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

User Contributions to Value Creation: An Ambiguous and Troublesome Parameter that Is Inconsistent with the European Proposal on a Significant Digital Presence

El presente artículo busca indagar en el origen, contenido y efectos del principio de creación de valor en materia de fiscalidad internacional, dado que ha sido recientemente promovido como nuevo mantra por parte de organismos como la OCDE y la UE. En particular, intentaremos descubrir qué implicaciones prácticas tendría su uso en modelos de negocios fuertemente dependientes de la contribución de los usuarios al proceso de creación de valor. Una vez hecho esto, analizaremos si el nuevo establecimiento permanente digital propuesto por la UE, teóricamente inspirado en esta nueva directriz de política fiscal, está debidamente alineado con ella.Depto. de Derecho Mercantil, Financiero y TributarioFac. de DerechoTRUEpu

Jurisdiction to tax corporate income pursuant to the presumptive benefit principle: a critical analysis of structural paradigms underlying corporate income taxation and proposals for reform

The book is based on a PhD thesis that obtained the prestigious European Academic Tax Thesis Award 2018 granted by the European Commission and the European Association of Tax Law Professors. "Jurisdiction to tax corporate income pursuant to the presumptive benefit principle" intends to demonstrate that the profit shifting phenomenon (i.e. the ability of companies to book their profits in jurisdictions other than those that host their economic activities) is real, severe, undesirable, and above all, the natural consequence of both the preservation of three fundamental paradigms that have historically underlain corporate income taxes and their precise legal configuration. In view of this, the book submits a number of proposals in relation to the aforementioned paradigms and in the light of the suggested “presumptive benefit principle” so as to counteract profit shifting risks and thus attain a more equitable allocation of taxing rights among States. This book provides a disruptive discourse on tax sovereignty in the field of corporate income taxation that endeavors to escape from long-standing tax policy tendencies and prejudices while considering the challenges posed by a globalized (and increasingly digitalized) economy. In particular, the book offers an innovative perspective on certain deep-rooted paradigms historically underlying corporate income taxation: - tax treatment of related parties within a corporate group along with the arm’s-length standard; - corporate tax residence standards; and - definition of source for corporate income tax purposes, with a particular emphasis on the permanent establishment concept. The book explores their respective origins, supposed tax policy rationales, structural problems and interactions; ultimately showing how the way tax jurisdiction is currently defined through them inherently tends to trigger profit shifting outcomes. In view of the conclusions of the study, the author suggests the use of a new version of the traditional benefit principle (the “presumptive benefit principle”) that would contribute to address the profit shifting phenomenon while serving as a practical guideline to achieve a more equitable allocation of taxing rights among jurisdictions. Finally, the book submits a number of proposals inspired by the aforementioned guideline that aspire to strike a balance between equity, effectiveness and technical feasibility. They include a new corporate tax residence test and, most notably, a proposal on a new remote-sales permanent establishment. García Antón (book review): “The outstanding book written by Eva Escribano has the extraordinary strength to comprise past, present and (foreseeable) future of international corporate taxation in less than 300 pages. Her analysis eschews the shallowness of our modern times to dissect the crumbling paradigms of international taxation and searches for new Tables of the Law" "Few books in the international tax arena have the ability to fully fledged offer the reader a compelling explanation of the causes of the “evil” and at the same time propose solutions rooted in a historic principle, such as the presumptive benefit principle, that go beyond mere patchworks. Accordingly, I am sure that her book will become a “must” reading for scholars, policymakers, tax advisors and students, who approach our thrilling discipline for the first time".Depto. de Derecho Mercantil, Financiero y TributarioFac. de DerechoTRUEpu

Alternative approaches to address the (yet to be defined) treaty shopping phenomenon

The present article intends to provide alternative solutions beyond the traditional countermeasures to counteract the treaty shopping phenomenon. It departs from the premise that the treaty shopping phenomenon has never been accurately defined, a fact that significantly conditions – and hinders – the process of conceiving measures to address it. Be that as it may, the paper briefly summarizes the key features of its three most paradigmatic countermeasures (beneficial ownership, limitation on benefits (LOBs) clauses and the principal purpose test) and further notes that the recently advocated international expansion of the latter two may not be appropriate (section 1). In this context, the paper advocates for four alternative approaches to neutralize treaty shopping. The first approach involves a reconsideration of domestic corporate tax residence tests, whose configuration ought to be regarded as the genuine ultimate root of treaty shopping concerns (section 2.1). The second and third involve a (re)interpretation and a minor amendment of Article 4.1 of tax treaties respectively (sections 2.2 and 2.3). The last one entails the adoption of a more targeted LOB clause (section 2.4). The first and fourth approaches rely on a specific (and personal) perception of the treaty shopping phenomenon (section 2.1).Ministerio de Economía y CompetitividadDepto. de Derecho Mercantil, Financiero y TributarioFac. de DerechoTRUEpu

Soluble ST2 as a New Oxidative Stress and Inflammation Marker in Metabolic Syndrome

Background: Metabolic syndrome (MS) is a complex and prevalent disorder. Oxidative stress and inflammation might contribute to the progression of MS. Soluble ST2 (sST2) is an attractive and druggable molecule that sits at the interface between inflammation, oxidative stress and fibrosis. This study aims to analyze the relationship among sST2, oxidative stress, inflammation and echocardiographic parameters in MS patients. Methods: Fifty-eight patients with MS were recruited and underwent physical, laboratory and transthoracic echocardiography examinations. Commercial ELISA and appropriate colorimetric assays were used to quantify serum levels of oxidative stress and inflammation markers and sST2. Results: Circulating sST2 was increased in MS patients and was significantly correlated with the oxidative stress markers nitrotyrosine and 8-hydroxy-2&prime;-deoxyguanosine as well as with peroxide levels. The inflammatory parameters interleukin-6, intercellular adhesion molecule-1 and myeloperoxidase were positively correlated with sST2. Noteworthy, sST2 was positively correlated with left ventricular mass, filling pressures and pulmonary arterial pressures. Conclusion: Circulating levels of sST2 are associated with oxidative stress and inflammation burden and may underlie the pathological remodeling and dysfunction of the heart in MS patients. Our results suggest that sST2 elevation precedes diastolic dysfunction, emerging as an attractive biotarget in MS

Monkeypox virus genomic accordion strategies

The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.We would like to thank the work of the Rapid Response Unit of the National Center for Microbiology, especially MªJosé Buitrago, and Cristobal Belda, ISCIII General Director. We also thank Anya Crane (Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health) for critically editing the manuscript and Jiro Wada (Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health) for helping with figure preparation. The work for this study performed at Instituto de Salud Carlos III was partially funded by Acción Estratégica “Impacto clínico y microbiológico del brote por el virus de la viruela del mono en pacientes en España (2022): proyecto multicéntrico MONKPOX-ESP22” (CIBERINFEC) (M.P.S.S.). The work for this study done at the Icahn School of Medicine at Mount Sinai Department of Microbiology as part of Global Health Emerging Pathogen Institute activities was funded by institutional funds (G.P.) from the Icahn School of Medicine at Mount Sinai Department of Microbiology in support of Global Health Emerging Pathogen Institute activities. This work was also supported in part through Laulima Govern ment Solutions, LLC, prime contract with the U.S. National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272201800013C. J.H.K. performed this work as an employee of Tunnell Government Services (TGS), a subcontractor of Laulima Government Solutions, LLC, under Contract No. HHSN272201800013C. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army. The views and conclusions contained in this document are those of the authors and should not be interpreted as necessarily representing the official policies, either expressed or implied, of the U.S. Department of Health and Human Services or of the institutions and companies affiliated with the authors, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.S

Совместная работа в виртуальных средах с помощью проблемно-ориентированного обучения

