A reference panel of 64,976 haplotypes for genotype imputation.

We describe a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry. Using this resource leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies, and it can help to discover and refine causal loci. We describe remote server resources that allow researchers to carry out imputation and phasing consistently and efficiently

Mendelian Randomization analysis reveals a causal influence of circulating sclerostin levels on bone mineral density and fractures

In bone, sclerostin is mainly osteocyte-derived and plays an important local role in adaptive responses to mechanical loading. Whether circulating levels of sclerostin also play a functional role is currently unclear, which we aimed to examine by two-sample Mendelian randomization (MR). A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank. Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β  = 0.11 per G allele, p = 4.4 × 10-11 ). B4GALNT3 is an N-acetyl-galactosaminyltransferase, adding a terminal LacdiNAc disaccharide to target glycocoproteins, found to be predominantly expressed in kidney, whereas GALNT1 is an enzyme causing mucin-type O-linked glycosylation. Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21). Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%). Our findings suggest that higher sclerostin levels are causally related to lower BMD and greater fracture risk. Hence, strategies for reducing circulating sclerostin, for example by targeting glycosylation enzymes as suggested by our GWAS results, may prove valuable in treating osteoporosis. © 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc

Energy Resolution Performance of the CMS Electromagnetic Calorimeter

The energy resolution performance of the CMS lead tungstate crystal electromagnetic calorimeter is presented. Measurements were made with an electron beam using a fully equipped supermodule of the calorimeter barrel. Results are given both for electrons incident on the centre of crystals and for electrons distributed uniformly over the calorimeter surface. The electron energy is reconstructed in matrices of 3 times 3 or 5 times 5 crystals centred on the crystal containing the maximum energy. Corrections for variations in the shower containment are applied in the case of uniform incidence. The resolution measured is consistent with the design goals

Mendelian Randomization Analysis Reveals a Causal Influence of Circulating Sclerostin Levels on Bone Mineral Density and Fractures

In bone, sclerostin is mainly osteocyte-derived and plays an important local role in adaptive responses to mechanical loading. Whether circulating levels of sclerostin also play a functional role is currently unclear, which we aimed to examine by two-sample Mendelian randomization (MR). A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank. Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10−49) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10−11). B4GALNT3 is an N-acetyl-galactosaminyltransferase, adding a terminal LacdiNAc disaccharide to target glycocoproteins, found to be predominantly expressed in kidney, whereas GALNT1 is an enzyme causing mucin-type O-linked glycosylation. Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = –0.12, 95% confidence interval [CI] –0.20 to –0.05) and eBMD (β = –0.12, 95% CI –0.14 to –0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21). Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%). Our findings suggest that higher sclerostin levels are causally related to lower BMD and greater fracture risk. Hence, strategies for reducing circulating sclerostin, for example by targeting glycosylation enzymes as suggested by our GWAS results, may prove valuable in treating osteoporosis

Hépatite C et grossesse (résultats préliminaires du protocole Alhice)

NICE-BU Médecine Odontologie (060882102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

EADS et les stratégies territoriales dans le Sud Ouest de la France.

Rapport National du programme EETSE initiative communautaire INTERREG III B SUDOE Mai 2005

Diagnostic performances of cervical ultrasound, sestamibi scintigraphy and contrast-enhanced 18 F-fluorocholine positron emission tomography in primary hyperparathyroidism.

International audiencePurpose: Preoperative localization of pathological parathyroids is crucial for a minimally invasive treatment of primary hyperparathyroidism (PHPT). This study compares contrast-enhanced 18F-fluorocholine positron emission tomography (FCH-PET/CT), cervical ultrasound (CU) and conventional scintigraphic imaging modalities (MIBI scintigraphy), combined and individually for preoperative localization of hyper-functional parathyroids in PHPT. The gold standard is histological examination. Methods: Data from consecutive patients with a clinical suspicion of PHPT were retrospectively collected. All three imaging modalities were systematically performed. MIBI scintigraphy, consisted of 99mTc-sestamibi/123I-sodium iodide SPECT/CT, 99mTc-sestamibi/123I-sodium iodide planar subtraction imaging and 99mTc-sestamibi planar dual-phase imaging. The ability of FCH-PET/CT, CU and MIBI scintigraphy to identify a hyper-functional parathyroid and specify the side or identify an ectopic location was noted. Patients underwent surgical exploration if at least one exam was positive. CU + MIBI scintigraphy combined was considered as a positive test if CU and MIBI scintigraphy separately showed a hyper-functional parathyroid gland on the same side, or the same ectopic location, and negative in other cases. The composite judgment criterion for pathological parathyroid combined histological analysis and normalization of PTH and calcium levels. Results: 149 pathological parathyroids were found in 143 of the 144 included patients. FCH-PET/CT diagnosed 148/149 pathological parathyroids. Only four false positives and one false negative were found. The FCH-PET/CT sensitivity of 99.3% was superior to that of CU at 75.2% (P < 0.0001), MIBI scintigraphy at 65.1% (P < 0.0001) and CU + MIBI scintigraphy combined at 89.9%, (P = 0.0009). 5/5 ectopic locations were diagnosed by FCH-PET/CT, 2/5 by MIBI and 0/5 by CU. Accuracy was better for FCH-PET/CT at 98% than CU at 84% (P < 0.0001), MIBI scintigraphy at 81% (P < 0.0001) or CU + MIBI scintigraphy at 91% (P < 0.0001). Among the 72 (50%) patients who had a negative CU + MIBI scintigraphy combined test, FCH-PET/CT correctly identified hyper-functional thyroids in 70 (97.2%) patients. Average FCH-PET/CT hyperfunctional parathyroid uptake was higher than the adjacent thyroid (SULmax 6.45 vs 2.15) (P < 0.0001). Conclusion: Accuracy of FCH-PET/CT is higher than CU and MIBI scintigraphy for localization of hyper-functional parathyroids, justifying the systematic use of FCH-PET/CT as the first-line method for PHPT diagnosis

EADS y las estrategias territoriales del suroeste europeo, European Report for Programa de la Iniciativa Comunitaria INTERREG IIIB SUDOE.

Universidad Autonoma de Madrid, Octubre, 358 p

Transposition favors the generation of large effect mutations that may facilitate rapid adaption

International audienc