Road trauma perceptions and the potential influence of the media

The United Nations Decade of Action for Road Safety (2011-2020) recognises the urgency of addressing global road trauma. Road crashes and attempts to reduce risky driving, including public education campaigns, receive media attention in many countries. In Australia, road fatalities have declined significantly. However, the extent of awareness about this success and of fatalities overall is unclear. A survey of 833 Australian drivers revealed the majority of participants under-estimated fatalities. Unexpectedly, some under-estimates appear based on recollections of media reports. The findings suggest lack of awareness of the extent of road deaths and that, paradoxically, media reports might contribute to underestimations. This represents a major public health challenge. Engaging community support for road safety, relative to other health/safety messages, may prove difficult if the extent of road trauma is misunderstood. Misperceptions about fatality levels may be a barrier to road users adopting safety precautions or supporting further road safety countermeasures.

The impact of temperature on years of life lost in Brisbane, Australia

Temperature is an important determinant of health. A better knowledge of how temperature affects population health is important not only to the scientific community, but also to the decision-makers who develop and implement early warning systems and intervention strategies to mitigate the health effects of extreme temperatures. The temperature–health relationship is also of growing interest as climate change is projected to shift the overall temperature distribution higher. Previous studies have examined the relative risks of temperature-related mortality, but the absolute measure of years of life lost is also useful as it combines the number of deaths with life expectancy. Here we use years of life lost to provide a novel measure of the impact of temperature on mortality in Brisbane, Australia. We also project the future temperature-related years of life lost attributable to climate change. We show that the association between temperature and years of life lost is U-shaped, with increased years of life lost for cold and hot temperatures. The temperature-related years of life lost will worsen greatly if future climate change goes beyond a 2 �C increase and without any adaptation to higher temperatures. This study highlights that public health adaptation to climate change is necessary.

The roles of the preproghrelin-derived peptides - ghrelin, desacyl ghrelin and obestatin - in prostate cancer

