Framework for Corporate and Financial Governance for Regulatory Bodies under the aegis of the Department of Health and Children

The document should be read as supplementary to existing requirements as set out both in statute â?" particularly legislation specific to your organisation, the Health Acts 1947-2004, Ombudsman Act, 1980, Data Protection Acts 1988 & 2003, Freedom of Information Acts 1997-2003, Ethics in Public Office Acts 1995 & 2001, Ombudsman for Children Act, 2002 and the Comptroller and Auditor General (Amendment) Act, 1993 – and in Government approved guidelines, including the Code of Practice for the Governance of State Bodies (2001), Public Financial Procedures, The Role and Responsibilities of Accounting Officers (2003) and Risk Management Guidance for Government Departments and Offices (2004). Read the report (PDF, 1.4mb)  

T regulatory cells in xenotransplantation.

The role of T regulatory cells (Treg) in the induction and maintenance of allograft tolerance is being studied to a great extent. In contrast, little is known on their potential to prevent graft rejection in the field of xenotransplantation, where acute vascular rejection mediated by cellular and humoral mechanisms and thrombotic microangiopathy still prevents long-term graft survival. In this regard, the induction of donor-specific tolerance through isolation and expansion of xenoantigen-specific recipient Treg is currently becoming a focus of interest. This review will summarize the present knowledge concerning Treg and their potential use in xenotransplantation describing in particular CD4(+)CD25(+)Foxp3(+) T cells, CD8(+)CD28(-) Treg, double negative CD4(-)CD8(-) T cells, and natural killer Treg. Although only studied in vitro so far, human CD4(+)CD25(+)Foxp3(+) Treg is currently the best characterized subpopulation of regulatory cells in xenotransplantation. CD8(+)CD28(-) Treg and double negative CD4(-)CD8(-) Treg also seem to be implicated in tolerance maintenance of xenografts. Finally, one study revealing a role for natural killer CD4(+)Valpha14(+) Treg in the prolongation of xenograft survival needs further confirmation. To our opinion, CD4(+)CD25(+)Foxp3(+) Treg are a promising candidate to protect xenografts. In contrast to cadaveric allotransplantation, the donor is known prior to xenotransplantation. This advantage allows the expansion of recipient Treg in a xenoantigen specific manner before transplantation.

Regulatory Impact Analysis (RIA) Public Health (Sunbeds) Bill 2013

There has been a growing body of evidence over recent years, that the use of sunbeds, especially by children, should be restricted because of the associated increased risk of skin cancer and other health problems. Regulatory Impact Analysis (RIA) of the Public Health (Sunbeds) Bill 2013

Melanopsin as a sleep modulator: circadian gating of the direct effects of light on sleep and altered sleep homeostasis in Opn4(-/-) mice.

Light influences sleep and alertness either indirectly through a well-characterized circadian pathway or directly through yet poorly understood mechanisms. Melanopsin (Opn4) is a retinal photopigment crucial for conveying nonvisual light information to the brain. Through extensive characterization of sleep and the electrocorticogram (ECoG) in melanopsin-deficient (Opn4(-/-)) mice under various light-dark (LD) schedules, we assessed the role of melanopsin in mediating the effects of light on sleep and ECoG activity. In control mice, a light pulse given during the habitual dark period readily induced sleep, whereas a dark pulse given during the habitual light period induced waking with pronounced theta (7-10 Hz) and gamma (40-70 Hz) activity, the ECoG correlates of alertness. In contrast, light failed to induce sleep in Opn4(-/-) mice, and the dark-pulse-induced increase in theta and gamma activity was delayed. A 24-h recording under a LD 1-hratio1-h schedule revealed that the failure to respond to light in Opn4(-/-) mice was restricted to the subjective dark period. Light induced c-Fos immunoreactivity in the suprachiasmatic nuclei (SCN) and in sleep-active ventrolateral preoptic (VLPO) neurons was importantly reduced in Opn4(-/-) mice, implicating both sleep-regulatory structures in the melanopsin-mediated effects of light. In addition to these acute light effects, Opn4(-/-) mice slept 1 h less during the 12-h light period of a LD 12ratio12 schedule owing to a lengthening of waking bouts. Despite this reduction in sleep time, ECoG delta power, a marker of sleep need, was decreased in Opn4(-/-) mice for most of the (subjective) dark period. Delta power reached after a 6-h sleep deprivation was similarly reduced in Opn4(-/-) mice. In mice, melanopsin's contribution to the direct effects of light on sleep is limited to the dark or active period, suggesting that at this circadian phase, melanopsin compensates for circadian variations in the photo sensitivity of other light-encoding pathways such as rod and cones. Our study, furthermore, demonstrates that lack of melanopsin alters sleep homeostasis. These findings call for a reevaluation of the role of light on mammalian physiology and behavior.

