Hypoxia-induced DNA hypermethylation in human pulmonary fibroblasts is associated with Thy-1 promoter methylation and the development of a pro-fibrotic phenotype

BACKGROUND: Pulmonary fibrosis is a debilitating and lethal disease with no effective treatment options. Understanding the pathological processes at play will direct the application of novel therapeutic avenues. Hypoxia has been implicated in the pathogenesis of pulmonary fibrosis yet the precise mechanism by which it contributes to disease progression remains to be fully elucidated. It has been shown that chronic hypoxia can alter DNA methylation patterns in tumour-derived cell lines. This epigenetic alteration can induce changes in cellular phenotype with promoter methylation being associated with gene silencing. Of particular relevance to idiopathic pulmonary fibrosis (IPF) is the observation that Thy-1 promoter methylation is associated with a myofibroblast phenotype where loss of Thy-1 occurs alongside increased alpha smooth muscle actin (α-SMA) expression. The initial aim of this study was to determine whether hypoxia regulates DNA methylation in normal human lung fibroblasts (CCD19Lu). As it has been reported that hypoxia suppresses Thy-1 expression during lung development we also studied the effect of hypoxia on Thy-1 promoter methylation and gene expression.

METHODS: CCD19Lu were grown for up to 8 days in hypoxia and assessed for global changes in DNA methylation using flow cytometry. Real-time PCR was used to quantify expression of Thy-1, α-SMA, collagen I and III. Genomic DNA was bisulphite treated and methylation specific PCR (MSPCR) was used to examine the methylation status of the Thy-1 promoter.

RESULTS: Significant global hypermethylation was detected in hypoxic fibroblasts relative to normoxic controls and was accompanied by increased expression of myofibroblast markers. Thy-1 mRNA expression was suppressed in hypoxic cells, which was restored with the demethylating agent 5-aza-2'-deoxycytidine. MSPCR revealed that Thy-1 became methylated following fibroblast exposure to 1% O2.

CONCLUSION: These data suggest that global and gene-specific changes in DNA methylation may play an important role in fibroblast function in hypoxia.

Select Document: Sir George Radcliffe’s “Original of Government” (1639) and Absolutist Political Theory in Stuart Ireland

A seventeenth-century manuscript miscellany, which once belonged to Archbishop James Ussher of Armagh, contains a short treatise on the origins of government by Sir George Radcliffe. Radcliffe was legal assistant to Sir Thomas Wentworth, lord deputy of Ireland (from January 1640 earl of Strafford and lord lieutenant). The treatise insisted on the divine origin of all human political power and implied that the best form of government was absolute monarchy, in which the monarch was free of all human law and subject to divine restraint alone. It will be suggested below that the composition of this treatise can be dated to the summer of 1639. This introduction will offer an outline of Radcliffe’s education and political career, explain the genesis of his treatise on government, point out some pertinent aspects of its argument, and finally assess the document’s significance.

Criminalising the payment for sex in northern ireland; sketching the contours of a moral panic

This paper examines recent legislative developments in Northern Ireland around Lord Morrow’s Human Trafficking & Exploitation (Further Provisions and Support for Victims) Bill that was passed unanimously in the Northern Ireland Assembly and which uniquely in the United Kingdom now makes it a criminal offence to pay for sexual services. I suggest that issues around sex trafficking, sexual slavery and prostitution in Northern Ireland bear all the hallmarks of Stan Cohen’s famous articulation of a moral panic (Cohen 1972) but also argue that his original for- mulation needs to be recast slightly to take account of the horizontal structuring of moral panics in contemporary society.

Dealing with the Legacy of Ethnic Conflict: Confronting ‘Othering’ through Transformative Adult Education—A Northern Ireland Case Study

Despite its peace process, Northern Ireland remains a deeply divided society. The legacy of a 30-year conflict has ensured that the state continues to be prone to outbreaks of violence over contentious issues such as Orange Order parading and the flying of national flags. This paper argues that in order to address this legacy, there is a need to confront the Othering processes that have helped to generate and sustain division. It will argue that programmes of adult education can play an important role in helping the conflicting groups to reimagine their ‘exclusive’ notions of the nation to one capable of incorporating the Other.

