New players for advanced prostate cancer and the rationalisation of insulin-sensitising medication

Obesity and type 2 diabetes are recognised risk factors for the development of some cancers and, increasingly, predict more aggressive disease, treatment failure, and cancer-specific mortality. Many factors may contribute to this clinical observation. Hyperinsulinaemia, dyslipidaemia, hypoxia, ER stress, and inflammation associated with expanded adipose tissue are thought to be among the main culprits driving malignant growth and cancer advancement. This observation has led to the proposal of the potential utility of “old players” for the treatment of type 2 diabetes and metabolic syndrome as new cancer adjuvant therapeutics. Androgen-regulated pathways drive proliferation, differentiation, and survival of benign and malignant prostate tissue. Androgen deprivation therapy (ADT) exploits this dependence to systemically treat advanced prostate cancer resulting in anticancer response and improvement of cancer symptoms. However, the initial therapeutic response from ADT eventually progresses to castrate resistant prostate cancer (CRPC) which is currently incurable. ADT rapidly induces hyperinsulinaemia which is associated with more rapid treatment failure. We discuss current observations of cancer in the context of obesity, diabetes, and insulin-lowering medication. We provide an update on current treatments for advanced prostate cancer and discuss whether metabolic dysfunction, developed during ADT, provides a unique therapeutic window for rapid translation of insulin-sensitising medication as combination therapy with antiandrogen targeting agents for the management of advanced prostate cancer.

Action for change? Embedding Aboriginal and Torres Strait Islander perspectives in early childhood education curricula

This thesis focuses on non-Indigenous educators’ work around embedding Indigenous perspectives in early childhood education curricula. In place of reporting examples of ‘good’ educational practice, the study questions how whiteness and racism continue to operate in diversity work that is seen to be productive and inclusive. The thesis argues for a more comprehensive framework for embedding Indigenous perspectives in before-school contexts to support educators’ efforts. New strategies for professional development are also suggested to support changes in disciplinary knowledge and pedagogy.

Children as change agents for sustainability : an action research case study in a kindergarten

At a time when global consumption and production levels are 25 percent higher than the Earth’s sustainable carrying capacity, there are worldwide calls to find ways to sustain the Earth for this and future generations. A central premise of this study is that education systems have an obligation to participate in this move towards sustainability and can respond by embedding education for sustainability into curricula. This study took early childhood education as its focus due to the teacherresearcher’s own concerns about the state of the planet, coupled with early childhood education’s established traditions of nature-based and child-centred pedagogy. The study explored the experiences of a class of kindergarten children as they undertook a Project Approach to learning about environmental sustainability. The Project Approach is an adaptation of Chard’s work which is situated within a constructivist theoretical framework (Chard, 2011). The Project Approach involves in-depth investigations around an identified topic of interest. It has three phases: introductory, synthesising and culminating phase. The study also investigated the learning journey of the classroom teacher/researcher who broadened her long-held co-constructivist teaching approaches to include transformative practices in order to facilitate curriculum which embedded education for sustainability. While coconstructivist approaches focus on the co-construction of knowledge, transformative practices are concerned with creating change. An action research case study was conducted. This involved twenty-two children who attended an Australian kindergarten. Data were collected and analysed over a seven week period. The study found that young children can be change agents for sustainability when a Project Approach is broadened to include transformative practices. The study also found that the child participants were able to think critically about environmental and sustainability issues, were able to create change in their local contexts, and took on the role of educators to influence others’ environmental behaviours. Another finding was that the teacher-researcher’s participation in the study caused a transformation of both her teaching philosophy and the culture at the kindergarten. An important outcome of the study was the development of a new curriculum model that integrates and has applicability for curriculum development and teacher practice.

