Therapeutic options for metastatic castration resistant prostate cancer : has the situation improved?

Limited treatment options for Castration Resistant Prostate Cancer (CRPC) still remain a major challenge. Despite therapeutic advances, most patients with malignant PCa have a poor prognosis. Since the year 2000, we have rapidly expanded our understanding of the molecular mechanisms underlying CRPC and this has led to an unprecedented number of new drug approvals within a short span of time. Recently, four new agents namely Abiraterone Acetate, Enzalutamide, Cabazitaxel, and Radium-223 have been shown to be effective in the post-chemotherapy setting in CRPC. The continued dependency of CRPC on androgen synthesis has seen the development of a number of new anti-androgen therapies, with abiraterone acetate and Enzalutamide being the most promising discoveries. Immunotherapeutic approaches have also found their niche in PCa with Sipuleucel-T shown to be effective in minimally asymptomatic CRPC. Research focussed on bone-targeting therapies has witnessed the arrival of promising new drugs with Denosumab and Radium-223 displaying improved survival of patients with CRPC. This review briefly discusses the findings and limitations from ongoing and completed clinical trials of novel treatments and regimens. In addition, potential mechanisms of therapy resistance and future challenges are discussed.

Thriller

Shifts in genre definitions and classifications over time are very much a part of a living art form such as cinema. Films that today we might identify as bearing some of the hallmarks of the thriller, but which were not understood as such at the time of release, have been made in Australia since the earliest days of narrative cinema. The Story of the Kelly Gang (Charles Tait, 1906) contains some of the thriller’s stock elements: crime, conspiracy, suspense, a chase, heroes and villains. The fact that these elements are not exclusive to the thriller underscores the point that genres change, evolve, and often overlap. While contemporary reportage attests that The Story of the Kelly Gang thrilled audiences, it was not named as a ‘thriller’ at the time. Even so, a genealogy of the thriller can be traced through Australian film history, despite quiescent periods.

Individuals, Innovation, and the Internet : Why Access is Essential

As each day passes, and as new and better devices and services are developed, more and more government and private services are being moved to an online format. This movement makes access to the internet an essential for 21st Century life. The internet has become so integrated in our lives that many of us cannot imagine how we could operate without it. This omnipresent ‘being’ affects all forms of ‘normal’ social and economic activity and does so in ways that we do not realize. Those with access are able to engage with government, business, and family and friends more easily, which can lead to an improved standard of living. For the disadvantaged, however – those with the desire but without the capacity – a lack of access can be socially isolating. "Between the idea And the reality Between the motion And the act Falls the Shadow – T. S. Elliott. “The Hollow Men” Engagement in the internet economy requires both physical access and the individual to have the necessary finances and skills to make and sustain their use. If governments and the international community want a fully functioning internet economy this requires that all individuals must be operating in it. That not all individuals do so means, very simply, that the internet economy is not fully functioning. The text contextualizes for policy makers and legislatures why it is essential to ensure that individuals have appropriate access to the internet and what can be done to achieve it. The interrelationship/overlap between why access is essential, how it can be achieved and the central role of the individual to the internet economy is explored and translated into the concept of connectedness. From this, solutions for ensuring connectedness for all individuals are developed. It is Dr Cradduck’s hope that in the not too distant future readers will puzzle over why texts such as this needed to be written.

The Fleet Store : devising a public retail exhibition to promote creative, innovative and sustainable business models for emerging fashion designers

