Neuroblastoma somatic mutations enriched in cis-regulatory elements collectively affect genes involved in embryonic development and immune system response

Background | The ever-growing interest towards noncoding cis-regulatory variants as cancer drivers is currently hampered by numerous challenges and limitations of variant prioritization and interpretation methods and tools. Methods | To overcome these limitations, I focused on active cis regulatory elements (aCREs) to design a customized panel for deep sequencing of 56 neuroblastoma tumor and normal DNA sample pairs. CREs were defined by a reanalysis of H3K27ac ChiP-seq peaks of 25 neuroblastoma cell lines. aCREs were further identified by the presence of open chromatin as defined by DNase Hypersensitivity sites. This provided a small subset of genomic regions with evident regulatory functions in which to search for driver mutations. I tested these regions for an excess of somatic mutations and assessed the statistical significance with a global approach accounting for chromatin accessibility and replication timing. Additional validation was provided by analyzing whole genome sequences of 151 neuroblastomas. For the mutated regions, I determined their candidate target genes through HiC data analysis. Results | I identified a significant excess of somatic mutations in aCREs of diverse genes including IPO7, HAND2, and ARID3A. A gene expression signature built on basis of these three, and nearby, interacting genes strongly correlated with negative prognostic markers and low survival rates of patients affected by neuroblastoma. Moreover, I observed a convergence of biological functions of the target genes of mutated aCREs and transcription factors with binding motifs altered by mutations towards processes related to embryonic development and immune system response. Conclusion | My strategy led me to identify somatic mutations in regulatory elements that collectively can drive neuroblastoma onset

Rivalité Canadien-Nordiques, un reflet du nationalisme québécois des années 1980

Québec, le soir du 30 octobre 1995. Le peuple québécois s'apprête à se prononcer pour une deuxième fois en moins de vingt ans sur son avenir politique au sein de la Confédération canadienne. Émotif et dramatique jusqu'à la toute fin, le référendum se solde par un échec serré au niveau du décompte électoral, mais il démontre à quel point le nationalisme québécois n'a pas reculé dans l'esprit des gens. L'année 1995 marque également la fin d'une autre période forte de l'histoire du Québec. L'annonce de la vente des Nordiques à des intérêts américains et le départ de la concession vers le Colorado vient mettre fin à une véritable saga entre les deux principales villes de la province. Décision liée à la nouvelle réalité économique de la LNH, la perte des Nordiques affecte bien plus que les citoyens de la capitale nationale. Les Québécois viennent de perdre une partie de leur patrimoine culturelle. C'est que la rivalité Canadiens-Nordiques a divisé pendant plus de quinze ans les familles québécoises, qui se réunissaient pour l'occasion à la Grande messe du hockey du samedi soir. L'attachement profond des Québécois à l'une ou l'autre des équipes va bien plus loin que la partisannerie sportive à proprement parler. La rivalité sportive Montréal-Québec s'insère dans une période charnière du nationalisme québécois. Faisant le pont entre les deux référendums, elle se substitue aux luttes politiques et constitutionnelles de la décennie 1980, pour devenir l'un des principaux exutoires de la fierté nationale québécoise de l'époque. À n'en point douter, cette rivalité a marqué profondément le Québec et les Québécois. Mis à part les cris, les huées, les bagarres et les buts, que se cache-t-il derrière la mythique rivalité Canadiens-Nordiques des années 80-90

Multi-criteria decision analysis for the assessment of non-clinical hospital services: Methodology and case study

