Spatial and temporal clusters of Barmah Forest virus disease in Queensland, Australia

Objective To identify the spatial and temporal clusters of Barmah Forest virus (BFV) disease in Queensland in Australia, using geographical information systems (GIS) and spatial scan statistic (SaTScan). Methods We obtained BFV disease cases, population and statistical local areas boundary data from Queensland Health and Australian Bureau of Statistics respectively during 1992-2008 for Queensland. A retrospective Poisson-based analysis using SaTScan software and method was conducted in order to identify both purely spatial and space-time BFV disease high-rate clusters. A spatial cluster size of a proportion of the population and a 200km circle radius and varying time windows from 1 month to 12 months were chosen (for the space-time analysis). Results The spatial scan statistic detected a most likely significant purely spatial cluster (including 23 SLAs) and a most likely significant space-time cluster (including 24 SLAs) in approximately the same location. Significant secondary clusters were also identified from both the analyses in several locations. Conclusions This study provides evidence of the existence of statistically significant BFV disease clusters in Queensland, Australia. The study also demonstrated the relevance and applicability of SaTScan in analysing on-going surveillance data to identify clusters to facilitate the development of effective BFV disease prevention and control strategies in Queensland, Australia.

Development and feasibility of a smartphone, ECG and GPS based system for remotely monitoring exercise in cardiac rehabilitation

Background Despite its efficacy and cost-effectiveness, exercise-based cardiac rehabilitation is undertaken by less than one-third of clinically eligible cardiac patients in every country for which data is available. Reasons for non-participation include the unavailability of hospital-based rehabilitation programs, or excessive travel time and distance. For this reason, there have been calls for the development of more flexible alternatives. Methodology and Principal Findings We developed a system to enable walking-based cardiac rehabilitation in which the patient's single-lead ECG, heart rate, GPS-based speed and location are transmitted by a programmed smartphone to a secure server for real-time monitoring by a qualified exercise scientist. The feasibility of this approach was evaluated in 134 remotely-monitored exercise assessment and exercise sessions in cardiac patients unable to undertake hospital-based rehabilitation. Completion rates, rates of technical problems, detection of ECG changes, pre- and post-intervention six minute walk test (6 MWT), cardiac depression and Quality of Life (QOL) were key measures. The system was rated as easy and quick to use. It allowed participants to complete six weeks of exercise-based rehabilitation near their homes, worksites, or when travelling. The majority of sessions were completed without any technical problems, although periodic signal loss in areas of poor coverage was an occasional limitation. Several exercise and post-exercise ECG changes were detected. Participants showed improvements comparable to those reported for hospital-based programs, walking significantly further on the post-intervention 6 MWT, 637 m (95% CI: 565–726), than on the pre-test, 524 m (95% CI: 420–655), and reporting significantly reduced levels of cardiac depression and significantly improved physical health-related QOL. Conclusions and Significance The system provided a feasible and very flexible alternative form of supervised cardiac rehabilitation for those unable to access hospital-based programs, with the potential to address a well-recognised deficiency in health care provision in many countries. Future research should assess its longer-term efficacy, cost-effectiveness and safety in larger samples representing the spectrum of cardiac morbidity and severity.

Validation of de-identified record linkage to ascertain hospital admissions in a cohort study

Background Cohort studies can provide valuable evidence of cause and effect relationships but are subject to loss of participants over time, limiting the validity of findings. Computerised record linkage offers a passive and ongoing method of obtaining health outcomes from existing routinely collected data sources. However, the quality of record linkage is reliant upon the availability and accuracy of common identifying variables. We sought to develop and validate a method for linking a cohort study to a state-wide hospital admissions dataset with limited availability of unique identifying variables. Methods A sample of 2000 participants from a cohort study (n = 41 514) was linked to a state-wide hospitalisations dataset in Victoria, Australia using the national health insurance (Medicare) number and demographic data as identifying variables. Availability of the health insurance number was limited in both datasets; therefore linkage was undertaken both with and without use of this number and agreement tested between both algorithms. Sensitivity was calculated for a sub-sample of 101 participants with a hospital admission confirmed by medical record review. Results Of the 2000 study participants, 85% were found to have a record in the hospitalisations dataset when the national health insurance number and sex were used as linkage variables and 92% when demographic details only were used. When agreement between the two methods was tested the disagreement fraction was 9%, mainly due to "false positive" links when demographic details only were used. A final algorithm that used multiple combinations of identifying variables resulted in a match proportion of 87%. Sensitivity of this final linkage was 95%. Conclusions High quality record linkage of cohort data with a hospitalisations dataset that has limited identifiers can be achieved using combinations of a national health insurance number and demographic data as identifying variables.

