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Asthma is a common chronic disorder in Western countries and is increasing in prevalence in both children and adults. Although genetic risk for atopy is an important factor for the development of asthma, it does not explain the tremendous increase in prevalence seen in recent decades. Environmental exposures in early life that affect immune maturation appear to be the key factors for the development of asthma. The indoor environment is a likely candidate since infants spend 90% of the time indoors at a time when immune deviation usually occurs. Exposure to indoor pollutants represents a potentially modifiable cause of allergic sensitization and asthma. In this context, it becomes important to establish which environmental factors might influence the development of asthma in predisposed individuals. Allergic reactions to certain environmental allergens such as house dust mites, cats, and cockroaches, have shown a high level of association with asthma prevalence, but in the last five years increasing attention is being paid to indoor environmental factors, other than allergens, that may be involved in the development of this disorder. The potential irritants include nitrogen dioxide, environmental tobacco smoke, formaldehyde, volatile organic compounds, and particulate matter (PM[subscript]2.5;10).The aim of the study was to examine the nature of the relationship between asthma and environmental exposure to indoor environmental irritants.A population based case-control study had been carried out in Perth, Western Australia. The study population consisted of young children (N = 192) aged between 6 months and 3 years old. Cases (n = 88) were asthmatic children who attended the Accident and Emergency Department at Princess Margaret Hospital for Children and were discharged with asthma as a primary diagnosis. Controls (n = 104) were children in the same age group as cases ++ / who had never been diagnosed with asthma, identified from birth records accessed through the Health Department of Western Australia. Information, regarding the respiratory conditions experienced by the study children and characteristics of the home, was collected using a standardised questionnaire. The questionnaire consists of questions about potential risk factors for asthma and these factors were grouped in three categories. The first category included information on personal and social factors such as age and gender of the child, and mother's and father's educational level. The second category was related to personal susceptibility factors such as child's allergy, parental and sibling's asthma, eczema and hay fever. The last category included environmental exposure in the house such as parental and visitors smoking inside the house, exposure to gas heating and cooking, kerosene space heaters, open fireplaces, and pets. Other questions related to environmental exposure were the presence of air conditioning, humidifiers, and type of floor covering in the child's bedroom and the living room. Measurements of indoor nitrogen dioxide (NO[subscript]2), formaldehyde (HCHO), volatile organic compounds (VOCs), particulate matter (PM[subscript]10), and house dust mite exposure were made on two occasions over one year, winter (middle June through September 1998) and summer (December 1998 through March 1999), Indoor temperature and relative humidity were also measured. The atopic status of the children was assessed by skin prick tests to common allergens.The study results indicated that age, gender, family history of asthma, atopy and domestic exposure to indoor environmental factors were significant predictors of asthma early in life. The study found that indoor exposure to formaldehyde, volatile organic compounds and house dust mite significantly increased the risk of ++ / having asthma. Presence of air conditioning appeared to be a protective factor for asthma.In conclusion, the study results confirmed the role of susceptibility factors in asthma and show that indoor environmental factors contribute as risk factors for asthma in early stage of fife. The observation that exposure to indoor air pollutants in early childhood is associated with asthma suggests the possibility that irritants in indoor air might be involved in the initiation phase of asthma. Since the quality of the indoor environment is potentially modifiable there might be opportunities for intervention to reduce asthma symptoms. In order to counteract the increasing prevalence in asthma, the significance of the indoor environment where children grow and spend most of their time need to be given greater attention.

This thesis is based on a research study examining the extent to which cultural background and cultural factors are taken into account by Child Protection Workers investigating allegations of child maltreatment due to inappropriate or excessive punishment. Profiles of child discipline practices within a cultural and historical context were developed and qualitative and quantitative data was gathered through a survey questionnaire sent to all the metropolitan offices of Family and Children's Services. Data was also collected from ethnic leaders, some of their community members and from refugees. The data collected was examined in relation to Child Maltreatment Guidelines of Family & Children's Services and current Child Protection Laws in Western Australia, with a particular focus on practice implications for child protection workers.