Non-clinical hospital services to support clinical activities, such as the sterilization service and clinical engineering, are an important technology asset in healthcare, and require constant improvement aimed to reduce economic burden and increase quality. The selection of the most effective healthcare service to adopt in a healthcare facility is a multi-criteria decision problem that classical Health Technology Assessment, being mostly focused on medicines, vaccines and medical devices, cannot easily address. Here we present a methodology based on Multi-Criteria Decision Analysis allowing a full assessment of non-clinical hospital services and supporting the selection of the most suitable solution in a certain environment. The methodology involves two different panels of experts: the first one includes international professionals and is aimed at selecting the assessment criteria that are relevant to the target service; the second one is a local panel whose members know the needs and peculiarities of the specific healthcare facility. This approach allows the final decision makers to take into account changes and constraints of their environment, but examining criteria that are internationally recognized as of interest. The proposed methodology, tested in a real context of an Italian Local Health Authority, is versatile and can be applied in any context, even out of the healthcare domain, especially if data in the literature are not sufficient to allow comparisons with similar services in different settings. Abbreviations: HTA, Health Technology Assessment; NCHS, Non-Clinical Hospital Services; CSSD, Central Sterile Services Department; MCDA, Multi-Criteria Decision Analysis; ASM, Local Healt

Technology and Service Assessment Tools in Healthcare

The role of clinical engineers is rapidly changing and the economic constraints have pulled them towards new responsibilities to manage. Particularly, the assessment of health technologies has covered one of the most important areas among clinical engineers\u2019 duties. Different techniques and methodologies for technology assessment and improvement are available in the literature and they are currently in use within hospitals and healthcare facilities. However, scientific research and practical needs seem to be misaligned, causing misuse of scientific results due to the lack of tools easy-to-use from practical perspective. This thesis aims at integrating methodologies, even derived from different sectors, for providing standardized and versatile tools that overcome the current issues, providing healthcare facility with a path to follow for choosing the best methodology to be used in diverse situations. Different case studies are presented, in order to cover the wide range of possibilities within health technology assessment (HTA). Particularly, technology assessment was performed on medical devices using both Hospital-Based HTA for an existing technology and horizon scanning for designing an innovative solution. Then the assessment was extended to hospital services, with particular attention to clinical engineering services, using Multi-Criteria Decision Analysis. Process improvement methodologies were also considered and applied to sterilization service that was also studied and assessed integrating the classical HTA approach with Multi-Criteria Decision Analysis. These studies allowed to identify a path useful from practical perspective and based on scientific approach aimed at helping healthcare professionals and clinical engineers to choose the best methodology in accordance to specific constraints and needs of particular situations

Augmented Reality Audio Editing

International audienceThe concept of augmented reality audio (ARA) characterizes techniques where a physically real sound and voice environment is extended with virtual, geolocalized sound objects. We show that the authoring of an ARA scene can be done through an iterative process composed of two stages: in the first one the author has to move in the rendering zone to apprehend the audio spatialization and the chronology of the audio events and in the second one a textual editing of the sequencing of the sound sources and DSP acoustics parameters is done. This authoring process is based on the join use of two XML languages, OpenStreetMap for maps and A2ML for Interactive 3D Audio. A2ML being a format for a cue-oriented interactive audio system, requests for interactive audio services are done through TCDL, a Tag-based Cue Dispatching language. This separation of modeling and audio rendering is similar to what is done for the web of documents with HTML and CSS style sheets

Detecting Plasma Produced by Laser in a Micromachining System as In-process Control

Automated systems have been used in industries with high-volume production because automation has led, for example, the possibility to reduce costs, increase productivity, and increase accuracy, among others. On the other hand, it is also known that the processing laser is ideal for all kind of controls. In this sense, the amount of material produced and removed by laser irradiation on the surface of the substrate might be used as a control variable. Therefore, plasma detector could be used as part of the control system in the machining process in gaseous environments. This work presents the results of the preliminary characterization of this detector designed to measure theplasma generated during laser machining in air (Pamb and Tamb).Fil: Toro Salazar, Cinthya Emma. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes). Proyecto Tandar; ArgentinaFil: Lasorsa, Carlos Alberto. Comisión Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes). Proyecto Tandar; ArgentinaFil: Rinaldi, Carlos Alberto. Comisión Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes). Proyecto Tandar; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

La migrazione delle prove INVALSI di Matematica da PPT a CBT. Uno studio sulle prove di pre-test per la II superiore