El objetivo es potenciar una competencia crucial como es el trabajo colaborativo y en equipo de los alumnos mediante la utilización de entornos virtuales en el aprendizaje en las enseñanzas universitarias basado en problemas Resulta innegable que el trabajo en equipo y colaborativo fomenta la motivación de los estudiantes y favorece el aprendizaje, debido al propio efecto social que genera la pertenencia a un grupo. Contribuyendo, asimismo, al desarrollo de la capacidad de debate y argumentación, el razonamiento crítico y creativo o la organización de procesos de trabajo complejos, entre otras muchas competencias esenciales. El proyecto pone el foco en el trabajo colaborativo en entornos digitales dentro del aprendizaje basado en problemas y persigue favorecer un modelo de aprendizaje más participativo, mediante el uso de los recursos que nos ofrecen las nuevas tecnologías de la comunicación, aumentando la interacción de los estudiantes, incluso en entornos digitales. El trabajo colaborativo supone la creación de grupos integrados por varios estudiantes con, a priori, el mismo nivel formativo, y con una asunción compartida del liderazgo y la responsabilidad en el proceso de aprendizaje. El trabajo colaborativo se basa, además, en la autonomía de trabajo de sus integrantes que presentan funcionalidades y competencias heterogéneas, y que tienen que desarrollar y fortalecer elementos como la confianza, la comunicación, la gestión de conflictos y solución de problemas y la adopción de decisiones.The aim is to enhance a crucial competence such as collaborative and teamwork of students through the use of virtual environments in problem-based learning in university education. It is undeniable that team and collaborative work fosters students' motivation and favours learning, due to the very social effect that belonging to a group generates. It also contributes to the development of debate and argumentation skills, critical and creative reasoning or the organisation of complex work processes, among many other essential competences. The project focuses on collaborative work in digital environments within problem-based learning and aims to promote a more participatory learning model, through the use of the resources offered by new communication technologies, increasing student interaction, even in digital environments. Collaborative work involves the creation of groups made up of several students with, a priori, the same level of training, and with a shared assumption of leadership and responsibility in the learning process. Collaborative work is also based on the working autonomy of its members, who have heterogeneous functionalities and competences, and who have to develop and strengthen elements such as trust, communication, conflict management and problem solving and decision-making.L'obiettivo è quello di migliorare una competenza cruciale come il lavoro collaborativo e di gruppo degli studenti attraverso l'uso di ambienti virtuali nell'apprendimento basato su problemi nell'istruzione universitaria. È innegabile che il lavoro di gruppo e collaborativo promuova la motivazione degli studenti e favorisca l'apprendimento, proprio per l'effetto sociale che l'appartenenza a un gruppo genera. Contribuisce inoltre allo sviluppo delle capacità di discussione e argomentazione, del ragionamento critico e creativo o dell'organizzazione di processi di lavoro complessi, oltre a molte altre competenze essenziali. Il progetto si concentra sul lavoro collaborativo in ambienti digitali nell'ambito dell'apprendimento basato su problemi e mira a promuovere un modello di apprendimento più partecipativo, attraverso l'uso delle risorse offerte dalle nuove tecnologie di comunicazione, aumentando l'interazione degli studenti, anche in ambienti digitali. Il lavoro collaborativo prevede la creazione di gruppi composti da più studenti con, a priori, lo stesso livello di formazione e con un'assunzione condivisa di leadership e responsabilità nel processo di apprendimento. Il lavoro collaborativo si basa anche sull'autonomia di lavoro dei suoi membri, che hanno funzionalità e competenze eterogenee e devono sviluppare e rafforzare elementi come la fiducia, la comunicazione, la gestione dei conflitti, la risoluzione dei problemi e il processo decisionale.L'objectif est d'améliorer une compétence cruciale telle que le travail collaboratif et d'équipe des étudiants par l'utilisation d'environnements virtuels dans l'apprentissage par problème dans l'enseignement universitaire. Il est indéniable que le travail en équipe et en collaboration stimule la motivation des élèves et favorise l'apprentissage, en raison de l'effet social même que génère l'appartenance à un groupe. Elle contribue également au développement des capacités de débat et d'argumentation, du raisonnement critique et créatif ou de l'organisation de processus de travail complexes, parmi de nombreuses autres compétences essentielles. Le projet se concentre sur le travail collaboratif dans les environnements numériques dans le cadre de l'apprentissage par problèmes et vise à promouvoir un modèle d'apprentissage plus participatif grâce à l'utilisation des ressources offertes par les nouvelles