Insulin increases De Novo Steroidogenesis in prostate cancer cells

Androgen-dependent pathways regulate maintenance and growth of normal and malignant prostate tissues. Androgen deprivation therapy (ADT) exploits this dependence and is used to treat metastatic prostate cancer; however, regression initially seen with ADT gives way to development of incurable castration-resistant prostate cancer (CRPC). Although ADT generates a therapeutic response, it is also associated with a pattern of metabolic alterations consistent with metabolic syndrome including elevated circulating insulin. Because CRPC cells are capable of synthesizing androgens de novo, we hypothesized that insulin may also influence steroidogenesis in CRPC. In this study, we examined this hypothesis by evaluating the effect of insulin on steroid synthesis in prostate cancer cell lines. Treatment with 10 nmol/L insulin increased mRNA and protein expression of steroidogenesis enzymes and upregulated the insulin receptor substrate insulin receptor substrate 2 (IRS-2). Similarly, insulin treatment upregulated intracellular testosterone levels and secreted androgens, with the concentrations of steroids observed similar to the levels reported in prostate cancer patients. With similar potency to dihydrotestosterone, insulin treatment resulted in increased mRNA expression of prostate-specific antigen. CRPC progression also correlated with increased expression of IRS-2 and insulin receptor in vivo. Taken together, our findings support the hypothesis that the elevated insulin levels associated with therapeutic castration may exacerbate progression of prostate cancer to incurable CRPC in part by enhancing steroidogenesis.

Hospital to home outreach for malnourished elders (HHOME) : a feasibility pilot

Objectives: Malnutrition is common in older hospitalised patients, and barriers to adequate intake in hospital limit the effectiveness of hospital-based nutrition interventions. This pilot study was undertaken to determine whether nutrition-focussed care at discharge and in the early post-hospital period is feasible and acceptable to patients and carers, and improves nutritional status. Design: Prospective cohort study Setting: Internal medicine wards of a tertiary teaching hospital in Brisbane, Australia Participants: Patients aged 65 and older admitted for at least 3 days, identified as malnourished or at risk of malnutrition using Mini Nutritional Assessment (MNA). Interventions: An interdisciplinary discharge team (specialist discharge planning nurse and accredited practicing dietitian) provided nutrition-focussed education, advice, service coordination and follow-up (home visits and telephone) for 6 weeks following hospitalisation Measurements: Nutritional intake, weight, functional status and MNA were recorded 6 and 12 weeks after discharge. Service intensity and changes to care were noted, and hospital readmissions recorded. Service feedback from patients and carers was sought using a brief questionnaire. Results: 12 participants were enrolled during the 6 week pilot (mean age 82 years, 50% male). All received 1-2 home visits, and 3-8 telephone calls. Four participants had new community services arranged, 4 were commenced on oral nutritional supplements, and 7 were referred to community dietetics services for follow-up. Two participants had a decline in MNA score of more than 10% at 12 week follow-up, while the remainder improved by at least 10%. Individualised care including community service coordination was valued by participants. Conclusion: The proposed model of care for older adults was feasible, acceptable to patients and carers, and associated with improved nutritional status at 12 weeks for most participants. The pilot data will be useful for design of intervention trials.

Supporting exceptional students to thrive mathematically

Providing an appropriate education for exceptional students in mathematics is mandated in educational policy in Australasia (Australian Curriculum, Assessment and Reporting Agency (ACARA), 2010; Ministry of Education, 2009, 2011) but a challenge for teachers and schools. ‘Exceptional students’ refer to two distinct populations, namely those who are gifted in mathematics and have the capability to perform very highly compared to age peers and those who experience learning difficulties in mathematics and may underperform (Diezmann, Lowrie, Bicknell, Faragher, & Putt, 2004).

Submarine pyroclastic deposits formed at the Soufrière Hills volcano, Montserrat (1995–2003) : what happens when pyroclastic flows enter the ocean?

The Soufrière Hills volcano, Montserrat, West Indies, has undergone a series of dome growth and collapse events since the eruption began in 1995. Over 90% of the pyroclastic material produced has been deposited into the ocean. Sampling of these submarine deposits reveals that the pyroclastic flows mix rapidly and violently with the water as they enter the sea. The coarse components (pebbles to boulders) are deposited proximally from dense basal slurries to form steep-sided, near-linear ridges that intercalate to form a submarine fan. The finer ash-grade components are mixed into the overlying water column to form turbidity currents that flow over distances >30 km from the source. The total volume of pyroclastic material off the east coast of Montserrat exceeds 280 × 106 m3, with 65% deposited in proximal lobes and 35% deposited as distal turbidites.

Assessment of flood-related recharge to alluvial aquifers of an irrigated catchment following extended drought conditions using 3D visualisation and environmental tracers, Lockyer Valley, southeast Queensland, Australia.

The Lockyer Valley in southeast Queensland, Australia, hosts an economically significant alluvial aquifer system which has been impacted by prolonged drought conditions (~1997 to ~ 2009). Throughout this time, the system was under continued groundwater extraction, resulting in severe aquifer depletion. By 2008, much of the aquifer was at <30% of storage but some relief occurred with rains in early 2009. However, between December 2010 and January 2011, most of southeast Queensland experienced unprecedented flooding, which generated significant aquifer recharge. In order to understand the spatial and temporal controls of groundwater recharge in the alluvium, a detailed 3D lithological property model of gravels, sands and clays was developed using GOCAD software. The spatial distribution of recharge throughout the catchment was assessed using hydrograph data from about 400 groundwater observation wells screened at the base of the alluvium. Water levels from these bores were integrated into a catchment-wide 3D geological model using the 3D geological modelling software GOCAD; the model highlights the complexity of recharge mechanisms. To support this analysis, groundwater tracers (e.g. major and minor ions, stable isotopes, 3H and 14C) were used as independent verification. The use of these complementary methods has allowed the identification of zones where alluvial recharge primarily occurs from stream water during episodic flood events. However, the study also demonstrates that in some sections of the alluvium, rainfall recharge and discharge from the underlying basement into the alluvium are the primary recharge mechanisms of the alluvium. This is indicated by the absence of any response to the flood, as well as the observed old radiocarbon ages and distinct basement water chemistry signatures at these locations. Within the 3D geological model, integration of water chemistry and time-series displays of water level surfaces before and after the flood suggests that the spatial variations of the flood response in the alluvium are primarily controlled by the valley morphology and lithological variations within the alluvium. The integration of time-series of groundwater level surfaces in the 3D geological model also enables the quantification of the volumetric change of groundwater stored in the unconfined sections of this alluvial aquifer during drought and following flood events. The 3D representation and analysis of hydraulic and recharge information has considerable advantages over the traditional 2D approach. For example, while many studies focus on singular aspects of catchment dynamics and groundwater-surface water interactions, the 3D approach is capable of integrating multiple types of information (topography, geological, hydraulic, water chemistry and spatial) into a single representation which provides valuable insights into the major factors controlling aquifer processes.

The effect of implementing a modified early warning scoring (MEWS) system on the adequacy of vital sign documentation

Introduction and objectives Early recognition of deteriorating patients results in better patient outcomes. Modified early warning scores (MEWS) attempt to identify deteriorating patients early so timely interventions can occur thus reducing serious adverse events. We compared frequencies of vital sign recording 24 h post-ICU discharge and 24 h preceding unplanned ICU admission before and after a new observation chart using MEWS and an associated educational programme was implemented into an Australian Tertiary referral hospital in Brisbane. Design Prospective before-and-after intervention study, using a convenience sample of ICU patients who have been discharged to the hospital wards, and in patients with an unplanned ICU admission, during November 2009 (before implementation; n = 69) and February 2010 (after implementation; n = 70). Main outcome measures Any change in a full set or individual vital sign frequency before-and-after the new MEWS observation chart and associated education programme was implemented. A full set of vital signs included Blood pressure (BP), heart rate (HR), temperature (T°), oxygen saturation (SaO2) respiratory rate (RR) and urine output (UO). Results After the MEWS observation chart implementation, we identified a statistically significant increase (210%) in overall frequency of full vital sign set documentation during the first 24 h post-ICU discharge (95% CI 148, 288%, p value <0.001). Frequency of all individual vital sign recordings increased after the MEWS observation chart was implemented. In particular, T° recordings increased by 26% (95% CI 8, 46%, p value = 0.003). An increased frequency of full vital sign set recordings for unplanned ICU admissions were found (44%, 95% CI 2, 102%, p value = 0.035). The only statistically significant improvement in individual vital sign recordings was urine output, demonstrating a 27% increase (95% CI 3, 57%, p value = 0.029). Conclusions The implementation of a new MEWS observation chart plus a supporting educational programme was associated with statistically significant increases in frequency of combined and individual vital sign set recordings during the first 24 h post-ICU discharge. There were no significant changes to frequency of individual vital sign recordings in unplanned admissions to ICU after the MEWS observation chart was implemented, except for urine output. Overall increases in the frequency of full vital sign sets were seen.

