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.

Waterfall : Nature and Culture

Many people take pleasure in visiting waterfalls and much has been written on the subject. Numerous accounts of Niagara Falls were published after Hennepin's late seventeenth-centure descriptions, particularly from the early nineteenth century, but is was only later that other waterfalls became the subject of books. George Holley's Niagara and Other Famous Cataracts of the World, published in 1883, and John Gibson's Great Waterfalls, Cataracts and Geysers, published in 1887, are early examples of global accounts of major falls. Most books about waterfalls are guides to the falls of a particular country, state or region. Apart from a few slim illustrated volumes, few books have been puslished on the world's waterfalls since Edward Rashleigh's Among the Waterfalls (1935). Most of these are slim pictorial volumes, some aimed at the children's market. Geologist Richard Maxwell Pearl published a series of waterfall articles in his journal Earth Science between 1973 and 1975, apparently with the intention of turning them into a book, but this never materialized. My book, the culmination of more than a decade of waterfalls research, is comprehensive in its approach, but is not intended to describe as many of the world's waterfalls as possible. This is far from my aim, and readers may be disappointed at my omission of falls they feel deserved mention. What I have attempted to do is celebrate the delights of these beautiful wonders of nature by considering them from many points of view, emphasizing the roles that they play in the human experience. To be as representative as possible, I draw on examples of waterfalls from all over the world, some famous, many not. North and South America, Europe, Africa, Asia and Oceania and, with recent global warming, the Earth's polar regions, all feature in the discussion. Even though there are already enough books and articles about Niagara Falls to fill a large library, it has been impossible to avoid making frequent reference to this great cataract, which has been so important in the history of travel and tourism, power generation, urban development and art. Amoung the issues that I consider is the human impact on waterfalls, particularly the effects of hydropower schemes and tourism development. Also considered are artificial waterfalls, which have long been features of the designed landscape. Their contemporay role is poignantly exemplified in the design of the National September 11 Memorial, in which the footprints of the Twin Towers are traced by walls of waterfalls. A geographer and urban and regional planner by training, I have ventured into many other fields of knowledge that are outside my areas of expertise. I apologize for any errors that I may have made in my book and invite correction.

Journalists and Twitter : how Australian news organisations adapt to a new medium

Twitter has developed an increasingly visible presence in Australian journalism, and in the discussion of news. Many journalists have begun to explore manageable approaches to incorporating Twitter into their work practices, and for some – like the ABC’s ‘star recruits’ Annabel Crabb and Latika Bourke – it has already become a career driver. This article examines the positioning of journalists as ‘personal brands’ on Twitter, by documenting the visibility of leading personal and institutional accounts during two major political events in Australia: the Rudd/Gillard leadership spill on 23 June 2010, and the day of the subsequent federal election on 21 August 2010. It highlights the fact that in third-party networks such as Twitter, journalists and news organisations no longer operate solely on their own terms, as they do on their own Websites, but gain and maintain prominence in the network and reach for their messages only in concert with other users. It places these observations in a wider context of journalist/audience relations, a decade after the emergence of the first citizen journalism Websites.

Factors influencing health behaviours of younger women after menopause-inducing cancer treatment

Objective To investigate the health promotion and risk reduction behaviors of younger women previously treated for cancer. Design and Sample Guided by the Precede-Proceed framework, a mixed-method descriptive investigation of the health behaviors of younger women with cancer treatment-induced menopause in one health jurisdiction in Australia was undertaken. Measures This article reports the results of the qualitative interview component of the study. Results Of the 85 women who responded to surveys that quantified their health behaviors, 22 consented to interviews that explored how and why these behaviors might occur. Conclusions Several predisposing, enabling and reinforcing factors that influenced participants will or ability to engage with health-promoting behaviors after cancer treatment were identified in the interviews. These include entrenched precancer diagnosis health behaviors, the disabilities resulting from cancer treatments, perceptions of risk, focused intervention by health professionals and the nature of participants social support. The results indicate a need for flexibility when planning public health initiatives to prepare this cohort for a healthy life after cancer, which accounts for their developmental, knowledge and posttreatment needs.

