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This paper presents an application to metal matrix composites (MMCs) of an enhanced elasto-viscoplastic Fast Fourier Transform (EVP-FFT) formulation coupled with a phenomenological continuum Mesoscale Field Dislocation Mechanics (MFDM) theory. Contrary to conventional crystal plasticity, which only accounts for plastic flow and hardening induced by statistically stored dislocations (SSDs), MFDM-EVP-FFT also describes the evolution of polarized geometrically necessary dislocation (GND) density and its effect on both plastic flow and hardening. Numerical results for a Fe–TiB2MMC made of a ferrite matrix (α-Fe) and elastic ceramic particles (TiB2) are presented. Full-field simulations are performed using synthetic periodic unit cells representative of the MMC, with single-crystalline and polycrystalline matrix, for different particle interspacing distances. A strong dependence of the predicted equivalent stress, cumulated plastic strain and GND density fields with particle interspacing distance is observed, in contrast with conventional crystal plasticity. Correlations between these mechanical fields and microstructural features, and their influence on local and global mechanical behavior are examined for the different MMC microstructures.

Background Mycoplasma genitalium (MG) is an emerging pathogen among men who have sex with men (MSM) with raising rates of antibiotic resistance. This study assessed the prevalence and incidence of MG infection in MSM enrolled in the open-label phase of the ANRS IPERGAY trial with on-demand tenofovir disoproxil fumarate/emtricitabine for human immunodeficiency virus prevention and the impact of doxycycline post-exposure prophylaxis (PEP). Methods 210 subjects were tested at baseline and at 6 months by real-time PCR assays for MG detection in urine samples and oropharyngeal and anal swabs. Resistance to azithromycin (AZM), to fluoroquinolones (FQs), and to doxycycline was investigated in the French National Reference Center of Bacterial Sexually Transmitted Infections (STIs). Results The all-site prevalence of MG at baseline was 10.5% (6.3% in urine samples, 4.3% in anal swabs, 0.5% in throat swabs) and remained unchanged at 6 months whether or not PEP was used: 9.9% overall, 10.2% with PEP, 9.6% without. The overall rate of MG resistance (prevalent and incident cases) to AZM and FQs was 67.6% and 9.1%, respectively, with no difference between arms. An in vivo mutation of the MG 16S rRNA, which could be associated with tetracycline resistance, was observed in 12.5% of specimens tested. Conclusions The prevalence of MG infection among MSM on pre-exposure prophylaxis was high and its incidence was not decreased by doxycycline prophylaxis with a similar high rate of AZM and FQ resistance, raising challenging issues for the treatment of this STI and supporting current recommendations to avoid testing or treatment of asymptomatic MG infection.

The affiliation details for Geltrude Mingrone are corrected below.

Objective The ENVOL study was designed to assess the psychosocial impact of disease and therapy in a French cohort of cryopyrin-associated periodic syndromes (CAPS) patients (and caregivers) treated with canakinumab. Methods The ENVOL study was a multicenter, observational study of CAPS patients given ≥1 canakinumab dose. Data were collected before treatment, at 6 and 12 months afterward, and at the last visit. Patients and caregivers completed questionnaires assessing changes from the 12 months of pretreatment to 12 months prior to interview. Data were analyzed retrospectively. Results The study included 10 physicians and 68 patients (53 adults, 15 children). Sixty-five patients (95.6%) were still receiving canakinumab at the last visit (median 5 years after starting therapy). The mean ± SD score for patient-reported general health increased from 7 ± 2.9 before canakinumab to 2.7 ± 2.7 after treatment (P 40% of respondents. Caregivers spent a median of 3 versus 0.5 hours/week on care in the 12 months of pretreatment versus 12 months prior to interview (P

With approximately 67 million individuals affected worldwide, autism spectrum disorder (ASD) is the fastest growing neurodevelopmental disorder (United Nations, 2011), with a prevalence estimated to be 1/100. In France ASD affects approximately 600,000 individuals (from childhood to adulthood, half of whom are also mentally retarded), who thus have a major handicap in communication and in adapting to daily life, which leads autism to be recognized as a national public health priority. ASD is a neurodevelopmental disorder that affects several domains (i.e., socio-emotional, language, sensori-motor, executive functioning). These disorders are expressed early in life with an age of onset around 18 months. Despite evidence suggesting a strong genetic link with ASD, the genetic determinant remains unclear. The clinical picture is characterized by impairments in social interaction and communication and the presence of restrictive and repetitive behaviors (DSM-5, ICD-10). However, in addition to these two main dimensions there is significant comorbidity between ASD and other neurodevelopmental disorders such as attention deficit hyperactivity disorder or with genetic and medical conditions. One of the diagnostic features of ASD is its early emergence: symptoms must begin in early childhood for a diagnosis to be given. Due to brain plasticity, early interventions are essential to facilitate clinical improvement. Therefore, general practitioners and pediatricians are on the front line to detect early signs of ASD and to guide both medical explorations and early rehabilitation.