Airborne Laser Scanning and the Archaeological Interpretation of Ireland’s First World War Landscape”:The Case Study of Randalstown Training Camp

The training of Irish soldiers for service in the British Army during the First World War required the establishment of training camps across the island, such as at Shane’s Castle Estate, close to Randalstown in County Antrim, Northern Ireland. The camp saw active use from 1914 to 1918 but after the war it was demilitarised and returned to use as farmland. Archaeological investigations have revealed that earthwork traces of the camp can still be identified in the modern landscape. Comparison of a map of the camp from 1915, Airborne Laser Scanning data and aerial photographs has enabled the footprint of the camp to be re-established, while also helping to identify the location of specific elements such as the remains of barrack huts, stores, mess halls and officers’ quarters.

Small Steps or Giant Leaps? Defining Reconciliation in the Transition from Conflict in Northern Ireland

The context of Northern Ireland in the transition of conflict has produced a range of efforts to bring about reconciliation. However, definitions and understandings of the nature of reconciliation differ. This paper draws together how reconciliation has been defined in theory in Northern Ireland and elsewhere, examines some models of practice in the light of that theory and illustrates the process of reconciliation through general initiatives in Northern Ireland and specific projects seeking to reconcile at community level. It is concluded that, while political and public processes can set a context and space for engagement to take place, reconciliation is fundamentally about personal encounter and relationship, which have to take place in a range of settings and at all levels of a society that has experienced conflict.

Nursing Home Care- Nursing Students as Carers discussing and addressing the negatives; a Northern Ireland Perspective

Abstract
The quality of nursing home care for some remains a significant cause of concern. This paper explores and discusses some of the significant critiques and limitations to nursing home care within the UK, particularly and including end of life care. The paper also explores some of the international literature by way of comparison.
Aim
To identify some of the characteristics contributing to the quality of holistic care within nursing homes
Methods
Two short narratives drawn from the experiences of nursing home care within Northern Ireland. The narrators (and co-authors to the paper) are first year student nurses who are also employed (part-time) as carers within nursing homes
Results
The paper identifies evidence of good nursing and care, together with evident quality in end of life care within nursing homes. The paper addresses the context of nursing home care and explores significant characteristics that reflect in the delivery of holistic care to nursing home residents, including the important role of a `culture’ of care, ongoing and specialist training( particularly and including within end of life care) and the important impact in the quality of nursing home leadership.
The paper concludes with some short recommendations to better develop practice within nursing homes

Oliver Cromwell and the 'Cromwellian' Settlement of Ireland

Oliver Cromwell remains a deeply controversial figure in Ireland. In the past decade, his role in the conquest has received sustained attention. However, in recent scholarship on the settlement of Ireland in the 1650s, he has enjoyed a peculiarly low profile. This trend has served to compound the interpretative problems relating to Cromwell and Ireland which stem in part from the traditional denominational divide in Irish historiography. This article offers a reappraisal of Cromwell's role in designing and implementing the far-reaching ‘Cromwellian’ land settlement. It examines the evidence relating to his dealings with Irish people, both Protestant and Catholic, and his attitude towards the enormous difficulties which they faced post-conquest. While the massacre at Drogheda in 1649 remains a blot on his reputation, in the 1650s Cromwell in fact emerged as an important and effective ally for Irish landowners seeking to defeat the punitive confiscation and transplantation policies approved by the Westminster parliament and favoured by the Dublin government.

The Republican Movement, 'Disappearing' and Framing the Past in Northern Ireland

Despite a rich body of research on the conflict and peace process in Northern Ireland, the ‘disappearances’ carried out by Republican armed groups have so far escaped scrutiny. In this article I examine how the Republican movement has framed the rationale behind ‘disappearing’ as a rational response to informing and as an example of historical continuity. In doing so, Republicans appear to attempt to confer legitimacy on their choice of target and normalize the use of the practice within a Republican framework. However, these rationales incorporate techniques of neutralization and attempts to contextualize the ‘disappearances’ in such a way as to distance the Irish Republican Army from agency. Such distancing speaks to a third, overarching rationale for ‘disappearing’: the avoidance of an embarrassment that has continued into the postconflict period. I consider why Republicans persist in claiming the ‘disappeared’ were legitimate targets, killed by a method for which there is historical precedent, when such framing left them open to criticism at a time when they were seeking to demonstrate that they had left violence behind. I conclude that Republican attempts to satisfy two audiences resulted in a gulf between their engagement in the process of recovering remains and their rhetoric surrounding this issue. In so doing, light is shed on some of the challenges the Republican movement faced in their transition away from violence. More broadly, the value of unpicking the framing of key actors in transitional processes is illuminated.

