Consequences of unlocking the cardiac myosin molecule in human myocarditis and cardiomyopathies

Myocarditis, often initiated by viral infection, may progress to autoimmune inflammatory heart disease, dilated cardiomyopathy and heart failure. Although cardiac myosin is a dominant autoantigen in animal models of myocarditis and is released from the heart during viral myocarditis, the characterization, role and significance of anti-cardiac myosin autoantibodies is poorly defined. In our study, we define the human cardiac myosin epitopes in human myocarditis and cardiomyopathies and establish a mechanism to explain how anti-cardiac myosin autoantibodies may contribute to heart disease. We show that autoantibodies to cardiac myosin in sera from myocarditis and dilated cardiomyopathies in humans targeted primarily epitopes in the S2 hinge region of cardiac myosin. In addition, anti-cardiac myosin antibodies in sera or purified IgG from myocarditis and cardiomyopathy targeted the beta-adrenergic receptor and induced antibody-mediated cAMP-dependent protein kinase A (PKA) cell signaling activity in heart cells. Antibody-mediated PKA activity in sera was abrogated by absorption with anti-human IgG. Antibody-mediated cell signaling of PKA was blocked by antigen-specific inhibition by human cardiac myosin or the beta-adrenergic receptor but not the alpha adrenergic receptor or bovine serum albumin. Propranolol, a beta blocker and inhibitor of the beta-adrenergic receptor pathway also blocked the antibody-mediated signaling of the beta-adrenergic receptor and PKA. The data suggest that IgG antibody against human cardiac myosin reacts with the beta-adrenergic receptor and triggers PKA signaling in heart cells. In summary, we have identified a new class of crossreactive autoantibodies against human cardiac myosin and the beta-adrenergic receptor in the heart. In addition, we have defined disease specific peptide epitopes in the human cardiac myosin rod S2 region in human myocarditis and cardiomyopathy as well as a mechanistic role of autoantibody in the pathogenesis of disease.

Health status and 6 years survival of 552 90+ Italian sib-ships recruited within the EU Project GEHA (GEnetics of Healthy Ageing).

In a scenario of increasing life expectancy worldwide, it is mandatory to identify the characteristics of a healthy aging phenotype, including survival predictors, and to disentangle those related to environment/lifestyle versus those related to familiarity/genetics. To this aim we comprehensively characterised a cohort of 1,160 Italian subjects of 90 years and over (90+, mean age 93 years; age range 90-106 years) followed for 6 years survival, belonging to 552 sib-ships (familiar longevity) recruited (2005-2008) within the EU-funded GEHA project in three Italian geographic areas (Northern, Central and Southern Italy) different for urban/rural and socio-economical characteristics. On the whole, the following factors emerged as significant predictors of survival after 90 years of age: absence of cognitive impairment and physical disability, high hand grip strength scores and body mass index (BMI) values, "excellent/good" self-reported health, high haemoglobin and total cholesterol levels and low creatinine levels. These parameters, excluding BMI values, were also significantly associated within sib-ships, suggesting a strong familial/genetic component. Geographical micro-heterogeneity of survival predictors emerged, such as functional and physical status being more important in Southern than in Central and Northern Italy. In conclusion, we identified modifiable survival predictors related to specific domains, whose role and importance vary according to the geographic area considered and which can help in interpreting the genetic results obtained by the GEHA project, whose major aim is the comprehensive evaluation of phenotypic and genetic data.

Race, space and politics in Mid-Victorian Ireland: the ethnologies of Abraham Hume and John McElheran

There has been much scholarly debate about the significance and influence of racialist thinking in the political and cultural history of nineteenth-century Ireland. With reference to that ongoing historiographical discussion, this paper considers the racial geographies and opposing political motivations of two Irish ethnologists, Abraham Hume and John McElheran, using their racialist regimes to query some of the common assumptions that have informed disagreements over the role and reach of racial typecasting in mid-nineteenth-century Ireland. As well as examining in detail the racial imaginaries promulgated by Hume and McElheran, the paper also argues for the importance of situating racialist discourse in the spaces in which it was communicated and contested. Further, in highlighting the ways in which Hume and McElheran collapsed together race, class and religion, the paper troubles the utility of a crisp analytical distinction between those disputed categories.

