EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer : analysis of data from the phase 3 FLEX study

Background: Findings from the phase 3 First-Line ErbituX in lung cancer (FLEX) study showed that the addition of cetuximab to first-line chemotherapy significantly improved overall survival compared with chemotherapy alone (hazard ratio [HR] 0·871, 95% CI 0·762-0·996; p=0·044) in patients with advanced non-small-cell lung cancer (NSCLC). To define patients benefiting most from cetuximab, we studied the association of tumour EGFR expression level with clinical outcome in FLEX study patients. Methods: We used prospectively collected tumour EGFR expression data to generate an immunohistochemistry score for FLEX study patients on a continuous scale of 0-300. We used response data to select an outcome-based discriminatory threshold immunohistochemistry score for EGFR expression of 200. Treatment outcome was analysed in patients with low (immunohistochemistry score <200) and high (≥200) tumour EGFR expression. The primary endpoint in the FLEX study was overall survival. We analysed patients from the FLEX intention-to-treat (ITT) population. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798. Findings: Tumour EGFR immunohistochemistry data were available for 1121 of 1125 (99·6%) patients from the FLEX study ITT population. High EGFR expression was scored for 345 (31%) evaluable patients and low for 776 (69%) patients. For patients in the high EGFR expression group, overall survival was longer in the chemotherapy plus cetuximab group than in the chemotherapy alone group (median 12·0 months [95% CI 10·2-15·2] vs 9·6 months [7·6-10·6]; HR 0·73, 0·58-0·93; p=0·011), with no meaningful increase in side-effects. We recorded no corresponding survival benefit for patients in the low EGFR expression group (median 9·8 months [8·9-12·2] vs 10·3 months [9·2-11·5]; HR 0·99, 0·84-1·16; p=0·88). A treatment interaction test assessing the difference in the HRs for overall survival between the EGFR expression groups suggested a predictive value for EGFR expression (p=0·044). Interpretation: High EGFR expression is a tumour biomarker that can predict survival benefit from the addition of cetuximab to first-line chemotherapy in patients with advanced NSCLC. Assessment of EGFR expression could offer a personalised treatment approach in this setting. Funding: Merck KGaA. © 2012 Elsevier 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.

Modelling the salient factors influencing retired business professionals' participation in episodic skilled volunteering in rural settings

Retired business professionals represent an unexplored source of skill support for struggling rural communities. This research examined the feasibility of drawing on this valuable pool of knowledge and experience by engaging retirees in short term, project based volunteering roles in rural, not for profit agencies. Using the theory of planned behaviour and the functional approach to volunteering, the program of study generated a model comprising the key psychological and contextual factors determining the volunteers' decision to provide skill assistance in rural settings. The model provides a useful resource for creating suitable volunteering opportunities and for informing volunteer recruitment strategies.

Factors influencing health professionals' response to victims of domestic violence

This thesis examined factors influencing health professional's response to victims of domestic violence in Vietnam. As this is the first time that this type of research has been conducted in Vietnam, it was expected that the results would contribute significantly to local knowledge and should add to global perspectives. Since it is the first questionnaire about this topic to be developed in Vietnam, the psychometric property of the questionnaire was primarily established, resulting in the questionnaire being recommended to use for further study. By explaining the factors that affect the intentions to respond of health workers, this project provides key data for authorities to design intervention strategies to improve the responses of health professionals to victims of domestic violence in Vietnam.

A Century of American Economic Review : Insights on Critical Factors in Journal Publishing

By using information collected from numerous American Economic Review publications from the last 100 years, Torgler and Piatti examine the top publishing institutions to determine their most renowned AER papers based on citation success. Areas of interest include how often an individual can publish in the AER, how equally successful citations are distributed and who the top AER publishing authors are. The book explores what the level of cooperation is among authors and what drives systems such as the alphabetical name ordering. Torgler and Piatti critically examine the individual characteristics of AER authors, editors, editorial board members and referees and even tackle more intricate details such as the frequency of female publications in the AER. The authors observe and analyse the relationship between academic age and publication performance to see if there is any pattern on these factors and citation success. The book then goes on to analyse data concerning awards, and whether awards can increase the probability of publishing in the AER at a later stage

