Vascular endothelial growth factor is an autocrine growth factor, signaling through neuropilin-1 in non-small cell lung cancer

Background The VEGF pathway has become an important therapeutic target in lung cancer, where VEGF has long been established as a potent pro-angiogenic growth factor expressed by many types of tumors. While Bevacizumab (Avastin) has proven successful in increasing the objective tumor response rate and in prolonging progression and overall survival in patients with NSCLC, the survival benefit is however relatively short and the majority of patients eventually relapse. The current use of tyrosine kinase inhibitors alone and in combination with chemotherapy has been underwhelming, highlighting an urgent need for new targeted therapies. In this study, we examined the mechanisms of VEGF-mediated survival in NSCLC cells and the role of the Neuropilin receptors in this process. Methods NSCLC cells were screened for expression of VEGF and its receptors. The effects of recombinant VEGF and its blockade on lung tumor cell proliferation and cell cycle were examined. Phosphorylation of Akt and Erk1/2 proteins was examined by high content analysis and confocal microscopy. The effects of silencing VEGF on cell proliferation and survival signaling were also assessed. A Neuropilin-1 stable-transfected cell line was generated. Cell growth characteristics in addition to pAkt and pErk1/2 signaling were studied in response to VEGF and its blockade. Tumor growth studies were carried out in nude mice following subcutaneous injection of NP1 over-expressing cells. Results Inhibition of the VEGF pathway with anti-VEGF and anti-VEGFR-2 antibodies or siRNA to VEGF, NP1 and NP2 resulted in growth inhibition of NP1 positive tumor cell lines associated with down-regulation of PI3K and MAPK kinase signaling. Stable transfection of NP1 negative cells with NP1 induced proliferation in vitro, which was further enhanced by exogenous VEGF. In vivo, NP1 over-expressing cells significantly increased tumor growth in xenografts compared to controls. Conclusions Our data demonstrate that VEGF is an autocrine growth factor in NSCLC signaling, at least in part, through NP1. Targeting this VEGF receptor may offer potential as a novel therapeutic approach and also support the evaluation of the role of NP1 as a biomarker predicting sensitivity or resistance to VEGF and VEGFR-targeted therapies in the clinical arena.

Recruiting and retaining plasmapheresis donors: A critical belief analysis

This paper identifies critical beliefs underpinning intentions to commence and continue plasmapheresis donation. Whole blood (n = 624) and first-time plasmapheresis (n = 460) donors completed a cross-sectional survey assessing the belief-base of the theory of planned behaviour and rated their plasmapheresis donation intentions. While the idea of red blood cells being returned was a key deterrent for all donors, critical beliefs underlying commencement and continuation in the plasmapheresis donor panel differed and varied as a function of blood donation history. Findings will assist the development of targeted persuasion messages to optimise recruitment and retention of plasmapheresis donors in a non-remunerated context.

The disaster flood experience: Older people’s poetic voices of resilience

This paper explores the experiences of older community-dwelling Australians evacuated from their homes during the 2011 and 2013 Queensland floods, applying the novel creative methodology of poetic inquiry as an analysis and interpretative tool. As well as exploring how older adults managed during a natural disaster, the paper documents the process and potential of poetic inquiry in gerontological research. The first and second poems highlight the different social resources older people have to draw on in their lives, especially during a crisis. Poem 1 (“Nobody came to help me”) illustrates how one older resident felt all alone during the flood, whereas Poem 2 (“They came from everywhere”), Poem 3 ("The Girls") and Poem 5 (“Man in Blue Shirt”) shows how supported – from both family and the wider community - other older residents felt. Poem 4 (“I can’t swim”) highlights one participant’s fear as the water rises. To date, few studies have explicitly explored older adult’s disaster experience, with this paper the first to utilise a poetic lens. We argue that poetic presentation enhances understanding of older residents’ unique experiences during a disaster, and may better engage a wider audience of policy-makers, practitioners, the general community and older people themselves in discussion about, and reflection on, the impact and experience of disasters.

How an urban Aboriginal and Torres Strait Islander primary health care service improved access to mental health care

Aboriginal and Torres Strait Islander people experience higher levels of psychological distress and mental ill health than their non-Indigenous counterparts, but underuse mental health services. Interventions are required to address the structural and functional access barriers that cause this underuse. In 2012, the Southern Queensland Centre of Excellence in Aboriginal and Torres Strait Islander Primary Health Care employed a psychologist and a social worker to integrate mental health care into its primary health care services. This research study examines the impact of this innovation.

Wastewater pollution abatement in China: A comparative study of fifteen industrial sectors from 1998 to 2010

This study analyzes the management of wastewater pollutants in a number of Chinese industrial sectors from 1998 to 2010. We use decomposition analysis to calculate changes in wastewater pollutant emissions that result from cleaner production processes, end-of-pipe treatment, structural changes in industry, and changes in the scale of production. We focus on one indicator of water quality and three pollutants: chemical oxygen demand (COD), petroleum, cyanide, and volatile phenols. We find that until 2002, COD emissions were mainly reduced through end-of-pipe treatments. Cleaner production processes didn’t begin contributing to COD emissions reductions until the introduction of a 2003 law that enforced their implementation. Petroleum emissions were primarily lowered through cleaner production mechanisms, which have the added benefit of reducing the input cost of intermediate petroleum. Diverse and effective pollution abatement strategies for cyanide and volatile phenols are emerging among industries in China. It will be important for the government to consider differences between industries should they choose to regulate the emissions of specific chemical substances.

Anti-tumour effects of antibodies targeting the extracellular cysteine-rich region of the receptor tyrosine kinase EphB4

EphB4 is a membrane-bound receptor tyrosine kinase (RTK) commonly over-produced by many epithelial cancers but with low to no expression in most normal adult tissues. EphB4 over-production promotes ligand-independent signaling pathways that increase cancer cell viability and stimulate migration and invasion. Several studies have shown that normal ligand-dependent signaling is tumour suppressive and therefore novel therapeutics which block the tumour promoting ligand-independent signaling and/or stimulate tumour suppressive ligand-dependent signaling will find application in the treatment of cancer. An EphB4-specific polyclonal antibody, targeting a region of 200 amino acids in the extracellular portion of EphB4, showed potent in vitro anti-cancer effects measured by an increase in apoptosis and a decrease in anchorage independent growth. Peptide exclusion was used to identify the epitope targeted by this antibody within the cysteine-rich region of the EphB4 protein, a sequence defined as a potential ligand interacting interface. Addition of antibody to cancer cells resulted in phosphorylation and subsequent degradation of the EphB4 protein, suggesting a mechanism that is ligand mimetic and tumour suppressive. A monoclonal antibody which specifically targets this identified extracellular epitope of EphB4 significantly reduced breast cancer xenograft growth in vivo confirming that EphB4 is a useful target for ligand-mimicking antibody-based anti-cancer therapies.

The tumour-promoting receptor tyrosine kinase, EphB4, regulates expression of Integrin-β8 in prostate cancer cells

Background The EphB4 receptor tyrosine kinase is overexpressed in many cancers including prostate cancer. The molecular mechanisms by which this ephrin receptor influences cancer progression are complex as there are tumor-promoting ligand-independent mechanisms in place as well as ligand-dependent tumor suppressive pathways. Methods We employed transient knockdown of EPHB4 in prostate cancer cells, coupled with gene microarray analysis, to identify genes that were regulated by EPHB4 and may represent linked tumor-promoting factors. We validated target genes using qRT-PCR and employed functional assays to determine their role in prostate cancer migration and invasion. Results We discovered that over 500 genes were deregulated upon EPHB4 siRNA knockdown, with integrin β8 (ITGB8) being the top hit (29-fold down-regulated compared to negative non-silencing siRNA). Gene ontology analysis found that the process of cell adhesion was highly deregulated and two other integrin genes, ITGA3 and ITGA10, were also differentially expressed. In parallel, we also discovered that over-expression of EPHB4 led to a concomitant increase in ITGB8 expression. In silico analysis of a prostate cancer progression microarray publically available in the Oncomine database showed that both EPHB4 and ITGB8 are highly expressed in prostatic intraepithelial neoplasia, the precursor to prostate cancer. Knockdown of ITGB8 in PC-3 and 22Rv1 prostate cancer cells in vitro resulted in significant reduction of cell migration and invasion. Conclusions These results reveal that EphB4 regulates integrin β8 expression and that integrin β8 plays a hitherto unrecognized role in the motility of prostate cancer cells and thus targeting integrin β8 may be a new treatment strategy for prostate cancer.

