Energy and population policies in Australia

The Australian Government is about to release Australia’s first sustainable population policy. Sustainable population growth, among other things, implies sustainable energy demand. Current modelling of future energy demand both in Australia and by agencies such as the International Energy Agency sees population growth as one of the key drivers of energy demand. Simply increasing the demand for energy in response to population policy is sustainable only if there is a radical restructuring of the energy system away from energy sources associated with environmental degradation towards one more reliant on renewable fuels and less reliant on fossil fuels. Energy policy can also address the present nexus between energy consumption per person and population growth through an aggressive energy efficiency policy. The paper considers the link between population policies and energy policies and considers how the overall goal of sustainability can be achieved. The methods applied in this analysis draw on the literature of sustainable development to develop elements of an energy planning framework to support a sustainable population policy. Rather than simply accept that energy demand is a function of population increase moderated by an assumed rate of energy efficiency improvement, the focus is on considering what rate of energy efficiency improvement is necessary to significantly reduce the standard connections between population growth and growth in energy demand and what policies are necessary to achieve this situation. Energy efficiency policies can only moderate unsustainable aspects of energy demand and other policies are essential to restructure existing energy systems into on-going sustainable forms. Policies to achieve these objectives are considered. This analysis shows that energy policy, population policy and sustainable development policies are closely integrated. Present policy and planning agencies do not reflect this integration and energy and population policies in Australia have largely developed independently and whether the outcome is sustainable is largely a matter of chance. A genuinely sustainable population policy recognises the inter-dependence between population and energy policies and it is essential that this is reflected in integrated policy and planning agencies

Energy and population policies in Australia

The Australian Government is about to release Australia’s first sustainable population policy. Sustainable population growth, among other things, implies sustainable energy demand. Current modelling of future energy demand both in Australia and by agencies such as the International Energy Agency sees population growth as one of the key drivers of energy demand. Simply increasing the demand for energy in response to population policy is sustainable only if there is a radical restructuring of the energy system away from energy sources associated with environmental degradation towards one more reliant on renewable fuels and less reliant on fossil fuels. Energy policy can also address the present nexus between energy consumption per person and population growth through an aggressive energy efficiency policy. The paper considers the link between population policies and energy policies and considers how the overall goal of sustainability can be achieved. The methods applied in this analysis draw on the literature of sustainable development to develop elements of an energy planning framework to support a sustainable population policy. Rather than simply accept that energy demand is a function of population increase moderated by an assumed rate of energy efficiency improvement, the focus is on considering what rate of energy efficiency improvement is necessary to significantly reduce the standard connections between population growth and growth in energy demand and what policies are necessary to achieve this situation. Energy efficiency policies can only moderate unsustainable aspects of energy demand and other policies are essential to restructure existing energy systems into on-going sustainable forms. Policies to achieve these objectives are considered. This analysis shows that energy policy, population policy and sustainable development policies are closely integrated. Present policy and planning agencies do not reflect this integration and energy and population policies in Australia have largely developed independently and whether the outcome is sustainable is largely a matter of chance. A genuinely sustainable population policy recognises the inter-dependence between population and energy policies and it is essential that this is reflected in integrated policy and planning agencies

