Rejets radioactifs et environnement du CERN en 2004

La radioactivité de l’environnement autour de l’Organisation Européenne pour la Recherche Nucléaire (CERN) et les doses de rayonnements qui en résultent pour la population avoisinante sont contrôlées par la Commission de Sécurité du CERN et de manière indépendante par les autorités compétentes des deux États Hôtes, l’Institut de Radioprotection et de Sûreté Nucléaire (IRSN) côté France et l’Office Fédéral de la Santé Publique (OFSP) côté Suisse. Dans ce rapport, les résultats de mesures concernent en particulier le territoire suisse. L’ensemble des mesures effectuées en 2004 prouve que le fonctionnement des installations du CERN était sans conséquence radiologique sur l’environnement et la population. Le contrôle des émissions montre que les rejets effectifs se situent également en 2004 nettement en dessous des limites réglementaires. Ce constat est confirmé par le contrôle des immissions dans l’environnement. Le CERN a bien respecté en 2004 comme dans les années précédentes la valeur directrice de dose liée à la source fixée à 0.3 mSv/an. L’impact réel représente en fait moins de 5% de cette valeur, comme l’indique l’estimation pour le groupe de référence, qui est de l’ordre de 0.01 mSv/an

Surface moisture measurement system electro-magnetic induction probe surface irregularity tests

Surface irregularities cause the EMI moisture measurement to infer too low of a free water content in the HLW tank

Free triiodothyronine (T3) is negatively associated with fasting ghrelin serum levels in a population sample of euthyroid subjects

Purpose: Ghrelin is an orexigenic peptide hormone secreted in times of stress and hunger. It is deeply involved in the regulation of metabolism and energy homeostasis, promoting energy intake and inhibiting energy expenditure on a metabolic level. In this regard, it has in many ways antagonistic effect on the thyroid hormones, which increase metabolism and thus energy expenditure. While there is reasonable evidence of a negative association between ghrelin and hormones of the hypothalamic-pituitary-thyroid (HPT-) axis from studies in patients with thyroid dysfunction and small intervention studies, large-scale studies in healthy subjects are lacking. Therefore, we studied the relationship between total ghrelin serum levels and serum levels of the thyroid hormones in a large sample of euthyroid subjects. Methods: Total ghrelin, thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were determined after an overnight fast in 1666 subjects participating in a population-based cross-sectional study ('LIFE') including 10,000 adults. 1012 subjects were included in this analysis. Multiple linear regression analyses were performed. Results: FT3 was negatively associated with serum ghrelin; total sample: β = - 0.0001, p < 0.001; men: β = - 0.0002, p = 0.013; women: β = - 0.0001, p = 0.010, adjusted for age, BMI, alcohol consumption, serum levels of TSH and fT4 and smoking status. No associations were found between ghrelin serum levels and serum levels of fT4 or TSH. Conclusion: This is to date the largest study investigating the relationship between total serum ghrelin and thyroid hormones. The results point to a complex interaction and should initiate further research

Association between self-rating depression scores and total ghrelin and adipokine serum levels in a large population-based sample

Background: Ghrelin and the adipokines leptin and adiponectin have been suggested to be involved in mood and anxiety regulation and to be altered in affective disorders. However, studies investigating the association between ghrelin, leptin and adiponectin and depressive symptomatology are scarce but might contribute to a better understanding of their involvement in mood regulation. We thus aimed investigating the association between depressive symptomatology and total ghrelin as well as leptin and adiponectin serum levels in a large population-based sample. Methods: Total serum ghrelin, adiponectin and leptin levels were determined in 1666 subjects of a population-based cross-sectional study (“LIFE”). The Center for Epidemiological Studies Depression Scale (CES-D) and the Inventory of Depressive Symptoms – Self Rating (IDS-SR) were administered. Multiple linear regression analyses were conducted to examine the association between total serum ghrelin, leptin and adiponectin and the intensity of depressive symptoms. Results: In the total sample (n = 1,092), neither ghrelin nor leptin or adiponectin serum levels showed a significant association with CES-D or IDS-SR sum scores (N = 1,092) or in depressed/non-depressed subjects. Leptin serum levels showed a significantly positive association with IDS-SR sum scores in elderly men (≥60 years; β = 0.122, 95% CI: 0.009; 0.236; p = 0.035). Conclusion: Our study suggests that peripheral levels of ghrelin and adipokines in a cross-sectional study design might not be sufficient to measure their involvement in depression, suggesting that associations are more complex and multi-layered. Copyright © 2022 Wittekind, Kratzsch, Biemann, Mergl, Riedel-Heller, Witte, Villringer and Kluge

Rejets radioactifs et environnement du CERN en 2003

La radioactivité de l’environnement autour de l’Organisation Européenne pour la Recherche Nucléaire (CERN) et les doses de rayonnements qui en résultent pour la population avoisinante sont contrôlées par la Commission de Sûreté du CERN et de manière indépendante par les autorités compétentes des deux Etats Hôtes, l’Institut de Radioprotection et de Sûreté Nucléaire (IRSN) côté France et l’Office Fédéral de la Santé Publique (OFSP) côté Suisse. Dans ce rapport, les résultats de mesures concernent en particulier le territoire suisse. L’ensemble des mesures effectuées en 2003 prouve que le fonctionnement des installations du CERN était sans conséquence radiologique sur l’environnement et la population. Le contrôle des émissions montre que les rejets effectifs se situent également en 2003 nettement en dessous des limites réglementaires. Ce constat est confirmé par le contrôle des immissions dans l’environnement. Le CERN a bien respecté en 2003 comme dans les années précédentes la valeur directrice de dose liée à la source fixée à 0.3 mSv/an. L’impact réel représente en fait moins de 10% de cette valeur, comme l’indique l’estimation pour le groupe critique, qui est de l’ordre de 0.03 mSv/an

