Nusinersen treatment and cerebrospinal fluid neurofilaments : An explorative study on Spinal Muscular Atrophy type 3 patients

The antisense oligonucleotide Nusinersen has been recently licensed to treat spinal muscular atrophy (SMA). Since SMA type 3 is characterized by variable phenotype and milder progression, biomarkers of early treatment response are urgently needed. We investigated the cerebrospinal fluid (CSF) concentration of neurofilaments in SMA type 3 patients treated with Nusinersen as a potential biomarker of treatment efficacy. The concentration of phosphorylated neurofilaments heavy chain (pNfH) and light chain (NfL) in the CSF of SMA type 3 patients was evaluated before and after six months since the first Nusinersen administration, performed with commercially available enzyme-linked immunosorbent assay (ELISA) kits. Clinical evaluation of SMA patients was performed with standardized motor function scales. Baseline neurofilament levels in patients were comparable to controls, but significantly decreased after six months of treatment, while motor functions were only marginally ameliorated. No significant correlation was observed between the change in motor functions and that of neurofilaments over time. The reduction of neurofilament levels suggests a possible early biochemical effect of treatment on axonal degeneration, which may precede changes in motor performance. Our study mandates further investigations to assess neurofilaments as a marker of treatment response

Supporting people with type 2 diabetes in effective use of their medicine through mobile health technology integrated with clinical care (SuMMiT-D Feasibility): a randomised feasibility trial protocol

Introduction: Type 2 diabetes is common, affecting over 400 million people worldwide. Risk of serious complications can be reduced through use of effective treatments and active self-management. However, people are often concerned about starting new medicines and face difficulties in taking them regularly. Use of brief messages to provide education and support self-management, delivered through mobile phone-based text-messages can be an effective tool for some long-term conditions. We have developed messages aiming to support patients’ self-management of type 2 diabetes in the use of medications and other aspects of self-management, underpinned by theory and evidence. The aim of this trial is to determine the feasibility of a large-scale clinical trial to test the effectiveness and cost-effectiveness of the intervention, compared to usual care. Methods and analysis: The feasibility trial will be a multi-centre individually randomised, controlled trial in primary care recruiting adults (≥35 years) with type 2 diabetes in England. Consenting participants will be randomised to receive short text-messages three times a week with messages designed to produce change in medication adherence or non-health related messages for six months. The aims are to test recruitment methods, retention to the study, the feasibility of data collection and the mobile-phone and web-based processes of a proposed definitive trial and to refine the text messaging intervention. The primary outcome is the rate of recruitment to randomisation of participants to the trial. Data, including patient reported measures, will be collected online at baseline and the end of the six-month follow-up period. With 200 participants (100 in each group), this trial is powered to estimate 80% follow up within 95% confidence intervals of 73.8% to 85.3%. The analysis will follow a pre-specified plan. Ethics and Dissemination: Ethics approval was obtained from the West of Scotland Research Ethics Committee 05. The results will be disseminated through conference presentations, peer-reviewed journals and will be published on the trial website: www.summit-d.org.</p

On Collaborator Selection in Creative Agent Societies : An Evolutionary Art Case Study

We study how artistically creative agents may learn to select favorable collaboration partners. We consider a society of creative agents with varying skills and aesthetic preferences able to interact with each other by exchanging artifacts or through collaboration. The agents exhibit interaction awareness by modeling their peers and make decisions about collaboration based on the learned peer models. To test the peer models, we devise an experimental collaboration process for evolutionary art, where two agents create an artifact by evolving the same artifact set in turns. In an empirical evaluation, we focus on how effective peer models are in selecting collaboration partners and compare the results to a baseline where agents select collaboration partners randomly. We observe that peer models guide the agents to more beneficial collaborations.Peer reviewe

A geo-chemo-mechanical study of a highly polluted marine system (Taranto, Italy) for the enhancement of the conceptual site model

The paper presents the results of the analysis of the geo-chemo-mechanical data gathered through an innovative multidisciplinary investigation campaign in the Mar Piccolo basin, a heavily polluted marine bay aside the town of Taranto (Southern Italy). The basin is part of an area declared at high environmental risk by the Italian government. The cutting-edge approach to the environmental characterization of the site was promoted by the Special Commissioner for urgent measures of reclamation, environmental improvements and redevelopment of Taranto and involved experts from several research fields, who cooperated to gather a new insight into the origin, distribution, mobility and fate of the contaminants within the basin. The investigation campaign was designed to implement advanced research methodologies and testing strategies. Differently from traditional investigation campaigns, aimed solely at the assessment of the contamination state within sediments lying in the top layers, the new campaign provided an interpretation of the geo-chemo-mechanical properties and state of the sediments forming the deposit at the seafloor. The integrated, multidisciplinary and holistic approach, that considered geotechnical engineering, electrical and electronical engineering, geological, sedimentological, mineralogical, hydraulic engineering, hydrological, chemical, geochemical, biological fields, supported a comprehensive understanding of the influence of the contamination on the hydro-mechanical properties of the sediments, which need to be accounted for in the selection and design of the risk mitigation measures. The findings of the research represent the input ingredients of the conceptual model of the site, premise to model the evolutionary contamination scenarios within the basin, of guidance for the environmental risk management. The study testifies the importance of the cooperative approach among researchers of different fields to fulfil the interpretation of complex polluted eco-systems

