Innermost Termination of Context-Sensitive Rewriting

Innermost context-sensitive rewriting (CSR) has been proved useful for modeling the computational behavior of programs of algebraic languages like Maude. We adapt the Dependency Pairs Framework to innermost CSR since, up to now, only few transformation-based techniques have been proposed, thus, establishing the new state-of-the-art in the area.Alarcón Jiménez, B. (2008). Innermost Termination of Context-Sensitive Rewriting. http://hdl.handle.net/10251/13630Archivo delegad

Towards a Framework for Proving Termination of Maude Programs

Maude es un lenguaje de programación declarativo basado en la lógica de reescritura que incorpora muchas características que lo hacen muy potente. Sin embargo, a la hora de probar ciertas propiedades computacionales esto conlleva dificultades. La tarea de probar la terminación de sistemas de reesctritura es de hecho bastante dura, pero aplicada a lenguajes de programación reales se concierte en más complicada debido a estas características inherentes. Esto provoca que métodos para probar la terminación de este tipo de programas requieran técnicas específicas y un análisis cuidadoso. Varios trabajos han intentado probar terminación de (un subconjunto de) programas Maude. Sin embargo, todos ellos siguen una aproximación transformacional, donde el programa original es trasformado hasta alcanzar un sistema de reescritura capaz de ser manejado con las técnicas y herramientas de terminación existentes. En la práctica, el hecho de transformar los sistemas originales suele complicar la demostración de la terminación ya que esto introduce nuevos símbolos y reglas en el sistema. En esta tesis, llevamos a cabo el problema de probar terminación de (un subconjunto de) programas Maude mediante métodos directos. Por un lado, nos centramos en la estrategia de Maude. Maude es un lenguaje impaciente donde los argumentos de una función son evaluados siempre antes de la aplicación de la función que los usa. Esta estrategia (conocida como llamada por valor) puede provocar la no terminación si los programas no están escritos cuidadosamente. Por esta razón, Maude (en concreto) incorpora mecanismos para controlar la ejecución de programas como las anotaciones sintácticas que están asociadas a los argumentos de los símbolos. En reescritura, esta estrategia sería conocida como reescritura sensible al contexto innermost (RSCI). Por otro lado, Maude también incorpora la posibilidad de declarar atributos.Alarcón Jiménez, B. (2011). Towards a Framework for Proving Termination of Maude Programs [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/11003Palanci

Innermost Termination of Context-Sensitive Rewriting

Innermost context-sensitive rewriting (CSR) has been proved useful for modeling the computational behavior of programs of algebraic languages like Maude, OBJ, etc, which incorporate an innermost strategy which is used to break down the nondeterminism which is inherent to reduction relations. Furthermore, innermost termination of rewriting is often easier to prove than termination. Thus, under appropriate conditions, a useful strategy for proving termination of rewriting is trying to prove termination of innermost rewriting. This phenomenon has also been investigated for context-sensitive rewriting. Up to now, only few transformation-based methods have been proposed and used to (specifically) prove termination of innermost CSR. Powerful and e cient techniques for proving (innermost) termination of (unrestricted) rewriting like the dependency pair framework have not been considered yet. In this work, we investigate the adaptation of the dependency pair framework to innermost CSR. We provide a suitable notion of innermost context-sensitive dependency pair and show how to extend and adapt the main notions which conform the framework (chain, termination problem, processor, etc.). Thanks to the innermost context-sensitive dependency pairs, we can now use powerful techniques for proving termination of innermost CSR. This is made clear by means of some benchmarks showing that our techniques dramatically improve over previously existing transformational techniques, thus establishing the new state-of-the-art in the area. We have implemented them as part of the termination tool MU-TERM.Alarcón Jiménez, B.; Lucas, S. (2011). Innermost Termination of Context-Sensitive Rewriting. http://hdl.handle.net/10251/1079