Coexpression of epidermal growth factor receptor with related factors is associated with a poor prognosis in non-small-cell lung cancer

The epidermal growth factor receptor (EGFR) is commonly expressed in non-small-cell lung cancer (NSCLC) and promotes a host of mechanisms involved in tumorigenesis. However, EGFR expression does not reliably predict prognosis or response to EGFR-targeted therapies. The data from two previous studies of a series of 181 consecutive surgically resected stage I-IIIA NSCLC patients who had survived in excess of 60 days were explored. Of these patients, tissue was available for evaluation of EGFR in 179 patients, carbonic anhydrase (CA) IX in 177 patients and matrix metalloproteinase-9 (MMP-9) in 169 patients. We have previously reported an association between EGFR expression and MMP-9 expression. We have also reported that MMP-9 (P=0.001) and perinuclear (p)CA IX (P=0.03) but not EGFR expression were associated with a poor prognosis. Perinuclear CA IX expression was also associated with EGFR expression (P<0.001). Multivariate analysis demonstrated that coexpression of MMP-9 with EGFR conferred a worse prognosis than the expression of MMP-9 alone (P<0.001) and coexpression of EGFR and pCA IX conferred a worse prognosis than pCA IX alone (P=0.05). A model was then developed where the study population was divided into three groups: group 1 had expression of EGFR without coexpression of MMP-9 or pCA IX (number=21); group 2 had no expression of EGFR (number=75); and group 3 had coexpression of EGFR with pCA IX or MMP-9 or both (number=70). Group 3 had a worse prognosis than either groups 1 or 2 (P=0.0003 and 0.027, respectively) and group 1 had a better prognosis than group 2 (P=0.036). These data identify two cohorts of EGFR-positive patients with diametrically opposite prognoses. The group expressing either EGFR and or both MMP-9 and pCA IX may identify a group of patients with activated EGFR, which is of clinical relevance with the advent of EGFR-targeted therapies. © 2004 Cancer Research UK.

Creating a Sustainability Scorecard as a predictive tool for measuring the complex social, economic and environmental impacts of industries, a case study : assessing the viability and sustainability of the dairy industry

Sustainability is a key driver for decisions in the management and future development of industries. The World Commission on Environment and Development (WCED, 1987) outlined imperatives which need to be met for environmental, economic and social sustainability. Development of strategies for measuring and improving sustainability in and across these domains, however, has been hindered by intense debate between advocates for one approach fearing that efforts by those who advocate for another could have unintended adverse impacts. Studies attempting to compare the sustainability performance of countries and industries have also found ratings of performance quite variable depending on the sustainability indices used. Quantifying and comparing the sustainability of industries across the triple bottom line of economy, environment and social impact continues to be problematic. Using the Australian dairy industry as a case study, a Sustainability Scorecard, developed as a Bayesian network model, is proposed as an adaptable tool to enable informed assessment, dialogue and negotiation of strategies at a global level as well as being suitable for developing local solutions.

Exploring influencing factors of short-lived buildings in China's urban renewal : evidence from Chongqing

With the fast development of urban sprawl and renewal in China, many buildings are “non-nature” short-lived, i.e. demolished after only a few years. For this concern, this research explores the influencing factors of short-lived buildings and provides the scientific foundation for sustainable urban management and planning. Cases for this research are 1734 buildings demolished in Jiangbei district, the middle region of Chongqing City. Internal and external factors for the short-lived buildings are identified by applying logistic analysis. The results indicate that nine factors have significant influence on short-lived buildings. This research also find that buildings with low density, utilization and compensation while high land development potential are more likely to become short-lived buildings.

