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.

A double-blind randomised controlled trial of a natural oil-based emulsion containing allantoin versus aqueous cream for managing radiation-induced skin reactions in patients with cancer

Background: Radiation-induced skin reaction (RISR) is one of the most common and distressing side effects of radiotherapy in patients with cancer. It is featured with swelling, redness, itching, pain, breaks in skin, discomfort, and a burning sensation. There is a lack of convincing evidence supporting any single practice in the prevention or management of RISR. Methods/Designs: This double-blinded randomised controlled trial aims to investigate the effects of a natural oil-based emulsion containing allantoin (as known as Moogoo Udder Cream®) versus aqueous cream in reducing RISR, improving pain, itching and quality of life in this patient group. One group will receive Moogoo Udder Cream®. Another group will receive aqueous cream. Outcome measures will be collected using patient self-administered questionnaire, interviewer administered questionnaire and clinician assessment at commencement of radiotherapy, weekly during radiotherapy, and four weeks after the completion of radiotherapy. Discussion: Despite advances of radiologic advances and supportive care, RISR are still not well managed. There is a lack of efficacious interventions in managing RISR. While anecdotal evidence suggests that Moogoo Udder Cream® may be effective in managing RISR, research is needed to substantiate this claim. This paper presents the design of a double blind randomised controlled trial that will evaluate the effects of Moogoo Udder Cream® versus aqueous cream for managing in RISR in patients with cancer. Trial registration: ACTRN 12612000568819

Numerical and experimental studies of cold-formed steel floor systems under standard fire conditions

Light gauge cold-formed steel frame (LSF) structures are increasingly used in industrial, commercial and residential buildings because of their non-combustibility, dimensional stability, and ease of installation. A floor-ceiling system is an example of its applications. LSF floor-ceiling systems must be designed to serve as fire compartment boundaries and provide adequate fire resistance. Fire rated floor-ceiling assemblies formed with new materials and construction methodologies have been increasingly used in buildings. However, limited research has been undertaken in the past and hence a thorough understanding of their fire resistance behaviour is not available. Recently a new composite panel in which an external insulation layer is used between two plasterboards has been developed at QUT to provide a higher fire rating to LSF floors under standard fire conditions. But its increased fire rating could not be determined using the currently available design methods. Research on LSF floor systems under fire conditions is relatively recent and the behaviour of floor joists and other components in the systems is not fully understood. The present design methods thus require the use of expensive fire protection materials to protect them from excessive heat increase during a fire. This leads to uneconomical and conservative designs. Fire rating of these floor systems is provided simply by adding more plasterboard sheets to the steel joists and such an approach is totally inefficient. Hence a detailed fire research study was undertaken into the structural and thermal performance of LSF floor systems including those protected by the new composite panel system using full scale fire tests and extensive numerical studies. Experimental study included both the conventional and the new steel floor-ceiling systems under structural and fire loads using a gas furnace designed to deliver heat in accordance with the standard time- temperature curve in AS 1530.4 (SA, 2005). Fire tests included the behavioural and deflection characteristics of LSF floor joists until failure as well as related time-temperature measurements across the section and along the length of all the specimens. Full scale fire tests have shown that the structural and thermal performance of externally insulated LSF floor system was superior than traditional LSF floors with or without cavity insulation. Therefore this research recommends the use of the new composite panel system for cold-formed LSF floor-ceiling systems. The numerical analyses of LSF floor joists were undertaken using the finite element program ABAQUS based on the measured time-temperature profiles obtained from fire tests under both steady state and transient state conditions. Mechanical properties at elevated temperatures were considered based on the equations proposed by Dolamune Kankanamge and Mahendran (2011). Finite element models were calibrated using the full scale test results and used to further provide a detailed understanding of the structural fire behaviour of the LSF floor-ceiling systems. The models also confirmed the superior performance of the new composite panel system. The validated model was then used in a detailed parametric study. Fire tests and the numerical studies showed that plasterboards provided sufficient lateral restraint to LSF floor joists until their failure. Hence only the section moment capacity of LSF floor joists subjected to local buckling effects was considered in this research. To predict the section moment capacity at elevated temperatures, the effective section modulus of joists at ambient temperature is generally considered adequate. However, this research has shown that it leads to considerable over- estimation of the local buckling capacity of joist subject to non-uniform temperature distributions under fire conditions. Therefore new simplified fire design rules were proposed for LSF floor joist to determine the section moment capacity at elevated temperature based on AS/NZS 4600 (SA, 2005), NAS (AISI, 2007) and Eurocode 3 Part 1.3 (ECS, 2006). The accuracy of the proposed fire design rules was verified with finite element analysis results. A spread sheet based design tool was also developed based on these design rules to predict the failure load ratio versus time, moment capacity versus time and temperature for various LSF floor configurations. Idealised time-temperature profiles of LSF floor joists were developed based on fire test measurements. They were used in the detailed parametric study to fully understand the structural and fire behaviour of LSF floor panels. Simple design rules were also proposed to predict both critical average joist temperatures and failure times (fire rating) of LSF floor systems with various floor configurations and structural parameters under any given load ratio. Findings from this research have led to a comprehensive understanding of the structural and fire behaviour of LSF floor systems including those protected by the new composite panel, and simple design methods. These design rules were proposed within the guidelines of the Australian/New Zealand, American and European cold- formed steel structures standard codes of practice. These may also lead to further improvements to fire resistance through suitable modifications to the current composite panel system.

