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More than half of the world’s population live in cities, and by 2050, it is expected that this proportion will reach almost 68%. These densely populated cities consume more than 75% of the world’s primary energy and are responsible for the emission of around 70% of anthropogenic carbon. Providing sustainable energy for the growing demand in cities requires multifaceted planning approach. In this study, we modeled the energy system of the Greater Montreal region to evaluate the impact of different environmental mitigation policies on the energy system of this region over a long-term period (2020–2050). In doing so, we have used the open-source optimization-based model called the Energy–Technology–Environment Model (ETEM). The ETEM is a long-term bottom–up energy model that provides insight into the best options for cities to procure energy, and satisfies useful demands while reducing carbon dioxide (CO2) emissions. Results show that, under a deep decarbonization scenario, the transportation, commercial, and residential sectors will contribute to emission reduction by 6.9, 1.6, and 1 million ton CO2-eq in 2050, respectively, compared with their 2020 levels. This is mainly achieved by (i) replacing fossil fuel cars with electric-based vehicles in private and public transportation sectors; (ii) replacing fossil fuel furnaces with electric heat pumps to satisfy heating demand in buildings; and (iii) improving the efficiency of buildings by isolating walls and roofs.

Objective Peritoneal or mesenteric tumours may correspond to several tumour types or tumour-like conditions, some of them being represented by histiocytosis. This rare condition often poses diagnostic difficulties that can lead to important time delay in targeted therapies. Our aim was to describe main features of histiocytoses with mesenteric localisation that can improve the diagnostic process.Design We performed a retrospective study on 22 patients, whose peritoneal/mesenteric biopsies were infiltrated by histiocytes.Results Abdominal pain was the revealing symptom in 10 cases, and 19 patients underwent surgical biopsies. The diagnosis of histiocytosis was proposed by initial pathologists in 41% of patients. The other initial diagnoses were inflammation (n=7), sclerosing mesenteritis (n=4) and liposarcoma (n=1). The CD163/CD68+CD1a- histiocytes infiltrated subserosa and/or deeper adipose tissues in 16 and 14 cases, respectively. A BRAFV600E mutation was detected within the biopsies in 11 cases, and two others were MAP2K1 mutated. The final diagnosis was histiocytosis in 18 patients, 15 of whom had Erdheim-Chester disease. The median diagnostic delay of histiocytosis was 9 months. Patients treated with BRAF or MEK inhibitors showed a partial response or a stable disease. One patient died soon after surgery, and five died by the progression of the disease.Conclusion Diagnosis of masses arising in the mesentery should be carefully explored as one of the possibilities in histiocytosis. This diagnosis is frequently missed on mesenteric biopsies. Molecular biology for detecting the mutations in BRAF or in genes of the MAP kinase pathway is a critical diagnostic tool.

Objetivo: presentar la construcción, aplicación y evaluación de una estrategia de gamificación para la enseñanza de metodología científica para estudiantes de graduación en enfermería. Método: diagnóstico de los problemas de la disciplina Metodología Científica del curso de enfermería de la Universidade do Estado do Pará; construcción de la estrategia; aplicación en seis clases a lo largo de tres semestres, entre 2017 y 2018; evaluación de los impactos y aceptación. Resultados: construcción de un sistema de evolución heurística, con impactos en asiduidad y puntualidad y autoevaluación positiva de la estrategia. Consideraciones Finales: la estrategia de gamificación demostró ser eficaz a la mejora del compromiso de los estudiantes de graduación en enfermería y con potencial para ser una herramienta pedagógica innovadora en la enseñanza de enfermería. La adopción de una estructura de evolución heurística distancia esta estrategia de iniciativas artificiales con el uso aislado de elementos de juegos. Se necesita asimismo evaluaciones más estrictas con grupo control.

