The prognostic and therapeutic value of EpHA2 in early colorectal cancer (CRC).

Background: EpHA2 is a 130 kD transmembrane glycoprotein belonging to ephrin receptor subfamily and involved in angiogenesis/tumour neovascularisation. High EpHA2 mRNA level has recently been implicated in cetuximab resistance. Previously, we found high EpHA2 levels in a panel of invasive colorectal cancer (CRC) cells, which was associated with high levels of stem-cell marker CD44. Our aim was to investigate the prognostic value of EpHA2 and subsequently correlate expression levels to known clinico-pathological variables in early stage CRC. Methods: Tissue samples from 509 CRC patients were analysed. EpHA2 expression was measured using IHC. Kaplan-Meier graphs were used. Univariate and multivariate analyses employed Cox Proportional Hazards Ratio (HR) method. A backward selection method (Akaike’s information criterion) was used to determine a refined multivariate model. Results: EpHA2 was highly expressed in CRC adenocarcinoma compared to matched normal colon tissue. In support of our preclinical invasive models, strong correlation was found between EpHA2 expression and CD44 and Lgr5 staining (p<0.001). In addition, high EpHA2 expression significantly correlated with vascular invasion (p=0.03).HR for OS for stage II/III patients with high EpHA2 expression was 1.69 (95%CI: 1.164-2.439; p=0.003). When stage II/III was broken down into individual stages, there was significant correlation between high EpHA2 expression and poor 5-years OS in stage II patients (HR: 2.18; 95%CI: 1.28-3.71; p=0.005).HR in the stage III group showed a trend to statistical significance (HR: 1.48; 95%CI=0.87-2.51; p=0.05). In both univariate and multivariate analyses of stage II patients, high EpHA2 expression was the only significant factor and was retained in the final multivariate model. Higher levels of EpHA2 were noted in our RAS and BRAF mutant CRC cells, and silencing EpHA2 resulted in significant decreases in migration/invasion in parental and invasive CRC sublines. Correlation between KRAS/NRAS/BRAFmutational status and EpHA2 expression in clinical samples is ongoing. Conclusions: Taken together, our study is the first to indicate that EpHA2 expression is a predictor of poor clinical outcome and a potential novel target in early stage CRC.

Negotiating Territoriality and Diversity: Young People’s Encounters in Northern Ireland Divided Communities

Neighborhoods across the globe are becoming increasingly ‘divers’, yet we still find their urban encounters reproduced through negotiating differences that escalates moods of social inequality and spatial imbalances. Research on ethnic division also stresses the spatial aspects of their production as shared urban spaces are mostly signified in the literature as ethnic ‘enclaves’. Territoriality and place attachment, in this sense, has a wide impact on the people’s everyday encounters while experiencing segregation. These historical narratives have produced communities that exhibit high levels of intracommunity relations and localized networking. This article investigates how youngster generations in Northern Ireland perceive, accept and respond to their differences, or perhaps how they act against it, to push the boundaries towards more diversity. In fact, the spatial and temporal encounters that occur among one community and the ‘Other’ signify a sort of negotiations and being more constructive about the future. The argument maintains that territoriality and place attachment has a wide impact on the young people’s everyday experiences. The empirical study shows how individuals and community groups position and identify themselves under the impact of social segregation. Building on social identity theories, I explain how people in Derry have established their own sense of belonging, of who they are, based on their group memberships which eventually became an important source of pride and self-esteem.

Social Ecological Constraints to Park Use in Communities with Quality Access

Evidence correlates physical activity, psychological restoration, and social health to proximity to parks and sites of recreation. The purpose of this study was to identify perceived constraints to park use in low-income communities facing significant health disparities, with access to underutilized parks. We used a series of focus groups with families, teens, and older adults in neighborhoods with similar demographic distribution and access to parks over 125 acres in size. Constraints to park use varied across age groups as well as across social ecological levels, with perceived constraints to individuals, user groups, communities, and society. Policies and interventions aimed at increasing park use must specifically address barriers across social ecological levels to be successful.

How do clinicians become teachers? A communities of practice perspective.

There is widespread acceptance that clinical educators should be trained to teach, but faculty development for clinicians is undermined by poor attendance and inadequate learning transfer. As a result there has been growing interest in situating teacher development initiatives in clinical workplaces. The relationship between becoming a teacher and clinical workplace contexts is under theorised. In response, this qualitative research set out to explore how clinicians become teachers in relation to clinical communities and institutions. Using communities of practice (CoP) as a conceptual framework this research employed the sensitising concepts of regimes of competence and vertical (managerial) and horizontal (professional) planes of accountability to elucidate structural influences on teacher development. Fourteen hospital physicians completed developmental timelines and underwent semi-structured interviews, exploring their development as teachers. Despite having very different developmental pathways, participants’ descriptions of their teacher identities and practice that were remarkably congruent. Two types of CoP occupied the horizontal plane of accountability i.e. clinical teams (Firms) and communities of junior doctors (Fraternities). Participants reproduced teacher identities and practice that were congruent with CoPs’ regimes of competence in order to gain recognition and legitimacy. Participants also constructed their teacher identities in relation to institutions in the vertical plane of accountability (i.e. hospitals and medical schools). Institutions that valued teaching supported the development of teacher identities along institutionally defined lines. Where teaching was less valued, clinicians adapted their teacher identities and practices to suit institutional norms. Becoming a clinical educator entails continually negotiating one’s identity and practice between two potentially conflicting planes of accountability. Clinical CoPs are largely conservative and reproductive of teaching practice whereas accountability to institutions is potentially disruptive of teacher identity and practice.