Inhibiting epidermal growth factor receptor at a distance.

The epidermal growth factor receptor (EGFR) tyrosine kinase is implicated in a large number of human cancers. Most EGFR inhibitors target the extracellular, growth factor-binding domain or the intracellular, ATP-binding domain. Here we describe molecules that inhibit the kinase activity of EGFR in a new way, by competing with formation of an essential intradimer coiled coil containing the juxtamembrane segment from each member of the receptor partnership. The most potent molecules we describe bind EGFR directly, decrease the proliferation of wild-type and mutant EGFR-dependent cells lines, inhibit phosphorylation of EGFR and downstream targets, and block coiled coil formation as judged by bipartite tetracysteine display. Potency is directly correlated with the ability to block coiled coil formation within full-length EGFR in cells

Seasonal facilitative and competitive trade‐offs between shrub seedlings and coastal grasses

Shrub expansion is occurring in grasslands globally and may be impacted by the balance of competition and facilitation with existing grasses. Along the mid‐Atlantic and Gulf coasts, the native shrub Morella cerifera (wax myrtle) is rapidly expanding and displacing other native coastal species. Recent research suggests that much of this expansion is due to warming winter temperatures, as temperatures below −15°C kill M. cerifera. The objective of this project was to understand the importance of species interactions with grasses on the growth and physiology of M. cerifera at the seedling life stage through both field and laboratory experiments. In the field, grasses were removed around seedlings and microclimate and shrub physiology and growth were measured. Seeds and seedlings were experimentally frozen to measure the freeze tolerance at both life stages. We found that grasses provided ~1.3°C insulation to shrubs during winter. A freezing threshold for M. cerifera seedlings was experimentally found between −6°C and −11°C, but seeds remained viable after being frozen to the coldest ecologically relevant temperatures. Seedlings competed for light with grasses during warm months and grew more where grasses were clipped, revealing a trade‐off between winter insulation and summer light competition. Morella cerifera exhibits ecosystem engineering at the seedling stage by significantly reducing summer maximum temperatures. When seedlings are very young (less than one year), grasses appear to improve germination and seedling survival. These phenomena enable rapid expansion of M. cerifera across the landscape and likely inform shrub expansion mechanisms in other systems. Although seedlings are small and relatively vulnerable, this life stage appears to have significant implications for ecosystem trajectory in grasslands undergoing shrub encroachment

Psychological ownership and music streaming consumption

Streaming is becoming the most common format from which people access, share and listen to music and it is suggested that such practices are indicative of a shift towards a ‘post-ownership’ economy. In the case of music, consumers may place greater value (emotional and monetary) on the physical product because of the lack of legal ownership and/or absence of perceived ownership associated with streaming. This article examines how experiences of ownership are articulated through music streaming formats via qualitative interviews and an online themed discussion group. Drawing from psychological ownership theory we identify motivations (place, identity and control), antecedents (investing the self, coming to intimately know the target, pride and controlling the target) and outcomes (loyalty, empowerment and social rewards) of psychological ownership that are evident in the consumers' experiences of music streaming. This has theoretical and managerial implications for our understanding of how consumers engage with the post-ownership economy

Sport fandom and parenthood

Research question: Sport fandom is acknowledged as offering consumers the opportunity to differentially engage as well as co-create value through network interaction, enhancing social well-being and social integration. However, recent research indicates that sport fandom escalates or de-escalates over time with calls to examine the intersection of parenting and sport fandom. This research focuses on mothers and fathers and examines how their sport fandom intensifies or declines as a consequence of having and raising children. This research will add to our understanding of fandom by identifying when and under what circumstances sport fandom is a bonding or detaching experience for parents and the role it plays in socialization and consumer behavior.  Research methods: The study adopts a multi-method interpretive qualitative approach, using in-depth interviews and an online discussion forum. The sampling frame consists of a total of thirty five parents using two stages of research (Stage 1 n=15, Stage 2 n=20). Participants are at varying stages of parenthood with single and mixed gender families.  Results and Findings: The study develops a typology of (de)escalating sport fandom during parenthood and differentiates between fandom as pertaining to an individual or social identity. Data also reveals varying dichotomies such as: excess and moderation, risk and reward, individual and shared behaviors (including customer-to-customer interaction) as well as perceptions of allegiance and disloyalty.  Implications: Knowledge of parenting and sport fandom will assist managers in developing effective loyalty schemes and marketing packages and will offer an understanding of the temporal effect of having children on fandom

General Practice from the perspective of a Learning Organisation

The focus of the study is situated in future directions for the health care of NSW residents. Across the world and in Australia it has been recognised that more emphasis needs to be placed on primary care with the goal of improving health outcomes and reducing health costs and health inequities. With the need to reposition the Australian healthcare workforce in response to federal health reforms and in order to meet the primary healthcare needs of future populations a key strategy of NSW 2021 is preventive health and effective management of chronic disease. The general practice microsystem is at the forefront of service provision. A narrative literature review technique was conducted to discuss and synthesise ideas concerning the application and enactment of learning organisation theory in Australia particularly regarding general practice microsystems. A narrative literature review offers the advantage of integrating qualitative and quantitative evidence and providing a broad coverage of issues on a topic. In order to overcome the perceived shortcomings of narrative reviews such as bias and lack of transparency, concepts investigated, search terminology used and inclusion and exclusion criteria for articles selected are carefully and succinctly explained. A mixed method approach was chosen for the study as it incorporates the use of qualitative and quantitative strategies and results in collection of data that represents differing lenses, perspectives and viewpoints. Quantitative data collection included data from staff (administrative, nurses and doctors), practice managers and patient questionnaires while qualitative data was derived from staff and practice manager interviews.The research reported in this paper is a project of the Australian Primary Health Care Research Institute which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research Evaluation and Development Strategy

Factors affecting recruitment and attrition in randomised controlled trials of Complementary and Alternative Medicine for pregnancy-related issues

Background. Randomised controlled trials (RCTs) investigating Complementary and Alternative Medicine (CAM) for pregnancy-related issues have encountered issues with recruitment and attrition. Little is known about the cause of these issues. Methods. Data was gathered from an antenatal CAM randomised controlled trial. During foetal anomaly appointments, women meeting inclusion criteria were invited to participate in the trial. Numbers of women invited and eligible were recorded. Reasons for noninterest were noted and analysed. Focus groups exploring trial experience of participants were also conducted. Findings. Of the 428 women invited to participate, 376 were eligible and just under a quarter participated. Reasons for nonparticipation included concerns about CAM and lack of interest in participation in research. Other factors negatively affecting recruitment included recruitment timing, competition for participants, limited support from staff, and inadequate trial promotion. Factors encouraging recruitment included being interested in research and seeking pain relief. Reasons for dropping out were time constraints, travel issues, work commitments, and pregnancy issues. Several women in the sham and usual care group dropped out due to dissatisfaction with treatment allocation. Conclusion. CAM researchers must explore problems encountered with recruitment and attrition so that evidence-based implementation strategies to address the issues can be developed