A phase II trial of brivanib in recurrent or persistent endometrial cancer: An NRG oncology/gynecologic oncology group study

PURPOSE Brivanib, an oral, multi-targeted tyrosine kinase inhibitor with activity against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR) was investigated as a single agent in a phase II trial to assess the activity and tolerability in recurrent or persistent endometrial cancer (EMC). PATIENTS AND METHODS Eligible patients had persistent or recurrent EMC after receiving one to two prior cytotoxic regimens, measurable disease, and performance status of ≤2. Treatment consisted of brivanib 800 mg orally every day until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) at six months and objective tumor response. Expression of multiple angiogenic proteins and FGFR2 mutation status was assessed. RESULTS Forty-five patients were enrolled. Forty-three patients were eligible and evaluable. Median age was 64 years. Twenty-four patients (55.8%) received prior radiation. Median number of cycles was two (range 1-24). No GI perforations but one rectal fistula were seen. Nine patients had grade 3 hypertension, with one experiencing grade 4 confusion. Eight patients (18.6%; 90% CI 9.6%-31.7%) had responses (one CR and seven PRs), and 13 patients (30.2%; 90% CI 18.9%-43.9%) were PFS at six months. Median PFS and overall survival (OS) were 3.3 and 10.7 months, respectively. When modeled jointly, VEGF and angiopoietin-2 expression may diametrically predict PFS. Estrogen receptor-α (ER) expression was positively correlated with OS. CONCLUSION Brivanib is reasonably well tolerated and worthy of further investigation based on PFS at six months in recurrent or persistent EMC.

A proposal for a clean technology directive: European patent law and climate change

This article charts the conflicted, dissonant policies of the European Union towards intellectual property and climate change. It contends that there is a mismatch between the empirical work of the European Patent Office and the quietist policy options contemplated by the European Union. This article contends that the European Union needs to develop a Clean Technology Directive to allow for a differentiated approach to patent law and clean technologies - especially given the past complicity of the European Union in global warming and climate change. It highlights essential elements in a comprehensive policy package for the reform of patent law - considering patentable subject matter; patent incentives; and patent exceptions.

Electronic games: Can they create value for the moderate drinking brand?

Purpose This paper aims to understand how experiential value can generate awareness, image, perceived quality and loyalty to the moderate drinking brand. Electronic games are increasingly used by social marketers in an attempt to support target audiences uptake of social behaviours. However, little is known of the value this creates for target audiences and its impact on the uptake of a social behaviour brand. Design/methodology/approach A survey of male adolescents (n = 137) was conducted to test proposed relationships between experiential value and consumer-based brand equity dimensions. The research tested the game “Don’t Turn a Night Out into a Nightmare” that was developed by the Australian Federal Government as part of a social marketing campaign. Data were analysed using linear regression and MANCOVA. Findings The findings indicate that there are significant relationships between consumer-based brand equity dimensions for the social behaviour brand of moderate drinking, indicating relevance of a commercial marketing theory for social marketing. Furthermore, findings show that different combinations of experiential value dimensions have an impact on different components of consumer-based brand equity. These findings indicate that when social marketers are developing electronic games, they must create different combinations of value in game play to achieve awareness, positive image, high perceived quality and, ultimately, loyalty to a behaviour. Practical implications Social marketers seeking to use electronic games to influence the uptake of behaviour brands such as moderate drinking must provide a more complete value package. Originality/value This paper is the first to examine how experiential value can influence the creation of brand equity for a social behaviour brand.

The importance of group-fit in new director selection

Purpose Director selection is an important yet under-researched topic. The purpose of this paper is to contribute to extant literature by gaining a greater understanding into how and why new board members are recruited. Design/methodology/approach This exploratory study uses in-depth interviews with Australian non-executive directors to identify what selection criteria are deemed most important when selecting new director candidates and how selection practices vary between organisations. Findings The findings indicate that appointments to the board are based on two key attributes: first, the candidates’ ability to contribute complementary skills and second, the candidates’ ability to work well with the existing board. Despite commonality in these broad criteria, board selection approaches vary considerably between organisations. As a result, some boards do not adequately assess both criteria when appointing a new director hence increasing the chance of a mis-fit between the position and the appointed director. Research limitations/implications The study highlights the importance of both individual technical capabilities and social compatibility in director selections. The authors introduce a new perspective through which future research may consider director selection: fit. Originality/value The in-depth analysis of the director selection process highlights some less obvious and more nuanced issues surrounding directors’ appointment to the board. Recurrent patterns indicate the need for both technical and social considerations. Hence the study is a first step in synthesising the current literature and illustrates the need for a multi-theoretical approach in future director selection research.

