Genetic polymorphisms and kidney transplant outcomes

Purpose of review: Gene polymorphism studies are growing at a quasiexponential rate and aim to improve immediate and long-term outcomes in renal transplantation. This review highlights recent evidence and potential future directions for genetic research studies.

Recent findings: Studies are largely based on immunity, inflammation and pharmacogenetics, investigating mostly 'surrogate' outcomes with sometimes conflicting results. However, the last 12 months has also heralded the emergence of important genome-wide association studies on transplantation, more robust replicated multicentre analyses of candidate gene variants, meta-analyses, and an increasing interest in copy number variation and donor genetics.

Summary: These studies set the scene for further investigation, aiming to understand pathways of disease and biomarkers of risk, and are leading to a greater understanding of the biology of transplantation. Future studies will require focus on donor : recipient and gene : environment interactions, and an integrated approach of 'transplantomics' to evaluate long-term outcomes in multinational collaborations.

Consideration of coastal risk in the Irish spatial planning process

The vulnerability of coastal areas to associated hazards is increasing due to population growth, development pressure and climate change. It is incumbent on coastal governance regimes to address the vulnerability of coastal inhabitants to these hazards. This is especially so at the local level where development planning and control has a direct impact on the vulnerability of coastal communities. To reduce the vulnerability of coastal populations, risk mitigation and adaptation strategies need to be built into local spatial planning processes. Local government, however, operates within a complex hierarchal governance framework which may promote or limit particular actions. It is important, therefore, to understand how local coastal planning practices are shaped by national and supranational entities. Local governments also have to respond to the demands of local populations. Consequently, it is important to understand local populations’ perceptions of coastal risk and its management. Adopting an in-depth study of coastal planning in County Mayo, Ireland, this paper evaluates: (a) how European and national policies and legislation shape coastal risk management at local level; (b) the incorporation of risk management strategies into local plans; and (c) local perception of coastal risks and risk management. Despite a strong steer from supranational and national legislation and policy, statutory local plans are found to be lacking in appropriate risk mitigation or adaptation strategies. Local residents appear to be lulled into a sense of complacency towards these risks because of the low level of attention afforded to them by the local planning authorities. To avoid potentially disastrous consequences for local residents and businesses, it is imperative that this situation is redressed urgently. Based on our analysis, we recommend: the development and implementation of a national ICZM strategy, supported by detailed local ICZM plans; and obliging local government to address known risks in their plans rather than defer them to project level decision making.

Carotenoids and health in older people

As the proportion of older people increases, so will chronic disease incidence and the proportion of the population living with disability. Therefore, new approaches to maintain health for as long as possible in this age group are required. Carotenoids are a group of polyphenolic compounds found predominantly in fruit and vegetables that have been proposed to have anti-inflammatory and antioxidant effects. Such properties may impact on the risk diseases which predominate in older people, and also ageing-related physiological changes. Working out the effect of carotenoid intake versus fruit and vegetable intake is difficult, and the strong correlation between individual carotenoid intakes also complicates any attempt to examine individual carotenoid health effects. Similarly, research to determine whether carotenoids consumed as supplements have similar benefits to increased dietary intake through whole foods, is still required. However, reviewing the recent evidence suggests that carotenoid intake and status are relatively consistently associated with reduced CVD risk, although β-carotene supplementation does not reduce CVD risk and increases lung cancer risk. Increased lycopene intake may reduce prostate cancer progression, with a potential role for carotenoids at other cancer sites. Lutein and zeaxanthin have a plausible role in the maintenance of eye health, whilst an association between carotenoid intake and cognitive and physical health appears possible, although research is limited to date. Given this accruing evidence base to support a specific role for certain carotenoids and ageing, current dietary advice to consume a diet rich in fruit and vegetables would appear prudent, and efforts maintained to encourage increased intake.

Susceptibility to Invasive Meningococcal Disease: Polymorphism of Complement System Genes and Neisseria meningitidis Factor H Binding Protein

BACKGROUND: Neisseria meningitidis can cause severe infection in humans. Polymorphism of Complement Factor H (CFH) is associated with altered risk of invasive meningococcal disease (IMD). We aimed to find whether polymorphism of other complement genes altered risk and whether variation of N. meningitidis factor H binding protein (fHBP) affected the risk association.

METHODS: We undertook a case-control study with 309 European cases and 5,200 1958 Birth Cohort and National Blood Service cohort controls. We used additive model logistic regression, accepting P<0.05 as significant after correction for multiple testing. The effects of fHBP subfamily on the age at infection and severity of disease was tested using the independent samples median test and Student's T test. The effect of CFH polymorphism on the N. meningitidis fHBP subfamily was investigated by logistic regression and Chi squared test.