Zoledronic acid preserves bone structure and increases survival but does not limit tumour incidence in a prostate cancer bone metastasis model

Background The bisphosphonate, zoledronic acid (ZOL), can inhibit osteoclasts leading to decreased osteoclastogenesis and osteoclast activity in bone. Here, we used a mixed osteolytic/osteoblastic murine model of bone-metastatic prostate cancer, RM1(BM), to determine how inhibiting osteolysis with ZOL affects the ability of these cells to establish metastases in bone, the integrity of the tumour-bearing bones and the survival of the tumour-bearing mice. Methods The model involves intracardiac injection for arterial dissemination of the RM1(BM) cells in C57BL/6 mice. ZOL treatment was given via subcutaneous injections on days 0, 4, 8 and 12, at 20 and 100 µg/kg doses. Bone integrity was assessed by micro-computed tomography and histology with comparison to untreated mice. The osteoclast and osteoblast activity was determined by measuring serum tartrate-resistant acid phosphatase 5b (TRAP 5b) and osteocalcin, respectively. Mice were euthanased according to predetermined criteria and survival was assessed using Kaplan Meier plots. Findings Micro-CT and histological analysis showed that treatment of mice with ZOL from the day of intracardiac injection of RM1(BM) cells inhibited tumour-induced bone lysis, maintained bone volume and reduced the calcification of tumour-induced endochondral osteoid material. ZOL treatment also led to a decreased serum osteocalcin and TRAP 5b levels. Additionally, treated mice showed increased survival compared to vehicle treated controls. However, ZOL treatment did not inhibit the cells ability to metastasise to bone as the number of bone-metastases was similar in both treated and untreated mice. Conclusions ZOL treatment provided significant benefits for maintaining the integrity of tumour-bearing bones and increased the survival of tumour bearing mice, though it did not prevent establishment of bone-metastases in this model. From the mechanistic view, these observations confirm that tumour-induced bone lysis is not a requirement for establishment of these bone tumours.

Spatio-temporal patterns of Barmah Forest virus disease in Queensland, Australia

Background Barmah Forest virus (BFV) disease is a common and wide-spread mosquito-borne disease in Australia. This study investigated the spatio-temporal patterns of BFV disease in Queensland, Australia using geographical information system (GIS) tools and geostatistical analysis. Methods/Principal Findings We calculated the incidence rates and standardised incidence rates of BFV disease. Moran's I statistic was used to assess the spatial autocorrelation of BFV incidences. Spatial dynamics of BFV disease was examined using semi-variogram analysis. Interpolation techniques were applied to visualise and display the spatial distribution of BFV disease in statistical local areas (SLAs) throughout Queensland. Mapping of BFV disease by SLAs reveals the presence of substantial spatio-temporal variation over time. Statistically significant differences in BFV incidence rates were identified among age groups (χ2 = 7587, df = 7327,p<0.01). There was a significant positive spatial autocorrelation of BFV incidence for all four periods, with the Moran's I statistic ranging from 0.1506 to 0.2901 (p<0.01). Semi-variogram analysis and smoothed maps created from interpolation techniques indicate that the pattern of spatial autocorrelation was not homogeneous across the state. Conclusions/Significance This is the first study to examine spatial and temporal variation in the incidence rates of BFV disease across Queensland using GIS and geostatistics. The BFV transmission varied with age and gender, which may be due to exposure rates or behavioural risk factors. There are differences in the spatio-temporal patterns of BFV disease which may be related to local socio-ecological and environmental factors. These research findings may have implications in the BFV disease control and prevention programs in Queensland.

Differential expression of chemokine and matrix re-modelling genes is associated with contrasting schistosome-induced hepatopathology in murine models

