Fine mapping and functional analysis of the multiple sclerosis risk gene CD6.

CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2(nd) SRCR domain with susceptibility to MS (P max(T) permutation = 1×10(-4)). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. - CD4(+) naïve cells, P = 0.0001; CD8(+) naïve cells, P<0.0001; CD4(+) and CD8(+) central memory cells, P = 0.01 and 0.05, respectively; and natural killer T (NKT) cells, P = 0.02; with the protective haplotype (RA) showing higher expression of CD6. However, no significant changes were observed in natural killer (NK) cells, effector memory and terminally differentiated effector memory T cells. Our findings reveal that this new MS-associated CD6 risk haplotype significantly modifies expression of CD6 on CD4(+) and CD8(+) T cells.

Meta-analysis of diagnostic test accuracy in neurosurgical practice.

Comparative effectiveness research (CER) allows evidence to be evaluated on the effectiveness, benefits, and detriments of management options, diagnostic tests, or ways to deliver health care. This process can be achieved in different ways, such as with well-designed randomized controlled trials or by meta-analyses. Several medical subspecialties are increasingly using CER, but CER remains underused by the neurosurgical community. Meta-analysis is a highly accurate method that permits results from multiple well-designed research studies to be quantitatively compared. Meta-analysis can be performed in many settings, such as the evaluation of treatment or of a diagnostic test or prognostic factor. Meta-analyses of randomized controlled treatment trials are well known, but there is a paucity of papers describing the ways to perform a meta-analysis of a diagnostic test. The aim of this paper is to improve neurosurgeons' familiarity with the meta-analysis of diagnostic test accuracy by describing and detailing each stage leading to publication.

The Relevance of the Principal-Agent Model for the Analysis of Public Policies : Do the Objectives Conflict ?

This paper aims to provide empirical support for the use of the principal-agent framework in the analysis of public sector and public policies. After reviewing the different conditions to be met for a relevant analysis of the relationship between population and government using the principal-agent theory, our paper focuses on the assumption of conflicting goals between the principal and the agent. A principal-agent analysis assumes in effect that inefficiencies may arise because principal and agent pursue different goals. Using data collected during an amalgamation project of two Swiss municipalities, we show the existence of a gap between the goals of the population and those of the government. Consequently, inefficiencies as predicted by the principal-agent model may arise during the implementation of a public policy, i.e. an amalgamation project. In a context of direct democracy where policies are regularly subjected to referendum, the conflict of objectives may even lead to a total failure of the policy at the polls.

Health literacy [Document électronique] : an economic perspective and data for Switzerland. Part 2, A review of health literacy measures and a cost assessment of limited health literacy

Summary : 1. Measuring health literacy in Switzerland: a review of six surveys: 1.1 Comparison of questionnaires - 1.2 Measures of health literacy in Switzerland - 1.3 Discussion of Swiss data on HL - 1.4 Description of the six surveys: 1.4.1 Current health trends and health literacy in the Swiss population (gfs-UNIVOX), 1.4.2 Nutrition, physical exercise and body weight : opinions and perceptions of the Swiss population (USI), 1.4.3 Health Literacy in Switzerland (ISPMZ), 1.4.4 Swiss Health Survey (SHS), 1.4.5 Survey of Health, Ageing and Retirement in Europe (SHARE), 1.4.6 Adult literacy and life skills survey (ALL). - 2 . Economic costs of low health literacy in Switzerland: a rough calculation. Appendix: Screenshots cost model

Genomic analysis of a nontoxigenic, invasive Corynebacterium diphtheriae strain from Brazil

We report the complete genome sequence and analysis of an invasive Corynebacterium diphtheriae strain that caused endocarditis in Rio de Janeiro, Brazil. It was selected for sequencing on the basis of the current relevance of nontoxigenic strains for public health. The genomic information was explored in the context of diversity, plasticity and genetic relatedness with other contemporary strains.

Efficacy of prescribed injectable diacetylmorphine in the Andalusian trial: Bayesian analysis of responders and non-responders according to a multi domain outcome index.

