The identification of therapeutic targets in metastatic melanoma

Metastatic melanoma, a cancer historically refractory to chemotherapeutic strategies, has a poor prognosis and accounts for the majority of skin cancer related mortality. Although the recent approval of two new drugs combating this disease, Ipilimumab and Vemurafenib (PLX4032), has demonstrated for the first time in decades an improvement in overall survival; the clinical efficacy of these drugs has been marred by severe adverse immune reactions and acquired drug resistance in patients, respectively. Thus, understanding the etiology of metastatic melanoma will contribute to the improvement of current therapeutic strategies while leading to the development of novel drug approaches. In order to identify recurrently mutated genes of therapeutic relevance in metastatic melanoma, a panel of stage III local lymph node melanomas were extensively characterised using high-throughput genomic technologies. This led to the identification of mutations in TFG in 5% of melanomas from a candidate gene sequencing approach using SNP array analysis, 24% of melanomas with mutations in MAP3K5 or MAP3K9 though unbiased whole-exome sequencing strategies, and inactivating mutations in NF1 in BRAF/NRAS wild type tumours though pathway analysis. Lastly, this thesis describes the development of a melanoma specific mutation panel that can rapidly identify clinically relevant mutation profiles that could guide effective treatment strategies through a personalised therapeutic approach. These findings are discussed in respect to a number of important issues raised by this study including the current limitation of next-generation sequencing technology, the difficulty in identifying ‘driver’ mutations critical to the development of melanoma due to high carcinogenic exposure by UV radiation, and the ultimate application of mutation screening in a personalised therapeutic setting. In summary, a number novel genes involved in metastatic melanoma have been identified that may have relevance for current therapeutic strategies in treating this disease.

Navigating in a sea of change : second set of working papers of the higher education policy project

This volume represents teh second collection of working papers and articles by participants in the Higher Education Policy Project (HEPP), a project funded by the Australian Research Council and based in the Graduate School of Education at the University of Queensland. The first volume, 'Higher Education in Transition: Working Papers of the Higher Education Policy Project (Bella, McCollow and Knight, 1993), took the broad theme of "higher education in transition" in order to introduce readers the HEPP and give them some idea of the breadth of the research being pursued by the HEPP research team itself and by the cohort of post-graduate students also associated with the project. Since then, higher education has remained in transition. Stubborn and resurgent questions continue: such as what a university ought to be, what forms of research should be supported in a mass system, and how institutional accountability can be demonstrated. In differing ways and using a variety of research perspectives and methodologies, the contributors to this volume explore these and other questions of relevance to higher education today.

Blogs, Twitter, and breaking news : the produsage of citizen journalism

Debates over the role and relevance of what has been described as citizen journalism have existed at least since the late 1990s; positions have ranged from the fulsome dismissal of such bottom-up journalism activities (and indeed, almost all user-led content creation) as being part of a new "cult ofthe amateur" (Keen, 2007) to nearly equally simplistic perspectives which predicted citizen journalists would replace the mainstream journalism industry within a short timeframe. A more considered, more realistic perspective would take a somewhat more moderate view. Aided by circumstances including the long-term financial crisis enveloping journalism industries in many developed nations, the creeping corporatization and politicization of journalistic activities in democratic and non-democratic countries alike, and the largely unmet challenge of new, Internet-based media fonns, citizen journalism (as well as other parajournalistic media, including TV comedy such as The Daily Show) has been able to make credible inroads into what used to be the domain of journalism proper.

Serious playground : using Second Life to engage high school students in urban planning

Virtual world platforms such as Second Life have been successfully used in educational contexts to motivate and engage learners. This article reports on an exploratory workshop involving a group of high school students using Second Life for an urban planning project. Young people are traditionally an under-represented demographic when it comes to participating in urban planning and decision making processes. The research team developed activities that combined technology with a constructivist approach to learning. Real world experiences and purposes ensured that the workshop enabled students to see the relevance of their learning. Our design also ensured that play remained an important part of the learning. By conceiving of the workshop as a ‘serious playground’ we investigated the ludic potential of learning in a virtual world.

