XIAP downregulation accompanies mebendazole growth inhibition in melanoma xenografts

Mebendazole (MBZ) was identified as a promising therapeutic on the basis of its ability to induce apoptosis in melanoma cell lines through a B-cell lymphoma 2 (BCL2)-dependent mechanism. We now show that in a human xenograft melanoma model, oral MBZ is as effective as the current standard of care temozolomide in reducing tumor growth. Inhibition of melanoma growth in vivo is accompanied by phosphorylation of BCL2 and decreased levels of X-linked inhibitor of apoptosis (XIAP). Reduced expression of XIAP on treatment with MBZ is partially mediated by its proteasomal degradation. Furthermore, exposure of melanoma cells to MBZ promotes the interaction of SMAC/DIABLO with XIAP, thereby alleviating XIAP's inhibition on apoptosis. XIAP expression on exposure to MBZ is indicative of sensitivity to MBZ as MBZ-resistant cells do not show reduced levels of XIAP after treatment. Resistance to MBZ can be reversed partially by siRNA knockdown of cellular levels of XIAP. Our data indicate that MBZ is a promising antimelanoma agent on the basis of its effects on key antiapoptotic proteins.

The Cyndi Lauper affect : bodies, girlhood and popular culture [Abstract]

Using a collective biography method informed by a Deleuzian theoretical approach (Davies & Gannon, 2009), this paper analyses embodied memories of girlhood becomings through affective engagements with resonating images in media and popular culture. In this approach to analysis we move beyond an impasse in some feminist cultural studies where studies of popular culture have been understood through theories of representation and reception that retain a sense of discrete subjectivity and linear effects. In these approaches, analysis focuses respectively on decoding and deciphering images in terms of their normative and ideological baggage, and, particularly with moving images, on psychological readings (Coleman, 2011; Driscoll, 2002). Understanding bodies and popular culture through Deleuzian notions of ‘becoming’ and ‘assemblage’ opens possibilities for feminist researchers to consider the ways in which bodies are not separate to images but rather, are known, felt, materialised and mobilised with/through images (Coleman, 2008, 2009, 2011). We tease out the implications of this new approach to media affects through two memories of girls’ engagements with media images, reconceived as moments of embodied being within affective flows of popular culture that might momentarily extend upon the ways of being and doing girlhood.

Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010 : a systematic analysis for the Global Burden of Disease Study 2010

Background Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). Methods Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. Findings Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient −0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. Interpretation Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. Funding Bill & Melinda Gates Foundation.

The relationship between self-esteem and psychological adjustment in young adolescents

The study adopts a multi-dimensional construct of self-esteem to examine the relationship between self-perception and psychological adjustment in order to identify specific dimensions that discriminate between disturbed and non-disturbed groups. The disturbed group (n = 33) is derived from a clinical sample and are matched with a non-disturbed group (n = 33) of adolescents. Results indicate that dimensional self-concept scores are significantly lower for clinical subjects while there are no significant differences between groups on the mathematics, honesty, and physical ability dimensions. These findings provide a more fine grained understanding of the relationship between self-esteem and psychological adjustment and emphasize the need to examine self-esteem in terms of its particular dimensions.

Parent and adolescent perceptions of family functioning : a comparison of clinic and non-clinic families

In this paper two studies are reported which compare (a) the perceptions of family functioning held by clinic and non-clinic adolescents, and (b) the perceptions of family functioning held by adolescents and their mothers in clinic and non-clinic families. In Study 1, matched group of clinic and non-clinic adolescents were compared on their responses to a 30-item scale (ICPS) designed to measure three factors of family functioning: Intimacy (high vs. low), Parenting Style (democratic vs. controlled) and Conflict (high vs. low). Clinic and non-clinic adolescents were also compared on their responses to a multi-dimensional measure of adolescent self-concept. Although there was little difference between the two groups of adolescents in terms of their perceptions of family functioning, there were strong relationships between the self-concept variables and the family functioning variables. In Study 2, comparisons were made between the perceptions of family functioning held by mothers and adolescents for both clinical and non-clinic families. There were no differences between the two groups of adolescents in terms of their perceptions of family functioning, although there were clear differences between the two groups of mothers. In addition, clinic adolescents and their mothers did not differ in their perceptions of the family, whereas adolescents in the non-clinic group saw their families significantly as less intimate and more conflicted than did their mothers.

Towards proximity-based passenger sensing on public transport buses

While substantial research on intelligent transportation systems has focused on the development of novel wireless communication technologies and protocols, relatively little work has sought to fully exploit proximity-based wireless technologies that passengers actually carry with them today. This paper presents the real-world deployment of a system that exploits public transit bus passengers’ Bluetooth-capable devices to capture and reconstruct micro- and macro-passenger behavior. We present supporting evidence that approximately 12% of passengers already carry Bluetooth-enabled devices and that the data collected on these passengers captures with almost 80 % accuracy the daily fluctuation of actual passengers flows. The paper makes three contributions in terms of understanding passenger behavior: We verify that the length of passenger trips is exponentially bounded, the frequency of passenger trips follows a power law distribution, and the microstructure of the network of passenger movements is polycentric.

