Molecular characterisation and expression analysis of interferon gamma in response to natural chlamydia infection in the koala, phascolarctos cinereus

Interferon gamma (IFNγ) is a key Th1 cytokine, with a principal role in the immune response against intracellular organisms such as Chlamydia. Along with being responsible for significant morbidity in human populations, Chlamydia is also responsible for wide spread infection and disease in many animal hosts, with reports that many Australian koala subpopulations are endemically infected. An understanding of the role played by IFNγ in koala chlamydial diseases is important for the establishment of better prophylactic and therapeutic approaches against chlamydial infection in this host. A limited number of IFNγ sequences have been published from marsupials and no immune reagents to measure expression have been developed. Through preliminary analysis of the koala transcriptome, we have identified the full coding sequence of the koala IFNγ gene. Transcripts were identified in spleen and lymph node tissue samples. Phylogenetic analysis demonstrated that koala IFNγ is closely related to other marsupial IFNγ sequences and more distantly related to eutherian mammals. To begin to characterise the role of this important cytokine in the koala's response to chlamydial infection, we developed a quantitative real time PCR assay and applied it to a small cohort of koalas with and without active chlamydial disease, revealing significant differences in expression patterns between the groups. Description of the IFNγ sequence from the koala will not only assist in understanding this species' response to its most important pathogen but will also provide further insight into the evolution of the marsupial immune system

The effect of MC1R variants and sunscreen on the response of human melanocytes in vivo to ultraviolet radiation and implications for melanoma.

We conducted a clinical trial to compare the molecular and cellular responses of human melanocytes and keratinocytes in vivo to solar-simulated ultraviolet radiation (SSUVR) in 57 Caucasian participants grouped according to MC1R genotype. We found that, on average, the density of epidermal melanocytes 14 days after exposure to 2 minimal erythemal dose (MED) SSUVR was twofold higher than baseline (unirradiated) skin. However, the change in epidermal melanocyte counts among people carrying germline MC1R variants (97% increase) was significantly less than those with wild-type MC1R (164% increase; P = 0.01). We also found that sunscreen applied to the skin before exposure to 2 MED SSUVR completely blocked the effects of DNA damage, p53 induction, and cellular proliferation in both melanocytes and keratinocytes.

Serum 25-hydroxyvitamin D concentration in relation to melanoma progress

Dr Wyatt’s study investigated the complex relationship between vitamin D and melanoma, specifically if vitamin D status is associated with more aggressive melanomas. Exposure to solar ultraviolet radiation is the principal risk factor for melanoma and also the main source of vitamin D. This research found that insufficient vitamin D at time of melanoma diagnosis is significantly associated with poorer prognosis (as defined by tumour thickness). These results will contribute to a more refined public health message concerning melanoma and vitamin D, particularly in Queensland, which has the highest global incidence of melanoma, but vitamin D deficiency is not uncommon.

Genotypes of the MTHFR C677T and MTRR A66G genes act independently to reduce migraine disability in response to vitamin supplementation

BACKGROUND: Migraine is a chronic disabling neurovascular condition that may in part be caused by endothelial and cerebrovascular disruption induced by hyperhomocysteinaemia. We have previously provided evidence indicating that reduction of homocysteine by vitamin supplementation can reduce the occurrence of migraine in women. The current study examined the genotypic effects of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene variants on the occurrence of migraine in response to vitamin supplementation. METHODS: This was a 6-month randomized, double-blinded placebo-controlled trial of daily vitamin B supplementation (B(6), B(9) and B(12)) on reduction of homocysteine and of the occurrence of migraine in 206 female patients diagnosed with migraine with aura. RESULTS: Vitamin supplementation significantly reduced homocysteine levels (P<0.001), severity of headache in migraine (P=0.017) and high migraine disability (P=0.022) in migraineurs compared with the placebo effect (P>0.1). When the vitamin-treated group was stratified by genotype, the C allele carriers of the MTHFR C677T variant showed a higher reduction in homocysteine levels (P<0.001), severity of pain in migraine (P=0.01) and percentage of high migraine disability (P=0.009) compared with those with the TT genotypes. Similarly, the A allele carriers of the MTRR A66G variants showed a higher level of reduction in homocysteine levels (P<0.001), severity of pain in migraine (P=0.002) and percentage of high migraine disability (P=0.006) compared with those with the GG genotypes. Genotypic analysis for both genes combined indicated that the treatment effect modification of the MTRR variant was independent of the MTHFR variant. CONCLUSION: This provided further evidence that vitamin supplementation is effective in reducing migraine and also that both MTHFR and MTRR gene variants are acting independently to influence treatment response in female migraineurs.