Reading images : the book club in the art gallery

This paper seeks to document and understand one instance of community-university engagement: that of an on-going book club organised in conjunction with public art exhibitions. The curator of the Queensland University of Technology (QUT) Art Museum invited the authors, three postgraduate research students in the faculty of Creative Writing and Literary Studies at QUT, to facilitate an informal book club. The purpose of the book club was to generate discussion, through engagement with fiction, around the themes and ideas explored in the Art Museum’s exhibitions. For example, during the William Robinson exhibition, which presented evocative images of the environment around Brisbane, Queensland, the book club explored texts that symbolically represented aspects of the Australian landscape in a variety of modes and guises. This paper emerges as a result of the authors’ observations during, and reflections on, their experiences facilitating the book club. It responds to the research question, how can we create a best practice model to engage readers through open-ended, reciprocal discussion of fiction, while at the same time encouraging interactions in the gallery space? To provide an overview of reading practices in book clubs, we rely on Jenny Hartley’s seminal text on the subject, The Reading Groups Book (2002). Although the book club was open to all members of the community, the participants were generally women. Elizabeth Long, in Book Clubs: Woman and the Uses of Reading in the Everyday (2003), offers a comprehensive account of women’s interactions as they engage in a reading community. Long (2003, 2) observes that an image of the solitary reader governs our understanding of reading. Long challenges this notion, arguing that reading is profoundly social (ibid), and, as women read and talk in book clubs, ‘they are supporting each other in a collective working-out of their relationship to a particular historical movement and the particular social conditions that characterise it’ (Long 2003, 22). Despite the book club’s capacity to act as a forum for analytical discussion, DeNel Rehberg Sedo (2010, 2) argues that there are barriers to interaction in such a space, including that members require a level of cultural capital and literacy before they feel comfortable to participate. How then can we seek to make book clubs more inclusive, and encourage readers to discuss and question outside of their comfort zone? How can we support interactions with texts and images? In this paper, we draw on pragmatic and self-reflective practice methods to document and evaluate the development of the book club model designed to facilitate engagement. We discuss how we selected texts, negotiating the dual needs of relevance to the exhibition and engagement with, and appeal to, the community. We reflect on developing questions and material prior to the book club to encourage interaction, and describe how we developed a flexible approach to question-asking and facilitating discussion. We conclude by reflecting on the outcomes of and improvements to the model.

Collaborative efforts to enhance power engineering education in Australia

A review of the issues for supporting learning of power engineering in Australia is presented in this paper. The learning needs of students and the support available in blended learning and through distance educations are explored in this review. Specific software tools to assist the learning environment are appraised and the relevance for the next generation of power engineers assessed.

Introduction : creative industries and cities

The 2000s were marked by a resurgence of interest in creativity and cities. If the rapid global proliferation of the Internet and digital media technologies in the 1990s had set off enthusiasm for a post-industrial ‘new economy’, where the significance of location would be in decline, the 2000s saw an energetic search by artists, entrepreneurs, investors, policy-makers, journalists and many others to uncover the well-springs of creativity and its relationship to place (Flew 2012a). This chapter begins with a discussion of the discourses or ‘scripts’ that have emerged to try and conceptualise the relationship between creativity and cities, notably theories of creative clusters, creative cities and creative class theories. Such work can be seen as representing a growth in the field of cultural economic geography although – as is noted in the chapter – it possesses some significant gaps. Among the issues that are drawn out in this book, and discussed in this chapter, are: the need to move beyond ‘imagined geographies’ of creative inner cities and come to terms with empirical evidence that suggests significant concentrations of the creative workforce in suburbs and regional cities; the relevance of urban cultural policy as a variable in the rise of cities as creative hubs or, in a different model, media capitals; and the challenges of bringing together cultural research with economic discourses in ways that get beyond caricatured representations of the ‘other’, as found, for instance, in some of the most influential framings of the concept of neo-liberalism.

Examination of socio-demographics and job satisfaction in Australian registered nurses

Aims and Objectives To examine relationships between socio-demographic factors and job satisfaction and to identify if these factors predict job satisfaction levels in an Australian registered nurses. Background Reports indicate that in Australia there are 30,000 qualified nurses no longer working in the healthcare and that current nursing shortages vary as a result of certain socio-demographic variables including type of nurse, geographic, location, sector, service and organisation. Furthermore it has been revealed that there is not only a real shortage but also a pseudo-shortage (i.e. either there are not enough nurses are available, or not enough are willing to work under existing workplace conditions). International studies have found significant relationships exist between some socio-demographic factors and job satisfaction in registered nurses however there is limited information available on relationships between socio-demographic factors and job satisfaction in nurses in the Australian context. Design A cross sectional survey was undertaken of Australian registered nurses. Methods Two thousand Australian registered nurses who were members of an industrial and professional organisation were sent the questionnaire in 2008. They were stratified and randomised according to gender. Six hundred and thirty-nine registered nurses responded. Descriptive analyses, correlation analyses, one- way ANOVA tests, simple linear regression and multivariable analyses were conducted to examine further if any relationships existed between the variables. Results The majority of respondents showed positive job satisfaction scores. An ANOVA found significant positive relationships existed between job satisfaction, specialty area, health sector and Australian states. Multivariable analyses found relationships existed between specialty area, health sector, and job satisfaction. Conclusions The variables specialty area and health sector were found to be significantly associated with job satisfaction. The different specialty areas and health sectors in relation to job satisfaction should be investigated further. Clinical Relevance The study results have provided new knowledge for policy makers, organisational and nursing leaders of the socio-demographic variables that may affect job satisfaction in registered nurses in the Australian context.

