Prognostic factors in patients with advanced non-small cell lung cancer : data from the phase III FLEX study

The FLEX study demonstrated that the addition of cetuximab to chemotherapy significantly improved overall survival in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). In the FLEX intention to treat (ITT) population, we investigated the prognostic significance of particular baseline characteristics. Individual patient data from the treatment arms of the ITT population of the FLEX study were combined. Univariable and multivariable Cox regression models were used to investigate variables with potential prognostic value. The ITT population comprised 1125 patients. In the univariable analysis, longer median survival times were apparent for females compared with males (12.7 vs 9.3 months); patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 compared with 1 compared with 2 (13.5 vs 10.6 vs 5.9 months); never smokers compared with former smokers compared with current smokers (14.6 vs 11.1 vs 9.0); Asians compared with Caucasians (19.5 vs 9.6 months); patients with adenocarcinoma compared with squamous cell carcinoma (12.4 vs 9.3 months) and those with metastases to one site compared with two sites compared with three or more sites (12.4 months vs 9.8 months vs 6.4 months). Age (<65 vs ≥65 years), tumor stage (IIIB with pleural effusion vs IV) and percentage of tumor cells expressing EGFR (<40% vs ≥40%) were not identified as possible prognostic factors in relation to survival time. In multivariable analysis, a stepwise selection procedure identified age (<65 vs ≥65 years), gender, ECOG PS, smoking status, region, tumor histology, and number of organs involved as independent factors of prognostic value. In summary, in patients with advanced NSCLC enrolled in the FLEX study, and consistent with previous analyses, particular patient and disease characteristics at baseline were shown to be independent factors of prognostic value. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798. © 2012 Elsevier Ireland Ltd.

Exploring the influences of country-level factors on mid-age women’s drink driving attitudes

Drink driving remains a major cause of serious and fatal car crashes in Australia and internationally. While this problem is more prevalent among male drivers, the rates of female intoxicated drivers have increased steadily over the past decades in many motorised countries. A combination of police enforcement, media awareness campaigns, and community initiatives has played a key role in reducing incidents of illegal drink driving by targeting public drink driving attitudes. However, important cultural differences in regards to the tolerance towards drink driving have been noted. While many countries, including Australia, have a legal Blood Alcohol Concentration (BAC) limit of .05 or higher, some countries have moved towards a zero –or low tolerance approach to drink driving; several European countries, including Sweden, Hungary, Slovakia, and Estonia currently enforce .00 or .02 BAC limits.

Sub-cellular localization of membrane proteins

In eukaryotes, numerous complex sub-cellular structures exist. The majority of these are delineated by membranes. Many proteins are trafficked to these in order to be able to carry out their correct physiological function. Assigning the sub-cellular location of a protein is of paramount importance to biologists in the elucidation of its role and in the refinement of knowledge of cellular processes by tracing certain activities to specific organelles. Membrane proteins are a key set of proteins as these form part of the boundary of the organelles and represent many important functions such as transporters, receptors, and trafficking. They are, however, some of the most challenging proteins to work with due to poor solubility, a wide concentration range within the cell and inaccessibility to many of the tools employed in proteomics studies. This review focuses on membrane proteins with particular emphasis on sub-cellular localization in terms of methodologies that can be used to determine the accurate location of membrane proteins to organelles. We also discuss what is known about the membrane protein cohorts of major organelles.

Treatment rationale study design for the MetLung trial : a randomized, double-blind phase III study of onartuzumab (MetMAb) in combination with erlotinib versus erlotinib alone in patients who have received standard chemotherapy for stage IIIB or IV met-positive non-small-cell lung cancer

We present the treatment rationale and study design of the MetLung phase III study. This study will investigate onartuzumab (MetMAb) in combination with erlotinib compared with erlotinib alone, as second- or third-line treatment, in patients with advanced non-small-cell lung cancer (NSCLC) who are Met-positive by immunohistochemistry. Approximately 490 patients (245 per treatment arm) will receive erlotinib (150 mg oral daily) plus onartuzumab or placebo (15 mg/kg intravenous every 3 weeks) until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death. The efficacy objectives of this study are to compare overall survival (OS) (primary endpoint), progression-free survival, and response rates between the 2 treatment arms. In addition, safety, quality of life, pharmacokinetics, and translational research will be investigated across treatment arms. If the primary objective (OS) is achieved, this study will provide robust results toward an alternative treatment option for patients with Met-positive second- or third-line NSCLC. © 2012 Elsevier Inc. All Rights Reserved.