Outdoor worker sun protection project : a comprehensive applied research project to demonstrate the effectiveness of sun protection measures which influence high risk outdoor workers in Queensland to adopt sun safe behaviour practices 2010 – 2013

The QUT Outdoor Worker Sun Protection (OWSP) project undertook a comprehensive applied health promotion project to demonstrate the effectiveness of sun protection measures which influence high risk outdoor workers in Queensland to adopt sun safe behaviours. The three year project (2010-2013) was driven by two key concepts: 1) The hierarchy of control, which is used to address risks in the workplace, advocates for six control measures that need to be considered in order of priority (refer to Section 3.4.2); and 2) the Ottawa Charter which recommends five action means to achieve health promotion (refer to Section 2.1). The project framework was underpinned by a participatory action research approach that valued peoples’ input, took advantage of existing skills and resources, and stimulated innovation (refer to Section 4.2). Fourteen workplaces (small and large) with a majority outdoor workforce were recruited across regional Queensland (Darling Downs, Northwest, Mackay and Cairns) from four industries types: 1) building and construction, 2) rural and farming, 3) local government, and 4) public sector. A workplace champion was identified at each workplace and was supported (through resource provision, regular contact and site visits) over a 14 to 18 month intervention period to make sun safety a priority in their workplace. Employees and employers were independently assessed for pre- and postintervention sun protection behaviours. As part of the intervention, an individualised sun safety action plan was developed in conjunction with each workplace to guide changes across six key strategy areas including: 1) Policy (e.g., adopt sun safety practices during all company events); 2) Structural and environmental (e.g., shade on worksites; eliminate or minimise reflective surfaces); 3) Personal protective equipment (PPE) (e.g., trial different types of sunscreens, or wide-brimmed hats); 4) Education and awareness (e.g., include sun safety in inductions and toolbox talks; send reminder emails or text messages to workers);5) Role modelling (e.g., by managers, supervisors, workplace champions and mentors); and 6) Skin examinations (e.g., allow time off work for skin checks). The participatory action process revealed that there was no “one size fits all” approach to sun safety in the workplace; a comprehensive, tailored approach was fundamental. This included providing workplaces with information, resources, skills, know how, incentives and practical help. For example, workplaces engaged in farming complete differing seasonal tasks across the year and needed to prepare for optimal sun safety of their workers during less labour intensive times. In some construction workplaces, long pants were considered a trip hazard and could not be used as part of a PPE strategy. Culture change was difficult to achieve and workplace champions needed guidance on the steps to facilitate this (e.g., influencing leaders through peer support, mentoring and role modelling). With the assistance of the project team the majority of workplaces were able to successfully implement the sun safety strategies contained within their action plans, up skilling them in the evidence for sun safety, how to overcome barriers, how to negotiate with all relevant parties and assess success. The most important enablers to the implementation of a successful action plan were a pro-active workplace champion, strong employee engagement, supportive management, the use of highly visual educational resources, and external support (provided by the project team through regular contact either directly through phone calls or indirectly through emails and e-newsletters). Identified barriers included a lack of time, the multiple roles of workplace champions, (especially among smaller workplaces), competing issues leading to a lack of priority for sun safety, the culture of outdoor workers, and costs or budgeting constraints. The level of sun safety awareness, knowledge, and sun protective behaviours reported by the workers increased between pre-and post-intervention. Of the nine sun protective behaviours that were assessed, the largest changes reported included a 26% increase in workers who “usually or always” wore a broad-brimmed hat, a 20% increase in the use of natural shade, a 19% increase in workers wearing long-sleeved collared shirts, and a 16% increase in workers wearing long trousers.