Tourist use of mopeds in Queensland

Tourist use of mopeds in Queensland is encouraged by licensing regulations permitting moped riding for car licence holders, who may lack prior knowledge or experience of moped or motorcycle use. Using official crash and registration data, this research examines moped use by tourists, identified as crash-involved riders holding an interstate or overseas licence. Tourists were more likely to be younger, female, in single vehicle crashes, and deemed at fault than Queensland licence holders. Potential safety issues include poor riding skills, inexperience, inattention and lack of protective clothing. Moped rental companies play an important role in managing client crash and injury risks. These risks could also be reduced through introduction of more stringent licensing requirements, though this may be detrimental to moped rental companies as well as to tourist mobility and enjoyment. The discussion considers the relevance of adventure tourism perspectives and theory to the use of mopeds by tourists.

Types of foot problems seen by Australian podiatrists

Background: Understanding frequency of foot problems can assist health care planners with resource deployment to new and emerging services such as paediatric podiatry and focus future research on the most salient foot conditions. Methods: A review of 2187 patient consultations during a three month period was conducted. Patient medical and podiatric history was coded using industry standards. All patients were recruited for convenience from a metropolitan university podiatry clinic. Results: 392 new patients were identified with mean age 40.6 years old (range 1–95), with 65% being female. Arthritic diseases, asthma, hypertension and allergies were the most common medical conditions reported. The frequency of new consultations in younger people (n = 102; 27%) exceeded those of the elderly (n = 75; 20%). Conversely, the elderly were nearly three times more prevalent in this cohort (n = 910; 43%) compared to younger people (n = 332; 16%). Conclusion: This study illustrates the diverse nature of pathology seen by podiatrists. Knowledge that skin lesions are highly prevalent is of relevance to health departments, given the aging nature of most populations. Moreover there appears to be a growing trend in the number of young people who present for care, however government funded access to these services are limited.

Is simulation training effective in increasing podiatrists' confidence in foot ulcer management?

Background: Foot ulcers are a frequent reason for diabetes-related hospitalisation. Clinical training is known to have a beneficial impact on foot ulcer outcomes. Clinical training using simulation techniques has rarely been used in the management of diabetes-related foot complications or chronic wounds. Simulation can be defined as a device or environment that attempts to replicate the real world. The few non-web-based foot-related simulation courses have focused solely on training for a single skill or “part task” (for example, practicing ingrown toenail procedures on models). This pilot study aimed to primarily investigate the effect of a training program using multiple methods of simulation on participants’ clinical confidence in the management of foot ulcers. Methods: Sixteen podiatrists participated in a two-day Foot Ulcer Simulation Training (FUST) course. The course included pre-requisite web-based learning modules, practicing individual foot ulcer management part tasks (for example, debriding a model foot ulcer), and participating in replicated clinical consultation scenarios (for example, treating a standardised patient (actor) with a model foot ulcer). The primary outcome measure of the course was participants’ pre- and post completion of confidence surveys, using a five-point Likert scale (1 = Unacceptable-5 = Proficient). Participants’ knowledge, satisfaction and their perception of the relevance and fidelity (realism) of a range of course elements were also investigated. Parametric statistics were used to analyse the data. Pearson’s r was used for correlation, ANOVA for testing the differences between groups, and a paired-sample t-test to determine the significance between pre- and post-workshop scores. A minimum significance level of p < 0.05 was used. Results: An overall 42% improvement in clinical confidence was observed following completion of FUST (mean scores 3.10 compared to 4.40, p < 0.05). The lack of an overall significant change in knowledge scores reflected the participant populations’ high baseline knowledge and pre-requisite completion of web-based modules. Satisfaction, relevance and fidelity of all course elements were rated highly. Conclusions: This pilot study suggests simulation training programs can improve participants’ clinical confidence in the management of foot ulcers. The approach has the potential to enhance clinical training in diabetes-related foot complications and chronic wounds in general.