Enduring documents : improving the forms, improving the outcomes

Most Australian states have introduced legislation to provide for enduring documents for financial, personal and health care decision making in the event of incapacity. Since the introduction of Enduring Powers of Attorney (EPAs) and Advance Health Directives (AHDs) in Queensland in 1998, concerns have continued to be raised by service providers, professionals and individuals about the uptake, understanding and appropriate use of these documents. In response to these concerns, the Department of Justice and Attorney-General (DJAG) convened a Practical Guardianship Initiatives Working Party. This group identified the limited evidence base available to address these concerns. In 2009, a multidisciplinary research team from the University of Queensland and the Queensland University of Technology was awarded $90,000 from the Legal Practitioners Interest on Trust Account Fund to undertake a review of the current EPA and AHD forms. The goal of the research was to gather data on the content and useability of the forms from the perspectives of a range of stakeholders, particularly those completing the EPA and AHD, witnesses of these documents, attorneys appointed under an EPA, and health professionals involved in the completion of an AHD or dealing with it in a clinical context. The researchers also sought to gather information from the perspective of Aboriginal and Torres Strait Islander (ATSI) individuals as well people from culturally and linguistically diverse (CALD) groups. Although the focus of the research was on the forms and the extent to which the current design, content and format represents a barrier to uptake, in the course of the research, some broader issues were identified which have an impact on the effectiveness of the EPA and AHD in achieving the goals of planning for financial and personal and health care in advance of losing capacity. The data gathered enabled the researchers to achieve the primary goal of the research: to make recommendations to improve the content and useability of the forms which hopefully will lead to an increased uptake and appropriate use of the forms. However, the researchers thought it was important not to ignore broader policy issues that were identified in the course of the research. These broader issues have been highlighted in this Report, and the researchers have responded to them in a variety of ways. For some issues, the researchers have suggested alterations that could be made to the forms to address the particular concerns. For other issues, the researchers have suggested that Government may need to take specific action such as educating the broader community with some attention to strategies that engage particular groups within communities. Other concerns raised can only be dealt with by legislative reform and, in some of these cases, the researchers have identified issues that Government may wish to consider further. We do note, however, that it is beyond the scope of this Report to recommend changes to the law. This three stage mixed methods project aimed to provide systematic evidence from a broad range of stakeholders in regard to: (i) which groups use and do not use these documents and why, (ii) the contribution of the length/complexity/format/language of the forms as barriers to their completion and/or effective use, and (iii) the issues raised by the current documents for witnesses and attorneys. Understanding and use of EPAs and AHDs were generally explored in separate but parallel processes. A purposive sampling strategy included users of the documents as principals and attorneys, and professionals, witnesses and service providers who assist others to execute or use the forms. The first component of this study built on existing knowledge using a Critical Reference Group and material provided by the DJAG Practical Guardianship Initiatives Working Party. This assisted in the development of the data collection tools for subsequent stages. The second component comprised semi-structured interviews and focus groups with a targeted sample of current users of the forms, potential users, witnesses and other professionals to provide in-depth information on critical issues. Outreach to Aboriginal and Torres Strait Islander Elders and individuals and workers with CALD groups ensured a broad sample of potential users of the two documents. Fifty individual interviews and three focus groups were completed. Most interviews and focus groups focused on perceptions of, and experiences with, either the EPA or the AHD form. In the interviews with Indigenous people and the CALD focus groups, however, respondents provided their perceptions and experiences of both documents. In general, these respondents had not used the forms and were responding to the documents made available in the interview or focus group. In total, seventy-seven individuals were involved in interviews or focus groups. The final component comprised on-line surveys for EPA principals, EPA attorneys, AHD principals, witnesses of EPAs and AHDs and medical practitioners with experience of AHDs as nominated and/or treating doctors. The surveys were developed from the initial component and the qualitative analysis of the interview and focus group data. A total of 116 surveys were returned from major cities and regional Queensland. The survey data was analysed descriptively for patterns and trends. It is important to note that the aim of the survey was to gain insight into issues and concerns relating to the documents and not to make generalisations to the broader population.