Innovative damage assessment of steel truss bridges using modal strain energy correlation

As a part of vital infrastructure and transportation network, bridge structures must function safely at all times. Bridges are designed to have a long life span. At any point in time, however, some bridges are aged. The ageing of bridge structures, given the rapidly growing demand of heavy and fast inter-city passages and continuous increase of freight transportation, would require diligence on bridge owners to ensure that the infrastructure is healthy at reasonable cost. In recent decades, a new technique, structural health monitoring (SHM), has emerged to meet this challenge. In this new engineering discipline, structural modal identification and damage detection have formed a vital component. Witnessed by an increasing number of publications is that the change in vibration characteristics is widely and deeply investigated to assess structural damage. Although a number of publications have addressed the feasibility of various methods through experimental verifications, few of them have focused on steel truss bridges. Finding a feasible vibration-based damage indicator for steel truss bridges and solving the difficulties in practical modal identification to support damage detection motivated this research project. This research was to derive an innovative method to assess structural damage in steel truss bridges. First, it proposed a new damage indicator that relies on optimising the correlation between theoretical and measured modal strain energy. The optimisation is powered by a newly proposed multilayer genetic algorithm. In addition, a selection criterion for damage-sensitive modes has been studied to achieve more efficient and accurate damage detection results. Second, in order to support the proposed damage indicator, the research studied the applications of two state-of-the-art modal identification techniques by considering some practical difficulties: the limited instrumentation, the influence of environmental noise, the difficulties in finite element model updating, and the data selection problem in the output-only modal identification methods. The numerical (by a planer truss model) and experimental (by a laboratory through truss bridge) verifications have proved the effectiveness and feasibility of the proposed damage detection scheme. The modal strain energy-based indicator was found to be sensitive to the damage in steel truss bridges with incomplete measurement. It has shown the damage indicator's potential in practical applications of steel truss bridges. Lastly, the achievement and limitation of this study, and lessons learnt from the modal analysis have been summarised.

Fire Tests of Cold-formed Steel Wall Systems

Cold-formed steel stud walls are an important component of Light Steel Framing (LSF) building systems used in commercial, industrial and residential buildings. In the conventional LSF stud wall systems, thin-walled steel studs are protected from fire by placing one or two layers of plasterboard on both sides with or without cavity insulation. However, there is very limited data about the structural and thermal performance of these wall systems while past research showed contradicting results about the benefits of cavity insulation. This research proposed a new LSF stud wall system in which a composite panel made of two plasterboards with insulation between them was used to improve the fire rating of walls. Full scale fire tests were conducted using both conventional steel stud walls with and without the use of cavity insulation and the new composite panel system. Eleven full scale load bearing wall specimens were tested to study the thermal and structural performances of the load bearing wall assemblies under standard fire conditions. These tests showed that the use of cavity insulation led to inferior fire performance of walls while also providing good explanations and supporting test data to overcome the incorrect industry assumptions about cavity insulation. Tests demonstrated that the use of external insulation in a composite panel form enhanced the thermal and structural performances of stud walls and increased their fire resistance rating significantly. This paper presents the details of the full scale fire tests of load-bearing wall assemblies lined with plasterboards and different types of insulation under varying load ratios. Test results including the temperature and deflection profiles of walls measured during the fire tests will be presented along with their failure modes and failure times.

