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A personalized approach is strongly advocated for treatment selection in Multiple Sclerosis patients due to the high number of available drugs. Machine learning methods proved to be valuable tools in the context of precision medicine. In the present work, we applied machine learning methods to identify a combined clinical and genetic signature of response to fingolimod that could support the prediction of drug response. Two cohorts of fingolimod-treated patients from Italy and France were enrolled and divided into training, validation, and test set. Random forest training and robust feature selection were performed in the first two sets respectively, and the independent test set was used to evaluate model performance. A genetic-only model and a combined clinical–genetic model were obtained. Overall, 381 patients were classified according to the NEDA-3 criterion at 2 years; we identified a genetic model, including 123 SNPs, that was able to predict fingolimod response with an AUROC= 0.65 in the independent test set. When combining clinical data, the model accuracy increased to an AUROC= 0.71. Integrating clinical and genetic data by means of machine learning methods can help in the prediction of response to fingolimod, even though further studies are required to definitely extend this approach to clinical applications [ABSTRACT FROM AUTHOR]

The WHO has included the spiritual dimension in its definition of palliative care since 1990, but this dimension is frequently confused with notions of religion. Yet, the spiritual suffering experienced by palliative care patients is primarily a matter of existential suffering. The objective of this study was to examine the ways in which the existential dimension was manifested in the experiences of those present in a palliative care unit. This anthropological monograph was conducted in a palliative care unit in a French University Hospital. The existential dimension appears to reside in the connections between individuals and the proximity of death appears to shed new light on the meaning of life. The mirror effect of death on life, could serve to encourage greater appreciation of the value of our connections with others, and the desire to take care of others, which offers new insight into forms of solidarity and social organisation. [ABSTRACT FROM AUTHOR]

The COVID-19 epidemic has forced most countries to impose contact-limiting restrictions at workplaces, universities, schools, and more broadly in our societies. Yet, the effectiveness of these unprecedented interventions in containing the virus spread remain largely unquantified. Here, we develop a simulation study to analyze COVID-19 outbreaks on three real-life contact networks stemming from a workplace, a primary school and a high school in France. Our study provides a fine-grained analysis of the impact of contact-limiting strategies at workplaces, schools and high schools, including: (1) Rotating strategies, in which workers are evenly split into two shifts that alternate on a daily or weekly basis; and (2) On-Off strategies, where the whole group alternates periods of normal work interactions with complete telecommuting. We model epidemics spread in these different setups using a stochastic discrete-time agent-based transmission model that includes the coronavirus most salient features: super-spreaders, infectious asymptomatic individuals, and pre-symptomatic infectious periods. Our study yields clear results: the ranking of the strategies, based on their ability to mitigate epidemic propagation in the network from a first index case, is the same for all network topologies (workplace, primary school and high school). Namely, from best to worst: Rotating week-by-week, Rotating day-by-day, On-Off week-by-week, and On-Off day-by-day. Moreover, our results show that below a certain threshold for the original local reproduction number R0local within the network (< 1.52 for primary schools, < 1.30 for the workplace, < 1.38 for the high school, and < 1.55 for the random graph), all four strategies efficiently control outbreak by decreasing effective local reproduction number to R0local < 1. These results can provide guidance for public health decisions related to telecommuting. Author summary: The COVID-19 epidemics has forced most countries to impose prolonged contact-limiting restrictions at workplaces, universities, schools. Using simulation and taking into account the most salient epidemiological features of SARS-CoV-2, we analyze the risk of outbreak and the impact of contact-limiting strategies on three real-life contact networks stemming from a workplace, a primary school and a high school. The strategies investigated involve (1) Rotation, in which workers are evenly split into two shifts that alternate on a daily or weekly basis; and (2) On-Off, where the whole group alternates periods of normal work interactions with complete telecommuting. Our study yields clear results, whatever the studied network (workplace, primary school and high school), we find that, from best to worst: Rotating week-by-week, Rotating day-by-day, On-Off week-by-week, and On-Off day-by-day can all help mitigate transmission below a certain epidemicity threshold. In the current context where institutions and companies have to quickly take local organizational decisions and review their planning or agendas, our results should help inform public health decisions. [ABSTRACT FROM AUTHOR]