Genetic variants of angiotensin converting enzyme and methylenetetrahydrofolate reductase may act in combination to increase migraine susceptibility

Migraine, with and without aura (MA and MO), is a prevalent and complex neurovascular disorder that is likely to be influenced by multiple genes some of which may be capable of causing vascular changes leading to disease onset. This study was conducted to determine whether the ACE I/D gene variant is involved in migraine risk and whether this variant might act in combination with the previously implicated MTHFR C677T genetic variant in 270 migraine cases and 270 matched controls. Statistical analysis of the ACE I/D variant indicated no significant difference in allele or genotype frequencies (P > 0.05). However, grouping of genotypes showed a modest, yet significant, over-representation of the DD/ID genotype in the migraine group (88%) compared to controls (81%) (OR of 1.64, 95% CI: 1.00–2.69, P = 0.048). Multivariate analysis, including genotype data for the MTHFR C677T, provided evidence that the MTHFR (TT) and ACE (ID/DD) genotypes act in combination to increase migraine susceptibility (OR = 2.18, 95% CI: 1.15–4.16, P = 0.018). This effect was greatest for the MA subtype where the genotype combination corresponded to an OR of 2.89 (95% CI:1.47–5.72, P = 0.002). In Caucasians, the ACE D allele confers a weak independent risk to migraine susceptibility and also appears to act in combination with the C677T variant in the MTHFR gene to confer a stronger influence on the disease.

The role of adenosine-related genes variants in susceptibility to essential hypertension

OBJECTIVE: To test markers within adenosine-related genes: A1 and A2a receptors (ADORA1, ADORA2a) and adenosine deaminase (ADA) for potential involvement in essential hypertension (EH). DESIGN: Case-control association study investigating gene variants for the ADORA1, ADORA2a and ADA genes. PARTICIPANTS: The study used a cohort of 249 unrelated hypertensive individuals who were diagnosed with hypertension, and an age, sex and ethnically matched group of 249 normotensive controls. RESULTS: The association analysis indicated that both allele and genotype frequencies did not differ significantly between the case and control groups (P > 0.05) for any of the markers tested. CONCLUSION: The adenosine-related gene variants do not appear to alter susceptibility to the disease in this group of essential hypertensives. However, involvement of these genes and the adenosine system cannot be conclusively excluded from essential hypertension pathogenesis as other gene variants may still be involved.

Why are pedestrian crashes so different in developing countries? A review of relevant factors in relation to their impact in Ethiopia

Much is known about pedestrian behaviour and crash risk in developed countries. In contrast, the literature on pedestrian crash risk in developing countries reveals wide gaps in knowledge and understanding, and a comprehensive assessment is lacking. In particular, pedestrian behaviour in developing countries is fundamentally different in comparison to developed countries, and is influenced by a variety of less well understood contributing factors, leading to difficulty in modelling and predicting pedestrian crash risk and in turn identifying effective safety countermeasures. This paper provides a comprehensive synthesis of the factors known to influence pedestrian crash risk in developing countries, then focuses on Ethiopia as a specific example. The paper identifies where critical gaps in knowledge exist regarding pedestrian crash risk and associated behaviour in developing countries--a set of knowledge gaps which collectively are significant. The paper concludes by articulating a critical research path moving forward, with the aim to achieve an improved understanding of developing country pedestrian crash risk, and an ultimate goal of identifying effective pedestrian safety countermeasures suited to the unique challenges faced by transport system managers in developing countries.