Prevalence of risk factors for undiagnosed obstructive sleep apnoea is high in truck drivers on UK roads

Objectives To determine the prevalence of symptoms and risk factors of obstructive sleep apnoea (OSA) in truck drivers at a UK large truck stop. Methods Over a 5 day period, truck drivers completed a short questionnaire at a major UK ‘truck stop’. The questionnaire asked about OSA rist factors and symptoms, and included the Epworth Sleepiness Scale (ESS). Additionally, measurements of height, weight and collar size were taken. 148 truck drivers participated and within this random group the risk factors of OSA that were looked for were:men age over 40 y, obesity, parge neck circumference, smoking, high ESS and bed partner reporting snoring with witnessed apnoeas. Results Our sample were all men, with 82% aged over 40 y. 47% were obese (compared with 23% for UK men in general) and average neck circumference was 42 cm (compared with 38 cm for UK men in general – Martin et al 1997). 31% smoked (vs 21% for general population), and ESS averaged 2.1 points higher than expected for a healthy population (Johns et al 1997). Snoring was quite evident at 57% (compared wth 40% for men in general) and witnessed apnoeas were almost double (7%) compared with 3.8% given by Ohayon et al (1997) generally for men. Conclusion 8 key symptoms and risk factors of OSA have been found to be prevalent in a sample of truck drivers on UK roads, and to greater extent that for estimates in the general male population. Bed partners of truck drivers reporting witnessed apnoeas strongly suggests this group has a high potential for undiagnosed OSA. OSA sufferers are known to be at high risk of causing road traffi c accidents. This, together with the large size of trucks, then the potential for serious road crashes is great. Truck drivers, especially those who are obese, ought to be a high priority population for OSA screening.

Locally weighted learning model predictive control for nonlinear and time varying dynamics

This paper proposes an online learning control system that uses the strategy of Model Predictive Control (MPC) in a model based locally weighted learning framework. The new approach, named Locally Weighted Learning Model Predictive Control (LWL-MPC), is proposed as a solution to learn to control robotic systems with nonlinear and time varying dynamics. This paper demonstrates the capability of LWL-MPC to perform online learning while controlling the joint trajectories of a low cost, three degree of freedom elastic joint robot. The learning performance is investigated in both an initial learning phase, and when the system dynamics change due to a heavy object added to the tool point. The experiment on the real elastic joint robot is presented and LWL-MPC is shown to successfully learn to control the system with and without the object. The results highlight the capability of the learning control system to accommodate the lack of mechanical consistency and linearity in a low cost robot arm.

Technological tools for science classrooms : choosing and using for productive and sustainable teaching and learning experiences

In this age of rapidly evolving technology, teachers are encouraged to adopt ICTs by government, syllabus, school management, and parents. Indeed, it is an expectation that teachers will incorporate technologies into their classroom teaching practices to enhance the learning experiences and outcomes of their students. In particular, regarding the science classroom, a subject that traditionally incorporates hands-on experiments and practicals, the integration of modern technologies should be a major feature. Although myriad studies report on technologies that enhance students’ learning outcomes in science, there is a dearth of literature on how teachers go about selecting technologies for use in the science classroom. Teachers can feel ill prepared to assess the range of available choices and might feel pressured and somewhat overwhelmed by the avalanche of new developments thrust before them in marketing literature and teaching journals. The consequences of making bad decisions are costly in terms of money, time and teacher confidence. Additionally, no research to date has identified what technologies science teachers use on a regular basis, and whether some purchased technologies have proven to be too problematic, preventing their sustained use and possible wider adoption. The primary aim of this study was to provide research-based guidance to teachers to aid their decision-making in choosing technologies for the science classroom. The study unfolded in several phases. The first phase of the project involved survey and interview data from teachers in relation to the technologies they currently use in their science classrooms and the frequency of their use. These data were coded and analysed using Grounded Theory of Corbin and Strauss, and resulted in the development of a PETTaL model that captured the salient factors of the data. This model incorporated usability theory from the Human Computer Interaction literature, and education theory and models such as Mishra and Koehler’s (2006) TPACK model, where the grounded data indicated these issues. The PETTaL model identifies Power (school management, syllabus etc.), Environment (classroom / learning setting), Teacher (personal characteristics, experience, epistemology), Technology (usability, versatility etc.,) and Learners (academic ability, diversity, behaviour etc.,) as fields that can impact the use of technology in science classrooms. The PETTaL model was used to create a Predictive Evaluation Tool (PET): a tool designed to assist teachers in choosing technologies, particularly for science teaching and learning. The evolution of the PET was cyclical (employing agile development methodology), involving repeated testing with in-service and pre-service teachers at each iteration, and incorporating their comments i ii in subsequent versions. Once no new suggestions were forthcoming, the PET was tested with eight in-service teachers, and the results showed that the PET outcomes obtained by (experienced) teachers concurred with their instinctive evaluations. They felt the PET would be a valuable tool when considering new technology, and it would be particularly useful as a means of communicating perceived value between colleagues and between budget holders and requestors during the acquisition process. It is hoped that the PET could make the tacit knowledge acquired by experienced teachers about technology use in classrooms explicit to novice teachers. Additionally, the PET could be used as a research tool to discover a teachers’ professional development needs. Therefore, the outcomes of this study can aid a teacher in the process of selecting educationally productive and sustainable new technology for their science classrooms. This study has produced an instrument for assisting teachers in the decision-making process associated with the use of new technologies for the science classroom. The instrument is generic in that it can be applied to all subject areas. Further, this study has produced a powerful model that extends the TPACK model, which is currently extensively employed to assess teachers’ use of technology in the classroom. The PETTaL model grounded in data from this study, responds to the calls in the literature for TPACK’s further development. As a theoretical model, PETTaL has the potential to serve as a framework for the development of a teacher’s reflective practice (either self evaluation or critical evaluation of observed teaching practices). Additionally, PETTaL has the potential for aiding the formulation of a teacher’s personal professional development plan. It will be the basis for further studies in this field.

Is recovery driven by central or peripheral factors? A role for the brain in recovery following intermittent-sprint exercise

Prolonged intermittent-sprint exercise (i.e., team sports) induce disturbances in skeletal muscle structure and function that are associated with reduced contractile function, a cascade of inflammatory responses, perceptual soreness, and a delayed return to optimal physical performance. In this context, recovery from exercise-induced fatigue is traditionally treated from a peripheral viewpoint, with the regeneration of muscle physiology and other peripheral factors the target of recovery strategies. The direction of this research narrative on post-exercise recovery differs to the increasing emphasis on the complex interaction between both central and peripheral factors regulating exercise intensity during exercise performance. Given the role of the central nervous system (CNS) in motor-unit recruitment during exercise, it too may have an integral role in post-exercise recovery. Indeed, this hypothesis is indirectly supported by an apparent disconnect in time-course changes in physiological and biochemical markers resultant from exercise and the ensuing recovery of exercise performance. Equally, improvements in perceptual recovery, even withstanding the physiological state of recovery, may interact with both feed-forward/feed-back mechanisms to influence subsequent efforts. Considering the research interest afforded to recovery methodologies designed to hasten the return of homeostasis within the muscle, the limited focus on contributors to post-exercise recovery from CNS origins is somewhat surprising. Based on this context, the current review aims to outline the potential contributions of the brain to performance recovery after strenuous exercise.

Environmental factors associated with active living in retirement village residents : findings from an exploratory qualitative enquiry

This exploratory enquiry employs qualitative methods to advance knowledge and understanding of physical environmental attributes related to active living among residents of Australian retirement villages. Six focus groups (n = 51 residents) were held and participants described how their current, and subsequently ideal, retirement village and neighborhood supported active lifestyles. Thematic analysis revealed three key environmental factors associated with active living: a positive social environment within the village; services and facilities provided in the village and wider neighborhood; and the presence of suitable pedestrian infrastructure. The unique discovery that environmental factors of both the retirement village and the surrounding neighborhood were associated with residents’ active living raises many questions for study. Findings informed the development of a survey instrument, and further understanding in this area has the potential to contribute to the design and siting practices of senior housing complexes within neighborhoods.

