Extracellular matrix sub-types and mechanical stretch impact human cardiac fibroblast responses to transforming growth factor beta

Understanding the impact of extracellular matrix sub-types and mechanical stretch on cardiac fibroblast activity is required to help unravel the pathophysiology of myocardial fibrotic diseases. Therefore, the purpose of this study was to investigate pro-fibrotic responses of primary human cardiac fibroblast cells exposed to different extracellular matrix components, including collagen sub-types I, III, IV, VI and laminin. The impact of mechanical cyclical stretch and treatment with transforming growth factor beta 1 (TGFβ1) on collagen 1, collagen 3 and alpha smooth muscle actin mRNA expression on different matrices was assessed using quantitative real-time PCR. Our results revealed that all of the matrices studied not only affected the expression of pro-fibrotic genes in primary human cardiac fibroblast cells at rest but also affected their response to TGFβ1. In addition, differential cellular responses to mechanical cyclical stretch were observed depending on the type of matrix the cells were adhered to. These findings may give insight into the impact of selective pathological deposition of extracellular matrix proteins within different disease states and how these could impact the fibrotic environment.

Mechanical stretch up-regulates the B-type natriuretic peptide system in human cardiac fibroblasts:a possible defense against transforming growth factor-β mediated fibrosis

BACKGROUND: Mechanical overload of the heart is associated with excessive deposition of extracellular matrix proteins and the development of cardiac fibrosis. This can result in reduced ventricular compliance, diastolic dysfunction, and heart failure. Extracellular matrix synthesis is regulated primarily by cardiac fibroblasts, more specifically, the active myofibroblast. The influence of mechanical stretch on human cardiac fibroblasts' response to pro-fibrotic stimuli, such as transforming growth factor beta (TGFβ), is unknown as is the impact of stretch on B-type natriuretic peptide (BNP) and natriuretic peptide receptor A (NPRA) expression. BNP, acting via NPRA, has been shown to play a role in modulation of cardiac fibrosis.

METHODS AND RESULTS: The effect of cyclical mechanical stretch on TGFβ induction of myofibroblast differentiation in primary human cardiac fibroblasts and whether differences in response to stretch were associated with changes in the natriuretic peptide system were investigated. Cyclical mechanical stretch attenuated the effectiveness of TGFβ in inducing myofibroblast differentiation. This finding was associated with a novel observation that mechanical stretch can increase BNP and NPRA expression in human cardiac fibroblasts, which could have important implications in modulating myocardial fibrosis. Exogenous BNP treatment further reduced the potency of TGFβ on mechanically stretched fibroblasts.

CONCLUSION: We postulate that stretch induced up-regulation of the natriuretic peptide system may contribute to the observed reduction in myofibroblast differentiation.

Paramilitary punishments in Belfast: policing beneath the peace

As an enduring legacy of the conflict, paramilitary policing remains an unpalatable but indisputable fact within Belfast's working-class, Republican communities. Historically, while much attention has been devoted to the causes and consequences of paramilitarism along with the terrorist threat posed by such organizations, little attention has been paid to the influence upon, or relations between, such nonstate policing actors, the communities in which they exist and the delivery of policing by the Police Service of Northern Ireland. While local and international literature surrounding paramilitary violence has tended towards political axiom or physical impact of such activity, the current paper presents an empirical study of the relations between communities and Republican paramilitary organizations who seek to exploit a perceived dearth of state-based policing at the community level within Belfast. Framing the ontology of paramilitary policing and its support from a community, rather than political or security perspective, the paper argues that continuing grass-roots support for this ‘new’ paramilitary policing within Republican communities of Belfast is more complex and nuanced than the political antecedents of the conflict from which such activity emerged – especially in terms of such support surviving successive political negotiations and police reforms since the ‘Good Friday’ Agreement of 1998.

Parading through the Peace Process:Anthropology, Governance and Crisis in Northern Ireland

Because the authors both did work on the North Ireland parades, they became integrally involved as fieldworking anthropologists in the monitoring of these events, and in the creation of policy for their management. They detail how they worked with individuals and groups at every level, from protestors on the street up to the Secretary of State for the region. Later funded to examine legal and policing approaches to protests in other countries, especially South Africa, they show how they used this comparative knowledge to urge the implementation of measures which appear to have led to a diminution of violence in the parades. Finally, they assess their own contribution to the peace process in terms of contingency, timing, luck, flexibility, and industry.

