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•Le stockage, étape la plus à risque de la perte de stérilité dans le temps.•Sachets : passage de la date limite d’utilisation de deux à quatre mois.•Pliages : passage de la date limite d’utilisation de deux à six mois.•Conteneurs : maintien de la date limite d’utilisation à six mois.•Impact positif de l’augmentation de la date limite d’utilisation.

Los indicadores del estado de pandemia se han basado en el número total de casos diagnosticados de la COVID-19, el número de personas hospitalizadas o en unidades de cuidados intensivos y los fallecimientos por la infección. El objetivo de este estudio es describir los datos disponibles sobre pruebas diagnósticas, servicio sanitario utilizado para el diagnóstico de COVID-19 y seguimiento/detección de casos.

Understanding the mechanisms of charge transport (CT) across biomolecules in solid-state devices is imperative to realize biomolecular electronic devices in a predictive manner. Although it is well-accepted that biomolecule–electrode interactions play an essential role, it is often overlooked. This paper reveals the prominent role of graphene interfaces with Fe-storing proteins in the net CT across their tunnel junctions. Here, ferritin (AfFtn-AA) is adsorbed on the graphene by noncovalent amine–graphene interactions confirmed with Raman spectroscopy. In contrast to junctions with metal electrodes, graphene has a vanishing density of states toward its intrinsic Fermi level (“Dirac point”), which increases away from the Fermi level. Therefore, the amount of charge carriers is highly sensitive to temperature and electrostatic charging (induced doping), as deduced from a detailed analysis of CT as a function of temperature and iron loading. Remarkably, the temperature dependence can be fully explained within the coherent tunneling regime due to excitation of hot carriers. Graphene is not only demonstrated as an alternative platform to study CT across biomolecular tunnel junctions, but it also opens rich possibilities in employing interface electrostatics in tuning CT behavior.

Liquid metal droplets, such as eutectic gallium–indium (EGaIn), are important in many research areas, such as soft electronics, catalysis, and energy storage. Droplet contact on solid surfaces is typically achieved without control over the applied force and without optimizing the wetting properties in different environments (e.g., in air or liquid), resulting in poorly defined contact areas. In this work, we demonstrate the direct manipulation of EGaIn microdroplets using an atomic force microscope (AFM) to generate repeated, on-demand making and breaking of contact on self-assembled monolayers (SAMs) of alkanethiols. The nanoscale positional control and feedback loop in an AFM allow us to control the contact force at the nanonewton level and, consequently, tune the droplet contact areas at the micrometer length scale in both air and ethanol. When submerged in ethanol, the droplets are highly nonwetting, resulting in hysteresis-free contact forces and minimal adhesion; as a result, we are able to create reproducible geometric contact areas of 0.8–4.5 μm2with the alkanethiolate SAMs in ethanol. In contrast, there is a larger hysteresis in the contact forces and larger adhesion for the same EGaIn droplet in air, which reduced the control over the contact area (4–12 μm2). We demonstrate the usefulness of the technique and of the gained insights in EGaIn contact mechanics by making well-defined molecular tunneling junctions based on alkanethiolate SAMs with small geometric contact areas of between 4 and 12 μm2in air, 1 to 2 orders of magnitude smaller than previously achieved.

ABSTRACTBackgroundThe frequency of low-value practices (LVPs) in the healthcare system is a worldwide challenge. This study aimed to evaluate the LVPs trend in Spanish primary care (PC), its frequency in both sexes, and estimate its related extra cost.MethodsA multicentric, retrospective, and national research project was conducted. Ten LVPs highly frequent and potentially harmful for patients were analyzed (majority of them related to prescription). Algorithms were applied to collect the data from 28,872,851 episodes registered into national databases (2015–2017).ResultsLVPs registered a total of 7,160,952 (26.5%) episodes plus a total of 259,326 avoidable PSA screening tests. In adults, a high frequency was found for inadequate prescription of paracetamol antibiotics, and benzodiazepines . Women received more jeopardizing practices (p ≤ 0.001). Pediatrics presented a downward of antibiotic and paracetamol-ibuprofen prescription combination. The estimated extra cost was close to €292 million (2.8% of the total cost in PC).ConclusionLVPs reduction during the analyzed period was moderate compared to studies following ‘Choosing Wisely list’ of LVPs and must improve to reduce patient risk and the extra related costs.

Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive sarcoma driven by the EWSR1::WT1 chimeric transcription factor. Despite this unique oncogenic driver, DSRCT displays a polyphenotypic differentiation of unknown causality. Using single-cell multi-omics on 12 samples from five patients, we find that DSRCT tumor cells cluster into consistent subpopulations with partially overlapping lineage- and metabolism-related transcriptional programs. In vitromodeling shows that high EWSR1::WT1 DNA-binding activity associates with most lineage-related states, in contrast to glycolytic and profibrotic states. Single-cell chromatin accessibility analysis suggests that EWSR1::WT1 binding site variability may drive distinct lineage-related transcriptional programs, supporting some level of cell-intrinsic plasticity. Spatial transcriptomics reveals that glycolytic and profibrotic states specifically localize within hypoxic niches at the periphery of tumor cell islets, suggesting an additional role of tumor cell-extrinsic microenvironmental cues. We finally identify a single-cell transcriptomics-derived epithelial signature associated with improved patient survival, highlighting the clinical relevance of our findings.

Understanding and controlling the orbital alignment of molecules placed between electrodes is essential in the design of practically-applicable molecular and nanoscale electronic devices. The orbital alignment is highly determined by the molecule–electrode interface. Dependence of orbital alignment on the molecular anchor group for single molecular junctions has been intensively studied; however, when scaling-up single molecules to large parallel molecular arrays (like self-assembled monolayers (SAMs)), two challenges need to be addressed: 1. Most desired anchor groups do not form high quality SAMs. 2. It is much harder to tune the frontier molecular orbitals viaa gate voltage in SAM junctions than in single molecular junctions. In this work, we studied the effect of the molecule–electrode interface in SAMs with a micro-pore device, using a recently developed tetrapodal anchor to overcome challenge 1, and the combination of a single layered graphene top electrode with an ionic liquid gate to solve challenge 2. The zero-bias orbital alignment of different molecules was signalled by a shift in conductance minimum vs.gate voltage for molecules with different anchoring groups. Molecules with the same backbone, but a different molecule–electrode interface, were shown experimentally to have conductances that differ by a factor of 5 near zero bias. Theoretical calculations using density functional theory support the trends observed in the experimental data. This work sheds light on how to control electron transport within the HOMO–LUMO energy gap in molecular junctions and will be applicable in scaling up molecular electronic systems for future device applications.

To realize molecular-scale electrical operations beyond the von Neumann bottleneck, new types of multifunctional switches are needed that mimic self-learning or neuromorphic computing by dynamically toggling between multiple operations that depend on their past. Here, we report a molecule that switches from high to low conductance states with massive negative memristive behaviour that depends on the drive speed and number of past switching events, with all the measurements fully modelled using atomistic and analytical models. This dynamic molecular switch emulates synaptic behavior and Pavlovian learning, all within a 2.4-nm-thick layer that is three orders of magnitude thinner than a neuronal synapse. The dynamic molecular switch provides all the fundamental logic gates necessary for deep learning because of its time-domain and voltage-dependent plasticity. The synapse-mimicking multifunctional dynamic molecular switch represents an adaptable molecular-scale hardware operable in solid-state devices, and opens a pathway to simplify dynamic complex electrical operations encoded within a single ultracompact component.

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A high number of thrombotic complications have been reported in critically ill patients with coronavirus disease 2019 (COVID-19) and appear to be related to a hypercoagulable state. Evidence regarding detection, management, and monitoring of COVID-19–associated coagulopathy is still missing. We propose to describe the thrombus viscoelastic properties to investigate the mechanisms of hypercoagulability in patients with COVID-19.

