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.

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.

Report of the Advisory Group on Post Primary Teacher Education

The occasion of this report on Teacher Education is timely. The teaching profession is now confronted with major challenges. Schooling has changed very radically in the recent past. Other review exercises of the education system have taken place and it is a time when a new legislative framework, better accommodated to the diversity of the range of duties and responsibilities of the teacher and school, is emerging. It is anticipated that the Report will stimulate debate, secure a new platform for development and provide for a framework for teacher education models which is better disposed towards the well being of the profession and the service to society it wishes to provide.

Techniques for CT and MR, post-processing, radiation

Brain perfusion can be assessed by CT and MR. For CT, two major techniques are used. First, Xenon CT is an equilibrium technique based on a freely diffusible tracer. First pass of iodinated contrast injected intravenously is a second method, more widely available. Both methods are proven to be robust and quantitative, thanks to the linear relationship between contrast concentration and x-ray attenuation. For the CT methods, concern regarding x-ray doses delivered to the patients need to be addressed. MR is also able to assess brain perfusion using the first pass of gadolinium based contrast agent injected intravenously. This method has to be considered as a semi-quantitative because of the non linear relationship between contrast concentration and MR signal changes. Arterial spin labeling is another MR method assessing brain perfusion without injection of contrast. In such case, the blood flow in the carotids is magnetically labelled by an external radiofrequency pulse and observed during its first pass through the brain. Each of this various CT and MR techniques have advantages and limits that will be illustrated and summarized.Learning Objectives:1. To understand and compare the different techniques for brain perfusion imaging.2. To learn about the methods of acquisition and post-processing of brain perfusion by first pass of contrast agent for CT and MR.3. To learn about non contrast MR methods (arterial spin labelling).