Cultural Policy

The development of cultural policy during the twentieth century is underscored by three key developments. First, the formation of the Arts Council of Great Britain in 1946, first headed by the Cambridge economist Lord Keynes, saw the scaffolding developed for ongoing government support for the arts. In doing so, it established the principle of an “arm’s length” relationship between the government of the day and individual artists, through the development of independent arts boards engaged in the peer review of creative works. Second, the formation of the Fifth Republic in France in 1958 saw the creation of a Ministry of Culture, headed by the writer André Malraux. Malraux and his successors have seen three major tasks for a national cultural policy: government support for the creation of new artistic and cultural works; the promotion and maintenance of cultural heritage; and enabling equitable access to creative works and creative opportunities through all segments of society. Finally, at a global level, agencies such as UNESCO have sought to promote national cultural policies as an element of national sovereignty, particularly in the developing world, and this has involved addressing sources of structural inequality in the distribution of global cultural and communications resources...

Construct design for efficient, effective and high-throughput gene silencing in plants

Post-transcriptional silencing of plant genes using anti-sense or co-suppression constructs usually results in only a modest proportion of silenced individuals. Recent work has demonstrated the potential for constructs encoding self-complementary 'hairpin' RNA (hpRNA) to efficiently silence genes. In this study we examine design rules for efficient gene silencing, in terms of both the proportion of independent transgenic plants showing silencing, and the degree of silencing. Using hpRNA constructs containing sense/anti-sense arms ranging from 98 to 853 nt gave efficient silencing in a wide range of plant species, and inclusion of an intron in these constructs had a consistently enhancing effect. Intron-containing constructs (ihpRNA) generally gave 90-100% of independent transgenic plants showing silencing. The degree of silencing with these constructs was much greater than that obtained using either co-suppression or anti-sense constructs. We have made a generic vector, pHANNIBAL, that allows a simple, single PCR product from a gene of interest to be easily converted into a highly effective ihpRNA silencing construct. We have also created a high-throughput vector, pHELLSGATE, that should facilitate the cloning of gene libraries or large numbers of defined genes, such as those in EST collections, using an in vitro recombinase system. This system may facilitate the large-scale determination and discovery of plant gene functions in the same way as RNAi is being used to examine gene function in Caenorhabditis elegans.

Putting people in planning: participatory democracy, community building and social inclusion

Like other Western nations, since the nineteenth century Australia has been a representative democracy, in which citizens elect parliamentary representatives to make decisions and develop policies on their behalf (see chapter 5). These representatives are supported in their decision making by an ‘arm’s-length’, ‘techno-bureaucratic administration’, which includes experts such as environmental planners (Fung and Wright 2003, p. 3). However, as the issues for decision-making become increasingly complex, and societies increasingly diverse, the idea of citizen participation in decision-making is ever more accepted. There is now a significant body of political theory arguing for a more participatory model of democracy (participatory democracy), a model that strives to create opportunities for all members of a society to contribute meaningfully to decisions about the matters affecting their lives.

Building distributed leadership for effective supervision of creative practice higher research degrees : final report 2014

