The expression, regulation and function of kallikrein 4 in prostate cancer

Prostate cancer is a significant health problem faced by aging men. Currently, diagnostic strategies for the detection of prostate cancer are either unreliable, yielding high numbers of false positive results, or too invasive to be used widely as screening tests. Furthermore, the current therapeutic strategies for the treatment of the disease carry considerable side effects. Although organ confined prostate cancer can be curable, most detectable clinical symptoms occur in advanced disease when primary tumour cells have metastasised to distant sites - usually lymph nodes and bone. Many growth factors and steroids assist the continued growth and maintenance of prostatic tumour cells. Of these mitogens, androgens are important in the development of the normal prostate but are also required to sustain the growth of prostate cancer cells in the early stage of the disease. Not only are androgens required in the early stage of disease, but also many other growth factors and hormones interact to cause uncontrolled proliferation of malignant cells. The early, androgen sensitive phase of disease is followed by an androgen insensitive phase, whereby androgens are no longer required to stimulate the growth of the tumour cells. Growth factors such as transforming growth factor  and  (TGF/), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), insulin-like growth factors (IGFs), Vitamin D and thyroid hormone have been suggested to be important at this stage of disease. Interestingly, some of the kallikrein family of genes, including prostate specific antigen (PSA), the current serum diagnostic marker for prostate cancer, are regulated by androgens and many of the aforementioned growth factors. The kallikrein gene family is a group of serine proteases that are involved in a diverse range of physiological processes: regulation of local blood flow, angiogenesis, tissue invasion and mitogenesis. The earliest members of the kallikrein gene family (KLK1-KLK3) have been strongly associated with general disease states, such as hypertension, inflammation, pancreatitis and renal disease, but are also linked to various cancers. Recently, this family was extended to include 15 genes (KLK1-15). Several newer members of the kallikrein family have been implicated in the carcinogenesis and tumour metastasis of hormone-dependent cancers such as prostate, breast, endometrial and ovarian cancer. The aims of this project were to investigate the expression of the newly identified kallikrein, KLK4, in benign and malignant prostate tissues, and prostate cancer cell lines. This thesis has demonstrated the elevated expression of KLK4 mRNA transcripts in malignant prostate tissue compared to benign prostates. Additionally, expression of the full length KLK4 transcript was detected in the androgen dependent prostate cancer cell line, LNCaP. Based on the above finding, the LNCaP cell line was chosen to assess the potential regulation of full length KLK4 by androgen, thyroid hormone and epidermal growth factor. KLK4 mRNA and protein was found to be up-regulated by androgen and a combination of androgen and thyroid hormone. Thyroid hormone alone produced no significant change in KLK4 mRNA or protein over the control. Epidermal growth factor treatment also resulted in elevated expression levels of KLK4 mRNA and protein. To assess the potential functional role(s) of KLK4/hK4 in processes associated with tumour progression, full length KLK4 was transfected into PC-3 cells - a prostate cancer cell line originally derived from a secondary bone lesion. The KLK4/hK4 over-expressing cells were assessed for their proliferation, migration, invasion and attachment properties. The KLK4 over-expressing clones exhibited a marked change in morphology, indicative of a more aggressive phenotype. The KLK4 clones were irregularly shaped with compromised adhesion to the growth surface. In contrast, the control cell lines (parent PC-3 and empty vector clones) retained a rounded morphology with obvious cell to cell adhesion, as well as significant adhesion to their growth surface. The KLK4 clones exhibited significantly greater attachment to Collagen I and IV than native PC-3s and empty vector controls. Over a 12 hour period, in comparison to the control cells, the KLK4 clones displayed an increase in migration towards PC-3 native conditioned media, a 3 fold increase towards conditioned media from an osteoblastic cell line (Saos-2) and no change in migration towards conditioned media from neonatal foreskin fibroblast cells or 20% foetal bovine serum. Furthermore, the increase in migration exhibited by the KLK4 clones was partially blocked by the serine protease inhibitor, aprotinin. The data presented in this thesis suggests that KLK4/hK4 is important in prostate carcinogenesis due to its over-expression in malignant prostate tissues, its regulation by hormones and growth factors associated with prostate disease and the functional consequences of over-expression of KLK4/hK4 in the PC-3 cell line. These results indicate that KLK4/hK4 may play an important role in tumour invasion and bone metastasis via increased attachment to the bone matrix protein, Collagen I, and enhanced migration due to soluble factors produced by osteoblast cells. This suggestion is further supported by the morphological changes displayed by the KLK4 over-expressing cells. Overall, this data suggests that KLK4/hK4 should be further studied to more fully investigate the potential value of KLK4/hK4 as a diagnostic/prognostic biomarker or in therapeutic applications.

Financial planners and philanthropic planning

This article reports findings from a survey of Canadian financial planners. The focus of the study is learning more about the depth and breadth of philanthropic planning that is included in their advising services to their high-net worth clients. The findings indicate that a minority of financial planners (1) regularly broach the topic of philanthropy in their counseling, (2) believe their clients are interested in philanthropy, and (3) feel sufficiently knowledgeable to assist their clients with philanthropic planning. The implications of these findings and recommendations for improvement are discussed.

Their children's first educators : parents' views about child sexual abuse prevention education

In this descriptive focus group study, we investigated parents’ views about child sexual abuse prevention education at home and in schools. Focus groups were conducted with a sample of 30 Australian adults who identified as the parent or caregiver of a child/children aged 0–5 years. The study explored (1) parents’ knowledge about child sexual abuse prevention, (2) the child sexual abuse prevention messages they provided to their children and the topics they discussed, (3) their attitudes towards child sexual abuse prevention education in schools, and (4) their preferences for content. Data analysis provided seven key themes in these four areas: knowledge (the inadequacy of their own prevention education; and how important is stranger danger now?); messages (bodies, touching, and relationships; the role of protective adults; and parent–child communication); attitudes (voice and choice); and preferences (not the nitty gritty, just the basics). The findings may be useful in assisting school authorities and providers of child sexual abuse prevention programs to better understand parents’ contributions to child sexual abuse prevention education, and their perspectives in relation to provision of school-based prevention programs.

Serious fears across cultures about the collapse of the world order

This chapter approaches resilience from an evolutionary psychology (socio-biological) perspective. It argues that the internal constitution and mental toughness of the individual will provide a core protection for life’s inevitable tests in the innumerable micro and macro environments humans find themselves. The many descriptors of the construct of resilience used in various studies are explored. Finally, the difference psychologists can make in the therapy of clients whose resilience is being tested, is examined by means of case examples.

Juggling competing public values : resolving conflicting agendas in social procurement in Queensland

Organisations within the not-for-profit sector provide services to individuals and groups government and for-profit organisations cannot or will not consider. This response by the not-for-profit sector to market failure and government failure is a well understood contribution to society by the nonprofit sector. Over time, this response has resulted in the development of a vibrant and rich agglomeration of services and programs that operate under a myriad of philosophical stances, service orientations, client groupings and operational capacities. In Australia, these organisations and services provide social support and service assistance to many people in the community; often targeting their assistance to clients facing the most difficult of clients with complex problems. Initially, in undertaking this role, the not-for-profit sector received limited sponsorship from government, relying on primarily on public donations to fund the delivery of services. (Lyons 2001). Over time governments assumed greater responsibility in the form of service grants to particular groups: ‘the worthy poor’. More recently, government has engaged in widespread procurement of services from the not-for-profit sector, which specify the nature of the outcomes to be achieved and, to a degree, the way in which the services will be provided. A consequence of this growing shift to a more marketised model of service contracting, often offered-up under the label of enhanced collaborative practice, has been increased competitiveness between agencies that had previously worked well together (Keast and Brown, 2006). One of the challenges which emerge from the procurement of services by government from third sector organisations is that public values such as effectiveness, efficiency, transparency and professionalism can be neglected (Jørgensen and Bozeman 2002), although this is not always the case (Brown, Furneaux and Gudmundsson 2012). While some approaches to the examination of social procurement - the intentional purchasing of social outcomes (Furneaux and Barraket 2011) - assumes that public values are lost in social procurement arrangements (Bozeman 2002; Jørgensen and Bozeman 2002), alternative approach suggest such inevitability is not the case. Instead, social procurement is seen to involve a set of tensions (Brown, Potoski and Slyke 2006) or a set of trade offs (Charles et al. 2007), which must be managed, and through such management, public values can be potentially safeguarded (Bruin and Dicke 2006). The potential trade-offs of public values in social procurement is an area in need of further research, and one which carries both theoretical and practical significance. Additionally, the juxtaposition of policies – horizontal integration and vertical efficiency – results in a complex, crowded and contested policy and practice environment (Keast et al., 2007),, with the potential for set of unintentional consequences arising from these arrangements. Further the involvement of for-profit, non-profit, and hybrid organisations such as social enterprises, adds further complexity in the number of different organisational forms engaged in service delivery on behalf of government. To address this issue, this paper uses information gleaned from a state-wide survey of not-for-profit organisations in Queensland, Australia which included within its focus organisational size, operational scope, funding arrangements and governance/management approaches. Supplementing this information is qualitative data derived from 17 focus groups and 120 interviews conducted over ten years of study of this sector. The findings contribute to greater understanding of the practice and theory of the future provision of social services.

Mothers of young children with special health care needs : maternal well-being and engagement in work

This thesis reports research focused on the well-being and employment experiences of mothers who have a child with special health care needs. Data are drawn from Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC). This is a public access database. The thesis uses the social ecological theory of Bronfenbrenner (1984) and the work of Zubrick et al. (2000) on human and social capital to inform the conceptual framework developed for the research. Four studies are reported. LSAC has a nationally representative sample of Australian children and their families. The study is tracking the development of 10,000 children, with data collected every two years, from 2004 to 2018. This thesis uses data from the Kindergarten Cohort of LSAC. The 4,983 children in the Kindergarten Cohort were aged 4 years at recruitment into the study in 2004. The analyses in this thesis use child and family data from Wave 1 (2004) and Wave 2 (2006) for a subsample of the children who are identified as having special health needs. This identification is based on a short screening questionnaire included in the Parent 1 Interview at each wave of the data collection. It is the children who are identified as having special health care needs which can be broadly defined as chronic health conditions or developmental difficulties. However, it is the well-being and employment experiences of the mothers of these children that are the primary focus in three of the four studies reported in this thesis.

Screening for alcohol and drug use in pregnancy

Objective - this study examined the clinical utility and precision of routine screening for alcohol and other drug use among women attending a public antenatal service. Study design - a survey of clients and audit of clinical charts. Participants and setting - clients attending an antenatal clinic of a large tertiary hospital in Queensland, Australia, from October to December 2009. Measurements and findings - data were collected from two sources. First, 32 women who reported use of alcohol or other drugs during pregnancy at initial screening were then asked to complete a full substance use survey. Second, data were collected from charts of 349 new clients who attended the antenatal clinic during the study period. Both sensitivity (86%, 67%) and positive predictive value (100%, 92%) for alcohol and other drug use respectively, were high. Only 15% of surveyed women were uncomfortable about being screened for substance use in pregnancy, yet the chart audit revealed poor staff compliance. During the study period, 25% of clients were either not screened adequately or not at all. Key conclusions and implications for practise - despite recommended universal screening in pregnancy and the apparent acceptance by our participants, alcohol and other drug (A&OD) screening in the antenatal setting remains problematic. Investigation into the reasons behind, and ways to overcome, the low screening rate could improve health outcomes for mothers and children in this at-risk group. Targeted education and training for midwives may form part of the solution as these clinicians have a key role in implementing prevention and early intervention strategies.

Cognitive behavior therapy and dialectical behavior therapy for treating obese emotional eaters

This study describes the treatment of obese individuals who rated high on emotional eating using four case studies that involved 22 sessions of either cognitive behavioral therapy (CBT) or dialectical behavioral therapy (DBT). Outcomes measures relating to weight, body mass index, emotional eating, depression, anxiety, and stress were all assessed with each participant prior to each baseline (three weekly sessions), during treatment and posttherapy. At the 8-week follow-up, the two cases that had received DBT had lost 10.1% and 7.6% of their initial body weight, whereas the two cases that had received CBT had lost 0.7% and 0.6% of their initial body weight. The two DBT cases also exhibited reductions in emotional distress, frequency of emotional eating or quantity of food eating in response to emotions, whereas the two CBT cases showed no overall reductions in these areas. Important processes from all four cases are described as are the implications to clinicians for developing more effective interventions for obese clients who engage in emotional eating.