Hidradenitis suppurativa (HS) is a chronic skin disorder of unknown etiology that manifests as recurrent, painful lesions. Cutaneous dysbiosis and unresolved inflammation are hallmarks of active HS, but their origin and interplay remain unclear. Our metabolomic profiling of HS skin revealed an abnormal induction of the kynurenine pathway of tryptophan catabolism in dermal fibroblasts, correlating with the release of kynurenine pathway–inducing cytokines by inflammatory cell infiltrates. Notably, overactivation of the kynurenine pathway in lesional skin was associated with local and systemic depletion in tryptophan. Yet the skin microbiota normally degrades host tryptophan into indoles regulating tissue inflammation via engagement of the aryl hydrocarbon receptor (AHR). In HS skin lesions, we detected contextual defects in AHR activation coinciding with impaired production of bacteria-derived AHR agonists and decreased incidence of AHR ligand-producing bacteria in the resident flora. Dysregulation of tryptophan catabolism at the skin-microbiota interface thus provides a mechanism linking the immunological and microbiological features of HS lesions. In addition to revealing metabolic alterations in patients with HS, our study suggests that correcting AHR signaling would help restore immune homeostasis in HS skin.

Attention deficit hyperactivity disorder (ADHD) is commonly associated with deficits in executive functions executive functions (EF), but children with this disorder frequently demonstrate co-occurring morphosyntactic impairment when assessed using standardized tests. On the other hand, children with developmental language disorder (DLD), a population defined by impaired linguistic functioning, are often diagnosed with comorbid EF deficits. We investigated EF and morphosyntax in 60 French-speaking children aged six to 12: 20 with typical development (TD), 20 with ADHD, and 20 with DLD. To obtain an EF profile for the different cognitive groups, we used standardized tests to assess lower-order EF skills, (i) selective attention and (ii) short-term memory capacity, and higher-order EF skills, (i) working memory capacity and (ii) attention shifting. To test morphosyntax, we used (i) a standardized omnibus test that elicited a variety of complex structures and (ii) a more fine-grained probe test that assessed the production of third person object clitic pronouns, a clinical marker of DLD in French. Children with ADHD and DLD were associated with different EF and morphosyntactic profiles: children in the ADHD group demonstrated higher-order EF weakness and difficulty on the omnibus morphosyntax task, whereas children with DLD showed both lower- and higher-order limitations and struggled with both morphosyntax tasks. Our findings indicate that deficits in morphosyntax are not characteristic of ADHD but that the performance of children with ADHD can mimic morphosyntactic impairment when all-encompassing omnibus tests evaluating various and unpredictable structures are used. If morphosyntax is tested using reliable markers of atypical language development and external cognitive-load factors are optimally reduced, there are significant discrepancies in the observed ADHD-DLD outcomes. Clinical implications that include perspectives for the differential diagnosis of ADHD and DLD are discussed.

Two main problems are studied in this article. The first one is the use of the extrusion process for controlled thermo-mechanical degradation of polyethylene for recycling applications. The second is the data-based modelling of such reactive extrusion processes. Polyethylenes (high density polyethylene (HDPE) and ultra-high molecular weight polyethylene (UHMWPE)) were extruded in a corotating twin-screw extruder under high temperatures (350 °C < T < 420 °C) for various process conditions (flow rate and screw rotation speed). These process conditions involved a decrease in the molecular weight due to degradation reactions. A numerical method based on the Carreau-Yasuda model was developed to predict the rheological behaviour (variation of the viscosity versus shear rate) from the in-line measurement of the die pressure. The results were successfully compared to the viscosity measured from offline measurement assuming the Cox-Merz law. Weight average molecular weights were estimated from the resulting zero-shear rate viscosity. Furthermore, the linear viscoelastic behaviours (Frequency dependence of the complex shear modulus) were also used to predict the molecular weight distributions of final products by an inverse rheological method. Size exclusion chromatography (SEC) was performed on five samples, and the resulting molecular weight distributions were compared to the values obtained with the two aforementioned techniques. The values of weight average molecular weights were similar for the three techniques. The complete molecular weight distributions obtained by inverse rheology were similar to the SEC ones for extruded HDPE samples, but some inaccuracies were observed for extruded UHMWPE samples. The Ludovic® (SC-Consultants, Saint-Etienne, France) corotating twin-screw extrusion simulation software was used as a classical process simulation. However, as the rheo-kinetic laws of this process were unknown, the software could not predict all the flow characteristics successfully. Finally, machine learning techniques, able to operate in the low-data limit, were tested to build predicting models of the process outputs and material characteristics. Support Vector Machine Regression (SVR) and sparsed Proper Generalized Decomposition (sPGD) techniques were chosen to predict the process outputs successfully. These methods were also applied to material characteristics data, and both were found to be effective in predicting molecular weights. More precisely, the sPGD gave better results than the SVR for the zero-shear viscosity prediction. Stochastic methods were also tested on some of the data and showed promising results.