RESULTS: Rs12085435 A in C8B was associated with odds ratio (OR) of IMD (0.35 [95% CI 0.19-0.67]; P = 0.03 after correction). A CFH haplotype tagged by rs3753396 G was associated with IMD (OR 0.56 [95% CI 0.42-0.76], P = 1.6x10-4). There was no bacterial load (CtrA cycle threshold) difference associated with carriage of this haplotype. Host CFH haplotype and meningococcal fHBP subfamily were not associated. Individuals infected with meningococci expressing subfamily A fHBP were younger than those with subfamily B fHBP meningococci (median 1 vs 2 years; P = 0.025).

DISCUSSION: The protective CFH haplotype alters odds of IMD without affecting bacterial load for affected heterozygotes. CFH haplotype did not affect the likelihood of infecting meningococci having either fHBP subfamily. The association between C8B rs12085435 and IMD requires independent replication. The CFH association is of interest because it is independent of known functional polymorphisms in CFH. As fHBP-containing vaccines are now in use, relationships between CFH polymorphism and vaccine effectiveness and side-effects may become important.

Communicating with children in care: why it is important and how it is done

This paper details some emerging findings from an ESRC project whose focus is social workers talking with and listening to children.

How much risk ought we to take? Exploring the possibilities of risk-sensitive consequentialism in the context of climate engineering

When it comes to assessing the deontic status of acts and policies in the context of risk and uncertainty, moral theories are often at a loss. In this paper we hope to show that employing a multi-dimensional consequentialist framework provides ethical guidance for decision-making in complex situations. The paper starts by briefly rehearsing consequentialist responses to the issue of risk, as well as their shortcomings. We then go on to present our own proposal based on three dimensions: wellbeing, fairness and probability. In the last section we apply our approach to a comparison of different climate policy options, including stratospheric solar-radiation management.

Chapter Three – Host–Parasite Interactions and the Evolution of Immune Defense

Parasites and pathogens are ubiquitous and act as an important selection pressure on animals. Here, drawing primarily on our own research, mostly on insects, we illustrate how host-parasite interactions have played a role in the evolution of a range of phenomena, including animal coloration, social behavior, foraging ecology, sexual selection, and life-history tradeoffs, as well as how variation in host behavior and ecology can drive variation in parasitism risk and host allocation of resources to immunity and other antiparasite defenses. We conclude by identifying key areas for future study.

Reviewing the Literature on the Breakdown of Foster Care Placements for Young People: Complexity and the Social Work Task

Young people in long-term foster care are at risk of experiencing poor social, emotional, behavioural and educational outcomes. Moreover, these placements have a significantly greater chance of breaking down compared to those involving children. This article critically evaluates the factors associated with this particular outcome. It was carried out through a literature review conducted by a social work practitioner in one Health and Social Care Trust in Northern Ireland. The findings evidenced that, apart from overriding safety concerns, placement breakdown was not a one-off event but rather a complex process involving the interplay between a range of dynamic risk and protective factors over time, operating in the wider context of the young person’s history and life experiences. The significance of these findings for social work practitioners is finally considered by identifying key theories to inform understanding and intervention.

Governing Public Health: EU Law, Regulation and Biopolitics

This book contributes towards EU studies and the growing discourse on law and public health. It uses the EU’s governance of public health as a lens through which to explore questions of legal competence and its development through policy and concrete techniques, processes and practices, risk and security, human rights and bioethics, accountability and legitimacy, democracy and citizenship, and the nature, essence and ‘future trajectory’ of the European integration project. These issues are explored first, by situating the EU's public health strategy within the overarching architecture of governance and subsequently by examining its operationalisation in relation to the key public health problems of cancer, HIV/AIDS and pandemic planning.

The book argues that the centrality and valorisation of scientific and technical knowledge and expertise in the EU's risk-based governance means that citizen participation in decision-making is largely marginalised and underdeveloped – and that this must change if public health and the quality, accountability and legitimacy of EU governance and its regulation are to be improved. Subsequently the book goes on to argue that the legitimating discourses of ethics and human rights, and the developing notion of EU (supra-)stewardship responsibility, can help to highlight the normative dimensions of governance and its interventions in public health. These discourses and dimensions provide openings and possibilities for citizens to power ‘technologies of participation’ and contribute important supplementary knowledge to decision-making.

Performance and Fault Tolerance of Preconditioned Iterative Solvers on Low-Power ARM Architectures

As the complexity of computing systems grows, reliability and energy are two crucial challenges asking for holistic solutions. In this paper, we investigate the interplay among concurrency, power dissipation, energy consumption and voltage-frequency scaling for a key numerical kernel for the solution of sparse linear systems. Concretely, we leverage a task-parallel implementation of the Conjugate Gradient method, equipped with an state-of-the-art pre-conditioner embedded in the ILUPACK software, and target a low-power multi core processor from ARM.In addition, we perform a theoretical analysis on the impact of a technique like Near Threshold Voltage Computing (NTVC) from the points of view of increased hardware concurrency and error rate.