Aucun traitement du rhume de l’adulte n’a réellement fait preuve d’une grande efficacité. Or, les prescriptions médicamenteuses sont nombreuses et variées, représentant à la fois un danger en termes de santé publique et de risque d’effet indésirable individuel, et un coût non justifié en termes de dépenses de santé. Après une analyse de la littérature et des données socioéconomiques, le rapport propose (i) de créer un « Observatoire national du rhume », (ii) d’améliorer la formation des médecins et des pharmaciens en se basant sur une nouvelle nosologie : l’IVVAS, (iii) de définir la place de l’antibiothérapie dans le traitement du rhume à partir des recommandations des sociétés savantes, (iv) de limiter l’usage de la corticothérapie le plus souvent inadaptée ainsi que l’usage des vasoconstricteurs en raison de leurs effets indésirables, en suggérant qu’ils ne soient délivrés que sur prescription médicale, (v) d’alerter le grand public des dangers de l’automédication et de la dangerosité et de l’inefficacité de nombreux traitements utilisés.

Patient safety in hospitals can be compromised by preventable adverse events (AE). Among the preventable AEs, hospital-acquired infections (HAIs) are one of the most burdensome, contributing to not only poorer patient outcomes but institutional burden through direct financial losses and increased patient length of stay.Technological innovations can enhance patient safety by automating tasks, introducing medication alerts, clinical reminders, improved diagnostic and consultation reports, facilitating information sharing, improving clinical decision-making, intercepting potential errors, reducing variation in practice, and managing workforce shortages as well as making complete patient data available.A multidisciplinary working group from three European countries was convened to discuss how to optimise the use of technology to reduce preventable AEs in acute care hospitals. The working group identified examples where they felt there were opportunities to streamline patient pathways, including antimicrobial stewardship, point of care testing, microbiology test reporting to streamline time from sample-taking to clinical decision and mobile automated dispensing systems, which can reduce the burden on overworked staff. The working group also discussed key factors that were critical to ensuring different stakeholders, both within and outside the hospital, could meaningfully contribute to improving patient safety. They agreed that technological approaches and advances would have limited impact without meaningful cultural changes at all levels of healthcare infrastructure to implement the benefits offered by current or future technologies.

To avoid crosstalk and suppress leakage currents in resistive random access memories (RRAMs), a resistive switch and a current rectifier (diode) are usually combined in series in a one diode–one resistor (1D–1R) RRAM. However, this complicates the design of next-generation RRAM, increases the footprint of devices and increases the operating voltage as the potential drops over two consecutive junctions1. Here, we report a molecular tunnel junction based on molecules that provide an unprecedented dual functionality of diode and variable resistor, resulting in a molecular-scale 1D–1R RRAM with a current rectification ratio of 2.5 × 104and resistive on/off ratio of 6.7 × 103, and a low drive voltage of 0.89 V. The switching relies on dimerization of redox units, resulting in hybridization of molecular orbitals accompanied by directional ion migration. This electric-field-driven molecular switch operating in the tunnelling regime enables a class of molecular devices where multiple electronic functions are preprogrammed inside a single molecular layer with a thickness of only 2 nm.

La rationalité de l’interchangeabilité des biosimilaires est basée sur de larges évidences scientifiques et de nombreuses expériences cliniques en vie réelle qui ne montrent aucun signe de baisse d’efficacité ni de tolérance différente en comparaison à la molécule princeps. La substitution des biosimilaires (acte pharmaceutique) reste cependant largement contestée dans de nombreux pays et notamment en France. Elle permettrait pourtant de réaliser de très importantes économies dans un contexte d’accélération majeure des dépenses de santé. Cette réticence n’est pas fondée au regard de la qualité des biosimilaires autorisés en Europe et de leur rigoureuse évaluation. Il est donc indispensable d’améliorer l’information des professionnels de santé et des patients sur ces biosimilaires.

