Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer

Background: Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and/or a survival factor in the disease. Methods: TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB 2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall survival. Cell proliferation/survival and invasion was examined in NSCLC cells following both selective TXS inhibition and stable TXS over-expression. Results: TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB 2levels were increased in protein (p < 0.05) and plasma (p < 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma (p < 0.001) and female patients (p < 0.05). No significant correlation with patient survival was observed. Selective TXS inhibition significantly reduced tumour cell growth and increased apoptosis, while TXS over-expression stimulated cell proliferation and invasiveness, and was protective against apoptosis. Conclusion: TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC. © 2011 Cathcart et al; licensee BioMed Central Ltd.

Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura

Matrix metalloproteinases (MMPs), in particular the gelatinases (MMP-2 and -9), play a significant role in tumour invasion and angiogenesis. The expression and activities of MMPs have not been characterised in malignant mesothelioma (MM) tumour samples. In a prospective study, gelatinase activity was evaluated in homogenised supernatants of snap frozen MM (n = 35), inflamed pleura (IP, n = 12) and uninflammed pleura (UP, n = 14) tissue specimens by semiquantitative gelatin zymography. Matrix metalloproteinases were correlated with clinicopathological factors and with survival using Kaplan-Meier and Cox proportional hazard models. In MM, pro- and active MMP-2 levels were significantly greater than for MMP-9 (P = 0.006, P<0.001). Active MMP-2 was significantly greater in MM than in UP (P=0.04). MMP-2 activity was equivalent between IP and MM, but both pro- and active MMP-9 activities were greater in IP (P=0.02, P=0.009). While there were trends towards poor survival with increasing total and pro-MMP-2 activity (P=0.08) in univariate analysis, they were both independent poor prognostic factors in multivariate analysis in conjunction with weight loss (pro-MMP-2 P = 0.03, total MMP-2 P = 0.04). Total and pro-MMP-2 also contributed to the Cancer and Leukemia Group B prognostic groups. MMP-9 activities were not prognostic. Matrix metalloproteinases, and in particular MMP-2, the most abundant gelatinase, may play an important role in MM tumour growth and metastasis. Agents that reduce MMP synthesis and/or activity may have a role to play in the management of MM. © 2003 Cancer Research UK.

Using GPS technology to (re)-examine operational definitions of 'neighbourhood' in place-based health research

BACKGROUND Inconsistencies in research findings on the impact of the built environment on walking across the life course may be methodologically driven. Commonly used methods to define 'neighbourhood', from which built environment variables are measured, may not accurately represent the spatial extent to which the behaviour in question occurs. This paper aims to provide new methods for spatially defining 'neighbourhood' based on how people use their surrounding environment. RESULTS Informed by Global Positioning Systems (GPS) tracking data, several alternative neighbourhood delineation techniques were examined (i.e., variable width, convex hull and standard deviation buffers). Compared with traditionally used buffers (i.e., circular and polygon network), differences were found in built environment characteristics within the newly created 'neighbourhoods'. Model fit statistics indicated that exposure measures derived from alternative buffering techniques provided a better fit when examining the relationship between land-use and walking for transport or leisure. CONCLUSIONS This research identifies how changes in the spatial extent from which built environment measures are derived may influence walking behaviour. Buffer size and orientation influences the relationship between built environment measures and walking for leisure in older adults. The use of GPS data proved suitable for re-examining operational definitions of neighbourhood.

People living in hilly residential areas in metropolitan Perth have less diabetes : spurious association or important environmental determinant?

BACKGROUND: Variations in 'slope' (how steep or flat the ground is) may be good for health. As walking up hills is a physiologically vigorous physical activity and can contribute to weight control, greater neighbourhood slopes may provide a protective barrier to weight gain, and help prevent Type 2 diabetes onset. We explored whether living in 'hilly' neighbourhoods was associated with diabetes prevalence among the Australian adult population. METHODS: Participants ([greater than or equal to]25years; n=11,406) who completed the Western Australian Health and Wellbeing Surveillance System Survey (2003-2009) were asked whether or not they had medically-diagnosed diabetes. Geographic Information Systems (GIS) software was used to calculate a neighbourhood mean slope score, and other built environment measures at 1600m around each participant's home. Logistic regression models were used to predict the odds of self-reported diabetes after progressive adjustment for individual measures (i.e., age, sex), socioeconomic status (i.e., education, income), built environment, destinations, nutrition, and amount of walking. RESULTS: After full adjustment, the odds of self-reported diabetes was 0.72 (95% CI 0.55-0.95) and 0.52 (95% CI 0.39-0.69) for adults living in neighbourhoods with moderate and higher levels of slope, respectively, compared with adults living in neighbourhoods with the lowest levels of slope. The odds of having diabetes was 13% lower (odds ratio 0.87; 95% CI 0.80-0.94) for each increase of one percent in mean slope. CONCLUSIONS: Living in a hilly neighbourhood may be protective of diabetes onset or this finding is spurious. Nevertheless, the results are promising and have implications for future research and the practice of flattening land in new housing developments.

