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.

The potential influence of Neoliberalism on the capacity and form of spatial adaptation

Human spatial environments must adapt to climate change. Spatial planning is central to climate change adaptation and potentially well suited to the task, however neoliberal influences and trends threaten this capacity. This paper explores the potential interaction of emerging research areas, the first of which pursues climate change adaptation through spatial planning and the second of which has observed the neoliberalisation of urban planning, The potential capacity and form of spatial adaptation within the context a planning environment influenced by neoliberal principles is evaluated. This influence relates to the themes of spatial scale, temporal scale, responsibility for action, strategies and mechanisms, accrual of benefits, negotiation of priorities and approach to uncertainty. This paper presents a conceptual framework of the influence of neoliberalism on spatial adaptation and presents examples of this approach in documents which underpin adaptation in Australia. It identifies the potential characteristics and the challenges and opportunities of spatial adaptation under a neoliberal frame. The neoliberal frame does not entirely preclude spatial adaptation but significantly influence its form. Neoliberal approaches involve individual action in response to private incentives and near term impacts while collective action, regulatory mechanisms and long term planning is approached cautiously. Challenges concern the degree to which collective action and a long term orientation are necessary, how individual adaptation relates to collective vulnerability and the prioritisation of adaptation by markets. Opportunities might involve the operability of individual and local adaptation, the existence of private incentives to adapt and the potential to align adaptation with entrepreneurial projects.

Learning processes in creative industries initiatives in developing countries : an examination of policy and practice

What does a dance group in Benin that mixes contemporary and ethnic dancing have in common with Mongolian felt producers that want to enter the design market in Europe? These are both examples of learning processes in Creative Industries initiatives in developing countries. Following the concept of sustainable development, I argue that the challenge for developing countries in contemporary society is to meet the very real need of people for economic development and opportunities for income generation, while at the same time avoiding unintended and unwanted consequences of economic development and globalisation. The concept of the Creative Industries may be a way to promote a development that is sustainable and avoids social exclusion of groups-at-risk. In line with this, I argue that the Creative Industries sector could, in fact, link economic development and the continuation and evolution of local traditions and cultural heritage. A pressing question then is: how can education and learning contribute to creating a context in which talent can flourish? This study aims to provide a comprehensive analysis of the research problem of this thesis: what elements are conducive for individual learning processes in creative development initiatives? In this, I argue that it is crucial to determine what ingredients and characteristics contribute to making these initiatives successful, that is, to meet their specific goals, in a developing context. This is explored through a staged analysis: an overview of quantitative data, an inventory and comparative case studies and, finally, the description and analysis of two in-depth case studies – felt design in Mongolia (Asia) and dance in Benin (Africa), in which I was an observer of the action phase of the local interventions. The analysis culminates in practice-related outcomes related to the operation of creative development initiatives, as well as the contribution to the academic debate on issues like the cultural gap between developed and developing countries, transformative learning and the connection of learning spaces.

Improvising a future in the performing arts : a new strategy to help performance studies students successfully shift between academic culture, professional culture, industry and career?

If there is one thing performance studies graduates should be good at, it is improvising – play and improvisation are central to the contemporary and cultural performance practices we teach and the methods by which we teach them. Objective, offer, acceptance, advancing, reversing, character, status, manipulation, impression management, relationship management – whether we know them from Keith Johnson’s theatre theories or Erving Goffman’s theatre theories, the processes by which we play out a story, scenario or social situation to our own benefit are familiar. We understand that identity, action, interaction and its personal, aesthetic, professional or political outcomes are unpredictable, and that we need to adapt to changeable and uncertain circumstances to achieve our aims. Intriguingly, though, in a Higher Education environment that increasingly emphasises employability, skills in play, improvisation and self-performance are never cited as critical graduate attributes. Is the ability to play, improve and produce spontaneous new self-performances learned in the academy worth articulating into an ability to play, improvise and product spontaneous new self-performances after graduates leave the academy and move into the role of a performing arts professional in industry? A study of the career paths of our performance studies graduates over the past decade suggests that addressing the challenges they face in moving between academic culture, professional culture, industry and career in terms of improvisation and play principles may be very productive. In articles on performing arts careers, graduates are typically advised to find a market for their work, and develop career self-management, management and marketing skills, together with an ability to find, make and maintain relationships and opportunities for themselves. Transitioning to career is cast as a challenging process, requiring these skills, because performing arts careers do not offer the security, status and stability of other careers. Our data confirms this. In our study, though, we found that strategies commonly used to build the resilience, self-reliance and persistence graduates require – talking about portfolio careers, parallel careers, and portable, transferable or translatable skills, for example – can engender panic as easily as they engender confidence. In this paper, I consider what happens when we re-articulate some of the skills scholars and industry stakeholders argue are critical in allowing graduates to shift successfully from academy to industry in terms of skills like improvisation, play and self-performance that are already familiar, meaningful and much-practiced amongst performance studies graduates.