Neuromuscular hamstring function in response to intermittent running and previous injury

This thesis examined the impact of previous hamstring injury and fatigue on the function of the hamstring muscles and their neural control. The work established the role of neuromuscular inhibition after hamstring injury and involved the development of a new field testing device for eccentric hamstring strength, which is now in high demand in elite sport worldwide. David has four peer-reviewed publications from this doctoral work.

Response to chemotherapy is predictive in relation to longer overall survival in an individual patient combined-analysis with pleural mesothelioma

Background: There is currently no early predictive marker of survival for patients receiving chemotherapy for malignant pleural mesothelioma (MPM). Tumour response may be predictive for overall survival (OS), though this has not been explored. We have thus undertaken a combined-analysis of OS, from a 42 day landmark, of 526 patients receiving systemic therapy for MPM. We also validate published progression-free survival rates (PFSRs) and a progression-free survival (PFS) prognostic-index model. Methods: Analyses included nine MPM clinical trials incorporating six European Organisation for Research and Treatment of Cancer (EORTC) studies. Analysis of OS from landmark (from day 42 post-treatment) was considered regarding tumour response. PFSR analysis data included six non-EORTC MPM clinical trials. Prognostic index validation was performed on one non-EORTC data-set, with available survival data. Results: Median OS, from landmark, of patients with partial response (PR) was 12·8 months, stable disease (SD), 9·4 months and progressive disease (PD), 3·4 months. Both PR and SD were associated with longer OS from landmark compared with disease progression (both p < 0·0001). PFSRs for platinum-based combination therapies were consistent with published significant clinical activity ranges. Effective separation between PFS and OS curves provided a validation of the EORTC prognostic model, based on histology, stage and performance status. Conclusion: Response to chemotherapy is associated with significantly longer OS from landmark in patients with MPM. © 2012 Elsevier Ltd. All rights reserved.

SRL 172 (killed Mycobacterium vaccae) in addition to standard chemotherapy improves quality of life without affecting survival, in patients with advanced non-small-cell lung cancer : phase III results

Background: This open-label, randomised phase III study was designed to further investigate the clinical activity and safety of SRL172 (killed Mycobacterium vaccae suspension) with chemotherapy in the treatment of non-small-cell lung cancer (NSCLC). Patients and methods: Patients were randomised to receive platinum-based chemotherapy, consisting of up to six cycles of MVP (mitomycin, vinblastine and cisplatin or carboplatin) with (210 patients) or without (209 patients) monthly SRL172. Results: There was no statistical difference between the two groups in overall survival (primary efficacy end point) over the course of the study (median overall survival of 223 days versus 225 days; P = 0.65). However, a higher proportion of patients were alive at the end of the 15-week treatment phase in the chemotherapy plus SRL172 group (90%), than in the chemotherapy alone group (83%) (P = 0.061). At the end of the treatment phase, the response rate was 37% in the combined group and 33% in the chemotherapy alone group. Patients in the chemotherapy alone group had greater deterioration in their Global Health Status score (-14.3) than patients in the chemotherapy plus SRL172 group (-6.6) (P = 0.02). Conclusion: In this non-placebo controlled trial, SRL172 when added to standard cancer chemotherapy significantly improved patient quality of life without affecting overall survival times. © 2004 European Society for Medical Oncology.

The role of epigenetics in resistance to cisplatin chemotherapy in lung cancer

Non-small cell lung cancer (NSCLC) is the most common cause of cancer related death in the world. Cisplatin and carboplatin are the most commonly used cytotoxic chemotherapeutic agents to treat the disease. These agents, usually combined with drugs such as gemcitabine or pemetrexed, induce objective tumor responses in only 20-30% of patients. Aberrant epigenetic regulation of gene expression is a frequent event in NSCLC. In this article we review the emerging evidence that epigenetics and the cellular machinery involved with this type of regulation may be key elements in the development of cisplatin resistance in NSCLC. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

Food availability, cost disparity and improvement in relation to accessibility and remoteness in Queensland

