Role of intratumoural heterogeneity in cancer drug resistance : molecular and clinical perspectives

Drug resistance continues to be a major barrier to the delivery of curative therapies in cancer. Historically, drug resistance has been associated with over-expression of drug transporters, changes in drug kinetics or amplification of drug targets. However, the emergence of resistance in patients treated with new-targeted therapies has provided new insight into the complexities underlying cancer drug resistance. Recent data now implicate intratumoural heterogeneity as a major driver of drug resistance. Single cell sequencing studies that identified multiple genetically distinct variants within human tumours clearly demonstrate the heterogeneous nature of human tumours. The major contributors to intratumoural heterogeneity are (i) genetic variation, (ii) stochastic processes, (iii) the microenvironment and (iv) cell and tissue plasticity. Each of these factors impacts on drug sensitivity. To deliver curative therapies to patients, modification of current therapeutic strategies to include methods that estimate intratumoural heterogeneity and plasticity will be essential.

Study Protocol - Alcohol Management Plans (AMPs) in remote indigenous communities in Queensland: their impacts on injury, violence, health and social indicators and their cost-effectiveness

Background In 2002/03 the Queensland Government responded to high rates of alcohol-related harm in discrete Indigenous communities by implementing alcohol management plans (AMPs), designed to include supply and harm reduction and treatment measures. Tighter alcohol supply and carriage restrictions followed in 2008 following indications of reductions in violence and injury. Despite the plans being in place for over a decade, no comprehensive independent review has assessed to what level the designed aims were achieved and what effect the plans have had on Indigenous community residents and service providers. This study will describe the long-term impacts on important health, economic and social outcomes of Queensland’s AMPs. Methods/Design The project has two main studies, 1) outcome evaluation using de-identified epidemiological data on injury, violence and other health and social indicators for across Queensland, including de-identified databases compiled from relevant routinely-available administrative data sets, and 2) a process evaluation to map the nature, timing and content of intervention components targeting alcohol. Process evaluation will also be used to assess the fidelity with which the designed intervention components have been implemented, their uptake and community responses to them and their perceived impacts on alcohol supply and consumption, injury, violence and community health. Interviews and focus groups with Indigenous residents and service providers will be used. The study will be conducted in all 24 of Queensland’s Indigenous communities affected by alcohol management plans. Discussion This evaluation will report on the impacts of the original aims for AMPs, what impact they have had on Indigenous residents and service providers. A central outcome will be the establishment of relevant databases describing the parameters of the changes seen. This will permit comprehensive and rigorous surveillance systems to be put in place and provided to communities empowering them with the best credible evidence to judge future policy and program requirements for themselves. The project will inform impending alcohol policy and program adjustments in Queensland and other Australian jurisdictions. The project has been approved by the James Cook University Human Research Ethics Committee (approval number H4967 & H5241).

Institutional response and Indigenous experiences of Cyclone Tracy

Early on Christmas morning 1974 Tropical Cyclone Tracy, a Category 4 storm, devastated the Northern Territory city of Darwin leaving only 6% of the city’s housing habitable. The extent of the disaster was largely the result of unregulated and poorly constructed buildings, predominantly housing. While the engineering and reconstruction process demonstrated a very successful response and adaptation to an existing and future risk, the impact of the cyclone of the local community and its Indigenous population in particular, had not been well recorded. NCCARF therefore commissioned a report on the Indigenous experience of Cyclone Tracy to document how Indigenous people were impacted by, responded to, and recovered from Cyclone Tracy in comparison to non-Indigenous groups. The report also considers the research literature on disasters and Indigenous people in the Northern Territory, with a specific focus on cyclones, and considers the socio-political context of Indigenous communities in Darwin prior to Cyclone Tracy.

