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.

Diversity, disruption, continuity: Parenting and social and emotional wellbeing amongst Aboriginal peoples and Torres Strait Islanders

This paper reviews the diversity in parenting values and practices amongst Aboriginal peoples and Torres Strait Islanders. Firstly, issues arising from the historical traumatic disruption of families’ attachments are discussed, Then the contribution Indigenous parenting makes to the development of healthy and vulnerable individuals becomes the central focus. Family therapists can draw from a broad understanding of the diversity of parenting values and practices in the context of a strength-based approach.

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.

The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women

Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2). This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively). In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR) = 1.17; 95% confidence interval (CI): 1.03–1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI), suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91–1.06; p = 0.68). FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis.

UK Design as a Global Industry : International Trade and Intellectual Property

The importance of design to the UK economy is widely recognised. It is one of the key pillars of the knowledge economy, it plays an important role in the innovation process, and it is one of a number of specialisms that help to set the UK apart from global competition. But despite this importance, the nature of design-intensive industries – the businesses that practice and sell design – is remarkably hard to pin down. This uncertainty renders it hard to analyse, and makes it difficult to develop clear, consistent policies to support the designers. The Hargreaves Review recommended that more research was needed to develop a clear evidence base for improving the intellectual property system for design. This report forms part of that evidence base. It examines how UK design figures in the global economy, and considers how the intellectual property system can best support its growth.

UK Design as a global industry : international trade and intellectual property Executive Summary

This is an independent report comissioned by the Intellectual Property Office (IPO) and supported by the Design Council.

Improving Indigenous women’s wellness through action research

Today in Australia, 75% of all Indigenous Australians reside in urban and peri-urban areas. In Brisbane, Indigenous Australians now number just over 45,000, and this number is rapidly increasing. Undertaking research with urban based Indigenous Australians is a relatively new phenomenon. Most past research with Indigenous people has been carried out in remote and regional areas. This paper focuses on a Participation Action Research project undertaken with Indigenous women in the highly urbanised area of North Brisbane. The project takes on the challenge of undertaking urban based Indigenous research. It opts not to centre on poor Indigenous women’s health statistics but instead centres on Indigenous women’s wellness and ways to talk about and work towards wellness. Through the cycles of dialogue with Indigenous women these concepts were teased out and manifested in two highly successful Women’s Wellness Summits. This paper will outline aspects of this project.

Pathways for developing a 'smart' workforce : does the achievement of formal workplace qualifications encourage participation in higher education?

The purpose of this paper is to investigate a public workforce education initiative in the context of State and agency policies designed to enhance employee capabilities to adapt to a volatile and changing environment. In particular, we are concerned with public employees’ experience of a higher educational pathway that resulted in their obtaining a Diploma level qualification. In addition to understanding the employees’ experience of this pathway we were interested in whether the experience contributed to their openness to the prospect of university level education. We conducted telephone interviews with a sample of participants from the program. Employees reported very positive experience of the program; in particular employees reported enhanced efficacy beliefs, a strong sense of achievement, and a feeling of recognition. This experience is explained by four main factors; (1) a program design that was well aligned with the employees learning needs, (2) strong support by organisational staff who delivered and assessed participants on capability criteria, (3) strong management support for employees’ participation, (4) an academic ceremony that provided participants with public recognition of their achievement by valued others. Participants’ motivation to participate was primarily intrinsic rather than extrinsic. Participants in the study reported that their experience in this educational pathway gave them the confidence to consider the possibility of university level education. The paper also discusses the practitioner-academic collaboration that led to the development of this paper.

Between a rock and a hard place : what do public sector leaders learn from the past as they lead into the future

The purpose of this paper is to bring leadership context into sharper focus and to suggest there are strong constraints on public leaders’ discretion to lead in ways consistent with NPM or NPL. Much of the existing public leadership research focuses on the individual leader and tends to give little attention to the influence of context. This lack of focus on leader context adversely affects our ability to build public leadership capacity. We draw on prior research to establish that (1) there are strong contextual constraints on public leaders’ capacity to lead in ways consistent with NPL, (2) public leaders are subject to contradictory messages and for the most part these contradictions are unacknowledged and unresolved, the impact of which is confusion and informal power-politics, (3) the task of leader transition from traditional leadership to new public leadership is very much underestimated and requires a new way to think about leadership development. On the basis of this analysis, we argue that public leaders find themselves between a rock and a hard place.

Negative change and job outcomes : the impact of subjective fit in public sector health care organization

There is an ongoing level of organizational-wide change (such as empowerment and downsizing) occurring within the Australian health care sector. However, there is a paucity of empirical evidence on how public and nonprofit sector nurses cope with these organizational-wide change initiatives and their consequences on individual and work outcomes. This will be the primary aim of the current paper. To this end, a path model is developed base on an integration of existing theoretical perspectives on occupational stress, change management, and person-organizational fit. Data were collected from 252 public and not-for-profit sector nurses. The path analysis suggests that public and nonprofit nurses experience positive and negative change initiatives. Negative change initiatives resulted in an increase in the level of administrative-related stressors. Nurses with more congruent values report less experience with administrative stressors. As nurses experienced more administrative stressors, they tend to report more job dissatisfaction. Nurses whose values were more congruent during organizational change reported higher level of psychological wellbeing. Nurses who were had higher level of psychological wellbeing were found to have higher job satisfaction, which subsequently led to a higher level of organizational commitment.

Transforming organizational leadership : a schema change perspective

Successful organizational transformation typically requires transformed leadership; that is, fundamental changes in the implicit leadership schema that underpin observed organizational leadership practice. The purpose of this study is to elaborate leadership schema change theory by investigating a case study in which the CEO of a public infrastructure organization sought to transform traditional organizational leadership to facilitate wider organization transformation. Data were generated through focus groups and semi-structured interviews at four points over a three-year period. Our findings suggest that (a) change leader initiatives do not necessarily activate the cognitive processing required to achieve leadership schema change, (b) collective schema change, defined in terms of the system of beliefs and values underlying the new leading-managing schema did not occur, however, (c) sub-schema change did occur. The research contributes to existing literature on implicit leadership schema change in three main ways. First, we provide a schema change framework to guide current and future research on schema change. Second, we highlight the role that both change leader initiatives and individual and social processing play in schema change. Finally, we stress the role of teleological processes in leadership schema change.