From evidence to action: a shared leadership approach

This paper proposes an organisational effectiveness model that applies the theoretical frameworks of shared leadership, appreciative inquiry, and knowledge creation. Similar to many libraries worldwide, Auraria Library technical services department struggled to establish efficient and effective workflow for electronic resources management. The library purchased an Electronic Resource Management System, as the literature suggests; however, this technology-enabled system did not resolve workflow issues. The Auraria Library case study demonstrates that a technical services division can successfully reorganize personnel, reassign responsibilities, and measure outcomes within an evidencebased shared leadership culture, which invites and enables participants to identify problems and create solutions amidst a dynamically changing electronic resources environment.

Valuing student and community voices in the university : action research as a framework for community service-learning

The Community Service-learning Lab (the Lab) was initiated as a university-wide service-learning experience at an Australian university. The Lab engages students, academics, and key community organisations in interdisciplinary action research projects to support student learning and to explore complex and ongoing problems nominated by the community partners. The current study uses feedback from the first offering of the Lab and focuses on exploring student experiences of the service learning project using an action research framework. Student reflections on this experience have revealed some positive outcomes of the Lab such as an appreciation for positive and strengths-based change. These outcomes are corroborated by collected reflections from community partners and academics. The students also identified challenges balancing the requirements for assessment and their goals to serve the community partner’s needs. This feedback has provided vital information for the academic team, highlighting the difficulties in balancing the agenda of the academic framework and the desire to give students authentic experiences.

Investigations Into the Significance of Lysine Residues in IGF-I

This PhD thesis presents novel and original research in the field of Insulin-like Growth Factor-I (or IGF-I) biology. IGF-I plays an essential role in promoting normal human growth and development; it also represents both a target and treatment for various diseases. This thesis provides interesting insights into previously uncharacterised mechanisms of action that underlie IGF-I biology. Such findings may lead to improved and novel treatments across a broad range of medical conditions.

Using participatory action research for heart self care amongst indigenous patients

This paper describes the initial phases of the Fluid Watchers Pacific Rim project: a participatory action research project that involves developing and trialling an iPad app to provide monitoring and self-care for Indigenous Australians with heart failure. The development phase involved working with health experts, an IT team and Indigenous heart-failure patients through three cycles of development and critical reflection. This was followed by a small pilot study to examine the app’s effectiveness. In this paper, the researchers explain why IT-supported health education can be successful in decreasing re-hospitalisation and improving self-management skills. They describe the steps they took to ensure community participation and ownership of the project and present the findings of their pilot study. This pilot project suggests that an iPad app may be a practical and successful way to provide health-care support for Indigenous Australian heart-failure patients.

Implementation and removal of an affirmative-action quota : the impact on task assignment and workers’ skill acquisition

Both the United States and Canada have federal legislation that attempts to address employment inequities across specific target groups. The US has a long tradition of affirmative action, dating back to President Kennedy’s 1961 Executive Order; Canada enacted its Employment Equity Act in 1986. Employment Equity/Affirmative Action policy has attracted significant controversy, with high profile court cases and the repeal of state/provincial legislation. Coate and Loury (1993) examine the theoretical impact of introducing affirmative action. Unfortunately the theoretical impact of affirmative action is ambiguous. The current paper employs a laboratory experiment to shed empirical light on this theoretical ambiguity.

Single-nucleotide polymorphism alleles in the insulin receptor gene are associated with typical migraine

We have identified a migraine locus on chromosome 19p13.3/2 using linkage and association analysis. We isolated 48 single-nucleotide polymorphisms within the locus, of which we genotyped 24 in a Caucasian population comprising 827 unrelated cases and 765 controls. Five single-nucleotide polymorphisms within the insulin receptor gene showed significant association with migraine. This association was independently replicated in a case-control population collected separately. We used experiments with insulin receptor RNA and protein to investigate functionality for the migraine-associated single-nucleotide polymorphisms. We suggest possible functions for the insulin receptor in migraine pathogenesis.