Resume Introduction Une atteinte interstitielle pulmonaire, une eruption cutanee et une elevation de l’enzyme de conversion peuvent suggerer d’autres diagnostics qu’une sarcoidose. Observation Un homme de 58 ans presentait depuis 2 ans une dyspnee avec une elevation du taux de l’enzyme de conversion et un syndrome interstitiel pulmonaire avec micronodules. Une sarcoidose etait evoquee. Une corticotherapie generale permettait l’amelioration de la dyspnee mais elle recidivait des l’arret. On notait des macules erythemateuses eczematiformes de la racine des membres, d’evolution fluctuante, avec histologiquement une folliculite aspecifique. L’identification d’une mycobacterie du complexe Mycobacterium avium (MAC) dans le lavage broncho-alveolaire faisait instaurer une antibiotherapie antimycobacterienne sans efficacite. La relecture de la tomodensitometrie pulmonaire et l’interrogatoire (utilisation quotidienne d’un jacuzzi depuis 7 ans) amenaient au diagnostic de pneumopathie d’hypersensibilite a MAC. Les lesions cutanees etaient, malgre leur aspect clinique eczematiforme, considerees comme des folliculites liees au jacuzzi (« hot tub folliculitis »). L’arret des bains bouillonnants et une breve corticotherapie generale permettaient la disparition des signes cliniques et une normalisation radiologique a 4 mois, sans recidive a 2 ans. Discussion Le « hot tub lung » est une pneumopathie d’hypersensibilite liee a la presence de MAC dans l’eau des jacuzzis. Elle regresse a l’arret de leur utilisation, sans autre traitement necessaire. La « hot tub folliculitis » liee a Pseudomonas aeruginosa se presente comme une eruption maculopapuleuse des zones couvertes (maillot) qui survient dans les 48 heures suivant une baignade et regresse en moins de deux semaines. Conclusion Notre cas est original par les atteintes pulmonaire et cutanee concomitantes liees a l’utilisation d’un jacuzzi, avec un mecanisme immuno-allergique pour la MAC et probablement infectieux pour les lesions cutanees.

Il blocco del plesso cervicale ha come indicazione principale l’anestesia per la chirurgia carotidea. Consente, inoltre, la chirurgia minore del collo. La conoscenza dell’anatomia e essenziale. Gli spazi di diffusione delimitano tre tipi di blocco del plesso cervicale (BPC): superficiale, intermedio e profondo. Quest’ultimo puo essere ottenuto mediante una o piu iniezioni, con o senza neurostimolatore. Piu moderna, la guida ecografica rende il BPC intermedio una tecnica sicura e facile da eseguire. L’apprendimento della tecnica anestetica e necessario per ridurre il rischio di sviluppare complicanze. Le complicanze sono principalmente correlate alla puntura vascolare, a un’iniezione peri- o intradurale e alla tossicita degli anestetici locali il cui assorbimento plasmatico e intenso in questa zona.

Placental syncytiotrophoblast (ST) is considered as the main placental endocrine tissue secreting progesterone, a steroid essential for maintenance of pregnancy. However, each step of progestins production has been poorly investigated in villous cytotrophoblast (VCT) regarding ST formation. We aimed to characterize progestins production during human differentiation of VCT into ST. VCTs were isolated from term placenta and cultivated, with or without forskolin (FSK), to stimulate trophoblast differentiation. Secreted progestins concentrations were determined by immuno-assay and Gas Chromatography-tandem mass spectrometry. Intracellular expression of cholesterol transporter and enzymes involved in steroidogenesis were studied by immunofluorescence, western-blot, and RT-qPCR. Progesterone and pregnenolone are produced by VCT and their secretion increases with VCT differentiation while 17-hydroxyprogesterone concentration remains undetectable. HSD3B1 enzyme expression increases whereas MLN64, the cholesterol placental mitochondrial transporter and P450SCC expressions do not. FSK induces progestins production. Progestins placental synthesis is effective since VCT and increases with ST formation thanks to mitochondria.

Background: Calcific aortic valve stenosis (CAVS) is a frequent and life-threatening cardiovascular disease for which there is currently no medical treatment available. To date, only 2 genes, LPA and PALMD , have been identified as causal for CAVS. We aimed to identify additional susceptibility genes for CAVS. Methods: A GWAS (genome-wide association study) meta-analysis of 4 cohorts, totaling 5115 cases and 354 072 controls of European descent, was performed. A TWAS (transcriptome-wide association study) was completed to integrate transcriptomic data from 233 human aortic valves. A series of post-GWAS analyses were performed, including fine-mapping, colocalization, phenome-wide association studies, pathway, and tissue enrichment as well as genetic correlation with cardiovascular traits. Results: In the GWAS meta-analysis, 4 loci achieved genome-wide significance, including 2 new loci: IL6 (interleukin 6) on 7p15.3 and ALPL (alkaline phosphatase) on 1p36.12. A TWAS integrating gene expression from 233 human aortic valves identified NAV1 (neuron navigator 1) on 1q32.1 as a new candidate causal gene. The CAVS risk alleles were associated with higher mRNA expression of NAV1 in valve tissues. Fine-mapping identified rs1800795 as the most likely causal variant in the IL6 locus. The signal identified colocalizes with the expression of the IL6 RNA antisense in various tissues. Phenome-wide association analyses in the UK Biobank showed colocalized associations between the risk allele at the IL6 lead variant and higher eosinophil count, pulse pressure, systolic blood pressure, and carotid artery procedures, implicating modulation of the IL6 pathways. The risk allele at the NAV1 lead variant colocalized with higher pulse pressure and higher prevalence of carotid artery stenosis. Association results at the genome-wide scale indicated genetic correlation between CAVS, coronary artery disease, and cardiovascular risk factors. Conclusions: Our study implicates 3 new genetic loci in CAVS pathogenesis, which constitute novel targets for the development of therapeutic agents.