Mastering medical terminology : Australia and New Zealand

Mastering Medical Terminology: Australia and New Zealand is medical terminology book of relevance to an audience in Australia and New Zealand. Australian terminology, perspectives, examples and spelling have been included and Australian pronunciation specified. The textbook is accompanied by a self-help workbook, an online workbook and a Smartphone app. Throughout Mastering Medical Terminology, review of medical terminology as it is used in clinical practice is highlighted. Features of the textbook, workbook and electronic product include: • Simple, non-technical explanations of medical terms • Workbook format with ample spaces to write answers • Explanations of clinical procedures, laboratory tests and abbreviations used in Australian clinical practice, as they apply to each body system and speciality area • Pronunciation of terms and spaces to write meanings of terms • Practical applications sections • Exercises that test understanding of terminology as students work through the text chapter by chapter • Review activities that pull together terminology to help students study • Comprehensive glossary and appendices for reference • Links to other useful references, such as websites and textbooks.

The development of a supportive care needs assessment tool for Indigenous people with cancer

Background: Little is known about the supportive care needs of Indigenous people with cancer and to date, existing needs assessment tools have not considered cultural issues for this population. We aimed to adapt an existing supportive care needs assessment tool for use with Indigenous Australians with cancer. Methods: Face-to-face interviews with Indigenous cancer patients (n = 29) and five focus groups with Indigenous key-informants (n = 23) were conducted to assess the face and content validity, cultural acceptability, utility and relevance of the Supportive Care Needs Survey - Short Form 34 (SCNS-SF34) for use with Indigenous patients with cancer. Results: All items from the SCNS-SF34 were shortened and changed to use more appropriate language (e.g. the word 'anxiety' was substituted with 'worry'). Seven questions were omitted (e.g. items on death and future considerations) as they were deemed culturally inappropriate or irrelevant and 12 items were added (e.g. accessible transport). Optional instructions were added before the sexual items. The design and response format of the SCNS-SF34 was modified to make it easier to use for Indigenous cancer patients. Given the extensive modifications to the SCNS-SF34 and the liklihood of a different factor structure we consider this tool to be a new tool rather than a modification. The Supportive care needs assessment tool for Indigenous people (SCNAT-IP) shows promising face and content validity and will be useful in informing services where they need to direct their attention for these patients. Conclusions: Indigenous people with cancer have language, customs and specific needs that are not accommodated within the standard SCNS-SF34. Our SCNAT-IP improves acceptability, relevance and face validity for Indigenous-specific concerns. Our SCNAT-IP will allow screening for supportive care needs that are specific to Indigenous cancer patients' and greatly inform targeted policy development and practice.

Deriving a preference-based measure for cancer using the EORTC QLQ-C30 : a confirmatory versus exploratory approach

Background: To derive preference-based measures from various condition-specific descriptive health-related quality of life (HRQOL) measures. A general 2-stage method is evolved: 1) an item from each domain of the HRQOL measure is selected to form a health state classification system (HSCS); 2) a sample of health states is valued and an algorithm derived for estimating the utility of all possible health states. The aim of this analysis was to determine whether confirmatory or exploratory factor analysis (CFA, EFA) should be used to derive a cancer-specific utility measure from the EORTC QLQ-C30. Methods: Data were collected with the QLQ-C30v3 from 356 patients receiving palliative radiotherapy for recurrent or metastatic cancer (various primary sites). The dimensional structure of the QLQ-C30 was tested with EFA and CFA, the latter based on a conceptual model (the established domain structure of the QLQ-C30: physical, role, emotional, social and cognitive functioning, plus several symptoms) and clinical considerations (views of both patients and clinicians about issues relevant to HRQOL in cancer). The dimensions determined by each method were then subjected to item response theory, including Rasch analysis. Results: CFA results generally supported the proposed conceptual model, with residual correlations requiring only minor adjustments (namely, introduction of two cross-loadings) to improve model fit (increment χ2(2) = 77.78, p < .001). Although EFA revealed a structure similar to the CFA, some items had loadings that were difficult to interpret. Further assessment of dimensionality with Rasch analysis aligned the EFA dimensions more closely with the CFA dimensions. Three items exhibited floor effects (>75% observation at lowest score), 6 exhibited misfit to the Rasch model (fit residual > 2.5), none exhibited disordered item response thresholds, 4 exhibited DIF by gender or cancer site. Upon inspection of the remaining items, three were considered relatively less clinically important than the remaining nine. Conclusions: CFA appears more appropriate than EFA, given the well-established structure of the QLQ-C30 and its clinical relevance. Further, the confirmatory approach produced more interpretable results than the exploratory approach. Other aspects of the general method remain largely the same. The revised method will be applied to a large number of data sets as part of the international and interdisciplinary project to develop a multi-attribute utility instrument for cancer (MAUCa).

Pairwise similarity of TopSig document signatures

This paper analyses the pairwise distances of signatures produced by the TopSig retrieval model on two document collections. The distribution of the distances are compared to purely random signatures. It explains why TopSig is only competitive with state of the art retrieval models at early precision. Only the local neighbourhood of the signatures is interpretable. We suggest this is a common property of vector space models.