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.

Catapulting into STEM education : female students’ interactions within a middle school engineering project

Despite efforts to motivate students to engage in Science, technology, engineering and mathematics (STEM) education, women are still underrepresented in these areas in the workforce and higher education. Targeting females at high school or earlier may be a key towards engaging them in STEM. In this paper we report on the research question: How do middle school females interact for learning about engineering education? This ethnographic study, part of a three-year longitudinal research project, investigated Year 8 female students’ learning about engineering concepts associated with designing, constructing, testing, and evaluating a catapult. Through a series of lead-up lessons and the four lesson catapult challenge (total of 18 x 45-minute lessons over 9 weeks), data from two girls within a focus group showed that the students needed to: (1) receive clarification on engineering terms to facilitate more fluent discourse, (2) question and debate conceptual understandings without peers being judgemental, and (3) have multiple opportunities for engaging with materials towards designing, constructing and explaining key concepts learnt. Implications for teachers undertaking STEM education are evident, including outlining expectations for clarifying STEM terms, outlining to students about interacting non-judgementally, and providing multiple opportunities for interacting within engineering education.

Facebook, Twitter, SMS and YouTube : the ramifications and risks for surgeons

Social media revolution has impacted on how people interact with one another. This has been a worldwide phenomenon. Whilst social media had its genesis in the personal and private realm its use has expanded exponentially to professional and business contexts, as well as being adopted by governments, politicians, journalists – everyone in just about every walk of life. Although at first the uptake was slow, surgeons and other health professionals are now using social media in their professional as well as personal capacity. This comes with significant advantages and opportunities for improving surgical practice and for facilitating attending communication, but it also comes with certain risks, including legal liability. This paper outlines the ways in which social media including, Facebook, Twitter, YouTube and SMS, is increasingly being employed in surgical practice and explains the legal and ethical consequences that may inadvertently arise in its official, as well as, unofficial use.

The exemplification of governance principles within state asset management laws and policies : the case of Indonesia

Efficient state asset management is crucial for governments as they facilitate the fulfillment of their public functions, which include the provision of essential services and other public administration support. In recent times economies internationally and particularly in South east Asia, have displayed increased recognition of the importance of efficiencies across state asset management law, policies and practice. This has been exemplified by a surge in notable instances of reform in state asset management. A prominent theme in this phenomenon is the consideration of governance principles within the re-conceptualization of state asset management law and related policy, with many countries recognizing variability in the quality of asset governance and opportunities for profit as being critical factors. This issue is very current in Indonesia where a major reform process in this area has been confirmed by the establishment of a new Directorate of State Asset Management. The incumbent Director-General of State Asset Management has confirmed a re-emphasis on adherence to governance principles within applicable state asset management law and policy reform. This paper reviews aspects of the challenge of reviewing and reforming Indonesian practice within state asset management law and policy specifically related to public housing, public buildings, parklands, and vacant land. A critical issue in beginning this review is how Indonesia currently conceptualizes the notion of asset governance and how this meaning is embodied in recent changes in law and policy and importantly in options for future change. This paper discusses the potential complexities uniquely Indonesian characteristics such as decentralisation and regional autonomy regime, political history, and bureaucratic culture.

Disaster resilience and local adaptation capacity in coastal Queensland

The 2011 floods illustrated once again Queensland’s vulnerability to flooding and similar disasters. Climate change will increase the frequency and magnitude of such events and will have a variety of other impacts. To deal with these impacts governments at all levels need to be prepared and work together. Like the rest of the nation most of the population of the state is located in the coastal areas and these areas are more vulnerable to the impacts of climate change. This paper examines climate change adaptation efforts in coastal Queensland. The aim is increasing local disaster resilience of people and property through fostering coordination between local and state government planning activities in coastal high hazard areas. By increasing the ability of local governments and state agencies to coordinate planning activities, we can help adapt to impacts of climate change. Towards that end, we will look at the ways that these groups currently interact, especially with regard to issues involving uncertainty related to climate change impacts. Through an examination of climate change related activities by Queensland’s coastal local governments and state level planning agencies and how they coordinate their planning activities at different levels we aim to identify the weaknesses of the current planning system in responding to the challenges of climate change adaptation and opportunities for improving the ways we plan and coordinate planning, and make recommendations to improve resilience in advance of disasters so as to help speed up recovery when they occur.