Prevalence of postpartum depression (PPD) ranges from 10 to 15 % of parturients. The impact of the PPD is major on the maternal bond and the health of both mother and child. Its physiopathological mechanisms appear to differ from other types of depression. Today, pharmacotherapy is based on nonspecific treatment, and recent therapeutic advances in this field require a comprehensive approach of the implication of the GABAergic system in the development of PPD. Neurosteroid levels during pregnancy and after parturition and the GABA-A-r modulation are thought to be involved in PPD.To evaluate if the GABAergic approach is relevant in postpartum depression management.We conducted a systematic review of literature based on the MEDLINE database with the following Medical Subject Headings (MeSH): "postpartum depression", "GABA", "ganaxolone", "brexanolone", "allopregnanolone", prior to September 2019. We selected articles in English: preclinical and clinical studies, literature review, observational and therapeutic studies.Preclinical models (mouse and rat) show changes in GABAergic inhibition in the peripartum period and correlation between allopregnanolone and GABA-A-r plasticity. This plasticity in the peripartum period maintains levels of inhibition adapted despite increased neurosteroid levels. KO models for the GABA-A-r δ subunit develop depression and anxiety symptoms in the postpartum period, and a change in the expression of the gene coding for the GABA-R alpha-4 subunit was found. Artificial inhibition of progesterone metabolism during post-partum increased depression symptoms. GABAergic fluctuation seems to be interrelated with other systems such as those of oxytocins. A synthetic neurosteroid (SGE-516) was tested on mouse models of PPD, KO for δ-GABA-A-r or KCC2, and showed decreased depressive symptoms and better mothering. Clinical studies confirm neurosteroid fluctuation and changes in the GABAergic system during the peripartum period. Allopregnanolone is the neurosteroid the most studied in PPD, and it is elevated in the brain during the pregnancy. Studies disagree on the presence of significant differences in allopregnanolone plasma levels during pregnancy or postpartum between women with PPD or not. Women with a history of PPD have greater susceptibility to neurosteroid withdrawal. Imagery and genetical data also show a link between allopregnanolone and PPD. The GABA-A-r may not recover in time following a reduced number during pregnancy, and this mismatch between neurosteroid levels and their receptor may trigger PPD. Several randomized controlled trials investigated brexanolone administrated IV, a synthetic formulation of allopregnanolone, and demonstrated a rapid and well tolerated reduction in depressive symptoms. In March 2019 brexanolone obtained FDA approval in PPD indication under the name Zulresso. However, there are differences in the time of beginning of PPD, which could constitute different subgroups of this disease, and which physiopathology could respond to different mechanisms. Prenatal depression does not respond to a GABAergic approach, but women without any risk factor or previous mood disorder developing PPD in the weeks following childbirth could be particularly responsive to this kind of treatment.Disability to modulate GABA-A-r expression during pregnancy and restore its previous state after parturition appears to trigger PPD. The GABAergic system is a promising pharmacotherapy target. From preclinical to clinical studies for about twenty years the GABAergic system has been incriminated and targeted in this challenging mental disease.

International audience; Les tumeurs de l’orbite représentent une pathologie relativement fréquente et posent des problèmes de diagnostic et de prise en charge. Elles peuvent être bénignes ou malignes. Tous les tissus contenus dans l’orbite peuvent être le siège d’un développement tumoral et de ce fait, elles sont très nombreuses. Parmi les tumeurs bénignes, on retiendra chez l’adulte les méningiomes et les hémangiomes caverneux et pour les tumeurs malignes, les lymphomes, les métastases, les tumeurs d’origine ORL, les tumeurs de la glande lacrymale. Elles se manifestent en général par une symptomatologie peu spécifique, le syndrome orbitaire, associant exophtalmie, troubles oculomoteurs, signes inflammatoires, douleurs et parfois masse palpable. L’imagerie (scanner RX, imagerie par résonance magnétique ou échographie Doppler couleur) confirme l’existence d’une tumeur, précise son siège, son extension, l’existence d’éventuelles métastases. La biopsie et l’examen anatomique et cytopathologique confirment le type bénin ou malin de la tumeur. À partir de ces trois éléments : clinique, imagerie et anatomie pathologique, la prise en charge est décidée, le plus souvent chirurgicale, selon l’avis d’une réunion de concertation pluridisciplinaire en cas de tumeur maligne. La radiothérapie et la chimiothérapie peuvent compléter le traitement.

Objectif Le debriefing est un element fondamental de l’apprentissage par simulation pleine echelle en sciences de la sante, mais reste un processus complexe et difficile a apprehender. L’objectif de cet article est de definir le debriefing postsimulation, d’en preciser les objectifs et de degager les grands principes du debriefing au regard des donnees de la litterature.

Introduction Le complexe de Carney (CNC) est un syndrome regroupant des neoplasies endocriniennes et non endocriniennes. Cette etude decrivant les caracteristiques des lesions mammaires des patientes avec CNC, les autres manifestations du CNC et le genotype PRKAR1A, s’est particulierement interessee aux carcinomes mammaires, cancer le plus frequent chez la femme et principale cause de deces par cancer dans le monde. Methodes Cette cohorte de 70 patients avec CNC provient d’un suivi prospectif multicentrique francais de 3 ans (Espiard et al. JCEM 2020). L’analyse des 50 femmes incluses a porte sur les manifestations de CNC (lesions mammaires particulierement), le genotype et les caracteristiques hormonales. Resultats Parmi les 38 femmes avec imagerie mammaire, dix presentaient des lesions benignes et six des carcinomes : un carcinome in-situ a 54 ans et cinq cancers invasif avant 50 ans et une recurrence controlaterale. La survenue du cancer mammaire chez les patientes avec CNC etait plus frequente et l’âge moyen 17 ans plus precoce (44,7 ans) que la population generale. Tous les cancers mammaires sont survenus chez des patientes mutees PRKAR1A, avec de bons facteurs pronostic : recepteurs hormonaux positifs, HER2 negatif, un seul cancer metastatique. Il n’y avait pas d’association entre les carcinomes mammaires et les manifestations du CNC ou facteurs de risque conventionnels. Discussion Les lesions mammaires sont frequentes chez les femmes atteintes de CNC. Le carcinome mammaire pourrait etre une « nouvelle » manifestation de cette maladie, une strategie de depistage et un suivi adequat pourraient etre proposes.

Adjuvant chemotherapy with carboplatin and paclitaxel is recommended for all high-grade ovarian or Fallopian tube cancers, stage FIGO I-IIA (grade A). After a complete first surgery, it is recommended to deliver 6 cycles of intravenous (grade A) or to propose intraperitoneal (grade B) chemotherapy, to be discussed with patient, according to the benefit/risk ratio. After a complete interval surgery for a FIGO III stage, the hyperthermic intra peritoneal chemotherapy (HIPEC) can be proposed in the same conditions of the OV-HIPEC trial (grade B). In case of tumor residue after surgery or FIGO stage IV, chemotherapy associated with bevacizumab is recommended (grade A). For BRCA mutated patient, Olaparib is recommended (grade B).