Short-term single treatment of chemotherapy results in the enrichment of ovarian cancer stem cell-like cells leading to an increased tumor burden

Over 80% of women diagnosed with advanced-stage ovarian cancer die as a result of disease recurrence due to failure of chemotherapy treatment. In this study, using two distinct ovarian cancer cell lines (epithelial OVCA 433 and mesenchymal HEY) we demonstrate enrichment in a population of cells with high expression of CSC markers at the protein and mRNA levels in response to cisplatin, paclitaxel and the combination of both. We also demonstrate a significant enhancement in the sphere forming abilities of ovarian cancer cells in response to chemotherapy drugs. The results of these in vitro findings are supported by in vivo mouse xenograft models in which intraperitoneal transplantation of cisplatin or paclitaxel-treated residual HEY cells generated significantly higher tumor burden compared to control untreated cells. Both the treated and untreated cells infiltrated the organs of the abdominal cavity. In addition, immunohistochemical studies on mouse tumors injected with cisplatin or paclitaxel treated residual cells displayed higher staining for the proliferative antigen Ki67, oncogeneic CA125, epithelial E-cadherin as well as cancer stem cell markers such as Oct4 and CD117, compared to mice injected with control untreated cells. These results suggest that a short-term single treatment of chemotherapy leaves residual cells that are enriched in CSC-like traits, resulting in an increased metastatic potential. The novel findings in this study are important in understanding the early molecular mechanisms by which chemoresistance and subsequent relapse may be triggered after the first line of chemotherapy treatment.

Temperature variability and childhood pneumonia : an ecological study

Background Few data on the relationship between temperature variability and childhood pneumonia are available. This study attempted to fill this knowledge gap. Methods A quasi-Poisson generalized linear regression model combined with a distributed lag nonlinear model was used to quantify the impacts of diurnal temperature range (DTR) and temperature change between two neighbouring days (TCN) on emergency department visits (EDVs) for childhood pneumonia in Brisbane, from 2001 to 2010, after controlling for possible confounders. Results An adverse impact of TCN on EDVs for childhood pneumonia was observed, and the magnitude of this impact increased from the first five years (2001–2005) to the second five years (2006–2010). Children aged 5–14 years, female children and Indigenous children were particularly vulnerable to TCN impact. However, there was no significant association between DTR and EDVs for childhood pneumonia. Conclusions As climate change progresses, the days with unstable weather pattern are likely to increase. Parents and caregivers of children should be aware of the high risk of pneumonia posed by big TCN and take precautionary measures to protect children, especially those with a history of respiratory diseases, from climate impacts.

Comparing multilevel and Bayesian spatial random effects survival models to assess geographical inequalities in colorectal cancer survival: a case study

Background Multilevel and spatial models are being increasingly used to obtain substantive information on area-level inequalities in cancer survival. Multilevel models assume independent geographical areas, whereas spatial models explicitly incorporate geographical correlation, often via a conditional autoregressive prior. However the relative merits of these methods for large population-based studies have not been explored. Using a case-study approach, we report on the implications of using multilevel and spatial survival models to study geographical inequalities in all-cause survival. Methods Multilevel discrete-time and Bayesian spatial survival models were used to study geographical inequalities in all-cause survival for a population-based colorectal cancer cohort of 22,727 cases aged 20–84 years diagnosed during 1997–2007 from Queensland, Australia. Results Both approaches were viable on this large dataset, and produced similar estimates of the fixed effects. After adding area-level covariates, the between-area variability in survival using multilevel discrete-time models was no longer significant. Spatial inequalities in survival were also markedly reduced after adjusting for aggregated area-level covariates. Only the multilevel approach however, provided an estimation of the contribution of geographical variation to the total variation in survival between individual patients. Conclusions With little difference observed between the two approaches in the estimation of fixed effects, multilevel models should be favored if there is a clear hierarchical data structure and measuring the independent impact of individual- and area-level effects on survival differences is of primary interest. Bayesian spatial analyses may be preferred if spatial correlation between areas is important and if the priority is to assess small-area variations in survival and map spatial patterns. Both approaches can be readily fitted to geographically enabled survival data from international settings

Missing in space: An evaluation of imputation methods for missing data in spatial analysis of risk factors for type II diabetes

Background Spatial analysis is increasingly important for identifying modifiable geographic risk factors for disease. However, spatial health data from surveys are often incomplete, ranging from missing data for only a few variables, to missing data for many variables. For spatial analyses of health outcomes, selection of an appropriate imputation method is critical in order to produce the most accurate inferences. Methods We present a cross-validation approach to select between three imputation methods for health survey data with correlated lifestyle covariates, using as a case study, type II diabetes mellitus (DM II) risk across 71 Queensland Local Government Areas (LGAs). We compare the accuracy of mean imputation to imputation using multivariate normal and conditional autoregressive prior distributions. Results Choice of imputation method depends upon the application and is not necessarily the most complex method. Mean imputation was selected as the most accurate method in this application. Conclusions Selecting an appropriate imputation method for health survey data, after accounting for spatial correlation and correlation between covariates, allows more complete analysis of geographic risk factors for disease with more confidence in the results to inform public policy decision-making.

