Evidence against close linkage of the loci for fraXq of Martin-Bell syndrome and for factor IX.

Linkage between the loci for fraXq of Martin-Bell syndrome and factor IX was studied in nine families exhibiting this syndrome by means of a restriction fragment length polymorphism at the factor IX locus. Computer analysis of the data indicates there to be no evidence for close linkage between the syndrome and the factor IX locus.

A vaccine against nicotine for smoking cessation: a randomized controlled trial.

BACKGROUND: Tobacco dependence is the leading cause of preventable death and disabilities worldwide and nicotine is the main substance responsible for the addiction to tobacco. A vaccine against nicotine was tested in a 6-month randomized, double blind phase II smoking cessation study in 341 smokers with a subsequent 6-month follow-up period. METHODOLOGY/PRINCIPAL FINDINGS: 229 subjects were randomized to receive five intramuscular injections of the nicotine vaccine and 112 to receive placebo at monthly intervals. All subjects received individual behavioral smoking cessation counseling. The vaccine was safe, generally well tolerated and highly immunogenic, inducing a 100% antibody responder rate after the first injection. Point prevalence of abstinence at month 2 showed a statistically significant difference between subjects treated with Nicotine-Qbeta (47.2%) and placebo (35.1%) (P = 0.036), but continuous abstinence between months 2 and 6 was not significantly different. However, in subgroup analysis of the per-protocol population, the third of subjects with highest antibody levels showed higher continuous abstinence from month 2 until month 6 (56.6%) than placebo treated participants (31.3%) (OR 2.9; P = 0.004) while medium and low antibody levels did not increase abstinence rates. After 12 month, the difference in continuous abstinence rate between subjects on placebo and those with high antibody response was maintained (difference 20.2%, P = 0.012). CONCLUSIONS: Whereas Nicotine-Qbeta did not significantly increase continuous abstinence rates in the intention-to-treat population, subgroup analyses of the per-protocol population suggest that such a vaccination against nicotine can significantly increase continuous abstinence rates in smokers when sufficiently high antibody levels are achieved. Immunotherapy might open a new avenue to the treatment of nicotine addiction. TRIAL REGISTRATION: Swiss Medical Registry 2003DR2327; ClinicalTrials.gov NCT00369616.

Approches exégétiques du Deutéronome. Brève histoire de la recherche sur le Deutéronome depuis Martin Noth.

Depuis la parution des Überlieferungsgeschitliche Studien de Martin Noth, le livre du Deutéronome joue un rôle central dans la discussion exégétique. L'A. cherche à faire le point sur le chemin parcouru depuis cinquante ans. Au niveau diachronique, aucun consensus n'apparaît sur les questions de la datation et des rédactions successives. Le modèle le plus performant semble être Deutéronome primitif sous Josias suivi à l'époque de l'exil de son insertion dans l'historiographie, puis de plusieurs retouches rédactionnelles. Au niveau théologique, les thèmes de la loi, de l'alliance, du pays, de l'exode et des pères en sont l'épine dorsale

Interlaboratory comparison of size measurements on nanoparticles using nanoparticle tracking analysis (NTA)

One of the key challenges in the field of nanoparticle (NP) analysis is in producing reliable and reproducible characterisation data for nanomaterials. This study looks at the reproducibility using a relatively new, but rapidly adopted, technique, Nanoparticle Tracking Analysis (NTA) on a range of particle sizes and materials in several different media. It describes the protocol development and presents both the data and analysis of results obtained from 12 laboratories, mostly based in Europe, who are primarily QualityNano members. QualityNano is an EU FP7 funded Research Infrastructure that integrates 28 European analytical and experimental facilities in nanotechnology, medicine and natural sciences with the goal of developing and implementing best practice and quality in all aspects of nanosafety assessment. This study looks at both the development of the protocol and how this leads to highly reproducible results amongst participants. In this study, the parameter being measured is the modal particle size.

Prescription de statines en prévention primaire: quel score de risque cardiovasculaire faut-il utiliser en Suisse? [Statin prescription in primary prevention: which cardiovascular risk score should be used in Switzerland?]

La prévention primaire des maladies cardiovasculaires par les médecins s'effectue par une prise en charge individualisée des facteurs de risque. L'indication à un traitement par statines se base sur une estimation du risque de survenue d'une maladie cardiovasculaire et sur le taux de LDL-cholestérol. Trois scores de risque sont couramment utilisés: le score PROCAM, le score Framingham, et le SCORE européen. En Suisse, le Groupe Suisse Lipides et Athérosclérose (GSLA) recommande en première instance l'utilisation du score PROCAM avec une adaptation du niveau de risque pour la Suisse. Une enquête a aussi montré que c'est le score le plus utilisé en Suisse. Dans cet article, les particularités de ces scores et leurs applications pratiques en ce qui concerne la prescription de statines en prévention primaire sont discutées. Les conséquences et les bénéfices potentiels de l'application de ces scores en Suisse sont également abordés. [Abstract] Primary prevention of cardiovascular disease by physicians is achieved by management of individual risk factors. The eligibility for treatment with statins is based on both an estimate of the risk of developing cardiovascular disease and the LDL-cholesterol. Three risk scores are commonly used : the PROCAM score, the Framingham score, and the European score. In Switzerland, the Swiss Group Lipids and Atherosclerosis (GSLA) recommends to use the PROCAM score with an adjustment of the level of risk for Switzerland. A survey also showed that PROCAM is the most used in Switzerland. In this article, the differences of these scores and their practical applications regarding the prescription of statins in primary prevention are discussed. The consequences and potential benefits of applying these scores in Switzerland are also discussed.