Open access spatial data and collaboration

On 19 June 2015, representatives from over 40 Australian research institutions gathered in Canberra to launch their Open Data Collections. The one day event, hosted by the Australian National Data Service (ANDS), showcased to government and a range of national stakeholders the rich variety of data collections that have been generated through the Major Open Data Collections (MODC) project. Colin Eustace attended the showcase for QUT Library and presented a poster that reflected the work that he and Jodie Vaughan generated through the project. QUT’s Blueprint 4, the University’s five-year institutional strategic plan, outlines the key priorities of developing a commitment to working in partnership with industry, as well as combining disciplinary strengths with interdisciplinary application. The Division of Technology, Information and Learning Support (TILS) has undertaken a number of Australian National Data Service (ANDS) funded projects since 2009 with the aim of developing improved research data management services within the University to support these strategic aims. By leveraging existing tools and systems developed during these projects, the Major Open Data Collection (MODC) project delivered support to multi-disciplinary collaborative research activities through partnership building between QUT researchers and Queensland government agencies, in order to add to and promote the discovery and reuse of a collection of spatially referenced datasets. The MODC project built upon existing Research Data Finder infrastructure (which uses VIVO open source software, developed by Cornell University) to develop a separate collection, Spatial Data Finder (https://researchdatafinder.qut.edu.au/spatial) as the interface to display the spatial data collection. During the course of the project, 62 dataset descriptions were added to Spatial Data Finder, 7 added to Research Data Finder and two added to Software Finder, another separate collection. The project team met with 116 individual researchers and attended 13 school and faculty meetings to promote the MODC project and raise awareness of the Library’s services and resources for research data management.

The psychosocial purpose of driving and its relationship with the risky driving behaviour of young novice drivers

Background The overrepresentation of young drivers in road crashes, injuries and fatalities around the world has resulted in a breadth of injury prevention efforts including education, enforcement, engineering, and exposure control. Despite multifaceted intervention, the young driver problem remains a challenge for injury prevention researchers, practitioners and policy-makers. The intractable nature of young driver crash risks suggests that a deeper understanding of their car use – that is, the purpose of their driving – is required to inform the design of more effective young driver countermeasures. Aims This research examined the driving purpose reported by young drivers, including the relationship with self-reported risky driving behaviours including offences. Methods Young drivers with a Learner or Provisional licence participated in three online surveys (N1 = 656, 17–20 years; N2 = 1051, 17–20 years; N3 = 351, 17–21 years) as part of a larger state-wide project in Queensland, Australia. Results A driving purpose scale was developed (the PsychoSocial Purpose Driving Scale, PSPDS), revealing that young drivers drove for psychosocial reasons such as for a sense of freedom and to feel independent. Drivers who reported the greatest psychosocial purpose for driving were more likely to be male and to report more risky driving behaviours such as speeding. Drivers who deliberately avoided on-road police presence and reported a prior driving-related offence had significantly greater PSPDS scores, and higher reporting of psychosocial driving purposes was found over time as drivers transitioned from the supervised Learner licence phase to the independent Provisional (intermediate) licence phase. Discussion and conclusions The psychosocial needs met by driving suggest that effective intervention to prevent young driver injury requires further consideration of their driving purpose. Enforcement, education, and engineering efforts which consider the psychosocial purpose of the driving are likely to be more efficacious than those which presently do not. Road safety countermeasures could reduce the young driver’s exposure to risk through such mechanisms as encouraging the use of public transport.