Judicial intervention in the affairs of unincorporated religious associations in New South Wales

The leading Australian High Court case of Cameron v Hogan (1934) 51 CLR 358 confirmed that associations which are 'social, sporting, political, scientific, religious, artistic or humanitarian in character’, and not formed ‘for private gain or material advantage’, are usually formed on a basis of mutual consent. Unless there is some clear, positive indication that the members wish to relate to each other in a legal fashion, the rules of the association will not be treated as an enforceable contract in contrast to the rules of incorporated bodies. Australian unincorporated associations experiencing internal disputes, like those in most other common law jurisdictions, have found courts reluctant to provide a remedy unless there is a proprietary interest or trust to protect. This is further compounded by the judicial view that an unincorporated association has no legal recognition as a ‘juristic person’. The right to hold property and the ability to sue and be sued are incidences of this recognition. By contrast, the law recognises ‘artificial’ legal persons such as corporations, who are given rights to hold property and to sue and be sued. However, when a number of individuals associate together for a non-commercial, lawful purpose, but not by way of a corporate structure, legal recognition ‘as a group’ is denied. Since 1934, a significant number of cases have distinguished or otherwise declined to follow this precedent of the High Court. A trenchant criticism is found in McKinnon v Grogan [1974] 1 NSWLR 295, 298 where Wootten J said that ‘citizens are entitled to look to the courts for the same assistance in resolving disputes about the conduct of sporting, political and social organisations as they can expect in relation to commercial institutions’. According to Wootten J at 298, if disputes are not settled by the courts, this would create a ‘legal-no-man's land, in which disputes are settled not in accordance with justice and the fulfilment of deliberately undertaken obligations, but by deceit, craftiness, and an arrogant disregard of rights’. Cameron v Hogan was decided in 1934. There is an increasing volume of first instance cases which distinguish or, in the words of Palmer J, ‘just pay lip service’ to this High Court decision. (Coleman v Liberal Party of Australia (2007) 212 FLR 271, 278). The dissenting cases seem to call for a judicial policy initiative. This would require recognition by judges that voluntary associations play a significant role in society and that members have a legitimate, enforceable expectation that the rules of the association will be observed by members and in the last resort, enforced by the courts without the need to prove contractual intention, the existence of a trust or the existence of a right of a proprietary nature. This thesis asks: what legal, as distinct from political, redress does an ordinary member have, when a rule is made or a process followed which is contrary to the underlying doctrines and philosophies embodied in the constitutional documents of an unincorporated religious association? When, if at all, will a court intervene to ensure doctrinal purity or to supervise the daily life of a large unincorporated religious association? My research objective is to examine and analyse leading cases and relevant legislation on the enforceability of the constitutions of large, unincorporated, religious associations with particular reference to the Anglican Church in New South Wales. Given its numerical size, wide geographical spread and presence since the foundation of New South Wales, the Anglican Church in New South Wales, contains a sufficient variety of ‘real life’ situations to be representative of the legal issues posed by Cameron v Hogan which may be faced by other large, unincorporated, religious associations in New South Wales. In contemporary society, large, unincorporated, religious associations play an important community role. The resolution of internal disputes in such associations should not remain captive to legal doctrines of an earlier age.

Integrated genomic characterization of endometrial carcinoma

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

The Cyndi Lauper affect : bodies, girlhood and popular culture

Using a collective biography method informed by a Deleuzian theoretical approach (Davies and Gannon 2009, 2012), this article analyses embodied memories of girlhood becomings through affective engagements with resonating images in media and popular culture. In this approach to analysis we move beyond the impasse in some feminist cultural studies where studies of popular culture have been understood through theories of representation and reception that retain a sense of discrete subjectivity and linear effects. In these approaches, analysis focuses respectively on decoding and deciphering images in terms of their normative and ideological baggage, and, particularly with moving images, on psychological readings. Understanding bodies and popular culture through Deleuzian notions of “becoming” and “assemblage” opens possibilities for feminist researchers to consider the ways in which bodies are not separate from images but are, rather, becomings that are known, felt, materialized and mobilized with/through images(Coleman 2008a, 2008b, 2008c, 2009, 2011; Ringrose and Coleman 2013). We tease out the implications of this new approach to media affects through three memories of girls’ engagements with media images, reconceived as moments of embodied being within affective flows of popular culture that might momentarily extend upon ways of being and doing girlhood.