BACKGROUND The objective of this research was to evaluate data from a randomized clinical trial that tested injectable diacetylmorphine (DAM) and oral methadone (MMT) for substitution treatment, using a multi-domain dichotomous index, with a Bayesian approach. METHODS Sixty two long-term, socially-excluded heroin injectors, not benefiting from available treatments were randomized to receive either DAM or MMT for 9 months in Granada, Spain. Completers were 44 and data at the end of the study period was obtained for 50. Participants were determined to be responders or non responders using a multi-domain outcome index accounting for their physical and mental health and psychosocial integration, used in a previous trial. Data was analyzed with Bayesian methods, using information from a similar study conducted in The Netherlands to select a priori distributions. On adding the data from the present study to update the a priori information, the distribution of the difference in response rates were obtained and used to build credibility intervals and relevant probability computations. RESULTS In the experimental group (n = 27), the rate of responders to treatment was 70.4% (95% CI 53.287.6), and in the control group (n = 23), it was 34.8% (95% CI 15.354.3). The probability of success in the experimental group using the a posteriori distributions was higher after a proper sensitivity analysis. Almost the whole distribution of the rates difference (the one for diacetylmorphine minus methadone) was located to the right of the zero, indicating the superiority of the experimental treatment. CONCLUSION The present analysis suggests a clinical superiority of injectable diacetylmorphine compared to oral methadone in the treatment of severely affected heroin injectors not benefiting sufficiently from the available treatments. TRIAL REGISTRATION Current Controlled Trials ISRCTN52023186.

A combined analysis of the short-term effects of photochemical air pollutants on mortality within the EMECAM project.

In recent years, some epidemiologic studies have attributed adverse effects of air pollutants on health not only to particles and sulfur dioxide but also to photochemical air pollutants (nitrogen dioxide and ozone). The effects are usually small, leading to some inconsistencies in the results of the studies. Furthermore, the different methodologic approaches of the studies used has made it difficult to derive generic conclusions. We provide here a quantitative summary of the short-term effects of photochemical air pollutants on mortality in seven Spanish cities involved in the EMECAM project, using generalized additive models from analyses of single and multiple pollutants. Nitrogen dioxide and ozone data were provided by seven EMECAM cities (Barcelona, Gijón, Huelva, Madrid, Oviedo, Seville, and Valencia). Mortality indicators included daily total mortality from all causes excluding external causes, daily cardiovascular mortality, and daily respiratory mortality. Individual estimates, obtained from city-specific generalized additive Poisson autoregressive models, were combined by means of fixed effects models and, if significant heterogeneity among local estimates was found, also by random effects models. Significant positive associations were found between daily mortality (all causes and cardiovascular) and NO(2), once the rest of air pollutants were taken into account. A 10 microg/m(3) increase in the 24-hr average 1-day NO(2)level was associated with an increase in the daily number of deaths of 0.43% [95% confidence interval (CI), -0.003-0.86%] for all causes excluding external. In the case of significant relationships, relative risks for cause-specific mortality were nearly twice as much as that for total mortality for all the photochemical pollutants. Ozone was independently related only to cardiovascular daily mortality. No independent statistically significant relationship between photochemical air pollutants and respiratory mortality was found. The results in this study suggest that, given the present levels of photochemical pollutants, people living in Spanish cities are exposed to health risks derived from air pollution.

Economic structure and key sectors analysis of greenhouse gas emissions in Uruguay

This paper identifies the key sectors in greenhouse gas emissions of the Uruguayan economy through input-output analysis. This allows to precisely determine the role played by the different productive sectors and their relationship with other sectors in the relation between the Uruguayan productive structure and atmospheric pollution. In order to guide policy design for GHG reduction, we decompose sectors liability between the pollution generated through their own production processes and the pollution indirectly generated in the production processes of other sectors. The results show that all the key polluting sectors for the different contaminants considered are relevant because of their own emissions, except for the sector Motor vehicles and oil retail trade, which is relevant in CO2 emissions because of its pure, both backward and forward, linkages. Finally, the best policy channels for controlling and reducing GHGs emissions are identified, and compared with the National Climate Change Response Plan (NCCRP) lines of action.

Spatial analysis of the relationship between mortality from cardiovascular and cerebrovascular disease and drinking water hardness.