Mantle peridotites exhumed in mountain belts provide important insights on the composition and evolution of the upper mantle, and additionally inform on metamorphic, geochemical, and tectonic processes -including seismic activity-at convergent margins. In this contribution, we present field, microstructural, and mineralogical data of fresh, pseudotachylyte-bearing mantle peridotites from the lawsonite eclogite-facies San Petrone unit, Alpine Corsica, France. The present case study represents the first example of subducted fresh peridotite associated with fresh lawsonite eclogite-facies assemblages. Two bodies of fresh peridotite are embedded in fully serpentinized ultramafic rocks forming the substratum of a subducted ocean-continent transition of the Piemonte-Liguria Basin. Clinopyroxene and spinel mineral chemistry indicates that the investigated peridotite samples were part of a refertilized mantle and, therefore, the San Petrone unit likely belonged to the more distal part of the ocean-continent transition. Because small bodies of fresh peridotite embedded in fully serpentinized rocks can hardly be identified by means of geophysical investigations, this finding suggests that small, yet disseminated bodies of fresh mantle peridotite can potentially be more abundant than previously supposed at ocean-continent transition and, potentially, at mid-ocean ridges and in subduction zones. The preservation of fresh mantle peridotite bodies in subducting slabs is also discussed with respect to its potential implications on intermediate depth seismicity and geochemical cycling -including production of natural energy sources-from rifting to subduction. [ABSTRACT FROM AUTHOR]

Abstract: With a half-life of 15.7Ma, a high mobility and the potential to accumulate in the biosphere, 129I is considered, in safety assessment calculations for radioactive waste repositories, to be one of the main contributors to the radiological dose. Several authors have reported that, at low concentration, I− is weakly retained on argillaceous rocks. This process is not yet well-understood and different hypotheses have been put forward as to whether reactive phases or experimental artifacts (e.g. pyrite oxidation) could be the reason for the retention of I− observed at low concentration. The aim of this study was to investigate the effect on I− mobility of (i) the redox conditions and (ii) the amount of pyrite and natural organic matter (NOM) contents of the rock. These questions were addressed by performing batch sorption, through-diffusion and out-diffusion experiments on rock samples of Toarcian argillaceous rock from Tournemire (Aveyron, France). One of the challenges faced during this study was to distinguish actual transport properties from experimental artifacts. A especially elaborate experimental set-up allowed limiting the (i) oxidation of both argillaceous rock and I−, and (ii) carbonate precipitation. A comparison of the batch sorption results obtained for two Toarcian clay specimens, that differed in their amount of pyrite and NOM, allowed relating I− sorption to pyrite oxidation. However, no evidence was found to associate the I− behavior to the NOM amounts. While the through-diffusion experiments showed a very slight sorption (distribution ratio (Rd )=0.016mLg−1) for the lowest I− concentration under oxic conditions, the out-diffusion tests performed after the through-diffusion experiments on the same cells showed significant sorption under both oxic and anoxic conditions, resulting in Rd ranging from 0.02mLg−1 to 1.25mLg−1. The range of Rd values was higher for the upstream reservoir under oxic conditions. The discrepancies observed between the through-diffusion and the out-diffusion experiments suggest a kinetic control of the I− uptake by argillaceous rocks under oxic and anoxic conditions. [Copyright &y& Elsevier]

Background: The literature has described the use of ketamine as an adjuvant treatment for opioid-refractory cancer pain. None of these studies have used the drug in a palliative care patient population. Aims: The primary objective of the study was to assess the efficacy of continuous intravenous infusion of ketamine in patients suffering from cancer pain refractory to opiates who had been admitted to palliative care units. Secondary objectives were to assess patients' satisfaction with and tolerance of ketamine. Methods: A randomized, double-blind, placebo-controlled study was designed, and the study setting included seven French adult palliative care units. Inclusion criteria were age ≥18 years, and cancer pain refractory to standard opiates. Evaluations were conducted at randomization (baseline), at ketamine or placebo introduction time (T0), and at 2 hours (T1), 24 hours (T2), and 48 hours (T3) after T0. The primary evaluation criterion was pain efficacy assessed using a patient self-rated Numeric Pain Intensity Scale (NPIS) at T1. The main secondary evaluation criteria were daily morphine dose, symptom evaluation (Edmonton Symptom Assessment Scale [ESAS]), and patient satisfaction (Pain Treatment Satisfaction Scale [PTSS]). Results: Twenty patients were analyzed (11 received ketamine and 9 received placebo). Self-reported pain did not differ between the two groups, as the symptoms continued to evolve during the study period. The tolerance for ketamine was satisfactory. Conclusion: The present study did not confirm the efficacy of the ketamine-morphine combination in refractory cancer pain. The results suggest that specific populations could be 'good responders' for this therapeutic approach. Further studies should be performed that take into account the difficulties of conducting clinical research in the palliative care context. [ABSTRACT FROM AUTHOR]

The article presents a study on the accuracy of using noninvasive hemoglobin measurement by Pulse CO-Oximetry in critically ill patients. The researchers conducted the observational and prospective study in a surgical intensive care unit (ICU) at the University Hospital in Poitiers, France. They found that noninvasive hemoglobin measurement with Pulse CO-Oximetry has trending and absolute accuracy similar to widely used hemoglobin measurement methods.

Résumé: Objectifs: Il existe peu de données sur la pratique de l’anesthésie locorégionale périphérique (ALRp) par les anesthésistes en formation en France, notamment depuis l’utilisation de l’échographie. Nous avons étudié les pratiques en ALRp des internes d’anesthésie-réanimation dans la région Poitou-Charentes. Type d’étude: Étude prospective descriptive multicentrique. Patients et méthodes: Les internes en anesthésie-réanimation ont complété un formulaire d’enquête après réalisation d’une ALRp. Résultats: Un total de 394 procédures ont été réalisées par 21 internes dans quatre hôpitaux. Le nombre et le volume médian d’anesthésique local administré par type d’ALRp sont : axillaire 245–25mL (62 %), interscalénique 29–21mL (7 %), supraclaviculaire 1–25mL (0,3 %), infraclaviculaire 2–25mL (0,5 %), fémoral 65–18mL (16,5 %) et sciatique 52–22mL (13 %). Le repérage a utilisé l’échographie seule pour 365 (93 %) des procédures et la neurostimulation seule pour 23 d’entre elles (6 %). La durée de la procédure a été inférieure à cinq minutes pour 200 (50,7 %) procédures et supérieure à 15minutes pour seulement 16 d’entre elles (4 %). Une seule ponction a été nécessaire pour 307 (78 %) des procédures. La réussite initiale du bloc a été obtenue pour 369 (93 %) procédures. Les internes en fin de cursus mettent moins de temps (p <0,0001), ont recours à moins de ponction (p <0,046) et se servent moins souvent de la neurostimulation (p <0,0001) sans différence concernant le taux de succès et le volume d’anesthésique local utilisé. Conclusion: La majorité des procédures d’ALRp effectuées par les internes dans la région Poitou-Charentes sont réalisées sous repérage échographique seul. La procédure est rapide, ne nécessitant le plus souvent qu’une seule ponction, et a un taux de réussite élevé, notamment chez les étudiants les plus expérimentés. [ABSTRACT FROM AUTHOR]