A Dependency Pair Framework for AvC-Termination

The development of powerful techniques for proving termination of rewriting modulo a set of equational axioms is essential when dealing with rewriting logic-based programming languages like CafeOBJ, Maude, ELAN, OBJ, etc. One of the most important techniques for proving termination over a wide range of variants of rewriting (strategies) is the dependency pair approach. Several works have tried to adapt it to rewriting modulo associative and commutative (AC) equational theories, and even to more general theories. However, as we discuss in this paper, no appropriate notion of minimality (and minimal chain of dependency pairs) which is well-suited to develop a dependency pair framework has been proposed to date. In this paper we carefully analyze the structure of in nite rewrite sequences for rewrite theories whose equational part is any combination of associativity and/or commutativity axioms, which we call AvC-rewrite theories. Our analysis leads to a more accurate and optimized notion of dependency pairs through the new notion of stably minimal term. We then develop a suitable dependency pair framework for proving termination of AvC-rewrite theories.Alarcón Jiménez, B.; Gutiérrez Gil, R.; Lucas, S.; Meseguer, J. (2011). A Dependency Pair Framework for AvC-Termination. http://hdl.handle.net/10251/1079

Cognitive Abilities in Agents

The aim of this chapter is to describe the cognitive abilities deployed on agents and multi-agent systems by using examples from applications carried out by the authors. Particularly, the following agent abilities are reviewed: problem solving, memory, decision making and learning capabilities. These abilities, which involve most of the research done in Artificial Intelligence during decades of dealing with isolated agents, are revised in order to incorporate the interaction of agents in a multi-agent environment. The results of incorporating such capabilities to agents are the enhancement of the generality and flexibility of the systems

Epidemiological and clinical characteristics of Streptococcus tigurinus endocarditis

Background: Streptococcus tigurinus was recently described as a new streptococcal species within the viridans group streptococci (VGS). The objectives of the present work were to analyse the clinical and microbiological characteristics of S. tigurinus isolated from patients with bacteraemias, to determine the prevalence of S. tigurinus among VGS endocarditis in Spain, and to compare the clinical characteristics and outcomes of endocarditis caused by S. tigurinus and other VGS. Methods: Retrospective nationwide study, performed between 2008 and 2016 in 9 Spanish hospitals from 7 different provinces comprising 237 cases of infective endocarditis. Streptococcal isolates were identified by sequencing fragments of their 16S rRNA, sodA and groEL genes. Clinical data of patients with streptococcal endocarditis were prospectively collected according to a pre-established protocol. Results: Patients with endocarditis represented 7/9 (77.8%) and 26/86 (30.2%) of the bacteraemias caused by S. tigurinus and other VGS, respectively (p < 0.001), in two of the hospital participants. Among patients with streptococcal endocarditis, 12 different Streptococcus species were recognized being S. oralis, S. tigurinus and S. mitis the three more common. No relevant statistical differences were observed in the clinical characteristics and outcomes of endocarditis caused by the different VGS species. Conclusions: In this multicenter study performed in Spain, S. tigurinus showed a higher predilection for the endocardial endothelium as compared to other VGS. However, clinical characteristics and outcomes of endocarditis caused by S. tigurinus did not significantly differ from endocarditis caused by other oral streptococci.JMM received a personal 80:20 research grant from the Institut d’InvestigacionsBiomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain during 2017–19. Nofunding entity played any role in the design of the study and data collection,analysis, and interpretation of data and in writing the manuscript

Soy Niña

Este libro pretende contribuir al reencuentro de la educación con esas finalidades que verdaderamente importan a una niña o un niño: ser feliz, jugar, vivir juntos y (no) aprender. Para ello hemos puesto el arte, nuestras experiencias y el saber acumulado al servicio del disfrute, el cuestionamiento, el análisis crítico y la construcción común de un presente deseable. Un texto colaborativo coordinado por Ignacio Calderón Almendros y realizado por alumnado de Educación y Cambio Social en el Grado en Educación Infantil de la Universidad de Málaga

Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality

AG has received support by NordForsk Nordic Trial Alliance (NTA) grant, by Academy of Finland Fellow grant N. 323116 and the Academy of Finland for PREDICT consortium N. 340541. The Richards research group is supported by the Canadian Institutes of Health Research (CIHR) (365825 and 409511), the Lady Davis Institute of the Jewish General Hospital, the Canadian Foundation for Innovation (CFI), the NIH Foundation, Cancer Research UK, Genome Québec, the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé (FRQS). TN is supported by a research fellowship of the Japan Society for the Promotion of Science for Young Scientists. GBL is supported by a CIHR scholarship and a joint FRQS and Québec Ministry of Health and Social Services scholarship. JBR is supported by an FRQS Clinical Research Scholarship. Support from Calcul Québec and Compute Canada is acknowledged. TwinsUK is funded by the Welcome Trust, the Medical Research Council, the European Union, the National Institute for Health Research-funded BioResource and the Clinical Research Facility and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London. The Biobanque Québec COVID19 is funded by FRQS, Genome Québec and the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé. These funding agencies had no role in the design, implementation or interpretation of this study. The COVID19-Host(a)ge study received infrastructure support from the DFG Cluster of Excellence 2167 “Precision Medicine in Chronic Inflammation (PMI)” (DFG Grant: “EXC2167”). The COVID19-Host(a)ge study was supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the Computational Life Sciences funding concept (CompLS grant 031L0165). Genotyping in COVID19-Host(a)ge was supported by a philantropic donation from Stein Erik Hagen. The COVID GWAs, Premed COVID-19 study (COVID19-Host(a)ge_3) was supported by "Grupo de Trabajo en Medicina Personalizada contra el COVID-19 de Andalucia"and also by the Instituto de Salud Carlos III (CIBERehd and CIBERER). Funding comes from COVID-19-GWAS, COVID-PREMED initiatives. Both of them are supported by "Consejeria de Salud y Familias" of the Andalusian Government. DMM is currently funded by the the Andalussian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018). The Columbia University Biobank was supported by Columbia University and the National Center for Advancing Translational Sciences, NIH, through Grant Number UL1TR001873. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or Columbia University. The SPGRX study was supported by the Consejería de Economía, Conocimiento, Empresas y Universidad #CV20-10150. The GEN-COVID study was funded by: the MIUR grant “Dipartimenti di Eccellenza 2018-2020” to the Department of Medical Biotechnologies University of Siena, Italy; the “Intesa San Paolo 2020 charity fund” dedicated to the project NB/2020/0119; and philanthropic donations to the Department of Medical Biotechnologies, University of Siena for the COVID-19 host genetics research project (D.L n.18 of March 17, 2020). Part of this research project is also funded by Tuscany Region “Bando Ricerca COVID-19 Toscana” grant to the Azienda Ospedaliero Universitaria Senese (CUP I49C20000280002). Authors are grateful to: the CINECA consortium for providing computational resources; the Network for Italian Genomes (NIG) (http://www.nig.cineca.it) for its support; the COVID-19 Host Genetics Initiative (https://www.covid19hg.org/); the Genetic Biobank of Siena, member of BBMRI-IT, Telethon Network of Genetic Biobanks (project no. GTB18001), EuroBioBank, and RD-Connect, for managing specimens. Genetics against coronavirus (GENIUS), Humanitas University (COVID19-Host(a)ge_4) was supported by Ricerca Corrente (Italian Ministry of Health), intramural funding (Fondazione Humanitas per la Ricerca). The generous contribution of Banca Intesa San Paolo and of the Dolce&Gabbana Fashion Firm is gratefully acknowledged. Data acquisition and sample processing was supported by COVID-19 Biobank, Fondazione IRCCS Cà Granda Milano; LV group was supported by MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016-02364358, Ricerca corrente Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, the European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS- “Liver Investigation: Testing Marker Utility in Steatohepatitis”, Programme “Photonics” under grant agreement “101016726” for the project “REVEAL: Neuronal microscopy for cell behavioural examination and manipulation”, Fondazione Patrimonio Ca’ Granda “Liver Bible” PR-0361. DP was supported by Ricerca corrente Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, CV PREVITAL “Strategie di prevenzione primaria nella popolazione Italiana” Ministero della Salute, and Associazione Italiana per la Prevenzione dell’Epatite Virale (COPEV). Genetic modifiers for COVID-19 related illness (BeLCovid_1) was supported by the "Fonds Erasme". The Host genetics and immune response in SARS-Cov-2 infection (BelCovid_2) study was supported by grants from