Peace Building and Conflict Transformation: A Case Study of Northern Ireland

This paper provides an overview of the transition from armed conflict to peace in Northern Ireland between 1994 and 2016. It discusses the main stages of the peace process and the main elements of the peace Agreement in relation to the development of global thinking around peacebuilding as set out in the United Nations 1992 report Agenda for Peace and the 2000 Brahimi Report. The paper argues that while Northern Ireland is often highlighted as a positive example of peacebuilding, it is not without its limitations and overall the experience of the past twenty years emphasises the importance of ensuring a broadly inclusive process and the need for a sustained commitment over a long period of time. 

Uppskattning av betalningsviljan för Peace & Love 2011

I denna uppsats skattas betalningsviljan hos besökarna på Peace & Love-festivalen år 2011. Med hjälp av enkätdata baserad på avslöjade och uttalade preferenser presenteras en regressionsanalys med olika oberoende variabler som karaktäriserar en festivalbesökare. Total budget är den beroende variabeln i regressionsanalysen och tolkas i uppsatsen som ekvivalent med besökarnas betalningsvilja. Analysen visar att män i genomsnitt spenderar 301 kronor mer än kvinnor, att turister i genomsnitt spenderar 1 124 kronor mer än en icke-turist samt att den genomsnittliga besökaren har en betalningsvilja på 4 183 kronor. Ett skattat konsumentöverskott har också värderats, vilket uppgick till 743 kronor per person och cirka 37 miljoner kronor totalt för de 50 000 festivalbesökarna. Uppsatsen tar inte hänsyn till de ekonomiska effekter som festivalen har på Borlänge som stad.

'Always Connected’: Transforming Teaching and Learning in Higher Education

The argument of this chapter is that the idea that young people and students being ‘always connected’ should not be seen as being polarized into good or bad, but instead there is a need to see being connected as ‘learning at the interstices’. It also suggests that there is a need to be aware of the impact of digital governance on teaching and learning space. This chapter therefore introduce questions about the value and impact of always being connected and the impact and possible transformation it could have on teaching and learning in higher education.

Public Protection? The Implication of Grayling's 'Transforming Rehabilitation' Agenda on the Safety of Women and Children

Abstract The Coalition Government's new Transforming Rehabilitation (TR) agenda jeopardises the work undertaken with perpetrators of domestic abuse by highly skilled, qualified probation staff. Under new changes outlined by Grayling, Lord Chancellor and Secretary of State for Justice, probation clients who are assessed as posing a medium/low risk of causing harm will be assigned to private sector/voluntary organisations rather than come under the remit of the National Probation Service. This article argues that victims of domestic abuse, primarily women and children, will be placed at an increased risk of harm given this latest TR strategy. The majority of domestic abuse cases will be assessed as posing a medium risk of causing harm and will receive lower levels of intervention by a variety of disparate agencies and organisations. The Ministry of Justice states that the National Probation Service will directly manage offenders who pose a high risk of serious harm to the public, this article will argue that all perpetrators of domestic abuse should be considered as an important exception to this stance, and should remain under the auspices of Probation supervision, irrespective of statistical risk assessment, as has sex offender case management and sex offender treatment programme delivery.

