Crizotinib versus chemotherapy in advanced ALK-positive lung cancer

BACKGROUND: In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK ) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK. Whether crizotinib is superior to standard chemotherapy with respect to efficacy is unknown. METHODS: We conducted a phase 3, open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen. Patients were randomly assigned to receive oral treatment with crizotinib (250 mg) twice daily or intravenous chemotherapy with either pemetrexed (500 mg per square meter of body-surface area) or docetaxel (75 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study. The primary end point was progression-free survival. RESULTS: The median progression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy group (hazard ratio for progression or death with crizotinib, 0.49; 95% confidence interval [CI], 0.37 to 0.64; P<0.001). The response rates were 65% (95% CI, 58 to 72) with crizotinib, as compared with 20% (95% CI, 14 to 26) with chemotherapy (P<0.001). An interim analysis of overall survival showed no significant improvement with crizotinib as compared with chemotherapy (hazard ratio for death in the crizotinib group, 1.02; 95% CI, 0.68 to 1.54; P=0.54). Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, alopecia, and dyspnea. Patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with crizotinib than with chemotherapy. CONCLUSIONS: Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non-small-cell lung cancer with ALK rearrangement. (Funded by Pfizer; ClinicalTrials.gov number, NCT00932893.) Copyright © 2013 Massachusetts Medical Society.

Developing cultural responsiveness in environmental design students through digital storytelling and photovoice

As the Latino population in the United States grows, it will become increasingly important for undergraduate students in environmental design and related disciplines to become more culturally responsive and learn how to understand and address challenges faced by population groups, such as Latino youth. To this end, we involved environmental design undergraduate students at the University of Colorado in a service-learning class to mentor Latino youth in the creation of multimedia narratives using photovoice and digital storytelling techniques. The introduction of technology was used as a bridge between the two groups and to provide a platform for the Latino youth to reveal their community experiences. Based on focus group results, we describe the impact on the undergraduate students and provide recommendations for similar programs that can promote cultural responsiveness through the use of digital technology and prepare environmental design students to work successfully in increasingly diverse communities.

Sustainability of a successful health and nutrition program in a remote Aboriginal community

OBJECTIVE: To assess the long term effect of a nutrition program in a remote Aboriginal community (Minjilang). DESIGN: Evaluation of nutritional outcomes over the three years before and the three years after a health and nutrition program that ran from June 1989 to June 1990. Turnover of food items at the community store was used as a measure of dietary intake at Minjilang and a comparison community. SETTING: A community of about 150 Aboriginal people live at Minjilang on Croker Island, 240 km north-east of Darwin. A similar community of about 300 people on another island was used as the comparison. RESULTS: The program produced lasting improvements in dietary intake of most target foods (including fruit, vegetables and wholegrain bread) and nutrients (including folate, ascorbic acid and thiamine). Sugar intake fell in both communities before the program, but the additional decrease in sugar consumption during the program at Minjilang "rebounded" in the next year. Dietary improvements in the comparison community were delayed and smaller than at Minjilang. CONCLUSIONS: The success of the program at Minjilang was linked to an ongoing process of social change, which in turn provided a stimulus for dietary improvement in the comparison community. When Aboriginal people themselves control and maintain ownership of community-based intervention programs, nutritional improvements can be initiated and sustained.

Dispute resolution across platforms : offshore gambling industry & EVE online

Contemporary online environments suffer from a regulatory gap; that is there are few options for participants between customer service departments and potentially expensive court cases in foreign jurisdictions. Whatever form of regulation ultimately fills that gap will be charged with determining whether specific behavior, within a specific environment, is fair or foul; whether it’s cheating or not. However, cheating is a term that, despite substantial academic study, remains problematic. Is anything the developer doesn’t want you to do cheating? Is it only if your actions breach the formal terms of service? What about the community norms, do they matter at all? All of these remain largely unresolved questions, due to the lack of public determination of cases in such environments, which have mostly been settled prior to legal action. In this paper, I propose a re-branding of participant activity in such environments into developer-sanctioned, advantage play, and cheating. Advantage play, ultimately, is activity within the environment in which the player is able to turn the mechanics of the environment to their advantage without breaching the rules of the environment. Such a definition, and the term itself, is based on the usage of the term within the gambling industry, in which advantage play is considered betting with the advantage in the players’ favor rather than that of the house. Through examples from both the gambling industry and the Massively Multiplayer Role-Playing Game Eve Online, I consider the problems in defining cheating, suggest how the term ‘advantage play’ may be useful in understanding participants behavior in contemporary environments, and ultimately consider the use of such terminology in dispute resolution models which may overcome this regulatory gap.