Tackling the health burden from household air pollution (HAP) : development and implementation of new WHO Guidelines

Household air pollution (HAP), arising mainly from the combustion of solid and other polluting fuels, is responsible for a very substantial public health burden, most recently estimated as causing 3.5 million premature deaths in 2010. These patterns of household fuel use have also important negative impacts on safety, prospects for poverty reduction and the environment, including climate change. Building on previous air quality guidelines, the WHO is developing new guidelines focused on household fuel combustion, covering cooking, heating and lighting, and although global, the key focus is low and middle income countries reflecting the distribution of disease burden. As discussed in this paper, currently in development, the guidelines will include reviews of a wide range of evidence including fuel use in homes, emissions from stoves and lighting, household air pollution and exposure levels experienced by populations, health risks, impacts of interventions on HAP and exposure, and also key factors influencing sustainable and equitable adoption of improved stoves and cleaner fuels. GRADE, the standard method used for guidelines evidence review may not be well suited to the variety and nature of evidence required for this project, and a modified approach is being developed and tested. Work on the guidelines is being carried out in close collaboration with the UN Foundation Global Alliance on Clean cookstoves, allowing alignment with specific tools including recently developed international voluntary standards for stoves, and the development of country action plans. Following publication, WHO plans to work closely with a number of countries to learn from implementation efforts, in order to further strengthen support and guidance. A case study on the situation and policy actions to date in Bhutan provide an illustration of the challenges and opportunities involved, and the timely importance of the new guidelines and associated research, evaluation and policy development agendas.

Corporate climate change-related governance practices and related disclosures : evidence from Australia

This paper investigates the climate change-related corporate governance disclosure practices of five major Australian energy-intensive companies over a 16-year period. In doing so, a content analysis instrument is developed to identify disclosures made in relation to various policies and procedures the organisations have in place for addressing the issues associated with climate change. This instrument is applied to the respective companies' annual reports and sustainability reports. An increasing trend is found in companies' climate change-related corporate governance disclosures over time; however, in many instances the disclosures provide limited insights into the climate change-related risks and opportunities confronting the sample companies.

Livestock production in a changing climate : adaptation and mitigation research in Australia

Climate change presents a range of challenges for animal agriculture in Australia. Livestock production will be affected by changes in temperature and water availability through impacts on pasture and forage crop quantity and quality, feed-grain production and price, and disease and pest distributions. This paper provides an overview of these impacts and the broader effects on landscape functionality, with a focus on recent research on effects of increasing temperature, changing rainfall patterns, and increased climate variability on animal health, growth, and reproduction, including through heat stress, and potential adaptation strategies. The rate of adoption of adaptation strategies by livestock producers will depend on perceptions of the uncertainty in projected climate and regional-scale impacts and associated risk. However, management changes adopted by farmers in parts of Australia during recent extended drought and associated heatwaves, trends consistent with long-term predicted climate patterns, provide some insights into the capacity for practical adaptation strategies. Animal production systems will also be significantly affected by climate change policy and national targets to address greenhouse gas emissions, since livestock are estimated to contribute ~10% of Australia’s total emissions and 8–11% of global emissions, with additional farm emissions associated with activities such as feed production. More than two-thirds of emissions are attributed to ruminant animals. This paper discusses the challenges and opportunities facing livestock industries in Australia in adapting to and mitigating climate change. It examines the research needed to better define practical options to reduce the emissions intensity of livestock products, enhance adaptation opportunities, and support the continued contribution of animal agriculture to Australia’s economy, environment, and regional communities.

HCI for city farms : design challenges & opportunities

Urban agriculture plays an important role in many facets of food security, health and sustainability. The city farm is one such manifestation of urban agriculture: it functions as a location centric social hub that supplies food, education, and opportunities for strengthening the diverse sociocultural fabrics of the local community. This paper presents the case of Northey Street City Farm in Brisbane, Australia as an opportunity space for design. The paper iden-tifies four areas that present key challenges and opportunities for HCI design that support social sustainability of the city farm: A preference for face-to-face contact leads to inconsistencies in shared knowledge; a dependence on volun-teers and very limited resources necessitates easily accessible interventions; other local urban agricultural activity needing greater visibility; and the vulner-ability of the physical location to natural phenomenon, in this instance flooding, present a design challenge and a need to consider disaster management.