1.Description of the Work The Fleet Store was devised as a creative output to establish an exhibition linked to a fashion business model where emerging designers were encouraged to research new and innovative strategies for creating design-driven and commercial collections for a public consumer. This was a project that was devised to break down the perceptions of emerging fashion designers that designing commercial collections linked to a sustainable business model is a boring and unnecessary process. The focus was to demystify the business of fashion and to link its importance to a design-driven and public outcome that is more familiar to fashion designers. The criterion for participation was that all designers had to be registered as a business with the Australian Taxation Office. Designers were chosen from the Creative Enterprise Australia Fashion Business Incubator, the QUT fashion graduate alumni and current QUT fashion design and double degree (fashion and business) students with existing businesses. The project evolved from a series of collaborative workshops where designers were introduced to new and innovative creative industries’ business models and the processes, costings and timings involved to create a niche, sustainable business for a public exhibition of design-driven commercial collections. All designers initiated their own business infra-structure but were then introduced to the concept of collaboration for successful and profitable exhibition and business outcomes. Collaborative strategies such as crowd funding, crowd sourcing, peer to peer mentoring and manufacturing were all researched, and strategies for the establishment of the retail exhibition were all devised in a collaborative environment. All participants also took on roles outside their ‘designer’ background to create a retail exhibition that was creative but also had critical mass and aesthetic for the consumer. The Fleet Store ‘popped up’ for 2 weeks (10 days), in a heritage-listed building in an inner city location. Passers-by were important, but the main consumer was enlisted by the use of interest and investment from crowd sourcing, crowd funding, ethical marketing, corporate social responsibility projects and collaborative public relations and social media strategies. The research has furthered discussion on innovative strategies for emerging fashion designers to initiate and maintain sustainable businesses and suggests that collaboration combined with a design-driven and business focus can create a sustainable and economically viable retail exhibition. 2. Research Statement Research Background The research field involved developing a new ethical, design-driven, collaborative and sustainable model for fashion design practice and management. The research asked can a public, design-driven, collaborative retail exhibition create a platform for promoting creative, innovative and sustainable business models for emerging fashion designers. The methodology was primarily practice-led as all participants were designers in their own right and the project manager acted as a mentor and curator to guide the process and analyse the potential of the research question. The Fleet Store offers new knowledge in design practice and management; with the creation of a model where design outcomes and business models are inextricably linked to the success of the creative output. Key innovations include extending the commercialisation of emerging fashion businesses by creating a curated retail gallery for collaborative and sustainable strategies to support niche fashion designer labels. This has contributed to a broader conversation on how to nurture and sustain competitive Australian fashion designers/labels. Research Contribution and Significance The Fleet Store has contributed to a growing body of research into innovative and sustainable business models for niche fashion and creative industries’ practitioners. All participants have maintained their business infra-structure and many are currently growing their businesses, using the strategies tested for the Fleet Store. The exhibition space was visited by over 1,000 people and sales of $27,000 were made in 10 days of opening. (Follow up sales of $3,000 has also been reported.) Three of the designers were ‘discovered’ from the exhibition and have received substantial orders from high profile national buyers and retailers for next season delivery. Several participants have since collaborated to create other pop up retail environments and are now mentoring other emerging designers on the significance of a collaborative retail exhibition to consolidate niche business models for emerging fashion designers.

Extinction risk in cloud forest fragments under climate change and habitat loss

Aim: To quantify the consequences of major threats to biodiversity, such as climate and land-use change, it is important to use explicit measures of species persistence, such as extinction risk. The extinction risk of metapopulations can be approximated through simple models, providing a regional snapshot of the extinction probability of a species. We evaluated the extinction risk of three species under different climate change scenarios in three different regions of the Mexican cloud forest, a highly fragmented habitat that is particularly vulnerable to climate change. Location: Cloud forests in Mexico. Methods: Using Maxent, we estimated the potential distribution of cloud forest for three different time horizons (2030, 2050 and 2080) and their overlap with protected areas. Then, we calculated the extinction risk of three contrasting vertebrate species for two scenarios: (1) climate change only (all suitable areas of cloud forest through time) and (2) climate and land-use change (only suitable areas within a currently protected area), using an explicit patch-occupancy approximation model and calculating the joint probability of all populations becoming extinct when the number of remaining patches was less than five. Results: Our results show that the extent of environmentally suitable areas for cloud forest in Mexico will sharply decline in the next 70 years. We discovered that if all habitat outside protected areas is transformed, then only species with small area requirements are likely to persist. With habitat loss through climate change only, high dispersal rates are sufficient for persistence, but this requires protection of all remaining cloud forest areas. Main conclusions: Even if high dispersal rates mitigate the extinction risk of species due to climate change, the synergistic impacts of changing climate and land use further threaten the persistence of species with higher area requirements. Our approach for assessing the impacts of threats on biodiversity is particularly useful when there is little time or data for detailed population viability analyses. © 2013 John Wiley & Sons Ltd.

The edge of glory: the relationship between metacritic scores and player experience

This study sought to examine how measures of player experience used in videogame research relate to Metacritic Professional and User scores. In total, 573 participants completed an online survey, where they responded the Player Experience of Need Satisfaction (PENS) and the Game Experience Questionnaire (GEQ) in relation to their current favourite videogame. Correlations among the data indicate an overlap between the player experience constructs and the factors informing Metacritic scores. Additionally, differences emerged in the ways professionals and users appear to allocate game ratings. However, the data also provide clear evidence that Metacritic scores do not reflect the full complexity of player experience and may be misleading in some cases.

The first 25 years of the Queensland Rugby Football League: Claims to legitimacy in annual reports

Despite the cultural importance of sporting organisations, little academic attention has been paid to the legitimising role of their annual reports. In this paper we examine the role of annual reports in establishing the legitimacy of a new organisation, the Queensland Rugby Football League (QRFL), founded in 1908. Contextualised with media reports from newspapers of the day, twelve annual reports from QRFL’s first 25 years are analysed and interpreted using insights from legitimacy theory. Through the presentation of audited financial statements and persuasive narrative accounts of its operations and success, QRFL made claims to pragmatic, moral and cognitive legitimacy as it sought to establish a niche as a new football code and organisation. This contextualised study situates the annual reports in their historical landscape, providing insights about how they contributed to QRFL’s efforts in overcoming the liability of newness in a competitive sports environment.

Green: Exploring the aestheticized use of chroma-key techniques and technologies in two intermedial productions

Peggy Shaw’s RUFF, (USA 2013) and Queensland Theatre Company’s collaboration with Queensland University of Technology, Total Dik!, (Australia 2013) overtly and evocatively draw on an aestheticized use of the cinematic techniques and technologies of Chroma Key to reveal the tensions in their production and add layers to their performances. In doing so they offer invaluable insight where the filmic and theatrical approaches overlap. This paper draws on Eckersall, Grehan and Scheer’s New Media Dramaturgy (2014) to reposition the frame as a contribution to intermedial theatre and performance practices in light of increasing convergence between seemingly disparate discourses. In RUFF, the scenic environment replicates a chroma-key ‘studio’ which facilitates the reconstruction of memory displaced after a stroke. RUFF uses the screen and projections to recall crooners, lounge singers, movie stars, rock and roll bands, and an eclectic line of eccentric family members living inside Shaw. While the show pays tribute to those who have kept her company across decades of theatrical performance, use of non-composited chroma-key technique as a theatrical device and the work’s taciturn revelation of the production process during performance, play a central role in its exploration of the juxtaposition between its reconstructed form and content. In contrast Total Dik! uses real-time green screen compositing during performance as a scenic device. Actors manipulate scale models, refocus cameras and generate scenes within scenes in the construction of the work’s examination of an isolated Dictator. The ‘studio’ is again replicated as a site for (re)construction, only in this case Total Dik! actively seeks to reveal the process of production as the performance plays out. Building on RUFF, and other works such as By the Way, Meet Vera Stark, (2012) and Hotel Modern’s God’s Beard (2012), this work blends a convergence of mobile technologies, models, and green screen capture to explore aspects of transmedia storytelling in a theatrical environment (Jenkins, 2009, 2013). When a green screen is placed on stage, it reads at once as metaphor and challenge to the language of theatre. It becomes, or rather acts, as a ‘sign’ that alludes to the nature of the reconstructed, recomposited, manipulated and controlled. In RUFF and in Total Dik!, it is also a place where as a mode of production and subsequent reveal, it adds weight to performance. These works are informed by Auslander (1999) and Giesenkam (2007) and speak to and echo Lehmann’s Postdramatic Theatre (2006). This paper’s consideration of the integration of studio technique and live performance as a dynamic approach to multi-layered theatrical production develops our understanding of their combinatory use in a live performance environment.

Four years on: Are the gazelles still running? A longitudinal study of firm performance after a period of rapid growth

This article examines variations in performance between fast-growth – the so-called gazelle – firms. Specifically, we investigate how the level of growth affects future profitability and how this relationship is moderated by firm strategy. Hypotheses are developed regarding the moderated growth–profitability relationship and are tested using longitudinal data from a sample of 964 Danish gazelle firms. We find a positive relationship between growth and profitability among gazelle firms. This relationship is moderated, however, by market strategy; it is stronger for firms pursuing a broad market strategy rather than a niche strategy. This study contributes to the current literature by providing a more nuanced view of the growth–profitability relationship and investigating the potential for the future performance of gazelle firms.

SECA: SNP effect concordance analysis using genome-wide association summary results

The genomics era provides opportunities to assess the genetic overlap across phenotypes at the measured genotype level; however, current approaches require individual-level genome-wide association (GWA) single nucleotide polymorphism (SNP) genotype data in one or both of a pair of GWA samples. To facilitate the discovery of pleiotropic effects and examine genetic overlap across two phenotypes, I have developed a user-friendly web-based application called SECA to perform SNP effect concordance analysis using GWA summary results. The method is validated using publicly available summary data from the Psychiatric Genomics Consortium.

