Abstract
During the LHC Run 3 the ALICE online computing farm will process up to 50 times more Pb-Pb events per second than in Run 2. The implied computing resource scaling requires a shift in the ...approach that comprises the extensive usage of Graphics Processing Units (GPU) for the processing. We will give an overview of the state of the art for the data reconstruction on GPUs in ALICE, with additional focus on the Inner Tracking System detector. A detailed teardown of adopted techniques, implemented algorithms and approaches and performance report will be shown. Additionally, we will show how we support different GPUs brands (NVIDIA and AMD) with a single code-base using an automatic code translation and generation for different target architectures. Strengths and possible weaknesses of this approach will be discussed. Finally, an overview of the next steps towards an even more comprehensive usage of GPUs in ALICE software will be illustrated.
Summary
Background
Exhaled nitric oxide (FeNO) is a biomarker for eosinophilic inflammation in the airways and for responsiveness to corticosteroids in asthmatics.
Objective
We sought to identify in ...adults the genetic determinants of fractional exhaled nitric oxide (FeNO) levels and to assess whether environmental and disease‐related factors influence these associations.
Methods
We performed a genome‐wide association study of FeNO through meta‐analysis of two independent discovery samples of European ancestry: the outbred EGEA study (French Epidemiological study on the Genetics and Environment of Asthma, N = 610 adults) and the Hutterites (N = 601 adults), a founder population living on communal farms. Replication of main findings was assessed in adults from an isolated village in Sardinia (Talana study, N = 450). We then investigated the influence of asthma, atopy and tobacco smoke exposure on these genetic associations, and whether they were also associated with FeNO values in children of the EAGLE (EArly Genetics & Lifecourse Epidemiology, N = 8858) consortium.
Results
We detected a common variant in RAB27A (rs2444043) associated with FeNO that reached the genome‐wide significant level (P = 1.6 × 10−7) in the combined discovery and replication adult data sets. This SNP belongs to member of RAS oncogene family (RAB27A) and was associated with an expression quantitative trait locus for RAB27A in lymphoblastoid cell lines from asthmatics. A second suggestive locus (rs2194437, P = 8.9 × 10−7) located nearby the sodium/calcium exchanger 1 (SLC8A1) was mainly detected in atopic subjects and influenced by inhaled corticosteroid use. These two loci were not associated with childhood FeNO values.
Conclusions and Clinical Relevance
This study identified a common variant located in RAB27A gene influencing FeNO levels specifically in adults and with a biological relevance to the regulation of FeNO levels. This study provides new insight into the biological mechanisms underlying FeNO levels in adults.
Abstract Background and aims Owing to the multiplicity of the key components of metabolic syndrome (MetS), its diagnosis is very complex. The lack of a unique definition is responsible for the ...prevalence variability observed among studies; therefore, a definition based on continuous variables was recommended. The aim of this study was to compare competing models of the MetS factor structure for selecting the one that explains the best clustering pattern and to propose an algorithm for computing MetS as a continuous variable. Methods and results Data were from isolated Sardinian populations ( n = 8102). Confirmatory factor analysis (CFA) and two-group CFA by gender were performed to evaluate the sex-specific factor structure of MetS. After selecting the best model, an algorithm was obtained using factor loadings/residual variances. The quality of the MetS score was evaluated by the receiver operating characteristics curve and the area under the curve. Cross-validation was performed to validate the score and to determine the best cut point. The best fit model was a bifactor one with a general factor (MetS) and three specific factors (f1: obesity/adiposity trait; f2: hypertension/blood pressure trait; and f3: lipid trait). Gender-specific algorithms were implemented to obtain MetS scores showing a good diagnostic performance (0.80 specificity and 0.80 sensitivity for the cut point). Furthermore, cross-validation confirmed these results. Conclusion These analyses suggested that the bifactor model was the most representative one. In addition, they provided a score and a cut point that are both clinically accessible and interpretable measures for MetS diagnosis and likely useful for evaluating the association with adverse cardiovascular disease and diabetes and for investigating the MetS genetic component.
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated ...glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Preliminary results of a study aiming to implement a new non-destructive methodology about physical and elastic characteristics of building materials are presented. Our target is to assess the state ...of decay of wall stones by means of the correlation of thermal and elastic waves. At first, thermal diffusivity and ultrasound velocities have been measured on samples of known mechanical properties. An effective testing procedure for the evaluation of the stone durability has been performed on a historical Church. In particular, the variation of ultrasonic velocity mainly due to cracks is mapped and compared with thermographic readings.
A novel approach for designing the next generation of vertex detectors foresees to employ wafer-scale sensors that can be bent to truly cylindrical geometries after thinning them to thicknesses of ...20–40 μm. To solidify this concept, the feasibility of operating bent MAPS was demonstrated using 1.5cm×3cm ALPIDE chips. Already with their thickness of 50µm, they can be successfully bent to radii of about 2cm without any signs of mechanical or electrical damage. During a subsequent characterisation using a 5.4GeV electron beam, it was further confirmed that they preserve their full electrical functionality as well as particle detection performance.
In this article, the bending procedure and the setup used for characterisation are detailed. Furthermore, the analysis of the beam test, including the measurement of the detection efficiency as a function of beam position and local inclination angle, is discussed. The results show that the sensors maintain their excellent performance after bending to radii of 2cm, with detection efficiencies above 99.9% at typical operating conditions, paving the way towards a new class of detectors with unprecedented low material budget and ideal geometrical properties.
Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we ...performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss.