Combining meta- and mega-analytic approaches for multi-site diffusion imaging based genetic studies: From the enigma-DTI working group

Meta-analyses estimate a statistical effect size for a test or an analysis by combining results from multiple studies without necessarily having access to each individual study's raw data. Multi-site meta-analysis is crucial for imaging genetics, as single sites rarely have a sample size large enough to pick up effects of single genetic variants associated with brain measures. However, if raw data can be shared, combining data in a "mega-analysis" is thought to improve power and precision in estimating global effects. As part of an ENIGMA-DTI investigation, we use fractional anisotropy (FA) maps from 5 studies (total N=2, 203 subjects, aged 9-85) to estimate heritability. We combine the studies through meta-and mega-analyses as well as a mixture of the two - combining some cohorts with mega-analysis and meta-analyzing the results with those of the remaining sites. A combination of mega-and meta-approaches may boost power compared to meta-analysis alone.

Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: A pilot project of the ENIGMA-DTI working group

The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA-DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18-85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/).

Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen’s d=−0.14, % difference=−1.24). This effect was driven by patients with recurrent MDD (Cohen’s d=−0.17, % difference=−1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen’s d=−0.20, % difference=−1.85) and a trend toward smaller amygdala (Cohen’s d=−0.11, % difference=−1.23) and larger lateral ventricles (Cohen’s d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

Quality in group service encounters: A theoretical exploration of the concept of a simultaneous multi‐customer co‐creation process

Purpose The purpose of this paper is to explore the concept of service quality for settings where several customers are involved in the joint creation and consumption of a service. The approach is to provide first insights into the implications of a simultaneous multi‐customer integration on service quality. Design/methodology/approach This conceptual paper undertakes a thorough review of the relevant literature before developing a conceptual model regarding service co‐creation and service quality in customer groups. Findings Group service encounters must be set up carefully to account for the dynamics (social activity) in a customer group and skill set and capabilities (task activity) of each of the individual participants involved in a group service experience. Research limitations/implications Future research should undertake empirical studies to validate and/or modify the suggested model presented in this contribution. Practical implications Managers of service firms should be made aware of the implications and the underlying factors of group services in order to create and manage a group experience successfully. Particular attention should be given to those factors that can be influenced by service providers in managing encounters with multiple customers. Originality/value This article introduces a new conceptual approach for service encounters with groups of customers in a proposed service quality model. In particular, the paper focuses on integrating the impact of customers' co‐creation activities on service quality in a multiple‐actor model.

Aligning and characterising group behaviours using role information

Techniques to align spatio-temporal data for large-scale analysis of human group behaviour have been developed. Application of the techniques to sports databases enable sport team's characteristic styles of play to be discovered and compared for tactical analysis. Applications in surveillance to recognise group activities in real-time for person re-identification from low-resolution video footage have also been developed.

Friends or foes: Group influence effects on moderate drinking behaviors

Drunkenness and the addictive consumption of alcohol remains a key social and public health concern. Advancing beyond traditional individualized prevention approaches, this research explores the role of social influences in determining individual and group influence in moderate-drinking decision-making and participatory actions. A social influence model of intentional moderate drinking actions is conceptualized and validated. Results show group norm as the single social influence predictor of intentions and desire to drink moderately, as opposed to well-known social influence factors (e.g., subjective norm, social identity and drinking contextual effects). Significantly, the peer-group is identified as a key influencer supporting moderate drinking practices, and i-intentions to drink moderately predict group-related we-intentions, which suggests that moderate drinking is a shared goal. These findings advance alcohol prevention research drawing attention to the power of group dynamics to support positive changes in youth drinking behaviors.

Media futures: A review essay on'The Future of Reputation','TV Futures', and'The Future of the Internet and How to Stop It'

In his 1987 book, The Media Lab: Inventing the Future at MIT, Stewart Brand provides an insight into the visions of the future of the media in the 1970s and 1980s. 1 He notes that Nicolas Negroponte made a compelling case for the foundation of a media laboratory at MIT with diagrams detailing the convergence of three sectors of the media—the broadcast and motion picture industry; the print and publishing industry; and the computer industry. Stewart Brand commented: ‘If Negroponte was right and communications technologies really are converging, you would look for signs that technological homogenisation was dissolving old boundaries out of existence, and you would expect an explosion of new media where those boundaries used to be’. Two decades later, technology developers, media analysts and lawyers have become excited about the latest phase of media convergence. In 2006, the faddish Time Magazine heralded the arrival of various Web 2.0 social networking services: You can learn more about how Americans live just by looking at the backgrounds of YouTube videos—those rumpled bedrooms and toy‐strewn basement rec rooms—than you could from 1,000 hours of network television. And we didn’t just watch, we also worked. Like crazy. We made Facebook profiles and Second Life avatars and reviewed books at Amazon and recorded podcasts. We blogged about our candidates losing and wrote songs about getting dumped. We camcordered bombing runs and built open‐source software. America loves its solitary geniuses—its Einsteins, its Edisons, its Jobses—but those lonely dreamers may have to learn to play with others. Car companies are running open design contests. Reuters is carrying blog postings alongside its regular news feed. Microsoft is working overtime to fend off user‐created Linux. We’re looking at an explosion of productivity and innovation, and it’s just getting started, as millions of minds that would otherwise have drowned in obscurity get backhauled into the global intellectual economy. The magazine announced that Time’s Person of the Year was ‘You’, the everyman and everywoman consumer ‘for seizing the reins of the global media, for founding and framing the new digital democracy, for working for nothing and beating the pros at their own game’. This review essay considers three recent books, which have explored the legal dimensions of new media. In contrast to the unbridled exuberance of Time Magazine, this series of legal works displays an anxious trepidation about the legal ramifications associated with the rise of social networking services. In his tour de force, The Future of Reputation: Gossip, Rumor, and Privacy on the Internet, Daniel Solove considers the implications of social networking services, such as Facebook and YouTube, for the legal protection of reputation under privacy law and defamation law. Andrew Kenyon’s edited collection, TV Futures: Digital Television Policy in Australia, explores the intersection between media law and copyright law in the regulation of digital television and Internet videos. In The Future of the Internet and How to Stop It, Jonathan Zittrain explores the impact of ‘generative’ technologies and ‘tethered applications’—considering everything from the Apple Mac and the iPhone to the One Laptop per Child programme.