Faced to an undetermined ovarian mass on ultrasound, an MRI is recommended and the ROMA score (combining CA125 and HE4) can be proposed (grade A). In case of suspected early stage ovarian or fallopian tube cancer, omentectomy (at least infracolonic), appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C) and pelvic and para-aortic lymphadenectomy are recommended (grade B) for all histological types, except for the expansive mucinous subtype where lymphadenectomy may be omitted (grade C). Minimally invasive surgery is recommended for early stage ovarian cancer, if there is no risk of tumor rupture (grade B). Laparoscopic exploration for multiple biopsies (grade A) and to evaluate carcinomatosis score (at least using the Fagotti score) (grade C) are recommended to estimate the possibility of a complete surgery (i.e. no macroscopic residue). Complete medial laparotomy surgery is recommended for advanced cancers (grade B). It is recommended in advanced cancers to perform para-aortic and pelvic lymphadenectomy in case of clinical or radiological suspicion of metastatic lymph node (grade B). In the absence of clinical or radiological lymphadenopathy and in case of complete peritoneal surgery during an initial surgery for advanced cancer, it is possible not to perform a lymphadenectomy because it does not modify the medical treatment and the overall survival (grade B). Primary surgery is recommended when no tumor residue is possible (grade B).

Introduction An extrafine pMDI formulation of the long-acting beta agonist formoterol fumarate (FF) was developed, and its efficacy and safety evaluated in a controlled clinical setting. Methods A double-blind, double-dummy, single dose, randomised, 4-way crossover, placebo controlled study was conducted to evaluate efficacy and safety of FF (6 µg) one puff or two puffs versus Foradil Aerolizer (FOR) 12 µg or placebo in moderate to severe asthmatic patients. Primary endpoint was 12 hour average FEV1. Secondary efficacy endpoints were onset and duration of action. Safety endpoints were vital signs, QTc, serum potassium and glucose. Results 53 asthmatic patients (mean age 34.4 years, 32 male and 21 female) were randomized and 52 were evaluable. Average FEV1 and peak FEV1 increased significantly after FF 6 and 12 µg, with a trend toward greater efficacy with the higher FF dose. Equivalence between FF 12 µg and FOR 12 µg was demonstrated. Median time to 15% onset was 10, 15 and 10 min for FF 12 µg, FF 6 µg and FOR, respectively confirming the rapid onset of action. Median time to 15% offset was 718, 480, 719 and 240 min for FF 12 µg, FF 6 µg, FOR and Placebo respectively suggesting that FF 12 µg provides an improved coverage of the 12 hour administration interval and demonstrating a marked dose-response. No clinically significant changes were observed for blood pressure and heart rate. Serum potassium and glucose remained within normal limits for the majority of subjects. QTcB was similar for all treatments and no values exceeded 470 m/sec. There were no serious adverse events. Frequency of treatment emergent adverse events was similar in the four treatments, with tremor the most common, as expected. Conclusions This study demonstrates that extrafine FF has similar efficacy and safety as compared to FOR. FF 12 µg shows a greater and more prolonged bronchodilation compared to FF 6 µg, and confirms a marked dose–response relation for FF. This has to be considered when assessing the most appropriate therapeutic dose of FF in asthmatics.

Psychomotor impairments in Autism Spectrum Disorders (ASD) have frequently been described in scientific literature. Such deficits impact upon the development of social motor function and interfere with the ability to adjust to everyday life. The inclusion of sensory-motor signs in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) confirms their importance in the diagnosis of ASD. Previous literature has shown the presence precocity of these signs, sometimes before the alteration of the social communication. To our knowledge, there are no existing clinical tools to measure sensory-psychomotor deficit, specifically in ASD. The current paper presents the construction and validation of a new scale, designed to evaluate sensory-psychomotor signs in Autism: 'the Sensory-psychomotor Particularities Scale in Autism' (SPSA).The scale is composed of 160 items describing common sensory-psychomotor signs in autism. These items are grouped into 20 variables: touch, nociception, vestibular sensitivity, proprioceptive sensitivity, vision, auditory, multimodality, tone, posture, balance, global coordination, manual dexterity, body schema, bodily self-consciousness, relational adjustment, emotional expression, use of objects, space, time and tonico-emotional regulation. For each item, the psychomotor therapist evaluated sensori-psychomotor signs according to a five-level Likert scale (0="the sign is never expressed by the person", 1="weakly expressed", 2="moderately expressed", 3="severely expressed" and 4="the sign is very characteristic of the person and very severely expressed"). This is completed by a family interview in order to assess the impact of these signs on everyday situations. The study included 111 children with autism. The presence of neurological and genetic diseases was exclusion criteria. For each child, a global developmental evaluation was carried out by an expert clinical team specializing in ASD. Standardized clinical tools were used: Autism Diagnostic Observation Schedule (ADOS), Childhood Autism Rating Scale (CARS), Behavior Summarized Evaluation scale (BSE-R), Repeated and Restricted Behavior scale (RRB), Movement Assessment Battery for Children (M-ABC), Motor Development Rating scale (MDR), Sensory Profile (SP). Developmental quotients (DQ) were evaluated using various tests depending on age and ability.Factor analysis produced three clinically relevant factors: F1: "sensory-emotional synchronization", F2: "multisensory integration" and F3: "motor skills": each containing a similar quantity of items. They account for roughly equal percentages of variance (18.9%, 18.0%, 16.8%, respectively). The factorial structure does not change if the 26 children with comorbid developmental coordination disorder are removed. The three factors show good internal consistency and excellent inter-rater reliability. F1 is comprised of 6 items: touch, nociception, proprioceptive sensitivity, vision, emotional expression and tonico-emotional regulation. This factor is significantly associated with items of the Sensory Profile (touch processing, poor registration, sensory seeking). F2 is comprised of 5 items: multimodality, bodily self-consciousness, relational adjustment, use of objects and space. This factor is associated with ADOS, BSE-R and RRB scores, and the item "touch processing" of the Sensory Profile. F3 is comprised of 4 items: tone, posture, global coordination, manual dexterity. This factor is associated with the M-ABC, the MDR and the item "low endurance" of the Sensory Profile.The SPSA is a relevant clinical tool to assess the severity of sensory-psychomotor clinical signs in order to describe the individual profiles of children with ASD. It represents a critical step in advancing knowledge of the complex and heterogeneous pattern of psychomotor development in autism. It could make a valuable contribution to the field, both in research and clinical practice.