The effects of ambient temperature on cerebrovascular mortality: An epidemiologic study in four climatic zones in China

Background Little evidence is available about the association between temperature and cerebrovascular mortality in China. This study aims to examine the effects of ambient temperature on cerebrovascular mortality in different climatic zones in China. Method We obtained daily data on weather conditions, air pollution and cerebrovascular deaths from five cities (Beijing, Tianjin, Shanghai, Wuhan, and Guangzhou) in China during 2004-2008. We examined city-specific associations between ambient temperature and the cerebrovascular mortality, while adjusting for season, long-term trends, day of the week, relative humidity and air pollution. We examined cold effects using a 1°C decrease in temperature below a city-specific threshold, and hot effects using a 1°C increase in temperature above a city-specific threshold. We used a meta-analysis to summarize the cold and hot effects across the five cities. Results Beijing and Tianjin (with low mean temperature) had lower thresholds than Shanghai, Wuhan and Guangzhou (with high mean temperature). In Beijing, Tianjin, Wuhan and Guangzhou cold effects were delayed, while in Shanghai there was no or short induction. Hot effects were acute in all five cities. The cold effects lasted longer than hot effects. The hot effects were followed by mortality displacement. The pooled relative risk associated with a 1°C decrease in temperature below thresholds (cold effect) was 1.037 (95% confidence interval (CI): 1.020, 1.053). The pooled relative risk associated with a 1°C increase in temperature above thresholds (hot effect) was 1.014 (95% CI: 0.979, 1.050). Conclusion Cold temperatures are significantly associated with cerebrovascular mortality in China, while hot effect is not significant. People in colder climate cities were sensitive to hot temperatures, while people in warmer climate cities were vulnerable to cold temperature.

New species of Metatrichia Coquillett (Diptera: Scenopinidae) from Australia and Venezuela

Two new species of the cosmopolitan genus Metatrichia Coquillett are described. Metatrichia dhimurru sp. nov. is described from Arnhem Land (Northern Territory), Australia and represents the third species of the genus to be described from the Australasian region. Metatrichia venezuelensis sp. nov. from Venezuela is the third extant species of the genus to be described from the New World.

Proceedings of the tropical fruits in human nutrition and health conference 2008

Horticultural industries are Queensland’s second largest primary producer, with a total gross value of more than $1.9 billion in 2008. Queensland’s diverse geography and climate supports the production of more than 120 horticultural products. With a growing worldwide demand for quality, nutritious food Queensland Primary Industries and Fisheries continues to focus its activities on accelerating growth within the sector. The conference, sponsored by the Organisation for Economic Cooperation and Development (OECD) and DPI&F is the first of its kind to examine the latest knowledge on the health properties of tropical fruits. Organising committee member and DPI&F science leader Dr Roger Stanley said the conference would develop international networks to accelerate research in the area.

Solubilities of solids in supercritical fluids using dimensionally consistent modified solvate complex models

New dimensionally consistent modified solvate complex models are derived to correlate solubilities of solids in supercritical fluids both in the presence and absence of entrainers (cosolvents). These models are compared against the standard solvate complex models [J.Chrastil, J. Phys. Chem. 86 (1982) 3016-3021; J.C. Gonzalez, M.R.Vieytes, A.M. Botana, J.M. Vieites, L.M. Botana, J. Chromatogr. A 910 (2001) 119-125; Y. Adachi, B.C.Y. Lu, Fluid Phase Equilb. 14 (1983) 47-156; J.M. del Valle, J.M. Aguilera, Ind. Eng. Chem. Res. 27 (1988) 1551-1553] by correlating the solubilities of 13 binary and 12 ternary systems. Though the newly derived models are not significantly better than the standard models in predicting the solubilities, they are dimensionally consistent. (C) 2009 Elsevier B.V. All rights reserved.

spin Precession of a Charged Particle in a Magnetic Field Including the Effects of General Relativity

Abstract is not available.

Studies on the ageing behaviour of Polyvinylchloride/ammonium perchlorate composite solid propellant

The effects of ageing on the properties of a complete polyvinyl chloride — dibutyl phthalate — ammonium perchlorate solid propellant have been studied by measurements of burning rates, thermal decomposition rates (by thermogravimetry and DTA) and calorimetric values. Ageing leads to loss of HCl by dehydrochlorination and a corresponding increase in heat of combustion.