Impacts of traditional husbandry practices on exploitable levels of genetic diversity in cultured 'Tra' catfish (Pangasianodon hypophthalmus) in the Mekong Delta, Vietnam

Sutchi catfish (Pangasianodon hypophthalmus) – known more universally by the Vietnamese name ‘Tra’ is an economically important freshwater fish in the Mekong Delta in Vietnam that constitutes an important food resource. Artificial propagation technology for Tra catfish has only recently been developed along the main branches of the Mekong River where more than 60% of the local human population participate in fishing or aquaculture. Extensive support for catfish culture in general, and that of Tra (P. hypophthalmus) in particular, has been provided by the Vietnamese government to increase both the scale of production and to develop international export markets. In 2006, total Vietnamese catfish exports reached approximately 286,602 metric tons (MT) and were valued at 736.87 $M with a number of large new export destinations being developed. Total value of production from catfish culture has been predicted to increase to approximately USD 1 billion by 2020. While freshwater catfish culture in Vietnam has a promising future, concerns have been raised about long-term quality of fry and the effectiveness of current brood stock management practices, issues that have been largely neglected to date. In this study, four DNA markers (microsatellite loci: CB4, CB7, CB12 and CB13) that were developed specifically for Tra (P. hypophthalmus) in an earlier study were applied to examine the genetic quality of artificially propagated Tra fry in the Mekong Delta in Vietnam. The goals of the study were to assess: (i) how well available levels of genetic variation in Tra brood stock used for artificial propagation in the Mekong Delta of Vietnam (breeders from three private hatcheries and Research Institute of Aquaculture No2 (RIA2) founders) has been conserved; and (ii) whether or not genetic diversity had declined significantly over time in a stock improvement program for Tra catfish at RIA2. A secondary issue addressed was how genetic markers could best be used to assist industry development. DNA was extracted from fins of catfish collected from the two main branches of the Mekong River inf Vietnam, three private hatcheries and samples from the Tra improvement program at RIA2. Study outcomes: i) Genetic diversity estimates for Tra brood stock samples were similar to, and slightly higher than, wild reference samples. In addition, the relative contribution by breeders to fry in commercial private hatcheries strongly suggest that the true Ne is likely to be significantly less than the breeder numbers used; ii) in a stock improvement program for Tra catfish at RIA2, no significant differences were detected in gene frequencies among generations (FST=0.021, P=0.036>0.002 after Bonferroni correction); and only small differences were observed in alleles frequencies among sample populations. To date, genetic markers have not been applied in the Tra catfish industry, but in the current project they were used to evaluate the levels of genetic variation in the Tra catfish selective breeding program at RIA2 and to undertake genetic correlations between genetic marker and trait variation. While no associations were detected using only four loci, they analysis provided training in the practical applications of the use of molecular markers in aquaculture in general, and in Tra culture, in particular.

Breastfeeding self-efficacy and alternative techniques to overcome maternal or infant breastfeeding challenges : a retrospective descriptive study

Background: Breastfeeding is the internationally accepted ideal in infant feeding. Ensuring mothers and babies receive optimal benefits, in both the short and long term, is dependent upon the successful establishment of breastfeeding in the first week. Many maternal and infant challenges can occur during the establishment of breastfeeding (Lactogenesis II). There are also many methods and devices (alternative techniques) which can be used to help, but the majority do not have an evidence-base. The mother.s self-confidence (self-efficacy) can be challenged by these unexpected circumstances, but understanding of the relationship is unclear. Method: This descriptive study used mail survey (including the Breastfeeding Self-Efficacy Scale . Short Form) to obtain the mother.s reports of their self-efficacy and their breastfeeding experience during the first week following birth, as well as actual use of alternative techniques. This study included all mothers of full term healthy singleton infants from one private hospital in Brisbane who began any breastfeeding. The data collection took place from November 2008 to February 2009. Ethical approval was granted from the research site and QUT Human Research Ethics Committee. Results: A total of 128 questionnaires were returned, a response rate of 56.9%. The sample was dissimilar to the Queensland population with regard to age, income, and education level, all of which were higher in this study. The sample was similar to the Queensland population in terms of parity and marital status. The rate of use of alternative techniques was 48.3%. The mean breastfeeding self-efficacy score of those who used any alternative technique was 43.43 (SD=12.19), and for those who did not, it was 58.32 (SD=7.40). Kruskal-Wallis analysis identified that the median self efficacy score for those who used alternative techniques was significantly lower than median self efficacy scores for those who did not use alternative techniques. The reasons women used alternative techniques varied widely, and their knowledge of alternative techniques was good. Conclusion: This study is the first to document breastfeeding self-efficacy of women who used alternative techniques to support their breastfeeding goals in the first week postpartum. An individualised clinical intervention to develop women.s self-efficacy with breastfeeding is important to assist mother/infant dyads encountering challenges to breastfeeding in the first week postpartum.

