Automatic, efficient and scalable provenance registration for FAIR HPC workflows

Provenance registration is becoming more and more important, as we increase the size and number of experiments performed using computers. In particular, when provenance is recorded in HPC environments, it must be efficient and scalable. In this paper, we propose a provenance registration method for scientific workflows, efficient enough to run in supercomputers (thus, it could run in other environments with more relaxed restrictions, such as distributed ones). It also must be scalable in order to deal with large workflows, that are more typically used in HPC. We also target transparency for the user, shielding them from having to specify how provenance must be recorded. We implement our design using the COMPSs programming model as a Workflow Management System (WfMS) and use RO-Crate as a well-established specification to record and publish provenance. Experiments are provided, demonstrating the run time efficiency and scalability of our solution.This work has been supported by the Spanish Government (PID2019-107255GB-C21), by Generalitat de Catalunya (contract 2017-SGR-01414) and the EU’s Horizon research and innovation programme under Grant agreement No 101058129 (DT-GEO). Also, it has been contributed in the CECH project, co-funded with 50% by the European Regional Development Fund under the framework of the ERFD Operative Programme for Catalunya 2014-2020, with a grant of 1.527.637,88 C. LRN, JMF and SCG are partly supported by INB Grant (PT17/0009/0001 - ISCIII-SGEFI / ERDF), and their work received funding from the EU’s Horizon 2020 research and innovation programme under grant agreements EOSC-Life No 824087, and EJP RD No 825575.Peer ReviewedPostprint (author's final draft

New insights into the genetic component of non-infectious uveitis through an Immunochip strategy

Background: Large-scale genetic studies have reported several loci associated with specific disorders involving uveitis. Our aim was to identify genetic risk factors that might predispose to uveitis per se, independent of the clinical diagnosis, by performing a dense genotyping of immune-related loci. Methods: 613 cases and 3693 unaffected controls from three European case/control sets were genotyped using the Immunochip array. Only patients with non-infectious non-anterior uveitis and without systemic features were selected. To perform a more comprehensive analysis of the human leucocyte antigen (HLA) region, SNPs, classical alleles and polymorphic amino acid variants were obtained via imputation. A meta-analysis combining the three case/control sets was conducted by the inverse variance method. Results: The highest peak belonged to the HLA region. A more detailed analysis of this signal evidenced a strong association between the classical allele HLA-A*2902 and birdshot chorioretinopathy (p=3.21E-35, OR=50.95). An omnibus test yielded HLA-A 62 and 63 as relevant amino acid positions for this disease. In patients with intermediate and posterior uveitis, the strongest associations belonged to the rs7197 polymorphism, within HLA-DRA (p=2.07E-11, OR=1.99), and the HLA-DR15 haplotype (DRB1*1501: p=1.16E-10, OR=2.08; DQA1*0102: p=4.37E-09, OR=1.77; DQB1*0602: p=7.26E-10, OR=2.02). Outside the HLA region, the MAP4K4/IL1R2 locus reached statistical significance (rs7608679: p=8.38E-07, OR=1.42). Suggestive associations were found at five other loci. Conclusions: We have further interrogated the association between the HLA region and non-infectious non-anterior uveitis. In addition, we have identified a new non-HLA susceptibility factor and proposed additional risk loci with putative roles in this complex condition

Informe del Comité de Bioética de España sobre los aspectos éticos y jurídicos de la maternidad subrogada