A token to the future : a digital ‘archive’ of early Australian children’s literature

This essay considers a specific digital ‘archive’ of early Australian children’s literature, known as the Children’s Literature Digital Resources (CLDR), which is located in AustLit: The Australian Literature Resource ( http://www.austlit.edu.au ). We examine what the CLDR collection can tell us about Australia’s history. To narrow the scope, we focus on how Australia was constructing itself as a nation with its own character, or national identity, in texts written for children from the latter part of the nineteenth century up until the end of World War II. Our approach is to consider how early Australian children’s literature included in the CLDR collection rhetorically constructs nation and place, and in so doing constructs an Australian identity for its implied readers.

The interactions between insulin and androgens in progression to castrate resistant prostate cancer

An association between the metabolic syndrome and reduced testosterone levels has been identified, and a specific inverse relationship between insulin and testosterone levels suggests that an important metabolic crosstalk exists between these two hormonal axes; however, the mechanisms by which insulin and androgens may be reciprocally regulated are not well described. Androgen-dependant gene pathways regulate the growth and maintenance of both normal and malignant prostate tissue, and androgen-deprivation therapy (ADT) in patients exploits this dependence when used to treat recurrent and metastatic prostate cancer resulting in tumour regression. A major systemic side effect of ADT includes induction of key features of the metabolic syndrome and the consistent feature of hyperinsulinaemia. Recent studies have specifically identified a correlation between elevated insulin and high-grade PCa and more rapid progression to castrate resistant disease. This paper examines the relationship between insulin and androgens in the context of prostate cancer progression. Prostate cancer patients present a promising cohort for the exploration of insulin stabilising agents as adjunct treatments for hormone deprivation or enhancers of chemosensitivity for treatment of advanced prostate cancer.

Effects of speeding and headway related variable message signs on driver behaviour and attitudes

This research project examined objective measures of driver behaviour and road users' perceptions on the usefulness and effectiveness of three specific VMS (Variable Message Signs) interventions to improve speeding and headway behaviours. The interventions addressed speeding behaviour alone (intervention 1), headway behaviour alone (intervention 2) and a combination of speeding and headway behaviour (intervention 3). Six VMS were installed along a segment of the Bruce Highway, with a series of three signs for each of the northbound and southbound traffic. Speeds and headway distances were measured with loop detectors installed before and after each VMS. Messages addressing speeding and headway were devised for display on the VMS. A driver could receive a message if they were detected as exceeding the posted speed limit (of 90km/hr) or if the distance to the vehicle in front was less than 2.0s. In addition to the on-road objective measurement of speeding and headway behaviours, the research project elicited self-reported responses to the speeding and headway messages from a sample of drivers via a community-based survey. The survey sought to examine the drivers' beliefs about the effectiveness of the signs and messages, and their views about the role, use, and effectiveness of VMS more generally.

Safety impacts of alcohol and other drugs in construction : development of an industry policy and cultural change management program

There is increasing concern about the impact of employees‟ alcohol and other drug (AOD) consumption on workplace safety and performance, particularly within the construction industry. While most Australian jurisdictions have identified this as a critical safety issue, information is limited regarding the prevalence of AODs in the workplace and there is limited evidential guidance regarding how to effectively and efficiently address such an issue. The current research aims to scientifically evaluate the use of AODs within the Australian construction industry in order to reduce the potential resulting safety and performance impacts and engender a cultural change in the workforce - to render it unacceptable to arrive at a construction workplace with impaired judgement from AODs. The study will adopt qualitative and quantitative methods to firstly evaluate the extent of general AOD use in the industry. Secondly, the development of an appropriate industry policy will adopt a non-punitive and rehabilitative approach developed in consultation with employers and employees across the infrastructure and building sectors, with the aim it be adopted nationally for adoption at the construction workplace. Finally, an industry specific cultural change management program and implementation plan will be developed through a nationally collaborative approach. Final results indicate that a proportion of those sampled in the construction sector may be at risk of hazardous alcohol consumption. A total of 286 respondents (58%) scored above the cut-off cumulative score for risky or hazardous alcohol. Other drug use was also identified as a major issue. Results support the need for evidence-based, preventative educational initiatives that are tailored to the industry. This paper will discuss the final survey and interview results.