Abstract: Diffusion parameters for HTO, 36Cl− , and 125I− were determined on Upper Toarcian argillite samples from the Tournemire Underground Research Laboratory (Aveyron, France) using the through diffusion technique. The direction of diffusion was parallel to the bedding plane. The purpose of the present study was 3-fold; it was intended (i) to confirm the I− interaction with Upper Toarcian argillite and to verify the effects of initial I− concentration on this affinity, as previously observed by means of radial diffusion experiments, (ii) to highlight any discrepancy between Cl− and I− diffusivity, and (iii) to investigate the effect of an increase of the ionic strength of the solution on the anionic tracers’ diffusive behaviour. The results show that the effective diffusion coefficient (De ) and diffusion accessible porosity (εa ) values obtained with an ionic strength (I.S.) synthetic pore water of 0.01eqL−1 are: De =2.35–2.50×10−11 m2 s−1 and εa =12.0–15.0% for HTO, and De =14.5–15.5×10−13 m2 s−1 and εa =2.5–2.9% for 36Cl−. Because of anionic exclusion effects, anions diffuse slower and exhibit smaller diffusion accessible porosities than HTO, taken as a water tracer. The associated effective diffusion coefficient (De ) and rock capacity factor (α) obtained for 125I are: De =7.00–8.60×10−13 m2 s−1 and α =4.3–7.2%. Such values make it possible to calculate low 125I distribution ratios (0.0057< RD <0.0192mLg−1) which confirm the trend indicating that the 125I rock capacity factor increases with the decrease of the initial I− concentration. Additional through-diffusion experiments were carried out with a higher ionic strength synthetic pore water (I.S.=0.11eqL−1). No evolution of HTO diffusion parameters was observed. The anionic tracers’ effective diffusion coefficient increased by a factor of two but no clear evolution of their accessible porosity was observed. Such a paradox could be related to the particularly small mean pore size of the Upper Toarcian argillite of Tournemire. The most significant finding of this study is the large discrepancy (factor of two) between the values of the effective diffusion coefficient for 125I and 36Cl. Whatever the ionic strength of the synthetic solution used, 125I exhibited De values two times lower than those of 36Cl. A detailed explanation for this difference cannot be given at present even if a hypothesis based on ion-pairing or on steric-exclusion cannot be excluded. This makes questionable the assumption usually made for quantifying 125I sorption and postulating that 36Cl and 125I would diffuse in the same porosity. In other terms, at Tournemire, 125I sorption could be more pronounced than previously indicated. [Copyright &y& Elsevier]

Background: Two billion peripheral venous catheters are sold globally each year, but the optimal skin disinfection and types of devices are not well established. We aimed to show the superiority of disinfection with 2% chlorhexidine plus alcohol over 5% povidone iodine plus alcohol in preventing infectious complications, and of closed integrated catheters, positive displacement needleless-connectors, disinfecting caps, and single-use prefilled flush syringes used in combination (innovation group) over open catheters and three-way stopcocks for treatment administration (standard group) in preventing catheter failure.Methods: We did an open-label, randomised-controlled trial with a two-by-two factorial design, for which we enrolled adults (age ≥18 years) visiting the emergency department at the Poitiers University Hospital, France, and requiring one peripheral venous catheter before admission to the medical wards. Before catheter insertion, patients were randomly assigned (1:1:1:1) using a secure web-based random-number generator to one of four treatment groups based on skin preparation and type of devices (innovative devices or standard devices; 2% chlorhexidine plus alcohol or 5% povidone iodine plus alcohol). Primary outcomes were the incidence of infectious complications (local infection, catheter colonisation, or bloodstream infections) and time between catheter insertion and catheter failure (occlusion, dislodgment, infiltration, phlebitis, or infection). This study is registered with ClinicalTrials.gov, NCT03757143.Findings: 1000 patients were recruited between Jan 7, and Sept 6, 2019, of whom 500 were assigned to the chlorhexidine plus alcohol group and 500 to the povidone iodine plus alcohol group (250 with innovative solutions and 250 with standard devices in each antiseptic group). No significant interaction was found between the two study interventions. Local infections occurred less frequently with chlorhexidine plus alcohol than with povidone iodine plus alcohol (0 [0%] of 496 patients vs six [1%] of 493 patients) and the same was observed for catheter colonisation (4/431 [1%] vs 70/415 [17%] catheters among the catheters cultured; adjusted subdistribution hazard ratio 0·08 [95% CI 0·02-0·18]). Median time between catheter insertion and catheter failure was longer in the innovation group compared with the standard group (50·4 [IQR 29·6-69·4] h vs 30·0 [16·6-52·6] h; p=0·0017). Minor skin reactions occurred in nine (2%) patients in the chlorhexidine plus alcohol group and seven (1%) patients in the povidone iodine plus alcohol group.Interpretation: For skin antisepsis, chlorhexidine plus alcohol provides greater protection of peripheral venous catheter-related infectious complications than does povidone iodine plus alcohol. Use of innovative devices extends the catheter complication-free dwell time.Funding: Becton Dickinson. [ABSTRACT FROM AUTHOR]