El Ministerio de Sanidad, Consumo y Bienestar Social (MSCBS) desde el año 2005ha venido promoviendo, en colaboración con las comunidades autónomas (CC. AA.) y las sociedades científicas (SC), entre ellas la Sociedad Española de Calidad Asistencial (SECA), la Estrategia de seguridad del paciente (ESP). La ESP 2015-2020 desarrolla aspectos relevantes de la seguridad del paciente (SP), como la gestión del riesgo, los sistemas de notificación y el aprendizaje de incidentes, así como promueve una respuesta adecuada cuando de forma inesperada ocurre un evento adverso (EA). El presente trabajo tiene como objetivo describir la situación actual de las diferentes CC. AA: en relación con estos aspectos.

Reaction conditions allowing a stereoretentive cross-coupling of alkenyl sulfides with Grignard reagents using ligand-free Pd catalysis are discussed here. The presence of an adequately positioned OH function is a key feature that allows a Mg-promoted Lewis acid activation of the mercaptide leaving group. This easy to implement procedure actually relies on an in situ generation of stable Pd nanoparticles by simply mixing Pd2(dba)3, the Grignard reagent, and the vinyl sulfide cross-coupling partner in THF. The efficiency of this procedure has been demonstrated in a natural product total synthesis context.

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Sterically stabilized diblock copolymer nanoparticles with a well-defined spherical morphology and tunable diameter were prepared by RAFT aqueous emulsion polymerization of benzyl methacrylate at 70 °C. The steric stabilizer precursor used for these syntheses contained pendent cis-diol groups, which means that such nanoparticles can react with a suitable aldehyde-functional surface via acetal bond formation. This principle is examined herein by growing an aldehyde-functionalized polymer brush from a planar silicon wafer and studying the extent of nanoparticle adsorption onto this model substrate from aqueous solution at 25 °C using a quartz crystal microbalance (QCM). The adsorbed amount, Γ, depends on both the nanoparticle diameter and the solution pH, with minimal adsorption observed at pH 7 or 10 and substantial adsorption achieved at pH 4. Variable-temperature QCM studies provide strong evidence for chemical adsorption, while scanning electron microscopy images recorded for the nanoparticle-coated brush surface after drying indicate mean surface coverages of up to 62%. This fundamental study extends our understanding of the chemical adsorption of nanoparticles on soft substrates.

ABSTRACTSeveral inflammatory markers such as cytokines, chemokines, and microRNAs (miRNAs) are well known to be induced during obesity and are strongly linked to their comorbidities. Among many others factors, the micronutrient status is suspected to reduce obesity-associated inflammation via blunting inflammatory signalling pathways. This is notably the case for active forms of vitamin A (all-trans retinoic acid ATRA) and vitamin D (1,25(OH)2D) as previously shown. In the present study, we aimed to implement a new bioinformatics approach to unveil commonly regulated signalling pathways through a combination of gene and miRNA expression sets impacted by ATRA and 1,25(OH)2D in adipocytes. In a first set of experiments, we focused only our attention on ATRA and demonstrated that it reduced LPS-mediated miRNA expression (miR-146a, miR-150, and miR-155) in mouse adipose tissue, in adipocyte cultures, and in adipocyte-derived vesicles. This result was confirmed in TNFα-induced miRNA in human adipocytes. Then, bioinformatic analysis highlighted that both ATRA and 1,25(OH)2D-regulated genes and miRNA converge to the canonical ‘nuclear factor Kappa B (NF-κB) signalling pathway.’ Altogether, these results showed that ATRA has anti-inflammatory effects on miRNA expression. In addition, the proposed bioinformatic model converges to NF-κB signalling pathway that has been previously demonstrated to be regulated by ATRA and 1,25(OH)2D, thus confirming the interest of such approach.

En las últimas décadas el mundo de la medicina se ha familiarizado con la valoración de los conflictos de interés (CDI). En las revista científicas se ha generalizado el requisito de que los autores declaren sus CDI en relación con los artículos que proponen publicar; otros aspectos sensibles que merecen atención son los CDI en la toma de decisiones sobre prescripción y los CDI de quienes ocupan puestos de responsabilidad en instituciones científicas, asistenciales o de representación profesional. Estos debates son coherentes con la preocupación de las sociedades democráticas por la justicia y la ética social que exigen juego limpio en la toma de decisiones que afectan a terceros, particularmente a los pacientes. En el presente trabajo se analiza el concepto de los CDI, los tipos de conflictos que pueden abarcar y se reflexiona sobre propuestas para la gestión de los mismos en la profesión médica.