El Comité de Bioética de España en su reunión plenaria del pasado 8 de mayo de 2017 acordó por unanimidad de los vocales presentes aprobar un Informe sobre los aspectos éticos y jurídicos de la maternidad subrogada, elaborado a iniciativa del propio Comité, dada la preocupación que suscitaba a sus miembros el debate presente en la opinión pública y en algunas instituciones sobre la conveniencia de regular o, al menos, dotar de legalidad, a los contratos de maternidad subrogada. Como se pone de manifiesto al inicio del Informe, la maternidad subrogada es uno de los temas bioéticos más controvertidos del momento por su carácter disruptivo sobre el modo en que la procreación humana, y las consecuentes relaciones de maternidad y filiación, han sido entendidas y reguladas hasta la actualidad, planteándose por primera vez en la historia la posibilidad de disociar la gestación de la maternidad. Ciertamente, no es un fenómeno nuevo, los primeros casos tuvieron lugar hace más de cuarenta años. Sin embargo, durante mucho tiempo tuvo un alcance limitado, no siendo hasta los últimos quince años cuando la práctica se ha extendido y, sobre todo, se ha internacionalizado. Los medios de comunicación se han venido haciendo eco de informaciones que han atraído la atención de la opinión pública, generando gran repercusión mediática los casos de personajes famosos que han recurrido a este medio para ser padres. En líneas generales, como se expone detalladamente en el Informe, son dos los principales problemas jurídicos que se plantean en España. El primero tiene que ver con el hecho de que la maternidad subrogada sea contraria a la ley nacional y, sin embargo, muchos españoles consigan ser padres recurriendo a ella en otros países donde es legal. ¿Se puede pretender que las leyes aprobadas en España tengan verdadera eficacia y que no solo sean de aplicación para quienes, por carecer de recursos y de temeridad, no pueden sortearlas en el extranjero? Hay otros ámbitos en los que los hechos son perseguibles, incluso penalmente, aunque se realicen en el extranjero

Informe del Comité de Bioética de España sobre el Anteproyecto de Ley Orgánica para la Protección de la Vida del Concebido y de los Derechos de la Mujer Embarazada

Texto enviado al Gobierno y votos particulares que elaboró el Comité de Bioética de España, en el que por mayoría se apoya el Anteproyecto del Gobierno para una norma de protección de la vida del concebido, anteproyecto posteriormente retirado

Effectiveness of the Epley's maneuver performed in primary care to treat posterior canal benign paroxysmal positional vertigo: study protocol for a randomized controlled trial

Background: Vertigo is a common medical condition with a broad spectrum of diagnoses which requires an integrated approach to patients through a structured clinical interview and physical examination. The main cause of vertigo in primary care is benign paroxysmal positional vertigo (BPPV), which should be confirmed by a positive D-H positional test and treated with repositioning maneuvers. The objective of this study is to evaluate the effectiveness of Epley's maneuver performed by general practitioners (GPs) in the treatment of BPPV. Methods/Design: This study is a randomized clinical trial conducted in the primary care setting. The study's scope will include two urban primary care centers which provide care for approximately 49,400 patients. All patients attending these two primary care centers, who are newly diagnosed with benign paroxysmal positional vertigo, will be invited to participate in the study and will be randomly assigned either to the treatment group (Epley's maneuver) or to the control group (a sham maneuver). Both groups will receive betahistine. Outcome variables will be: response to the D-H test, patients' report on presence or absence of vertigo during the previous week (dichotomous variable: yes/no), intensity of vertigo symptoms on a Likert-type scale in the previous week, total score on the Dizziness Handicap Inventory (DHI) and quantity of betahistine taken. We will use descriptive statistics of all variables collected. Groups will be compared using the intent-to-treat approach and either parametric or nonparametric tests, depending on the nature and distribution of the variables. Chi-square test or Fisher's exact test will be conducted to compare categorical measures and Student's t-test or Mann-Whitney U-test will be used for intergroup comparison variables. Discussion: Positive results from our study will highlight that treatment of benign paroxysmal positional vertigo can be performed by trained general practitioners (GPs) and, therefore, its widespread practice may contribute to improve the quality of life of BPPV patients

Detection of early seeding of Richter transformation in chronic lymphocytic leukemia

Richter transformation (RT) is a paradigmatic evolution of chronic lymphocytic leukemia (CLL) into a very aggressive large B cell lymphoma conferring a dismal prognosis. The mechanisms driving RT remain largely unknown. We characterized the whole genome, epigenome and transcriptome, combined with single-cell DNA/RNA-sequencing analyses and functional experiments, of 19 cases of CLL developing RT. Studying 54 longitudinal samples covering up to 19 years of disease course, we uncovered minute subclones carrying genomic, immunogenetic and transcriptomic features of RT cells already at CLL diagnosis, which were dormant for up to 19 years before transformation. We also identified new driver alterations, discovered a new mutational signature (SBS-RT), recognized an oxidative phosphorylation (OXPHOS)high-B cell receptor (BCR)low-signaling transcriptional axis in RT and showed that OXPHOS inhibition reduces the proliferation of RT cells. These findings demonstrate the early seeding of subclones driving advanced stages of cancer evolution and uncover potential therapeutic targets for RT

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries