Prognostic significance of IGF and ECM induced signalling proteins in breast cancer patients

Breast cancer is a leading contributor to the burden of disease in Australia. Fortunately, the recent introduction of diverse therapeutic strategies have improved the survival outcome for many women. Despite this, the clinical management of breast cancer remains problematic as not all approaches are sufficiently sophisticated to take into account the heterogeneity of this disease and are unable to predict disease progression, in particular, metastasis. As such, women with good prognostic outcomes are exposed to the side effects of therapies without added benefit. Furthermore, women with aggressive disease for whom these advanced treatments would deliver benefit cannot be distinguished and opportunities for more intensive or novel treatment are lost. This study is designed to identify novel factors associated with disease progression, and the potential to inform disease prognosis. Frequently overlooked, yet common mediators of disease are the interactions that take place between the insulin-like growth factor (IGF) system and the extracellular matrix (ECM). Our laboratory has previously demonstrated that multiprotein insulin-like growth factor-I (IGF-I): insulin-like growth factor binding protein (IGFBP): vitronectin (VN) complexes stimulate migration of breast cancer cells in vitro, via the cooperative involvement of the insulin-like growth factor type I receptor (IGF-IR) and VN-binding integrins. However, the effects of IGF and ECM protein interactions on the dissemination and progression of breast cancer in vivo are unknown. It was hypothesised that interactions between proteins required for IGF induced signalling events and those within the ECM contribute to breast cancer metastasis and are prognostic and predictive indicators of patient outcome. To address this hypothesis, semiquantitative immunohistochemistry (IHC) analyses were performed to compare the extracellular and subcellular distribution of IGF and ECM induced signalling proteins between matched normal, primary cancer, and metastatic cancer among archival formalin-fixed paraffin-embedded (FFPE) breast tissue samples collected from women attending the Princess Alexandra Hospital, Brisbane. Multivariate Cox proportional hazards (PH) regression survival models in conjunction with a modified „purposeful selection of covariates. method were applied to determine the prognostic potential of these proteins. This study provides the first in-depth, compartmentalised analysis of the distribution of IGF and ECM induced signalling proteins. As protein function and protein localisation are closely correlated, these findings provide novel insights into IGF signalling and ECM protein function during breast cancer development and progression. Distinct IGF signalling and ECM protein immunoreactivity was observed in the stroma and/or in subcellular locations in normal breast, primary cancer and metastatic cancer tissues. Analysis of the presence and location of stratifin (SFN) suggested a causal relationship in ECM remodelling events during breast cancer development and progression. The results of this study have also suggested that fibronectin (FN) and ¥â1 integrin are important for the formation of invadopodia and epithelial-to-mesenchymal transition (EMT) events. Our data also highlighted the importance of the temporal and spatial distribution of IGF induced signalling proteins in breast cancer metastasis; in particular, SFN, enhancer-of-split and hairy-related protein 2 (SHARP-2), total-akt/protein kinase B 1 (Total-AKT1), phosphorylated-akt/protein kinase B (P-AKT), extracellular signal-related kinase-1 and extracellular signal-related kinase-2 (ERK1/2) and phosphorylated-extracellular signal-related kinase-1 and extracellular signal-related kinase-2 (P-ERK1/2). Multivariate survival models were created from the immunohistochemical data. These models were found to fit well with these data with very high statistical confidence. Numerous prognostic confounding effects and effect modifications were identified among elements of the ECM and IGF signalling cascade and corroborate the survival models. This finding provides further evidence for the prognostic potential of IGF and ECM induced signalling proteins. In addition, the adjusted measures of associations obtained in this study have strengthened the validity and utility of the resulting models. The findings from this study provide insights into the biological interactions that occur during the development of breast tissue and contribute to disease progression. Importantly, these multivariate survival models could provide important prognostic and predictive indicators that assist the clinical management of breast disease, namely in the early identification of cancers with a propensity to metastasise, and/or recur following adjuvant therapy. The outcomes of this study further inform the development of new therapeutics to aid patient recovery. The findings from this study have widespread clinical application in the diagnosis of disease and prognosis of disease progression, and inform the most appropriate clinical management of individuals with breast cancer.