Building distributed leadership for effective supervision of creative practice higher research degrees is an Office for Learning and Teaching (OLT) funded project, conducted in partnership between Queensland University of Technology, The University of Melbourne, Auckland University of Technology, University of New South Wales and University of Western Sydney. The project was initiated to develop a cooperative approach to establishing an understanding of the contextual frameworks of the emergent field of creative practice higher degrees by research (HDRs); capturing early insights of administrators and supervisors; gathering exemplars of good practices; and establishing an in-common understanding of effective approaches to supervision. To this end, the project has produced: • A literature review, to provide a research foundation for creative practice higher research degree supervision (Chapter 3). • A contextual review of disciplinary frameworks for HDR programs, produced through surveys of postgraduate research administrators (Section 4.1), and an analysis of institutional materials and academic development programs for supervisors (Section 4.2). • A National Symposium, Effective Supervision of Creative Arts Research Degrees (ESCARD), at QUT in Brisbane in February 2013, with 62 delegates from 20 Australasian Universities, at which project findings were disseminated, and delegates presented case studies and position papers, and participated in discussions on key issues for supervisors (Appendix 1). • Resources, including a booklet for supervisors: 12 Principles for the Effective Supervision of Creative Practice Higher Research Degrees, which encapsulates attitudes, insights and good practices of experienced and new supervisors. It was produced through a content analysis of interviews with twenty-five supervisors in creative disciplines (visual and performing arts, music, new media, creative writing and design) (Printed booklet, PDF, Appendix 3). • A project website to disseminate project outcomes , which holds project findings, relevant references, and a repository of case studies and position papers by supervisors and program administrators. • A call for papers for a special issue ‘Supervising Practice: Perspectives on the Supervision of Creative Practice Research Higher Degrees’ of ACCESS Journal: Critical Perspectives on Communication, Cultural & Policy Studies (ERA ranked A quality) in 2014 (Appendix 2). • A community of supervisory practice initiated through project partnerships, a national symposium where supervisors from across Australasia met in dialogue for the first time, resource sharing, and joint publishing opportunities. • A set of recommendations for supervision capacity building and academic development, produced through the triangulation of literature and contextual reviews, analysis of institutional frameworks, interviews with supervisors and national dialogues. It is anticipated that the project’s outcomes will support experienced and new supervisors in this emergent field, and so benefit HDR students, and will enable creative disciplines to build supervision capacity, and so to accommodate growth in postgraduate enrolments. Funded as a pilot project, the project set out to establish a robust research base to provide a foundation for future work involving sharing good practices, resource building, and designing effective approaches to academic development for supervisors. Recommendations that were produced out of this project include the need to extend beyond generic, formal training for supervisors to academic development that harnesses and extends distributed leadership; focuses on local, disciplinary contexts; has a strong emphasis on case studies; provides diverse resources; and facilitates dialogue between supervisors. Recommendations also include developing frameworks for mentoring new supervisors and building a national network to facilitate cross-institutional discourse, disseminate good practices, and share insights into the management of risk factors, ethical issues, and preparing candidates for examination. As a pilot investigation, the outcomes of this project lay the ground for this future work.

12 principles for the effective supervision of creative practice higher research degrees, dispatches from the field

In late 2012 and early 2013 we interviewed 25 experienced and early career supervisors of creative practice higher research degrees. This journey spanned five universities and a broad range of disciplines including visual art, music, performing art, new media, creative writing, fashion, graphic design, interaction design and interior design. Some of the supervisors we interviewed were amongst the first to complete and supervise practice-led and practice-based PhDs; some have advocated for and defined this emergent field; and some belong to the next generation of supervisors who have confidently embarked on this exciting and challenging path. Their reflections have brought to light many insights gained over the past decade. Here we have drawn together common themes into a collection of principles and best practice examples. We present them as advice rather than rules, as one thing that the supervisors were unanimous about is the need to avoid proscriptive models and frameworks, and to foster creativity and innovation in what is still an emergent field of postgraduate supervision. It is with thanks to all of the supervisors who contributed to these conversations, and their generosity in sharing their practices, that we present their advice, exemplars and case studies.

Harm, responsibility, age and consent

This article explores the contradictory ways in which adolescents just under the age of consent are represented in illegal sexual relations with both men and women who are over the age of consent. We are specifically interested in the ways in which the gender of the adolescent and the adult affect public perceptions, legal responses and perceptions of harm of sexual relations. We argue that the development of an indiscriminate legal and policy narrative of child abuse which increasingly includes all aspects of adolescent sexuality, ‘erases’ adolescent subjectivity. By exploring the nuanced ways in which the historical construction of childhood as sexually innocent intersects with current cultural scripts of femininity and masculinity, this article hopes to add to the small but growing literature on the issue of sexual consent, sexual ethics and sexual citizenship for young people.

Punishment Avoidance and Intentional Risky Driving Behaviour : What are the Implications for ‘Getting Away with it’?

Every motorised jurisdiction mandates legal driving behaviour which facilitates driver mobility and road user safety through explicit road rules that are enforced by regulatory authorities such as the Police. In road safety, traffic law enforcement has been very successfully applied to modify road user behaviour, and increasingly technology is fundamental in detecting illegal road user behaviour. Furthermore, there is also sound evidence that highly visible and/or intensive enforcement programs achieve long-term deterrent effects. To illustrate, in Australia random breath testing has considerably reduced the incidence and prevalence of driving whilst under the influence of alcohol. There is, however, evidence that many road rules continue to be broken, including speeding and using a mobile phone whilst driving, and there are many instances where drivers are not detected or sufficiently sanctioned for these transgressions. Furthermore, there is a growing body of evidence suggesting that experiences of punishment avoidance – that is, successful attempts at avoiding punishment such as drivers talking themselves out of a ticket, or changing driving routes to evade detection –are associated with and predictive of the extent of illegal driving behaviour and future illegal driving intentions. Therefore there is a need to better understand the phenomenon of punishment avoidance to enhance our traffic law enforcement procedures and therefore safety of all road users. This chapter begins with a review of the young driver road safety problem, followed by an examination of contemporary deterrence theory to enhance our understanding of both the experiences and implications of punishment avoidance in the road environment. It is noteworthy that in situations where detection and punishment remain relatively rare, such as on extensive road networks, the research evidence suggests that experiences of punishment avoidance may have a stronger influence upon risky driving behaviour than experiences of punishment. Finally, data from a case study examining the risky behaviour of young drivers will be presented, and the implications for ‘getting away with it’ will be discussed.