The benefits of tree-based models for stock selection

The identification of the primary drivers of stock returns has been of great interest to both financial practitioners and academics alike for many decades. Influenced by classical financial theories such as the CAPM (Sharp, 1964; Lintner, 1965) and APT (Ross, 1976), a linear relationship is conventionally assumed between company characteristics as derived from their financial accounts and forward returns. Whilst this assumption may be a fair approximation to the underlying structural relationship, it is often adopted for the purpose of convenience. It is actually quite rare that the assumptions of distributional normality and a linear relationship are explicitly assessed in advance even though this information would help to inform the appropriate choice of modelling technique. Non-linear models have nevertheless been applied successfully to the task of stock selection in the past (Sorensen et al, 2000). However, their take-up by the investment community has been limited despite the fact that researchers in other fields have found them to be a useful way to express knowledge and aid decision-making...

A dual-scale modelling approach for drying hygroscopic porous media

A new dualscale modelling approach is presented for simulating the drying of a wet hygroscopic porous material that couples the porous medium (macroscale) with the underlying pore structure (microscale). The proposed model is applied to the convective drying of wood at low temperatures and is valid in the so-called hygroscopic range, where hygroscopically held liquid water is present in the solid phase and water exits only as vapour in the pores. Coupling between scales is achieved by imposing the macroscopic gradients of moisture content and temperature on the microscopic field using suitably-defined periodic boundary conditions, which allows the macroscopic mass and thermal fluxes to be defined as averages of the microscopic fluxes over the unit cell. This novel formulation accounts for the intricate coupling of heat and mass transfer at the microscopic scale but reduces to a classical homogenisation approach if a linear relationship is assumed between the microscopic gradient and flux. Simulation results for a sample of spruce wood highlight the potential and flexibility of the new dual-scale approach. In particular, for a given unit cell configuration it is not necessary to propose the form of the macroscopic fluxes prior to the simulations because these are determined as a direct result of the dual-scale formulation.

Et tu, George? Campaign journalism and the politics of compromise

There is a category of film about journalism in which journalism is not the star, but the supporting player, and journalists not the protagonists but the Greek chorus, commenting on and also changing the realities they report. In such films the news media are a structuring presence driving the plot, shaping the narrative, constructing what we might think of as a pseudo-reality. Like Daniel Boorstin’s notion of the pseudo-event (introduced in his still-relevant book The Image, 1962), this pseudo-reality is so-named because it would not exist were it not for the demands of the news media’s hunger for stories, and knowledge of the damage they can do with those stories, on the calculations and actions of the key actors. Pseudo-realities form as responses to what political actors think journalists and their organisations need and want, or as efforts to shape journalistic accounts in ways favourable to themselves. Films about politics often feature pseudorealities of this kind, in which the events and actions driving the plot have only a tenuous relationship with important things going on in the everyday world beyond the political arena. Everything we see is about image, perception, appearance.

Using expedited 10g protein counter (EP-10) for meal planning

Precise protein quantification and recommendation is essential in clinical dietetics, particularly in the management of individuals with chronic kidney disease, malnutrition, burns, wounds, pressure ulcers, and those in active sports. The Expedited 10g Protein Counter (EP-10) was developed to simplify the quantification of dietary protein for assessment and recommendation of protein intake.1 Instead of using separate protein exchanges for different food groups to quantify the dietary protein intake of an individual, every exchange in the EP-10 accounts for an exchange each of 3g non-protein-rich food and 7g protein-rich food (Table 1). The EP-10 was recently validated and published in the Journal of Renal Nutrition recently.1 This study demonstrated that using the EP-10 for dietary protein intake quantification had clinically acceptable validity and reliability when compared with the conventional 7g protein exchange while requiring less time.2 In clinical practice, the use of efficient, accurate and practical methods to facilitate assessment and treatment plans is important. The EP-10 can be easily implemented in the nutrition assessment and recommendation for a patient in the clinical setting. This patient education tool was adapted from materials printed in the Journal of Renal Nutrition.1 The tool may be used as presented or adapted to assist patients to achieve their recommended daily protein intake.