A Submission to the Senate Legal and Constitutional Affairs Committee on the Copyright Amendment (Online Infringement) Bill 2015 (Cth)

The film company, Roadshow, the pay television company Foxtel, and Rupert Murdoch’s News Corp and News Limited — as well as copyright industries — have been clamouring for new copyright powers and remedies. In the summer break, the Coalition Government has responded to such entreaties from its industry supporters and donors, with a new package of copyright laws and policies. There has been significant debate over the proposals between the odd couple of Attorney-General George Brandis and the Minister for Communications, Malcolm Turnbull. There has been deep, philosophical differences between the two Ministers over the copyright agenda. The Attorney-General George Brandis has supported a model of copyright maximalism, with strong rights and remedies for the copyright empires in film, television, and publishing. He has shown little empathy for the information technology companies of the digital economy. The Attorney-General has been impatient to press ahead with a copyright regime. The Minister for Communications, Malcolm Turnbull, has been somewhat more circumspect,recognising that there is a need to ensure that copyright laws do not adversely impact upon competition in the digital economy. The final proposal is a somewhat awkward compromise between the discipline-and-punish regime preferred by Brandis, and the responsive regulation model favoured by Turnbull. In his new book, Information Doesn’t Want to Be Free: Laws for the Internet Age, Cory Doctorow has some sage advice for copyright owners: Things that don’t make money: * Complaining about piracy. * Calling your customers thieves. * Treating your customers like thieves. In this context, the push by copyright owners and the Coalition Government to have a copyright crackdown may well be counter-productive to their interests. This submission considers a number of key elements of the Coalition Government’s Copyright Crackdown. Part 1 examines the proposals in respect of the Copyright Amendment (Online Infringement) Bill 2015 (Cth). Part 2 focuses upon the proposed Copyright Code. Part 3 considers the question of safe harbours for intermediaries. Part 4 examines the question of copyright exceptions – particularly looking at the proposal of the Australian Law Reform Commission for the introduction of a defence of fair use. Part 5 highlights the recommendations of the IT Pricing Inquiry and the Harper Competition Policy Review in respect of copyright law, consumer rights, and competition law.

Breast and prostate cancer survivor responses to group exercise and supportive group Psychotherapy

This study qualitatively examined an 8 week group exercise and counseling intervention for breast and prostate cancer survivors. Groups exercised 3 days per week, 50 minutes per session,performing moderate intensity aerobic and resistance training. Groups also underwent 90 minute supportive group psychotherapy sessions once per week. Survivors discussed their experiences in focus groups post intervention. Transcripts were analyzed using interpretative phenomenological analysis. Survivors described how exercise facilitated counseling by creating mutual aid and trust, and counseling helped participants with self-identity, sexuality, and returning to normalcy. When possible, counselors and fitness professionals should create partnerships to optimally support cancer survivors.

Defining anthropometric cut-off levels related to metabolic risk in a group of Sri Lankan children

Background: Body mass index (BMI) is widely used as a measure of adiposity. However, currently used cut-off values are not sensitive in diagnosing obesity in South Asian populations. Aim: To define BMI and waist circumference (WC), cut-off values representing percentage fat mass (%FM) associated with adverse health outcomes. Subjects and methods: A cross-sectional descriptive study of 285 5–14 year old Sri Lankan children (56% boys) was carried out. Fat mass (FM) was assessed using the isotope (D2O) dilution technique based on 2C body composition model. BMI and WC cut-off values were defined based on %FM associated with adverse health outcomes. Results: Sri Lankan children had a low fat free mass index (FFMI) and a high fat mass index (FMI). Individuals with the same BMI had %FM distributed over a wide range. Lean body tissue grew very little with advancing age and weight gain was mainly due to increases in body fat. BMI corresponding to 25% in males and 35% in females at 18 years was 19.2 kg/m2 and 19.7 kg/m2, respectively. WC cut-off values for males and females were 68.4 cm and 70.4 cm, respectively. Conclusion: This chart analysis clearly confirms that Sri Lankan children have a high %FM from a young age. With age, more changes occur in FM than in fat free mass (FFM). Although the newly defined BMI and WC cut-off values appear to be quite low, they are comparable to some recent data obtained in similar populations.