Evaluations of BIM : frameworks and perspectives

This paper examines the evaluation of BIM-enabled projects. It provides a critical review of the three main areas of measurement, namely technology, organization/people and process. Using two documented case studies of BIM implementation, the paper illustrates the benefits realized by project owners and contractors, and illustrates a lack of attention relative to contextual factors affecting the adoption and deployment of BIM. The paper has three main contributions. First, it identifies and discusses the lack of and difficulty surrounding standardized assessment methods for evaluating BIM-enabled projects. Second, it proposes a conceptual model that includes contextual attributes and demonstrates how the proposed framework reaches beyond simple evaluation to encompass the documentation of BIM’s benefits, lessons learned, challenges and adopted solutions. Third, it shows how the framework can account for existing business processes, organizational process assets, and enterprise level factors. The paper aims to provide a conceptual basis for evaluation and a starting point for benchmarking.

The Queensland Indigenous alcohol diversion program : a health agency’s journey

Drug and alcohol diversion programs provide offenders with the opportunity to divert from the criminal justice or child safety systems, and enter into treatment to address their illicit drug or alcohol use. However, low participation by Indigenous Australians in diversion programs has been recognised as an issue, with Indigenous Australians being much less likely to be diverted into treatment (NIDAC 2009: 9). QIADP represents a unique opportunity to improve Indigenous access to diversion programs. QIADP is an Indigenous-specific alcohol diversion program in its final, third year as a pilot, with the evaluation due December 2009. Many lessons have been learnt by Queensland Health as to what works and doesn’t work in the provision of alcohol-related treatment with this population, including how partnerships with other governmental departments and NGOs can enhance the quality of treatment and ways to build clinical cultural competence in the workforce and programmatic system. This presentation shares the practical lessons QH has learnt in delivering alcohol treatment within an Indigenous-specific diversion program. This includes solutions that others may find useful for application elsewhere, such as the holistic range of treatment options found helpful, and the relationship issues to work through to support a partnership response.

miR-126 in human cancers : clinical roles and current perspectives

miR-126 has been implicated in the processes of inflammation and angiogenesis. Through these processes, miR-126 is implicated in cancer biology, but its role there has not been well reviewed. The aim of this review is to examine the molecular mechanisms and clinicopathological significance of miR-126 in human cancers. miR-126 was shown to have roles in cancers of the gastrointestinal tract, genital tracts, breast, thyroid, lung and some other cancers. Its expression was suppressed in most of the cancers studied. The molecular mechanisms that are known to cause aberrant expression of miR-126 include alterations in gene sequence, epigenetic modification and alteration of dicer abundance. miR-126 can inhibit progression of some cancers via negative control of proliferation, migration, invasion, and cell survival. In some instances, however, miR-126 supports cancer progression via promotion of blood vessel formation. Downregulation of miR-126 induces cancer cell proliferation, migration, and invasion via targeting specific oncogenes. Also, reduced levels of miR-126 are a significant predictor of poor survival of patients in many cancers. In addition, miR-126 can alter a multitude of cellular mechanisms in cancer pathogenesis via suppressing gene translation of numerous validated targets such as PI3K, KRAS, EGFL7, CRK, ADAM9, HOXA9, IRS-1, SOX-2, SLC7A5 and VEGF. To conclude, miR-126 is commonly down-regulated in cancer, most likely due to its ability to inhibit cancer cell growth, adhesion, migration, and invasion through suppressing a range of important gene targets. Understanding these mechanisms by which miR-126 is involved with cancer pathogenesis will be useful in the development of therapeutic targets for the management of patients with cancer.

The Politics of Urban Cultural Policy : Global Perspectives

The Politics of Urban Cultural Policy brings together a range of international experts to critically analyze the ways that governmental actors and non-governmental entities attempt to influence the production and implementation of urban policies directed at the arts, culture, and creative activity. Presenting a global set of case studies that span five continents and 22 cities, the essays in this book advance our understanding of how the dynamic interplay between economic and political context, institutional arrangements, and social networks affect urban cultural policy-making and the ways that these policies impact urban development and influence urban governance. The volume comparatively studies urban cultural policy-making in a diverse set of contexts, analyzes the positive and negative outcomes of policy for different constituencies, and identifies the most effective policy directions, emerging political challenges, and most promising opportunities for building effective cultural policy coalitions. The volume provides a comprehensive and in-depth engagement with the political process of urban cultural policy and urban development studies around the world. It will be of interest to students and researchers interested in urban planning, urban studies and cultural studies.