The relationship between abdominal obesity and depression in the general population : a systematic review and meta-analysis

Obesity has been widely regarded as a public health concern because of its adverse impact on individuals’ health. Systematic reviews have been published in examining the effect of obesity on depression, but with major emphasis on general obesity as measured by the body mass index. Despite a stronger effect of abdominal obesity on individuals’ physical health outcomes, to our best knowledge, no systematic review was undertaken with regard to the relationship between abdominal obesity and depression. This paper reports the results of a systematic review and meta-analysis of cross-sectional studies examining the relationship between abdominal obesity and depression in a general population. Multiple electronic databases were searched until the end of September 2009. 15 articles were systematically reviewed and meta-analyzed. The analysis showed that the odds ratio of having depression for individuals with abdominal obesity was 1.38 (95% CI, 1.22–1.57) as compared to those who are not obese. Furthermore, it was found that this relationship did not vary with potential confounders including gender, age, measurement of depression and abdominal obesity, and study quality.

Attachment Security and Alexithymia in a Heavy Drinking Population

Attachment difficulties have been proposed as a key risk factor for the development of alexithymia, a multifaceted personality trait characterised by difficulties identifying and describing feelings, a lack of imagination and an externally oriented thinking style. The present study investigated the relationship between attachment and alexithymia in an alcohol dependent population. Participants were 210 outpatients in a Cognitive Behavioural Treatment Program assessed on the Toronto Alexithymia Scale (TAS-20) and the Revised Adult Attachment Scale (RAAS). Significant relationships between anxious attachment and alexithymia factors were confirmed. Furthermore, alexithymic alcoholics reported significantly higher levels of anxious attachment and significantly lower levels of closeness (secure attachment) compared to non-alexithymic alcoholics. These findings highlight the importance of assessing and targeting anxious attachment among alexithymic alcoholics in order to improve alcohol treatment outcomes. Keywords: Attachment, alexithymia, alcohol dependence.

The application of Bowen’s family system theory (BFST) to the Malay population in Malaysia

The rapid economic development and social changes in Malaysia recently have led to many psychosocial problems in young people, such as drug addiction, child sexual abuse and mental illness. The Malaysian government is beginning to focus more attention on its social welfare and human service needs in order to alleviate these psychosocial problems. Although counselling is accepted and widespread in Malaysia, the practice of family therapy is not as accepted as it is still a widely held belief that family problems need to be kept within the family. However, changes are imminent and thus the theoretical basis of family therapy needs to be culturally relevant. Bowen‟s Family Systems Theory (BFST) is already one of the major theories taught to tertiary counselling students in Malaysian universities. The main tenet of Bowen‟s theory is that the family as a system may be unstable unless each member of the family is well differentiated. High differentiation levels in the family allow a person to both leave the family‟s boundaries in search of uniqueness and to continually return to the family fold in order to establish a more mature sense of belonging. The difficulty, however, is that while Bowen has claimed that his theory is universal nearly all of the research confirming the theory has been conducted in the United States of America. The only known study outside America, however, did show that Bowen‟s theory applied to a Filipino population but, one of the theory‟s propositions that differentiation is intergenerational was not supported in this non-American sample. The American sample that was compared to the Malay sample was taken from Skowron and Friedlander‟s (1998) study. One hundred and twenty-seven faculty staff in an American university completed the Differentiation of Self Inventory (DSI) to measure level of differentiation of self. This thesis therefore, set out to determine whether Bowen‟s theory applied to another non-American sample, the Malaysian community. The research also investigated if the intergenerational effect was present in the Malaysian sample as well as explored the role of socio-economic status on Bowen‟s theory of differentiation and gender effect. Three hundred and seventy-four families completed four measures to examine these research questions: the Differentiation of Self Inventory (DSI), the Family Inventory of Life Event (FILE), the Depression Anxiety and Stress Scale (DASS) and the Connor-Davidson Resilience Scale (CD-RISC). The results of the study showed that differentiation of self is a valid construct for the Malay population. However, all four subscales of the Differentiation of Self Inventory (DSI); emotional reactivity (ER), emotional cut-off (EC), fusion with other (FO) and I position (IP), showed significant differences compared to the American sample from Skowron and Friedlander‟s (1998) study. The Malay sample scored higher in emotional reaction (ER), fusion with other (FO), but lower on emotional cut-off (EC) and I position (IP) than the American sample. The intergenerational effect was found in the Malay population as the parent‟s level of differentiation correlated with their children‟s level of differentiation. It was found that stress as measured by the Family Inventory of Life Event (FILE) and as measured by the Depression Anxiety and Stress Scale (DASS) were not correlated with the level of differentiation of self in parents. However, gender had a significant effect in predicting the level of differentiation among parents in Malay population with females scores higher on emotional reactivity (ER) and fusion with other (FO) than males. An additional finding was that resilience can be predicted from the level of differentiation of self in children in the Malay sample. There was also a positive correlation between the level of differentiation of self in parents and resilience in their children. Findings from this study indicate that the concept of differentiation of self is applicable to a Malay sample; however, the implementation of the theory should be applied with cultural sensitivity.

Reduced variance in monozygous twins for multiple MR parameters : implications for disease studies and the genetic basis of brain structure

Twin studies offer the opportunity to determine the relative contribution of genes versus environment in traits of interest. Here, we investigate the extent to which variance in brain structure is reduced in monozygous twins with identical genetic make-up. We investigate whether using twins as compared to a control population reduces variability in a number of common magnetic resonance (MR) structural measures, and we investigate the location of areas under major genetic influences. This is fundamental to understanding the benefit of using twins in studies where structure is the phenotype of interest. Twenty-three pairs of healthy MZ twins were compared to matched control pairs. Volume, T2 and diffusion MR imaging were performed as well as spectroscopy (MRS). Images were compared using (i) global measures of standard deviation and effect size, (ii) voxel-based analysis of similarity and (iii) intra-pair correlation. Global measures indicated a consistent increase in structural similarity in twins. The voxel-based and correlation analyses indicated a widespread pattern of increased similarity in twin pairs, particularly in frontal and temporal regions. The areas of increased similarity were most widespread for the diffusion trace and least widespread for T2. MRS showed consistent reduction in metabolite variation that was significant in the temporal lobe N-acetylaspartate (NAA). This study has shown the distribution and magnitude of reduced variability in brain volume, diffusion, T2 and metabolites in twins. The data suggest that evaluation of twins discordant for disease is indeed a valid way to attribute genetic or environmental influences to observed abnormalities in patients since evidence is provided for the underlying assumption of decreased variability in twins.

Peer state assessment of TxDOT maintenance program and practices, part II : test section survey findings and recommendations

This paper presents a road survey as part of a workshop conducted by the Texas Department of Transportation (TxDOT) to evaluate and improve the maintenance practices of the Texas highway system. Directors of maintenance from six peer states (California, Kansas, Georgia, Missouri, North Carolina, and Washington) were invited to this 3-day workshop. One of the important parts of this workshop was a Maintenance Test Section Survey (MTSS) to evaluate a number of pre-selected one-mile roadway sections. The workshop schedule allowed half a day to conduct the field survey and 34 sections were evaluated. Each of the evaluators was given a booklet and asked to rate the selected road sections. The goals of the MTSS were to: 1. Assess the threshold level at which maintenance activities are required as perceived by the evaluators from the peer states; 2. Assess the threshold level at which maintenance activities are required as perceived by evaluators from other TxDOT districts; and 3. Perform a pilot evaluation of the MTSS concept. This paper summarizes the information obtained from survey and discusses the major findings based on a statistical analysis of the data and comments from the survey participants.

Renal bioenergetics during early gram-negative mammalian sepsis and angiotensin II infusion

Purpose: To measure renal adenosine triphosphate (ATP) (bioenergetics) during hypotensive sepsis with or without angiotensin II (Ang II) infusion. Methods: In anaesthetised sheep implanted with a renal artery flow probe and a magnetic resonance coil around one kidney, we induced hypotensive sepsis with intravenous Escherichia coli injection. We measured mean arterial pressure (MAP), heart rate, renal blood flow RBF and renal ATP levels using magnetic resonance spectroscopy. After 2 h of sepsis, we randomly assigned sheep to receive an infusion of Ang II or vehicle intravenously and studied the effect of treatment on the same variables. Results: After E. coli administration, the experimental animals developed hypotensive sepsis (MAP from 92 ± 9 at baseline to 58 ± 4 mmHg at 4 h). Initially, RBF increased, then, after 4 h, it decreased below control levels (from 175 ± 28 at baseline to 138 ± 27 mL/min). Despite decreased RBF and hypotension, renal ATP was unchanged (total ATP to inorganic phosphate ratio from 0.69 ± 0.02 to 0.70 ± 0.02). Ang II infusion restored MAP but caused significant renal vasoconstriction. However, it induced no changes in renal ATP (total ATP to inorganic phosphate ratio from 0.79 ± 0.03 to 0.80 ± 0.02). Conclusions:During early hypotensive experimental Gram-negative sepsis, there was no evidence of renal bioenergetic failure despite decreased RBF. In this setting, the addition of a powerful renal vasoconstrictor does not lead to deterioration in renal bioenergetics.

The role of insulin and IGF2 signalling on metabolic pathways in prostate cancer progression

Prostate cancer (CaP) is the most commonly diagnosed cancer in males in Australia, North America, and Europe. If found early and locally confined, CaP can be treated with radical prostatectomy or radiation therapy; however, 25-40% patients will relapse and go on to advanced disease. The most common therapy in these cases is androgen deprivation therapy (ADT), which suppresses androgen production from the testis. Lack of the testicular androgen supply causes cells of the prostate to undergo apoptosis. However, in some cases the regression initially seen with ADT eventually gives way to a growth of a population of cancerous cells that no longer require testicular androgens. This phenotype is essentially fatal and is termed castrate resistant prostate cancer (CRPC). In addition to eventual regression, there are many undesirable side effects which accompany ADT, including development of a metabolic syndrome, which is defined by the U.S. National Library of Medicine as “a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes.” This project will focus on the effect of ADT induced hyperinsulinemia, as mimicked by treating androgen receptor positive CaP cells with insulin in a serum (hormone) deprived environment. While this side effect is not widely explored, in this thesis it is demonstrated for the first time that insulin upregulates pathways important to CaP progression. Our group has previously shown that during CaP progression, the enzymes necessary for de novo steroidogenesis are upregulated in the LNCaP xenograft model, total steroid levels are increased in tumours compared to pre castrate levels, and de novo steroidogenesis from radio-labelled acetate has been demonstrated. Because of the CaP dependence on AR for survival, we and other groups believe that CaP cells carry out de novo steroidogenesis to survive in androgen deprived conditions. Because (a) men on ADT often develop metabolic syndrome, and (b) men with lifestyle-induced obesity and hyperinsulinemia have worse prognosis and faster disease progression, and because (c) insulin causes steroidogenesis in other cell lines, the hypothesis that insulin may contribute to CaP progression through upregulation of steroidogenesis was explored. Insulin upregulates steroidogenesis enzymes at the mRNA level in three AR positive cell lines, as well as upregulating these enzymes at the protein level in two cell lines. It has also been demonstrated that insulin increases mitochondrial (functional) levels of steroid acute regulatory protein (StAR). Furthermore, insulin causes increased levels of total steroids in and induction of de novo steroid synthesis by insulin has been demonstrated at levels induced sufficient to activate AR. The effect of insulin analogs on CaP steroidogenesis in LNCaP and VCaP cells has also been investigated because epidemiological studies suggest that some of the analogs developed may have more cancer stimulatory effects than normal insulin. In this project, despite the signalling differences between glargine, X10, and insulin, these analogs did not appear to induce steroidogenesis any more potently that normal insulin. The effect of insulin of MCF7breast cancer cells was also investigated with results suggesting that breast cancer cells may be capable of de novo steroidogenesis, and that increase in estradiol production may be exacerbated by insulin. Insulin has also been long known to stimulate lipogenesis in the liver and adipocytes, and has been demonstrated to increase lipogenesis in breast cancer cells; therefore, investigation of the effect of insulin on lipogenesis, which is a hallmark of aggressive cancers, was investigated. In CaP progression sterol regulatory element binding protein (SREBP) is dysregulated and upregulates fatty acid synthase (FASN), acetyl CoA-carboxylase, and other lipogenesis genes. SREBP is important for steroidogenesis and in this project has been shown to be upregulated by insulin in CaP cells. Fatty acid synthesis provides building blocks of membrane growth, provides substrates for acid oxidation, the main energy source for CaP cells, provides building blocks for anti-apoptotic and proinflammatory molecules, and provides molecules that stimulate steroidogenesis. In this project it has been shown that insulin upregulates FASN and ACC, which synthesize fatty acids, as well as upregulating hormone sensitive lipase (HSL), diazepam-binding inhibitor (DBI), and long-chain acyl-CoA synthetase 3 (ACSL3), which contribute to lipid activation of steroidogenesis. Insulin also upregulates total lipid levels and de novo lipogenesis, which can be suppressed by inhibition of the insulin receptor (INSR). The fatty acids synthesized after insulin treatment are those that have been associated with CaP; furthermore, microarray data suggests insulin may upregulate fatty acid biosynthesis, metabolism and arachidonic acid metabolism pathways, which have been implicated in CaP growth and survival. Pharmacological agents used to treat patients with hyperinsulinemia/ hyperlipidemia have gained much interest in regards to CaP risk and treatment; however, the scientific rationale behind these clinical applications has not been examined. This thesis explores whether the use of metformin or simvastatin would decrease either lipogenesis or steroidogenesis or both in CaP cells. Simvastatin is a 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitor, which blocks synthesis of cholesterol, the building block of steroids/ androgens. It has also been postulated to down regulate SREBP in other metabolic disorders. It has been shown in this thesis, in LNCaP cells, that simvastatin inhibited and decreased insulin induced steroidogenesis and lipogenesis, respectively, but increased these pathways in the absence of insulin. Conversely, metformin, which activates AMP-activated protein kinase (AMPK) to shut down lipogenesis, cholesterol synthesis, and protein synthesis, highly suppresses both steroidogenesis and lipogenesis in the presence and absence of insulin. Lastly, because it has been demonstrated to increase steroidogenesis in other cell lines, and because the elucidation of any factors affecting steroidogenesis is important to understanding CaP, the effect of IGF2 on steroidogenesis in CaP cells was investigated. In patient samples, as men progress to CRPC, IGF2 mRNA and the protein levels of the receptors it may signal through are upregulated. It has also been demonstrated that IGF2 upregulates steroidogenic enzymes at both the mRNA and protein levels in LNCaP cells, increases intracellular and secreted steroid/androgen levels in LNCaPs to levels sufficient to stimulate the AR, and upregulated de novo steroidogenesis in LNCaPs and VCaPs. As well, inhibition of INSR and insulin-like growth factor 1 receptor (IGF1R), which IGF2 signals through, suggests that induction of steroidogenesis may be occurring predominantly through IGF1R. In summary, this project has illuminated for the first time that insulin is likely to play a large role in cancer progression, through upregulation of the steroidogenesis and lipogenesis pathways at the mRNA and protein levels, and production levels, and demonstrates a novel role for IGF-II in CaP progression through stimulation of steroidogenesis. It has also been demonstrated that metformin and simvastatin drugs may be useful in suppressing the insulin induction of these pathways. This project affirms the pathways by which ADT- induced metabolic syndrome may exacerbate CaP progression and strongly suggests that the monitoring and modulation of the metabolic state of CaP patients could have a strong impact on their therapeutic outcomes.

Can the Cardiac ARIA Index Improve Cardiac Care for Australia's Indigenous Population?

Background: Timely access to appropriate cardiac care is critical for optimising outcomes. Our aim was to derive an objective, comparable, geographic measure reflecting access to cardiac services for Australia's 20,387 population locations. Methods: An expert panel defined a single patient care pathway. Using geographic information systems (GIS) the numeric/alpha index was modelled in two phases. The acute phase index (numeric) ranged from 1 (access to tertiary centre with PCI ≤1 h) to 8 (no ambulance service, >3 h to medical facility, air transport required). The aftercare index was modelled into 5 alphabetic categories; A (Access to general practitioner, pharmacy, cardiac rehabilitation, pathology ≤1 h) to E (no services available within 1 h). Results: Approximately 70% or 13.9 million people lived within a CardiacARIAindex category 1A location. Disparity continues in access to category 1A cardiac services for 5.8 million (30%) of all Australians, 60% of Aboriginal and Torres Strait Islander people and 32% of people over 65 years of age. In a cardiac emergency only 40% of the Indigenous population reside within one hour of category 1 hospital. Approximately 30% (81,491 Indigenous persons) are more than one to three hours from basic cardiac services. Conclusion: Geographically, the majority of Australian's have timely access for survival of a cardiac event. The CardiacARIAindex objectively demonstrates that the healthcare system may not be providing for the needs of 60% of Indigenous people residing outside the 1A geographic radius. Innovative clinical practice maybe required to address these disparities.

H. pylori-infection and antibody immune response in a rural Tanzanian population

Abstract Background: Helicobacter pylori (H. pylori) infection is ubiquitous in sub-Saharan Africa, but paradoxically gastric cancer is rare. Methods: Sera collected during a household-based survey in rural Tanzania in 1985 were tested for anti-H. pylori IgG and IgG subclass antibodies by enzyme immunoassay. Odds ratios (OR) and confidence intervals (CI) of association of seropositivity with demographic variables were computed by logistic regression models. Results: Of 788 participants, 513 were aged ≤17 years. H. pylori seropositivity increased from 76% at 0–4 years to 99% by ≥18 years of age. Seropositivity was associated with age (OR 11.5, 95% CI 4.2–31.4 for 10–17 vs. 0–4 years), higher birth-order (11.1; 3.6–34.1 for ≥3rd vs. 1st born), and having a seropositive next-older sibling (2.7; 0.9–8.3). Median values of IgG subclass were 7.2 for IgG1 and 2.0 for IgG2. The median IgG1/IgG2 ratio was 3.1 (IQR: 1.7–5.6), consistent with a Th2- dominant immune profile. Th2-dominant response was more frequent in children than adults (OR 2.4, 95% CI 1.3–4.4). Conclusion: H. pylori seropositivity was highly prevalent in Tanzania and the immunological response was Th2-dominant. Th2-dominant immune response, possibly caused by concurrent bacterial or parasitic infections, could explain, in part, the lower risk of H. pylori-associated gastric cancer in Africa.