Experimental studies of non-load bearing steel wall systems under fire conditions

Fire safety of buildings has been recognised as very important by the building industry and the community at large. Traditionally, increased fire rating is provided by simply adding more plasterboards to light gauge steel frame (LSF) walls, which is inefficient. Many research studies have been undertaken to investigate the thermal behaviour of traditional LSF stud wall systems under standard fire conditions. However, no research has been undertaken on the thermal behaviour of LSF stud walls using the recently proposed composite panel. Extensive fire testing of both non-load bearing and load bearing wall panels was conducted in this research based on the standard time-temperature curve in AS1530.4. Three groups of LSF wall specimens were tested with no insulation, cavity insulation and the new composite panel based on an external insulation layer between plasterboards. This paper presents the details of this experimental study into the thermal performance of non-load bearing walls lined with various configurations of plasterboard and insulation. Extensive descriptive and numerical results of the tested non-load bearing wall panels given in this paper provide a thorough understanding of their thermal behaviour, and valuable time-temperature data that can be used to validate numerical models. Test results showed that the innovative composite stud wall systems outperformed the traditional stud wall systems in terms of their thermal performance, giving a much higher fire rating.

Finite element modelling of load bearing steel stud walls under real building fires

Fire safety has become an important part in structural design due to the ever increasing loss of properties and lives during fires. Conventionally the fire rating of load bearing wall systems made of Light gauge Steel Frames (LSF) is determined using fire tests based on the standard time-temperature curve given in ISO 834 (ISO, 1999). The standard time-temperature curve given in ISO 834 (ISO, 1999) originated from the application of wood burning furnaces in the early 1900s. However, modern commercial and residential buildings make use of thermoplastic materials, which mean considerably high fuel loads. Hence a detailed fire research study into the performance of LSF walls was undertaken using the developed real fire curves based on Eurocode parametric curves (ECS, 2002) and Barnett’s BFD curves (Barnett, 2002) using both full scale fire tests and numerical studies. It included LSF walls without any insulation, and the recently developed externally insulated composite panel system. This paper presents the details of the numerical studies and the results. It also includes brief details of the development of real building fire curves and experimental studies.

Fire tests of load bearing steel stud walls exposed to real building fires

Abstract. Fire resistance has become an important part in structural design due to the ever increasing loss of properties and lives every year. Conventionally the fire rating of load bearing Light gauge Steel Frame (LSF) walls is determined using standard fire tests based on the time-temperature curve given in ISO 834 [1]. Full scale fire testing based on this standard time-temperature curve originated from the application of wood burning furnaces in the early 1900s and it is questionable whether it truly represents the fuel loads in modern buildings. Hence a detailed fire research study into the performance of LSF walls was undertaken using real design fires based on Eurocode parametric curves [2] and Barnett’s ‘BFD’ curves [3]. This paper presents the development of these real fire curves and the results of full scale experimental study into the structural and fire behaviour of load bearing LSF stud wall systems.

Effect of caffeine on adenosine-induced reversible perfusion defects assessed by automated analysis

Objectives This prospective study investigated the effects of caffeine ingestion on the extent of adenosine-induced perfusion abnormalities during myocardial perfusion imaging (MPI). Methods Thirty patients with inducible perfusion abnormalities on standard (caffeine-abstinent) adenosine MPI underwent repeat testing with supplementary coffee intake. Baseline and test MPIs were assessed for stress percent defect, rest percent defect, and percent defect reversibility. Plasma levels of caffeine and metabolites were assessed on both occasions and correlated with MPI findings. Results Despite significant increases in caffeine [mean difference 3,106 μg/L (95% CI 2,460 to 3,752 μg/L; P < .001)] and metabolite concentrations over a wide range, there was no statistically significant change in stress percent defect and percent defect reversibility between the baseline and test scans. The increase in caffeine concentration between the baseline and the test phases did not affect percent defect reversibility (average change −0.003 for every 100 μg/L increase; 95% CI −0.17 to 0.16; P = .97). Conclusion There was no significant relationship between the extent of adenosine-induced coronary flow heterogeneity and the serum concentration of caffeine or its principal metabolites. Hence, the stringent requirements for prolonged abstinence from caffeine before adenosine MPI—based on limited studies—appear ill-founded.