This study is the first to describe disparity and change in the food supply between metropolitan, rural and remote stores by Accessibility/Remoteness Index of Australia (ARIA)1 category. A total of 92 stores (97% response rate) within five aggregate ARIA categories participated throughout Queensland in 2000. There was a strong association between ARIA category and the cost of the basket of basic foods, with prices being significantly higher (20% and 31% respectively) in the ‘remote’ and ‘very remote’ categories than in the ‘highly accessible’ category. The association with ARIA was less marked for fruit and vegetables than for other food groups, but not for tobacco and take-away food items. Basic food items were less available in the more remote stores. Over the past two years, relative improvements in food prices have been seen in stores in the ‘very remote’ category, with observed increases less than the consumer price index (CPI) for food. Some factors which may have contributed to this improvement are discussed.

A stepped-wedge cluster randomised controlled trial for evaluating rates of falls among inpatients in aged care rehabilitation units receiving tailored multimedia education in addition to usual care : a trial protocol

Introduction Falls are the most frequent adverse event reported in hospitals. Approximately 30% of in-hospital falls lead to an injury and up to 2% result in a fracture. A large randomised trial found that a trained health professional providing individualised falls prevention education to older inpatients reduced falls in a cognitively intact subgroup. This study aims to investigate whether this efficacious intervention can reduce falls and be clinically useful and cost-effective when delivered in the real-life clinical environment. Methods A stepped-wedge cluster randomised trial will be used across eight subacute units (clusters) which will be randomised to one of four dates to start the intervention. Usual care on these units includes patient's screening, assessment and implementation of individualised falls prevention strategies, ongoing staff training and environmental strategies. Patients with better levels of cognition (Mini-Mental State Examination >23/30) will receive the individualised education from a trained health professional in addition to usual care while patient's feedback received during education sessions will be provided to unit staff. Unit staff will receive training to assist in intervention delivery and to enhance uptake of strategies by patients. Falls data will be collected by two methods: case note audit by research assistants and the hospital falls reporting system. Cluster-level data including patient's admissions, length of stay and diagnosis will be collected from hospital systems. Data will be analysed allowing for correlation of outcomes (clustering) within units. An economic analysis will be undertaken which includes an incremental cost-effectiveness analysis. Ethics and dissemination The study was approved by The University of Notre Dame Australia Human Research Ethics Committee and local hospital ethics committees. Results The results will be disseminated through local site networks, and future funding and delivery of falls prevention programmes within WA Health will be informed. Results will also be disseminated through peer-reviewed publications and medical conferences.

Footprints to pathways : reconciliation action planning in industry to sustain Indigenous employment in Queensland

This paper provides an introductory discussion to a study focusing on industry Reconciliation Action Plans (RAP) and sustaining Indigenous employment in Queensland. Indigenous people continue to experience deep and persistent disadvantage in employment, which limits their life prospects (McLachlan, Gilgillan & Gordon, 2013). A major contributing factor to this detriment is irregular employment and or unemployment. A reasonable standard of living has been found to be determined by access to economic resources such as income and wealth. Denial of this access, denies access to income streams, social status, and engagement in meaningful activities. Hence, job loss and joblessness are triggers of disadvantage (McLachlan, et al., 2013). For young Indigenous people, lack of access has lasting effects particularly if they have multiple characteristics that place them at risk of disadvantage. The project aims to develop knowledge and understanding of Industry RAPs mediate employment opportunities for Indigenous people and how young Indigenous people conceive of their employment options and the processes by which employers can best support Indigenous people. It adopts two theoretical frameworks to investigate the aim of the study : (1) Lave and Wenger’s (1991) theory of communities of practice and, (2) Sen’s (1993) capability approach which provides a structure for examining individual well-being in the context of societal inequality. This paper discusses the first research question of the study: What are Industry Reconciliation Action Plans? What is included in RAPs? Why do Industries develop RAPs? How do RAPs attract, recruit, retain, and tenure Indigenous people? The project’s significance rests with its focus on Industry, employers, policies and practices that aid the attraction and retention of Indigenous people in employment.