Genetic risk score analysis indicates migraine with and without comorbid depression are genetically different disorders

Migraine and major depressive disorder (MDD) are comorbid, moderately heritable and to some extent influenced by the same genes. In a previous paper, we suggested the possibility of causality (one trait causing the other) underlying this comorbidity. We present a new application of polygenic (genetic risk) score analysis to investigate the mechanisms underlying the genetic overlap of migraine and MDD. Genetic risk scores were constructed based on data from two discovery samples in which genome-wide association analyses (GWA) were performed for migraine and MDD, respectively. The Australian Twin Migraine GWA study (N = 6,350) included 2,825 migraine cases and 3,525 controls, 805 of whom met the diagnostic criteria for MDD. The RADIANT GWA study (N = 3,230) included 1,636 MDD cases and 1,594 controls. Genetic risk scores for migraine and for MDD were used to predict pure and comorbid forms of migraine and MDD in an independent Dutch target sample (NTR-NESDA, N = 2,966), which included 1,476 MDD cases and 1,058 migraine cases (723 of these individuals had both disorders concurrently). The observed patterns of prediction suggest that the 'pure' forms of migraine and MDD are genetically distinct disorders. The subgroup of individuals with comorbid MDD and migraine were genetically most similar to MDD patients. These results indicate that in at least a subset of migraine patients with MDD, migraine may be a symptom or consequence of MDD. © 2013 Springer-Verlag Berlin Heidelberg.

Exploring expectations of nonprofit management capabilities

Management capabilities have been widely researched in the private and public sectors, yet there is less evidence relating to the nonprofit sector. Increasing pressures to balance the demands of organizational values with business performance in this sector leads to a focus on the managerial capabilities required to meet these expectations. This article reports an exploratory study of capability expectations of managers within an Australian nonprofit organization. Using semistructured interviews, data were collected from 21 managers across three hierarchical levels. Findings indicate that while there is some overlap with managerial requirements in the private and public sectors, there are some unique aspects of nonprofit operations which warrant further investigation. Specifically, there was an emphasis on personal knowledge and experience (i.e., self-awareness, discipline, knowledge, and strategic thinking) and having a commitment to the nonprofit sector and values of the organization. Expectations also varied depending on the level of management within the organization.

Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 × 10−8) loci, some including known iron-related genes (​HFE, ​SLC40A1, ​TF, ​TFR2, ​TFRC, ​TMPRSS6) and others novel (​ABO, ​ARNTL, ​FADS2, ​NAT2, ​TEX14). SNPs at ​ARNTL, ​TF, and ​TFR2 affect iron markers in ​HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.

Social networking sites and participatory reluctance: A case study of Gaydar, user resistance and interface rejection

This article conceptualises ‘participatory reluctance’ as a particular orientation to social media that problematises binarised notions of connection and disconnection in social networking sites. It qualitatively examines how the concept has functioned within gay men’s social networking service, Gaydar, among 18- to 28-year-old users of the site in Brisbane, Australia. Participatory reluctance is shown to be a central aspect of the culture of this space, fostered among the studied demographic by the convergence of the growing global push for marriage equality and increasing normalisation of the kinds of gay male identities commonly adopted among this group, with three key factors rooted primarily in Gaydar’s design: (1) young users’ perceptions of the site as a space for procuring casual sex; (2) their perceptions of the imagined user as embodying existing stereotypes of gay masculinity, and; (3) a lack of genuine alternatives in terms of niche digital spaces for gay men’s social networking.

Designing 'other' citizens into the city: Investigating perceptions of architectural opportunities for wildlife habitat in the Brisbane CBD

Traditional perceptions of the human-animal relationship in the urban context typically see the spatial rejection of wildlife from the built environment and limiting of biodiversity conservation programs to areas of natural reserve. As urban growth places further spatial demands on natural habitat and contributes to continued global biodiversity loss, the recently introduced conservation approach of reconciliation ecology makes a call promoting ecological stewardship through embedding wildlife habitat within human dominated areas. Coinciding with this, the architectural sphere has seen a recent trend of design investigation addressing artificial animal habitat as features of the built environment. Although these precedents are currently a niche and scattered trend they show potential to address the human-animal dualism challenging the framework of reconciliation ecology. This research explores the role design plays in influencing perceptions of urban wildlife habitat, particularly considering the need to create and communicate value around wildlife biodiversity as a component of urban cultural place-making and ecological literacy. The study purpose sets out to establish a set of approaches and cultural preferences with which to direct further classification and development of this architectural trend. Brisbane is utilised as a case study city, as a locale containing proximities of relatively high wildlife and human populations in an urban setting and an established legislative biodiversity heritage and ethic. Through use of a qualitative and quantitative questionnaire targeting Brisbane residents, the research methodology established that although respondents perceptions generally aligned with traditional prejudice against wildlife around human buildings, artificial habitat intervention would be supported within the CBD provided it allowed for adequate distancing of humans from wildlife and conformed with contextual surroundings, or otherwise addressed habitat through redevelopment at an urban scale. As such further research directions for artificial habitat should focus on integration of artificial habitat as a component of façade design or green infrastructure programs.