Time-weighted lactate as a predictor of adverse outcome in acute heart failure

The role of dynamic changes in lactate concentrations on prognosis in acute heart failure has been poorly investigated. The aim of this study was to explore the predictive value of 24 h time-weighted lactate (LACTW ) in patients with acute heart failure

Long-term sustainability of a distributed RI: the EPOS case

The European Plate Observing System (EPOS) is a distributed research infrastructure (RI) with the mission to establish and maintain sustainable and long-term access to solid Earth science data and services by integrating the diverse national research infrastructures under a common federated framework governed by EPOS ERIC (European Research Infrastructure Consortium). This paper presents the EPOS approach to ensure financial viability and to tackle the challenge of long-term sustainability of the RI during its operational phase. The EPOS approach to sustainable operation considers the scientific impact and the promotion of scientific research as the preconditions to achieve long-term sustainability. Enabling scientific excellence implies that high-quality data and services are provided reliably and continuously to establish the RI as the enabler of investigations to solid Earth scientists. The strategic approach and the solutions adopted by EPOS ERIC to address the long-term sustainability of a pan-European distributed RI are discussed in this paper focusing on the governance structure, considered as the qualifying dimension that gathers and connects the financial, legal and technical dimensions. The governance and the financial models are discussed to delineate the legal framework necessary to operate the EPOS RI relying on the implemented technical solutions. A sufficiently stable investment environment is necessary to allow the RI to concentrate on providing high quality services for their user communities. This paper discusses the current actions and challenges to be addressed for achieving this goal.publishedVersio

Data Management in Distributed, Federated Research Infrastructures: The Case of EPOS

Data management is a key activity when Open Data stewardship through services complying with the FAIR principles is required, as it happens in many National and European initiatives. Existing guidelines and tools facilitate the drafting of Data Management Plans by focusing on a set of common parameters or questions. In this paper we describe how data management is carried out in EPOS, the European Research Infrastructure for providing access to integrated data and services in the solid Earth domain. EPOS relies on a federated model and is committed to remain operational in the long term. In EPOS, five key dimensions were identified for the Federated Data Management, namely the management of: thematic data; e-infrastructure for data integration; community of data providers committed to data provision processes; sustainability; and policies. On the basis of the EPOS experience, which is to some extent applicable to other research infrastructures, we propose additional components that may extend the EU Horizon 2020 Data Management Guidelines template, thus comprehensively addressing the Federated Data Management in the context of distributed Research Infrastructures

Ethical Criteria for the Admission and Management of Patients in the ICU Under Conditions of Limited Medical Resources: A Shared International Proposal in View of the COVID-19 Pandemic

Introduction The present pandemic has exposed us to unprecedented challenges that need to be addressed not just for the current state, but also for possible future similar occurrences. It is worth pointing out that discussions on the allocation of medical resources may not necessarily refer to an exception, but, unfortunately, to a regular condition for a large part of humanity (1). The criteria for admission to an Intensive Care Unit (ICU) setting generally take into account multiple factors. There must be a diagnostic and prognostic basis for the decisions made, considering both biological factors and patient values and wishes. Furthermore, the decision-making process should, whenever possible, respect the patient's advance directives as well as the relationship with the patient's family or attorney. Therapeutic neglect should be avoided. Having applied standard clinical evaluation criteria for the appropriate treatment of patients with COVID-19, including consideration of prognosis, if a hospital then finds itself unable to provide optimal treatment (e.g., due to a disproportion between the number of patients and the availability of beds, healthcare providers, ventilators, and drugs in the ICU), it becomes necessary to evaluate, case by case, how to achieve justice and the best possible good for the greatest number of patients. It is therefore mandatory to explore alternative solutions; these include increasing available beds and healthcare providers, implementing alternative, though suboptimal, approaches (where appropriate), transferring patients to other clinical units, etc. Making these decisions properly also involves the recovery of the political role of medicine and science (2). If the imbalance between needs and resources reaches a critical level, an emergency triage protocol, following the operational and ethical indications of “disaster medicine,” should be activated. These have been deployed in major and serious natural (earthquakes or tsunamis for example) and technological (factory explosions, public transport accidents for example) disasters, as well as following terrorist attacks (3, 4). The question of the feasibility of developing a clinical evaluation algorithm to support the decision-making of the triage team remains open, though many such protocols have been written. According to the above, we propose the following five ethical criteria for the triage of patients in conditions of limited resources, such as the COVID pandemic. They are the result of an interdisciplinary and intercultural dialogue between specialists from different disciplines. Several of the authors are working in the main epicenters of the crisis and currently are playing a central role in the bioethical, clinical, social and legal aspects of the management of the COVID-19 pandemic

Hyperactive HRAS dysregulates energetic metabolism in fibroblasts from patients with Costello syndrome via enhanced production of reactive oxidizing species