General practitioners’ management of the long-term sick role

In this paper, we use qualitative research techniques to examine the role of general practitioners in the management of the long-term sickness absence. In order to uncover the perspectives of all the main agents affected by the actions of general practitioners, a case study approach focussing on one particular employment sector, the public health service, is adopted. The role of family physicians is viewed from the perspectives of health service managers, occupational health physicians, employees / patients, and general practitioners. Our argument is theoretically framed by Talcott Parsons’s model of the medical contribution to the sick role, along with subsequent conceptualisations of the social role and position of physicians. Sixty one semi-structured interviews and three focus group interviews were conducted in three Health and Social Care Trusts in Northern Ireland between 2010 and 2012. There was a consensus among respondents that general practitioners put far more weight on the preferences and needs of their patients than they did on the requirements of employing organisations. This was explained by respondents in terms of the propinquity and longevity of relationships between doctors and their patients, and by the ideology of holistic care and patient advocacy that general practitioners viewed as providing the foundations of their approach to patients. The approach of general practitioners was viewed negatively by managers and occupational health physicians, and more positively by general practitioners and patients. However, there is some evidence that general practitioners would be prepared to forfeit their role as validators of sick leave. Given the imperatives of both state and capital to reduce the financial burden of long-term sickness, this preparedness puts into doubt the continued role of general practitioners as gatekeepers to legitimate long-term sickness absence.

(Re)-Introducing Themes of Religion and Spirituality to Professional Social Work Training in the Land of ‘Saints and Scholars’.

This chapter begins by alluding to Ireland’s historical reputation as the land of “Saints and Scholars” and then briefly charts its demise from this position. A parallel process in relation to religiously motivated provision of health and social care is outlined. The inclusion of themes of religion and spirituality within the current professional social work codes in the USA and Britain and the framework for social work training in Northern Ireland is noted. In this context the lack of any substantive inclusion of themes of religion and/or spirituality within the Bachelor of Social Work (BSW) degree at Queens University Belfast will be situated. A series of intersecting reasons for this lack of inclusion are proposed in terms of the experience of living through the recent troubled history of Northern Ireland and a variety of biases in academic thought.
A rationale for the re-introduction of inputs on religion and spirituality is articulated in terms of the widespread resurgence of these themes within health and social care and psychotherapy literature and the new emphasis on practicing in culturally sensitive ways in Britain. The first steps to re-introduce these themes under the higher context marker of “culturally competent practice” are described and an analysis of data from the students’ feedback presented along with illustrative quotations. The dissonance between the initial misgivings of staff and the overwhelmingly positive responses of students are highlighted. The chapter concludes with a discussion of lessons learned through the process with an emphasis on how the inclusion of these themes can result in better practice for service users, including those impacted by “the Troubles” in Northern Ireland.

When terror hits home: Identity Fused Americans who saw Boston bombing victims as “family” provided aid

When tragedy strikes a group, only some group members characteristically rush to the aid of the victims. What motivates the altruism of these exceptional individuals? Here, we provide one set of answers based on data collected before and shortly after the 15 April 2013, Boston Marathon bombings. The results of three studies indicated that Americans who were strongly “fused” with their country were especially inclined to provide various forms of support to the bombing victims. Moreover, the degree to which participants reported perceiving fellow Americans as psychological kin statistically mediated links between fusion and pro-group outcomes. Together, these findings shed new light on relationships between personal and group identity, cognitive representations of group members, and personally costly, pro-group actions.

Rough Waters, Dark Shadows and Cross-Cutting Winds:the impact of European Union enlargement on Turkey’s EU accession negotiations

For a multiplicity of socio-economic, geo-political, strategic and identity-based reasons, Turkey’s progress towards EU membership is often treated as a sui generis case. Yet although Turkey’s accession negotiations with the European Union (EU) are essentially a bilateral – and often stormy – affair, they take place within a wider and dynamic process of enlargement in which not only can the gloomy – sometimes dark – shadows of past and prospective enlargements be clearly detected, but so too can the often chill winds from ongoing, parallel negotiations with other candidates. How the EU negotiates accession and what it expects from candidates has continued to evolve since the EU began drawing up its framework for negotiations with Turkey ten years ago. This paper charts this evolution by first identifying changes in the light of Croatia’s negotiating experience, the ‘lessons learnt’ by the EU in meeting the challenges of Bulgarian and Romanian accession, the EU’s handling of Iceland’s membership bid and accession negotiations, and the revised approach to negotiating accession evident in the more recent frameworks for accession negotiations with Montenegro and Serbia. The paper then explores the extent to which these changes have impacted on the approach the EU has adopted in framing and progressing accession negotiations with Turkey. In doing so, it questions both the consistency with which the EU’s negotiates accession and the extent to which Turkey’s progress towards EU membership is conditioned by the broader dynamics of EU enlargement as opposed to simply the dynamics within EU-Turkey relations and domestic Turkish reform efforts.

