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.

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.

The impact of organizational boundaries on (re)building capabilities

The literature concerning firm boundaries has focussed extensively on the rationale for different boundary choices and the economic efficiencies that such choices can make. There is also an acknowledged position that a firm’s boundary choices may impact the ability of a firm to maintain and even build new capabilities, though such choices may not be optimal from an economic efficiency perspective. It is in this context that we seek to investigate how firms make this potential trade-off in respect of their boundary choices and how these choices are implemented across a wide range of activities. Using qualitative data from three public sector construction oriented organizations, we observe that neither pure make nor buy decisions assisted significantly in capability building. Dual modes – where firms make and buy the same product or service simultaneously – provided firms with some opportunities to manage this paradox, but the most successful decisions seemed to occur in respect of using intermediate governance modes such as alliances. We also observed that the boundary choice was just one dimension of the capability building process and firms pursuing the same boundary choice decisions often had quite divergent outcomes on the basis of their boundary management and the ability of knowledge to move across firm boundaries.

Identification and occupational stress : a stress-buffering perspective

Occupational stress research has consistently demonstrated many negative effects of work stressors on employee adjustment (i.e., job-related attitudes and health). Considerable literature also describes potential moderators of this relationship. While research has revealed that different workplace identifications can have significant positive effects on employee adjustment, it has neglected to investigate their potential stress-buffering effects. Based on identity theories, it was predicted that stress-buffering effects of different types of identifications (distal versus proximal) would be revealed when the identification type and employee adjustment outcome type (distal versus proximal) were congruent. Predictions were tested with an employee sample from five human service nonprofit organizations (N = 337). Hierarchical multiple regression analyses revealed that main and moderated effects relating to identification supported the notion that occupational stress would be reduced when there was congruence of distal and proximal identifications and distal and proximal outcome types. However, stress-buffering effects were also found for high identifiers and low identifiers that were not in line with hypotheses posing questions for the definitions of distal and proximal identifications. Findings are discussed in terms of theoretical and practical implications.

Australian Research to Encourage School Students’ Positive Use of Technology to Reduce Cyberbullying

Information and Communications Technology (ICT) has spread rapidly in Australia. Mobile phones, which increasingly have advanced capabilities including Internet access, mobile television and multimedia storage, are owned by 22% of Australian children aged 9-11 years and 73% of those aged 12-14 years (Australian Bureau of Statistics, 2012b), as well as by over 90% of Australians aged 15 years and over(Australian Communications and Media Authority (ACMA), 2010). Nearly 80% of Australian households have access to the Internet and 73% have a broadband Internet connection, ensuring that Internet access is typically reliable and high-speed (Australian Bureau of Statistics, 2012a). Ninety percent of Australian children aged 5-14 years (comprising 79% of 5-8 year olds; 96% of 9-11 year olds; and 98% of 12-14 year olds) reported having accessed the Internet during 2011-2012, a significant increase from 79% in 2008-2009 (Australian Bureau of Statistics, 2012b). Approximately 90% of 5-14 year olds have accessed the Internet both from home and from school, with close to 49% accessing the Internet from other places (Australian Bureau of Statistics, 2012b). Young people often make use of borrowed Internet access (e.g. in friends’ homes), commercial access (e.g. cybercafés), public access (e.g. libraries), and mobile device access in areas offering free Wi-Fi (Lim, 2009).

