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.

Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations

Purpose The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR/ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation-positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS). Patients and Methods In this phase III study, eligible patients with stage IIIB/IV lung adenocarcinoma were screened for EGFR mutations. Mutation-positive patients were stratified by mutation type (exon 19 deletion, L858R, or other) and race (Asian or non-Asian) before two-to-one random assignment to 40 mg afatinib per day or up to six cycles of cisplatin plus pemetrexed chemotherapy at standard doses every 21 days. The primary end point was PFS by independent review. Secondary end points included tumor response, overall survival, adverse events, and patient-reported outcomes (PROs). Results A total of 1,269 patients were screened, and 345 were randomly assigned to treatment. Median PFS was 11.1 months for afatinib and 6.9 months for chemotherapy (hazard ratio [HR], 0.58; 95% CI, 0.43 to 0.78; P = .001). Median PFS among those with exon 19 deletions and L858R EGFR mutations (n = 308) was 13.6 months for afatinib and 6.9 months for chemotherapy (HR, 0.47; 95% CI, 0.34 to 0.65; P = .001). The most common treatmentrelated adverse events were diarrhea, rash/acne, and stomatitis for afatinib and nausea, fatigue, and decreased appetite for chemotherapy. PROs favored afatinib, with better control of cough, dyspnea, and pain. Conclusion Afatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations.

Circle Stories

Research background: Circle Stories was a live performance curated by Brydie-Leigh Bartleet, Naomi Sunderland, Gavin Carfoot and the Winanjjikari Music Centre as part of the Desert Harmony Festival 2013. The performance was the culmination of five years of research into intercultural performing arts practice, undertaken in partnership with Barkly Regional Arts. This work has built on existing scholarly work in community service learning by Marilynne Boyle-Baise, approaches to intercultural music making with Australian First Peoples by Karl Neuenfeldt, and studies of Indigenous popular music by Peter Dunbar-Hall and Chris Gibson. The performance followed the popular songwriters’ circle approach, in which Aboriginal musicians and elders presented their songs along with tertiary music students, as part of a broader dialogue with each other and the audience. Each performance provided an opportunity to highlight the importance of music in the development of intercultural knowledge and understanding. The project asked the research question, how can collaborative music performance foster mutual learning, intercultural knowledge and reconciliation? Research contribution: The project development and performance of Circle Stories identified that mutual learning and intercultural knowledge can result most effectively through long-term and meaningful relationships underpinning collaborative creative practice. Research significance: Following a general call for proposals, the performance was peer reviewed and selected for inclusion in the Desert Harmony Festival program. The research context of the work is detailed in Brydie-Leigh Bartleet and Gavin Carfoot 2013. "Desert harmony: Stories of collaboration between Indigenous musicians and university students." International Education Journal: Comparative Perspectives 12 (1): 180-196.

Practice and Procedures - costs - offer to settle by plaintiff under UCPR r360 for amount of claim plus costs

In JLG Industries Inc v Teetree Pty Ltd [2002] QDC 031 the court considered the implications in terms of costs of an offer to settle by the plaintiff under the UCPR where the element of compromise involved only acceptance of the amount of claim without interest.

Biological performance of a polycaprolactone-based scaffold plus recombinant human morphogenetic protein-2 (rhBMP-2) in an ovine thoracic interbody fusion model

PURPOSE. We develop a sheep thoracic spine interbody fusion model to study the suitability of polycaprolactone-based scaffold and recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute within the thoracic spine. The surgical approach is a mini- open thoracotomy with relevance to minimally invasive deformity correction surgery for adolescent idiopathic scoliosis. To date there are no studies examining the use of this biodegradable implant in combination with biologics in a sheep thoracic spine model. METHODS. In the present study, six sheep underwent a 3-level (T6/7, T8/9 and T10/11) discectomy with randomly allocated implantation of a different graft substitute at each of the three levels; (i) calcium phosphate (CaP) coated polycaprolactone-based scaffold plus 0.54μg rhBMP-2, (ii) CaP coated PCL- based scaffold alone or (iii) autograft (mulched rib head). Fusion was assessed at six months post-surgery. RESULTS. Computed Tomographic scanning demonstrated higher fusion grades in the rhBMP-2 plus PCL- based scaffold group in comparison to either PCL-based scaffold alone or autograft. These results were supported by histological evaluations of the respective groups. Biomechanical testing revealed significantly higher stiffness for the rhBMP-2 plus PCL- based scaffold group in all loading directions in comparison to the other two groups. CONCLUSION. The results of this study demonstrate that rhBMP-2 plus PCL- based scaffold is a viable bone graft substitute, providing an optimal environment for thoracic interbody spinal fusion in a large animal model.