Abstract not available

The transcription factor Pax5 is essential for commitment to the B lineage as the development of these cells is arrested at an early stage in the bone marrow of Pax5 deficient mice. Pax5 deficient pro-B cells display remarkable plasticity and are able to differentiate into other cell lineages both in vitro and in vivo. Several Pax5 target genes have been previously reported but none are able to explain the developmental block observed at the early to late pro-B cell stage. To determine the exact mechanisms by which Pax5 controls B cell development, I have undertaken a cDNA microarray screen with a custom generated B cell-specific cDNA library. By identifying genes that are differentially expressed between Pax5 deficient and wild type pro-B cells, I have identified a number of potential Pax5 target genes. The microarray screen identified lymphoid-restricted membrane protein (Lrmp or Jaw1) as a novel Pax5 activated transcript. Using RT-PCR and a Pax5-estrogen receptor inducible system, I confirmed that Jaw1 is a direct Pax5 target gene whose expression is confined, in resting cells, to the earliest stages of B and T cell development. The biological relevance of Jaw1 for cell fate specification has been tested by transducing bone marrow progenitor cells with murine retroviral vectors and reconstituting haemopoiesis in vivo. I have reported that over-expression of Jaw1 in these cells results in a decrease in the development of B and NK lymphocytes and a marked increase in the development of myeloid cells in the bone marrow of reconstituted mice. This result suggests that Jaw1 may play an important role in the early development of lymphocytes in the bone marrow. Whilst initial analysis of Jaw1 deficient mice has revealed no overt defects in lymphopoiesis, I postulate that Jaw1 is involved in IP3-induced calcium signaling downstream of the pre-BCR and BCR. This hypothesis has resulted from analysis of the function of IRAG, the only known Jaw1 homologue combined with data that Jaw1 is expressed in early B cells in the BM as well as in germinal centers in the spleen. Pax5 mutant mice usually die before weaning and the cause of death is currently unknown, suggesting that Pax5 is expressed in a previously unreported tissue. To investigate this hypothesis I produced a monoclonal antibody to Pax5 and screened for novel expression domains during embryonic development and also in neonate mice. These studies did not detect any new Pax5 expression domains, but did reveal that this antibody cross-reacts with Pax2 and/or Pax8 in the developing kidney and brain. Biochemical analysis of the serum from Pax5 deficient mice also did not reveal the likely cause of death in these animals, beyond the general signs of dehydration and starvation that are likely to be secondary to the underlying defect. / Doctor of Philosophy (PhD)

After many years of research focusing on different aspects of human experience conducted both within design research and outside of it, no clear understanding of experience or ways it might be researched have yet been developed. Many conferences, academic papers, and design studies have described partial structures, formulas and hypotheses that have so far provided inadequate understandings of what constitutes experience and how it might be understood (especially in design){Engage, 2005 #263, p.68}. The first difficulty is that there are no suitable design research methods available to enable design researchers to study experience. Secondly, the nature of what is being studied (what constitutes experience) is unclear and thirdly (due to the absence of the first two) no well reasoned way has yet been found to make this type of information useful to designers. This research project set out to find a way to understand everyday human experience from the point of view of design, but first the tools and methods to do this kind of research had themselves to be researched. The personal experiences of a niche group of transport users were chosen as the research vehicle for an explorative research project. Using hermeneutical phenomenology to guide the philosophical orientation as well as many aspects of the methodological approach, field research was conducted in Australia and Europe. From this approach, taxonomy of the vehicle experience (ToE) was developed. A process of deeply (hermeneutically) exploring the information contained in this taxonomy produced a second set of methods (The SEEing process) that causes a deep understanding of the experience to emerge in the design researcher. Both these methods were successfully trialled in Australia and Germany and an analysis of the results is presented. The ToE-SEEing methodology described in this paper provides firstly, a structured approach to understanding a specific experiential situation. Secondly, the methods enable a fundamental and clear understanding of the deeper essences of the experience to be seen with a degree of clarity, such that informed design can take place. This methodology will be helpful to those for whom it is important to have a deep understanding of the experience they wish to design for, and it will be especially helpful for informing those responsible for decisions (design or otherwise) effecting the quality of others experience with goods or services. ToE-SEEing has been shown to be teachable, learnable and useful as a design methodology. / Doctor of Philosophy (PhD)