Inspiratory muscle warm-up does not improve cycling time-trial performance

Purpose: This study examined the effects of an active cycling warm-up, with and without the addition of an inspiratory muscle warm-up (IMW), on 10-km cycling time-trial performance

Computational prediction of protein subdomain stability in MYBPC3 enables clinical risk stratification in hypertrophic cardiomyopathy and enhances variant interpretation

PURPOSE: Variants in MYBPC3 causing loss of function are the most common cause of hypertrophic cardiomyopathy (HCM). However, a substantial number of patients carry missense variants of uncertain significance (VUS) in MYBPC3. We hypothesize that a structural-based algorithm, STRUM, which estimates the effect of missense variants on protein folding, will identify a subgroup of HCM patients with a MYBPC3 VUS associated with increased clinical risk. METHODS: Among 7,963 patients in the multicenter Sarcomeric Human Cardiomyopathy Registry (SHaRe), 120 unique missense VUS in MYBPC3 were identified. Variants were evaluated for their effect on subdomain folding and a stratified time-to-event analysis for an overall composite endpoint (first occurrence of ventricular arrhythmia, heart failure, all-cause mortality, atrial fibrillation, and stroke) was performed for patients with HCM and a MYBPC3 missense VUS. RESULTS: We demonstrated that patients carrying a MYBPC3 VUS predicted to cause subdomain misfolding (STRUM+, ΔΔG ≤ −1.2 kcal/mol) exhibited a higher rate of adverse events compared with those with a STRUM- VUS (hazard ratio = 2.29, P = 0.0282). In silico saturation mutagenesis of MYBPC3 identified 4,943/23,427 (21%) missense variants that were predicted to cause subdomain misfolding. CONCLUSION: STRUM identifies patients with HCM and a MYBPC3 VUS who may be at higher clinical risk and provides supportive evidence for pathogenicity

Imputation of missing values of tumour stage in population-based cancer registration

<p>Abstract</p> <p>Background</p> <p>Missing data on tumour stage information is a common problem in population-based cancer registries. Statistical analyses on the level of tumour stage may be biased, if no adequate method for handling of missing data is applied. In order to determine a useful way to treat missing data on tumour stage, we examined different imputation models for multiple imputation with chained equations for analysing the stage-specific numbers of cases of malignant melanoma and female breast cancer.</p> <p>Methods</p> <p>This analysis was based on the malignant melanoma data set and the female breast cancer data set of the cancer registry Schleswig-Holstein, Germany. The cases with complete tumour stage information were extracted and their stage information partly removed according to a MAR missingness-pattern, resulting in five simulated data sets for each cancer entity. The missing tumour stage values were then treated with multiple imputation with chained equations, using polytomous regression, predictive mean matching, random forests and proportional sampling as imputation models. The estimated tumour stages, stage-specific numbers of cases and survival curves after multiple imputation were compared to the observed ones.</p> <p>Results</p> <p>The amount of missing values for malignant melanoma was too high to estimate a reasonable number of cases for each UICC stage. However, multiple imputation of missing stage values led to stage-specific numbers of cases of T-stage for malignant melanoma as well as T- and UICC-stage for breast cancer close to the observed numbers of cases. The observed tumour stages on the individual level, the stage-specific numbers of cases and the observed survival curves were best met with polytomous regression or predictive mean matching but not with random forest or proportional sampling as imputation models.</p> <p>Conclusions</p> <p>This limited simulation study indicates that multiple imputation with chained equations is an appropriate technique for dealing with missing information on tumour stage in population-based cancer registries, if the amount of unstaged cases is on a reasonable level.</p

Biological activity differences between TGF-β1 and TGF-β3 correlate with differences in the rigidity and arrangement of their component monomers

[Image: see text] TGF-β1, -β2, and -β3 are small, secreted signaling proteins. They share 71–80% sequence identity and signal through the same receptors, yet the isoform-specific null mice have distinctive phenotypes and are inviable. The replacement of the coding sequence of TGF-β1 with TGF-β3 and TGF-β3 with TGF-β1 led to only partial rescue of the mutant phenotypes, suggesting that intrinsic differences between them contribute to the requirement of each in vivo. Here, we investigated whether the previously reported differences in the flexibility of the interfacial helix and arrangement of monomers was responsible for the differences in activity by generating two chimeric proteins in which residues 54–75 in the homodimer interface were swapped. Structural analysis of these using NMR and functional analysis using a dermal fibroblast migration assay showed that swapping the interfacial region swapped both the conformational preferences and activity. Conformational and activity differences were also observed between TGF-β3 and a variant with four helix-stabilizing residues from TGF-β1, suggesting that the observed changes were due to increased helical stability and the altered conformation, as proposed. Surface plasmon resonance analysis showed that TGF-β1, TGF-β3, and variants bound the type II signaling receptor, TβRII, nearly identically, but had small differences in the dissociation rate constant for recruitment of the type I signaling receptor, TβRI. However, the latter did not correlate with conformational preference or activity. Hence, the difference in activity arises from differences in their conformations, not their manner of receptor binding, suggesting that a matrix protein that differentially binds them might determine their distinct activities