The policy-making structure of European regulatory networks and the domestic adoption of standards

European regulatory networks (ERNs) constitute the main governance instrument for the informal co-ordination of public regulation at the European Union (EU) level. They are in charge of co-ordinating national regulators and ensuring the implementation of harmonized regulatory policies across the EU, while also offering sector-specific expertise to the Commission. To this aim, ERNs develop 'best practices' and benchmarking procedures in the form of standards, norms and guidelines to be adopted in member states. In this paper, we focus on the Committee of European Securities Regulators and examine the consequences of the policy-making structure of ERNs on the domestic adoption of standards. We find that the regulators of countries with larger financial industries tend to occupy more central positions in the network, especially among newer member states. In turn, network centrality is associated with a more prompt domestic adoption of standards.

Services standardization in the United-States and in Europe: an institutional analysis of private authority

This contribution explores the role of international standards in the rules governing the internationalisation of the service economy. It analyses on a cross-institutional basis patterns of authority in the institutional setting of service standards in the European and Amercian context. The entry into force of the World Trade Organisation (WTO) in 1995 gave international standards a major role in harmonising the technical specifications of goods and services traded on the global market Despite the careful wording of the WTO, a whole range of international bodies still have the capacity to define generic as well as detailed technical specifications affecting how swelling offshore services are expected to be traded on worldwide basis. The analysis relies on global political economy approaches to identify constitutive patterns of authority mediating between the political and the economic spheres on a transnational space. It extends to the area of service standards the assumption that the process of globalisation is not opposing states and markets, but a joint expression of both of them including new patterns and agents of structural change through formal and informal power and regulatory practices. The paper argues that service standards reflect the significant development of a form of transnational hybrid authority, that blurs the distinction between private and public actors, whose scope spread all along from physical measures to societal values, and which reinforces the deterritorialisation of regulatory practices in contemporary capitalism. It provides evidence of this argument by analysing the current European strategy regarding service standardization in response to several programming mandate of the European Commission and the American views on the future development of service standards.

Strength and limitations of regulatory T Cells for immunotherapy in transplantation.

In many experimental models, CD4+CD25+Foxp3+ regulatory T cells (nTreg) have been identifi ed as key players in promoting peripheral transplantation (Tx) tolerance. We have been focusing on therapies based on antigen-specifi c nTreg that can control effector T cells (Teff) and prevent allograft rejection. The use of nTreg in immunotherapeutic protocols for solid organ Tx is however limited by their overall low numbers as well as the low precursor frequency of alloantigen cross-reactive nTreg expected to be found in a normal individual. Moreover, although we previously described robust protocols to generate and expand antigen-specifi c nTreg in vitro, the process requires careful selection of highly pure nTreg and cumbersome ex-vivo manipulations, rendering this strategy not easily applicable in clinical solid organ Tx. In this study, we aimed to expand Treg directly in vivo and determine their suppressive function, effi cacy and stability in promoting donor-specifi c tolerance in a stringent murine Tx model. Our data suggest that IL-2-based therapies lead to a signifi cant increase of Treg in vivo. The expanded Treg suppressed Teff proliferation (albeit slightly less effi ciently than nTreg isolated from control mice) and allowed prolonged graft survival of major MHC-mismatched skin grafts in wild-type non-lymphopenic recipients. The expanded Treg alone were however not suffi cient to induce tolerance in stringent experimental conditions. Rapamycin reduced the frequency of Teff but did not impede expansion of Treg. Pro-infl ammatory stimuli hindered the expansion of Treg and resulted in an increase in the frequency of CD4+IFN-γ+ and CD4+IL17+ T cells. We propose that IL-2-based treatments would be an effi cient method for expanding functional Treg in vivo without affecting other immune cell populations, thereby favorably shifting the pool of alloreactive T cells towards regulation in response to an allograft. However, we also highlight some potential limitations of Treg expansion such as concomitant infl ammatory events.

Regulatory T cell defects are associated with autoimmunity in Wiskott-Aldrich Syndrome protein deficient mice

Abstract : The Wiskott-Aldrich Syndrome (WAS) is an X-linked recessive human primary immunodeficiency. It is caused by mutations in the gene encoding the hermatopoietic specific regulator of the actin cytoskeleton Wiskott-Aldrich Syndrome Protein (WASP). Importantly, a majority of affected patients develop autoimmunity including an inflammatory bowel disease (IBD)-like disease. WASP deficient mice share many similarities with the human WAS. One of these similarities is the spontaneous development of colitis. I have focused my dissertation studies on the pathogenesis of colitis in WASP deficient mice. Prior work from our laboratory had shown that lymphocytes were required and that CD4+ T cells sufficient for colitis development. This colitis was associated with a predominant Th2-cytokine skewing. I have contributed in exploring whether the Th2 cytokine IL-4 plays a role in disease maintenance. Using two approaches to neutralize IL-4, we found that this cytokine plays a role in disease maintenance. Natural CD4*CD25*Foxp3* regulatory T cells (nTreg cells) have been implicated in the pathogenesis of several autoimmune disorders. We found that WASP deficient mice have reduced nTreg cell numbers in peripheral lymphoid organs. This was associated with functional defects in suppressing T cell proliferation and preventing colitis induced by transfer of naïve T cells into SCID recipient, which lack lymphocytes. WASP deficiency affected homing of nTreg cells to lymphoid compartments, IL-2-mediated activation and secretion of the immunomodulatory cytokine IL-10. Finally, we could prevent colitis onset via adoptive transfer of WT nTreg cells prior to colitis development. This suggests that nTreg cells dysfunction is one of the mechanisms underlying colitis development in WASP deficient mice. Future directions will aim at deciphering the role of other immune cell types, the bacterial flora, and various cytokines in colitis development in this murine model of colitis. In addition, we believe that colitis in WASP deficient mice could serve as a useful tool to evaluate nTreg cells manipulation as novel therapeutic approach for IBD.

Regulatory Reform of the International Education Sector and the Student Immigration Regime

Ireland has a strong reputation for delivery of high-quality education services both to our own citizens and those who come here from abroad. A degree from an Irish university, Institute of Technology or high-quality private sector provider is an indicator of significant educational achievement, highly valued by our students and employers alike. Ireland is also a specialist in high-quality English Language tuition. Many thousands of students from the EU and around the world come to Ireland for full-time or short-term programmes.

Innate signaling promotes formation of regulatory nitric oxide-producing dendritic cells limiting T-cell expansion in experimental autoimmune myocarditis.

BACKGROUND: Activation of innate pattern-recognition receptors promotes CD4+ T-cell-mediated autoimmune myocarditis and subsequent inflammatory cardiomyopathy. Mechanisms that counterregulate exaggerated heart-specific autoimmunity are poorly understood. METHODS AND RESULTS: Experimental autoimmune myocarditis was induced in BALB/c mice by immunization with α-myosin heavy chain peptide and complete Freund's adjuvant. Together with interferon-γ, heat-killed Mycobacterium tuberculosis, an essential component of complete Freund's adjuvant, converted CD11b(hi)CD11c(-) monocytes into tumor necrosis factor-α- and nitric oxide synthase 2-producing dendritic cells (TipDCs). Heat-killed M. tuberculosis stimulated production of nitric oxide synthase 2 via Toll-like receptor 2-mediated nuclear factor-κB activation. TipDCs limited antigen-specific T-cell expansion through nitric oxide synthase 2-dependent nitric oxide production. Moreover, they promoted nitric oxide synthase 2 production in hematopoietic and stromal cells in a paracrine manner. Consequently, nitric oxide synthase 2 production by both radiosensitive hematopoietic and radioresistant stromal cells prevented exacerbation of autoimmune myocarditis in vivo. CONCLUSIONS: Innate Toll-like receptor 2 stimulation promotes formation of regulatory TipDCs, which confine autoreactive T-cell responses in experimental autoimmune myocarditis via nitric oxide. Therefore, activation of innate pattern-recognition receptors is critical not only for disease induction but also for counterregulatory mechanisms, protecting the heart from exaggerated autoimmunity.

Global regulation of the knowledge-based economy: The rise of standards in educational services

This article examines the extent and limits of non-state forms of authority in international relations. It analyses how the information and communication technology (ICT) infrastructure for the tradability of services in a global knowledge-based economy relies on informal regulatory practices for adjustment of ICT-related skills. Companies and associations provide training and certification programmes as part of a growing market for educational services setting their own standards. The existing literature on non-conventional forms of authority in the global political economy has emphasised that the consent of actors subject to informal rules and explicit or implicit state recognition remains crucial for the effectiveness of those new forms of power. However, analyses based on a limited sample of actors tend toward a narrow understanding of the issues and fail to fully explore the differentiated space in which non-state authority is emerging. This paper examines the form of authority underpinning the global knowledge-based economy within the broader perspective of the issues likely to be standardised by technical ICT specification, the wide range of actors involved, and the highly differentiated space where standards become authoritative. The empirical findings highlight the role of different private actors in establishing international educational norms in this field. They also pinpoint the limits of profit-oriented standard-settings, notably with regard to generic norms.