Installation of ECR2 at LNS and Preliminary tests

The source ECR2 has been built in 1998 by Pantechnik, according to the design suggested by LNS Ion Source Group. This design entails some improvements with respect to a standard CAPRICE-type source: a) the magnetic field (up to 1.6 T axial, 1.1 T radial) allows to operate the source at 14 GHz in High B mode and at 18 GHz; b) two frequency heating can be used; c) an aluminum made plasma chamber is used in place of the stainless steel one. The main features of ECR2 along with a review of the preliminary tests will be outlined. Typical currents for fully stripped nitrogen are about 25 emA; for the heaviest ions, 1 emA of Kr28+ and 10 emA of Ta27+ have been measured. The installation at LNS has been completed recently and the details will be given

Production of intense highly charged ion beams with SERSE

The source SERSE is operational at LNS since June 1998 and many improvements have been carried out in this period. The frequency has been increased from 14.5 GHz to 18 GHz and the use of two frequency heating has given positive results. Metallic ion production has been tested by means of a high temperature oven and the preliminary results are described. Tests of magnetic field scaling and frequency scaling have confirmed the results of previous tests with SC-ECRIS at lower frequency and seems to suggest that the upgrading of the source to higher frequency may be considered

A pooled analysis of fall incidence from placebo‐controlled trials of denosumab

Recent studies suggest that the RANK/RANKL system impacts muscle function and/or mass. In the pivotal placebo‐controlled fracture trial of the RANKL inhibitor denosumab in women with postmenopausal osteoporosis, treatment was associated with a lower incidence of non‐fracture‐related falls (p = 0.02). This ad hoc exploratory analysis pooled data from five placebo‐controlled trials of denosumab to determine consistency across trials, if any, of the reduction of fall incidence. The analysis included trials in women with postmenopausal osteoporosis and low bone mass, men with osteoporosis, women receiving adjuvant aromatase inhibitors for breast cancer, and men receiving androgen deprivation therapy for prostate cancer. The analysis was stratified by trial, and only included data from the placebo‐controlled period of each trial. A time‐to‐event analysis of first fall and exposure‐adjusted subject incidence rates of falls were analyzed. Falls were reported and captured as adverse events. The analysis comprised 10,036 individuals; 5030 received denosumab 60 mg subcutaneously once every 6 months for 12 to 36 months and 5006 received placebo. Kaplan–Meier estimates showed an occurrence of falls in 6.5% of subjects in the placebo group compared with 5.2% of subjects in the denosumab group (hazard ratio = 0.79; 95% confidence interval 0.66–0.93; p = 0.0061). Heterogeneity in study designs did not permit overall assessment of association with fracture outcomes. In conclusion, denosumab may reduce the risk of falls in addition to its established fracture risk reduction by reducing bone resorption and increasing bone mass. These observations require further exploration and confirmation in studies with muscle function or falls as the primary outcome

Summary of the performances of the superconducting electron cyclotron resonance ion source at 14 GHz

This article deals with the most recent performance of the superconducting electron cyclotron resonance ion source (SERSE) working at 14 GHz with high magnetic fields after the required conditioning and optimization of several operating parameters. SERSE has now achieved an outstanding level of performance in delivering highly charged ion beams in argon and oxygen gases: the results obtained while operating in a stainless steel chamber and with an aluminum liner are shown and discussed

LocusZoom: regional visualization of genome-wide association scan results

Summary: Genome-wide association studies (GWAS) have revealed hundreds of loci associated with common human genetic diseases and traits. We have developed a web-based plotting tool that provides fast visual display of GWAS results in a publication-ready format. LocusZoom visually displays regional information such as the strength and extent of the association signal relative to genomic position, local linkage disequilibrium (LD) and recombination patterns and the positions of genes in the region

The Metabochip, a Custom Genotyping Array for Genetic Studies of Metabolic, Cardiovascular, and Anthropometric Traits

PMCID: PMC3410907This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Identification of tag single-nucleotide polymorphisms in regions with varying linkage disequilibrium

We compared seven different tagging single-nucleotide polymorphism (SNP) programs in 10 regions with varied amounts of linkage disequilibrium (LD) and physical distance. We used the Collaborative Studies on the Genetics of Alcoholism dataset, part of the Genetic Analysis Workshop 14. We show that in regions with moderate to strong LD these programs are relatively consistent, despite different parameters and methods. In addition, we compared the selected SNPs in a multipoint linkage analysis for one region with strong LD. As the number of selected SNPs increased, the LOD score, mean information content, and type I error also increased

BoostMe accurately predicts DNA methylation values in whole-genome bisulfite sequencing of multiple human tissues

Abstract Background Bisulfite sequencing is widely employed to study the role of DNA methylation in disease; however, the data suffer from biases due to coverage depth variability. Imputation of methylation values at low-coverage sites may mitigate these biases while also identifying important genomic features associated with predictive power. Results Here we describe BoostMe, a method for imputing low-quality DNA methylation estimates within whole-genome bisulfite sequencing (WGBS) data. BoostMe uses a gradient boosting algorithm, XGBoost, and leverages information from multiple samples for prediction. We find that BoostMe outperforms existing algorithms in speed and accuracy when applied to WGBS of human tissues. Furthermore, we show that imputation improves concordance between WGBS and the MethylationEPIC array at low WGBS depth, suggesting improved WGBS accuracy after imputation. Conclusions Our findings support the use of BoostMe as a preprocessing step for WGBS analysis.https://deepblue.lib.umich.edu/bitstream/2027.42/143848/1/12864_2018_Article_4766.pd

Investigation of altering single-nucleotide polymorphism density on the power to detect trait loci and frequency of false positive in nonparametric linkage analyses of qualitative traits

Genome-wide linkage analysis using microsatellite markers has been successful in the identification of numerous Mendelian and complex disease loci. The recent availability of high-density single-nucleotide polymorphism (SNP) maps provides a potentially more powerful option. Using the simulated and Collaborative Study on the Genetics of Alcoholism (COGA) datasets from the Genetics Analysis Workshop 14 (GAW14), we examined how altering the density of SNP marker sets impacted the overall information content, the power to detect trait loci, and the number of false positive results. For the simulated data we used SNP maps with density of 0.3 cM, 1 cM, 2 cM, and 3 cM. For the COGA data we combined the marker sets from Illumina and Affymetrix to create a map with average density of 0.25 cM and then, using a sub-sample of these markers, created maps with density of 0.3 cM, 0.6 cM, 1 cM, 2 cM, and 3 cM. For each marker set, multipoint linkage analysis using MERLIN was performed for both dominant and recessive traits derived from marker loci. Our results showed that information content increased with increased map density. For the homogeneous, completely penetrant traits we created, there was only a modest difference in ability to detect trait loci. Additionally, as map density increased there was only a slight increase in the number of false positive results when there was linkage disequilibrium (LD) between markers. The presence of LD between markers may have led to an increased number of false positive regions but no clear relationship between regions of high LD and locations of false positive linkage signals was observed

Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity