The High Frequency Component of Heart Rate Variability and Delta EEG Power during Sleep in Healthy Women and Women with Irritable Bowel Syndrome

Thesis (Ph.D.)--University of Washington, 2016-06

Genetic effects on alcohol dependence risk: re-evaluating the importance of psychiatric and other heritable risk factors

Background. Genetic influences have been shown to play a major role in determining the risk of alcohol dependence (AD) in both women and men; however, little attention has been directed to identifying the major sources of genetic variation in AD risk. Method. Diagnostic telephone interview data from young adult Australian twin pairs born between 1964 and 1971 were analyzed. Cox regression models were fitted to interview data from a total of 2708 complete twin pairs (690 MZ female, 485 MZ male, 500 DZ female, 384 DZ male, and 649 DZ female/male pairs). Structural equation models were fitted to determine the extent of residual genetic and environmental influences on AD risk while controlling for effects of sociodemographic and psychiatric predictors on risk. Results. Risk of AD was increased in males, in Roman Catholics, in those reporting a history of major depression, social anxiety problems, and conduct disorder, or (in females only) a history of suicide attempt and childhood sexual abuse; but was decreased in those reporting Baptist, Methodist, or Orthodox religion, in those who reported weekly church attendance, and in university-educated males. After allowing for the effects of sociodemographic and psychiatric predictors, 47 % (95 % CI 28-55) of the residual variance in alcoholism risk was attributable to additive genetic effects, 0 % (95 % CI 0-14) to shared environmental factors, and 53 % (95 % CI 45-63) to non-shared environmental influences. Conclusions. Controlling for other risk factors, substantial residual heritability of AD was observed, suggesting that psychiatric and other risk factors play a minor role in the inheritance of AD.

Evidence for Concurrent Effects of Exposure to Environmental Cadmium and Lead on Hepatic CYP2A6 Phenotype and Renal Function Biomarkers in Non Smokers

We examined the interrelationships between phenotype of hepatic cytochrome P450 2A6 (CYP2A6), nephropathy, and exposure to cadmium and lead in a group of 118 healthy Thai men and women who had never smoked. Their urinary Cd excretion ranged from 0.05 to 2.36 mug/g creatinine, whereas their urinary Pb excretion ranged from 0.1 to 12 mug/g creatinine. Average age and Cd burden of women and men did not differ. Women, however, on average showed a 46% higher urinary Pb excretion (p < 0.001) and lower zinc status, suggested by lower average serum Zn and urinary Zn excretion compared with those in men. Cd-linked nephropathy was detected in both men and women. However, Pb-linked nephropathy was seen only in women, possibly because of higher Pb burden coupled with lower protective factors, notably of Zn (P < 0.001), in women compared with men. In men, Pb burden showed a negative association with CYP2A6 activity (adjusted beta = -0.29, p = 0.003), whereas Cd burden showed a positive association with CYP2A6 activity (adjusted beta = 0.38, p = 0.001), suggesting opposing effects of Cd and Pb on hepatic CYP2A6 phenotype. The weaker correlation between Cd burden CYP2A6 activity in women despite similarity in Cd burden between men and women is consistent with opposing effects of Pb and Cd on hepatic CYP2A6 phenotypic expression. A positive correlation between Cd-linked nephropathy (urinary N-acetyl-beta-D-glucosaminidase excretion) and CYP2A6 activity in men (r = 0.39, p = 0.002) and women (r = 0.37, p = 0.001) suggests that Cd induction of hepatic CYP2A6 expression and Cd-linked nephropathy occurred simultaneously.

Violence against young Australian women and association with reproductive events: a cross-sectional analysis of a national population sample

Objective: This study aimed to investigate associations between violence and younger women's reproductive events using Survey 1 (1996) data of the Younger cohort of the Australian Longitudinal Study of Women's Health (ALSWH). Methods: Multinomial regression, using composite variables for both violence and reproductive events, adjusting for socioeconomic variables and weighted for rural and remote areas. Results: 23.8% of 14,784 women aged 18 to 23 years reported violence; 12.6% reported non-partner violence in the previous year; and 11.2% reported ever having had a violent relationship with a partner. Of the latter group, 43% (4.8% overall) also reported violence in the past year. Compared with women reporting no violence, women reporting partner but not recent violence (OR 2.55, 95% Cl 2.10-3.09) or partner and recent violence (OR 3.96, 95% Cl 3.18-4.93) were significantly more likely to have had one or more pregnancies. Conversely, having had a pregnancy (2,561) was associated with an 80% increase in prevalence of any violence and a 230% increase in partner violence. Among women who had a pregnancy, having had a miscarriage or termination was associated with violence. Partner and recent violence is strongly associated with having had a miscarriage, whether alone (OR = 2.85, 95% Cl 1.74-4.66), with a termination (OR = 4.60, 2.26-9.35), or with birth, miscarriage and a termination (OR 4.12, 1.89-9.00). Conclusions and implications: Violence among young women of childbearing age is a factor for which doctors should be vigilant, well-trained and supported to identify and manage effectively.

Mice and men: Their promoter properties

Using the two largest collections of Mus musculus and Homo sapiens transcription start sites ( TSSs) determined based on CAGE tags, ditags, full- length cDNAs, and other transcript data, we describe the compositional landscape surrounding TSSs with the aim of gaining better insight into the properties of mammalian promoters. We classified TSSs into four types based on compositional properties of regions immediately surrounding them. These properties highlighted distinctive features in the extended core promoters that helped us delineate boundaries of the transcription initiation domain space for both species. The TSS types were analyzed for associations with initiating dinucleotides, CpG islands, TATA boxes, and an extensive collection of statistically significant cis- elements in mouse and human. We found that different TSS types show preferences for different sets of initiating dinucleotides and ciselements. Through Gene Ontology and eVOC categories and tissue expression libraries we linked TSS characteristics to expression. Moreover, we show a link of TSS characteristics to very specific genomic organization in an example of immune- response- related genes ( GO: 0006955). Our results shed light on the global properties of the two transcriptomes not revealed before and therefore provide the framework for better understanding of the transcriptional mechanisms in the two species, as well as a framework for development of new and more efficient promoter- and gene- finding tools.

Gendered dichotomies and segregation patterns in computing jobs in Australia

The uneven distribution of women and men in IT employment is often depicted as reflecting adistinction between 'hard' and 'soft' tasks, skills and attributes. This article uses detailed occupational data on professional computing jobs in Australia to examine the extent to which patterns of gender segregation are consistent with such dichotomies. Additionally, we draw on qualitative interview data from aset oforganisational case studies for insights into the ways in which segregation patterns are reproduced and/or reshaped at"the workplace level. While perceptions ofgendered dichotomies were evident among many of our interviewees, overall our analysis shows considerably more complexity, with segregation patterns not necessarily aligned with clear-cut dichotomies and career directions often directly influenced by the organisation ofworking time in particular occupational streams.