Alcohol and other drugs in construction

Evidence from the infrastructure and building sectors suggests issues of drugs and alcohol and its association with safety risk on construction sites. While most Australian jurisdictions have identified this as a critical safety issue, information is limited regarding the prevalence of alcohol and other drugs in the workplace and there is limited evidential guidance on how to effectively and efficiently address such an issue. A nationally consistent collaborative approach across the construction workforce - involving employers and employees; clients, unions; contractors and sub-contractors is required to engender a cultural change in the construction workforce – in a similar manner to the on-going initiative in securing a cultural change to drink-driving in our society where peer intervention and support is encouraged. A study to address these issues has three key objectives. Firstly, using the standard World Health Organisation Alcohol Use Disorders Identification Test (AUDIT), and a wide ranging set of structured interviews, a national qualitative and quantitative assessment of the use of drugs and alcohol is being undertaken. Secondly, the development of an appropriate industry policy with an adoption of an educative and rehabilitative approach is planned in consultation with employers and employees across the infrastructure and building sectors, with an aim of national adoption. Finally, an industry-specific cultural change management program will be developed through a nationally collaborative approach to reducing the risk of impaired performance on construction sites and increasing workers’ commitment to drugs and alcohol safety. The study outcomes stand to benefit not only occupational health and safety, through a greater understanding of the safety impacts of alcohol and other drugs at work, but also alcohol and drug use as a wider community health issue. This presentation will provide an analysis and discussion of the data collected in objective 1 and how the final results will inform the subsequent phases of the study.

Evaluation of the Type I child car restraints fitting service in WA

Child passenger injury remains a major road safety issue despite advances in biomechanical understanding and child restraint design. In Australia, one intervention with parents to encourage universal and consistent use of the most appropriate restraint as well as draw their attention to critical aspects of installation is the RoadWise Type 1 Child Car Restraints Fitting Service, WA. A mixed methods evaluation of this service was conducted in early 2010. Evaluation results suggest that it has been effective in ensuring good quality training of child restraint fitters. In addition, stakeholder and user satisfaction with the Service is high, with participants agreeing that the Service is valuable to the community, and fitters regarding the training course, materials and post-training support as effective. However, a continuing issue for interventions of this type is whether the parents who need them perceive this need. Evidence from the evaluation suggests that only about 25% of parents who could benefit from the Service actually use it. This may be partly due to parental perceptions that such services are not necessary or relevant to them, or to overconfidence about the ease of installing restraints correctly. Thus there is scope for improving awareness of the Service amongst groups most likely to benefit from it (e.g. new parents) and for alerting parents to the importance of correct installation and getting their self-installed restraints checked. Efforts to inform and influence parents should begin when their children are very young, preferably at or prior to birth and/or before the parent installs the first restraint.

Factors contributing to design-build (DB) project delivery system implementation in road infrastructure projects in Indonesia

Design-build (DB) project delivery systems have increasingly been adopted by many private and public sector organizations worldwide due to the many advantages offered on projects by such systems. However, many Indonesian road infrastructure projects are still delivered using the traditional design-bid-build (DBB) project delivery system. In order to provide evidence of the benefits of DB, it is essential to identify the factors that can contribute to successful DB implementation and this paper aims to provide evidence of such factors that can promote the successful implementation of DB project delivery systems on Indonesian road infrastructure projects. Four main factors and 28 indicators were identified from an extensive literature review, and a Delphi questionnaire survey was conducted amongst 20 experts drawn from the Indonesian road infrastructure construction sector. The first round Delphi study found that regulation, competency of clients, ability to manage DB projects and external conditions were the major factors that can promote successful DB implementation.