La cultura de seguridad del paciente se fundamenta en el aprendizaje a partir de los eventos adversos, en el desarrollo de estrategias preventivas para evitar su ocurrencia y en reconocer y acompañar a los que han sufrido un daño innecesario e involuntario derivado de la atención sanitaria recibida. Avanzar en la cultura de seguridad del paciente lleva consigo facilitar la implantación de estos comportamientos en los profesionales sanitarios con normativas acordes. El objetivo fue escribir las normativas de algunas comunidades autónomas y proponer cambios normativos a nivel nacional.

We have developed a new separation device to concentrate and collect ions from several milliliter sample volumes to microliter fractions. Unlike most conventional platforms, this device has circular architecture. The electrophoretic migration operates from the outer perimeter toward the center. Separations can be performed both in continuous (zone electrophoresis) and discontinuous (moving boundary) electrolyte systems. We use a discontinuous electrolyte system comprising a leading and a terminating electrolyte to concentrate samples containing small organic anions and DNA fragment. The agarose gel stabilizes the boundary between the leading and terminating electrolytes. The milliliter volume sample is mixed with the terminating electrolyte and migrates through the gel toward the center. The concentrated total sample is collected in microliter fraction at the center. The potential for preparative concentration of DNA is demonstrated using a DNA ladder. Because zone migration accelerates as it moves toward the center, we named this method Epitachophoresis from the Greek word “επιταχυνω (epitachýnο)”, meaning “acceleration”. To the best of our knowledge, this unique circular architecture has not been previously described.

Période de vulnérabilité, la fin de vie est marquée par une appétence relationnelle des malades, qui concerne l’entourage, les soignants mais aussi éventuellement un animal, celui du malade ou inscrit dans un projet de service de médiation animale. Un tel projet a été mis en place au sein de l’unité de soins palliatifs, dont l’un des volets est relatif à la présence d’un chat résident permanent de l’unité. L’impact de sa présence a été étudié par un questionnaire de satisfaction auprès des patients et des familles. Trente-six questionnaires sur une période de trois mois ont été étudiés. Les résultats montrent que la chatte a fréquenté presque toutes les chambres et circulé dans les parties communes. Patients et entourage ont des eu interactions avec elle, sous forme de caresses. Elle a apporté distraction, détente et réconfort pour plus de la moitié des personnes interrogées, et dans une moindre mesure diminution de l’anxiété. La satisfaction globale a été majeure : 84,4 % des personnes ont estimé la présence de la chatte très satisfaisante et 15,6 % satisfaisante. Les limites étaient notamment la faiblesse de l’échantillon et la brièveté de la période d’étude. D’autres items auraient pu être étudiés : impact sur l’humeur, la fatigue, l’appétit, la perception de l’état de santé. L’impact sur les soignants serait une autre piste de réflexion.

Among the different developed solid-state nanopores, nanopores constructed in a monolayer of molybdenum disulfide (MoS2) stand out as powerful devices for single-molecule analysis or osmotic power generation. Because the ionic current through a nanopore is inversely proportional to the thickness of the pore, ultrathin membranes have the advantage of providing relatively high ionic currents at very small pore sizes. This increases the signal generated during translocation of biomolecules and improves the nanopores’ efficiency when used for desalination or reverse electrodialysis applications. The atomic thickness of MoS2nanopores approaches the inter-base distance of DNA, creating a potential candidate for DNA sequencing. In terms of geometry, MoS2nanopores have a well-defined vertical profile due to their atomic thickness, which eliminates any unwanted effects associated with uneven pore profiles observed in other materials. This protocol details all the necessary procedures for the fabrication of solid-state devices. We discuss different methods for transfer of monolayer MoS2, different approaches for the creation of nanopores, their applicability in detecting DNA translocations and the analysis of translocation data through open-source programming packages. We present anticipated results through the application of our nanopores in DNA translocations and osmotic power generation. The procedure comprises four parts: fabrication of devices (2–3 d), transfer of MoS2and cleaning procedure (24 h), the creation of nanopores within MoS2(30 min) and performing DNA translocations (2–3 h). We anticipate that our protocol will enable large-scale manufacturing of single-molecule-analysis devices as well as next-generation DNA sequencing.

This study aims to broaden understanding into the process by which resident physicians deal with illness and to identify areas for improvement regarding healthcare of residents and teaching physicians training to support them adequately. A qualitative study of ten semi-structured interviews with residents who had suffered a serious illness and a focus group of teaching physicians were conducted. Analysis of the interview transcripts was performed using the grounded theory approach, with information divided into five categories: Differences between residents as patients and general patients; confidentiality; feelings and attitudes; learning from illness; and impact on work and training. There are differences between residents and the general population: In the initial stage, diagnosis is made promptly with preferential treatment shown by colleagues. Subsequently, the lack of clear guidelines can lead to poor follow-up. They accept a loss of confidentiality in the process. One of the most serious concerns felt by residents is the impact of their illness on their training as specialists, meaning that teaching physicians are charged with the important role of guaranteeing the resident’s proper recovery, return to work, and readaptation to the training program. Teaching physicians demand their own training be reinforced in these aspects. There is a need to assess the great diversity observed in training-related decisions made by teaching physicians when residents fall ill. Given the differences observed, more research is required to improve the care provided to sick residents and particularly the teaching physicians training to handle them.

This paper studies wholesale electricity markets where an exogenous price cap is enforced, compromising both short- and long-term incentives. To guarantee capacity adequacy, policy-makers may provide support for generation through a capacity remuneration mechanism (CRM) and/or encourage demand response (DR). Such mechanisms are formalised within a common simple analytical framework, clarifying how these mechanisms relate to each other. We then divide them into two categories, depending on whether their implementation requires transactions to be made based explicitly on spot prices higher than the price cap. While mechanisms that keep implicit these high marginal costs are likely to be preferred from a political perspective, they also appear to be less efficient. If they are to be implemented nonetheless, we suggest that the price cap should be set higher than the marginal cost of the most expensive plant, and highlight that challenges for demand-response integration in CRMs remain.

We present here the combination of in situ non invasive techniques to investigate a precious 15th century illuminated manuscript of Petrarch’s work, De remediis utriusque fortunaeheld in the Méjanes library in Aix-en-Provence (France). X-Ray fluorescence spectroscopy, mapping and point analysis, and visible reflectance hyperspectral imaging allow an unprecedented analysis of this manuscript. They provide new clues for its attribution by revealing a partly hidden coat of arms and describing the illuminator’s palette and techniques in detail. We reveal the identity of the first possessor of this manuscript, Tanguy IV du Châtel, known as a 15th century bibliophile close to Louis XI. This information is a further element contributing to the attribution of the richly illuminated folio 6 of this manuscript to François Le Barbier. Pigments and dyes used for this folio have been investigated with particular emphasis on the study of the superimposed colours thus providing a better understanding of the artist’s technique and know-how.

La actividad médica despliega un conjunto de competencias encaminadas a mejorar el estado de salud de las personas. En este camino se realizan diagnósticos, se hacen elecciones de pruebas y tratamientos y se toman decisiones sobre hacer y no hacer que afectan a la vida de los pacientes. En este artículo, proponemos una reflexión ante el sobrediagnóstico y sobretratamiento en relación con los factores que lo promueven y el impacto que tienen en la sociedad, en el funcionamiento del sistema sanitario y también directamente en los pacientes. Finalmente, realizamos unas propuestas de cómo redirigir este exceso considerando que la atención primaria es un lugar privilegiado para actuar en adecuar y minimizar el impacto de las actuaciones del sistema sanitario en la salud de los ciudadanos y reducir los incidentes de seguridad del paciente ligados al sobrediagnóstico y al uso inadecuado de pruebas y tratamientos que no aportan valor a la salud de los pacientes.