.] genealogical records from the Mormon Historical Demography Project (MHDP) to records from the 1880 Manuscript Census of Utah Territory. Our primary objective is to recount the linkage methods involved and to evaluate the representativeness of the genealogical records as reflected in the correspondence between longitudinal and census data. The data sets concern population characteristics household size family characteristics and fertility. (EXCERPT)