Indigenous knowledge and effective parent–school partnerships : issues and insights

Towards the last decade of the last millennium, Indigenous knowledge was central to international scholarly debates relating to decolonising knowledge. Indigenous scholars, particularly those from Australia, New Zealand, Canada, and the United States, advanced many of these debates. They argued for Indigenous knowledge to be used as the epistemological standpoint for intellectual engagements and the methodology for resisting colonial constructions of the colonised other (Rigney 1997; Smith 1999, 2005). However, the challenge of engaging Indigenous knowledge to inform research and educational processes, in many respects, is still a contested debate in Western-oriented universities and institutions of higher education. This chapter discusses findings of the Parent–School Partnership Initiative (hereafter referred to as PSPI) project conducted by the Oodgeroo Unit staff and the Aboriginal and Torres Strait Islander Education Focus Group for the Caboolture Shire, in South East Queensland. The state government sponsored initiative examined factors that promote and enhance parent–school engagement with students’ schooling, and contributed to Aboriginal and Torres Strait Islander students’ learning and completion of secondary schooling within the participating schools. We argue in this chapter for the importance of recognising Indigenous knowledge and its place in enhancing parent–school partnerships.

Queensland Government Agency Libraries Review: Options Paper

The Queensland Government Agency Libraries Review was undertaken during the period January-June 2010. The research project was sponsored jointly by the Director-General, Department of the Premier and Cabinet, and the Director-General, Department of Public Works. The objective of the project was to examine future options for the Queensland Government library and research services that provide clients with efficient and cost-effective access to the information they need to conduct government business, to develop a picture of the services provided, the information resources managed, the client base and staffing. The review also considered the environmental factors impacting on contemporary government libraries to determine possible strategies that would ensure a strong and sustainable future for the services. The review process culminated in identifying potential options for future service delivery. The preferred option involves a proposal for the centralizing responsibility for the coordination of a network of Queensland Government Libraries and Research Centres (QGLR). The establishment of a network of research centres, with a central point for coordination of common strategies, systems and processes will enable library and research services to flow around individual agencies, and provide clearer avenues for multi-disciplinary work that characterises contemporary government policy and government services. The key elements of the proposal include the development of a single library and research portal for all government officers, which can be tailored to meet their particular research needs; increasing the visibility and accessibility of information and knowledge resources to those officers regardless of their agency affiliation; introducing better, more cost effective purchasing and licensing arrangements; and the potential to have a voice of influence in the strategic agenda for the government’s use of information and research.

Mandatory auditor rotation : Australian evidence

A key part of the auditor independence reforms in Australia, as represented by Corporate Law Economic Reform Program (Audit Reform and Corporate Disclosure) Act 2004 (Cth) (CLERP 9), mandates audit partner rotation. The change was criticised predominantly due to the costs imposed on both the audit firms and the audit clients. This study examines the Australian experience post-CLERP 9 with mandated auditor rotation. Based on data of audit partner rotation over 2003–2009 (on average 1200 listed Australian companies over the sample period), we show that audit partner tenure sat at a median of 2–3 years, but that the maximum audit partner tenure was as high as 20 years in the pre-CLERP 9 period. For around 85% of the market, audit partner rotation occurred voluntarily at between 1–5 years. The interesting result is that for 15% of the market, the mandated audit partner rotation had a significant impact on corporate governance practice. There is also a greater observed impact of mandatory rotation on audit engagements involving the non-global auditing firms. These findings inform the debate as to the ‘costliness’ of the law reform.

Regulatory responses to auditor independence dilemmas – who takes the stronger line?

A key part of corporate governance reforms in Australia, as represented by CLERP 9, addresses concerns over the audit function and the role of independent auditors in monitoring managers and providing useful information to stakeholders about the financial position of the company. In comparing the regulatory responses to auditor independence dilemmas, there have been claims that CLERP 9 is less ‘stringent’ than the reforms imposed by the Sarbanes Oxley Act in the US. This paper looks at three particular situations that have been the subject of recent reform to strengthen independence: the mandatory rotation of auditors, recruitment of former auditors as board members, and provision of non-audit services to clients. In each case, we compare the similarities and differences of the regulatory response between Australia and US, to distil the efficacy of the CLERP 9 approach.