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.

An international comparison of the continuing professional development process (CPD) in Australia, New Zealand and the United Kingdom

Background: The Pharmacy Board of Australia stipulated that for renewal of registration, pharmacists must have accrued a minimum of 20 CPD credits over the 2010-11 registration years (1). Mandatory CPD is not new in Pharmacy. The UK and New Zealand have both established systems of CPD in recent years. The purpose of this study is to investigate established CPD processes in the UK and New Zealand with the view to making recommendations for the implementation of the CPD process in Australia. Objectives: To compare the acquisition and guidance on documentation of CPD credit points in Australia, New Zealand and the United Kingdom. Methodology: A comparative online search of the websites of each of the registering authorities was undertaken. Any practice standards or guidelines which relate to registration or continuing professional development were analysed and compared. Results: In New Zealand the Pharmacy Council require Pharmacists to have a minimum of 12 outcome credits over a 3-year period for recertification (2, 3). The outcome credit related to each CPD action and is based on relevance to the pharmacist and their practice. It is graded between one, for CPD which has occasional relevance to practice and three which have considerable relevance to practice. There are examples of completed CPD recording sheets on their website (8). In the UK, The General Pharmaceutical Council require Pharmacists to make a minimum of nine CPD entries per year (4) and detailed guidance on how to record CPD activities is provided (5,7). The Pharmacy Board of Australia divides CPD activities into three groups (6). Of the 20 credits required annually only 10 can be gained from group one activities, which is information accessed without assessment. There is only brief guidance on the recording of CPD. Discussion: The GPhC in the UK provided the most comprehensive guidance on acquisition of CPD credit points and documentation (5,7) The Pharmacy Council of New Zealand made CPD points relevant to practice.(2,8) The Pharmacy Board of Australia provided limited information for pharmacists on CPD activities, which may impede pharmacist participation. Information may assist in increasing pharmacists’ engagement in CPD activities. In conclusion, there is variation between the three countries in the amount and type of information provided about CPD requirements.

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

We argue that safeguards are necessary to ensure human rights are adequately protected. All systems of blocking access to online content necessarily raise difficult and problematic issues of infringement of freedom of speech and access to information. Given the importance of access to information across the breadth of modern life, great care must be taken to ensure that any measures designed to protect copyright by blocking access to online locations are proportionate. Any measures to block access to online content must be carefully tailored to avoid serious and disproportionate impact on human rights. This means first that the measures must be effective and adapted to achieve a legitimate purpose. The experience of foreign jurisdictions suggests that this legislation is unlikely to be effective. Unless and until there is clear evidence that the proposed scheme is likely to increase effective returns to Australian creators, this legislation should not be introduced. Second, the principle of proportionality requires ensuring that the proposed legislation does not unnecessarily burden legitimate speech or access to information. As currently worded, the draft legislation may result in online locations being blocked even though they would, if operated in Australia, not contravene Australian law. This is unacceptable, and if introduced, the law should be drafted so that it is clearly limited only to foreign locations where there is clear and compelling evidence that the location would authorise copyright infringement if it were in Australia. Third, proportionality requires that measures are reasonable and strike an appropriate balance between competing interests. This draft legislation provides few safeguards for the public interest or the interests of private actors who would access legitimate information. New safeguards should be introduced to ensure that the public interest is well represented at both the stage of the primary application and at any applications to rescind or vary injunctions. We recommend that: The legislation not be introduced unless and until there is compelling evidence that it will have a real and significant positive impact on the effective incomes of Australian creators. The ‘facilitates an infringement’ test in s 115A(1)(b) should be replaced with ‘authorises infringement’. The ‘primary purpose’ test in s 115A(1)(c) should be replaced with: “the online location has no substantial non-infringing uses”. An explicit role for public interest groups as amici curiae should be introduced. Costs of successful applications should be borne by applicants. Injunctions should be valid only for renewable two year terms. Section 115A(5) should be clarified, and cl (b) and (c) be removed. The effectiveness of the scheme should be evaluated in two years.

Drivers of local food consumption: A comparative study

Purpose The aim of this paper is to empirically explore antecedents of local food purchase intention in two food producing countries with different cultural backgrounds. Design/methodology/approach An online survey was employed to collect data from consumers located in Chile (n=283) and Australia (n=300). A proposed model is tested with structural equation modelling (SEM). Findings Attitude towards consuming local food is a strong and direct driver of intentions to purchase local food in both countries. Attitude toward supporting local agri-businesses and consumer ethnocentrism are found to positively impact attitude towards consuming local food in both countries. Attitude towards local agri-businesses also has a direct effect on intentions to purchase local food in Australia, but not in Chile. Interestingly, subjective norms are not found to affect intentions to consume local food in either country. Research limitations/implications The paper examines factors affecting the attitude toward and behavioural intention regarding local food consumption and develops an extended model of local food consumption. An outcome of this new model is the inclusion of personal variables, which influence local food purchasing behaviour. Practical implications Producers and retailers need to develop campaigns explaining how consuming local food supports local businesses and farmers, which will reinforce personal values associated with local consumption. Originality/value This is the first study to demonstrate that positive attitudes toward local foods are important drivers of local food purchase behaviour, independent of the cultural characteristics or level of economic development within a country.