technologies de communication, en augmentant l'interaction des étudiants, même dans les environnements numériques. Le travail collaboratif implique la création de groupes composés de plusieurs étudiants ayant, a priori, le même niveau de formation, et assumant ensemble le leadership et la responsabilité du processus d'apprentissage. Le travail collaboratif repose également sur l'autonomie de travail de ses membres, qui ont des fonctionnalités et des compétences hétérogènes, et qui doivent développer et renforcer des éléments tels que la confiance, la communication, la gestion des conflits, la résolution de problèmes et la prise de décision.Ziel ist es, durch den Einsatz virtueller Umgebungen beim problembasierten Lernen in der Hochschulbildung eine entscheidende Kompetenz wie die Zusammenarbeit und die Teamarbeit von Studierenden zu fördern. Es ist unbestreitbar, dass Team- und Kooperationsarbeit die Motivation der Schüler fördert und das Lernen begünstigt, und zwar aufgrund des sozialen Effekts, den die Zugehörigkeit zu einer Gruppe bewirkt. Sie trägt auch zur Entwicklung von Diskussions- und Argumentationsfähigkeiten, kritischem und kreativem Denken oder der Organisation komplexer Arbeitsprozesse bei, neben vielen anderen wichtigen Kompetenzen. Das Projekt konzentriert sich auf die kollaborative Arbeit in digitalen Umgebungen im Rahmen des problembasierten Lernens und zielt darauf ab, ein partizipativeres Lernmodell zu fördern, indem die von den neuen Kommunikationstechnologien gebotenen Ressourcen genutzt werden und die Interaktion zwischen den Studierenden auch in digitalen Umgebungen verstärkt wird. Bei der Zusammenarbeit werden Gruppen gebildet, die sich aus mehreren Studenten zusammensetzen, die von vornherein das gleiche Ausbildungsniveau haben und die gemeinsam die Leitung und Verantwortung für den Lernprozess übernehmen. Die Zusammenarbeit beruht auch auf der Arbeitsautonomie ihrer Mitglieder, die über heterogene Funktionen und Kompetenzen verfügen und Elemente wie Vertrauen, Kommunikation, Konfliktmanagement, Problemlösung und Entscheidungsfindung entwickeln und stärken müssen.O objectivo é reforçar uma competência crucial como a colaboração e o trabalho de equipa dos estudantes através da utilização de ambientes virtuais na aprendizagem baseada em problemas no ensino universitário. É inegável que o trabalho em equipa e em colaboração promove a motivação dos estudantes e favorece a aprendizagem, devido ao próprio efeito social que a pertença a um grupo gera. Também contribui para o desenvolvimento de capacidades de debate e argumentação, de raciocínio crítico e criativo ou para a organização de processos de trabalho complexos, entre muitas outras competências essenciais. O projecto centra-se no trabalho colaborativo em ambientes digitais no âmbito da aprendizagem baseada em problemas e visa promover um modelo de aprendizagem mais participativo através da utilização dos recursos oferecidos pelas novas tecnologias de comunicação, aumentando a interacção dos estudantes, mesmo em ambientes digitais. O trabalho colaborativo envolve a criação de grupos compostos por vários estudantes com, a priori, o mesmo nível de formação, e com uma assunção partilhada de liderança e responsabilidade no processo de aprendizagem. O trabalho colaborativo baseia-se também na autonomia de trabalho dos seus membros, que têm funcionalidades e competências heterogéneas, e que têm de desenvolver e reforçar elementos tais como confiança, comunicação, gestão de conflitos e resolução de problemas e tomada de decisões.Цель - повысить такую важную компетенцию, как совместная и командная работа студентов посредством использования виртуальных сред в проблемно-ориентированном обучении в университетском образовании. Неоспоримо, что командная и совместная работа повышает мотивацию учащихся и способствует обучению, благодаря тому самому социальному эффекту, который порождает принадлежность к группе. Она также способствует развитию навыков ведения дискуссий и аргументации, критического и творческого мышления или организации сложных рабочих процессов, а также многих других важных компетенций. Проект сосредоточен на совместной работе в цифровой среде в рамках проблемно-ориентированного обучения и направлен на продвижение модели обучения с более широким участием, посредством использования ресурсов, предлагаемых новыми коммуникационными технологиями, увеличивая взаимодействие студентов даже в цифровой среде. Совместная работа предполагает создание групп, состоящих из нескольких студентов, имеющих априори одинаковый уровень подготовки, и совместно принимающих на себя руководство и ответственность в процессе обучения. Совместная работа также основана на рабочей автономии ее членов, которые обладают разнородными функциональными возможностями и компетенциями, и которые должны развивать и укреплять такие элементы, как доверие, коммуникация, управление конфликтами, решение проблем и принятие решений.Depto. de Derecho del Trabajo y Seguridad SocialFac. de DerechoFALSEUniversidad Complutense de Madridsubmitte

Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trialResearch in context

Summary: Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols