Meta-analysis of individual patient data from randomized trials of chemotherapy plus cetuximab as first-line treatment for advanced non-small cell lung cancer

OBJECTIVES: Four randomized phase II/III trials investigated the addition of cetuximab to platinum-based, first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis was performed to examine the benefit/risk ratio for the addition of cetuximab to chemotherapy. MATERIALS AND METHODS: The meta-analysis included individual patient efficacy data from 2018 patients and individual patient safety data from 1970 patients comprising respectively the combined intention-to-treat and safety populations of the four trials. The effect of adding cetuximab to chemotherapy was measured by hazard ratios (HRs) obtained using a Cox proportional hazards model and odds ratios calculated by logistic regression. Survival rates at 1 year were calculated. All applied models were stratified by trial. Tests on heterogeneity of treatment effects across the trials and sensitivity analyses were performed for all endpoints. RESULTS: The meta-analysis demonstrated that the addition of cetuximab to chemotherapy significantly improved overall survival (HR 0.88, p=0.009, median 10.3 vs 9.4 months), progression-free survival (HR 0.90, p=0.045, median 4.7 vs 4.5 months) and response (odds ratio 1.46, p<0.001, overall response rate 32.2% vs 24.4%) compared with chemotherapy alone. The safety profile of chemotherapy plus cetuximab in the meta-analysis population was confirmed as manageable. Neither trials nor patient subgroups defined by key baseline characteristics showed significant heterogeneity for any endpoint. CONCLUSION: The addition of cetuximab to platinum-based, first-line chemotherapy for advanced NSCLC significantly improved outcome for all efficacy endpoints with an acceptable safety profile, indicating a favorable benefit/risk ratio.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Electronic workplace surveillance and employee privacy : a comparative analysis of privacy protection in Australia and the United States

More than a century ago in their definitive work “The Right to Privacy” Samuel D. Warren and Louis D. Brandeis highlighted the challenges posed to individual privacy by advancing technology. Today’s workplace is characterised by its reliance on computer technology, particularly the use of email and the Internet to perform critical business functions. Increasingly these and other workplace activities are the focus of monitoring by employers. There is little formal regulation of electronic monitoring in Australian or United States workplaces. Without reasonable limits or controls, this has the potential to adversely affect employees’ privacy rights. Australia has a history of legislating to protect privacy rights, whereas the United States has relied on a combination of constitutional guarantees, federal and state statutes, and the common law. This thesis examines a number of existing and proposed statutory and other workplace privacy laws in Australia and the United States. The analysis demonstrates that existing measures fail to adequately regulate monitoring or provide employees with suitable remedies where unjustifiable intrusions occur. The thesis ultimately supports the view that enacting uniform legislation at the national level provides a more effective and comprehensive solution for both employers and employees. Chapter One provides a general introduction and briefly discusses issues relevant to electronic monitoring in the workplace. Chapter Two contains an overview of privacy law as it relates to electronic monitoring in Australian and United States workplaces. In Chapter Three there is an examination of the complaint process and remedies available to a hypothetical employee (Mary) who is concerned about protecting her privacy rights at work. Chapter Four provides an analysis of the major themes emerging from the research, and also discusses the draft national uniform legislation. Chapter Five details the proposed legislation in the form of the Workplace Surveillance and Monitoring Act, and Chapter Six contains the conclusion.

Documenting reproduction and inequality : revisiting Jean Anyon’s “Social class and school knowledge”

Jean Anyon’s (1981) “Social class and school knowledge” was a landmark work in North American educational research. It provided a richly detailed qualitative description of differential, social-class-based constructions of knowledge and epistemological stance. This essay situates Anyon’s work in two parallel traditions of critical educational research: the sociology of the curriculum and classroom interaction and discourse analysis. It argues for the renewed importance of both quantitative and qualitative research on social reproduction and equity in the current policy context.

Assessment in education : principles, policy and practice

The English examination system provides a market in which a limited number of providers are accredited to offer curriculum-based examinations in many subject areas and at several levels. The most significant are the General Certificate of Secondary Education (GCSE) and the General Certificate of Education, Advanced (A level). Because these examinations are used for high-stakes purposes, including higher education and employment selection for individuals and programme evaluation for institutions, it is desired that scores from various exams be ‘comparable’ in several respects: across syllabuses and examination boards within a subject area, across years, and even across subject areas. Just how to accomplish this goal has been a topic of continual research and debate for over 50 years, through many changes of examination and institutional structures. But ever year, tens of thousands of scores must be reported, and every year, users expect them to ‘be comparable’ and use them as if they are.