Public realm and transport, international best practice case studies and opportunities for Brisbane

This report was prepared for Lat 27 Pty Ltd for the purpose of conducting a City Centre Public Realm and Active Transport Study for Urban Renewal Brisbane, Brisbane City Council. In this review, we highlight some key learnings and recommendations from innovative projects across the globe to inform public realm design and help facilitate active transport in subtropical Brisbane. Traditionally, Australian cities have been have been based on northern European models. This report is informed by the view that planners and urban designers must look beyond that paradigm to redefine and re-conceptualise our city in a different way, one that values our unique local identity and climate. In re-designing Brisbane’s public realm, therefore, design interventions and responses must celebrate our unique identity and outdoor lifestyle and address the subtropical climate's reality of life in warm humid summers and cool dry winters. The current period of rapid urban change, and the imperative to adapt to climate change, together offer an opportunity to prioritise and integrate design features that provide shade and shelter from sun and summer rain, open and permeable urban environments that facilitate cooling air movement, and connections to water and nature, so that the urban built form co-exists within an inviting, functional and memorable natural landscape. To inform this transformation, this review provides insight into international experiences and best practices. To date, although there is much practice-based knowledge, academic studies outlining learnings and recommendations from case studies (especially in a subtropical context) remain rare. Thus, a range of sources (industry reports, websites, journal articles and books) have been utilised.

Teaching about trafficking : opportunities and challenges for critical engagement

When I was first invited to teach a women's studies course called Sex Trafficking in 2002, most of my students had never heard of the issue. Internet and literature searches for "trafficking" mostly turned up references to trafficking in drugs and weapons, not people. When I revised the course for a topical capstone in Criminology, Justice, and Policy Studies in 2006, all of my students had heard about human trafficking, and a handful had already studied it in other classes. The availability of books, films, scholarly articles, and advocacy pieces had all increased exponentially since I first became engaged in the field. This bounty provided a wealth of resources for teaching but also presented a greater challenge when it came to deciding which texts to include. It also added to the inevitable pedagogical angst over what to leave out. I came to know about trafficking by accident, when I was hired as a research assistant at The Protection Project (TPP) in 1999. In my time at TPP I authored a literature review on human trafficking. At that time, my comprehensive database of sources contained fewer than one hundred books and articles, a few UN documents, a handful of films, and some websites from nongovernmental organizations. My review of the literature inevitably reflected the ideological chasm between those who saw trafficking as primarily a labor, migration, and rights issue and those who saw it as primarily a sexual exploitation issue. On the policy end, these ideological orientations created bizarre bedfellows of individuals and organizations that otherwise would have been at odds. The ideological divide has not diminished in the intervening years, and it is important to be aware of and to negotiate this in designing a course on trafficking. As a feminist teacher, I was very aware of the divisions among feminists on the subject of trafficking, and was interested in communicating these differences to students who were not well versed in the varieties of feminist thought. I was also mindful of the difficulties my American students had in engaging with some of the course texts and issues the first time around. For some students, moral judgments about prostitutes were as far as they were able to go in engaging with the course. These students could not find a way in to think about the many issues involved in trafficking. How could I reach them? In this article, I share some of my texts and tactics with others who might find themselves in a position to teach about human trafficking. I include my case for why feminist teachers should teach trafficking, an overview of the debate that divides the field, my rationale for organizing the course the way that I did, issues to consider when designing a course on trafficking, and some suggested readings, films, and web resources.

Challenges and opportunities in the journey of the design-led innovation champions

The purpose of this study is to deepen our knowledge and understanding of the challenges faced by design champions in proposing and applying design methods and insights in existing firms. This study investigates the early stages of the journey of the design champions as they incorporate design into operational and strategic conversations and practices, and their progress in mastering these challenges as opportunities in a firm context. Little research on this topic has been reported, yet it is of growing interest as more firms turn to design-led innovation to shape their strategies and practices. Interviews with design champions were used to investigate first hand the experience and reflections the many challenges provide. Findings from the study provide some early insights that can be extended through further research.