Reproducible and label-free biosensor for the selective extraction and rapid detection of proteins in biological fluids

Erythropoietin (EPO), a glycoprotein hormone of ∼34 kDa, is an important hematopoietic growth factor, mainly produced in the kidney and controls the number of red blood cells circulating in the blood stream. Sensitive and rapid recombinant human EPO (rHuEPO) detection tools that improve on the current laborious EPO detection techniques are in high demand for both clinical and sports industry. A sensitive aptamer-functionalized biosensor (aptasensor) has been developed by controlled growth of gold nanostructures (AuNS) over a gold substrate (pAu/AuNS). The aptasensor selectively binds to rHuEPO and, therefore, was used to extract and detect the drug from horse plasma by surface enhanced Raman spectroscopy (SERS). Due to the nanogap separation between the nanostructures, the high population and distribution of hot spots on the pAu/AuNS substrate surface, strong signal enhancement was acquired. By using wide area illumination (WAI) setting for the Raman detection, a low RSD of 4.92% over 150 SERS measurements was achieved. The significant reproducibility of the new biosensor addresses the serious problem of SERS signal inconsistency that hampers the use of the technique in the field. The WAI setting is compatible with handheld Raman devices. Therefore, the new aptasensor can be used for the selective extraction of rHuEPO from biological fluids and subsequently screened with handheld Raman spectrometer for SERS based in-field protein detection.

Residents’ experiences of privacy and comfort in multi-storey apartment dwellings in subtropical Brisbane

Dwellings in multi-storey apartment buildings (MSAB) are predicted to increase dramatically as a proportion of housing stock in subtropical cities over coming decades. The problem of designing comfortable and healthy high-density residential environments and minimising energy consumption must be addressed urgently in subtropical cities globally. This paper explores private residents’ experiences of privacy and comfort and their perceptions of how well their apartment dwelling modulated the external environment in subtropical conditions through analysis of 636 survey responses and 24 interviews with residents of MSAB in inner urban neighbourhoods of Brisbane, Australia. The findings show that the availability of natural ventilation and outdoor private living spaces play important roles in resident perceptions of liveability in the subtropics where the climate is conducive to year round “outdoor living”. Residents valued choice with regard to climate control methods in their apartments. They overwhelmingly preferred natural ventilation to manage thermal comfort, and turned to the air-conditioner for limited periods, particularly when external conditions were too noisy. These findings provide a unique evidence base for reducing the environmental impact of MSAB and increasing the acceptability of apartment living, through incorporating residential attributes positioned around climate-responsive architecture.

Extending the validity of the Feeding Practices and Structure Questionnaire

Background Feeding practices are commonly examined as potentially modifiable determinants of children’s eating behaviours and weight status. Although a variety of questionnaires exist to assess different feeding aspects, many lack thorough reliability and validity testing. The Feeding Practices and Structure Questionnaire (FPSQ) is a tool designed to measure early feeding practices related to non-responsive feeding and structure of the meal environment. Face validity, factorial validity, internal reliability and cross-sectional correlations with children’s eating behaviours have been established in mothers with 2-year-old children. The aim of the present study was to further extend the validity of the FPSQ by examining factorial, construct and predictive validity, and stability. Methods Participants were from the NOURISH randomised controlled trial which evaluated an intervention with first-time mothers designed to promote protective feeding practices. Maternal feeding practices (FP) and child eating behaviours were assessed when children were aged 2 years and 3.7 years (n=388). Confirmatory Factor analysis, group differences, predictive relationships, and stability were tested. Results The original 9-factor structure was confirmed when children were aged 3.7±0.3 years. Cronbach’s alpha was above the recommended 0.70 cut-off for all factors except Structured Meal Timing, Over Restriction and Distrust in Appetite which were 0.58, 0.67 and 0.66 respectively. Allocated group differences reflected behaviour consistent with intervention content and all feeding practices were stable across both time points (range of r= 0.45-0.70). There was some evidence for the predictive validity of factors with 2 FP showing expected relationships, 2 FP showing expected and unexpected relationships and 5 FP showing no relationship. Conclusions Reliability and validity was demonstrated for most subscales of the FPSQ. Future validation is warranted with culturally diverse samples and with fathers and other caregivers. The use of additional outcomes to further explore predictive validity is recommended as well as testing construct validity and test-retest reliability of the questionnaire.