Most end-stage renal disease kidneys display accumulation of extracellular matrix (ECM) in the renal tubular compartment (tubular interstitial fibrosis - TIF) which is strongly correlated with the future loss of renal function. Although inflammation is a key event in the development of TIF, it can also have a beneficial anti-fibrotic role depending in particular on the stage of the pathology. Chemokines play an important role in monocyte extravasation in the inflammatory process. CCL2 has already been shown to be involved in the development of TIF but CCL7, a close relative of CCL2 and able to bind to similar receptors, has not been studied in renal disease. We therefore studied chemokine CCL7 in a model of unilateral ureteral obstruction (UUO)-induced TIF. We observed that the role of CCL7 differs depending on the stage of the pathology. In early stages (0-8 days), CCL7 deficient (CCL7-KO) mice displayed attenuated TIF potentially involving two mechanisms: an early (0-3 days) decrease of inflammatory cell infiltration followed (3-8 days) by a decrease in tubular ECM production independent of inflammation. In contrast, during later stages of obstruction (10-14 days), CCL7-KO mice displayed increased TIF which was again associated with reduced inflammation. Interestingly, the switch between this anti- to profibrotic effect was accompanied by an increased influx of immunosuppressive regulatory T cells. In conclusion, these results highlight for the first time a dual role for CCL7 in the development of renal TIF, deleterious in early stages but beneficial during later stages.

RESUMO Objetivo Verificar a correlação entre a independência funcional e o risco de quedas em um grupo de idosos institucionalizados. Método Estudo transversal, observacional, quantitativo, realizado em três Instituições de Longa Permanência para Idosos no Município de Belém, de ambos os gêneros, avaliados por meio do Índice de Katz e Índice de Tinetti. Para análise utilizou-se o teste de Qui-quadrado de Pearson, adotando-se um nível de significância de p-valor < 0.05. E a correlação dos dados foi realizada pelo teste de correlação de Pearson, com significância de 5% (p

The plasma refraction index can be calculated by different methods. In this paper, a physical approach is presented and applied to non-linear situations. We have particularly focused on the case where the mass of the electrons subjected to the wave becomes relativistic. In the case of a circularly polarized high intensity wave, ionization is considered.

Seeds of the parasitic weed Phelipanche ramosa are well adapted to their hosts because they germinate and form haustorial structures to connect to roots in response to diverse host-derived molecular signals. P. ramosa presents different genetic groups that are preferentially adapted to certain hosts. Since there are indications that microbes play a role in the interaction especially in the early stages of the interaction, we studied the microbial diversity harbored by the parasitic seeds with respect to their host and genetic group. Twenty-six seed lots from seven cropping plots of three different hosts—oilseed rape, tobacco, and hemp—in the west of France were characterized for their bacterial and fungal communities using 16S rRNA gene and ITS (Internal transcribed spacer) sequences, respectively. First seeds were characterized genetically using twenty microsatellite markers and phenotyped for their sensibility to various germination stimulants including strigolactones and isothiocyanates. This led to the distinction of three P. ramosa groups that corresponded to their host of origin. The observed seed diversity was correlated to the host specialization and germination stimulant sensitivity within P. ramosa species. Microbial communities were both clustered by host and plot of origin. The seed core microbiota was composed of seventeen species that were also retrieved from soil and was in lower abundances for bacteria and similar abundances for fungi compared to seeds. The host-related core microbiota of parasitic seeds was limited and presumably well adapted to the interaction with its hosts. Two microbial candidates of Sphingobacterium species and Leptosphaeria maculans were especially identified in seeds from oilseed rape plots, suggesting their involvement in host recognition and specialization as well as seed fitness for P. ramosa by improving the production of isothiocyanates from glucosinolates in the rhizosphere of oilseed rape.