This article describes an INVALSI trial for passing from paper based tests to computer-based tests conducted in the 2016 math pre-test campaign for the second class of the secondary school (level 10). The purpose of the study is to compare paper & pencil and computer-based delivery of the same test, in relation to the student’s ability and to the item functioning in terms of difficulty(b), discrimination (Id), and percentage of missing. A nationally representative sample of 10th grade students was administered computer-based mathematics test. In addition a parallel sample of students was administered the same test in paper & pencil mode. The results show that test in computer- based mode was significantly harder statistically than the paper-based test. There are no significant differences in the estimated student’s ability.Questo articolo dà conto dei risultati di una sperimentazione INVALSI per il passaggio da prove cartacee a prove computer based condotta nella campagna di pre-test del 2016 di matematica del livello 10. Scopo dello studioè il confronto fra la somministrazione cartacea e quella computer based della stessa prova, sia in relazione alla stima dell’abilità degli studenti sia in relazione al comportamento degli item in termini di parametri di difficoltà, di indice di discriminatività e di percentuale di risposte omesse. A un campione rappresentativo a livello nazionale degli studenti di livello 10 è stata somministrata una prova di matematica in modalità computer based e a un campione parallelo la stessa prova in modalità cartacea. I risultati mostrano che la prova in formato computer based risulta mediamente più difficile della prova in formato cartaceo. Non ci sono invece differenze significative nella stima dell’abilità degli studenti

Opinion diversity and community formation in adaptive networks

It is interesting and of significant importance to investigate how network structures co-evolve with opinions. The existing models of such co-evolution typically lead to the final states where network nodes either reach a global consensus or break into separated communities, each of which holding its own community consensus. Such results, however, can hardly explain the richness of real-life observations that opinions are always diversified with no global or even community consensus, and people seldom, if not never, totally cut off themselves from dissenters. In this article, we show that, a simple model integrating consensus formation, link rewiring and opinion change allows complex system dynamics to emerge, driving the system into a dynamic equilibrium with co-existence of diversified opinions. Specifically, similar opinion holders may form into communities yet with no strict community consensus; and rather than being separated into disconnected communities, different communities remain to be interconnected by non-trivial proportion of inter-community links. More importantly, we show that the complex dynamics may lead to different numbers of communities at steady state with a given tolerance between different opinion holders. We construct a framework for theoretically analyzing the co-evolution process. Theoretical analysis and extensive simulation results reveal some useful insights into the complex co-evolution process, including the formation of dynamic equilibrium, the phase transition between different steady states with different numbers of communities, and the dynamics between opinion distribution and network modularity, etc.Comment: 12 pages, 8 figures, Journa

Mathematics described proficiency levels: connecting psychometric and teaching analyses

International audienc

Differential modulation of intracellular Ca2+ responses associated with calcium-sensing receptor activation in renal collecting duct cells.

In this work, we studied G protein-coupled Extracellular Calcium Sensing Receptor (CaR) signaling in mouse cortical collecting duct cells (MCD4) expressing endogenous CaR. Intracellular [Ca2+] measurements performed with real time video imaging revealed that CaR stimulation with 5mM Ca2+, 300µM Gd3+ and with 10µM of specific allosteric modulator NPS-R 568, all resulted in an increase in [Ca2+]i although displaying different features. Specifically, Ca2+ as well as stimulation with NPS-R 568 induced a rapid peak of [Ca2+]i while stimulation with Gd3+ induced transient intracellular Ca2+ oscillations. PLC inhibition completely abolished any [Ca2+]i increase after stimulation with CaR agonists. Inhibition of Rho or Rho kinase (ROK) abolished [Ca2+]i oscillations induced by Gd3+, while the peak induced by high Ca2+ was similar to control. Conversely, emptying the intracellular calcium stores abolished the response to Gd3+. On the other hand, the inhibition of calcium influx did not alter calcium changes. We conclude that in our cell model, CaR stimulation with distinct agonists activates two distinct transduction pathways, both PLC-dependent. The transient cytosolic Ca2+ oscillations produced by Gd3+ are modulated by Rho-Rho kinase signaling, whereas the rapid peak of intracellular Ca2+ in response to 5mM [Ca2+]o is mainly due to PLC/IP3 pathway activation