Previously published scientific papers have reported a negative correlation between drinking water hardness and cardiovascular mortality. Some ecologic and case-control studies suggest the protective effect of calcium and magnesium concentration in drinking water. In this article we present an analysis of this protective relationship in 538 municipalities of Comunidad Valenciana (Spain) from 1991-1998. We used the Spanish version of the Rapid Inquiry Facility (RIF) developed under the European Environment and Health Information System (EUROHEIS) research project. The strategy of analysis used in our study conforms to the exploratory nature of the RIF that is used as a tool to obtain quick and flexible insight into epidemiologic surveillance problems. This article describes the use of the RIF to explore possible associations between disease indicators and environmental factors. We used exposure analysis to assess the effect of both protective factors--calcium and magnesium--on mortality from cerebrovascular (ICD-9 430-438) and ischemic heart (ICD-9 410-414) diseases. This study provides statistical evidence of the relationship between mortality from cardiovascular diseases and hardness of drinking water. This relationship is stronger in cerebrovascular disease than in ischemic heart disease, is more pronounced for women than for men, and is more apparent with magnesium than with calcium concentration levels. Nevertheless, the protective nature of these two factors is not clearly established. Our results suggest the possibility of protectiveness but cannot be claimed as conclusive. The weak effects of these covariates make it difficult to separate them from the influence of socioeconomic and environmental factors. We have also performed disease mapping of standardized mortality ratios to detect clusters of municipalities with high risk. Further standardization by levels of calcium and magnesium in drinking water shows changes in the maps when we remove the effect of these covariates.

Analysis of genes encoding penicillin-binding proteins in clinical isolates of Acinetobacter baumannii.

There is limited information on the role of penicillin-binding proteins (PBPs) in the resistance of Acinetobacter baumannii to β-lactams. This study presents an analysis of the allelic variations of PBP genes in A. baumannii isolates. Twenty-six A. baumannii clinical isolates (susceptible or resistant to carbapenems) from three teaching hospitals in Spain were included. The antimicrobial susceptibility profile, clonal pattern, and genomic species identification were also evaluated. Based on the six complete genomes of A. baumannii, the PBP genes were identified, and primers were designed for each gene. The nucleotide sequences of the genes identified that encode PBPs and the corresponding amino acid sequences were compared with those of ATCC 17978. Seven PBP genes and one monofunctional transglycosylase (MGT) gene were identified in the six genomes, encoding (i) four high-molecular-mass proteins (two of class A, PBP1a [ponA] and PBP1b [mrcB], and two of class B, PBP2 [pbpA or mrdA] and PBP3 [ftsI]), (ii) three low-molecular-mass proteins (two of type 5, PBP5/6 [dacC] and PBP6b [dacD], and one of type 7 (PBP7/8 [pbpG]), and (iii) a monofunctional enzyme (MtgA [mtgA]). Hot spot mutation regions were observed, although most of the allelic changes found translated into silent mutations. The amino acid consensus sequences corresponding to the PBP genes in the genomes and the clinical isolates were highly conserved. The changes found in amino acid sequences were associated with concrete clonal patterns but were not directly related to susceptibility or resistance to β-lactams. An insertion sequence disrupting the gene encoding PBP6b was identified in an endemic carbapenem-resistant clone in one of the participant hospitals.

Assessing heterogeneity of effects on blood pressure in a meta-analysis of pharmacist interventions trials

Background: Recent reviews of randomized control trials have shown that pharmacist interventions improve cardiovascular diseases (CVD) risk factors in outpatients. Various interventions were evaluated in different settings, and a substantial heterogeneity was observed in the effect estimates. To better express uncertainties in the effect estimates, prediction intervals (PI) have been proposed but are, however, rarely reported. Objective: Pooling data from two systematic reviews, we estimated the effect of pharmacist interventions on systolic blood pressure (BP), computed PI, and evaluated potential causes of heterogeneity. Methods: Data were pooled from systematic reviews assessing the effect of pharmacist interventions on CVD risk factors in patients with or without diabetes, respectively. Effects were estimated using random effect models. Results: Systolic BP was the outcome in 31 trials including 12 373 patients. Pharmacist interventions included patient educational interventions, patient-reminder systems, measurement of BP, medication management and feedback to physician, or educational intervention to health care professionals. Pharmacist interventions were associated with a large reduction in systolic BP (-7.5 mmHg; 95% CI: -9.0 to -5.9). There was a substantial heterogeneity (I2: 66%). The 95% PI ranged from -13.9 to -1.0 mmHg. The effect tended to be larger if the intervention was conducted in a community pharmacy and if the pharmacist intervened at least monthly. Conclusion: On average, the effect of pharmacist interventions on BP was substantial. However, the wide PI suggests that the effect differed between interventions, with some having modest effects and others very large effects on BP. Part of the heterogeneity could be due to differences in the setting and in the frequency of the interventions.