Community Perspectives On Public Order Policing in Northern Ireland

In 2011 the Chief Constable of the PSNI commissioned a review of public order policing in Northern Ireland, following closely behind a review of public order policing in Britain undertaken by Her Majesty’s Inspectorate of Constabulary (HMIC) (2011). As part of the review, the PSNI decided to adopt a ‘twin-track’ approach, with an internal review of organisational practice, experiences and roles/responsibilities; and an independent external review of community experiences of public order policing across the country. The external strand to the review was publically tendered during the first half of 2012 and was awarded to a joint bid by the University of Ulster and the Institute for Conflict Research. The overall aim of the research was to inform the PSNI’s review of public order policing in the widest possible sense so that community experiences and attitudes may be considered by the PSNI as part of decisions taken about future changes in police strategy and tactics on public order issues, with full cognisance of their community impact. In regard to the specific objectives, the research was tasked with the following:

• Provide qualitative information on community experiences and attitudes to public order policing;
• Identify critical issues, dilemmas and debates resulting from public order policing as delivered by the PSNI – both in terms of communities directly and indirectly affected;
• Highlight issues for the PSNI consideration in terms of carrying out its task of maintaining public order while upholding the human rights of all; and
• Explore the above issues in respect of both the PSNI’s style and tactics, along with community attitudes and approaches.

Consultation on 'Co-operating to safeguard children and young people in Northern Ireland'

This draft policy has been updated to reflect changes in structures and legislation. The draft policy outlines how communities, organisations and individuals must work to ensure children and young people in Northern Ireland are safeguarded as effectively as possible. Consultation Documents Draft Co-operating to Safeguard Children and Young People (PDF 356KB) Draft Co-operating to Safeguard Children and Young People (MS WORD 463KB) Co-operating to Safeguard Children and Young People - (easy read) (PDF 15MB) Preliminary Equality Screening, Disability Duties and Human Rights Assessment (PDF 99KB) Regulatory Impact Assessment, and Rural proofing Assessments (PDF 37KB)   Consultation Response Questionnaire Consultation Response Questionnaire (MS Word 38KB)   How to respond to the consultation Please use the questionnaire to tell us your views on the draft policy. An Equality Impact Assessment, a Regulatory Impact Assessment and Rural Proofing templates are attached in respect of the draft policy. The deadline for responses is 5.00 pm on 21 August 2015. Please email the questionnaire response to: Child.Safeguarding@dhsspsni.gov.uk Or post it to: DHSSPSNIChild Safeguarding Policy TeamRoom A3.5Castle BuildingsStormont EstateBelfastBT4 3SQ The Department will consider requests to produce this document in other languages or in alternative formats – Braille, audio, large print or as a PDF document. If you require the document in these or other formats please contact us using the details provided above or telephone 02890522543.

Demographic trends in suicide in the UK and Ireland 1980 - 2010.

Background Ireland has the 17th highest suicide rate in the EU and the 4th highest among 15 to 24-year-old males (WHO 2012). Suicide is the leading cause of death in this age group; death by hanging accounted for 69 % of suicides in 2010. Methods This study examines youth suicide rates from 1980 to 2010 in Ireland and compares them to the rates in Northern Ireland, Scotland, England and Wales. Irish data were obtained from the Central Statistics Office and their annual reports on Vital Statistics. Northern Irish data were obtained from the Northern Ireland Statistics and Research Agency website; Scottish data were from the General Register Office for Scotland and English/Welsh data from the Office for National Statistics website. Results There has been a threefold increase in young male suicide in Ireland over the past three decades (8.9 - 29.7 per 100,000). In contrast, there has been approximately a threefold reduction in deaths by road traffic accidents in young men in the same period (42.7 - 16.2 per 100,000). Suicide rates in young men are similar in Scotland and Northern Ireland for the same period but are 50 % lower in England and Wales. Despite the rates of hanging as a method of suicide increasing in all jurisdictions, the overall rate in England and Wales has continued to decline. Conclusion The suicide rate in Ireland remains very high and strategies to address this are urgently required. Our study indicates that national suicide prevention strategies can be effective.

Bioarchaeology of Two Oneota Burial Sites: 13AM43A and 13AM103, Allamakee County, Iowa, Research Papers: Vol. 41, no. 1

This is a report of a burial and human skeletal remains that were excavated from two different burial sites in Iowa. The report was written and published by the Office of the State Archaeologist, The University of Iowa, Iowa City

Bioarchaeology of Two Mill Creek Sites from Northwest Iowa: 13PM248 and 13WD402, Research Papers of Office of the State Archaeologist, September 9, 2016 Vol. 41, no. 2

This is a report of a human skeletal remains and artifacts that were excavated from a burial sites in Iowa. The report was written and published by the Office of the State Archaeologist, The University of Iowa, Iowa City