The progress in understanding and treatment of diabetic retinopathy

In most countries, diabetic retinopathy is the most frequently occurring complication of diabetes mellitus and remains a leading cause of vision loss globally. Its etiology and pathology have been extensively studied for half a century, yet there are disappointingly few therapeutic options. Although some new treatments have been introduced for diabetic macular edema (DME) (e.g. intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') and new steroids), up to 50% of patients fail to respond. Furthermore, for people with proliferative diabetic retinopathy (PDR), laser photocoagulation remains a mainstay therapy, even though it is inherently a destructive procedure. This review summarizes the clinical features of diabetic retinopathy and its risk factors. It describes details of retinal pathology and the cell culture approaches and animal models that are used to mimic its key components, advance understanding of its pathogenesis, and enable identification of new therapeutic targets. We emphasise that although there have been significant advances, there is still a pressing need for a better understanding basic mechanisms to enable development of reliable and robust means to identify patients at highest risk, and to intervene effectively before vision loss occurs.

Implementing Risk Management::A Study of Major Malaysian Corporations

This study presents findings from a series of interviews with Risk Managers and/or Chief Risk Officers from major Malaysian companies about the prerequisites for the effective implementation of Risk Management programmes. The interviews highlight the importance of a number of factors, including: a strong commitment from the Board of Directors and Management in general, a desire for an appropriate risk culture, the development of formal Risk Management frameworks and policies, a recognition of the importance of risk communication, the appointment of a Chief Risk Officer (CRO) and the development of a complementary system of internal audit.

Oil and Dependency::The Case of Kazakhstan

Following the collapse of the Soviet Union in 1991, the newly independent oil-rich country of Kazakhstan has become a major recipient of foreign direct investment (FDI). Although international organisations such as the IMF and UNCTAD have claimed that FDI could be considered an engine in the transition from state socialism and as a powerful force for integration of this region into the global economy; this investment also poses significant risks to Kazakhstan. These risks fall into two broad categories: The first category can be broadly described as issues associated with the “resource curse” or the “Dutch Disease”. The term Dutch Disease describes a situation where booming demand in oil exporting countries, due to high oil revenues, leads to shift of an economy’s productive resources from the tradeable sector to the non-tradeable sector. The second category is associated with the over-dependency of oil exporting countries on a relatively small number of large multinational corporations (MNCs). This over-dependency can lead to a situation where licenses and concessions are granted at less favourable conditions than if they were auctioned in an efficient market. Examining the licensing policy of the Kazakhstani Energy and Mineral Resource Ministry, this paper notes that the latter issue of over-dependency has become less of a risk due to deliberate efforts to diversify investment relationships. Notwithstanding this situation there is some evidence that it remains difficult for oil exporting nations such as Kazakhstan to ensure that oil revenues are channelled into sustainable economic development.

Risk in Private Finance Initiative Projects::A Public Sector Perspective

The management of public sector risk is increasingly seen as a priority area of UK government policy. This has been highlighted recently by the Prime Minister Gordon Brown who stated that “the issue of public risk is one of the most challenging areas of policy-making for any government” (Strategic Risk, 2008). In response to these challenges, the UK Prime Minister has appointed a new body - the Risk and Regulation Advisory Council (RRAC) which is tasked with improving the way risk to the public is understood and managed. One area of particular concern with regard to the governance of public sector risks involves projects procured via the Private Finance Initiative (PFI). These projects involve long-term contracts, complex multi-party interactions and thus create various risks to public sector clients. Today, most PFI actors acknowledge the potentially adverse effects of these risks and make an effort to prevent or mitigate undesirable results. As a consequence, issues of risk allocation, risk transfer and risk management have become central to the PFI procurement process. This paper provides an overview of the risk categories and risk types which are relevant to the public sector in PFI projects. It analyses risk as a feature of uncertain future project-related events and examines potential pitfalls which can be associated with PFI risk management on the basis of a case study of a high-profile PFI hospital in Scotland. The paper concludes that, despite the trend towards diminished risk profiles during the operational phase, the public sector continues to be exposed to significant risks when engaging in PFI-based procurement.

Does the UK Local Finance Improvement Trust (Lift) Initiative Improve Risk Management in Public-Private Procurement?

The UK government introduced the Private Finance Initiative (PFI) and, latterly, the Local Improvement Finance Trust (LIFT) in an attempt to improve public service provision. As a variant of PFI, LIFT seeks to create a framework for the effective provision of primary care facilities. Like conventional PFI procurement, LIFT projects involve long-term contracts, complex multi-party interactions and thus create various risks to public sector clients. This paper investigates the advantages and disadvantages of LIFT with a focus on how this approach facilitates or impedes risk management from the public sector client perspective. Our paper concludes that LIFT has a potential for creating additional problems, including the further reduction of public sector control, conflicts of interest, the inappropriate use of enabling funds, and higher than market rental costs affecting the uptake of space in the buildings by local health care providers. However, there is also evidence that LIFT has facilitated new investment and that Primary Care Trusts (PCTs) have themselves started addressing some of the weaknesses of this procurement format through the bundling of projects and other forms of regional co-operation.