6 versus 12 month performance of polycaprolactone-based scaffold plus recombinant human morphogenetic protein-2 (rhBMP-2) in an ovine thoracic interbody fusion model

Introduction Well-designed biodegradable scaffolds in combination with bone growth factors offer a valuable alternative to the current gold standard autograft in spinal fusion surgery Yong et al. (2013). Here we report on 6- vs 12- month data set evaluating the longitudinal performance of a CaP coated polycaprolactone (PCL) scaffold loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute within a large preclinical animal model. Methods Twelve sheep underwent a 3-level (T6/7, T8/9 and T10/11) discectomy with randomly allocated implantation of a different graft substitute at each of the three levels; (i) calcium phosphate (CaP) coated polycaprolactone based scaffold plus 0.54µg rhBMP-2, (ii) CaP coated PCL- based scaffold alone or (iii) autograft (mulched rib head). Fusion assessments were performed via high resolution clinical computed tomography and histological evaluation were undertaken at six (n=6) and twelve (n=6) months post-surgery using the Sucato grading system (Sucato et al. 2004). Results The computed tomography fusion grades of the 6- and 12- months in the rhBMP-2 plus PCL- based scaffold group were 1.9 and 2.1 respectively, in the autograft group 1.9 and 1.3 respectively, and in the scaffold alone group 0.9 and 1.17 respectively. There were no statistically significant differences in the fusion scores between 6- and 12- month for the rhBMP plus PCL- based scaffold or PCL – based scaffold alone group however there was a significant reduction in scores in the autograft group. These scores were seen to correlate with histological evaluations of the respective groups. Conclusions The results of this study demonstrate the efficacy of scaffold-based delivery of rhBMP-2 in promoting higher fusion grades at 6- and 12- months in comparison to the scaffold alone or autograft group within the same time frame. Fusion grades achieved at six months using PCL+rhBMP-2 are not significantly increased at twelve months post-surgery.

Basic finance made accessible in Excel 2007 : "the big 5, plus 2"

The basic principles and equations are developed for elementary finance, based on the concept of compound interest. The five quantities of interest in such problems are present value, future value, amount of periodic payment, number of periods and the rate of interest per period. We consider three distinct means of computing each of these five quantities in Excel 2007: (i) use of algebraic equations, (ii) by recursive schedule and the Goal Seek facility, and (iii) use of Excel's intrinsic financial functions. The paper is intended to be used as the basis for a lesson plan and contains many examples and solved problems. Comment is made regarding the relative difficulty of each approach, and a prominent theme is the systematic use of more than one method to increase student understanding and build confidence in the answer obtained. Full instructions to build each type of model are given and a complete set of examples and solutions may be downloaded (Examples.xlsx and Solutions.xlsx).

Abandoning the Magic Circle

As a concept, the magic circle is in reality just 4 years old. Whilst often accredited to Johan Huizinga (1955), the modern usage of term in truth belongs to Katie Salen and Eric Zimmerman. It became in academia following the publication of “Rules of Play” in 2003. Because of the terminologyused, it carries with it unhelpful preconceptions that the game world, or play-space, excludes reality. In this paper, I argue that Salen and Zimmerman (2003) have taken a term used as an example, and applied a meaning to it that was never intended, based primarily upon definitions given by other authors, namely Apter (1991) and Sniderman (n.d.). I further argue that the definition itself contains a logical fallacy, which has prevented the full understanding of the definition in later work. Through a study of the literature in Game Theory, and examples of possible issues which could arise in contemporary games, I suggest that the emotions of the play experience continue beyond the play space, and that emotions from the “real world” enter it with the participants. I consider a reprise of the Stanley Milgram Obedience Experiment (2006), and what that tells us about human emotions and the effect that events taking place in a virtual environment can have upon them. I evaluate the opinion espoused by some authors of there being different magic circles for different players, and assert that this is not a useful approach to take when studying games, because it prevents the analysis of a game as a single entity. Furthermore I consider the reasons given by other authors for the existence of the Magic Circle, and I assert that the term “Magic Circle” should be discarded, that it has no relevance to contemporary games, and indeed it acts as a hindrance to the design and study of games. I conclude that the play space which it claims to protect from the courts and other governmental authorities would be better served by the existing concepts of intent, consent, and commonly accepted principles associated with international travel.

Stepping outside the circle : a reflective practice framework for creative facilitators

Stepping Outside the Circle was a practice-based research project focussed on creating a professional reflection framework for creative facilitators working within the community, education, corporate and health and wellbeing sectors. Underpinned by theories of critical reflection, transformative learning, reflexivity and agency, this study explored the potential benefits of multimodal inquiry processes, adapting existing reflective practice models for the unique requirements of creative facilitation contexts. Through application of the key findings from this research, synthesised in a practitioner resource, it is hoped that individual practitioners and creative organisations may develop their understanding of evaluation strategies, self- reflexivity, professional sustainability and practitioner self-care.