Fondation Léon Fredericq and from Fonds de la Recherche Scientifique (FNRS). The INMUNGEN-CoV2 study was funded by the Consejo Superior de Investigaciones Científicas. KUL is supported by the German Research Foundation (LU 1944/3-1) SweCovid is funded by the SciLifeLab/KAW national COVID-19 research program project grant to Michael Hultström (KAW 2020.0182) and the Swedish Research Council to Robert Frithiof (2014-02569 and 2014-07606). HZ is supported by Jeansson Stiftelser, Magnus Bergvalls Stiftelse. The COMRI cohort is funded by Technical University of Munich, Munich, Germany. Genotyping for the COMRI cohort was performed and funded by the Genotyping Laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki, Helsinki, Finland. These funding agencies had no role in the design, implementation or interpretation of this study.Background: There is considerable variability in COVID-19 outcomes amongst younger adults—and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium. Method: The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors. Findings: We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2–1·6) and COVID-19 related mortality (HR 1·5, 95%CI 1·3–1·8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2·0, 95%CI 1·6-2·6), venous thromboembolism (OR 1·7, 95%CI 1·2-2·4), and hepatic injury (OR 1·6, 95%CI 1·2-2·0). Risk allele carriers ≤ 60 years had higher odds of death or severe respiratory failure (OR 2·6, 95%CI 1·8-3·9) compared to those > 60 years OR 1·5 (95%CI 1·3-1·9, interaction p-value=0·04). Amongst individuals ≤ 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31·8% (95%CI 27·6-36·2) were risk variant carriers, compared to 13·9% (95%CI 12·6-15·2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those ≤ 60 years improved when including the risk allele (AUC 0·82 vs 0·84, p=0·016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors. Interpretation: The major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality—and these are more pronounced amongst individuals ≤ 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management.Academy of Finland Fellow grant N. 323116Academy of Finland for PREDICT consortium N. 340541.Canadian Institutes of Health Research (CIHR) (365825 and 409511)Lady Davis Institute of the Jewish General HospitalCanadian Foundation for Innovation (CFI)NIH FoundationCancer Research UKGenome QuébecPublic Health Agency of CanadaMcGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé (FRQS)Japan Society for the Promotion of Science for Young ScientistsCIHR scholarship and a joint FRQS and Québec Ministry of Health and Social Services scholarshipFRQS Clinical Research ScholarshipCalcul QuébecCompute CanadaWelcome TrustMedical Research CouncEuropean UnionNational Institute for Health Research-funded BioResourceClinical Research Facility and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation TrustKing’s College LondonGenome QuébecPublic Health Agency of CanadaMcGill Interdisciplinary Initiative in Infection and ImmunityFonds de Recherche Québec Santé(DFG Grant: “EXC2167”)(CompLS grant 031L0165)Stein Erik Hagen"Grupo de Trabajo en Medicina Personalizada contra el COVID-19 de Andalucia"Instituto de Salud Carlos III (CIBERehd and CIBERER)COVID-19-GWASCOVID-PREMED initiatives"Consejeria de Salud y Familias" of the Andalusian GovernmentAndalusian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018)Columbia UniversityNational Center for Advancing Translational SciencesNIH Grant Number UL1TR001873Consejería de Economía, Conocimiento, Empresas y Universidad #CV20-10150MIUR grant “Dipartimenti di Eccellenza 2018-2020”“Intesa San Paolo 2020 charity fund” dedicated to the project NB/2020/0119Tuscany Region “Bando Ricerca COVID-19 Toscana”CINECA consortiumNetwork for Italian Genomes (NIG)COVID-19 Host Genetics InitiativeGenetic Biobank of SienaEuroBioBankRD-ConnectRicerca Corrente (Italian Ministry of Health)Fondazione Humanitas per la RicercaBanca Intesa San PaoloDolce&Gabbana Fashion FirmCOVID-19 BiobankFondazione IRCCS Cà Granda MilanoMyFirst Grant AIRC n.16888Ricerca Finalizzata Ministero della Salute RF-2016-02364358Ricerca corrente Fondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoEuropean Union (EU) Programme Horizon 2020 (under grant agreement No. 777377)“Photonics” “101016726”Fondazione Patrimonio Ca’ Granda “Liver Bible” PR-0361CV PREVITAL “Strategie di prevenzione primaria nella popolazione Italiana” Ministero della Salute, and Associazione Italiana per la Prevenzione dell’Epatite Virale (COPEV)"Fonds Erasme"Fondation Léon FredericqFonds de la Recherche Scientifique (FNRS)Consejo Superior de Investigaciones CientíficasGerman Research Foundation (LU 1944/3-1)SciLifeLab/KAW national COVID-19 research program project (KAW 2020.0182)Swedish Research Council (2014-02569 and 2014-07606)Jeansson Stiftelser, Magnus Bergvalls StiftelseTechnical University of Munich, Munich, GermanyGenotyping Laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki, Helsinki, Finlan

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group