Theory-based self-management programs for promoting recovery in community-dwelling stroke survivors : a systematic review

Background Post-stroke recovery is demanding. Increasing studies have examined the effectiveness of self-management programs for stroke survivors. However no systematic review has been conducted to summarize the effectiveness of theory-based stroke self-management programs. Objectives The aim is to present the best available research evidence about effectiveness of theory-based self-management programs on community-dwelling stroke survivors’ recovery. Inclusion criteria Types of participants All community-residing adults aged 18 years or above, and had a clinical diagnosis of stroke. Types of interventions Studies which examined effectiveness of a self-management program underpinned by a theoretical or conceptual framework for community-dwelling stroke survivors. Types of studies Randomized controlled trials. Types of outcomes Primary outcomes included health-related quality of life and self-management behaviors. Secondary outcomes included physical (activities of daily living), psychological (self-efficacy, depressive symptoms), and social outcomes (community reintegration, perceived social support). Search Strategy A three-step approach was adopted to identify all relevant published and unpublished studies in English or Chinese. Methodological quality The methodological quality of the included studies was assessed using the Joanna Briggs Institute critical appraisal checklist for experimental studies. Data Collection A standardized JBI data extraction form was used. There was no disagreement between the two reviewers on the data extraction results. Data Synthesis There were incomplete details about the number of participants and the results in two studies, which makes it impossible to perform meta-analysis. A narrative summary of the effectiveness of stroke self-management programs is presented. Results Three studies were included. The key issues of concern in methodological quality included insufficient information about random assignment, allocation concealment, reliability and validity of the measuring instruments, absence of intention-to-treat analysis, and small sample sizes. The three programs were designed based on the Stanford Chronic Disease Self-management program and were underpinned by the principles of self-efficacy. One study showed improvement in the intervention group in family and social roles three months after program completion, and work productivity at six months as measured by the Stroke Specific Quality of Life Scale (SSQOL). The intervention group also had an increased mean self-efficacy score in communicating with physicians six months after program completion. The mean changes from baseline in these variables were significantly different from the control group. No significant difference was found in time spent in aerobic exercise between the intervention and control groups at three and six months after program completion. Another study, using SSQOL, showed a significant interaction effect by treatment and time on family roles, fine motor tasks, self-care, and work productivity. However there was no significant interaction by treatment and time on self-efficacy. The third study showed improvement in quality of life, community participation, and depressive symptoms among the participants receiving the stroke self-management program, Stanford Chronic Disease Self-management program, or usual care six months after program completion. However, there was no significant difference between the groups. Conclusions There is inconclusive evidence about the effectiveness of theory-based stroke self-management programs on community-dwelling stroke survivors’ recovery. However the preliminary evidence suggests potential benefits in improving stroke survivors’ quality of life and self-efficacy.

Corneal confocal microscopy detects early nerve regeneration in diabetic neuropathy after simultaneous pancreas and kidney transplantation

Diabetic neuropathy is associated with increased morbidity and mortality. To date, limited data in subjects with impaired glucose tolerance and diabetes demonstrate nerve fiber repair after intervention. This may reflect a lack of efficacy of the interventions but may also reflect difficulty of the tests currently deployed to adequately assess nerve fiber repair, particularly in short-term studies. Corneal confocal microscopy (CCM) represents a novel noninvasive means to quantify nerve fiber damage and repair. Fifteen type 1 diabetic patients undergoing simultaneous pancreas-kidney transplantation (SPK) underwent detailed assessment of neurologic deficits, quantitative sensory testing (QST), electrophysiology, skin biopsy, corneal sensitivity, and CCM at baseline and at 6 and 12 months after successful SPK. At baseline, diabetic patients had a significant neuropathy compared with control subjects. After successful SPK there was no significant change in neurologic impairment, neurophysiology, QST, corneal sensitivity, and intraepidermal nerve fiber density (IENFD). However, CCM demonstrated significant improvements in corneal nerve fiber density, branch density, and length at 12 months. Normalization of glycemia after SPK shows no significant improvement in neuropathy assessed by the neurologic deficits, QST, electrophysiology, and IENFD. However, CCM shows a significant improvement in nerve morphology, providing a novel noninvasive means to establish early nerve repair that is missed by currently advocated assessment techniques.

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.

