Querying phenotype-genotype relationships on patient datasets using semantic web technology: the example of cerebrotendinous xanthomatosis

Background: Semantic Web technology can considerably catalyze translational genetics and genomics research in medicine, where the interchange of information between basic research and clinical levels becomes crucial. This exchange involves mapping abstract phenotype descriptions from research resources, such as knowledge databases and catalogs, to unstructured datasets produced through experimental methods and clinical practice. This is especially true for the construction of mutation databases. This paper presents a way of harmonizing abstract phenotype descriptions with patient data from clinical practice, and querying this dataset about relationships between phenotypes and genetic variants, at different levels of abstraction. Methods: Due to the current availability of ontological and terminological resources that have already reached some consensus in biomedicine, a reuse-based ontology engineering approach was followed. The proposed approach uses the Ontology Web Language (OWL) to represent the phenotype ontology and the patient model, the Semantic Web Rule Language (SWRL) to bridge the gap between phenotype descriptions and clinical data, and the Semantic Query Web Rule Language (SQWRL) to query relevant phenotype-genotype bidirectional relationships. The work tests the use of semantic web technology in the biomedical research domain named cerebrotendinous xanthomatosis (CTX), using a real dataset and ontologies. Results: A framework to query relevant phenotype-genotype bidirectional relationships is provided. Phenotype descriptions and patient data were harmonized by defining 28 Horn-like rules in terms of the OWL concepts. In total, 24 patterns of SWQRL queries were designed following the initial list of competency questions. As the approach is based on OWL, the semantic of the framework adapts the standard logical model of an open world assumption. Conclusions: This work demonstrates how semantic web technologies can be used to support flexible representation and computational inference mechanisms required to query patient datasets at different levels of abstraction. The open world assumption is especially good for describing only partially known phenotype-genotype relationships, in a way that is easily extensible. In future, this type of approach could offer researchers a valuable resource to infer new data from patient data for statistical analysis in translational research. In conclusion, phenotype description formalization and mapping to clinical data are two key elements for interchanging knowledge between basic and clinical research.The work presented in this paper has been developed in the funded national project Gestión de Terminologías Médicas para Arquetipos (TIN2009-14159-C05-05) by the Ministerio de Educación y Ciencia. This work was partly supported by the network REGENPSI (2009/019) from the Program of Consolidation and Structure of Competitive Units, Consellería de Educación e Ordenación Universitaria, Xunta de Galicia, and by FEDER funds for regional development. PNR was supported by a grant from the Deutsche Forschungsgemeinschaft (DFGRO2005/4-2)S

6He + 9Be reactions at 16.8 MeV

6 pags.; 6 figs.Reactions of a 16.8 MeV 6He beam with a 9Be target have been investigated using highly segmented detector setup covering a large solid angle. Data on elastic and quasi-free scattering, as well as two-neutron transfer, are reported. The results for elastic scattering are fairly well reproduced by a CDCC calculation, in agreement with the interpretation of a breakup effect already observed for the scattering of 6He on other light targets. Exotic quasi-free scattering of 6He on α-cluster in 9Be is clearly observed. Inclusive and coincident events were used to extract information on the two-neutron transfer reaction 9Be(6He, α)11Be. Sequential decay of the 11Be state at the excitation energy Ex = 10.6 MeV through different channels is discussed. © 2010 SIF, Springer-Verlag Berlin Heidelberg.We would like to thank the technical staff at the RNB facility at the CRC-Louvain-la-Neuve for their valuable contributions to this work.Peer Reviewe

Shape study of the N = Z nucleus Kr-72 via beta decay

10 pags.; 11 figs.; 2 tabs.; PACS number(s): 23.40.Hc, 29.30.Kv, 27.50.+e, 21.10.Pc; Open Access funded by Creative Commons Atribution Licence 3.0The beta decay of the N = Z nucleus Kr-72 has been studied with the total absorption spectroscopy technique at ISOLDE (CERN). A total B(GT) = 0.79(4)g(A)(2)/4 pi has been found up to an excitation energy of 2.7 MeV. The B(GT) distribution obtained is compared with predictions from state-of-the-art theoretical calculations to learn about the ground state deformation of Kr-72. Although a dominant oblate deformation is suggested by direct comparison with quasiparticle random phase approximation (QRPA) calculations, beyond-mean-field and shell-model calculations favor a large oblate-prolate mixing in the ground state. Published by the American Physical SocietyJ.A.B. acknowledges the predoctoral grant BES-2008-009412 associated with the research project FPA2007-62170 funded by Ministerio de Ciencia e Innovacion (Spain). This work has ´ been partly supported by the Spanish Ministerio de Economía y Competitividad (MINECO) through projects FPA2012- 32443, FPA2011-24553, FPA2011-29854-C04-01, FPA2013- 41267-P, FPA2014-52823-C2-1-P and FIS2011-23565, by STFC-UK (Grant No. ST/F012012/1) and by the European Union by means of the European Commission within its Seventh Framework Programme (FP7) via ENSAR (Contract No. 262010)Peer Reviewe