Asking for it? Practices and structures that perpetuate employee silence in pursuing customised work arrangements

A component of broader scholarship addressing the social context in which individuals work, has focused on the role of ‘employee voice’ in determining flexible-work outcomes (Donnelly et al., 2012). Employee voice incorporates a spectrum of practices designed to give employees a say in organisational decisions (Dundon et al., 2004). This paper extends work on voice and workplace flexibility in two ways. First, it focuses not simply on ‘voice’ but on its antithesis, employee silence, which is defined (following Van Dyne et al., 2003) as the intentional withholding of ideas and opinions. We utilise an alternative reading of silence to the majority of literature which interprets it as a product of employee motivation, by focusing on the role of management and by adopting a framework which considers silence as a control dialectic (Donaghey et al., 2011). Second, the study examines silence with respect to preferences for customising the terms/conditions of employment beyond narrowly defined notions of ‘flexible work’ (e.g., reduced hours; home-working). The study utilises 30 telephone interviews with employees who had been previously identified as ‘discontent non-requesters’ (Skinner and Pocock, 2011: 75), that is they had expressed a desire to request flexible working provisions, but had not done so. Interviewees were asked to articulate the reasons for, and consequences of, their silence. The findings reveal nuanced workplace practices and structures that close down possibilities for employee voice and perpetuate silence on matters relating to customising work. They also illustrate a disjuncture between espoused organizational goals and everyday practices and norms encountered in workplaces.

A conceptualization of complexity in IS-driven organizational transformations

Organizational transformations reliant on successful ICT system developments (continue to) fail to deliver projected benefits even when contemporary governance models are applied rigorously. Modifications to traditional program, project and systems development management methods have produced little material improvement to successful transformation as they are unable to routinely address the complexity and uncertainty of dynamic alignment of IS investments and innovation. Complexity theory provides insight into why this phenomenon occurs and is used to develop a conceptualization of complexity in IS-driven organizational transformations. This research-in-progress aims to identify complexity formulations relevant to organizational transformation. Political/power based influences, interrelated business rules, socio-technical innovation, impacts on stakeholders and emergent behaviors are commonly considered as characterizing complexity while the proposed conceptualization accommodates these as connectivity, irreducibility, entropy and/or information gain in hierarchically approximation and scaling, number of states in a finite automata and/or dimension of attractor, and information and/or variety.

Continuous positive air pressure treatment for obstructive sleep apnoea patients : effects on sleep quality and quantity as measured by actigraphy

Objectives Actigraphy can reliably assess sleep in healthy adults and be used to estimate total sleep time in suspected obstructive sleep apnoea (OSA) patients. We compared sleep quality for Continuous Positive Air Pressure (CPAP) treated OSA patients and controls, evaluating the impact of stopping CPAP for one night. Methods 11 men, aged 51–75 years (m = 65.6 years), compliant CPAP users, treated for 1–19 years (m = 7.8 years) wore Cambridge Neurotechnology Ltd actiwatches for one night while using CPAP and for one night sleeping without CPAP. A control group of 11 healthy men, aged 63–74 years (m = 64.1 years) slept normally whilst wearing an actiwatch. Subsequent daytime sleepiness was recorded using Karolinska sleepiness scores (KSS). Results Actimetry showed no significant differences between actual sleep time, sleep efficiency, sleep disturbance index or number of wake bouts when comparing OSA participants using CPAP, with controls; there was no difference in subsequent daytime sleepiness, control KSS = 4.21, OSA KSS = 4.17. Without CPAP there was no significant difference in sleep length or sleep onset latency compared with using CPAP, but there was a significant impact on sleep quality as shown by: increased sleep disturbance index from 7.9 to 13.8 [t(10) = 3.510, P < 0.05], decreased percent of actual sleep from 92.05% to 86.15% [t(10) = 3.51, P < 0.05], decreased sleep efficiency from 86.6% to 81% [t(10) = 2.204, P < 0.05] and increased number of wake bouts from 29 to 42.5 [t(10) = 3.877, P < 0.05]. Daytime sleepiness became significantly worse increasing from KSS 4.17 to 6.27 [t(10) = )4.96, P < 0.05]. Conclusion There was no disparity in sleep quality or KSS scores between CPAP treated OSA patients and healthy controls of a similar age. Treated OSA patients obtained quality sleep with no elevated day time sleepiness. However, cessation of treatment for one night caused sleep quality to deteriorate despite a comparable sleep time; the deterioration in sleep quality could explain the increase in daytime sleepiness. OSA patients need to know that even short-term noncompliance with CPAP treatment significantly impairs sleep quality, leading to excessive sleepiness during monotonous tasks such as driving. Actigraphy successfully identified nights of non-compliance in treated OSA patients; but did not differentiate between the sleep of CPAP treated OSA patients and healthy controls.