Relationship between cigarette smoking and abdominal obesity

BACKGROUND: Although smokers tend to have a lower body-mass index (BMI) than non-smokers, smoking may affect body fat (BF) distribution. Some studies have assessed the association between smoking, BMI and waist circumference (WC), but, to our knowledge, no population-based studies assessed the relation between smoking and BF composition. We assessed the association between amount of cigarette smoking, BMI, WC and BF composition. METHODS: Data was analysed from a cross-sectional population-based study including 6187 Caucasians aged 32-76 and living in Switzerland. Height, weight and WC were measured. BF, expressed in percent of total body weight, was measured by electrical bioimpedance. Obesity was defined as a BMI>=30 kg/m2 and normal weight as a BMI<25 kg/m2. Abdominal obesity was defined as a WC>=102 cm for men and >=88 cm for women and normal WC as <94 cm for men and <80 cm for women. In men, excess BF was defined as %BF >=28.1, 28.7, 30.6 and 32.6 for age groups 32-44, 45-54, 55-64 and 65-76, respectively; the corresponding values for women were 35.9, 36.5, 40.5 and 44.4. Cigarette smoking was assessed using a self-reported questionnaire. RESULTS: 29.3% of men and 25.0% of women were smokers. Prevalence of obesity, abdominal obesity, and excess of BF was 16.9% and 26.6% and 14.2% in men and 15.0%, 33.0% and 27.5% in women, respectively. Smokers had lower age-adjusted mean BMI, WC and percent of BF compared to non-smokers. However, among smokers,mean age-adjusted BMI,WC and BF increased with the number of cigarettes smoked per day: among light (1-10 cig/day), moderate (11-20) and heavy smokers (>20), mean +/-SE %BF was 22.4 +/−0.3, 23.1+/−0.3 and 23.5+/−0.4 for men, and 31.9+/−0.3, 32.6+/−0.3 and 32.9+/−0.4 for women, respectively. Mean WC was 92.9+/−0.6, 94.0+/−0.5 and 96.0+/−0.6 cm for men, and 80.2+/−0.5, 81.3+/−0.5 and 83.3+/−0.7 for women, respectively. Mean BMI was 25.7+/−0.2, 26.0+/−0.2, and 26.1+/−0.2 kg/m2 for men; and 23.6+/−0.2, 24.0+/−0.2 and 24.1+/−0.3 for women, respectively. Compared with light smokers, the age-adjusted odds ratio (95% Confidence Interval) for excess of BF was 1.04 (0.58 to 1.85) formoderatesmokers and 1.06 (0.57 to 1.99) for heavy smokers in men (p-trend = 0.9), and 1.35 (0.92 to 1.99) and 2.26 (1.38 to 3.72), respectively, in women (p-trend = 0.04). Odds ratio for abdominal obesity vs. normal WC was 1.32 (0.81 to 2.15) for moderate smokers and 1.95 (1.16 to 3.27) for heavy smokers in men (p-trend < 0.01), and 1.15 (0.79 to 1.69) and 2.36 (1.41 to 3.93) in women (p-trend = 0.03). Odds ratio for obesity vs. normal weight was 1.35 (0.76 to 2.41) for moderate smokers and 1.33 (0.71 to 2.49) for heavy smokers in men (p-trend = 0.9) and 0.78 (0.45 to 1.35) and 1.44 (0.73 to 2.85), in women (p-trend = 0.08). CONCLUSIONS: WC and BF were positively and dose-dependently associated with the number of cigarettes smoked per day in women, whereas onlyWC was dose dependently and significantly associated with the amount of cigarettes smoked per day in men. This suggests that heavy smokers, especially women, are more likely to have an excess of BF and to accumulate BF in the abdomen compared to lighter smokers.

A genome-wide association study of neuroticism in a population-based sample.

Neuroticism is a moderately heritable personality trait considered to be a risk factor for developing major depression, anxiety disorders and dementia. We performed a genome-wide association study in 2,235 participants drawn from a population-based study of neuroticism, making this the largest association study for neuroticism to date. Neuroticism was measured by the Eysenck Personality Questionnaire. After Quality Control, we analysed 430,000 autosomal SNPs together with an additional 1.2 million SNPs imputed with high quality from the Hap Map CEU samples. We found a very small effect of population stratification, corrected using one principal component, and some cryptic kinship that required no correction. NKAIN2 showed suggestive evidence of association with neuroticism as a main effect (p < 10(-6)) and GPC6 showed suggestive evidence for interaction with age (p approximately = 10(-7)). We found support for one previously-reported association (PDE4D), but failed to replicate other recent reports. These results suggest common SNP variation does not strongly influence neuroticism. Our study was powered to detect almost all SNPs explaining at least 2% of heritability, and so our results effectively exclude the existence of loci having a major effect on neuroticism.