Unpacking the opportunities for change within a family owned manufacturing SME : a design led innovation case study

The following paper presents insights found during an ongoing industry engagement with a family-owned manufacturing SME in Australia. The initial findings presented as a case study look at the opportunities available to the firm engaging in a design led approach to innovation. Over the period of one year, the first author’s immersion within the firm seeks to unpack the cultural, strategic, product opportunities and challenges when adopting design led innovation. This can provide a better understanding of how a firm can more effectively assess their value proposition in the market and what factors of the business are imperative in stimulating competitive difference. The core insight identified from this paper is that design led innovation cannot be seen and treated as a discrete event, nor a series of steps or stages; rather the whole business model needs to be in focus to achieve holistic, sustainable innovation. Initial insights were found through qualitative interviews with internal employees including: overcoming silos; moving from reactive to proactive design; empowerment; vision for growth and the framing of innovation.

Pervasive technology and public transport : opportunities beyond telematics

The advancements of technology in the field of public transport have been considerable. Information Technology (IT) has made the dissemination of information effortless, contributing to reduced perceived waiting time, increased sense of security, and value for money. Nevertheless, and in light of the ever more obvious widespread presence of powerful mobile devices, it seems that the use of technology may be geared towards supplementary services other than telematics. Looking at it from a passenger’s perspective, this article provides an overview of what IT-based services are currently offered in public transport and what is their assessed impact. We finalise by putting forward possible directions that future services might follow, and stress out the necessity to come up with frameworks that enable for the impact assessment on service quality and customer satisfaction.

Employment opportunities in Australia for educational researchers: A review of recent advertisements

The Australian Association for Research in Education (AARE) by promoting the conference theme has identified a need to be more proactive to ensure growth in the number of educational researchers. Within the Higher Education sector there are a number of methods used to encourage interest in a particular area, and these include policy, funding, sponsorship, employment and scholarships. There are three types of employment for academics: Research, Lecturing and Teaching and Learning and two types of scholarships: either students self-identify the topic or topics are targeted with associated funding. The aim of this study is to review the academic positions and targeted scholarships of Australian Universities and research organisations gathered from advertisements in a national newspaper. This will establish a baseline of recent practice from July to December, 2006 and identify opportunities for researchers in all Disciplines and specifically in education. Results reveal the two main groups for academics are Research and Lecturing, with a small number in Teaching and Learning. Although the Education Discipline is well represented overall (3rd in 12 Disciplines after Health and Science) in terms of research opportunities education then moves to 10th position. A further significant finding is the highly contractual nature of research versus the more stable, tenured environment for lecturing. There are a number of implications arising from this short study. Firstly, the Discipline of Education as a targeted area for research alone is significantly under-represented in the advertised positions but is well represented in lecturing where the role always requires teaching and research. Thus it seems the amount of time devoted to research by academics in the education Discipline is significantly lower than for health or science. Secondly, there are few industry/Government targeted scholarships in the education Discipline therefore any growth in numbers of educational researchers through postgraduate study is not expanded by funding to meet identified needs. In conclusion AARE, an association interested in promoting the growth of educational research, has an obvious need to encourage and review the outcomes of this study and perhaps adopt some of the successful strategies employed by other Disciplines to improve the opportunities for educational researchers in the future.

Therapeutic immunisation of rabbits with cottontail rabbit papillomavirus (CRPV) virus-like particles (VLP) induces regression of established papillomas

There is overwhelming evidence that persistent infection with high-risk human papillomaviruses (HR-HPV) is the main risk factor for invasive cancer of the cervix. Due to this global public health burden, two prophylactic HPV L1 virus-like particles (VLP) vaccines have been developed. While these vaccines have demonstrated excellent type-specific prevention of infection by the homologous vaccine types (high and low risk HPV types), no data have been reported on the therapeutic effects in people already infected with the low-risk HPV type. In this study we explored whether regression of CRPV-induced papillomas could be achieved following immunisation of out-bred New Zealand White rabbits with CRPV VLPs. Rabbits immunised with CRPV VLPs had papillomas that were significantly smaller compared to the negative control rabbit group (P ≤ 0.05). This data demonstrates the therapeutic potential of PV VLPs in a well-understood animal model with potential important implications for human therapeutic vaccination for low-risk HPVs. © 2008 Govan et al; licensee BioMed Central Ltd.

A longitudinal study of mental health in refugees from Burma : the impact of therapeutic interventions

Objective: The present study seeks to examine the impact of therapeutic interventions for people from refugee backgrounds within a naturalistic setting. Method: Sixty-two refugees from Burma were assessed soon after arriving in Australia. All participants received standard interventions provided by a resettlement organisation which included therapeutic interventions, assessment, social assistance, and referrals where appropriate. At the completion of service provision a follow-up assessment was conducted. Results: Over the course of the intervention, participants experienced a significant decrease in symptoms of post-traumatic stress disorder, anxiety, depression and somatisation. Pre-intervention symptoms predicted symptoms post-intervention for post-traumatic stress, anxiety, and somatisation. Post-migration living difficulties, the number of traumas experienced, and the number of contacts with the service agency were unrelated to all mental health outcomes. Conclusions: In the first Australian study of its kind, reductions in mental health symptoms post-intervention were significantly linked to pre-intervention symptomatology and the number of therapy sessions predicted post-intervention symptoms of post-traumatic stress. Future studies need to include larger samples and control groups to verify findings.

Direct fabrication as a patient-targeted therapeutic in a clinical environment

A paradigm shift is taking place in orthopaedic and reconstructive surgery. This transition from using medical devices and tissue grafts towards the utilization of a tissue engineering approach combines biodegradable scaffolds with cells and/or biological molecules in order to repair and/or regenerate tissues. One of the potential benefits offered by solid freeform fabrication (SFF) technologies is the ability to create such biodegradable scaffolds with highly reproducible architecture and compositional variation across the entire scaffold due to their tightly controlled computer-driven fabrication. Many of these biologically activated materials can induce bone formation at ectopic and orthotopic sites, but they have not yet gained widespread use due to several continuing limitations, including poor mechanical properties, difficulties in intraoperative handling, lack of porosity suitable for cellular and vascular infiltration, and suboptimal degradation characteristics. In this chapter, we define scaffold properties and attempt to provide some broad criteria and constraints for scaffold design and fabrication in combination with growth factors for bone engineering applications. Lastly, we comment on the current and future developments in the field, such as the functionalization of novel composite scaffolds with combinations of growth factors designed to promote cell attachment, cell survival, vascular ingrowth, and osteoinduction.

Legal, cultural and practical developments in responding to female genital mutilation : can an absolute human right emerge?

Female genital mutilation (FGM) is a cultural practice involving the deliberate, non-therapeutic physical modification of young girls’ genitalia. FGM can take several forms, ranging from smaller incisions, to removal of the clitoris and labia, and narrowing or even closing of the vagina. FGM predates and has no basis in the Koran, or any other religious text. Rather, it is a cultural tradition, particularly common in Islamic societies in regions of Africa, motivated by a patriarchal society’s desire to control female bodies and lives. The primary reason for this desire for control is to ensure virginity at marriage, thereby preserving family honour, within a patriarchal social structure where females’ value as persons is intrinsically connected to, and limited to, their worth as virgin brides. Recent efforts at legal prohibition and practical eradication in a growing number of African nations mark a significant turning point in how societies treat females. This shift in cultural power has been catalysed by a concern for female health, but it has also been motivated by an impulse to promote the human rights of girls and women. Although FGM remains widely practiced and there is much progress yet to be made before its eradication, the rights-based approach which has grown in strength embodies a marked shift in cultural power which reflects progress in women’s and children’s rights in the Western world, but which is now being applied in a different cultural context. This chapter reviews the nature of FGM, its prevalence, and health consequences. It discusses recent legal, cultural and practical developments, especially in African nations. Finally, this chapter raises the possibility that an absolute human right against FGM may emerge.