Prostate cancer is the second most common cause of cancer related deaths in Western men. Despite the significant improvements in current treatment techniques, there is no cure for advanced metastatic, castrate-resistant disease. Early detection and prevention of progression to a castrate-resistant state may provide new strategies to improve survival. A number of growth factors have been shown to act in an autocrine/paracrine manner to modulate prostate cancer tumour growth. Our laboratory has previously shown that ghrelin and its receptors (the functional GHS-R1a and the non-functional GHS-R1b) are expressed in prostate cancer specimens and cell lines. We have shown that ghrelin increases cell proliferation in the PC3 and LNCaP prostate cancer cell lines through activation of ERK1/2, suggesting that ghrelin could regulate prostate cancer cell growth and play a role in the progression of the disease. Ghrelin is a 28 amino-acid peptide hormone, identified to be the natural ligand of the growth hormone secretagogue receptor (GHS-R1a). It is well characterised as a growth hormone releasing and as an orexigenic peptide that stimulates appetite and feeding and regulates energy expenditure and bodyweight. In addition to its orexigenic properties, ghrelin has been shown to play a regulatory role in a number of systems, including the reproductive, immune and cardiovascular systems and may play a role in a number of pathological conditions such as chronic heart failure, anorexia, cachexia, obesity, diabetes and cancer. In cancer, ghrelin and its receptor are expressed in a range of tumours and cancer cell lines and ghrelin has been demonstrated to modulate cell proliferation, apoptosis, migration and invasion in some cell types. The ghrelin gene (GHRL) encodes preproghrelin peptide, which is processed to produce three currently known functional peptides - ghrelin, desacyl ghrelin and obestatin. Prohormone convertases (PCs) have been shown to cleave the preproghrelin peptide into two primary products - the 28 amino acid peptide, ghrelin, and the remaining 117 amino acid C-terminal peptide, C-ghrelin. C-ghrelin can then be further processed to produce the 23 amino acid peptide, obestatin. Ghrelin circulates in two different forms - an octanoylated form (known as ghrelin) and a non-octanoylated form, desacyl ghrelin. The unique post-translational addition of octanoic acid to the serine 3 residue of the propeptide chain to form acylated ghrelin is catalysed by ghrelin O-acyltransferase (GOAT). This modification is necessary for binding of ghrelin to its only known functional receptor, the GHS-R1a. As desacyl ghrelin cannot bind and activate the GHS-R1a, it was initially thought to be an inactive peptide, despite the fact that it circulates at much higher levels than ghrelin. Further research has demonstrated that desacyl ghrelin is biologically active and shares some of the actions of ghrelin, as well as having some opposing and distinct roles. Interestingly, both ghrelin and desacyl ghrelin have been shown to modulate apoptosis, cell differentiation and proliferation in some cell types, and to stimulate cell proliferation through activation of ERK1/2 and PI3K/Akt pathways. The third known peptide product of the ghrelin preprohormone, obestatin, was initially thought to oppose the actions of ghrelin in appetite regulation and food intake and to mediate its effects through the G protein-coupled receptor 39 (GPR39). Subsequent research failed to reproduce the initial findings, however, and the possible anorexigenic effects of obestatin, as well as the identity of its receptor, remain unclear. Obestatin plays some important physiological roles, including roles in improving memory, the inhibition of thirst and anxiety, increased secretion of pancreatic juice, and regulation of cell proliferation, survival, apoptosis and differentiation. Preliminary studies have also shown that obestatin stimulates cell proliferation in some cell types through activation of ERK1/2, Akt and PKC pathways. Overall, however, at the commencement of this PhD project, relatively little was known regarding the functions and mechanisms of action of the preproghrelin-derived functional peptides in modulating prostate cancer cell proliferation. The roles of obestatin, and desacyl ghrelin as potential growth factors had not previously been investigated, and the potential expression and regulation of the preproghrelin processing enzymes, GOAT and prohormone convertases was unknown in prostate cancer cell lines. Therefore, the overall objectives of this study were to: 1. investigate the effects of obestatin on cell proliferation and signaling in prostate cancer cell lines 2. compare the effects of desacyl ghrelin and ghrelin on cell proliferation and signaling in prostate cancer cell lines 3. investigate whether prostate cancer cell lines possess the necessary enzymatic machinery to produce ghrelin and desacyl ghrelin and if these peptides can regulate GOAT expression Our laboratory has previously shown that ghrelin stimulates cell proliferation in the PC3 and LNCaP prostate cancer cell line through activation of the ERK1/2 pathway. In this study it has been demonstrated that treatments with either ghrelin, desacyl ghrelin or obestatin over 72 hours significantly increased cell proliferation in the PC3 prostate cancer cell line but had no significant effect in the RWPE-1 transformed normal prostate cell line. Ghrelin (1000nM) stimulated cell proliferation in the PC3 prostate cancer cell line by 31.66 6.68% (p<0.01) with the WST-1 method, and 13.55 5.68% (p<0.05) with the CyQUANT assay. Desacyl ghrelin (1000nM) increased cell proliferation in PC3 cells by 21.73 2.62% (p<0.01) (WST-1), and 15.46 7.05% (p<0.05) (CyQUANT) above untreated control. Obestatin (1000nM) induced a 28.37 7.47% (p<0.01) (WST-1) and 12.14 7.47% (p<0.05) (CyQUANT) significant increase in cell proliferation in the PC3 prostate cancer cell line. Ghrelin and desacyl ghrelin treatments stimulated Akt and ERK phosphorylation across a range of concentrations (p<0.01). Obestatin treatment significantly stimulated Akt, ERK and PKC phosphorylation (p<0.05). Through the use of specific inhibitors, the MAPK inhibitor U0126 and the Akt1/2 kinase inhibitor, it was demonstrated that ghrelin- and obestatin-induced cell proliferation in the PC3 prostate cancer cell line is mediated through activation of ERK1/2 and Akt pathways. Although desacyl ghrelin significantly stimulated Akt and ERK phosphorylation, U0126 failed to prevent desacyl ghrelin-induced cell proliferation suggesting ghrelin and desacyl ghrelin might act through different mechanisms to increase cell proliferation. Ghrelin and desacyl ghrelin have shown a proliferative effect in osteoblasts, pancreatic -cells and cardiomyocytes through activation of ERK1/2 and PI3K/Akt pathways. Here it has been shown that ghrelin and its non-acylated form exert the same function and stimulate cell proliferation in the PC3 prostate cancer cell line through activation of the Akt pathway. Ghrelin-induced proliferation was also mediated through activation of the ERK1/2 pathway, however, desacyl ghrelin seems to stimulate cell proliferation in an ERK1/2-independent manner. As desacyl ghrelin does not bind and activate GHSR1a, the only known functional ghrelin receptor, the finding that both ghrelin and desacyl ghrelin stimulate cell proliferation in the PC3 cell line suggests that these peptides could be acting through the yet unidentified alternative ghrelin receptor in this cell type. Obestatin treatment also stimulated PKC phosphorylation, however, a direct role for this pathway in stimulating cell proliferation could not be proven using available PKC pathway inhibitors, as they caused significant cell death over the extended timeframe of the cell proliferation assays. Obestatin has been shown to stimulate cell proliferation through activation of PKC isoforms in human retinal epithelial cells and in the human gastric cancer cell line KATO-III. We have demonstrated that all of the prostate-derived cell lines examined (PC3, LNCaP, DU145, 22Rv1, RWPE-1 and RWPE-2) expressed GOAT and at least one of the prohormone convertases, which are known to cleave the proghrelin peptide, PC1/3, PC2 and furin, at the mRNA level. These cells, therefore, are likely to possess the necessary machinery to cleave the preproghrelin protein and to produce the mature ghrelin and desacyl ghrelin peptides. In addition to prohormone convertases, the presence of octanoic acid is essential for acylated ghrelin production. In this study octanoic acid supplementation significantly increased cell proliferation in the PC3 prostate cancer cell line by over 20% compared to untreated controls (p<0.01), but surprisingly, not in the DU145, LNCaP or 22Rv1 prostate cancer cell lines or in the RWPE-1 and RWPE-2 prostate-derived cell lines. In addition, we demonstrated that exogenous ghrelin induced a statistically significant two-fold decrease in GOAT mRNA expression in the PC3 cell line (p<0.05), suggesting that ghrelin could pontentially downregulate its own acylation and, therefore, regulate the balance between ghrelin and desacyl ghrelin. This was not observed, however, in the DU145 and LNCaP prostate cancer cell lines. The GOAT-ghrelin system represents a direct link between ingested nutrients and regulation of ghrelin production and the ghrelin/desacyl ghrelin ratio. Regulation of ghrelin acylation is a potentially attractive and desirable tool for the development of better therapies for a number of pathological conditions where ghrelin has been shown to play a key role. The finding that desacyl ghrelin stimulates cell proliferation in the PC3 prostate cancer cell line, and responds to ghrelin in the same way, suggests that this cell line expresses an alternative ghrelin receptor. Although all the cell lines examined expressed both GHS-R1a and GHS-R1b mRNA, it remains uncertain whether these cell lines express the unidentified alternative ghrelin receptor. It is possible that the varied responses seen could be due to the expression of different ghrelin receptors in different cell lines. In addition to GOAT, prohormone convertases and octanoic acid availability may regulate the production of different peptides from the ghrelin preprohormone. The studies presented in this thesis provide significant new information regarding the roles and mechanisms of action of the preproghrelin-derived peptides, ghrelin, desacyl ghrelin and obestatin, in modulating prostate cancer cell line proliferation. A number of key questions remain to be resolved, however, including the identification of the alternative ghrelin/desacyl ghrelin receptor, the identification of the obestatin receptor, a clarification of the signaling mechanisms which mediate cell proliferation in response to obestatin treatment and a better understanding of the regulation at both the gene and post-translational levels of functional peptide generation. Further studies investigating the role of the ghrelin axis using in vivo prostate cancer models may be warranted. Until these issues are determined, the potential for the ghrelin axis, to be recognised as a novel useful target for therapy for cancer or other pathologies will be uncertain.