Principles of Taxation Law 2013

Taxation law can be an incredibly complex subject to absorb, particularly when time is limited. Written specifically for students, Principles of Taxation Law 2013 brings much needed clarity to this area of law. Utilising many methods to make this often daunting subject achievable, particular features of the 2013 edition include: • seven parts: overview and structure, principles of income, deductions and offsets, timing issues, investment and business entities, tax avoidance and administration, and indirect taxes; • clearly structured chapters within those parts grouped under helpful headings; • flowcharts, diagrams and tables, end of chapter practice questions, and case summaries; • an appendix containing all of the up to date and relevant rates; and • the online self-testing component mentor, which provides questions for students of both business and law. Every major aspect of the Australian tax system is covered, with chapters on topics such as goods and services tax, superannuation, offsets, partnerships, capital gains tax, trusts, company tax and tax administration. All chapters have been thoroughly revised. Principles of Taxation Law 2013 is the perfect tool to guide the reader from their initial exposure to the subject to success in taxation law exams.

Australian Tax Analysis : Cases, Commentary, Commercial Applications and Questions [9th Ed.]

Now in its ninth edition, Australian Tax Analysis: Cases, Commentary, Commercial Applications and Questions has a proven track record as a high-level work for students of taxation law written by a team of authors with many years experience. Taking into account the fact that the volume of material needed to be processed by today’s taxation student can be overwhelming, the well-chosen extracts and thought-provoking commentary in Australian Tax Analysis, 9th edition, provide readers with the depth of knowledge, and reasoning and analytical skills which will be required of them as practitioners. In addition to the carefully selected case extracts and the helpful commentary, each chapter is supplemented by engaging practice questions involving problem solving, commercial decision-making, legal analysis and quantitative application. All these elements combined make Australian Tax Analysis an invaluable aid to the understanding of a subject which can be both technical and complex.

Cultural politics and iconography : an introduction

This collection of papers reflects on the many dimensions of contemporary narratives of iconography in public culture in Australia and Asia. The idea for the volume arose from a series of seminars held at the Centre for Cross-Cultural Research in 2002. The series ‘Iconographies’ was convened by Penny Edwards and centred on research undertaken in the Asia-Pacific, with papers that interrogated national and cultural icons. Just as a biography might examine the makings of a particular personality and her or his shaping of inner and outer worlds, so also iconographic narratives that trace and explore both the evolution and appropriation of particular icons help us mark key moments in the cultural politics of communities, nations and global public spheres. The present volume has two papers (Taylor and Seth) from that series and others on the themes of iconography and iconoclasm that were solicited from a group of interdisciplinary authors working on these themes.

Asymptomatic hypoechoic regions on patellar tendon ultrasound : a 4-year clinical and ultrasound followup of 46 tendons

Patellar tendon ultrasound appearance is commonly used in clinical practice to diagnose patellar tendinopathy and guide management. Using a longitudinal study design we examined whether or not the presence of a hypoechoic ultrasonographic lesion in an asymptomatic patellar tendon conferred a risk for developing jumper's knee compared with a tendon that was ultrasonographically normal. Ultrasonographic, symptomatic and anthropometric assessment was completed at baseline and followup. Magnetic resonance imaging was performed on four tendons that resolved ultrasonographically in the study period. Forty-six patellar tendons were followed over 47 ± 11.8 months. Eighteen tendons were hypoechoic at baseline and 28 were ultrasonographically normal. Five tendons resolved ultrasonographically in the study period. Magnetic resonance imaging in four of these tendons was normal. Seven normal patellar tendons at baseline developed a hypoechoic area but only two became symptomatic. Analysis of ultrasonography at baseline and clinical outcome with Fisher's exact test shows there is no association between baseline ultrasound changes and symptoms at followup. In this study there is no statistically significant relationship between ultrasonographic patellar tendon abnormalities and clinical outcome in elite male athletes. Management of jumper's knee should not be solely based on ultrasonographic appearance; clinical assessment remains the cornerstone of appropriate management.

Soundage : a practice-led approach to Gertrude Stein, sound, and generative language

In this practice-led research project I work to show how a re-reading and a particular form of listening to the sound-riddled nature of Gertrude Stein's work, Two: Gertrude Stein and her Brother, presents us with a contemporary theory of sound in language. This theory, though in its infancy, is a particular enjambment of sounded language that presents itself as an event, engaged with meaning, with its own inherent voice. It displays a propensity through engagement with the 'other' to erupt into love. In this thesis these qualities are reverberated further through the work of Seth Kim-Cohen's notion of the non-cochlear, Simon Jarvis's notion of musical thinking, Jean-Jacques Lecercle's notion of délire or nonsense, Luce Irigaray's notion of jouissant love and the Bracha Ettinger's notion of the generative matrixial border space. This reading then is simultaneously paired with my own work of scoring and creating a digital opera from Stein's work, thereby testing and performing Stein's theory. In this I show how a re-reading and relistening to Stein's work can be significant to feminist ethical language frames, contemporary philosophy, sonic art theory and digital language frames. Further significance of this study is that when the reverberation of Stein's engagements with language through sound can be listened to, a pattern emerges, one that encouragingly problematizes subjectivity and interweaves genres/methods and means, creating a new frame for sound in language, one with its own voice that I call soundage.