Celebrating and sustaining Indigenous knowledges through higher education

In its intervention at the 10th session of the United Nations Permanent Forum on Indigenous Issues 2010, the World Indigenous Network Higher Education Consortium (WINHEC) acknowledged that despite a history of protracted but limited attempts by Governments globally to address the low participation and graduation rates of Indigenous peoples from higher education at post graduate level, this continues to be an area of considerable concern. This paper speaks to the development of an innovative academic process that profiles the ground breaking work of WINHEC and a cohort of Indigenous academics in developing academic programs designed to address this systemic failure. The concept of these programs was endorsed in 2006 at a WINHEC conference where Indigenous representatives from across the world met to discuss in part, historical and contempory impediments to Indigenous success within higher education. The goal of WINHEC has been to develop a nested suite of inventive postgraduate awards founded within the scholarship of Indigenous Knowledge which encapsulates an epistemological approach. This has been a ground breaking process that has included collaborative and intellectual contributions of Indigenous academics from diverse cultural nations across the globe and, in particular, Australia. In 2012 the culmination of this dream and the suite of courses developed, honours and embrace the uniqueness of Indigenous Knowledge and the cultural integrity of Indigenous Leadership.

Celebrating and sustaining Indigenous knowledges through research

This paper reports on the growth of research within the World Indigenous Nations Higher Education Consortium (WINHEC). The focus is the research and later, research and journal working group. The intent is to discuss the publication of the WINHEC Journal, discussion papers and other activities such as the development of the Research Standards while analysing the underpinning imperatives to such work. The paper will also examine the complexity of progressing research, founded in local knowledge, aligned internationally to broader conceptions of Indigenous knowledge. The suggestion underlying this paper is that if research is undertaken from a position of Indigenous knowledge and epistemology, it will celebrate and sustain Indigenous people.

Indigenous epistemology : creating an international Indigenous higher education space in the wake of the western “university of excellence”

Interest in the participation of Indigenous peoples in higher education has, in recent times, gained momentum with an increasing number of advocates challenging the global history of culturally inept policies and practices imposed within the western higher education system. To address the challenges being presented by Indigenous communities and other groups (often relegated under the banner of disadvantaged or equity) Western Universities are promoting a shift toward inclusive policies and practices. Frustrated with the offerings of the Western Higher Education system, a global movement of Indigenous academics, Elders and knowledge holders are developing strategies to meet the educational needs of their own communities, in order to find a way forward. The mobilization of Elders and Indigenous academics has resulted in the development of a global higher education network which is proving to be a significant force in changing the position of Indigenous participation in higher education. The World Indigenous Network Higher Education Consortium (WINHEC) has presented a significant challenge to those barriers within the western higher education system that has historically demonstrated an inability to develop culturally inclusive practices within their institutions. This paper examines the development of a world Indigenous higher education movement and its contribution to the history of the “university” within the context of western higher education institutions. Outlined in this examination will be a synopsis of the development of the “University of Excellence” and the creation of an international Indigenous space within higher education.

Signet-ring cell carcinoma of colorectum : current perspectives and molecular biology

PURPOSE Colorectal signet-ring cell carcinoma (SRCC) is rare, and very little detailed information on the molecular biology of the disease is available. METHODS The literature on the clinical, pathological and, in particular, the molecular biology of this rare entity was critically reviewed. The reviewed articles take into account a total of 1,817 cases of SRCC, but only 143 cases have molecular data available. The characteristics of two patients with colorectal SRCC were also discussed. RESULTS Colorectal SRCC mostly occurs in younger patients, is larger and has different site predilection compared with conventional colorectal adenocarcinoma. It can occur as one of the synchronous cancers in the colorectum. The cancer is usually diagnosed at advanced stages because of the late manifestation of symptoms, and aggressive treatment strategy is required. Limited reports in the literature have shown that the variant of colorectal cancer demonstrated a different pattern of genetic alterations of common growth kinase-related oncogenes (K-ras, BRAF), tumour suppressor genes (p53, p16), gene methylation and cell adhesion-related genes related to the Wingless signalling pathway (E-cadherin and beta-catenin) from conventional colorectal adenocarcinoma. Colorectal SRCC also showed high expression of mucin-related genes and genes related to the gastrointestinal system. There was also a higher prevalence of microsatellite instability-high tumours and low Cox-2 expression in colorectal SRCC as opposed to conventional adenocarcinoma. CONCLUSIONS Colorectal SRCC has unique molecular pathological features. The unique molecular profiles in SRCC may provide molecular-based improvements to patient management in colorectal SRCC.