The view from here : educational program creates momentum for positive change

Kate Nayton, Elaine Fielding and Elizabeth Beattie describe how they developed a successful program to educate hospital staff about dementia care. The program may soon be trialled in other acute care facilities.

Nutrition prescription to achieve positive outcomes in Chronic Kidney Disease : a systematic review

In Chronic Kidney Disease (CKD), management of diet is important in prevention of disease progression and symptom management, however evidence on nutrition prescription is limited. Recent international CKD guidelines and literature was reviewed to address the following question “What is the appropriate nutrition prescription to achieve positive outcomes in adult patients with chronic kidney disease?” Databases included in the search were Medline and CINAHL using EBSCOhost search engine, Embase and the Cochrane Database of Systematic Reviews published from 2000 to 2009. International guidelines pertaining to nutrition prescription in CKD were also reviewed from 2000 to 2013. Three hundred and eleven papers and eight guidelines were reviewed by three reviewers. Evidence was graded as per the National Health and Medical Research Council of Australia criteria. The evidence from thirty six papers was tabulated under the following headings: protein, weight loss, enteral support, vitamin D, sodium, fat, fibre, oral nutrition supplements, nutrition counselling, including protein and phosphate, nutrients in peritoneal dialysis solution and intradialytic parenteral nutrition, and was compared to international guidelines. While more evidence based studies are warranted, the customary nutrition prescription remains satisfactory with the exception of Vitamin D and phosphate. In these two areas, additional research is urgently needed given the potential of adverse outcomes for the CKD patient.

Social media, data analytics and videogames development : Halfbrick case study

Social media platforms are of interest to interactive entertainment companies for a number of reasons. They can operate as a platform for deploying games, as a tool for communicating with customers and potential customers, and can provide analytics on how players utilize the; game providing immediate feedback on design decisions and changes. However, as ongoing research with Australian developer Halfbrick, creators of $2 , demonstrates, the use of these platforms is not universally seen as a positive. The incorporation of Big Data into already innovative development practices has the potential to cause tension between designers, whilst the platform also challenges the traditional business model, relying on micro-transactions rather than an up-front payment and a substantial shift in design philosophy to take advantage of the social aspects of platforms such as Facebook.

Psychological stress and employee engagement

“The challenge today is not just retaining talented people, but fully engaging them, capturing their minds and hearts at each stage of their work lives” (Kaye & Jordan-Evans, 2003, p. 11). Engaged employees produce positive work outcomes such as increased productivity satisfaction, and reduced turnover (Kahn, 1990, 1992; Saks, 2006). Engaged employees also impact on customers and co-workers’ positive experiences such as increased customer satisfaction (Wagner & Harter, 2006). Further, engaged employees demonstrate higher levels of trust in management and share more positive experiences with co-workers than disengage employees (Payne, Cangemi, Fuqua, & Muhleakamp, 1998). Past studies show that having a high proportion of engaged employees increases organizational performance, such as profitability and reputation (Wagner & Harter, 2006; Fleming & Asplund, 2007; Ketter, 2008). Having experienced the benefits of having engaged employees, organizations have become more aware of this issue and have been focusing on facilitating engagement climate within workplaces. Recently, an interest in positive psychology, instead of negative aspects of human behaviours, has become a focus for both scholars and practitioners. The trend towards positive psychology has led to the emergence of the concept of work engagement(Chughtai & Buckley, 2008). This article reviews literatures in the area of positive psychology and psychological stress, and discusses how organizations can increase work engagement among their organizational members. The remainder of this article is organised in four sections. First, we define work engagement as used in this article and psychological outcomes of work engagement. Second, we identify ways to increase work engagement among employees. Following this, we further discuss how gender roles influence individuals’ engagement at work. The final sections conclude the paper with a discussion of the practical implications.

How emergent roles and structures create trust In hastily formed inter-organizational teams

Many activities, from disaster response to project management, require cooperation among people from multiple organizations who initially lack interpersonal relationships and trust. Upon entering inter-organizational settings, pre-existing identities and expectations, along with emergent social roles and structures, may all influence trust between colleagues. To sort out these effects, we collected time-lagged data from three cohorts of military MBA students, representing 2,224 directed dyads, shortly after they entered graduate school. Dyads that shared organizational identity, boundary-spanning roles, and similar network positions (structural equivalence) were likely to have stronger professional ties and greater trust.

Organizational probes : exploring playful interactions in work environment

Playfulness, with non-intrusive elements, can be considered a useful resource for enhancing social awareness and community building within work organizations. Taking inspirations from the cultural probes approach, we developed organizational probes as a set of investigation tools that could provide useful information about employees’ everyday playful experiences within their work organizations. In an academic work environment, we applied our organizational probes over a period of three weeks. Based on the collected data we developed two design concepts for playful technologies in work environments.

Developing a culture to support peer review of teaching in higher education

This presentation addresses issues related to leadership, academic development and scholarship of teaching and learning, and highlights research funded by the Australian Office of Learning and Teaching (OLT) designed to embed and sustain peer review of teaching within the culture of 5 Australian universities: Queensland University of Technology, University of Technology, Sydney, University of Adelaide, Curtin University, and Charles Darwin University. Peer review of teaching in higher education will be emphasised as a professional process for providing feedback on teaching and learning practice, which if sustained, can become an effective ongoing strategy for academic development (Barnard et al, 2011; Bell, 2005; Bolt and Atkinson, 2010; McGill & Beaty 2001, 1992; Kemmis & McTaggart, 2000). The research affirms that using developmental peer review models (Barnard et al, 2011; D'Andrea, 2002; Hammersley-Fletcher & Orsmond, 2004) can bring about successful implementation, especially when implemented within a distributive leadership framework (Spillane & Healey, 2010). The project’s aims and objectives were to develop leadership capacity and integrate peer review as a cultural practice in higher education. The research design was a two stage inquiry process over 2 years. The project began in July 2011 and encompassed a development and pilot phase followed by a cascade phase with questionnaire and focus group evaluation processes to support ongoing improvement and measures of outcome. Leadership development activities included locally delivered workshops complemented by the identification and support of champions. To optimise long term sustainability, the project was implemented through existing learning and teaching structures and processes within the respective partner universities. Research outcomes highlight the fundamentals of peer review of teaching and the broader contextual elements of integration, leadership and development, expressed as a conceptual model for embedding peer review of teaching within higher education. The research opens a communicative space about introduction of peer review that goes further than simply espousing its worth and introduction. The conceptual model highlights the importance of development of distributive leadership capacity, integration of policies and processes, and understanding the values, beliefs, assumptions and behaviors embedded in an organizational culture. The presentation overviews empirical findings that demonstrate progress to advance peer review requires an ‘across-the-board’ commitment to embed change, and inherently demands a process that co-creates connection across colleagues, discipline groups, and the university sector. Progress toward peer review of teaching as a cultural phenomenon can be achieved and has advantages for academic staff, scholarship, teaching evaluation and an organisation, if attention is given to strategies that influence the contexts and cultures of teaching practice. Peer review as a strategy to develop excellence in teaching is considered from a holistic perspective that by necessity encompasses all elements of an educational environment and has a focus on scholarship of teaching. The work is ongoing and has implication for policy, research, teaching development and student outcomes, and has potential application world-wide.