Prognostic significance of IGF and ECM induced signalling proteins in breast cancer patients

Breast cancer is a leading contributor to the burden of disease in Australia. Fortunately, the recent introduction of diverse therapeutic strategies have improved the survival outcome for many women. Despite this, the clinical management of breast cancer remains problematic as not all approaches are sufficiently sophisticated to take into account the heterogeneity of this disease and are unable to predict disease progression, in particular, metastasis. As such, women with good prognostic outcomes are exposed to the side effects of therapies without added benefit. Furthermore, women with aggressive disease for whom these advanced treatments would deliver benefit cannot be distinguished and opportunities for more intensive or novel treatment are lost. This study is designed to identify novel factors associated with disease progression, and the potential to inform disease prognosis. Frequently overlooked, yet common mediators of disease are the interactions that take place between the insulin-like growth factor (IGF) system and the extracellular matrix (ECM). Our laboratory has previously demonstrated that multiprotein insulin-like growth factor-I (IGF-I): insulin-like growth factor binding protein (IGFBP): vitronectin (VN) complexes stimulate migration of breast cancer cells in vitro, via the cooperative involvement of the insulin-like growth factor type I receptor (IGF-IR) and VN-binding integrins. However, the effects of IGF and ECM protein interactions on the dissemination and progression of breast cancer in vivo are unknown. It was hypothesised that interactions between proteins required for IGF induced signalling events and those within the ECM contribute to breast cancer metastasis and are prognostic and predictive indicators of patient outcome. To address this hypothesis, semiquantitative immunohistochemistry (IHC) analyses were performed to compare the extracellular and subcellular distribution of IGF and ECM induced signalling proteins between matched normal, primary cancer, and metastatic cancer among archival formalin-fixed paraffin-embedded (FFPE) breast tissue samples collected from women attending the Princess Alexandra Hospital, Brisbane. Multivariate Cox proportional hazards (PH) regression survival models in conjunction with a modified „purposeful selection of covariates. method were applied to determine the prognostic potential of these proteins. This study provides the first in-depth, compartmentalised analysis of the distribution of IGF and ECM induced signalling proteins. As protein function and protein localisation are closely correlated, these findings provide novel insights into IGF signalling and ECM protein function during breast cancer development and progression. Distinct IGF signalling and ECM protein immunoreactivity was observed in the stroma and/or in subcellular locations in normal breast, primary cancer and metastatic cancer tissues. Analysis of the presence and location of stratifin (SFN) suggested a causal relationship in ECM remodelling events during breast cancer development and progression. The results of this study have also suggested that fibronectin (FN) and ¥â1 integrin are important for the formation of invadopodia and epithelial-to-mesenchymal transition (EMT) events. Our data also highlighted the importance of the temporal and spatial distribution of IGF induced signalling proteins in breast cancer metastasis; in particular, SFN, enhancer-of-split and hairy-related protein 2 (SHARP-2), total-akt/protein kinase B 1 (Total-AKT1), phosphorylated-akt/protein kinase B (P-AKT), extracellular signal-related kinase-1 and extracellular signal-related kinase-2 (ERK1/2) and phosphorylated-extracellular signal-related kinase-1 and extracellular signal-related kinase-2 (P-ERK1/2). Multivariate survival models were created from the immunohistochemical data. These models were found to fit well with these data with very high statistical confidence. Numerous prognostic confounding effects and effect modifications were identified among elements of the ECM and IGF signalling cascade and corroborate the survival models. This finding provides further evidence for the prognostic potential of IGF and ECM induced signalling proteins. In addition, the adjusted measures of associations obtained in this study have strengthened the validity and utility of the resulting models. The findings from this study provide insights into the biological interactions that occur during the development of breast tissue and contribute to disease progression. Importantly, these multivariate survival models could provide important prognostic and predictive indicators that assist the clinical management of breast disease, namely in the early identification of cancers with a propensity to metastasise, and/or recur following adjuvant therapy. The outcomes of this study further inform the development of new therapeutics to aid patient recovery. The findings from this study have widespread clinical application in the diagnosis of disease and prognosis of disease progression, and inform the most appropriate clinical management of individuals with breast cancer.