Syndromics: A Bioinformatics Approach for Neurotrauma Research

Substantial scientific progress has been made in the past 50 years in delineating many of the biological mechanisms involved in the primary and secondary injuries following trauma to the spinal cord and brain. These advances have highlighted numerous potential therapeutic approaches that may help restore function after injury. Despite these advances, bench-to-bedside translation has remained elusive. Translational testing of novel therapies requires standardized measures of function for comparison across different laboratories, paradigms, and species. Although numerous functional assessments have been developed in animal models, it remains unclear how to best integrate this information to describe the complete translational “syndrome” produced by neurotrauma. The present paper describes a multivariate statistical framework for integrating diverse neurotrauma data and reviews the few papers to date that have taken an information-intensive approach for basic neurotrauma research. We argue that these papers can be described as the seminal works of a new field that we call “syndromics”, which aim to apply informatics tools to disease models to characterize the full set of mechanistic inter-relationships from multi-scale data. In the future, centralized databases of raw neurotrauma data will enable better syndromic approaches and aid future translational research, leading to more efficient testing regimens and more clinically relevant findings

Reporting guideline for the early stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI

A growing number of artificial intelligence (AI)-based clinical decision support systems are showing promising performance in preclinical, in silico, evaluation, but few have yet demonstrated real benefit to patient care. Early stage clinical evaluation is important to assess an AI system’s actual clinical performance at small scale, ensure its safety, evaluate the human factors surrounding its use, and pave the way to further large scale trials. However, the reporting of these early studies remains inadequate. The present statement provides a multistakeholder, consensus-based reporting guideline for the Developmental and Exploratory Clinical Investigations of DEcision support systems driven by Artificial Intelligence (DECIDE-AI). We conducted a two round, modified Delphi process to collect and analyse expert opinion on the reporting of early clinical evaluation of AI systems. Experts were recruited from 20 predefined stakeholder categories. The final composition and wording of the guideline was determined at a virtual consensus meeting. The checklist and the Explanation & Elaboration (E&E) sections were refined based on feedback from a qualitative evaluation process. 123 experts participated in the first round of Delphi, 138 in the second, 16 in the consensus meeting, and 16 in the qualitative evaluation. The DECIDE-AI reporting guideline comprises 17 AI specific reporting items (made of 28 subitems) and 10 generic reporting items, with an E&E paragraph provided for each. Through consultation and consensus with a range of stakeholders, we have developed a guideline comprising key items that should be reported in early stage clinical studies of AI-based decision support systems in healthcare. By providing an actionable checklist of minimal reporting items, the DECIDE-AI guideline will facilitate the appraisal of these studies and replicability of their findings

Σεληνιάζομαι en Mateo 17,15: Anotaciones filológicas y propuesta de traducción

Translating consists in reproducing in the receptor language the closestnatural equivalent of the source-language message, first in terms ofmeaning and secondly in terms of style.A conscientious translator will want the closest natural equivalent.Eugene A. Nida y Charles R. TaberThe context does not merely help us understand meaning—itvirtually makes meaning.Moisés Silva. A diferencia de Marcos (9,14-29) y de Lucas (9,37-43), que atribuyen explícitamente la enfermedad a un “espíritu mudo” (πνεῦμα ἄλαλον) y a un “espíritu” (πνεῦμα) respectivamente, la caracterización de la afección del muchacho en Mateo 17,15 se da con el inusual σεληνιάζομαι que la mayoría de los traductores y comentaristas traducen como “epiléptico”, y otros, más apegados a la etimología, como “lunático”.1 Incluso algunos, con claros visos de ambigüedad interpretativa, titulan la perícopa “curación de un epiléptico”, pero, a la hora de ofrecer una traducción, se inclinan por “lunático”. El siguiente comentario de Ulrich Luz es sintomático: Moon sickness is epilepsy, the “holy illness” that according to a widespread view in antiquity could be caused by the moon goddess Selene and be connected with the phases of the moon. In antiquity epilepsy was explained either as a supernatural phenomenon—as“being possessed” (ἐπιληψία) by a divine power (=“ἱερῆς νούσου”) or by demons—or in medical literature as a natural illness that “does not seem to be more divine or holy than other illnesses”.3 Ahora bien, la traducción de σεληνιάζομαι en Mateo 17,15 resulta compleja por cuatro motivos: (1) por ser un lexema de baja frecuencia, propio del idiolecto mateano (Mt 4,24 y 17,15); (2) por consideraciones etimológicas, a saber, las disímiles connotaciones del término σελήνη/ Luna en la antigüedad; (3)en el versículo 15, y a diferencia de Lucas 9,39, se describen dos manifestaciones —caer en el fuego y en el agua— que no necesariamente están asociadas con ataques epilépticos;4 (4)en el versículo 18, el evangelista describe el accionar jesuano como un exorcismo. A juzgar por el conjunto de estos datos, no resulta evidente justificar la traducción de σεληνιάζομαι en Mateo 17,15 —y, por consiguiente, en Mateo 4,24— por“epiléptico”..