Symmetrical Solutions, Asymmetrical Realities: Beyond the Politics of Paralysis

The historic significance of the Good Friday Agreement and its role in ending organized political violence is acknowledged at the outset. The article then goes on to probe the roots of the political paralysis built into the architecture of the Agreement that are predicated on a misplaced political and cultural symmetry between the “two communities.” It is suggested that the institutionalized relationship between Northern Ireland and the rest of the U.K. facilitates a cross-party, populist, socio-economic consensus among the nationalist and unionist political parties on the welfare state, taxation and maintaining the massive British subvention to the region. This in turn allows them to concentrate on a divisive culturalist politics, i.e., on antagonistic forms of cultural and identity politics over such issues as flags, parades, and the legacy of the “Troubles” which spills over into gridlock into many areas of regional administration. The article argues for a much broader understanding of culture and identity rooted in the different, if overlapping and interdependent, material realities of both communities while challenging the idea of two cultures/identities as fixed, mutually exclusive, non-negotiable and mutually antagonistic. It then focuses on the importance of Belfast as a key arena which will determine the long-term prospects of an alternative and more constructive form of politics, and enable a fuller recognition of the fundamental asymmetries and inter-dependence between the “two communities.” In the long run, this involves re-defining and reconstructing what is meant by the “Union” and a “United Ireland.”

Assessment matters-mentors need support in their role

BACKGROUND:
In the UK the Nursing and Midwifery Council (NMC) standards to support learning and assessment in practice state that mentors are responsible and accountable for the assessment of pre-registration nursing students in practice. This study was undertaken to explore mentors' experience of assessing nursing students in practice post implementation of the NMC standards.
METHOD:
Five focus groups were conducted with mentors (N=35) who had assessed adult pre-registration nursing students in the previous 12 months. The focus groups were recorded, transcribed and analysed to generate categories.
RESULTS:
Five categories were identified from the data: Changing roles and responsibilities; Exploring the past to understand the present; Just knowing; The odds; Time to mentor. The findings highlighted that mentors were aware of their role and responsibility for the assessment of students in practice. However, many felt this was a new responsibility and role in which they lacked experience. Some existing mentors felt that they may not have had the necessary preparation to effectively assess students in practice and identified their need for support.
CONCLUSION:
Given that mentors are expected to be competent assessors of students in practice and protect the public through gate-keeping professional registration, this study suggests that serious consideration should be given to how mentors are prepared and the ongoing support and education they receive in assessment.

Consensus and Confusion in Molluscan Trees: Evaluating Morphological and Molecular Phylogenies

Mollusks are the most morphologically disparate living animal phylum, they have diversified into all habitats, and have a deep fossil record. Monophyly and identity of their eight living classes is undisputed, but relationships between these groups and patterns of their early radiation have remained elusive. Arguments about traditional morphological phylogeny focus on a small number of topological concepts but often without regard to proximity of the individual classes. In contrast, molecular studies have proposed a number of radically different, inherently contradictory, and controversial sister relationships. Here, we assembled a dataset of 42 unique published trees describing molluscan interrelationships. We used these data to ask several questions about the state of resolution of molluscan phylogeny compared to a null model of the variation possible in random trees constructed from a monophyletic assemblage of eight terminals. Although 27 different unique trees have been proposed from morphological inference, the majority of these are not statistically different from each other. Within the available molecular topologies, only four studies to date have included the deep-sea class Monoplacophora; but 36.4% of all trees are not significantly different. We also present supertrees derived from 2 data partitions and 3 methods, including all available molecular molluscan phylogenies, which will form the basis for future hypothesis testing. The supertrees presented here were not constructed to provide yet another hypothesis of molluscan relationships, but rather to algorithmically evaluate the relationships present in the disparate published topologies. Based on the totality of available evidence, certain patterns of relatedness among constituent taxa become clear. The internodal distance is consistently short between a few taxon pairs, particularly supporting the relatedness of Monoplacophora and the chitons, Polyplacophora. Other taxon pairs are rarely or never found in close proximity, such as the vermiform Caudofoveata and Bivalvia. Our results have specific utility for guiding constructive research planning in order to better test relationships in Mollusca as well as other problematic groups. Taxa with consistently proximate relationships should be the focus of a combined approach in a concerted assessment of potential genetic and anatomical homology, while unequivocally distant taxa will make the most constructive choices for exemplar selection in higher-level phylogenomic analyses.