Vascular endothelial growth factor (VEGF) is an angiogenic and neurotrophic factor, secreted by endothelial cells, known to impact various physiological and disease processes from cancer to ...cardiovascular disease and to be pharmacologically modifiable. We sought to identify novel loci associated with circulating VEGF levels through a genome-wide association meta-analysis combining data from European-ancestry individuals and using a dense variant map from 1000 genomes imputation panel. Six discovery cohorts including 13,312 samples were analyzed, followed by in-silico and de-novo replication studies including an additional 2,800 individuals. A total of 10 genome-wide significant variants were identified at 7 loci. Four were novel loci (5q14.3, 10q21.3, 16q24.2 and 18q22.3) and the leading variants at these loci were rs114694170 (MEF2C, P = 6.79 x 10(-13)), rs74506613 (JMJD1C, P = 1.17 x 10(-19)), rs4782371 (ZFPM1, P = 1.59 x 10(-9)) and rs2639990 (ZADH2, P = 1.72 x 10(-8)), respectively. We also identified two new independent variants (rs34528081, VEGFA, P = 1.52 x 10(-18); rs7043199, VLDLR-AS1, P = 5.12 x 10(-14)) at the 3 previously identified loci and strengthened the evidence for the four previously identified SNPs (rs6921438, LOC100132354, P = 7.39 x 10(-1467); rs1740073, C6orf223, P = 2.34 x 10(-17); rs6993770, ZFPM2, P = 2.44 x 10(-60); rs2375981, KCNV2, P = 1.48 x 10(-100)). These variants collectively explained up to 52% of the VEGF phenotypic variance. We explored biological links between genes in the associated loci using Ingenuity Pathway Analysis that emphasized their roles in embryonic development and function. Gene set enrichment analysis identified the ERK5 pathway as enriched in genes containing VEGF associated variants. eQTL analysis showed, in three of the identified regions, variants acting as both cis and trans eQTLs for multiple genes. Most of these genes, as well as some of those in the associated loci, were involved in platelet biogenesis and functionality, suggesting the importance of this process in regulation of VEGF levels. This work also provided new insights into the involvement of genes implicated in various angiogenesis related pathologies in determining circulating VEGF levels. The understanding of the molecular mechanisms by which the identified genes affect circulating VEGF levels could be important in the development of novel VEGF-related therapies for such diseases.
Abstract Background Some patients with idiopathic pulmonary fibrosis (IPF) develop severe acute respiratory failure (ARF) requiring admission to an intensive care unit (ICU) and ventilatory support. ...A limited number of observational studies have reported that noninvasive ventilation (NIV) can be an effective treatment to support breathing and to prevent use of invasive mechanical ventilation in these patients. This study aimed to retrospectively investigate the clinical status and outcomes in IPF patients receiving NIV for ARF and to identify those clinical and laboratory characteristics, which could be considered risk factors for its failure. Methods This is a retrospective analysis of short-term outcomes in 18 IPF patients being administered NIV for ARF. This study was conducted in a 4-bed respiratory ICU (RICU) in a university hospital. Eighteen IPF patients who were administered NIV between January 1, 2005, and April 30, 2013, were included. The outcome measures are the need for endotracheal intubation despite NIV treatment and mortality rate during their RICU stay. The length of the patients' stay in the RICU and their survival rate following RICU admission were also evaluated. Results Noninvasive ventilation was successful in 8 patients and unsuccessful in 10 who required endotracheal intubation. All the patients in the NIV failure group died within 20.2 ± 15.3 days of intubation. The patients in the NIV success group spent fewer days in the RICU (11.6 ± 4.5 vs 24.6 ± 13.7; P = .0146). The median survival time was significantly shorter for the patients in the NIV failure with respect to the success group (18.0 95% confidence interval {CI}, 9.0-25.0 vs 90.0 95% CI, 65.0-305.0 days; P < .0001); the survival rate at 90 days was, likewise, lower in the NIV failure group (0% vs 34% ± 19.5%). At admission, the patients in the failure group had significantly higher respiratory rate values (36.9 ± 7.8 vs 30.5 ± 3.3 breaths/min; P = .036), plasma N-terminal fragment of the prohormone of B-type natriuretic peptide (NT-proBNP) levels (4528.8 ± 4012.8 vs 634.6 ± 808.0 pg/mL; P = .023) and serum C-reactive protein values (72.0 ± 50.0 vs 20.7 ± 24.0 μ g/mL; P = .0289) with respect to those in the success group. Noninvasive ventilation failure was correlated to the plasma NT-proBNP levels at RICU admission ( P = .0326) with an odds ratio of 12.2 (95% CI, 1.2 to infinity) in the patients with abnormally high values (>900 pg/mL). Conclusions The outcome of IPF patients who were administered NIV was quite poor. The use of NIV was, nevertheless, found to be associated with clinical benefits in selected IPF patients, preventing the need for intubation and reducing the rate of complications/death. Elevated plasma NT-proBNP levels at the time of ICU admission is a simple clinical marker for poor NIV outcome.
A novel approach for designing the next generation of vertex detectors foresees to employ wafer-scale sensors that can be bent to truly cylindrical geometries after thinning them to thicknesses of ...20-40\(\mu\)m. To solidify this concept, the feasibility of operating bent MAPS was demonstrated using 1.5\(\times\)3cm ALPIDE chips. Already with their thickness of 50\(\mu\)m, they can be successfully bent to radii of about 2cm without any signs of mechanical or electrical damage. During a subsequent characterisation using a 5.4GeV electron beam, it was further confirmed that they preserve their full electrical functionality as well as particle detection performance. In this article, the bending procedure and the setup used for characterisation are detailed. Furthermore, the analysis of the beam test, including the measurement of the detection efficiency as a function of beam position and local inclination angle, is discussed. The results show that the sensors maintain their excellent performance after bending to radii of 2cm, with detection efficiencies above 99.9% at typical operating conditions, paving the way towards a new class of detectors with unprecedented low material budget and ideal geometrical properties.
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