Adolescent growth provides a unique opportunity for the growing body to adapt to external stimuli. A positive association between site-specific mechanical loading and increases in regional bone mineral content (BMC) during adolescence is established. Mechanical loads associated with middle-distance running expose the skeleton to a combination of compressive ground reaction forces and muscular contraction. Previous studies concerning musculoskeletal health in active adolescents are largely limited to planar, two-dimensional measures of bone mineral status, using Dual X-ray Absorptiometry (DXA). Intrinsic bone material properties are accurately measured using DXA. However, the interaction between bone material and structural properties that reflects the mechanical integrity of bone require a combination of imaging modalities. Magnetic Resonance Imaging (MRI) provides a three-dimensional geometric and biomechanical assessment of bone. When MRI is integrated with DXA technology, an effective non-invasive method of assessing in vivo bone strength is achieved. The impact of high training volumes on musculoskeletal development of male and female adolescent athletes engaged in repetitive, high magnitude mechanical loading has not been investigated. Specifically, differences in total body and regional bone mineral, bone and muscle geometry, bone biomechanical indices and bone strength at differentially-loaded skeletal sites have not been compared between adolescent middle-distance runners and age- and gender-matched non-athletic controls. Objectives: (i) to investigate the effects of intense sports participation involving mechanical loading patterns on bone mineral, bone and muscle geometry, biomechanical indices and estimated regional bone strength between elite adolescent male and female middle-distance runners and age- and gender-matched controls (ii) to examine factors predictive of total body BMC, distal tibial bone geometry, distal tibial bone strength, and Hip Strength Analysis (HSA)- derived indicators of bone strength at the femoral neck. Methods: Four groups of 20 adolescents were comprised of male (mean (SD) age 16.8 ± 0.6 yr, physical activity 14.1 ± 5.7 hr.wk-1) and female (age 16 ± 1.7 yr, physical activity 8.9 ± 2.1 hr.wk-1) middle-distance runners, and male (16.4 ± 0.7 yr, physical activity 2.2 ± 0.7 hr.wk-1) and female (age 16 ± 1.8 yr, physical activity 2.0 ± 0.07 hr.wk-1) controls. Total body and regional BMC were calculated using DXA. Distal tibial bone and muscle cross-sectional areas (CSA) were assessed using MRI. To calculate distal tibial bone strength index (BSI), a region of interest representing 10% of the mid distal tibia was analysed for DXA-derived bone mineral and was combined with bone geometry and biomechanical properties from MRI assessments. Calculations for femoral neck strength were acquired from DXA-derived HSA software. Results: No differences were found between male athletes and controls for unadjusted BMC at total body or regional sites. After covarying for fat mass (kg), male athletes displayed greater BMC at the lumbar spine (p = 0.001), dominant proximal femur (p = 0.001) and dominant leg (p = 0.03) than male controls. No differences were found in distal tibial bone geometry, bone strength at the distal tibia or HSA-derived indicators of bone strength at the femoral neck between male athletes and controls. Lean tissue mass and fat mass were the strongest predictors of total body BMC (R2 = 0.71), total muscle CSA explained 43.5% of variance in BSI at the distal tibia, and femur length and neck of femur CSA explained 33.4% of variance at the femoral neck. In females, athletes displayed greater unadjusted BMC at the proximal femur (+3.9 ±1.4 g, p = 0.01), dominant femoral neck (+0.5 ± 0.12 g, p = 0.01) and dominant tibia (+4.1 ± 2.1 g, p = 0.05) than female controls. After covarying for fat mass (kg), female athletes displayed greater (p = 0.001) total body, dominant proximal femur and dominant leg BMC than female controls. Female athletes also showed greater distal tibial cortical CSA (+30.9 ± 9.5 mm2, p = 0.003), total muscle (+240.2 ± 86.4 mm2, p = 0.03) and extensor muscle (+46.9 ±19.5 mm2, p = 0.02) CSA, smaller medullary cavity (-32.3 ± 14.7 mm2, p = 0.03) CSA and greater BSI at the distal tibia (+28037 ± 8214.7 g/cm3.mm4, p = 0.002) than female controls. Lean tissue mass and fat mass were the strongest predictors of total body BMC (R2 = 65), hours of physical weekly activity and total muscle CSA explained 58.3% of the variance of distal tibial BSI, and neck of femur CSA accounted for 64.6% of the variance in a marker of femoral neck HSA. Conclusion: High training loads are associated with positive musculoskeletal outcomes in adolescent middle-distance runners compared to non-athletic controls. Exposure to similar high training loads may advantage female adolescent athletes, more than male adolescent athletes compared with less active peers in bone strength at the distal tibia.

In the design of all marine craft the prediction of a vessel??s resistance characteristics is a major consideration. The accurate prediction of resistance is particularly important in the design of modern high-speed vessels where the primary contractual obligation placed upon the builder is the vessel??s achievable speed. Investigation was made of the methods of Doctors and Day, whereby the traditional Michell wave-resistance theory, published in 1898, is improved on through a better understanding of the hydrodynamics of transom sterns and the application of statistically determined form factors. One of the difficulties with the Michell theory is how to account for the hollow that forms behind a transom stern, a feature prevalent in high-speed vessels. A common approach in the numerical prediction of wave resistance for transom-stern vessels is to discretize the hollow as a geometrically-smooth addition to the vessel. Therefore, of great importance in accurate prediction of wave resistance is the hydrodynamics of, and in particular, the length and depth of the hollow formed behind the transom stern. Accordingly, a systematic series of transom-stern models were tank tested at various drafts and speeds in order to determine experimentally the length and depth of the hollow as a function of vessel speed, draft and beam. From the experimental data, algorithms for the determination of the length and depth of the transom hollow, have been developed and utilised in the discretization of the transom hollow for prediction of resistance using the Michell wave- resistance theory. Application of the developed hollow algorithms produced significant improvements in correlation of the experimental and theoretical predictions of total resistance, particularly in the lower Froude range. In addition to the transom-hollow investigation, form factors were obtained using least-squares regression of existing experimental data. The form factors were based on the major geometric parameters of the models used. In the research presented here, the method was applied to a large range of published resistance data for high-speed displacement vessels. Considerable improvement in correlation, between theoretical and experimental predictions of total resistance, was obtained by incorporating the calculated form-factors into the total resistance formulation.