A state-wide systems approach to embedding the learning and teaching of sustainability in teacher education

Education systems have a key role to play in preparing future citizens to engage in sustainable living practices and help create a more sustainable world. Many schools throughout Australia have begun to develop whole-school approaches to sustainability education that are supported by national and state policies and curriculum frameworks. Preservice teacher education, however, lags behind in building the capacity of new teachers to initiate and implement such approaches (ARIES, 2010). This proposed project seeks to develop a state-wide systems approach to embedding Education for Sustainability (EfS) in teacher education that is aligned with the Australian National Curriculum and the aspirations for EfS in the Melbourne Declaration and other national documents. Representatives from all teacher education institutions and other agents of change in the Queensland education system will be engaged in a multilevel systems approach, involving collaboration at the state, institutional and course levels, to develop curriculum practices that reflect a shared vision of EfS.

Applying the ecological model of behavior change to a physical activity trial in retirement communities : description of the study protocol

Objectives To describe the intervention protocol for the first multilevel ecological intervention for physical activity in retirement communities that addresses individual, interpersonal and community influences on behavior change. Design A cluster randomized controlled trial design was employed with two study arms: a physical activity intervention and an attention control successful aging condition. Setting Sixteen continuing care retirement communities in San Diego County. Participants Three hundred twenty older adults, aged 65 years and older, are being recruited to participate in the trial. In addition, peer leaders are being recruited to lead some study activities, especially to sustain the intervention after study activities ceased. Intervention Participants in the physical activity trial receive individual, interpersonal and community intervention components. The individual level components include pedometers, goal setting and individual phone counseling. The interpersonal level components include group education sessions and peer-led activities. The community level components include resource audits and enumeration, tailored walking maps, and community improvement projects. The successful aging group receives individual and group attention about successful aging topics. Measurements The main outcome is light to moderate physical activity, measured objectively by accelerometry. Other objective outcomes included physical functioning, blood pressure, physical fitness, and cognitive functioning. Self report measures include depressive symptoms and health related quality of life. Results The intervention is being delivered successfully in the communities and compliance rates are high. Conclusion Ecological Models call for interventions that address multiple levels of the model. Previous studies have not included components at each level and retirement communities provide a model environment to demonstrate how to implement such an intervention.

Embedding EfS in teacher education : an introductory guide to using the systems change model

Welcome to this introductory guide on using a systems change model to embed Education for Sustainability (EfS) into teacher education. Pressing sustainability issues such as climate change, biodiversity loss and depletion of non-renewable resources pose new challenges for education. The importance of education in preparing future citizens to engage in sustainable living practices and help create a more sustainable world is widely acknowledged. As a result many universities around the world are beginning to recognize the need to integrate EfS into their teacher education programs. However, evidence indicates that there is little or no core EfS knowledge or pedagogy in pre-service teacher courses available to student teachers in a thorough and systematic fashion. Instead efforts are fragmented and individually or, at best, institutionally-based and lacking a systems approach to change, an approach that is seen as essential to achieving a sustainable society (Henderson & Tilbury, 2004). The result is new teachers are graduating without the necessary knowledge or skills to teach in ways that enable them to prepare their students to cope well with the new and emerging challenges their communities face. This guide has been prepared as part of a teaching and learning research project that applied a systems change approach to embedding the learning and teaching of sustainability into pre-service teacher education. The processes, outcomes and lessons learnt from this project are presented here as a guide for navigating pathways to systemic change in the journey of re-orienting teacher education towards sustainability. The guide also highlights how a systems change approach can be used to successfully enact change within a teacher education system. If you are curious about how to introduce and embed EfS into teacher education – or have tried other models and are looking for a more encompassing, transformative approach – this guide is designed to help you. The material presented in this guide is designed to be flexible and adaptive. However you choose to use the content, our aim is to help you and your students develop new perspectives, promote discussion and to engage with a system-wide approach to change.