Abstract Outputs from new state‐of‐the‐art climate models under the Coupled Model Inter‐comparison Project phase 6 (CMIP6) promise improvement and enhancement of climate change projections information for Australia. Here we focus on three key aspects of CMIP6: what is new in these models, how the available CMIP6 models evaluate compared to CMIP5, and their projections of the future Australian climate compared to CMIP5 focussing on the highest emissions scenario. The CMIP6 ensemble has several new features of relevance to policymakers and others, for example, the integrated matrix of socioeconomic and concentration pathways. The CMIP6 models show incremental improvements in the simulation of the climate in the Australian region, including a reduced equatorial Pacific cold tongue bias, slightly improved rainfall teleconnections with large‐scale climate drivers, improved representation of atmosphere and ocean extreme heat events, as well as dynamic sea level. However, important regional biases remain, evident in the excessive rainfall over the Maritime Continent and rainfall pattern biases in the nearby tropical convergence zones. Projections of Australian temperature and rainfall from the available CMIP6 ensemble broadly agree with those from CMIP5, except for a group of CMIP6 models with higher climate sensitivity and greater warming and increase in some extremes after 2050. CMIP6 rainfall projections are similar to CMIP5, but the ensemble examined has a narrower range of rainfall change in austral summer in Northern Australia and austral winter in Southern Australia. Overall, future national projections are likely to be similar to previous versions but perhaps with some areas of improved confidence and clarity.

The Taquari River Basin, located in the Alkaline Complex of Poços de Caldas, in the south of Minas Gerais, Brazil, is situated in an old volcanic caldera. In the study area there are fields and pastures; agriculture with cultivation of vegetables; rose plantations; and native forest, in addition to the Mineral Treatment Unit of Caldas (UTM-Caldas), which is part of the Industrial Complex of Poços de Caldas (CIPC), a uranium mining and processing facility. The main objective of this work was to investigate the isotopic Pb signatures of river sediments, rocks, mining tailings and fertilizer samples collected in the region surrounding UTM-Caldas in order to identify environments with influences from geogenic and / or anthropogenic sources. The results showed that there is an anthropic contribution (fertilizers and mining tailings) in some sectors of the Taquari river basin, generating possible concerns about the amount of elements that can be transferred to the water bodies. In addition, there is a significant geogenic contribution of naturally enriched areas, which have distinct situations that also generate an increase in the concentration of chemical elements in water bodies.

Summary: Inferring genome-scale metabolic networks in emerging model organisms is challenged by incomplete biochemical knowledge and partial conservation of biochemical pathways during evolution. Therefore, specific bioinformatic tools are necessary to infer biochemical reactions and metabolic structures that can be checked experimentally. Using an integrative approach combining genomic and metabolomic data in the red algal model Chondrus crispus, we show that, even metabolic pathways considered as conserved, like sterols or mycosporine-like amino acid synthesis pathways, undergo substantial turnover. This phenomenon, here formally defined as “metabolic pathway drift,” is consistent with findings from other areas of evolutionary biology, indicating that a given phenotype can be conserved even if the underlying molecular mechanisms are changing. We present a proof of concept with a methodological approach to formalize the logical reasoning necessary to infer reactions and molecular structures, abstracting molecular transformations based on previous biochemical knowledge. : Bioinformatics; Genomics; Metabolomics Subject Areas: Bioinformatics, Genomics, Metabolomics

