Exponentially-fitted Gauss-Laguerre quadrature rule for integrals over an unbounded interval

New quadrature formulae are introduced for the computation of integrals over the whole positive semiaxis when the integrand has an oscillatory behavior with decaying envelope. The new formulae are derived by exponential fitting, and they represent a generalization of the usual Gauss-Laguerre formulae. Their weights and nodes depend on the frequency of oscillation in the integrand, and thus the accuracy is massively increased. Rules with one up to six nodes are treated with details. Numerical illustrations are also presented

Mass spectrometry application on the detection of Sildenafil in aqueous phases

Sildenafil, the active ingredient of Viagra (Figure n.1), is a drug helpful in solving erectile dysfunction problems and recently entered the list of emerging contaminants. The use of these pharmaceuticals is increasingly widespread among perfectly healthy young people (20 or 30 years old) who make them a dangerous abuse for "recreational" purposes together with ecstasy: the result is a synergistic amplification of their final effects, such as the feeling of euphoria, confusion, disorientation, hallucinations, tremors or, in severe cases, irregular heartbeat and even coma. According to the 2018 annual report prepared by the Italian Medicines Agency (AIFA), this compounds’ consumption had increased over time from 2.9 DDD (Defined Daily Dose assumed per 1000 inhabitants in the referred year) in 2014 to 3.6 DDD in 2018. Unfortunately, it is impossible to detect the actual quantity used from the population (young and patients) because the internet network is becoming a way of purchasing to avoid medical prescriptions. Indeed, some researchers [1] report that illicit trading with pharmaceuticals products from the Internet is not wholly conscious of the risks for health concerning the quality of these products, such as the possible presence of toxic impurities [2]. The increase in demand is powering the illegal trade via the web, and, consequently, the risk of using an ineffective/harmful to health drug is very high [3,4]. The human body does not fully utilize these drugs. An unknown quantity, probably transformed, is excreted with urine and faeces. The high consumption of this substance, globally accomplished by legal and illegal ways, and the fact that Wastewater treatment plants (WWTP) cannot remove all types of contaminants that enter the sewer legitimates thinking that they can pose a severe threat to ecosystems and human health [5]. The unambiguous analytical determination of the active parent drug and the identification of its transformation products are therefore indispensable to try understanding if the quantity found of this drug in wastewater and surface water is linked to actual medical use and to verify whether tertiary purification treatments of wastewater are effective in the removal. In this work, the identification and quantification of this pharmaceutical product in water and synthetic wastewater were performed by LC-ESI-LTQ/MS and confirmed by CID-MSn. Thanks to high mass precision and MS/MS capability, determination and structural interpretation of sildenafil and its transformation products were achieved

Management of sagittal craniosynostosis morphological comparison of 8 surgical techniques

The aim of this study was to carry out a retrospective multicenter study comparing the morphological outcome of 8 techniques used for the management of sagittal synostosis versus a large cohort of control patients. Computed tomography (CT) images were obtained from children CT-scanned for non-craniosynostosis related events (n=241) and SS patients at pre-operative and post-operative follow-up stages (n=101). No significant difference in morphological outcomes was observed between the techniques considered in this study. However, the majority of techniques showed a tendency for relapse. Further, the more invasive procedures at older ages seem to lead to larger intracranial volume compared to less invasive techniques at younger ages. This study can be a first step towards future multicenter studies, comparing surgical results and offering a possibility for objective benchmarking of outcomes between methods and centers

Triangulating molecular evidence to prioritize candidate causal genes at established atopic dermatitis loci

Genome-wide association studies for atopic dermatitis (AD) have identified 25 reproducible loci. We attempt to prioritize candidate causal genes at these loci using extensive molecular resources compiled into a bioinformatics pipeline. We identified a list of 103 molecular resources for AD aetiology, including expression, protein and DNA methylation QTL datasets in skin or immune-relevant tissues which were tested for overlap with GWAS signals. This was combined with functional annotation using regulatory variant prediction, and features such as promoter-enhancer interactions, expression studies and variant fine-mapping. For each gene at each locus, we condensed the evidence into a prioritization score. Across the investigated loci, we detected significant enrichment of genes with adaptive immune regulatory function and epidermal barrier formation among the top prioritized genes. At 8 loci, we were able to prioritize a single candidate gene (IL6R, ADO, PRR5L, IL7R, ETS1, INPP5D, MDM1, TRAF3). In addition, at 6 of the 25 loci, our analysis prioritizes less familiar candidates (SLC22A5, IL2RA, MDM1, DEXI, ADO, STMN3). Our analysis provides support for previously implicated genes at several AD GWAS loci, as well as evidence for plausible additional candidates at others, which may represent potential targets for drug discovery