Excessive alcohol consumption in young men: is there an association with their earlier family situation? A baseline-analysis of the C-SURF-study (Cohort Study on Substance Use Risk Factors).

AIMS: To determine whether parental factors earlier in life (parenting, single parent family, parental substance use problem) are associated with patterns of alcohol consumption among young men in Switzerland. METHODS: This analysis of a population based sample from the Cohort Study on Substance Use Risk Factors (C-SURF) included 5,990 young men (mean age 19.51 years), all attending a mandatory recruitment process for the army. These conscripts reported on parental monitoring and rule-setting, parental behaviour and family structure. The alcohol use pattern was assessed through abstention, risky single occasion drinking (RSOD), volume drinking and dependence. Furthermore, the impact of age, family socio-economic status, educational level of the parents, language region and civil status was analysed. RESULTS: A parental substance use problem was positively associated with volume drinking and alcohol dependence in young Swiss men. Active parenting corresponded negatively with RSOD, volume drinking and alcohol dependence. Single parent family was not associated with a different alcohol consumption pattern compared to standard family. CONCLUSION: Parental influences earlier in life such as active parenting (monitoring, rule-setting and knowing the whereabouts) and perceived parental substance use problem are associated with alcohol drinking behaviour in young male adults. Therefore, health professionals should stress the importance of active parenting and parental substance use prevention in alcohol prevention strategies.

L'analyse des renvois régionaux et interrégionaux en pratique médicale ambulatoire. [Analysis of regional and interregional referrals in ambulatory medical practice].

This article examines, in two Swiss cantons, the interdependence from a medical care point of view of various regions (health planning zones in one canton, political districts in the other). The volume and the destination of patient referrals prescribed by physicians in ambulatory practice are analyzed. The available data (on 1609 referrals) were gathered by the practitioners themselves, during a National Ambulatory Medical Care Survey type study in February-March 1981, in which 203 physicians participated. Several indicators are proposed (including an integration coefficient and an attraction coefficient for each zone); they show marked differences among the regions. This dynamic approach, based on the effective behavior of physicians, appears to be of major interest for health planning purposes (as compared with the frequent practice to use mainly parameters in relation with the availability of care services--the "supply"--numbers of professionals and/or health facilities).

An analysis of the metabolic patterns of two rural communities affected by soy expansion in the North of Argentina

The soy expansion model in Argentina generates structural changes in traditional lifestyles that can be associated with different biophysical and socioeconomic impacts. To explore this issue, we apply an innovative method for integrated assessment - the Multi Scale Integrated Analysis of Societal and Ecosystem Metabolism (MuSIASEM) framework - to characterize two communities in the Chaco Region, Province of Formosa, North of Argentina. These communities have recently experienced the expansion of soy production, altering their economic activity, energy consumption patterns, land use, and human time allocation. The integrated characterization presented in the paper illustrates the differences (biophysical, socioeconomic, and historical) between the two communities that can be associated with different responses. The analysis of the factors behind these differences has important policy implications for the sustainable development of local communities in the area.

Gender inequality in health among elderly people in a combined framework of socioeconomic position, family characteristics and social support

This study analyses gender inequalities in health among elderly people in Catalonia (Spain) by adopting a conceptual framework that globally considers three dimensions of health determinants : socio-economic position, family characteristics and social support. Data came from the 2006 Catalonian Health Survey. For the purposes of this study a sub-sample of people aged 65–85 years with no paid job was selected (1,113 men and 1,484 women). The health outcomes analysed were self-perceived health status, poor mental health status and long-standing limiting illness. Multiple logistic regression models separated by sex were fitted and a hierarchical model was fitted in three steps. Health status among elderly women was poorer than among the men for the three outcomes analysed. Whereas living with disabled people was positively related to the three health outcomes and confidant social support was negatively associated with all of them in both sexes, there were gender differences in other social determinants of health. Our results emphasise the importance of using an integrated approach for the analysis of health inequalities among elderly people, simultaneously considering socio-economic position, family characteristics and social support, as well as different health indicators, in order fully to understand the social determinants of the health status of older men and women.