Enhancing opportunities to feed forward ; developing problem solving skills using web based scenarios

Universities often struggle to satisfy students’ need for feedback. This is an area where student satisfaction with courses of study can be low. Yet it is clear that one of the properties of good teaching is giving the highest quality feedback on student work. The term ‘feedback’ though is most commonly associated with summative assessment given by a teacher after work is completed. The student can often be a passive participant in the process. This paper looks at the implementation of a web based interactive scenario completed by students prior to summative assessment. It requires students to participate actively to develop and improve their legal problem solving skills. Traditional delivery of legal education focuses on print and an instructor who conveys the meaning of the written word to students. Today, mixed modes of teaching are often preferred and they can provide enhanced opportunities for feeding forward with greater emphasis on what students do. Web based activities allow for flexible delivery; they are accessible off campus, at a time that suits the student and may be completed by students at their own pace. This paper reports on an online interactive activity which provides valuable formative feedback necessary to allow for successful completion of a final problem solving assignment. It focuses on how the online activity feeds forward and contributes to the development of legal problem solving skills. Introduction to Law is a unit designed and introduced for completion by undergraduate students from faculties other than law but is focused most particularly on students enrolled in the Bachelor of Entertainment Industries degree, a joint initiative of the faculties of Creative Industries, Business and Law at the Queensland University of Technology in Australia. The final (and major) assessment for the unit is an assignment requiring students to explain the legal consequences of particular scenarios. A number of cost effective web based interactive scenarios have been developed to support the unit’s classroom activities. The tool commences with instruction on problem solving method. Students then view the stimulus which is a narrative produced in the form of a music video clip. A series of questions are posed which guide students through the process and they can compare their responses with sample answers provided. The activity clarifies the problem solving method and expectations for the summative assessment and allows students to practise the skill. The paper reports on the approach to teaching and learning taken in the unit including the design process and implementation of the activity. It includes an evaluation of the activity with respect to its effectiveness as a tool to feed forward and reflects on the implications for the teaching of law in higher education.

Complications related to therapeutic anticoagulation in total hip arthroplasty

Bleeding related wound complications cause significant morbidity in lower limb arthroplasty surgery. Patients who require therapeutic anticoagulation in the peri operative period are potentially at higher risk of these complications. This is a retrospective case control study reviewing all primary total hip replacements performed in a single center over a five year period and comparing outcomes of the patients on warfarin with a double-matched control group of patients not on warfarin. The warfarin group had significantly higher risk of deep joint infection (9% vs 2.2%), haematoma/ wound ooze (28% vs 4%) and superficial infection (13.5% vs 2.2%). Managing the total hip arthroplasty patient with therapeutic anticoagulation is a balance between the risk of thromboembolic disease and bleeding related complications. Improved understanding of this risk will better allow the patient to make an informed decision regarding their elective arthroplasty surgery.

Diversification for sustainable development in rural and regional Australia : how local community leaders conceptualise the impacts and opportunities from agriculture, tourism and mining

Although the multiple economic, environmental and social challenges threatening the viability of rural and regional communities in Australia are well-known, little research has explored how community leaders conceptualise the impact and opportunities associated with economic diversification from agriculture into alternative industries, such as tourism and mining. This qualitative research, utilising the Darling Downs in Queensland as a case study, documents how 28 local community leaders have experienced this economic diversification process. The findings reveal that local community leaders have a deep understanding about the opportunities and challenges presented by diversification, articulating a clear vision about how to achieve the best possible future for their region. Despite excitement about growth, there were concerns about preserving heritage, the increased pressure on local infrastructure and an ageing population. By documenting local leader’s insights, these findings may help inform planning for rural and regional communities and facilitate management of the exciting yet challenging process of growth and diversification