Building an effective trade practices commission : the role of Professor Robert Baxt AO

Bob Baxt, the third Chairman of the Trade Practices Commission, served for a single three year term from 1988 to 1991. He followed Bob McComas, who had deliberately adopted a non-litigious approach to preserving the competitive process, believing that he understood business as an insider and that much of what it did was not anti-competitive, when correctly viewed. Baxt was far more pro-active in his approach, and more closely aligned with that of the first Chairman, Ron Bannerman. Baxt sought to push the frontiers of investigation and precedent, and perhaps, more significantly, sought to influence his Ministers, the government, public servants and public opinion about the need to expand the coverage of the Trade Practices Act, increase penalties and properly resource the Commission so that it could perform its assigned roles. This article examines Baxt’s early and on-going role in teaching Australian students and professionals through his interdisciplinary Trade Practices Workshops, the political context of Baxt’s tenure, including his relations with the Attorney-General ,Michael Duffy, and his skilful handling of the Queensland Wire case.

An old language for a new landscape

Because aesthetics can have a profound effect upon the human relationship to the non-human environment the importance of aesthetics to ecologically sustainable designed landscapes has been acknowledged. However, in recognition that the physical forms of designed landscapes are an expression of the social values of the time, some design professionals have called for a new aesthetic ― one that reflects these current ecological concerns. To address this, some authors have suggested various theoretical design frameworks upon which such an aesthetic could be based. Within these frameworks there is an underlying theme that the patterns and processes of natural systems have the potential to form a new aesthetic for landscape design —an aesthetic based on fractal rather than Euclidean geometry. Perry, Reeves and Sim (2008) have shown that it is possible to differentiate between different landscape forms by fractal analysis. However, this research also shows that individual scenes from within very different landscape forms can possess the same fractal properties. Early data, revealed by transforming landscape images from the spatial to the frequency domain, using the fast Fourier transform, suggest that fractal patterning can have a significant effect within the landscape. In fact, it may be argued that any landscape design that includes living processes will include some design element whose ultimate form can only be expressed through the mathematics of fractal geometry. This paper will present ongoing research into the potential role of fractal geometry as a basis for a new form language – a language that may articulate an aesthetic for landscape design that echoes our ecological awakening.

Perceptions of aging across 26 cultures and their culture-level associates

College students (N = 3,435) in 26 cultures reported their perceptions of age-related changes in physical, cognitive, and socioemotional areas of functioning and rated societal views of aging within their culture. There was widespread cross-cultural consensus regarding the expected direction of aging trajectories with (1) perceived declines in societal views of aging, physical attractiveness, the ability to perform everyday tasks, and new learning, (2) perceived increases in wisdom, knowledge, and received respect, and (3) perceived stability in family authority and life satisfaction. Cross-cultural variations in aging perceptions were associated with culture-level indicators of population aging, education levels, values, and national character stereotypes. These associations were stronger for societal views on aging and perceptions of socioemotional changes than for perceptions of physical and cognitive changes. A consideration of culture-level variables also suggested that previously reported differences in aging perceptions between Asian and Western countries may be related to differences in population structure.

Business Leaders Hall of Fame collection

"Qld Business Leaders Hall of Fame" is a research project that includes interviews with eminent Qlders that produced oral history interviews and digital stories about their life/company's achievements. This model was able to test and evaluate the use of oral history and digital storytelling for learning and community heritage purposes. Interviewees include; Sir John and Valmai Pidgeon, Joseph Saragossi, Robert Bryan, Clem Jones, Jim Kennedy, Sr Angela Mary, Castelmaine Perkins, Burns and Philp, Qantas, Don Argus & Steve Irwin.

Louis Nowra, 'Radiance' (Sydney: Currency Press, 1993)

Louis Nowra wrote 'Radiance' especially for the three actors who performed it in the play’s premier season at Belvoir Street Theatre in September 1993. And the Currency Press playscript / programme produced for that season foregrounds these three performers – Rachael Maza, Lydia Miller and Rhoda Roberts – in such a way that the usual distinction between dramatis personae and the actors who play them is considerably diminished. Both the blurb on the back cover and Nowra’s introduction emphasise this special relationship between text and actors, but it is the front cover shot which particularly reflects the conjunction between the two. Rather than depicting a scene from performance, or a ‘graphic’ suggesting something of the play’s thematic content, the front cover of Radiance features the three actors in a posed promotional shot. Arms joined warmly, lovingly, about each other’s waist, bodies turned away from but faces towards the camera, it is the actors we see, not their characters. It’s a very joyful image; they’re positively beaming. Radiant. They look as if they could really be the three half-sisters they portray, except that such moments of blithe sorority are just about non-existent in the play.