Research in Early Childhood Education for Sustainability : International Perspectives and Provocations

Sustainability is a global issue that urgently needs addressing, the most serious consequences of which concern children and future generations. This insightful research text tackles one of the most significant contemporary issues of our times – the nexus between society and environment – and how early childhood education can contribute to sustainable living. By offering international and multidisciplinary research perspectives on Early Childhood Education for Sustainability, each chapter explores and investigates the complex topic of sustainability and its relationship to early childhood education. A particular emphasis that runs through this text is young children as empowered citizens, capable of both contributing to and creating change for sustainability. The chapter authors work from, or are aligned with, a transformative education paradigm that suggests the socio-constructivist frameworks currently underpinning Early Childhood Education require reframing in light of the social transformations necessary to address humanity’s unsustainable, unjust and unhealthy living patterns. This research text is designed to be provocative and challenging; in so doing it seeks to encourage exploration of current understandings about Early Childhood Education for Sustainability, offers new dimensions for more deeply informed practice, and proposes avenues for further research in this field.

Information Experience : New Perspectives and Research Directions

In this closing chapter the editors review key themes that have emerged through the book. We recognize the varied and dynamic nature of information experience across multiple contexts, and present our own conceptualization of information experience. Finally, we consider possible future directions for information experience research.

Information Experience : Contemporary Perspectives

The purpose of this book is to open a conversation on the idea of information experience, which we understand to be a complex, multidimensional engagement with information. In developing the book we invited colleagues to propose a chapter on any aspect of information experience, for example conceptual, methodological or empirical. We invited them to express their interpretation of information experience, to contribute to the development of this concept. The book has thus become a vehicle for interested researchers and practitioners to explore their thinking around information experience, including relationships between information experience, learning experience, user experience and similar constructs. It represents a collective awareness of information experience in contemporary research and practice. Through this sharing of multiple perspectives, our insights into possible ways of interpreting information experience, and its relationship to other concepts in information research and practice, is enhanced. In this chapter, we introduce the idea of information experience. We also outline the book and its chapters, and bring together some emerging alternative views and approaches to this important idea.

Writing Indigenous vampires: Aboriginal gothic or Aboriginal fantastic?

The usual postmodern suspicions about diligently deciphering authorial intent or stridently seeking fixed meaning/s and/or binary distinctions in an artistic work aside, this self-indulgent essay pushes the boundaries regarding normative academic research, for it focusses on my own (minimally celebrated) published creative writing’s status as a literary innovation. Dedicated to illuminating some of the less common denominators at play in Australian horror, my paper recalls the creative writing process involved when I set upon the (arrogant?) goal of creating a new genre of creative writing: that of the ‘Aboriginal Fantastic’. I compare my work to the literary output of a small but significant group (2.5% of the population), of which I am a member: Aboriginal Australians. I narrow my focus even further by examining that creative writing known as Aboriginal horror. And I reduce the sample size of my study to an exceptionally small number by restricting my view to one type of Aboriginal horror literature only: the Aboriginal vampire novel, a genre to which I have contributed professionally with the 2011 paperback and 2012 e-book publication of That Blackfella Bloodsucka Dance! However, as this paper hopefully demonstrates, and despite what may be interpreted by some cynical commentators as the faux sincerity of my taxonomic fervour, Aboriginal horror is a genre noteworthy for its instability and worthy of further academic interrogation. (first paragraph)