Triangulating molecular evidence to prioritize candidate causal genes at established atopic dermatitis loci

GWASs for atopic dermatitis have identified 25 reproducible loci. We attempt to prioritize the candidate causal genes at these loci using extensive molecular resources compiled into a bioinformatics pipeline. We identified a list of 103 molecular resources for atopic dermatitis etiology, including expression, protein, and DNA methylation quantitative trait loci datasets in the skin or immune-relevant tissues, which were tested for overlap with GWAS signals. This was combined with functional annotation using regulatory variant prediction and features such as promoter‒enhancer interactions, expression studies, and variant fine mapping. For each gene at each locus, we condensed the evidence into a prioritization score. Across the investigated loci, we detected significant enrichment of genes with adaptive immune regulatory function and epidermal barrier formation among the top-prioritized genes. At eight loci, we were able to prioritize a single candidate gene (IL6R, ADO, PRR5L, IL7R, ETS1, INPP5D, MDM1, TRAF3). In addition, at 6 of the 25 loci, our analysis prioritizes less familiar candidates (SLC22A5, IL2RA, MDM1, DEXI, ADO, STMN3). Our analysis provides support for previously implicated genes at several atopic dermatitis GWAS loci as well as evidence for plausible additional candidates at others, which may represent potential targets for drug discovery

Metabolomics analysis in adults with High Bone Mass identifies a relationship between bone resorption and circulating citrate which replicates in the general population

Objective: Bone turnover, which regulates bone mass, may exert metabolic consequences, particularly on markers of glucose metabolism and adiposity. To better understand these relationships, we examined cross-sectional associations between bone turnover markers (BTMs) and metabolic traits in a population with high bone mass (HBM, BMD Z-score>+3.2). Design: β-C-terminal telopeptide of type-I collagen (β-CTX), procollagen type-1 amino-terminal propeptide (P1NP) and osteocalcin were assessed by electrochemiluminescence immunoassays. Metabolic traits, including lipids and glycolysis-related metabolites, were measured using Nuclear Magnetic Resonance spectroscopy. Associations of BTMs with metabolic traits were assessed using Generalized Estimating Equation linear regression, accounting for within-family correlation, adjusting for potential confounders (age, sex, height, weight, menopause, bisphosphonate and oral glucocorticoid use). Results: 198 adults with HBM had complete data, mean [SD] age 61.6 [13.7] years; 77% female. Of 23 summary metabolic traits, citrate was positively related to all BTMs: adjusted ββ-CTX=0.050 (95% CI 0.024,0.076),p=1.71x10-4, βosteocalcin=6.54x10-4 (1.87x10-4,0.001),p=0.006 and βP1NP=2.40x10-4 (6.49x10-5,4.14x10-4),p=0.007 (β= increase in citrate (mmol/L) per 1μg/L BTM increase). Inverse relationships of β-CTX (β=-0.276 -0.434,-0.118],p=6.03x10-4) and osteocalcin (-0.004 [-0.007,-0.001],p=0.020) with triglycerides were also identified. We explored the generalizability of these associations in 3,664 perimenopausal women (age 47.9 [4.4] years) from a UK family cohort. We confirmed a positive, albeit lower magnitude, association between β-CTX and citrate (adjusted βwomen=0.020 [0.013,0.026],p=1.95x10-9) and an inverse association of similar magnitude between β-CTX and triglycerides (β=-0.354 [-0.471,-0.237],p=3.03x10-9). Conclusions: Bone resorption is positively related to circulating citrate and inversely related to triglycerides. Further studies are justified to determine whether plasma citrate or triglyceride concentrations are altered by factors known to modulate bone resorption, such as bisphosphonates