KRAS variation and risk of endometriosis

Endometriosis is a common gynaecological disease with symptoms of pelvic pain and infertility which affects 7-10% of women in their reproductive years. Activation of an oncogenic allele of Kirsten rat sarcoma viral oncogene homologue (KRAS) in the reproductive tract of mice resulted in the development of endometriosis. We hypothesized that variation in KRAS may influence risk of endometriosis in humans. Thirty tagSNPs spanning a region of 60.7 kb across the KRAS locus were genotyped using iPLEX chemistry on a MALDI-TOF MassARRAY platform in 959 endometriosis cases and 959 unrelated controls, and data were analysed for association with endometriosis. Genotypes were obtained for most individuals with a mean completion rate of 99.1%. We identified six haplotype blocks across the KRAS locus in our sample. There were no significant differences between cases and controls in the frequencies of individual single-nucleotide polymorphisms (SNPs) or haplotypes. We also developed a rapid method to screen for 11 common KRAS and BRAF mutations on the Sequenom MassARRAY system. The assay detected all mutations previously identified by direct sequencing in a panel of positive controls. No germline variants for KRAS or BRAF were detected. Our results demonstrate that any risk of endometriosis in women because of common variation in KRAS must be very small.

Variation in the walking time to bus stop by the degree of transit captivity

Measures of transit accessibility are important in evaluating transit services, planning for future services and investment on land use development. Existing tools measure transit accessibility using averaged walking distance or walking time to public transit. Although the mode captivity may have significant implications on one’s willingness to walk to use public transit, this has not been addressed in the literature to date. Failed to distinguish transit captive users may lead to overestimated ridership and spatial coverage of transit services. The aim of this research is to integrate the concept of transit captivity into the analysis of walking access to public transit. The conventional way of defining “captive” and “choice” transit users showed no significant difference in their walking times according to a preliminary analysis. A cluster analysis technique is used to further divide “choice” users by three main factors, namely age group, labour force status and personal income. After eliminating “true captive” users, defined as those without driver’s licence or without a car in respective household, “non-true captive” users were classified into a total of eight groups having similar socio-economic characteristics. The analysis revealed significant differences in the walking times and patterns by their level of captivity to public transit. This paper challenges the rule-of-thumb of 400m walking distance to bus stops. In average, people’s willingness to walk dropped drastically at 268m and continued to drop constantly until it reached the mark of 670m, where there was another drastic drop of 17%, which left with only 10% of the total bus riders willing to walk 670m or more. This research found that mothers working part time were the ones with lowest transit captivity and thus most sensitive to the walking time, followed by high-income earners and the elderly. The level of captivity increases when public transit users earned lesser income, such as students and students working part time.

Investigating variation in bus ridership rates within localised areas of a sub-tropical city

This thesis makes a significant contribution to knowledge and understanding of 'Human Travel Behaviour' in relation to transportation research. It holds some important merits that have not been proposed before. It develops a new, comprehensive and meaningful relationship that includes bus transit ridership change due to weather variables, seasonality and transit quality of service within a single daily ridership rate estimation model. The research incorporated both temporal and spatial influences on ridership within a modelling structure, named as the Nested Model Structure. It provides a complete picture of ridership variation across the sub-tropical city of Brisbane, Australia.

HR-MAS NMR spectroscopy shows regional metabolite variation in bovine articular cartilage

Mechanical stress is an important external factor effecting the development and maintenance of articular cartilage. The metabolite profile of diseased cartilage has been well studied but there is limited information about the variation in metabolite profile of healthy cartilage. With the importance of load in maintaining healthy cartilage, regional differences in metabolite profile associated with differences in load may provide information on how load contributes to the maintenance of healthy cartilage. HR-MAS NMR spectroscopy allows the assessment of tissue samples without modification and was used for assessing the difference in metabolic profile between the load bearing and non-load bearing regions of the bovine articular cartilage. In this preliminary study, we examined cartilage from tibia and femur of four knee joints. Sixteen pairs of 1D-NOESY spectra were acquired. Principle component analysis (PCA) identified chemical shifts responsible for variance. SBASE (AMIX) and the Human Metabolome Database were used in conjunction with previous reported cartilage data for identifying metabolites associated with the PCA results. The major contributors to load-related differences in metabolite profile were N-acetyl groups, lactate and phosphocholine peaks. Integrals of these regions were further analysed using a Student's t-test. In load bearing cartilage regions. N-acetyl groups and phosphocholine were found at significantly higher concentration (p < 0.05 and p < 0.005, respectively) in both femur and tibia, while lactate was reduced in load bearing cartilage (p < 0.005). The results of this pilot HR-MAS NMR study demonstrate its ability to provide useful metabolite information for healthy cartilage.

Natural variation and Biogeography of the melon fruit fly, Zeugodacus cucurbitae (Diptera : Tephritidae), in Southeast-Asia and the west-pacific

This thesis used multidisciplinary approaches which greatly enhance our understanding of population structure and can be particularly powerful tools for resolving variation of melon fly over geographic and temporal scales, and for determining invasive pathways. The results from this thesis reinforce the value of integrating multiple data sets to better understand and resolve natural variation within an important pest to determine whether there are cryptic species, discrete lineages or host races, and to identify dispersal pathways in an invasive pest. These results are instructive for regional biosecurity, trade and quarantine, and provide important background for future area-wide management programmes. The integrative methodology adopted in this thesis is applicable to a variety of other insect pests.

Regional variation in social isolation amongst older Australians

Regional studies globally have a strong focus on understanding the causes of variation in the economic performance and wellbeing of regions and this emphasis acknowledges that the strength of the local or regional economy plays a determinant role in shaping quality of life. Regional research has been less active in considering spatial variation in other factors that are critical to individual and societal wellbeing. For example, the regional studies community has been absent from the debate on the social determinants of health and how these influences vary spatially. This paper considers the results of a cross sectional survey of Australians aged 65 and over that focussed on social connections and wellbeing. It examines regional variations in the incidence of social isolation within the older population. It finds that while the incidence of self-reported social isolation amongst older persons is broadly consistent with earlier studies, it demonstrates a spatial patterning that is unexpected. The paper considers community-building activities in addressing the impacts of social isolation, including the role of urban design, and suggests that there is a need to supplement the national overview presented there through more detailed studies focussed on individual localities.

Chromosomal rearrangements, phenotypic variation and modularity: A case study from a contact zone between house mouse Robertsonian races in Central Italy

The Western European house mouse, Mus musculus domesticus, is well-known for the high frequency of Robertsonian fusions that have rapidly produced more than 50 karyotipic races, making it an ideal model for studying the mechanisms of chromosomal speciation. The mouse mandible is one of the traits studied most intensively to investigate the effect of Robertsonian fusions on phenotypic variation within and between populations. This complex bone structure has also been widely used to study the level of integration between different morphogenetic units. Here, with the aim of testing the effect of different karyotypic assets on the morphology of the mouse mandible and on its level of modularity, we performed morphometric analyses of mice from a contact area between two highly metacentric races in Central Italy. We found no difference in size, while the mandible shape was found to be different between the two Robertsonian races, even after accounting for the genetic relationships among individuals and geographic proximity. Our results support the existence of two modules that indicate a certain degree of evolutionary independence, but no difference in the strength of modularity between chromosomal races. Moreover, the ascending ramus showed more pronounced interpopulation/race phenotypic differences than the alveolar region, an effect that could be associated to their different polygenic architecture. This study suggests that chromosomal rearrangements play a role in the house mouse phenotypic divergence, and that the two modules of the mouse mandible are differentially affected by environmental factors and genetic makeup.