Traversability estimation for a planetary rover via experimental kernel learning in a Gaussian process framework

A critical requirement for safe autonomous navigation of a planetary rover is the ability to accurately estimate the traversability of the terrain. This work considers the problem of predicting the attitude and configuration angles of the platform from terrain representations that are often incomplete due to occlusions and sensor limitations. Using Gaussian Processes (GP) and exteroceptive data as training input, we can provide a continuous and complete representation of terrain traversability, with uncertainty in the output estimates. In this paper, we propose a novel method that focuses on exploiting the explicit correlation in vehicle attitude and configuration during operation by learning a kernel function from vehicle experience to perform GP regression. We provide an extensive experimental validation of the proposed method on a planetary rover. We show significant improvement in the accuracy of our estimation compared with results obtained using standard kernels (Squared Exponential and Neural Network), and compared to traversability estimation made over terrain models built using state-of-the-art GP techniques.

Working towards a ‘thirdspace’ in the teaching of writing to middle years students

The teaching of writing, particularly in the middle years of schooling, is impacted on by converging, and at times, contradictory pedagogical spaces. Perceptions about the way in which writing should be taught are clearly affected by standardised testing regimes in Australia. That is, much writing is taught as a genre process, yet results on standardised tests such as National Assessment Program in Literacy and Numeracy (NAPLAN) show that the writing component consistently receives the lowest scores (ACARA, 2013. Research shows that creative and individualised approaches are necessary for quality writing (Grainger, Goouch & Lambirth, 2005). This paper investigates the writing practices of students in years 5 to 7 in two culturally and linguistically diverse schools. It shows that the writing practices of these students are greatly influenced by teachers’ perceptions about what is required by external testing bodies such as the Australian Curriculum, Assessment and Reporting Authority (ACARA). The paper will then highlight how socio-spatial theory (Lefebvre, 1991) can be applied to explain these practices and offers the notion of a more productive ‘thirdspace’ (Soja, 1996) for improvement in the teaching of writing.

Residential voltage dip and swell mitigation using Plug-in Hybrid Electric Vehicle in smart grid

Solutions to remedy the voltage disturbances have been mostly suggested only for industrial customers. However, not much research has been done on the impact of the voltage problems on residential facilities. This paper proposes a new method to reduce the effect of voltage dip and swell in smart grids equipped by communication systems. To reach this purpose, a voltage source inverter and the corresponding control system are employed. The behavior of a power system during voltage dip and swell are analyzed. The results demonstrate reasonable improvement in terms of voltage dip and swell mitigation. All simulations are implemented in MATLAB/Simulink environment.

Advancing Nursing Practice in Pain Management

This book showcases the development and evaluation of innovative examples of pain management initiatives by advanced practitioners. It considers each service development or community initiative both in terms of advanced practice nursing and pain management. There is a wide range of examples of innovation in pain management included - from the introduction of ketamine use in one trust, to wider issues around meeting the needs of pain management in the community. The book considers issues including use of research, education and interprofessional working in the advanced practitioner role. Each chapter looks at development of the service, challenges of implementation, evaluation of the service's success and justifying the importance of the advanced nurse in the service's achievements.

Stagnancy in Indonesia’s reformed state asset management policies and practices : a wicked problem?

The policies and regulations governing the practice of state asset management have emerged as an urgent question among many countries worldwide for there is heightened awareness of the complex and crucial role that state assets play in public service provision. Indonesia is an example of such country, introducing a ‘big-bang’ reform in state asset management laws, policies, regulations, and technical guidelines. Indonesia exemplified its enthusiasm in reforming state asset management policies and practices through the establishment of the Directorate General of State Assets in 2006. The Directorate General of State Assets have stressed the new direction that it is taking state asset management laws and policies through the introduction of Republic of Indonesia Law Number 38 Year 2008, which is an amended regulation overruling Republic of Indonesia Law Number 6 Year 2006 on Central/Regional Government State Asset Management. Law number 38/2008 aims to further exemplify good governance principles and puts forward a ‘the highest and best use of assets’ principle in state asset management. The purpose of this study is to explore and analyze specific contributing influences to state asset management practices, answering the question why innovative state asset management policy implementation is stagnant. The methodology of this study is that of qualitative case study approach, utilizing empirical data sample of four Indonesian regional governments. Through a thematic analytical approach this study provides an in-depth analysis of each influencing factors to state asset management reform. Such analysis suggests the potential of an ‘excuse rhetoric’; whereby the influencing factors identified are a smoke-screen, or are myths that public policy makers and implementers believe in, as a means to ex-plain stagnant implementation of innovative state asset management practice. Thus this study offers deeper insights of the intricate web that influences state as-set management innovative policies to state asset management policy makers; to be taken into consideration in future policy writing.