Shortfalls in malnutrition coding : a mandate for action

The International Classification of Diseases, Version 10, Australian modification (ICD-10- AM) is commonly used to classify diseases in hospital patients. ICD-10-AM defines malnutrition as “BMI < 18.5 kg/m2 or unintentional weight loss of ≥ 5% with evidence of suboptimal intake resulting in subcutaneous fat loss and/or muscle wasting”. The Australasian Nutrition Care Day Survey (ANCDS) is the most comprehensive survey to evaluate malnutrition prevalence in acute care patients from Australian and New Zealand hospitals1. This study determined if malnourished participants were assigned malnutritionrelated codes as per ICD-10-AM. The ANCDS recruited acute care patients from 56 hospitals. Hospital-based dietitians evaluated participants’ nutritional status using BMI and Subjective Global Assessment (SGA). In keeping with the ICD-10-AM definition, malnutrition was defined as BMI <18.5kg/m2, SGA-B (moderately malnourished) or SGA-C (severely malnourished). After three months, in this prospective cohort study, hospitals’ health information/medical records department provided coding results for malnourished participants. Although malnutrition was prevalent in 32% (n= 993) of the cohort (N= 3122), a significantly small number were coded for malnutrition (n= 162, 16%, p<0.001). In 21 hospitals, none of the malnourished participants were coded. This is the largest study to provide a snapshot of malnutrition-coding in Australian and New Zealand hospitals. Findings highlight gaps in malnutrition documentation and/or subsequent coding, which could potentially result in significant loss of casemix-related revenue for hospitals. Dietitians must lead the way in developing structured processes for malnutrition identification, documentation and coding.

Independent, marked associations of alleles of the insulin receptor and dipeptidyl carboxypeptidase-I genes with essential hypertension

1. There is evidence to suggest that essential hypertension is a polygenic disorder and that it arises from yet-to-be-identified predisposing variants of certain genes that influence blood pressure. The cloning of various hormone, enzyme, adrenoceptor and hormone receptor genes whose products are involved in blood pressure control and the identification of polymorphisms of these has permitted us to test their genetic association with hypertension. 2. Cross-sectional analyses of a number of candidate gene markers were performed in hypertensive and normotensive subjects who were selected on the basis of both parents being either hypertensive or normotensive, respectively, and the difference in total alleles on all chromosomes for each polymorphism between the hypertensive and normotensive groups was test by χ analysis with one degree of freedom. 3. A marked association was observed between hypertension and insertion alleles of polymorphisms of the insulin receptor gene (INSR) (P<0.0040) and the dipeptidyl carboxypeptidase-1 (angiotensin I-converting enzyme; kininase II) gene (DCP1) (P<0.0018). No association with hypertension was evident, however, for polymorphisms of the growth hormone, low-density lipoprotein receptor, renal kallikrein, α2- and β1-adrenoreceptor, atrial natriuretic factor and insulin genes. 4. All but one of the hypertensive subjects had at least one of the hypertension-associated alleles, and although subjects homozygous for both were three times more frequent in the hypertensive group, examination of the nine possible genotypes suggested that the INSR and DCP1 alleles are independent markers for hypertension. 5. The present results suggest that genetic variant(s) in close linkage disequilibrium with polymorphisms at INSR and DCP1 may be involved in part in the aetiology of essential hypertension.

Association of a RFLP for the insulin receptor gene, but not insulin, with essential hypertension

Insulin has cardiovascular actions and patients with essential hypertension display insulin resistance. A cross-sectional study of the R1 RFLP of the insulin receptor gene (INSR) was carried out in 67 hypertensive (HT) and 75 normotensive (NT) subjects whose parents had a similar blood pressure status at age ≥50. The frequency of the minor (+) allele was 0.31 in HTs and 0.44 in NTs, and the difference between observed alleles in all subjects in each group was significant (χ2 = 4.8, P<0.05). Allele frequencies of a BglI RFLP of the insulin gene, however, did not differ between the HT and NT groups. The data thus provide evidence in favour of an association of HT with a polymorphism at the INSR locus (19p 13.3-13.2), so implicating this locus, and possibly a genetic variant of the insulin receptor itself, in HT.