Commuting mode choice in transit oriented development: Disentangling the effects of competitive neighbourhoods, travel attitudes, and self-selection

This research identifies the commuting mode choice behaviour of 3537 adults living in different types of transit oriented development (TOD) in Brisbane by disentangling the effects of their “evil twin” transit adjacent developments (TADs), and by also controlling for residential self-selection, travel attitudes and preferences, and socio-demographic effects. A TwoStep cluster analysis was conducted to identify the natural groupings of respondents’ living environment based on six built environment indicators. The analysis resulted in five types of neighbourhoods: urban TODs, activity centre TODs, potential TODs, TADs, and traditional suburbs. HABITAT survey data were used to derive the commute mode choice behaviour of people living in these neighbourhoods. In addition, statements reflecting both respondents’ travel attitudes and living preferences were also collected as part of the survey. Factor analyses were conducted based on these statements and these derived factors were then used to control for residential self-selection. Four binary logistic regression models were estimated, one for each of the travel modes used (e.g. public transport, active transport, less sustainable transport such as the car/taxi, and other), to differentiate between the commuting behaviour of people living in the five types of neighbourhoods. The findings verify that urban TODs enhance the use of public transport and reduce car usage. No significant difference was found in the commuting behaviour between respondents living in traditional suburbs and TADs. The results confirm the hypothesis that TADs are the “evil twin” of TODs. The data indicates that TADs and the mode choices of residents in these neighbourhoods is a missed transport policy opportunity. Further policy efforts are required for a successive transition of TADs into TODs in order to realise the full benefits of these. TOD policy should also be integrated with context specific TOD design principles.

Using decision trees to understand structure in missing data

Objectives Demonstrate the application of decision trees – classification and regression trees (CARTs), and their cousins, boosted regression trees (BRTs) – to understand structure in missing data. Setting Data taken from employees at three different industry sites in Australia. Participants 7915 observations were included. Materials and Methods The approach was evaluated using an occupational health dataset comprising results of questionnaires, medical tests, and environmental monitoring. Statistical methods included standard statistical tests and the ‘rpart’ and ‘gbm’ packages for CART and BRT analyses, respectively, from the statistical software ‘R’. A simulation study was conducted to explore the capability of decision tree models in describing data with missingness artificially introduced. Results CART and BRT models were effective in highlighting a missingness structure in the data, related to the Type of data (medical or environmental), the site in which it was collected, the number of visits and the presence of extreme values. The simulation study revealed that CART models were able to identify variables and values responsible for inducing missingness. There was greater variation in variable importance for unstructured compared to structured missingness. Discussion Both CART and BRT models were effective in describing structural missingness in data. CART models may be preferred over BRT models for exploratory analysis of missing data, and selecting variables important for predicting missingness. BRT models can show how values of other variables influence missingness, which may prove useful for researchers. Conclusion Researchers are encouraged to use CART and BRT models to explore and understand missing data.

A network DEA quantity and quality-orientated production model: An application to Australian university research services

The motivation for this analysis is the recently developed Excellence in Research for Australia (ERA) program developed to assess the quality of research in Australia. The objective is to develop an appropriate empirical model that better represents the underlying production of higher education research. In general, past studies on university research performance have used standard DEA models with some quantifiable research outputs. However, these suffer from the twin maladies of an inappropriate production specification and a lack of consideration of the quality of output. By including the qualitative attributes of peer-reviewed journals, we develop a procedure that captures both quality and quantity, and apply it using a network DEA model. Our main finding is that standard DEA models tend to overstate the research efficiency of most Australian universities.