The development of a simple multi-nodal tool to identify performance issues in existing commercial buildings

Australia’s building stock includes many older commercial buildings with numerous factors that impact energy performance and indoor environment quality. The built environment industry has generally focused heavily on improving physical building design elements for greater energy efficiency (such as retrofits and environmental upgrades), however there are noticeable ‘upper limits’ to performance improvements in these areas. To achieve a stepchange improvement in building performance, the authors propose that additional components need to be addressed in a whole of building approach, including the way building design elements are managed and the level of stakeholder engagement between owners, tenants and building managers. This paper focuses on the opportunities provided by this whole-of-building approach, presenting the findings of a research project undertaken through the Sustainable Built Environment National Research Centre (SBEnrc) in Australia. Researchers worked with a number of industry partners over two years to investigate issues facing stakeholders at base building and tenancy levels, and the barriers to improving building performance. Through a mixed-method, industry-led research approach, five ‘nodes’ were identified in whole-of-building performance evaluation, each with interlinking and overlapping complexities that can influence performance. The nodes cover building management, occupant experience, indoor environment quality, agreements and culture, and design elements. This paper outlines the development and testing of these nodes and their interactions, and the resultant multi-nodal tool, called the ‘Performance Nexus’ tool. The tool is intended to be of most benefit in evaluating opportunities for performance improvement in the vast number of existing low-performing building stock.

Gender, emotions and fly-in fly-out work

This paper explores the emotional life of fly‑in fly‑out (FIFO) workers and their families, through an analysis of more than 500 postings made on an online chat forum for mining families. Building on literature on fly‑in fly‑out workers and understandings of emotions as socially constructed, analysis shows how posters to the forum, typically women whose male partners are FIFO workers, construct gendered emotional identities for their partners (sometimes referred to as 'Mr Miner'), and for themselves, as 'mining women', 'mining widows' or the 'mining missus'. Inherent in the creation of gendered emotional subject positions is the process of women undertaking emotion work on and behalf of themselves, their male partners and their children. The findings demonstrate the overarching normative dimensions of women's emotional self‑transformations in the service of their mining partners' careers and the attendant reproduction of everyday patriarchal relations in the private lives of mining families.

Lumbar epidural steroids are not cost effective in sciatica

Background Lumbar Epidural Steroids Injections (ESI’s) have previously been shown to provide some degree of pain relief in sciatica. Number Needed To Treat (NNT) to achieve 50% pain relief has been estimated at 7 from the results of randomised controlled trials. Pain relief is temporary. They remain one of the most commonly provided procedures in the UK. It is unknown whether this pain relief represents good value for money. Methods 228 patients were randomised into a multi-centre Double Blind Randomised Controlled Trial. Subjects received up to 3 ESI’s or intra-spinous saline depending on response and fall off with the first injection. All other treatments were permitted. All received a review of analgesia, education and physical therapy. Quality of life was assessed using the SF36 at 6 points and compared using independent sample t-tests. Follow up was up to 1 yr. Missing data was imputed using last observation carried forward (LOCF). QALY’s (Quality of Life Years) were derived from preference based heath values (summary health utility score). SF-6D health state classification was derived from SF-36 raw score data. Standard gambles (SG) were calculated using Model 10. SG scores were calculated on trial results. LOCF was not used for this. Instead average SG were derived for a subset of patients with observations for all visits up to week 12. Incremental QALY’s were derived as the difference in the area between the SG curve for the active group and placebo group. Results SF36 domains showed a significant improvement in pain at week 3 but this was not sustained (mean 54 Active vs 61 Placebo P<0.05). Other domains did not show any significant gains compared with placebo. For derivation of SG the number in the sample in each period differed. In week 12, average SG scores for active and placebo converged. In other words, the health gain for the active group as measured by SG was achieved by the placebo group by week 12. The incremental QALY gained for a patient under the trial protocol compared with the standard care package was 0.0059350. This is equivalent to an additional 2.2 days of full health. The cost per QALY gained to the provider from a patient management strategy administering one epidural as suggested by results was £25 745.68. This result was derived assuming that the gain in QALY data calculated for patients under the trial protocol would approximate that under a patient management strategy based on the trial results (one ESI). This is above the threshold suggested by some as a cost effective treatment. Conclusions The transient benefit in pain relief afforded by ESI’s does not appear to be cost-effective. Further work is needed to develop more cost-effective conservative treatments for sciatica.