“They’re My Two Favourites” versus “The Bigger Scheme of Things” : pro-Am historians remember Australian television

This chapter reports on eleven interviews with Pro-Am archivists of Australian television which aimed to find out how they decide what materials are important enough to archive. Interviewees mostly choose to collect materials in which they have a personal interest. But they are also aware of the relationship between their own favourites and wider accounts of Australian television history, and negotiate between these two positions. Most interviewees acknowledged Australian television’s links with British and American programming, but also felt that Australian television is distinctive. They argued that Australian television history is ignored in a way that isn’t true for the UK or the US. Several also argued that Australian television has had a ‘naïve’ nature that has allowed it to be more experimental.

In the bank or on the ground : an examination of financial reserves in Australian international aid organisations

This study contributes to the understanding of the contribution of financial reserves to sustaining nonprofit organisations. Recognising the limited recent Australian research in the area of nonprofit financial vulnerability, it specifically examines financial reserves held by signatories to the Code of Conduct of the Australian Council for International Development (ACFID) for the years 2006 to 2010. As this period includes the Global Financial Crisis, it presents a unique opportunity to observe the role of savings in a period of heightened financial threats to sustainability. The need for nonprofit entities to maintain reserves, while appearing intuitively evident, is neither unanimously accepted nor supported by established theoretic constructs. Some early frameworks attempt to explain the savings behaviour of nonprofit organisations and its role in organisational sustainability. Where researchers have considered the issue, its treatment has usually been either purely descriptive or alternatively, peripheral to a broader attempt to predict financial vulnerability. Given the importance of nonprofit entities to civil society, the sustainability of these organisations during times of economic contraction, such as the recent Global Financial Crisis, is a significant issue. Widespread failure of nonprofits, or even the perception of failure, will directly affect, not only those individuals who access their public goods and services, but would also have impacts on public confidence in both government and the sectors’ ability to manage and achieve their purpose. This study attempts to ‘shine a light’ on the paradox inherent in considering nonprofit savings. On the one hand, a public prevailing view is that nonprofit organisations should not hoard and indeed, should spend all of their funds on the direct achievement of their purposes. Against this, is the commonsense need for a financial buffer if only to allow for the day to day contingencies of pay rises and cost increases. At the entity level, the extent of reserves accumulated (or not) is an important consideration for Management Boards. The general public are also interested in knowing the level of funds held by nonprofits as a measure of both their commitment to purpose and as an indicator of their effectiveness. There is a need to communicate the level and prevalence of reserve holdings, balancing the prudent hedging of uncertainty against a sense of resource hoarding in the mind of donors. Finally, funders (especially governments) are interested in knowing the appropriate level of reserves to facilitate the ongoing sustainability of the sector. This is particularly so where organisations are involved in the provision of essential public goods and services. At a scholarly level, the study seeks to provide a rationale for this behaviour within the context of appropriate theory. At a practical level, the study seeks to give an indication of the drivers for savings, the actual levels of reserves held within the sector studied, as well as an indication as to whether the presence of reserves did mitigate the effects of financial turmoil during the Global Financial Crisis. The argument is not whether there is a need to ensure sustainability of nonprofits, but rather how it is to be done and whether the holding of reserves (net assets) is an essential element is achieving this. While the study offers no simple answers, it does appear that the organisations studied present as two groups, the ‘savers’ who build reserves and keep ‘money in the bank’ and ‘spender-delivers’ who put their resources ‘on the ground’. To progress an understanding of this dichotomy, the study suggests a need to move from its current approach to one which needs to more closely explore accounts based empirical donor attitude and nonprofit Management Board strategy.