Enabling Others in Social Work: Reflexivity and the Theory of Social Domains

This paper sets out a framework to structure reflexivity in social work practice. Based on the thinking of the sociologist, Derek Layder, it comprises five domains that impact on the individual and social life, namely: (i) psycho-biography – referring to a person’s unique experience throughout the life-course; (ii) situated activity – highlighting the impact of every day social interaction; (iii) social settings – addressing the role of organizations in social life; (iv) culture – covering the influence of attitudes, beliefs, tastes and ideas on symbolic meaning; and (v) politico-economy – alluding to the ramifications of political and economic forces on people’s lives. It is contended that power circulates throughout each domain as an enabling and constraining force. The paper then outlines a process for using the reflexive framework in ‘enabling’ activities such as practice learning, supervision, mentoring and coaching. By applying the framework in these contexts, it is argued that social workers can reflect critically on their role and develop emancipatory forms of practice.

Behind the Headlines: Media Representation of Children and Young People in Northern Ireland:Summary of Research Findings

Funded by the Economic and Social Research Council this partnership project between the Childhood, Transition and Social Justice Initiative at Queen’s University and Include Youth focuses on the negative stereotyping of children and young people and the role and responsibilities of the media in the creation and transmission of negative images. Engaging with children, young people, organisations working with children and young people and media representatives, the project uses research evidence to explore negative media representation and its consequences for children’s rights, public reaction and policy initiatives in Northern Ireland. This report represents a summary of the findings of engagement with 141 children and young people. It outlines how they feel they are presented by the media and the impacts of this. It concludes by noting ways forward in challenging negative portrayals.

Intra and Interorganizational Learning Networks and the Implementation of Quality Improvement Initiatives: The Case of a Portuguese Teaching Hospital

Learning has an important position in the development of employees and their expertise. This article focuses on the role and utilization of intra and interorganizational formal and informal learning within different types of learning networks. Specifically, we investigate different types of networks (inter- or intraorganizational) and different types of learning (formal or informal) that can occur within such networks. Our qualitative case study is based on 46 expert interviews involving 49 interviewees, through which we explore how formal and informal learning was used in the development and implementation of quality improvement initiatives at a large public teaching hospital in Portugal. Our analysis suggests that formal and informal learning can take place within different types of learning networks that draw on internal resources as well as on the collaboration with external entities. The article argues that it is important for HRD managers, seeking to support organizational learning, to understand how different types of learning take place, and which features of learning networks support these processes.

Families and Poverty: Everyday life on a low income

The recent radical cutbacks of the welfare state in the UK have meant that poverty and income management continue to be of great importance for intellectual, public and policy discourse. Written by leading authors in the field, the central interest of this innovative book is the role and significance of family in a context of poverty and low-income. Based on a micro-level study carried out in 2011 and 2012 with 51 families in Northern Ireland, it offers new empirical evidence and a theorisation of the relationship between family life and poverty. Different chapters explore parenting, the management of money, family support and local engagement. By revealing the ordinary and extraordinary practices involved in constructing and managing family and relationships in circumstances of low incomes, the book will appeal to a wide readership, including policy makers.

Cathepsin S: therapeutic, diagnostic, and prognostic potential

Cathepsin S is a member of the cysteine cathepsin protease family. It is a lysosomal protease which can promote degradation of damaged or unwanted proteins in the endo-lysosomal pathway. Additionally, it has more specific roles such as MHC class II antigen presentation, where it is important in the degradation of the invariant chain. Unsurprisingly, mis-regulation has implicated cathepsin S in a variety of pathological processes including arthritis, cancer, and cardiovascular disease, where it becomes secreted and can act on extracellular substrates. In comparison to many other cysteine cathepsin family members, cathepsin S has uniquely restricted tissue expression and is more stable at a neutral pH, which supports its involvement and importance in localised disease microenvironments. In this review, we examine the known involvement of cathepsin S in disease, particularly with respect to recent work indicating its role in mediating pain, diabetes, and cystic fibrosis. We provide an overview of current literature with regards cathepsin S as a therapeutic target, as well as its role and potential as a predictive diagnostic and/or prognostic marker in these diseases.