Study of the scattering of halo nuclei around the Coulomb barrier

During the past ten years the present collaboration has carried out several experiments related with the study of radioactive nuclei. One of the topics in which we have centered our research, is the scattering of halo nuclei at energies around the Coulomb barrier. As part of this study, we present in this work a review of the results obtained from the scattering of 6He, 11Be and 11Li. The presence of a >halo> in these exotic nuclei is found to have a striking effect on the dynamics of these reactions, making their study an interesting experimental problem and a challenge for existing reaction theories.Peer Reviewe

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Scattering of halo nuclei on heavy targets at energies around the Coulomb barrier : The case of 11Be on 197Au

This work reports on the scattering of 11Be on 197Au at energies around and below the Coulomb barrier. By experimentally identifying the elastic scattering, inelastic scattering and breakup channels, and comparing them with different calculations, valuable information on the 11Be structure and its B(E1) distribution to the continuum are obtained. On top of that, a deeper understanding of the scattering process at low energies is achieved for reactions of this kind, making these studies extendable to other loosely-bound systems like 17,19

Estudio de reacciones de 6He en Pb a energías próximas a la barrera coulombiana

Depto. de Estructura de la Materia, Física Térmica y ElectrónicaFac. de Ciencias FísicasTRUEpu

Introducción del concepto de multiplicación en Segundo de Primaria, con materia manipulativo LEGO

Treball Final de Grau en Mestre o Mestra d'Educació Primària. Codi: MP1040. Curs acadèmic: 2017-2018En el presente trabajo de final de grado, se introduce el concepto de multiplicación en el aula de segundo de primaria a través de material manipulativo. En este caso, se utilizan piezas Lego que se están convirtiendo en un material cada vez más utilizado en educación. También se utiliza el aprendizaje cooperativo, que junto a la utilización del material manipulativo y del juego hacen posible conseguir un aprendizaje significativo. Por una parte, se mide mediante un Pre-Test y un Post-Test la actitud y la motivación del alumnado frente a las matemáticas. Por otra parte , mediante la observación directa se mide que el alumnado entiende el concepto de multiplicación y si es capaz de afianzar las tablas de multiplicar durante lo que dura el proceso. También utilizando la observación directa se llega a unas conclusiones de cómo trabajan por medio del aprendizaje cooperativo, y cómo afecta a la motivación el uso de juegos y del material manipulativo de Lego. A lo largo del trabajo, se justifica la intervención realizada, y en el Marco Teórico se habla: de la situación actual de las matemáticas, del material manipulativo, de la forma de introducir la multiplicación en el aula, del aprendizaje cooperativo, de la importancia del juego en educación y por último de la motivación. El trabajo finaliza explicando la metodología utilizada y las conclusiones extraídas a lo largo del período de intervención en el aula, que es de seis sesiones

Synthesis of new antimicrobial pyrrolo[2,1-a]isoquinolin-3-ones

The attractive structure of the pyrroloisoquinoline moiety, together with its potential antimicrobial activity, encouraged us to prepare six 8-substituted and seven 8,9-disubstituted-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinolin-3-ones in a few steps with good yields. We applied a convenient methodology via double intramolecular cyclization conducted by a Bischler-Napieralski cyclodehydration-imine reduction sequence, which is widely employed in the synthesis of isoquinoline alkaloids. Therefore, we synthesized three series of these pyrrolo[2,1-a]isoquinolin-3-ones characterized by the substituent at the 8-position or 8,9-positions of the aromatic ring: (a) different side chains are attached to an 8-OH group (series 1); (b) a chlorine atom is attached to the 8-position (series 2); and (c) 8- and 9-carbons are bearing an identical group (series 3). The compounds bearing a benzylic moiety at the 8-position, for example, 8-benzyloxy-pyrrolo[2,1-a]isoquinolin-3-one (1a) and 8-(4-fluorobenzyloxy)-pyrrolo[2,1-a]isoquinolin-3-one (1e), as well as, a 8-chloro-9-methoxy moiety including the 8-chloro-9-methoxy-pyrrolo[2,1-a]isoquinolin-3-one (2a), provided the most fungicide and bactericide agents, respectively.Moreno, L.; Parraga, J.; Galan, A.; Cabedo Escrig, N.; Primo Millo, J.; Cortes, D. (2012). Synthesis of new antimicrobial pyrrolo[2,1-a]isoquinolin-3-ones. Bioorganic and Medicinal Chemistry. 20(22):6589-6597. doi:10.1016/j.bmc.2012.09.033S65896597202

Understanding 6He induced reactions at energies around the Coulomb barrier

El pdf del artículo es la versión post-print.Recent developments aimed to understand the observed features arising in the scattering of the Borromean nucleus 6He on heavy targets are discussed and compared with recent data for 6He+208Pb measured at the RIB facility at Louvain‐la‐Neuve at energies around the Coulomb barrier. The analysis of the elastic scattering data in terms of the optical model, reveals the presence of a long range absorption mechanism, that manifests in the form of a large value of the imaginary diffuseness parameter. The elastic data have been also compared with three−body CDCC calculations, based on a di‐neutron model of 6He, and four−body CDCC calculations, based on a more realistic three‐body model of this nucleus. Finally, the angular and energy distribution of α particles emitted at backward angles are discussed and compared with different theoretical approaches. We find that these α particles are produced mainly by a two‐neutron transfer mechanism to very excited states in the residual nucleus.Peer Reviewe