Il trattamento conservativo del piede torto varo equino e riconosciuto da tutte le equipe di ortopedici pediatrici come una necessita immediata, urgente e ineludibile. Questa gestione comprende, tuttavia, delle realta molto diverse: ogni equipe ha i suoi principi, spesso molto diversi o, anche, contraddittori, in particolare in materia di contenzioni. La metodica funzionale, la metodica che utilizza gessi successivi e la metodica mista con manipolazioni e stecche hanno, tuttavia, gli stessi obiettivi fondamentali: fare in modo di dover operare il minor numero possibile di piedi torti; se la chirurgia e necessaria, bisogna fare in modo che essa sia limitata. Per le equipe che hanno al loro interno dei fisioterapisti specializzati, le manipolazioni e le contenzioni si impongono fin dalla nascita come un’urgenza. Tuttavia, per la giovane generazione di ortopedici pediatrici, posta di fronte ai problemi di organizzare una nuova equipe poco esperta e alla mancanza di risultati soddisfacenti, la tendenza e di accantonare progressivamente una metodica funzionale dai risultati pienamente riconosciuti ma che richiede molto tempo per la sua attuazione, per lasciare maggiore spazio a una metodica piu facilmente riproducibile, meno costosa e ampiamente sostenuta da Ponseti e dai suoi seguaci: la metodica che utilizza gessi successivi. Questo articolo tentera di placare i dibattiti annoiati o appassionati che persistono tra le diverse equipe impegnate nel trattamento del piede equino, dimostrando che, tra tutte queste tecniche, e interessante arrivare a rilevare chiaramente piu consenso che disaccordo.

El tratamiento conservador del pie zambo equinovaro es reconocido por todos los equipos de ortopedistas pediatras como una necesidad inmediata, urgente e ineludible. Sin embargo, este tratamiento abarca realidades muy diversas: cada equipo tiene sus principios, a menudo muy distintos, incluso contradictorios, sobre todo en materia de contenciones. El metodo funcional, el metodo con yesos sucesivos, el metodo mixto con manipulaciones y ferulas tienen, sin embargo, los mismos objetivos fundamentales: operar la menor cantidad posible de pies zambos y, si la cirugia es necesaria, tratar de que sea limitada. En los equipos integrados por kinesiterapeutas especializados, las manipulaciones y las contenciones se consideran desde el nacimiento como una urgencia. En cambio, para la nueva generacion de ortopedistas pediatras, confrontada a la conformacion de un equipo con profesionales poco experimentados y a la falta de resultados satisfactorios, la tendencia es empujar hacia una via muerta un metodo funcional plenamente reconocido pero que consume mucho tiempo para adoptar por completo un metodo reproducible con mas facilidad, menos costoso y ampliamente sometido a consideracion de los ortopedistas por Ponseti y sus adeptos: el metodo mediante yesos sucesivos. En este articulo se intentaran apaciguar los debates, tediosos o apasionados, que subsisten entre los equipos implicados en el tratamiento del pie zambo, demostrando la utilidad de obtener mas consenso que desacuerdo en cuanto al uso de todas estas tecnicas.

Many cancer predisposition syndromes are preceded or accompanied by a range of typical skin signs. Gorlin syndrome is a rare multisystem inherited disorder which can predispose to basal cell carcinomas (BCCs), childhood medulloblastomas in addition to various developmental abnormalities; the majority of cases are due to mutations in the PTCH1 gene. Approximately 5% of cases have been attributed to a mutation in the SUFU gene. Certain phenotypic features have been identified as being more prevalent in individuals with a SUFU mutation such as childhood medulloblastoma, infundibulocystic BCCs and trichoepitheliomas. Recently hamartomatous skin lesions have also been noted in families with childhood medulloblastoma, a "Gorlin like" phenotype and a SUFU mutation. Here we describe a family previously diagnosed with Gorlin syndrome with a novel SUFU splice site deleterious genetic variant, who have several dermatological features including palmar sclerotic fibromas which has not been described in relation to a SUFU mutation before. We highlight the features more prominent in individuals with a SUFU mutation. It is important to note that emerging therapies for treatment of BCCs in patients with a PTCH1 mutation may not be effective in those with a SUFU mutation.

International audience

International audience

International audience; A portable stereo gamma camera has been built, based on two hybrid pixelated detectors, each of them comprising a 1 mm thick CdTe substrate bump-bonded to the Timepix readout chip, a pixelated CMOS ASIC consisting of 256 × 256 pixels with 55 µm pitch.The technique described in this paper allows the automatic estimation of the distances between the prototype and the located radioactive sources by using triangulation based on epipolar geometry. The 3-D Cartesian coordinates of the sources are provided even when they are hidden behind an occluding material, such as a wall, or inside a barrel. Furthermore, the combination of the prototype with a depth sensor enables a wide range of applications, including the 3-D volumetric reconstruction of the scene under study as well as the capability of autonomously determining if an object is occluding the located radioactive sources.We discuss here the main features of the whole methodology developed and we also present the experimental results obtained at laboratory scale.

Correction for ‘Isoprene chain shuttling polymerisation between cis and trans regulating catalysts: straightforward access to a new material’ by Y. Phuphuak et al., Chem. Commun., 2017, 53, 5330–5333.