Gisèle Pickering,1,2 Nicolas Macian,2 Noémie Delage,3 Pascale Picard,3 Jean-Michel Cardot,4 Sophia Sickout-Arondo,2 Fatiha Giron,2 Christian Dualé,2 Bruno Pereira,5 Fabienne Marcaillou3 1University Clermont Auvergne Neurodol, Clermont-Ferrand, France; 2Clinical Pharmacology Department CPC/CIC Inserm 1405, University Hospital, Clermont-Ferrand, France; 3Pain Clinic, CHU Clermont-Ferrand, Clermont-Ferrand, France; 4University Clermont Auvergne MEDIS, CHU Clermont-Ferrand, Clermont-Ferrand, France; 5DRCI, CHU Clermont-Ferrand, Clermont-Ferrand, France Introduction: Fibromyalgia is characterized by widespread and chronic pain, and its prevalence is increasing worldwide. Milnacipran, an antidepressant, is often prescribed for fibromyalgia with a possible beneficial effect on central pain modulation. The aim of this study was to evaluate if milnacipran could modify the status of conditioned pain modulation (CPM) in patients suffering from fibromyalgia.Design and setting: Randomized, double-blind controlled trial.Subjects and methods: Women with fibromyalgia received milnacipran 100 mg or placebo. The primary end point was the evolution of CPM with treatments after a 30-second painful stimulus. Secondary outcomes included the predictability of milnacipran efficacy from CPM performance, evolution of global pain, mechanical sensitivity, thermal pain threshold, mechanical allodynia, cognitive function, and tolerance.Results: Fifty-four women with fibromyalgia (46.7±10.6 years) were included and randomized, and 24 patients were analyzed in each group. At inclusion, CPM was dysfunctional (CPM30=-0.5±1.9), and global pain was 6.5±1.8. After treatment, there was a nonsignificant CPM difference between milnacipran and placebo (CPM30=-0.46±1.22 vs -0.69±1.43, respectively, p=0.55) and 18.8% vs 6.3% (p=0.085) patients did reactivate CPM after milnacipran vs placebo. Initial CPM was not a predictor of milnacipran efficacy. Global pain, mechanical and thermal thresholds, allodynia, cognition, and tolerance were not significantly different between both groups.Conclusion: Milnacipran did not display a significant analgesic effect after 1-month treatment, but the tendency of milnacipran to reactivate CPM in a number of patients must be explored with longer treatment duration in future studies and pleads for possible subtypes of fibromyalgia patients. Keywords: fibromyalgia, CPM, milnacipran, antidepressants, pain

Following the emergence of #Me Too, three specialists, sociologists and politicists, propose to analyse the links between this phenomenon of denunciation of sexist and sexual assaults and the professional world. These three researchers put this movement and its variations into perspective. If the work place is one of its hotbeds, the cross-discussion between these three contributions underlines that the challenge of gender social relations exceeds work and extends to multiple social spheres in the society.

Les techniques de génie végétal sont de plus en plus mobilisées pour restaurer les milieux érodés ou dégradés comme les talus ou les berges des rivières. Parmi les pratiques utilisées, on peut citer l'ensemencement qui consiste à répandre sur le sol des mélanges de graines d'espèces le plus souvent herbacées. En s'appuyant sur le suivi de dix-huit chantiers de restauration de berge, cet article s'intéresse à la réussite des ensemencements réalisés en fonction de différents paramètres : recours à des semences certifiées, poids des graines et présence relative des espèces spontanées.

In this paper, we have explored the possibility of assigning the humanthemed engravings from La Marche to their authors, according to the method outlined by J.M. Apellaniz in the 1980s. The method employed here follows the first of the three stages postulated by Apellaniz: macroscopic observation, microscopic analysis and experimental protocol. From our study emerged a pattern of five groups and sixteen hands at work in this site. We believe, therefore, that it is possible to speak of La Marche as an “art workshop”, where portable art was produced and taught.

Abstract Our current view of DNA methylation processes is strongly moving: First, even if it was generally admitted that DNMT3A and DNMT3B are associated with de novo methylation and DNMT1 is associated with inheritance DNA methylation, these distinctions are now not so clear. Secondly, since one decade, many partners of DNMTs have been involved in both the regulation of DNA methylation activity and DNMT recruitment on DNA. The high diversity of interactions and the combination of these interactions let us to subclass the different DNMT-including complexes. For example, the DNMT3L/DNMT3A complex is mainly related to de novo DNA methylation in embryonic states, whereas the DNMT1/PCNA/UHRF1 complex is required for maintaining global DNA methylation following DNA replication. On the opposite to these unspecific DNA methylation machineries (no preferential DNA sequence), some recently identified DNMT-including complexes are recruited on specific DNA sequences. The coexistence of both types of DNA methylation (un/specific) suggests a close cooperation and an orchestration between these systems to maintain genome and epigenome integrities. Deregulation of these systems can lead to pathologic disorders.

In this paper, we study how uncertainties weighing on the climate system impact the optimal technological pathways the world energy system should take to comply with stringent mitigation objectives. We use the TIAM-World model that relies on the TIMES modelling approach. Its climate module is inspired by the DICE model. Using robust optimization techniques, we assess the impact of the climate system parameter uncertainty on energy transition pathways under various climate constraints. Unlike other studies we consider all the climate system parameters which is of primary importance since: (i) parameters and outcomes of climate models are all inherently uncertain (parametric uncertainty); and (ii) the simplified models at stake summarize phenomena that are by nature complex and non-linear in a few, sometimes linear, equations so that structural uncertainty is also a major issue. The use of robust optimization allows us to identify economic energy transition pathways under climate constraints for which the outcome scenarios remain relevant for any realization of the climate parameters. In this sense, transition pathways are made robust. We find that the abatement strategies are quite different between the two temperature targets. The most stringent one is reached by investing massively in carbon removal technologies such as bioenergy with carbon capture and storage (BECCS) which have yields much lower than traditional fossil fuelled technologies.

1C1m-Fc, a promising anti-TEM-1 DOTA conjugate, was labeled with 64Cu to target cancer cells for PET imaging and predicting the efficacy and safety of a previously studied [177Lu]Lu-1C1m-Fc companion therapy. DOTA-conjugated 1C1m-Fc was characterized by mass spectrometry, thin layer chromatography and immunoreactivity assessment. PET/CT and biodistribution studies were performed in human neuroblastoma xenografted mice. Absorbed doses were assessed from biodistribution results and extrapolated to 177Lu based on the [64Cu]Cu-1C1m-Fc data. The immunoreactivity was ≥ 70% after 48 h of incubation in serum, and the specificity of [64Cu]Cu-1C1m-Fc for the target was validated. High-resolution PET/CT images were obtained, with the best tumor-to-organ ratios reached at 24 or 48 h and correlated with results of the biodistribution study. Healthy organs receiving the highest doses were the liver, the kidneys and the uterus. [64Cu]Cu-1C1m-Fc could be of interest to give an indication of 177Lu dosimetry for parenchymal organs. In the uterus and the tumor, characterized by specific TEM-1 expression, the 177Lu-extrapolated absorbed doses are overestimated because of the lack of later measurement time points. Nevertheless, 1C1m-Fc radiolabeled with 64Cu for imaging would appear as an interesting radionuclide companion for therapeutic application with [177Lu]Lu-1C1m-Fc.

Malnutrition has been reported in alcohol use disorder patients as having a possible influence on cognitive function. The aim of this study was to analyse the prevalence of ascorbic acid (AA) deficiency in inpatients admitted for alcohol detoxification and the associated factors, including cognitive impairment in the early period of abstinence. A retrospective chart review was conducted. The AA level was categorised into three groups: deficiency (AAD) (p = 0.037) and sedative use disorder (β = −2.77, p = 0.046) were associated with the MoCA score. AAD and AAI are frequent in inpatients admitted for alcohol detoxification. A low level of AA was associated with cognitive impairment in the early period of abstinence.

Traumatic brain injury (TBI) is a leading cause of death and disability all over the world. TBI leads to (1) an inflammatory response, (2) white matter injuries and (3) neurodegenerative pathologies in the long term. In humans, TBI occurs most often in children and adolescents or in the elderly, and it is well known that immune responses and the neuroregenerative capacities of the brain, among other factors, vary over a lifetime. Thus, age-at-injury can influence the consequences of TBI. Furthermore, age-at-injury also influences the pharmacological effects of drugs. However, the post-TBI inflammatory, neuronal and functional consequences have been mostly studied in experimental young adult animal models. The specificity and the mechanisms underlying the consequences of TBI and pharmacological responses are poorly understood in extreme ages. In this review, we detail the variations of these age-dependent inflammatory responses and consequences after TBI, from an experimental point of view. We investigate the evolution of microglial, astrocyte and other immune cells responses, and the consequences in terms of neuronal death and functional deficits in neonates, juvenile, adolescent and aged male animals, following a single TBI. We also describe the pharmacological responses to anti-inflammatory or neuroprotective agents, highlighting the need for an age-specific approach to the development of therapies of TBI.

