1,721,521 research outputs found
High throughput sequencing analysis for the molecular diagnosis of Inherited Thrombocytopenias
No full textInherited thrombocytopenias are a heterogenous group of rare genetic disorders characterized by reduced platelet count sometimes combined with bleeding tendency and/or other clinical defects. The molecular diagnosis of ITs is essential to make clinical decision and infer personalized prognosis and risks.
More than 30 genes have been identified that harbor mutations responsible for ITs (Balduini et al., 2017). In addition, ITs often show phenotypic overlaps that hamper the correct diagnosis with the traditional diagnostic algorithm based on step-wise specialized investigations.
However, the advent of next generation sequencing has changed the diagnostic approach of diseases characterized by high genetic heterogeneity like ITs.
In order to improve the diagnosis of IT, we designed a targeted next generation sequencing panel (IT-NGS) to screen the 28 genes more commonly mutated in ITs. Ninety-seven consecutive probands with a suspicious of ITs had been sequenced.
The analysis led us to reach a definite diagnosis for 37 probands. In these probands we identified known or novel likely pathogenic mutations causing specific diseases, including monoallelic Bernard Soulier syndrome (N=14), biallelic Bernard Soulier syndrome (N=4), ACTN1-related thrombocytopenia (N=4), MYH9-related disease (N=7), ANKRD26-related thrombocytopenia (N=4), congenital amegakaryocytic thrombocytopenia (N=1), grey platelet syndrome (N=1), Wiskott-Aldrich syndrome (N=1) and Acute Myelogenous Leukemia (N=1). In another 34 cases we identified variants of uncertain significance (VUS) whose pathogenic role has to be supported by segregation analysis and in-depth functional studies. Since 17 probands had no potential candidate variant impacting IT-NGS genes, they are eligible for whole exome sequencing (WES) to clone novel genes involved in ITs.
In conclusion, since some IT forms predispose to additional acquired disease during life, an accurate diagnosis is essential to infer personalized prognosis and define proper treatments and follow-up.
Because of clinical and genetic heterogeneity, the molecular diagnosis of ITs represents a lengthy and expensive challenge using conventional technologies.
The use of IT-NGS in clinical practice aided by specific investigations clarifying the role of variant of uncertain significance, overcomes these issues facilitating a definite diagnosis in patients with a suspicious of known ITs forms
What’s behind increasing wage inequality? Explaining the Italian case using RIF-OLS
Get PDFThis paper aims to identify how and to what extent the Italian labour market structure, in terms of job composition and institutional changes, shaped the dynamics of wages and wage inequality in the decade between 2007 and 2017. We investigate the main determinants behind the rise in wage inequality in Italy by using Recentered Influence Function (RIF) regressions. This econometric approach allows - on the one hand - to directly assess the effects on the unconditional distribution and on "beyond the mean" statistics, like the Gini coefficient. On the other, it decomposes inequality into endowment and wage effects, following the standard Oaxaca-Blinder technique. We observe that working structures and institutional changes - contractual arrangements (permanent vs temporary contracts) and working hours (full-time vs part-time) - are the main factors in explaining the deterioration in wages at the bottom of the income distribution scale, and the consequent increase in wage inequality
The role of tasks, contractual arrangements and job composition in explaining the dynamics of wage inequality: Evidence from France
No full textStudio del trasporto e diffusione di inquinanti radioattivi nel suolo e sottosuolo
No full textNel presente lavoro è stato affrontato lo studio del trasporto e della destinazione degli inquinanti radioattivi nel suolo e sottosuolo tramite l’utilizzo della piattaforma software FRAMES ed in particolare del modulo MEPAS.
La prima parte dell’opera è stata dedicata alla trattazione della radioattività, analizzandone gli aspetti generali e soffermandosi sul concetto di rifiuto radioattivo e sulla gestione e sullo smaltimento dello stesso.
Si sono poi analizzati i principali modelli di trasporto per la valutazione del destino dei contaminanti nell’ambiente, fase complessa nella valutazione del rischio o in qualsiasi altra valutazione di impatto ambientale. Lo studio complessivo del problema ha richiesto la suddivisioni in tre momenti distinti, che si riferiscono al modello concettuale di analisi di rischio:
le sorgenti di contaminazione;
le vie di migrazione;
i bersagli di contaminazione
Response to Giangregorio et al.: "Intensity is a subjective construct" (Letter)
No full textWe thank the Too Fit to Fracture consensus panel members for their letter to the editor regarding our recent publication [1], and for the opportunity to highlight a central feature of the LIFTMOR trial. Giangregorio and colleagues suggest that we misinterpreted the Too Fit to Fracture exercise recommendations by citing their work to support our statement “it is widely held that high-intensity exercises should not be attempted by individuals with established osteoporosis”. They contend that the Too Fit to Fracture exercise recommendations encourage individuals with osteoporosis to undertake progressive resistance training (PRT) at 8–10 repetitions which they describe as high-intensity [2]. (We note that the recommendation in the original Too Fit to Fracture publication we cited was actually 8–12 repetitions [ref. 3, Table 6, p 832]). We believe the issue is not a case of misinterpretation on our part [1], rather mis-definition of the term “high-intensity” on the part of the Too Fit to Fracture team [2, 3].No Full Tex
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Automatic extraction of acoustic features to predict Alzheimer's disease among English-speaking subjects
No full textDementia is a disease characterized by the decline of cognitive function. Previous studies have shown that speech conveys information about health and cognitive status. The current work aims at validating the capability of a set of acoustic features automatically extracted from voice recordings to classify the level of cognitive decline. To reach this aim, the Pitt Corpus, a dataset of 458 recordings of English-speaking subjects, has been exploited. A Support Vector Machine classifier achieved the best classification performance, with an F1-score of 78% to distinguish people with a diagnosis of Alzheimer's Disease (AD) from non-AD subjects. An improvement of the classification performance was achieved by two gender-based classifiers, which obtained an F1-score of 83% and 88% for female-based and male-based classifiers, respectively. The results of this study confirmed the possibility to predict AD based on acoustic features automatically extracted from voice recordings. Since no manual intervention was required in data processing, the proposed algorithm is a good candidate for being implemented on a mobile application so as to implement an ecological momentary assessment of people at risk of cognitive decline
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