Introduction Les biotherapies anti-TNFα (infliximab et adalimumab, principalement) sont utilisees pour traiter les sarcoidoses severes et/ou refractaires. L’etude STAT a montre une reponse clinique dans 64 % des cas, principalement pour les atteintes neurologiques, cardiaques, cutanees, et ORL [1] . Il n’y a, cependant, pas de donnees concernant le profil et le devenir des patients non repondeurs aux anti-TNFα. Objectif Decrire les patients non repondeurs inclus dans le registre national francais des sarcoidoses traitees par anti-TNFα (STAT). Patients et methodes Etude de cohorte retrospective a partir d’un appel a observations national en juillet 2014. Etaient inclus les patients atteints de sarcoidose histologiquement prouvees et/ou de neurosarcoidose probable selon la classification de Zajicek consideres comme non-repondeurs aux anti-TNFα. Resultats Parmi 132 patients, 14 patients etaient identifies comme refractaires aux anti-TNFα. Cinq patients ont ete exclus (un deces, 3 donnees manquantes, 1 diagnostic final alternatif). L’âge median des 9 patients inclus, (6 femmes) etait de 48 ans (29–70) a l’initiation des anti-TNFα. La maladie atteignait en moyenne 4,2 organes et les patients avaient recu en moyenne 2 traitements immunosuppresseurs (IS) avant les anti-TNFα. Huit patients avaient recus de l’infliximab et un patient avait recu 3 anti-TNFα differents. Quatre patients recevaient un IS en meme temps que les anti-TNFα. La duree mediane de traitement anti-TNFα etait de 7 mois (3–24). Apres un suivi median de 35 mois (19–128) post-traitement anti-TNFα, 2 patients avaient finalement une reponse complete, 5 avaient une reponse partielle et 2 avait une maladie evolutive. Les patients recevaient en moyenne 2 nouvelles lignes de traitements IS. Les traitements de premiere ligne etaient le methotrexate (n = 5) et le cyclophosphamide (n = 2). Dans 6 cas, la reponse clinique etait obtenue avec un traitement IS recu anterieurement par le patient. Conclusion Dans les sarcoidoses refractaires, les immunosuppresseurs conservent leur utilite meme en cas d’echec des anti-TNFα.

Resume Le developpement du diabete de type 2 (DT2) est favorise par une insulinoresistance predominant aux niveaux musculaire et hepatique, associee a une diminution de la capacite d’insulinosecretion, notamment du pic precoce prandial d’insuline. Les facteurs de risque de DT2 dans une population non obese ont ete peu etudies. La glycemie a jeun constitue le parametre biologique le plus fortement associe au risque de DT2 incident. Un HDL-cholesterol bas et une hypertriglyceridemie constituent egalement des marqueurs associes au risque de DT2 chez le sujet non obese. Une elevation, meme moderee, des enzymes hepatiques, alanine aminotransferase (ALAT) et gamma-glutamyltransferase (GGT) est un marqueur de risque independant pour le DT2 incident et peut aider, en pratique clinique, a identifier une population non obese a plus haut risque de diabete.

This paper presents the studies made on the definition and design of a decentralized and modular electrical architecture of Power Conditioning Unit (PCU). The modular PCU is able to cover a large range of mission demands by adapting the number of power modules (PM) while the electrical interfaces remain the same. A decentralized architecture is proposed where each module is able to control the solar arrays and to manage the batteries. It appears that this kind of architecture becomes feasible thanks to digital circuits and using a communication bus [1]. Breadboards are being tested in order to validate the concept. Reliability and robustness aspects are studied and a redundant architecture is tested.

Assessing disease activity in patients suffering from autoimmune diseases is complex. Symptoms are multiple, often subjective and there are no reliable biomarkers. Many activity scores have been implemented to compare treatment efficacy in clinical trials. Their use in clinical practice is largely unknown. We performed a practical survey to analyze the use of activity scores in clinical practice to consider treatment response and to assess the determinants of their use.A sample of French internists answered a questionnaire about activity scores of systemic lupus erythematosus, Sjögren's syndrome, autoimmune myositis and necrotizing vasculitis of small vessels. The frequency of use of these tools, the causes of their non-use, and the general opinion of practitioners about the place of theses scores in current practice were described.The form was completed by 92 internists. Seventy percent of them supported the use of activity scores in consultations, but actually used them in less than 25% of patient visits. The reasons for the low use of these scores are mainly the ignorance of their existence (42%) and their length or complexity (28%).The discrepancy between the ratio of practitioners who believe that scores have a place in daily practice and their actual use shows that the current scores do not meet the needs. The implementation of easily usable activity scores in inflammatory diseases remains a challenge for the internists.

With approximately 67 million individuals affected worldwide, autism spectrum disorder (ASD) is the fastest growing neurodevelopmental disorder (United Nations, 2011), with a prevalence estimated to be 1/100. In France ASD affects approximately 600,000 individuals (from childhood to adulthood, half of whom are also mentally retarded), who thus have a major handicap in communication and in adapting to daily life, which leads autism to be recognized as a national public health priority. ASD is a neurodevelopmental disorder that affects several domains (i.e., socio-emotional, language, sensori-motor, executive functioning). These disorders are expressed early in life with an age of onset around 18 months. Despite evidence suggesting a strong genetic link with ASD, the genetic determinant remains unclear. The clinical picture is characterized by impairments in social interaction and communication and the presence of restrictive and repetitive behaviors (DSM-5, ICD-10). However, in addition to these two main dimensions there is significant comorbidity between ASD and other neurodevelopmental disorders such as attention deficit hyperactivity disorder or with genetic and medical conditions. One of the diagnostic features of ASD is its early emergence: symptoms must begin in early childhood for a diagnosis to be given. Due to brain plasticity, early interventions are essential to facilitate clinical improvement. Therefore, general practitioners and pediatricians are on the front line to detect early signs of ASD and to guide both medical explorations and early rehabilitation.

Interstitial lung disease, cutaneous rash and elevated serum angiotensin converting enzyme (ACE) may suggest diagnoses other than sarcoidosis.A 58-year-old man had presented dyspnoea for 2 years with increased angiotensin-converting enzyme, as well as an interstitial syndrome and micronodules. The possibility of sarcoidosis was raised. Systemic corticosteroids resulted in improvement of the dyspnoea although it recurred on dose reduction. We noted fluctuating eczematous macules of the limbs with a histology of aspecific folliculitis. The identification of Mycobacterium avium complex (MAC) in the bronchoalveolar wash prompted us to initiate antimycobacterial therapy, but this was to no avail. Review of the CT-scan and questioning of the patient (daily use of a Jacuzzi for 7 years) resulted in diagnosis of hypersensitivity pneumonitis due to MAC. The cutaneous lesions were taken to indicate "hot tub folliculitis". Discontinuation of hot-tub use and a short course of oral corticosteroids resulted in healing within 4 months, with no recurrence at 2 years.HTL is a form of hypersensitivity pneumonitis due to the presence of MAC in the water of Jacuzzis. This condition regresses spontaneously without treatment on discontinuation of Jacuzzi use. Hot-tub folliculitis due to Pseudomonas aeruginosa (PA) presents as macules and papules on covered skin areas (swimsuit) within 48hours of bathing and often declines within 2 weeks.Our case is original as regards the concomitant lung and cutaneous involvement associated with Jacuzzi use, with an immunoallergic mechanism for the MAC and probably an infectious mechanism for the PA.

Background The application of safety principles from the aviation industry to the operating room has offered hope in reducing surgical complications. This study aimed to assess the impact on major surgical complications of adding an aviation-based team training programme after checklist implementation. Methods A prospective parallel-group cluster trial was undertaken between September 2011 and March 2013. Operating room teams from 31 hospitals were assigned randomly to participate in a team training programme focused on major concepts of crew resource management and checklist utilization. The primary outcome measure was the occurrence of any major adverse event, including death, during the hospital stay within the first 30 days after surgery. Using a difference-in-difference approach, the ratio of the odds ratios (ROR) was estimated to compare changes in surgical outcomes between intervention and control hospitals. Results Some 22 779 patients were enrolled, including 5934 before and 16 845 after team training implementation. The risk of major adverse events fell from 8·8 to 5·5 per cent in 16 intervention hospitals (adjusted odds ratio 0·57, 95 per cent c.i. 0·48 to 0·68; P < 0·001) and from 7·9 to 5·4 per cent in 15 control hospitals (odds ratio 0·64, 0·50 to 0·81; P < 0·001), resulting in the absence of difference between arms (ROR 0·90, 95 per cent c.i. 0·67 to 1·21; P = 0·474). Outcome trends revealed significant improvements among ten institutions, equally distributed across intervention and control hospitals. Conclusion Surgical outcomes improved substantially, with no difference between trial arms. Successful implementation of an aviation-based team training programme appears to require modification and adaptation of its principles in the context of the the surgical milieu. Registration number: NCT01384474 (http://www.clinicaltrials.gov).

International audience; Iron-rich alloys in the Fe-Ti-B system are being studied for their potential as a new generation of lightened steel-matrix composites reinforced by titanium diborides. In this work, the iron-rich corner of the Fe-Ti-B ternary system was investigated at temperatures between 1150 degrees C and 1400 degrees C. For this purpose, fourteen key alloys containing up to 5 mass % Ti and B were selected on the basis of preliminary thermodynamic calculations and processed in an induction furnace by melting the starting materials at 1630 degrees C for 1 h. Two types of experiments were performed: (i) long-duration annealing experiments, involving a liquid phase, performed by the electromagnetic phase separation technique at temperatures between 1175 degrees C and 1250 degrees C and (ii) differential thermal analysis of samples during heating up to 1400 degrees C and cooling with different cooling and heating rates (2, 5 and 10 degrees C min(-1)). Samples were characterized by X-ray diffraction, scanning electron microscopy, field electron gun scanning electron microscopy and complementary chemical analysis, combining electron microprobe analysis, inductively coupled plasma and secondary ion mass spectrometry, were performed. On the basis of an analysis of the solidification paths of the fourteen alloys as well as solid/liquid equilibria investigations, a partial liquidus projection in the investigated region was proposed. Moreover, the composition and melting temperature of the gamma Fe-TiB2-Fe2B ternary eutectic alloy are determined with good accuracy. This study is a first step towards an extended experimental work on the iron-rich corner of the Fe-Ti-B ternary system. (C) 2015 Elsevier B.V. All rights reserved.

Introduction L’hyperplasie macronodulaire bilaterale primitive des surrenales (HMBS) est une cause rare de syndrome de Cushing. Le traitement classique par surrenalectomie bilaterale impose au patient un traitement substitutif a vie. Un traitement medical anticortisolique est possible si refus/contre-indication a la chirurgie ou dans les presentations cliniques moderees. Objectif Etudier l’efficacite et la tolerance du traitement par metyrapone dans l’HMBS. Methode Etude retrospective monocentrique de 30 patients traites par metyrapone entre 2011 et 2016. Resultats Quatre-vingt pour cent de femmes, âge moyen 56,6 ans, duree moyenne de traitement 12,1 mois (0,36–44,9 mois). Tous les patients avaient au moins un parametre d’evaluation de la secretion du cortisol perturbe sur lequel ils etaient suivis : elevation de la cortisolurie/24 h (13/30), elevation du cortisol minuit plasmatique (3/30) ou salivaire (14/30). La dose moyenne finale de metyrapone etait de 1392 mg/j (500–4000 mg/j). Respectivement a 3 mois, puis aux dernieres nouvelles : la cortisolurie/24 h etait normalisee chez 9/13 puis 7/7 patients ; la cortisolemie minuit etait normalisee chez 0/3 puis 1 patient/3 ; le cortisol salivaire minuit etait normal chez 4/14 puis 10/12 patients. Elevation de l’ACTH (+1,4 pmol/L [−1,6 a 11,9] ; p = 0,04). Tendance a l’amelioration du poids, de la pression arterielle, de l’equilibre glycemique. La metyrapone a ete interrompue chez 10 patients : surrenalectomie (6/10), intolerance (3/10), inefficacite (1/10). Des effets indesirables etaient signales chez 15 patients dont troubles digestifs (7/30) et vertiges (4/30). Conclusion La metyrapone permet de controler l’autonomie surrenalienne chez 70 % des patients avec une tolerance correcte et un benefice clinique a long terme a confirmer.