Le parti Podemos revendique de « construire le peuple », c’est-à-dire de constituer la représentation politique d’un nouveau « nous le peuple » démocratique, issu du mouvement des Indignés du 15 M 2011. Défendant depuis 2014 une conception du peuple comme « gente » – les gens – dans la lignée inclusive du 15 M, le parti Podemos s’est trouvé depuis 2016 traversé par de profonds débats portant sur la nature même de son projet politique. Notre analyse part donc de la mise en usage du terme gente dans le contexte du 15 M 2011, pour étudier la représentation du peuple dans la formulation proposée par Podemos d’une « hypothèse populiste ». Quel peuple pour quel populisme ? est en effet la question à laquelle se trouvent actuellement confrontés le parti Podemos et, plus largement, les mouvements populistes à l’échelle européenne.

Abstract Background Neuropathic pain is difficult to treat, and the efficacy of recommended drugs remains limited. N-methyl-d-aspartate receptors are implicated, and antagonists are a pharmacological option. Ketamine is widely used in French pain clinics, but without consensus or recommendations. Furthermore, the association of ketamine with magnesium has been poorly studied. The aim of the present study is to evaluate the benefit of ketamine with or without magnesium in refractory neuropathic pain. Methods/design A randomized, double-blind, crossover, placebo-controlled study will be performed in Clermont-Ferrand University Hospital, Clermont-Ferrand, France. The aim is to evaluate the effect of ketamine with or without magnesium in 22 patients with neuropathic pain. Intravenous ketamine/placebo, ketamine/magnesium sulfate, or placebo/placebo will be administered consecutively to each patient, in random order, once at 5-week intervals. The primary endpoint is the AUC of pain intensity assessed on a 0–10 Numeric Pain Rating Scale for a 5-week period. Data analysis will be performed on an intention-to-treat basis, and all statistical tests (except primary analysis) will be performed with an α risk of 5% (two-sided). Discussion Considering the poor efficacy of the drugs available for neuropathic pain, ketamine with or without magnesium sulfate may be a valuable therapeutic option that needs to be standardized. Trial registration EudraCT number– 2015-000142-29 . Registered on April 9, 2015; version 1.4

This study investigates syntax in Autism Spectrum Disorders (ASD), its parallelism with Specific Language Impairment (SLI) and its relation to other aspects of cognition. We focus on (1) 3rd person accusative clitic (ACC3) production, a clinical marker of SLI hypothesized to relate to WM, and (2) 1st person accusative clitic (ACC1) production, preserved in SLI but hypothesized to be affected in ASD due to Theory-of-Mind (ToM) difficulties. Participants included 21 individuals with ASD (aged 5-16), 22 individuals with SLI (aged 5-16), age-matched and younger TD controls (N = 44). Clinical groups showed similar deficits for ACC3 and general morphosyntax. Closer analysis revealed that a subgroup of children with ASD displayed intact grammar except for ACC1, where children with SLI performed well. Better ToM scores implied better ACC1 scores in ASD. Difficulties with WM emerged for ASD and SLI and correlated only with performance on ACC3. Non-verbal reasoning was unrelated to syntactic measures.

As for research on sector-coupled energy systems, few studies comprehensively deal with energy carriers and energy demand sectors. Moreover, few studies have analyzed energy conversion functions such as Power-to-Gas, Power-to-Heat, and Vehicle-to-Grid on the energy system performance. This study clarifies the required renewable resources and costs in the sector-coupled energy system and cost-optimal installed capacity and operation. We formulated an optimization model considering sector coupling and conducted a case study applying the model in the Tohoku region. As a result, due to sector coupling, the total primary energy supply (TPES) is expected to decrease, and system costs are expected to increase from 1.8 to 2.4 times the current level. System costs were minimized when maximizing the use of V2G by electric vehicles and district heating systems (DHS). From the hourly analysis, it becomes clear that the peak cut effect by Power-to-Heat and the peak shift effect by Vehicle-to-Grid result in leveling the output of electrolyzer and fuel synthesizer, which improves the capacity factor reducing capacity addition. Since a large amount of renewable energy is required to realize the designed energy system, it is necessary to reduce the energy demand mainly in the industrial sector. Besides, in order to reduce costs, it is required to utilize electric vehicles by V2G and provide policy support for district heating systems in Japan.