Passenger transmission and productiveness of transit lines with high loads

Deterministic transit capacity analysis applies to planning, design and operational management of urban transit systems. The Transit Capacity and Quality of Service Manual (1) and Vuchic (2, 3) enable transit performance to be quantified and assessed using transit capacity and productive capacity. This paper further defines important productive performance measures of an individual transit service and transit line. Transit work (p-km) captures the transit task performed over distance. Passenger transmission (p-km/h) captures the passenger task delivered by service at speed. Transit productiveness (p-km/h) captures transit work performed over time. These measures are useful to operators in understanding their services’ or systems’ capabilities and passenger quality of service. This paper accounts for variability in utilized demand by passengers along a line and high passenger load conditions where passenger pass-up delay occurs. A hypothetical case study of an individual bus service’s operation demonstrates the usefulness of passenger transmission in comparing existing and growth scenarios. A hypothetical case study of a bus line’s operation during a peak hour window demonstrates the theory’s usefulness in examining the contribution of individual services to line productive performance. Scenarios may be assessed using this theory to benchmark or compare lines and segments, conditions, or consider improvements.

Say goodbye to the fries : graduate careers in media, cultural and communication studies

This article addresses the paucity of systematic data on graduate careers in the arts and humanities in the broader context of enduring public and policy debates about the benefits of education to society, the relation between public and private good that is derivable from education, and the specific disciplinary angle that can be brought to bear on these questions from media, cultural and communication studies. We report findings from a survey of ten years of graduates from Queensland University of Technology’s courses in media, cultural and communication studies which indicate very high employment levels and generally positive accounts of the relevance of courses to working life. A major insight that can be drawn from the research is that media, cultural and communication studies deliver capabilities, skills and orientations which are themselves strongly aligned with the kinds of transferable generic attributes which facilitate transition into the workplace.

How do perceptions of risk associated with driving while fatigued and perceptions of effectiveness of countermeasures effect willingness to engage in fatigue reducing countermeasures?

Sleep-related and fatigue-related driving is an important contributory factor in fatal and serious injury crashes - Accounts for approx 19% - Similar in magnitude to drink driving

'It had to be my choice' Indigenous smoking cessation and negotiations of risk, resistance and resilience

While Australia is considered a world leader in tobacco control, smoking rates within the Aboriginal and Torres Strait Islander population have not declined at the same rate. This failure highlights an obvious shortcoming of mainstream anti-smoking efforts to effectively understand and engage with the socio-cultural context of Indigenous smoking and smoking cessation experiences. The purpose of this article is to explore the narrative accounts of 20 Indigenous ex-smokers within an urban community and determine the motivators and enablers for successful smoking cessation. Our findings indicated that health risk narratives and the associated social stigma produced through anti-smoking campaigns formed part of a broader apparatus of oppression among Indigenous people, often inspiring resistance and resentment rather than compliance. Instead, a significant life event and supportive relationships were the most useful predictors of successful smoking cessation acting as both a motivator and enabler to behavioural change. Indigenous smoking cessation narratives most commonly involved changing and reordering a person’s life and identity and autonomy over this process was the critical building block to reclaiming control over nicotine addiction. Most promisingly, at an individual level, we found the important role that individual health professionals played in encouraging and supporting Indigenous smoking cessation through positive rather than punitive interactions. More broadly, our findings highlighted the central importance of resilience, empowerment, and trust within health promotion practice.

A particle-based micromechanics approach to simulate structural changes of plant cells during drying

This paper is concerned with applying a particle-based approach to simulate the micro-level cellular structural changes of plant cells during drying. The objective of the investigation was to relate the micro-level structural properties such as cell area, diameter and perimeter to the change of moisture content of the cell. Model assumes a simplified cell which consists of two basic components, cell wall and cell fluid. The cell fluid is assumed to be a Newtonian fluid with higher viscosity compared to water and cell wall is assumed to be a visco-elastic solid boundary located around the cell fluid. Cell fluid is modelled with Smoothed Particle Hydrodynamics (SPH) technique and for the cell wall; a Discrete Element Method (DEM) is used. The developed model is two-dimensional, but accounts for three-dimensional physical properties of real plant cells. Drying phenomena is simulated as fluid mass reductions and the model is used to predict the above mentioned structural properties as a function of cell fluid mass. Model predictions are found to be in fairly good agreement with experimental data in literature and the particle-based approach is demonstrated to be suitable for numerical studies of drying related structural deformations. Also a sensitivity analysis is included to demonstrate the influence of key model parameters to model predictions.