Relationship between EGFR expression, EGFR mutation status, and the efficacy of chemotherapy plus cetuximab in FLEX study patients with advanced non-small-cell lung cancer

INTRODUCTION: The phase III FLEX study (NCT00148798) in advanced non-small-cell lung cancer indicated that the survival benefit associated with the addition of cetuximab to cisplatin and vinorelbine was limited to patients whose tumors expressed high levels of epidermal growth factor receptor (EGFR) (immunohistochemistry score of >/=200; scale 0-300). We assessed whether the treatment effect was also modulated in FLEX study patients by tumor EGFR mutation status. METHODS: A tumor mutation screen of EGFR exons 18 to 21 included 971 of 1125 (86%) FLEX study patients. Treatment outcome in low and high EGFR expression groups was analyzed across efficacy endpoints according to tumor EGFR mutation status. RESULTS: Mutations in EGFR exons 18 to 21 were detected in 133 of 971 tumors (14%), 970 of which were also evaluable for EGFR expression level. The most common mutations were exon 19 deletions and L858R (124 of 133 patients; 93%). In the high EGFR expression group (immunohistochemistry score of >/=200), a survival benefit for the addition of cetuximab to chemotherapy was demonstrated in patients with EGFR wild-type (including T790M mutant) tumors. Although patient numbers were small, those in the high EGFR expression group whose tumors carried EGFR mutations may also have derived a survival benefit from the addition of cetuximab to chemotherapy. Response data suggested a cetuximab benefit in the high EGFR expression group regardless of EGFR mutation status. CONCLUSIONS: The survival benefit associated with the addition of cetuximab to first-line chemotherapy for advanced non-small-cell lung cancer expressing high levels of EGFR is not limited by EGFR mutation status.

Review of the ACT Road Ready and Road Ready Plus Novice Driver Road Safety Education Course Material

This report documents research that was commissioned in order to review the materials used in the Road Ready program for relevancy and acceptability to the target audiences as part of the implementation of the ACT Road Safety Strategy Action Plan. Relevant literature on young driver crash risk and best practice principles in driver education was reviewed as a first step (Section 2). The evidence for effectiveness of driver education programs in Australia was summarised (Section 3) and a separate review of the use of incentives in relation to driver education was performed. The brief called for an expert review of the materials and delivery design for both the Road Ready and Road Ready Plus programs. This is reported in Section 5, along with the overall recommendations for program improvement. More specific comments on individual modules in the Road Ready program are listed at the end of Section 5. Lastly, feedback from stakeholders, specifically the facilitators and teachers of the programs, as well as former students who have completed the Road Ready program, was sought. Interviews and surveys were conducted with these groups. Summaries of the methods and findings are contained in Section 6.

Longitudinal performance of polycaprolactone-based scaffold plus recombinant human morphogenetic protein-2 (rhBMP-2) in large preclinical animal model : 6- versus 12 months

There is strong current interest in the use of biodegradable scaffolds in combination with bone growth factors as a valuable alternative to the current gold standard autograft in spinal fusion surgery Yong et al. (2013). Here we report on 6- vs 12- month data set evaluating the longitudinal performance of a CaP coated polycaprolactone (PCL) scaffold loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute within a preclinical ovine thoracic spine. The results of this study demonstrate the efficacy of scaffold-based delivery of rhBMP-2 in promoting higher fusion grades at 6- and 12- months in comparison to the scaffold alone or autograft group within the same time frame. Fusion grades achieved at six months using PCL+rhBMP-2 are not significantly increased at twelve months post surgery.

A multimodal physiotherapy programme plus deep water running for improving cancer-related fatigue and quality of life in breast cancer survivors

The aim of the study was to assess the feasibility and effectiveness of aquatic‐based exercise in the form of deep water running ( DWR ) as part of a multimodal physiotherapy programme ( MMPP ) for breast cancer survivors. A controlled clinical trial was conducted in 42 primary breast cancer survivors recruited from community‐based P rimary C are C entres. Patients in the experimental group received a MMPP incorporating DWR , 3 times a week, for an 8‐week period. The control group received a leaflet containing instructions to continue with normal activities. Statistically significant improvements and intergroup effect size were found for the experimental group for P iper F atigue S cale‐ R evised total score ( d = 0.7, P = 0.001), as well as behavioural/severity ( d = 0.6, P = 0.05), affective/meaning ( d = 1.0, P = 0.001) and sensory ( d = 0.3, P = 0.03) domains. Statistically significant differences between the experimental and control groups were also found for general health ( d = 0.5, P < 0.05) and quality of life ( d = 1.3, P < 0.05). All participants attended over 80% of sessions, with no major adverse events reported. The results of this study suggest MMPP incorporating DWR decreases cancer‐related fatigue and improves general health and quality of life in breast cancer survivors. Further, the high level of adherence and lack of adverse events indicate such a programme is safe and feasible.

The "virtuous circle": A case study examining the case for better embedding of Work Integrated Learning approaches into university journalism cirriculums

This paper explores the potential to focus and develop the approach to Work Integrated Learning (WIL)in journalism courses where this method is seen as a core principal of the program. It argues that, in many cases, such approaches are ill-defined and underdeveloped, a fact that weakens the possibility for strong course outcomes. It then examines the particular case of QUT coverage of the 2014 G20 Leader's summit to illustrate how an all-of-course WIL approach to G20 coverage-coupled with a tailored interaction with the library-might provide an enhanced student experience as well as unlock the potential for greater knowledge transfer between university journalism courses and industry partners.