Germline-activating mutations in HRAS cause Costello syndrome (CS), a cancer prone multisystem disorder characterized by reduced postnatal growth. In CS, poor weight gain and growth are not caused by low caloric intake. Here, we show that constitutive plasma membrane translocation and activation of the GLUT4 glucose transporter, via reactive oxygen species-dependent AMP-activated protein kinase α and p38 hyperactivation, occurs in primary fibroblasts of CS patients, resulting in accelerated glycolysis and increased fatty acid synthesis and storage as lipid droplets. An accelerated autophagic flux was also identified as contributing to the increased energetic expenditure in CS. Concomitant inhibition of p38 and PI3K signaling by wortmannin was able to rescue both the dysregulated glucose intake and accelerated autophagic flux. Our findings provide a mechanistic link between upregulated HRAS function, defective growth and increased resting energetic expenditure in CS, and document that targeting p38 and PI3K signaling is able to revert this metabolic dysfunction.n

Studio e sviluppo di un nuovo guidance channel biodegradabile per interfacce neurali rigenerative

La lesione del nervo periferico (PNI) è un danno comune che interessa individui di ogni ceto sociale e provoca in molti pazienti disabilità permanenti. L’obiettivo di questo lavoro di tesi consiste nella realizzazione e caratterizzazione di un canale guida nervoso (NGC) biodegradabile e biocompatibile, come supporto di un elettrodo di un’interfaccia neurale rigenerativa, capace di: fornire supporto meccanico per le nuove fibre rigenerative; guidare gli assoni rigenerati dal moncone del nervo prossimale a quello distale; consentire lo scambio di nutrienti e delle sostanze di scarto con l’ambiente esterno; evitare l'infiltrazione del tessuto fibrotico; comportarsi come un canale che consenta la diffusione di fattori neurotropici e neurotrofici secreti dai monconi nervosi; consentire la suturazione stabile dell’NCG sui monconi del nervo danneggiato nella fase di impianto; accogliere e fornire supporto meccanico a lungo termine per un elettrodo di tipo thin-film. Idealmente, l’NGC realizzato può fornire un microambiente adeguato per la rigenerazione del nervo riducendo la formazione del neuroma, di cicatrici e il germogliamento collaterale dei nuovi assoni. Inoltre, poiché i fattori neurotrofici secreti dai monconi rimangono intrappolati all'interno del condotto, si verifica un accumulo che determina una maggiore concentrazione di tali molecole che favoriscono la rigenerazione nervosa

Immagini di sé in adolescenza

Lo scopo della ricerca è quello di indagare in primo luogo le modalità attraverso cui soggetti in età adolescenziale tendono a descrivere spontaneamente se stessi e successivamente confrontare tali rappresentazioni con quelle emergenti da questionari strutturati di personalità e con la reputazione nel gruppo dei pari. Lo studio è stato condotto con 378 ragazzi (263 maschi e 115 femmine), età media 14.5 anni, frequentanti il primo anno di scuola superiore (2 licei e 2 istituti professionali). Ogni soggetto è stato invitato a compilare il questionario di Kuhn e McParland (1954) "Twenty statements" in cui veniva richiesto di rispondere per 20 volte alla domanda aperta "Chi sono io?". Successivamente è stato somministrato un questionario per valutare l'immagine di sè (Offer Self-Image Questionnaire) e una scala di nomina per valutare l'opinione dei compagni sulle dimesnioni dell'aggressività, del ritiro sociale e delle abilità sociali. per ciascun soggetto è stato poi rilevato il profitto scolastico di fine anno. Una prima analisi dei risultati delle risposte al "Twenty statements" mette in evidenza che circa il 70% delle descrizioni di sè sono di tipo attributivo, ovverosia i ragazzi tendono a presentarsi attraverso termini che fanno riferimento a caratteristiche personali (es. simpatico, disponibile, intelligente, timido, ecc.); percentuali inferiori (10% rispettivamente) fanno riferimento a categorie di tipo fisico (es., forte, atletico, slanciato, ecc.) e sociale (es. studente, italiano, figlio, ecc.). Ancora più basse le percentuali riferite ad altre categorie. Oltre il 60% delle risposte ha una valenza di tipo positivo, senza distinzioni di genere, mentre nei maschi sono prevalenti rispetto alle femmine risposte di tipo neutrale (es. sono uno studente, sono tifoso, ecc.). Questo risultato relativo ad una positiva immagine di sè in adolescenza conferma quanto riscontrato da altri studi empirici e coincide con le risposte all'Offer Self Image. Tuttavia, appaiono alcune differenze rispetto a quanto rilevato da numerose ricerche effettuate con strumenti self-report in relazione al risultato scolastico. In particolare, il modo in cui gli adolescenti descrivono spontaneamente se stessi non sembra differenziare i soggetti in rapporto al migliore o peggiore risultato. L'elaborazione dei dati tutt'ora in corso consentirà di evidenziare ulteriori convergenze o divergenze tra i due metodi di valutazione