Cold and heat waves in the United States

Extreme cold and heat waves, characterised by a number of cold or hot days in succession, place a strain on people’s cardiovascular and respiratory systems. The increase in deaths due to these waves may be greater than that predicted by extreme temperatures alone. We examined cold and heat waves in 99 US cities for 14 years (1987–2000) and investigated how the risk of death depended on the temperature threshold used to define a wave, and a wave’s timing, duration and intensity. We defined cold and heat waves using temperatures above and below cold and heat thresholds for two or more days. We tried five cold thresholds using the first to fifth percentiles of temperature, and five heat thresholds using the ninety-fifth to ninety-ninth percentiles. The extra wave effects were estimated using a two-stage model to ensure that their effects were estimated after removing the general effects of temperature. The increases in deaths associated with cold waves were generally small and not statistically significant, and there was even evidence of a decreased risk during the coldest waves. Heat waves generally increased the risk of death, particularly for the hottest heat threshold. Cold waves of a colder intensity or longer duration were not more dangerous. Cold waves earlier in the cool season were more dangerous, as were heat waves earlier in the warm season. In general there was no increased risk of death during cold waves above the known increased risk associated with cold temperatures. Cold or heat waves earlier in the cool or warm season may be more dangerous because of a build up in the susceptible pool or a lack of preparedness for cold or hot temperatures.

Estimating the effects of environmental exposures using a weighted mean of monitoring stations

The health effects of environmental hazards are often examined using time series of the association between a daily response variable (e.g., death) and a daily level of exposure (e.g., temperature). Exposures are usually the average from a network of stations. This gives each station equal importance, and negates the opportunity for some stations to be better measures of exposure. We used a Bayesian hierarchical model that weighted stations using random variables between zero and one. We compared the weighted estimates to the standard model using data on health outcomes (deaths and hospital admissions) and exposures (air pollution and temperature) in Brisbane, Australia. The improvements in model fit were relatively small, and the estimated health effects of pollution were similar using either the standard or weighted estimates. Spatial weighted exposures would be probably more worthwhile when there is either greater spatial detail in the health outcome, or a greater spatial variation in exposure.

An evolving perspective on physical activity counselling by medical professionals

Background Physical inactivity is a modifiable risk factor for many chronic conditions and a leading cause of premature mortality. An increasing proportion of adults worldwide are not engaging in a level of physical activity sufficient to prevent or alleviate these adverse effects. Medical professionals have been identified as potentially powerful sources of influence for those who do not meet minimum physical activity guidelines. Health professionals are respected and expected sources of advice and they reach a large and relevant proportion of the population. Despite this potential, health professionals are not routinely practicing physical activity promotion. Discussion Medical professionals experience several known barriers to physical activity promotion including lack of time and lack of perceived efficacy in changing physical activity behaviour in patients. Furthermore, evidence for effective physical activity promotion by medical professionals is inconclusive. To address these problems, new approaches to physical activity promotion are being proposed. These include collaborating with community based physical activity behaviour change interventions, preparing patients for effective brief counselling during a consultation with the medical professional, and use of interactive behaviour change technology. Summary It is important that we recognise the latent risk of physical inactivity among patients presenting in clinical settings. Preparation for improving patient physical activity behaviours should commence before the consultation and may include physical activity screening. Medical professionals should also identify suitable community interventions to which they can refer physically inactive patients. Outsourcing the majority of a comprehensive physical activity intervention to community based interventions will reduce the required clinical consultation time for addressing the issue with each patient. Priorities for future research include investigating ways to promote successful referrals and subsequent engagement in comprehensive community support programs to increase physical activity levels of inactive patients. Additionally, future clinical trials of physical activity interventions should be evaluated in the context of a broader framework of outcomes to inform a systematic consideration of broad strengths and weaknesses regarding not only efficacy but cost-effectiveness and likelihood of successful translation of interventions to clinical contexts.

Developing guidelines for intervention to reduce risk of low-speed vehicle run-overs of young children

In Australia, research suggests that up to one quarter of child pedestrian hospitalisations result from driveway run-over incidents (Pinkney et al., 2006). In Queensland, these numbers equate to an average of four child fatalities and 81 children presenting at hospital emergency departments every year (The Commission for Children, Young People and Child Guardian). National comparison shows that these numbers represent a slightly higher per capita rate (23.5% of all deaths). To address this issue, the current research was undertaken with the aim to develop an educative intervention based on data collected from parents and caregivers of young children. Thus, the current project did not seek to use available intervention or educational material, but to develop a new evidence-based intervention specifically targeting driveway run-overs involving young children. To this end, general behavioural and environmental changes that caregivers had undertaken in order to reduce the risk of injury to any child in their care were investigated. Broadly, the first part of this report sought to: • develop a conceptual model of established domestic safety behaviours, and to investigate whether this model could be successfully applied to the driveway setting; • explore and compare sources of knowledge regarding domestic and driveway child safety; and • examine the theoretical implications of current domestic and driveway related behaviour and knowledge among caregivers. The aim of the second part of this research was to develop and test the efficacy of an intervention based on the findings in the first part of the research project. Specifically, it sought to: • develop an educational driveway intervention that is based on current safety behaviours in the domestic setting and informed by existing knowledge of driveway safety and behaviour change theory; and • evaluate its efficacy in a sample of parents and caregivers.

A human-simulated immune evolutionary computation approach

Premature convergence to local optimal solutions is one of the main difficulties when using evolutionary algorithms in real-world optimization problems. To prevent premature convergence and degeneration phenomenon, this paper proposes a new optimization computation approach, human-simulated immune evolutionary algorithm (HSIEA). Considering that the premature convergence problem is due to the lack of diversity in the population, the HSIEA employs the clonal selection principle of artificial immune system theory to preserve the diversity of solutions for the search process. Mathematical descriptions and procedures of the HSIEA are given, and four new evolutionary operators are formulated which are clone, variation, recombination, and selection. Two benchmark optimization functions are investigated to demonstrate the effectiveness of the proposed HSIEA.

Infertility resolved with or without fertility treatment in Australian women aged 31-36 years: A prospective, population-based study [abstract]

Birth outcomes during a three year period were compared for women with a history of infertility who did or did not use fertility treatment with hormones and/or in vitro fertilisation. Participants in the Australian Longitudinal Study on Women’s Health born in 1973-78 were randomly selected from the universal public health insurance database and completed up to five mailed surveys (1996-2009). Participants reported on their infertility and use of treatment at age 28-33 years (survey 4 (S4) in 2006) and 31-36 years (survey 5 (S5) in 2009). The odds of resolved infertility at S5 were estimated using logistic regression with adjustment for age, area of residence, private health insurance and male infertility. Among 7280 women who responded to both S4 and S5, 18.6% (n=1378) reported infertility. More than half (n=804, 56.8%) of these women did not use treatment and 43.9% (n=347) gave birth between S4 and S5. Compared to infertile women who did not use treatment, women who used treatment were more likely at S5 to have recently given birth (odds ratio (OR) = 1.59, 95% CI 1.26-2.00) or be pregnant (OR = 1.77, 1.27-2.46). Further, women who used treatment were more likely to have twins (3.37, 1.18-9.62), premature births (1.52, 0.95-2.43), or low birthweight babies (1.83, 0.70-2.53) compared to women who gave birth without using treatment. Many women aged up to 36 years with a history of infertility can conceive naturally over a three year period without the use of treatment.Women who have never had a prior birth may need to use treatment to resolve their infertility but they are at higher risk of poorer perinatal outcomes, such as premature or low birthweight babies.

