Post-genomic update on a classical candidate gene for coronary artery disease: ESR1.

BACKGROUND: After age, sex is the most important risk factor for coronary artery disease (CAD). The mechanism through which women are protected from CAD is still largely unknown, but the observed sex difference suggests the involvement of the reproductive steroid hormone signaling system. Genetic association studies of the gene-encoding Estrogen Receptor α (ESR1) have shown conflicting results, although only a limited range of variation in the gene has been investigated. METHODS AND RESULTS: We exploited information made available by advanced new methods and resources in complex disease genetics to revisit the question of ESR1's role in risk of CAD. We performed a meta-analysis of 14 genome-wide association studies (CARDIoGRAM discovery analysis, N=≈87,000) to search for population-wide and sex-specific associations between CAD risk and common genetic variants throughout the coding, noncoding, and flanking regions of ESR1. In addition to samples from the MIGen (N=≈6000), WTCCC (N=≈7400), and Framingham (N=≈3700) studies, we extended this search to a larger number of common and uncommon variants by imputation into a panel of haplotypes constructed using data from the 1000 Genomes Project. Despite the widespread expression of ERα in vascular tissues, we found no evidence for involvement of common or low-frequency genetic variation throughout the ESR1 gene in modifying risk of CAD, either in the general population or as a function of sex. CONCLUSIONS: We suggest that future research on the genetic basis of sex-related differences in CAD risk should initially prioritize other genes in the reproductive steroid hormone biosynthesis system.

Decoupled post-glacial history in mutualistic plant-insect interactions: insights from the yellow loosestrife (Lysimachia vulgaris) and its associated oil-collecting bees (Macropis europaea and M-fulvipes)

AimWe take a comparative phylogeographical approach to assess whether three species involved in a specialized oil-rewarding pollination system (i.e. Lysimachia vulgaris and two oil-collecting bees within the genus Macropis) show congruent phylogeographical trajectories during post-glacial colonization processes. Our working hypothesis is that within specialized mutualistic interactions, where each species relies on the co-occurrence of the other for survival and/or reproduction, partners are expected to show congruent evolutionary trajectories, because they are likely to have followed parallel migration routes and to have shared glacial refugia. LocationWestern Palaearctic. MethodsOur analysis relies on the extensive sampling of 104 Western Palaearctic populations (totalling 434, 159 and 74 specimens of Lysimachiavulgaris, Macropiseuropaea and Macropisfulvipes, respectively), genotyped with amplified fragment length polymorphism. Based on this, we evaluated the regional genetic diversity (Shannon diversity and allele rarity index) and genetic structure (assessed using structure, population networks, isolation-by-distance and spatial autocorrelation metrics) of each species. Finally, we compared the general phylogeographical patterns obtained. ResultsContrary to our expectations, the analyses revealed phylogeographical signals suggesting that the investigated organisms demonstrate independent post-glacial trajectories as well as distinct contemporaneous demographic parameters, despite their mutualistic interaction. Main conclusionsThe mutualistic partners investigated here are likely to be experiencing distinct and independent evolutionary dynamics because of their contrasting life-history traits (e.g. dispersal abilities), as well as distinct hubs and migration routes. Such conditions would prevent and/or erase any signature of co-structuring of lineages in space and time. As a result, the lack of phylogeographical congruence driven by differences in life-history traits might have arisen irrespective of the three species having shared similar Pleistocene glacial refugia.

La era post-descentralización : la consolidación de servidores

Aquest projecte estudia el concepte de consolidació de servidors en l'aspecte més general. Consta de dues parts ben diferenciades: l'una d'àmbit teòric i l'altra d'aplicació pràctica d'una solució en concret.

La diversité des motivations des employés publics : recherche exploratoire dans un contexte post-bureaucratique en Suisse

Durant les dernières décennies, la recherche portant sur la motivation des fonctionnaires a été dominée par deux courants théoriques : l'approche dite des choix rationnels, et celle portant sur la motivation au service public. Dans l'environnement post-bureaucratique actuel, cette vision simplifiée, qui reflète aussi dans une certaine mesure la dichotomie « public-privé », ne reflète plus de manière adéquate la complexité et l'hétérogénéité des motivations des agents publics. Basée sur des données empiriques qualitatives et quantitatives, une typologie originale des motivations dans l'univers post-bureaucratique est développée et testée dans plusieurs organisations publiques suisses. Elle révèle des facteurs de motivations qui combinent de manière originale des éléments classiques de la bureaucratie avec d'autres sources de motivation caractéristiques de formes modernes d'administration publique.

Infection by Mycobacterium leprae of household contacts of lepromatous leprosy patients from a post-elimination leprosy region of Colombia

The Leprosy Control Program of Antioquia, (post-elimination leprosy state of Colombia), had registered by 1999, 56 lepromatous leprosy patients and their household contacts (HHC). Our interest was to detect Mycobacterium leprae infection in these HHC. Clinical examination, acid-fast bacillary staining (AFB) in nasal secretions, and slit skin samples, IgM anti-PGL-I in serum and Lepromine A (Mitsuda) reactivity were tested. Two hundred forty eight HHC were studied, 49% were male. After clinical examination, two HHC were diagnosed as multi bacillary patients; 13% showed positive IgM anti-PGL-I titers; Mitsuda reaction (> 4 mm) was positive in 59%; AFB was negative in all samples, except in the two new patients. HHC were classified according to test results.Group 1: two new multi bacillary patients. Group 2: 15 HHC seropositive, Mitsuda-negative. Group 3: 13 HHC seropositive, Mitsuda-positive. Group 4: 130 HHC seronegative, Mitsuda-positive. Group 5: 88 HHC seronegative, Mitsuda-negative. These results are an indication that the transmission of the infection is still happening in a region considered in the post elimination phase. The two new patients represent an infection source for others contacts, and groups 2 and 3 are infected HHC that could develop the disease in future. Follow up of high risk population is necessary to achieve real elimination of leprosy.

Mycobacterium bovis identification by a molecular method from post-mortem inspected cattle obtained in abattoirs of Mato Grosso do Sul, Brazil

The presence of Mycobacterium bovis in bovine carcasses with lesions suggestive of tuberculosis was evaluated. Seventy-two carcass samples were selected during slaughter inspection procedures in abattoirs in the state of Mato Grosso do Sul, Brazil. Seventeen (23.6%) of samples showed colonies suggestive of mycobacteria that were confirmed to be acid-fast bacilli by Ziehl-Neelsen staining. Polymerase chain reaction (PCR) using primers specific for M. bovis identified M. bovis in 13 (76.5%) isolates. The PCR-restriction enzyme pattern analysis using gene encoding for the 65-kDa protein and two restriction enzymes identified the remaining four isolates that were represented by two M. tuberculosis complex and two nontuberculous mycobacteria. The results are indicative of infection of slaughter cattle by M. bovis and other mycobacteria in the state of Mato Grosso do Sul.

New insights into the anti-inflammatory actions of aspirin- induction of nitric oxide through the generation of epi-lipoxins

Aspirin has always remained an enigmatic drug. Not only does it present with new benefits for treating an ever-expanding list of apparently unrelated diseases at an astounding rate but also because aspirin enhances our understanding of the nature of these diseases processe. Originally, the beneficial effects of aspirin were shown to stem from its inhibition of cyclooxygenase-derived prostaglandins, fatty acid metabolites that modulate host defense. However, in addition to inhibiting cyclooxygenase activity aspirin can also inhibit pro-inflammatory signaling pathways, gene expression and other factors distinct from eicosanoid biosynthesis that drive inflammation as well as enhance the synthesis of endogenous protective anti-inflammatory factors. Its true mechanism of action in anti-inflammation remains unclear. Here the data from a series of recent experiments proposing that one of aspirin's predominant roles in inflammation is the induction of nitric oxide, which potently inhibits leukocyte/endothelium interaction during acute inflammation, will be discussed. It will be argued that this nitric oxide-inducing effects are exclusive to aspirin due to its unique ability, among the family of traditional anti-inflammatory drugs, to acetylate the active site of inducible cyclooxygenase and generate a family of lipid mediators called the epi-lipoxins that are increasingly being shown to have profound roles in a range of host defense responses.

Strategic review of health inequalities in England post 2010 (Marmot review consultation paper)

In November 2008, Professor Sir Michael Marmot was asked to advise the Secretary of State for Health on the future development of a health inequalities strategy in England post-2010. The consultation relates to the first phase of the review and is based on submissions from nine task groups, who considered the evidence base across the social determinants of health. This document discusses issues raised during this first phase of the review and identifies key questions for respondents. The consultation document is set out in the following sections: Section 1 The Review Consultation: Aims and consultation questions Section 2 The Strategic Review of Health inequalities: The Background to the Review, the remit, structure, context and the social determinants approach to health inequalities. Section 3 Key Strategic Themes: A summary of a thematic analysis of proposals made by the Review task groups. Each task group was asked to assess national and international evidence about interventions and policies from within their policy area, which would likely lead to reductions in health inequalities. Section 4 Cross-Cutting Challenges for the Review: A summary of challenges currently under consideration by the Review.

Anti Bullying Procedures for Primary and Post Primary Schools

The role of the school is to provide an appropriate education for all its pupils. A stable, secure learning environment is an essential requirement to achieve this goal. Bullying behaviour, by its very nature, undermines and dilutes the quality of education. Research shows that bullying can have short and long-term effects on the physical and mental well-being of pupils, on engagement with school, on self-confidence and on the ability to pursue ambitions and interests. School-based bullying can be positively and firmly addressed through a range of school-based measures and strategies through which all members of the school community are enabled to act effectively in dealing with this behaviour. While it is recognised that home and societal factors play a substantial role both in the cause and in the prevention of bullying, the role of the school in preventative work is also crucial and should not be underestimated. School-based initiatives can either reinforce positive efforts or help counteract unsuccessful attempts of parents to change unacceptable behaviour. Parents and pupils have a particularly important role and responsibility in helping the school to prevent and address school-based bullying behaviour and to deal with any negative impact within school of bullying behaviour that occurs elsewhere. In this document, any reference(s) to parent(s) can be taken to refer also to guardian(s) where applicable.

Anti Bullying Procedures for Primary and Post Primary Schools - Appendix 1 Template anti-bullying policy

Anti Bullying Procedures for Primary and Post Primary Schools - Appendix 1 Template anti-bullying policy. Provided by the Department of Education and Skills, Ireland.

Anti Bullying Procedures for Primary and Post Primary Schools - Appendix 2 Practical tips for building a positive school culture and climate

Anti Bullying Procedures for Primary and Post Primary Schools - Appendix 2 Practical tips for building a positive school culture and climate. Provided by the Department of Education and Skills, Ireland.

Anti Bullying Procedures for Primary and Post Primary Schools - Appendix 3 Template for recording bullying behaviour

Anti Bullying Procedures for Primary and Post Primary Schools - Appendix 3 Template for recording bullying behaviour. Provided by the Department of Education and Skills, Ireland.

Anti Bullying Procedures for Primary and Post Primary Schools - Appendix 4 Checklist for annual review of the anti-bullying policy and its implementation

The Board of Management (the Board) must undertake an annual review of the school’s anti-bullying policy and its implementation. The following checklist must be used for this purpose. The checklist is an aid to conducting this review and is not intended as an exhaustive list. In order to complete the checklist, an examination and review involving both quantitative and qualitative analysis, as appropriate across the various elements of the implementation of the school’s anti-bullying policy will be required.

Investing Effectively in Information and Communication Technology in Schools, 2008-2013

Learning is changing. A pivotal force in bringing about this change is the use of information and communications technology (ICT) which provides richer, more immediate, world-relevant educational resources and opportunities. When used well, ICT enriches learning and enhances teaching. It invigorates classroom activities and is a powerful motivational tool that encourages learners to progress in more personalised and self-directed ways. Ireland has achieved rapid change and growth in the past decade, but to sustain this we must prepare the next generation for the knowledge society in which they will live. The challenge we face is to ensure that the emphasis on ICT in schools shifts, in the immediate future, from technology provision to a focus on its deliberate use by the learner. Fostering personal creativity has always been a desirable educational value. The pursuit of creativity and inventiveness are now pivotal skills in a knowledge economy and the embedding of ICT in learning can greatly facilitate their development. Web 2.0 will facilitate greater interactivity and enable greater levels of user-generated content. It is crucial that young people acquire the ICT and related skills to support these new opportunities.

OECD Review of Migrant Education - Country Report for Ireland

Immigration is a relatively new phenomenon in Ireland. Between 8 and 10% of students in Irish schools have an immigrant background representing many countries, cultures and languages. Their education outcomes are, on average, similar to their Irish-born peers. Irish schools experienced a rapid increase in the inflow of immigrant students only in recent years, and the main focus of migrant education is first-generation immigrants. Currently about 10% of students in primary schools and about 8% of students in post-primary schools have immigrant backgrounds. Unlike most other OECD countries, first-generation immigrant students in Ireland, on average, achieve education outcomes similar to their Irish-born peers, possibly because the socio-economic backgrounds of these students are similar to or higher than those of their Irish-born peers.