Ovaries maintain and produce functional female gametes, oocytes, for fertilisation. Oocytes develop inside cellular assemblies, the ovarian follicles, before birth and can reside there for up to 50 years in the human. Despite recent inroads, the precise mechanisms of initial follicle recruitment and growth remain unclear. Although the pituitary gonadotrophins play a role in this developmental process, locally produced factors have been implicated strongly in initiation of follicle growth. It is known that fibroblast growth factor 2 (FGF2) is a powerful mitogen for follicular granulosa cells in culture and initial studies undertaken in this project were successful in detecting FGF2 gene expression in ovarian biopsies from fertile healthy women. To further elucidate which cells were expressing FGF2, laser microdissection was employed to isolate differentially staged follicle populations. Real-time RT-PCR was used to quantify mRNA in relation to follicle development. Decreasing levels of FGF2 expression were detected as follicles developed. Non-radioactive in situ hybridisation confirmed FGF2 mRNA localisation in granulosa cells of preantral follicles. FGF2 protein localisation was assessed with immunohistochemistry; two primary antibodies raised against different fragments of human FGF2 were used. Both antibodies detected FGF2 in the oocyte cytoplasm of putative non-growing follicles, whereas only one of the antibodies showed additional reactivity to the basement membrane region of these same follicles. These results suggest different isoforms of FGF2 may localise specifically to different cellular sites. Follicle stimulating hormone receptor (FSHR) gene expression was also investigated in follicles using laser microdissection, real-time RT-PCR and in situ hybridisation. FSHR mRNA was detected in all follicle populations, including the smallest putative non-growing follicles. Disparity to other published works was attributed to the position of primer annealing, and thus the ability to detect alternatively spliced transcripts. In conclusion, the work presented here provides evidence that FGF2 and FSHR are present in small follicles and that their actions may be stimulatory or inhibitory to initial follicle recruitment.

A German pathologist first described defects in the elastic tissues of human arteries over one hundred years ago. Much evidence now supports the involvement of these elastic tissue defects (ETDs) in the initiation and progression of atherosclerosis, although this association is not well accepted. Recent research has determined that the migration of medial smooth muscle cells into the intima (and therefore the start of the atherosclerotic process) is initiated in an attempt to repair these defects and in addition, that there is a correlation between the extent of intimal thickening and the degree of elastic tissue disruption. The Brown Norway (BN) strain appears to have an increased predilection, having a significantly greater incidence of ETDs within the caudal and renal arteries and the abdominal aorta compared with other rat strains. These defects appear morphologically identical to those observed in the arteries of young humans. The purpose of this study was to determine the magnitude of the genetic and environmental components in the formation of these ETDs in the aorta. Previous studies have demonstrated that the spontaneous formation of elastic tissue defects in the abdominal aorta of the Brown Noway rat is a genetically inherited phenotype, passed from parent to offspring in an autosomal dominant manner. Following crossbreeding of the BN rat with four other strains (two hypertensive and two normotensive) it was determined that, although the inheritance mode of the ETD phenotype followed an autosomal dominant pattern, the expression or penetrance of this phenotype was reduced in F₁ all crossbred groups. Moreover, the early postnatal growth profile of the F₁ pups appeared to be differentially associated with defect formation. To further examine the relationship between aortic ETDs and birthweight, a well-studied model of in utero growth restriction was investigated in the BN rat. On day 18 of a 23-day gestation the uterine arteries were ligated, which resulted in offspring that were 14% smaller than un-operated control pups. This short-term insult resulted in significantly increased numbers of ETDs in growth-restricted animals at 8 weeks of age, an effect that was also observed in 16-week old males. The effect of in utero growth restriction on ETDs in the guinea pig and ApoE knockout mouse was also examined, to determine if ETDs (and subsequent early atherosclerotic events) may be influenced by the exposure to a growth-restricting event in utero. Despite this work leading to the novel characterisation of ETDs in the guinea pig aorta, the growth restricting surgery resulted in poor maternal and pup outcomes, which limited the conclusions that could be drawn from these studies. Furthermore, microarray techniques were employed to examine changes in aortic gene expression following growth restriction, by comparing amplified mRNA extracts from 8-week old growth restricted BN pup aortas with extracts from a group of average birthweight, un-operated BN pups. In combination, these studies propose both genetic inheritance and the in utero environment regulate elastic tissue defect phenotype, which in turn potentially affects the initiation and progression of early atherosclerosis.