The pathological outcomes of schistosomiasis are largely dependent on the molecular and cellular mechanisms of the host immune response. In this study, we investigated the contribution of variations in host gene expression to the contrasting hepatic pathology observed between two inbred mouse strains following Schistosoma japonicum infection. Whole genome microarray analysis was employed in conjunction with histological and immunohistochemical analysis to define and compare the hepatic gene expression profiles and cellular composition associated with the hepatopathology observed in S. japonicum-infected BALB/c and CBA mice. We show that the transcriptional profiles differ significantly between the two mouse strains with high statistical confidence. We identified specific genes correlating with the more severe pathology associated with CBA mice, as well as genes which may confer the milder degree of pathology associated with BALB/c mice. In BALB/c mice, neutrophil genes exhibited striking increases in expression, which coincided with the significantly greater accumulation of neutrophils at granulomatous regions seen in histological sections of hepatic tissue. In contrast, up-regulated expression of the eosinophil chemokine CCL24 in CBA mice paralleled the cellular influx of eosinophils to the hepatic granulomas. Additionally, there was greater down-regulation of genes involved in metabolic processes in CBA mice, reflecting the more pronounced hepatic damage in these mice. Profibrotic genes showed similar levels of expression in both mouse strains, as did genes associated with Th1 and Th2 responses. However, imbalances in expression of matrix metalloproteinases (e.g. MMP12, MMP13) and tissue inhibitors of metalloproteinases (TIMP1) may contribute to the contrasting pathology observed in the two strains. Overall, these results provide a more complete picture of the molecular and cellular mechanisms which govern the pathological outcome of hepatic schistosomiasis. This improved understanding of the immunopathogenesis in the murine model schistosomiasis provides the basis for a better appreciation of the complexities associated with chronic human schistosomiasis.

The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women

Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2). This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively). In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR) = 1.17; 95% confidence interval (CI): 1.03–1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI), suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91–1.06; p = 0.68). FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis.

Unique residues involved in activation of the multitasking protease/chaperone HtrA from Chlamydia trachomatis

DegP, a member of the HtrA family of proteins, conducts critical bacterial protein quality control by both chaperone and proteolysis activities. The regulatory mechanisms controlling these two distinct activities, however, are unknown. DegP activation is known to involve a unique mechanism of allosteric binding, conformational changes and oligomer formation. We have uncovered a novel role for the residues at the PDZ1:protease interface in oligomer formation specifically for chaperone substrates of Chlamydia trachomatis HtrA (DegP homolog). We have demonstrated that CtHtrA proteolysis could be activated by allosteric binding and oligomer formation. The PDZ1 activator cleft was required for the activation and oligomer formation. However, unique to CtHtrA was the critical role for residues at the PDZ1:protease interface in oligomer formation when the activator was an in vitro chaperone substrate. Furthermore, a potential in vivo chaperone substrate, the major outer membrane protein (MOMP) from Chlamydia, was able to activate CtHtrA and induce oligomer formation. Therefore, we have revealed novel residues involved in the activation of CtHtrA which are likely to have important in vivo implications for outer membrane protein assembly.

Monte Carlo evaluation of collapsed-cone convolution calculations in head and neck radiotherapy treatment plans

The presence of air and bone interfaces makes the dose distribution for head and neck cancer treatments difficult to accurately predict. This study compared planning system dose calculations using the collapsed-cone convolution algorithm with EGSnrcMonte Carlo simulation results obtained using the Monte Carlo DICOMToolKit software, for one oropharynx, two paranasal sinus and three nodal treatment plans. The difference between median doses obtained from the treatment planning and Monte Carlo calculations was found to be greatest in two bilateral treatments: 4.8%for a retropharyngeal node irradiation and 6.7% for an ethmoid paranasal sinus treatment. These deviations in median dose were smaller for two unilateral treatments: 0.8% for an infraclavicular node irradiation and 2.8% for a cervical node treatment. Examination of isodose distributions indicated that the largest deviations between Monte Carlo simulation and collapsed-cone convolution calculations were seen in the bilateral treatments, where the increase in calculated dose beyond air cavities was most significant.

Critical Factors of Promoting Market Demand of Sustainable Housing in Australia

Strong regulatory pressure on environmental issues and the improved public awareness will continue to influence the market demand for sustainable housing in the coming years. Despite this potential, the voluntary up-take rate of sustainable practices is not as high as expected within the new built housing industry. This is in contrast to the influx of emerging building technologies, new materials and innovative designs as seen in office buildings and exemplar homes built worldwide. One possible reason for this is that key stakeholders such as developers, builders and consumers do not fully understand and appreciate the tangible and mutual benefits of sustainability in their professional and business activities. This situation warrants the study of a multifaceted strategy that integrates the needs of multiple stakeholders. This research investigates multiple factors that affect key stakeholder’s benefits in sustainable housing implementation. Drawing insights from a quantitative study on a questionnaire survey and a qualitative study of in-depth interviews with key stakeholders in the Australian housing industry, 11 critical factors of driving market demand for sustainable housing were unearthed. Their inter-relationships were identified with the aid of Interpretive Structural Modelling. The study concludes with a hierarchical model that amalgamates the strategies for the decision making of key stakeholders.