A new approach for trip generation estimation for use in traffic impact assessments

Findings from an online survey conducted by Queensland University of Technology (QUT) shows that Australia is suffering from a lack of data reflecting trip generation for use in Traffic Impact Assessments (TIAs). Current independent variables for trip generation estimation are not able to create robust outcomes as well. It is also challenging to account for the impact of the new development on public and active transport as well as the effect of trip chaining behaviour in Australian TIA studies. With this background in mind, research is being implemented by QUT to find a new approach developing a combined model of trip generation and mode choice with consideration of trip chaining effects. It is expected that the model will provide transferable outcomes as it is developed based on socio-demographic parameters. Child Care Centres within the Brisbane area have been nominated for model development. At the time, the project is in the data collection phase. Findings from the pilot survey associated with capturing trip chaining and mode choice information reveal that applying questionnaire is able to capture required information in an acceptable level. The result also reveals that several centres within an area should be surveyed in order to provide sufficient data for trip chaining and modal split analysis.

A rhetorical study of in-flight real estate advertisements as a potential site of ethical transformation in Chinese cities

Real estate markets in Chinese cities are in transition. Advertising for new developments in these markets often reflects changing city aspirations and branding rather than environmental and social experience. This paper investigates real estate marketing as a site of potential ethical transformation of values related to new urban development. It uses Kenneth Burke’s rhetorical analysis as an approach to coding real estate representations from in-flight magazine advertisements as a means of capturing environmental and social viewpoints in China during 2008 - 2009. Both Chinese and foreign participants coded representations into four code modalities. These were based on anthropocentric - non-anthropocentric environmental orientations and nationalistic - universal social orientations. The results suggested that new developments in China are more likely to be understood as based on environmental resource use for continued national economic expansion rather than for a more sustainable world. Emerging patterns in coded representations have opened up the possibility of greater social choices that were however difficult to unambiguously decode from Chinese real estate advertising. From this it is concluded that it may take some time before real estate demand shifts in response to representations of Chinese eco-cities being promoted by Chinese policy makers in the 2000s.

The delta opioid receptor antagonist, SoRI-9409, decreases yohimbine stress-induced reinstatement of ethanol-seeking

A major problem in treating alcohol use disorders (AUDs) is the high rate of relapse due to stress and re-exposure to cues or an environment previously associated with alcohol use. Stressors can induce relapse to alcohol-seeking in humans or reinstatement in rodents. Delta opioid peptide receptors (DOP-Rs) play a role in cue-induced reinstatement of ethanol-seeking; however, their role in stress-induced reinstatement of ethanol-seeking is not known. The objective of this study was to determine the role of DOP-Rs in yohimbine-stress-induced reinstatement of ethanol-seeking. Male, Long-Evans rats were trained to self-administer 10% ethanol in daily 30-minute operant self-administration sessions using a FR3 schedule of reinforcement, followed by extinction training. Once extinction criteria were met, we examined the effects of the DOP-R antagonist, SoRI-9409 (0–5 mg/kg, i.p.) on yohimbine (2 mg/kg, i.p.) stress-induced reinstatement. Additionally, DOP-R-stimulated [35S]GTPS binding was measured in brain membranes and plasma levels of corticosterone (CORT) were determined. Pre-treatment with SoRI-9409 decreased yohimbine stress-induced reinstatement of ethanol-seeking but did not affect yohimbine-induced increases in plasma CORT levels. Additionally, yohimbine increased DOP-R-stimulated 35[S]GTPS binding in brain membranes of ethanol-trained rats, an effect that was inhibited by SoRI-9409. This suggests that the DOP-R plays an important role in yohimbine-stress-induced reinstatement of ethanol-seeking behavior, and DOP-R antagonists may be promising candidates for further development as a treatment for AUDs.