Selenium-79 is considered as a critical radionuclide in safety assessment of high-level radioactive waste deep geological repository in clay-rich formations, owing to its long half-life and its anionic form in three relevant oxidation states (VI, IV,-II). An in-depth understanding of the diffusive transport properties of Se is therefore essential, especially due to its high sensitivity to oxido-reduction conditions. Here, the mobility of selenite and selenate in claystone samples (Callovo-Oxfordian, East of Paris Basin, France) under anoxic conditions is assessed by combining batch and diffusion experiments, and synchrotron-based spectroscopic mapping of diffusion fronts. Results showed that selenite and selenate behaved distinctly. Selenate diffused similarly to the reference anionic tracer, 36Cl−, without significant sorption or reduction. Selenite showed a sorption behaviour that increased with the decrease of the initial concentration from 10−3 to 10−6 mol L−1, values of distribution ratio (R d) from batch experiments ranging from 10 to about 250 mL g−1. Selenite in-diffusion experiments showed that a pure diffusion model with reversible sorption was able to roughly reproduce the evolution of dissolved selenite in solution over time. However, additional reactions were required to properly describe the irregular shape of the selenite diffusion profiles in the solid. Mapping of Se oxidation state in diffusion fronts within the claystone coupons showed the presence of reduced Se (Se (0), Se(-I) and/or Se(-II)) along a fringe located at about 2 mm beneath the surface, possibly explaining the irregular shape of diffusion profiles. In the superficial zone (0–2 mm), oxidizing perturbations are assumed to account for the preservation of selenite under this oxidation state. These perturbations would also bias batch results in the same manner. Deeper in the claystone sample, diffusing selenite was observed, with a content steadily decreasing up to 7 mm from the inlet. The results suggest that, even after more than 500 days of diffusion, Se reduction would occur progressively along the diffusion pathways. • Selenate diffused similarly to 36Cl−, without significant sorption or reduction. • Selenite sorption increases with [Se(IV)] 0 decreasing from 10−3 to 10−6 mol L−1 • Oxidation state of selenium diffusing in clay rock was mapped using micro-XAS. • Irregular shape of Se(IV) diffusion profile is related to oxido-reduction processes. • In the first 2 mm of rock oxidizing artifacts preserve Se(IV) under this oxidation state. [ABSTRACT FROM AUTHOR]

Background Preoperative fasting is well codified worldwide. In contrast, the literature on the postoperative fasting (POF) is scarce, leading to potentially wide discrepancies among anaesthesiology practices. This survey assessed French POF practices. Methods From March 2013 to January 2014, a survey was conducted among anaesthesiologists, members of the French Society of Anaesthesiology and Intensive Care Medicine (SFAR). The POF durations of either fluid or solid food intake was assessed according to airway management procedures (endotracheal intubation [EI] or laryngeal mask [LMA]) and age of the patients (adult or paediatric). Results Seven hundred and fifty-four surveys were returned (67% from public hospital practitioners and 33% from private hospital and clinic practitioners). The majority of anaesthesiologists allowed fluid intake 2 h after EI and immediately after discharge from PACU following LMA. For solid food resumption, it was 2 h for children and 4 h for adults after EI and 2 h for both children and adults after LMA. Regardless of the airway management procedures, fasting was permitted immediately after PACU discharge more frequently in public than in private hospitals (36% vs. 33%, P < 0.05). Four hours after the end of surgery, the rate was significantly higher in private than in public hospitals (93% vs. 89 %, P < 0.001). Conclusions All in all, POF lasted less than 4 hours after surgery regardless of airway management. They were shorter with regard to fluid intake, paediatric patients and LMA in comparison with solid food, adult patients and EI respectively. [ABSTRACT FROM AUTHOR]