Birth outcomes after spontaneous or assisted conception among infertile Australian women aged 28 to 36 years: A prospective, population-based study

Objective To examine the extent to which the odds of birth, pregnancy, or adverse birth outcomes are higher among women aged 28 to 36 years who use fertility treatment compared with untreated women. Design Prospective, population-based. Setting Not applicable. Patient(s) Participants in the ALSWH born in 1973 to 1978 who reported on their infertility and use of in vitro fertilization (IVF) or ovulation induction (OI). Intervention(s) Postal survey questionnaires administered as part of ALSWH. Main Outcome Measure(s) Among women treated with IVF or OI and untreated women, the odds of birth outcomes estimated by use of adjusted logistic regression modeling. Result(s) Among 7,280 women, 18.6% (n = 1,376) reported infertility. Half (53.0%) of the treated women gave birth compared with 43.8% of untreated women. Women with prior parity were less likely to use IVF compared with nulliparous women. Women using IVF or OI, respectively, were more likely to have given birth after treatment or be pregnant compared with untreated women. Women using IVF or OI were as likely to have ectopic pregnancies, stillbirths, or premature or low birthweight babies as untreated women. Conclusion(s) More than 40% of women aged 28–36 years reporting a history of infertility can achieve births without using treatment, indicating they are subfertile rather than infertile.

Suicide rates in Shandong, China, 1991–2010 : rapid decrease in rural rates and steady increase in male–female ratio

Background China has one of the highest suicide rates in the world; however, the recent trends in suicide have not been adequately studied. This study aimed to examine the potential changes in the rates and characteristics in a Chinese population. Methods Data on suicide deaths in 1991–2010 were extracted from the Shandong Disease Surveillance Point (DSP) mortality dataset based on ICD-10 codes. The temporal trend in age-adjusted suicide rates for each subpopulation was tested using log-linear Poisson regression analysis. Results From 1991 to 2010, there was a marked decrease in the overall suicide rate in Shandong, with an average reduction of 8% per year. The decrease trend was stronger in rural than in urban areas and more evident in females than in males. Similar decreases were observed for all age groups. Pesticide ingestion and hanging remained the top two methods for suicide. Limitations There are likely quality concerns in the morality data, such as underreporting and misclassification, as well as low accuracy in determining the underlying causes of deaths. The representativeness of the DSP system may also be problematic due to the rapid changes in economy and demography. Conclusions Completed suicides in Shandong have sharply declined over the past 20 years. Higher rates in females versus males and in rural versus urban areas, which were previously considered to be distinguishing features of suicide in China, are becoming less pronounced.

Malnutrition and falls risk in community-dwelling older adults

Background and Aims: Falls and fall-related injuries result in reduced functioning, loss of independence, premature nursing home admissions and mortality. Malnutrition is associated with falls in the acute setting, but little is known about malnutrition and falls risk in the community. The aim of this study was to assess the association between malnutrition risk, falls risk and falls over a one-year period in community-dwelling older adults. Methods: Two hundred and fifty four subjects >65 years of age were recruited to participate in a study in order to identify risk factors for falls. Malnutrition risk was determined using the Mini Nutritional Assessment–Short Form. Results: 28.6% had experienced a fall and according to the Mini Nutritional Assessment-Short Form 3.9% (n=10) of subjects were at risk of malnutrition. There were no associations between malnutrition risk, the risk of falls, nor actual falls in healthy older adults in the community setting. Conclusions: There was a low prevalence of malnutrition risk in this sample of community-dwelling older adults and no association between nutritional risk and falls. Screening as part of a falls prevention program should focus on the risk of developing malnutrition as this is associated with falls.

Prostate cancer biomarkers and the emerging proteomic techniques used in biomarker research

Prostate cancer (CaP) is the second leading cause of cancer-related deaths in North American males and the most common newly diagnosed cancer in men world wide. Biomarkers are widely used for both early detection and prognostic tests for cancer. The current, commonly used biomarker for CaP is serum prostate specific antigen (PSA). However, the specificity of this biomarker is low as its serum level is not only increased in CaP but also in various other diseases, with age and even body mass index. Human body fluids provide an excellent resource for the discovery of biomarkers, with the advantage over tissue/biopsy samples of their ease of access, due to the less invasive nature of collection. However, their analysis presents challenges in terms of variability and validation. Blood and urine are two human body fluids commonly used for CaP research, but their proteomic analyses are limited both by the large dynamic range of protein abundance making detection of low abundance proteins difficult and in the case of urine, by the high salt concentration. To overcome these challenges, different techniques for removal of high abundance proteins and enrichment of low abundance proteins are used. Their applications and limitations are discussed in this review. A number of innovative proteomic techniques have improved detection of biomarkers. They include two dimensional differential gel electrophoresis (2D-DIGE), quantitative mass spectrometry (MS) and functional proteomic studies, i.e., investigating the association of post translational modifications (PTMs) such as phosphorylation, glycosylation and protein degradation. The recent development of quantitative MS techniques such as stable isotope labeling with amino acids in cell culture (SILAC), isobaric tags for relative and absolute quantitation (iTRAQ) and multiple reaction monitoring (MRM) have allowed proteomic researchers to quantitatively compare data from different samples. 2D-DIGE has greatly improved the statistical power of classical 2D gel analysis by introducing an internal control. This chapter aims to review novel CaP biomarkers as well as to discuss current trends in biomarker research from two angles: the source of biomarkers (particularly human body fluids such as blood and urine), and emerging proteomic approaches for biomarker research.

Macrophage inhibitory cytokine-1 (MIC-1/GDF15) slows cancer development but increases metastases in TRAMP prostate cancer prone mice

Macrophage inhibitory cytokine-1 (MIC-1/GDF15), a divergent member of the TGF-β superfamily, is over-expressed by many common cancers including those of the prostate (PCa) and its expression is linked to cancer outcome. We have evaluated the effect of MIC-1/GDF15 overexpression on PCa development and spread in the TRAMP transgenic model of spontaneous prostate cancer. TRAMP mice were crossed with MIC-1/GDF15 overexpressing mice (MIC-1fms) to produce syngeneic TRAMPfmsmic-1 mice. Survival rate, prostate tumor size, histopathological grades and extent of distant organ metastases were compared. Metastasis of TC1-T5, an androgen independent TRAMP cell line that lacks MIC-1/GDF15 expression, was compared by injecting intravenously into MIC-1fms and syngeneic C57BL/6 mice. Whilst TRAMPfmsmic-1 survived on average 7.4 weeks longer, had significantly smaller genitourinary (GU) tumors and lower PCa histopathological grades than TRAMP mice, more of these mice developed distant organ metastases. Additionally, a higher number of TC1-T5 lung tumor colonies were observed in MIC-1fms mice than syngeneic WT C57BL/6 mice. Our studies strongly suggest that MIC-1/GDF15 has complex actions on tumor behavior: it limits local tumor growth but may with advancing disease, promote metastases. As MIC-1/GDF15 is induced by all cancer treatments and metastasis is the major cause of cancer treatment failure and cancer deaths, these results, if applicable to humans, may have a direct impact on patient care.

Hospital utilisation among people born in refugee-source countries : an analysis of hospital admissions, Victoria, 1998–2004

Objective: To investigate whether hospital utilisation and health outcomes in Victoria differ between people born in refugee-source countries and those born in Australia. Design and setting: Analysis of a statewide hospital discharge dataset for the 6 financial years from 1 July 1998 to 30 June 2004. Hospital admissions of people born in eight countries for which the majority of entrants to Australia arrived as refugees were included in the analysis. Main outcome measures: Age-standardised rates and rate ratios for: total hospital admissions; emergency admissions; surgical admissions; total days in hospital; discharge at own risk; hospital deaths; admissions due to infectious and parasitic diseases; and admissions due to mental and behavioural disorders. Results: In 2003–04, compared with the Australia-born Victorian population, people born in refugee-source countries had lower rates of surgical admission (rate ratio [RR], 0.85; 95% CI, 0.81–0.88), total days in hospital (RR, 0.74; 95% CI, 0.73–0.75), and admission due to mental and behavioural disorders (RR, 0.70; 95% CI, 0.65–0.76). Over the 6-year period, rates of total days in hospital and rates of admission due to mental and behavioural disorders for people born in refugee-source countries increased towards Australian-born averages, while rates of total admissions, emergency admissions, and admissions due to infectious and parasitic diseases increased above the Australian-born averages. Conclusions: Use of hospital services among people born in refugee-source countries is not higher than that of the Australian-born population and shows a trend towards Australian-born averages. Our findings indicate that the Refugee and Humanitarian Program does not currently place a burden on the Australian hospital system.