Mental Health Social Work and the Troubles in Northern Ireland: A Study of Practitioner Experiences

• Summary: During the last decade increasing attention has been paid to the impact of the Troubles1 on social work in Northern Ireland. In this paper, the authors describe the first survey used to test some of the assumptions which exist in the literature. An 87-item questionnaire was applied to a range of social work staff currently working in, or associated with, mental health settings. One hundred and one questionnaires were returned: it is estimated that this represented over 70 per cent of mental health social workers in Northern Ireland. • Findings: The design of the questionnaire elicited both qualitative and quantitative data. The findings reveal a workforce with complex religious and national identities and many of the respondents have experienced relatively high levels of Troubles-related incidents whilst carrying out their duties in a variety of organizational and geographical settings. High proportions of respondents received minimal agency support and training to equip them to deal with Troubles-related problems faced by them during this period. • Applications: The authors conclude that the profession and employing agencies should pay greater attention to past and present effects of the Troubles on social work practice and develop appropriate strategies for supporting, training and resourcing staff in this neglected area.

Emotional speech: towards a new generation of databases

Research on speech and emotion is moving from a period of exploratory research into one where there is a prospect of substantial applications, notably in human-computer interaction. Progress in the area relies heavily on the development of appropriate databases. This paper addresses the issues that need to be considered in developing databases of emotional speech, and shows how the challenge of developing apropriate databases is being addressed in three major recent projects - the Belfast project, the Reading-Leeds project and the CREST-ESP project. From these and other studies the paper draws together the tools and methods that have been developed, addresses the problems that arise and indicates the future directions for the development of emotional speech databases.

Endostatin modulates VEGF-mediated barrier dysfunction in the retinal microvascular endothelium

Recent evidence indicates that the anti-angiogenic peptide endostatin may modulate some of the vasomodulatory effects of vascular endothelial growth factor (VEGF) in the retina, including reduction of blood retinal barrier function although it remains uncertain how endostatin promotes endothelial barrier properties. The current study has sought to examine how physiological levels of endostatin alters VEGF-induced inner BRB function using an in vitro model system and evaluation of occludin and ZO-1 regulatory responses. In addition, the ability of exogenous endostatin to regulate VEGF-mediated retinal vascular permeability in vivo was investigated.

Retinal microvascular endothelial cells (RMEC's) were exposed to various concentrations of endostatin. In parallel studies, RMEC monolayers were treated with vascular endothelial growth factor (VEGF165). Vasopermeability of RMEC monolayers and occludin expression were determined.

Blood retinal barrier integrity was quantified in mouse retina using Evans Blue assay following intravitreal delivery of VEGF165, endostatin or a VEGF/endostatin combination.

Endostatin increased the levels of expression of occludin whilst causing no significant change in FITC-dextran flux across the RMEC monolayer. Endostatin reversed the effects of VEGF165-enhanced permeability between microvascular endothelial cells and induced phosphorylation of occludin. Evans Blue leakage from retinas treated with VEGF was 2.0 fold higher than that of contra-lateral untreated eyes (P<0.05) while leakage of eyes from endostatin treated animals was unchanged. When eyes were injected with a combination of VEGF165 and endostatin there was a significant reduction in retinal vasopermeability when compared to VEGF-injected eyes (P<0.05).

We conclude that endostatin can promote integrity of the retinal endothelial barrier, possibly by preventing VEGF-mediated alteration of tight junction integrity. This suggests that endostatin may be of clinical benefit in ocular disorders where significant retinal vasopermeability changes are present.

BRCA1 Suppresses Osteopontin-mediated Breast Cancer

BRCA1 is a well described breast cancer susceptibility gene thought to be involved primarily in DNA repair. However, mutation within the BRCA1 transcriptional domain is also implicated in neoplastic transformation of mammary epithelium, but responsible mechanisms are unclear. Here we show in a rat mammary model system that wild type (WT) BRCA1 specifically represses the expression of osteopontin (OPN), a multifunctional estrogen-responsive gene implicated in oncogenic transformation, particularly that of the breast. WT.BRCA1 selectively binds OPN-activating transcription factors estrogen receptor alpha, AP-1, and PEA3, inhibits OPN promoter transactivation, and suppresses OPN mRNA and protein both from an endogenous gene and a relevant model inducible gene. WT.BRCA1 also inhibits OPN-mediated neoplastic transformation characterized by morphology change, anchorage-independent growth, adhesion to fibronectin, and invasion through Matrigel. A mutant BRCA1 allele (Mut.BRCA1) associated with familial breast cancer lacks OPN suppressor effects, binds to WT.BRCA1, and impedes WT.BRCA1 suppression of OPN. Stable transfection of rat breast tumor cell lines with Mut.BRCA1 dramatically up-regulates OPN protein and induces anchorage independent growth. In human primary breast cancer, BRCA1 mutation is significantly associated with OPN overexpression. Taken together, these data suggest that BRCA1 mutation may confer increased tissue-specific cancer risk, in part by disruption of BRCA1 suppression of OPN gene transcription.