Bcl-2 genes and growth factors in the pathology of ischaemic acute renal failure

For the past decade, an attempt has been made by many research groups to define the roles of the growing number of Bcl-2 gene family proteins in the apoptotic process. The Bcl-2 family consists of pro-apoptotic (or cell death) and anti-apoptotic (or cell survival) genes and it is the balance in expression between these gene lineages that may determine the death or survival of a cell. The majority of studies have analysed the role/s of the Bcl-2 genes in cancer development. Equally important is their role in normal tissue development, homeostasis and non-cancer disease states. Bcl-2 is crucial for normal development in the kidney, with a deficiency in Bcl-2 producing such malformation that renal failure and death result. As a corollary, its role in renal disease states in the adult has been sought. Ischaemia is one of the most common causes of both acute and chronic renal failure. The section of the kidney that is most susceptible to ischaemic damage is the outer zone of the outer medulla. Within this zone the proximal tubules are most sensitive and often die by necrosis or desquamate. In the distal nephron, apoptosis is the more common form of cell death. Recent results from our laboratory have indicated that ischaemia-induced acute renal failure is associated with up-regulation of two anti-apoptotic Bcl-2 proteins (Bcl-2 and Bcl-XL) in the damaged distal tubule and occasional up-regulation of Bax in the proximal tubule. The distal tubule is a known reservoir for several growth factors important to renal growth and repair, such as insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF). One of the likely possibilities for the anti-cell death action of the Bcl-2 genes is that the protected distal cells may be able to produce growth factors that have a further reparative or protective role via an autocrine mechanism in the distal segment and a paracrine mechanism in the proximal cells. Both EGF and IGF-1 are also up-regulated in the surviving distal tubules and are detected in the surviving proximal tubules, where these growth factors are not usually synthesized. As a result, we have been using in vitro methods to test: (i) the relative sensitivities of renal distal and proximal epithelial cell populations to injury caused by mechanisms known to act in ischaemia-reperfusion; (ii) whether a Bcl-2 anti-apoptotic mechanism acts in these cells; and (iii) whether an autocrine and/or paracrine growth factor mechanism is initiated. The following review discusses the background to these studies as well as some of our preliminary results.

Factors associated with the isolation of Nontuberculous mycobacteria (NTM) from a large municipal water system in Brisbane, Australia

Background Nontuberculous mycobacteria (NTM) are normal inhabitants of a variety of environmental reservoirs including natural and municipal water. The aim of this study was to document the variety of species of NTM in potable water in Brisbane, QLD, with a specific interest in the main pathogens responsible for disease in this region and to explore factors associated with the isolation of NTM. One-litre water samples were collected from 189 routine collection sites in summer and 195 sites in winter. Samples were split, with half decontaminated with CPC 0.005%, then concentrated by filtration and cultured on 7H11 plates in MGIT tubes (winter only). Results Mycobacteria were grown from 40.21% sites in Summer (76/189) and 82.05% sites in winter (160/195). The winter samples yielded the greatest number and variety of mycobacteria as there was a high degree of subculture overgrowth and contamination in summer. Of those samples that did yield mycobacteria in summer, the variety of species differed from those isolated in winter. The inclusion of liquid media increased the yield for some species of NTM. Species that have been documented to cause disease in humans residing in Brisbane that were also found in water include M. gordonae, M. kansasii, M. abscessus, M. chelonae, M. fortuitum complex, M. intracellulare, M. avium complex, M. flavescens, M. interjectum, M. lentiflavum, M. mucogenicum, M. simiae, M. szulgai, M. terrae. M. kansasii was frequently isolated, but M. avium and M. intracellulare (the main pathogens responsible for disease is QLD) were isolated infrequently. Distance of sampling site from treatment plant in summer was associated with isolation of NTM. Pathogenic NTM (defined as those known to cause disease in QLD) were more likely to be identified from sites with narrower diameter pipes, predominantly distribution sample points, and from sites with asbestos cement or modified PVC pipes. Conclusions NTM responsible for human disease can be found in large urban water distribution systems in Australia. Based on our findings, additional point chlorination, maintenance of more constant pressure gradients in the system, and the utilisation of particular pipe materials should be considered.