Building peace by supporting post-conflict electoral processes

Les élections post-conflit ou élections de sortie de crise organisées sous l’égide de la communauté internationale en vue de rétablir la paix dans les pays sortant de violents conflits armés ont un bilan mixte caractérisé par le succès ou l’échec selon les cas. Ce bilan mitigé représente le problème principal auquel cette recherche tente de répondre à travers les questions suivantes : l’assistance électorale étrangère est-elle efficace comme outil de rétablissement de la paix dans les sociétés post-conflit? Qu’est ce qui détermine le succès ou l’échec des élections post-conflit à contribuer efficacement au rétablissement de la paix dans les sociétés déchirées par la guerre? Pour résoudre cette problématique, cette thèse développe une théorie de l’assistance électorale en période post-conflit centrée sur les parties prenantes à la fois du conflit armé et du processus électoral. Cette théorie affirme que l’élément clé pour le succès des élections post-conflit dans le rétablissement de la paix est le renforcement de la capacité de négociation des parties prenantes à la fois dans le processus de paix et dans le processus électoral post-conflit. Dans les situations post-conflit, une assistance électorale qui se voudrait complète et efficace devra combiner à la fois le processus électoral et le processus de paix. L’assistance électorale sera inefficace si elle se concentre uniquement sur les aspects techniques du processus électoral visant à garantir des élections libres, transparentes et équitables. Pour être efficace, l’accent devra également être mis sur les facteurs supplémentaires qui peuvent empêcher la récurrence de la guerre, tels que l’habilité des individus et des groupes à négocier et à faire des compromis sur les grandes questions qui peuvent menacer le processus de paix. De fait, même des élections transparentes comme celles de 1997 au Liberia saluées par la communauté internationale n’avaient pas réussi à établir des conditions suffisantes pour éviter la reprise des hostilités. C’est pourquoi, pour être efficace, l’assistance électorale dans les situations de post-conflit doit prendre une approche globale qui priorise l’éducation civique, la sensibilisation sur les droits et responsabilités des citoyens dans une société démocratique, le débat public sur les questions qui divisent, la participation politique, la formation au dialogue politique, et toute autre activité qui pourrait aider les différentes parties à renforcer leur capacité de négociation et de compromis. Une telle assistance électorale fera une contribution à la consolidation de la paix, même dans le contexte des élections imparfaites, comme celles qui se sont détenues en Sierra Leone en 2002 ou au Libéria en 2005. Bien que la littérature sur l’assistance électorale n’ignore guère l’importance des parties prenantes aux processus électoraux post-conflit (K. Kumar, 1998, 2005), elle a fortement mis l’accent sur les mécanismes institutionnels. En effet, la recherche académique et professionnelle est abondante sur la réforme des lois électorales, la reforme constitutionnelle, et le développement des administrations électorales tels que les commissions électorales, ainsi que l’observation électorale et autres mécanismes de prévention de la fraude électorale, etc. (Carothers & Gloppen, 2007). En d’autres termes, les décideurs et les chercheurs ont attribué jusqu’à présent plus d’importance à la conception et au fonctionnement du cadre institutionnel et des procédures électorales. Cette thèse affirme qu’il est désormais temps de prendre en compte les participants eux-mêmes au processus électoral à travers des types d’assistance électorale qui favoriseraient leur capacité à participer à un débat pacifique et à trouver des compromis aux questions litigieuses. Cette approche plus globale de l’assistance électorale qui replace l’élection post-conflit dans le contexte plus englobant du processus de paix a l’avantage de transformer le processus électoral non pas seulement en une expérience d’élection de dirigeants légitimes, mais aussi, et surtout, en un processus au cours duquel les participants apprennent à régler leurs points de vue contradictoires à travers le débat politique dans un cadre institutionnel avec des moyens légaux et légitimes. Car, si le cadre institutionnel électoral est important, il reste que le résultat du processus électoral dépendra essentiellement de la volonté des participants à se conformer au cadre institutionnel et aux règles électorales.

Deliberative democracy and the Tasmanian forest peace process

The Sparta and the Athens Of Our Age At Daggers Drawn: Polities, Perceptions, and Peace

While historically notions of democracy have varied widely, democratic peace theory has generally defined it in procedural terms. This article takes a close look at the Anglo-French confrontation of 1840. I show that while leaders on both sides were prepared to risk war to gain bargaining advantages, only the French left really wanted to fight. Why? By today's criteria, Britain was incontestably more democratic, with its monarch's powers far more restricted and its suffrage several times as large. Nevertheless, both sides considered France more democratic, with French republicans despising Britain as an aristocratic oligarchy. While Spencer Weart is right to argue that democratic republics may be hostile to oligarchic ones, they will not necessarily define each other according to modern procedural criteria. Instead, they may judge regimes by the broader social structures that shape power relationships and by outcomes, possibly explaining wars or near misses between democracies.