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.

Virtual community, purchasing behaviour, and emotional well-being

The benefits of virtual communities in increasing firms' profits, instilling knowledge in consumers, and enhancing consumers' social experience and enjoyment are widely recognised. However, relatively little is known about how the use of a virtual community could influence consumers' emotional well-being. This study examines the relationships among virtual community features (structural and experiential routes) as antecedents of virtual community engagement, including quality of use of virtual communities (time spent online and level of information exchange), electronic word-of-mouth (eWOM) purchasing behaviour, and consumers' emotional experience. Furthermore, by extending the cultural perspective to virtual community engagement, this study examines the role of collectivistic values on the aforementioned relationships. The proposed hypotheses are tested on the basis of data collected from 286 members of different virtual communities in Taiwan. The results partially support the theory that features of virtual communities influenced the quality of use, which then has a subsequent effect on consumer eWOM purchasing and emotional well-being. The results of the empirical analysis add credence to the proposed relationships. The role of collectivistic values is also partially supported. A detailed discussion of the findings and limitations of this study is provided.

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.

Investigating the concept of potential quality: An exploratory study in the real estate industry

Purpose The purpose of this research is to examine the concept of “potential quality” – that is, a company's tangible search qualities (such as the physical servicescape and virtual servicescape) – within the context of the real‐estate industry in the USA. Design/methodology/approach This qualitative study collects data by conducting personal in‐depth interviews with 34 respondents who had been recent buyers or renters of property. The data are then coded and themed to identify quality dimensions relevant to this industry. Findings The results indicate that a buyer's perception of the overall service quality of real‐estate service consists of two components: the interaction with a realtor (process quality); and the virtual servicescape, especially the firm's website design and content (potential quality). The study concludes that existing scales (such as SERVQUAL and RESERV) fail to capture the tangible component of service quality sufficiently in the real‐estate industry. Research limitations/implications The study uses data from only one industry (real estate) and from only one demographic segment (professionals in higher education). Practical implications Service providers of intangible, high‐contact services must appreciate the importance of the virtual servicescape as a surrogate quality indicator that can help to reduce information asymmetries and consumers' uncertainty with regard to initiating a business relationship. Real estate firms need to pay attention to the training of agents and the design and content of their e‐service systems. Originality/value This study integrates potential quality, process quality, and outcome quality in a comprehensive proposed model. In particular, the study identifies “potential quality” as a combination of the attributes of the virtual service environment and the physical service environment.

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.

Harry Potter and the lexicon of doom

In a three day trial in April 2008, the United States District Court for the Southern District of New York considered whether the Harry Potter Lexicon infringed the intellectual property rights of J.K. Rowling and Warner Brothers. The case has attracted great media attention. As John Crace, a reporter for The Guardian, observed: “On one side: global-celebrity author J.K. Rowling. On the other: an amateur fan site devoted to the world's favourite boy wizard. At stake: the soul of Harry Potter.” J.K. Rowling is the author of the seven book Harry Potter series, which tell the story of a young wizard, Harry Potter, and his battles with Voldemort, the Lord of Darkness. As the court papers noted, “The Harry Potter Books are a modern day publishing phenomenon and success story.” Warner Brothers sought and obtained the film rights to the series. The entertainment company has thus far produced five films; a sixth is due in November 2008; and the final instalment is planned. The Harry Potter Lexicon is a reference guide created by Steven Vander Ark, a former grade school teacher. He has organised a large volume of material on the Harry Potter books and the Harry Potter films on a website in an alphabetical listing, from “A-Z”. The founder of RDR Books, Roger Rapoport, approached Ark to publish the Harry Potter Lexicon in a book form. Ark agreed to this request, and provided the publisher with a condensed version of the web-site. After RDR Books announced its intention to publish the reference book, J.K. Rowling and Warner Brothers brought a legal action in the United States District Court for the Southern District of New York, alleging that the publishers of the Harry Potter Lexicon were in breach of various intellectual property rights. A spokesperson for Warner Brothers and J.K. Rowling observed: "A fan’s affectionate enthusiasm should not obscure acts of plagiarism. The publishers knew what they were doing. The problem remains that the Lexicon takes an enormous amount of Ms. Rowling’s work and adds virtually no original commentary of its own. As we’ve said in court, it takes too much and adds too little. Authors have a duty to prevent the exploitation of their works by people who contribute nothing original, creative or interpretive." The litigation involves the intersection of copyright law, trade mark law, and consumer protection law. It has a wider significance because it deals with the protection of authorial rights; the use of literary indexes, supplements and reference guides; and the clash between character merchandising and fan fiction.