Objectifs Le glutamate est le principal neurotransmetteur excitateur dans le systeme nerveux central. Les recepteurs metabotropiques du glutamate (mGluR) sont des recepteurs couples a des proteines G, activant des systemes de seconds messagers intracellulaires, pour moduler la neurotransmission glutamatergique. Le sous-type mGluR5 semble etre un regulateur important du systeme glutamatergique en raison de son implication dans differents mecanismes impliques dans la neurogenese et la maintenance synaptique. Plusieurs equipes ont developpe des radiotraceurs specifiques du ce systeme et plus precisement du mGluR5. Dans ce travail, nous avons verifie la pharmacocinetique cerebrale d’un radioligand TEP du mGluR5, le [18]F-FPEB, chez le volontaire sain et propose un protocole d’acquisition adapte aux populations pathologiques. Materiels et methodes Des acquisitions cerebrales dynamiques TEP/TDM (Philips Ingenuity 64) ont ete realisees chez 10 volontaires hommes (âge moyen ± ET : 31 ± 12 ans), pendant 90 min, apres injection intraveineuse de [18F]-FPEB (257 ± 29 MBq). Afin d’obtenir des courbes activite-temps (TAC) et a l’aide du referentiel MNI-AAL, nous avons defini des regions d’interet (ROI) sur differentes structures cerebrales. Resultats Apres un pic maximal obtenu environ 10 min pi, nous avons observe que la fixation du [18F]-FPEB etait maximale au niveau du cortex cingulaire (anterieur et posterieur) et du striatum puis cette fixation decroit ensuite lentement et de facon lineaire jusqu’a la fin de l’acquisition pour l’ensemble des regions cerebrales. Sur les regions connues pour etre moins riches en recepteur mGluR5, et surtout pour le cervelet, la fixation est inferieure aux autres regions. Ceci permet de proposer le cervelet comme region de reference non specifique. Conclusion Pour une acquisition de 90 min, nos resultats sont similaires a ceux obtenus par les equipes americaines qui ont developpe le [18F]-FPEB (Wong et al., 2013, Park et al., 2015, Leurquin-Sterk G et al., 2016). Ils nous permettent egalement de proposer un protocole d’acquisition adapte a des patients avec des durees plus courtes (20 min). Finalement, nos resultats ont confirme l’utilisation du cervelet comme region de reference pour la quantification de la densite de mGluR5. Remerciements Ce travail s’integre dans le programme de l’Agence nationale pour la recherche « Investissements d’Avenir » n°ANR-11-LABX-0018-01), IRON et finance par la Region Centre Val-de-Loire.

Resume Le diabetologue est confronte a une multiplication des options therapeutiques pour le diabete de type 2, ce qui complexifie les choix medicamenteux et met en exergue l’importance d’une reevaluation appropriee du traitement antidiabetique. Il existe une heterogeneite dans la reponse glycemique avec les antidiabetiques, en particulier avec les dernieres classes therapeutiques. La necessite d’une evaluation rigoureuse de l’efficacite mais aussi de la tolerance du traitement instaure s’est impose dans les recommandations internationales pour la prise en charge du diabete de type 2 comme le NICE. Les criteres d’evaluation les plus importants sont l’amplitude de la reduction de l’HbA 1c (au moins 0.5 % a 6 mois), l’effet sur le poids, la tolerance et l’evitement des hypoglycemies, la preservation de la qualite de vie. Une telle reevaluation permet de lutter contre l’inertie clinique, source de perte de temps et de chances pour le patient.

Background: The prevalence of anemia has been studied in well-defined populations, but no large study is available for less restricted populations with various disorders. Design: Two-phase nationwide study: (i) a cross-sectional study including 1351 patients aimed to define the prevalence and characteristics of anemic patients seen in France, and (ii) a prospective longitudinal study of 398 anemic patients aimed to define factors associated with survival. Results: Anemia was present in 874 (65%) patients according to WHO criteria, and 573 (42%) patients had hemoglobin levels

The present paper deals with specific safety issues resulting from the coupling of a nuclear reactor (very high temperature reactor, VHTR) with a hydrogen production plant (HYPP). The first part is devoted to the safety approach consisting in taking into account the safety standards and rules dedicated to the nuclear facility as well as those dedicated to the process industry. This approach enabled two main families of events to be distinguished: the so-called internal events taking place in the coupling circuit (transients, breaks in pipes and in heat exchangers) and the external events able to threat the integrity of the various equipments (in particular the VHTR containment and emergency cooling system) that could result from accidents in the HYPP. By considering a hydrogen production by means of the iodine/sulfur (IS) process, the consequences of the both families of events aforementioned have been assessed in order to provide an order of magnitude of the effects of the incidents and accidents and also in order to propose safety provisions to mitigate these effects when it is necessary. The study of transients induced by a failure of a part of the HYPP has shown the possibility to keep the part of the HYPP unaffected by the transient under operation by means of an adapted regulation set. Moreover, the time to react in case of transfer of corrosive products in the VHTR containment has been assessed as well as the thermohydraulic loading that would experience the coupling pipes in case of very fast uncoupling of the facilities aiming at avoiding an excessive pressurization of the VHTR containment. Regarding the external events, by applying a method used in the process industries, the bounding representative scenarios have been identified on the basis of their consequences but also on the basis of their occurrence frequency. The consequences of the selected bounding scenarios, calculated taking into the source-term, the atmospheric dispersion and the pressure and toxic effects induced respectively by a hydrogen unconfined vapour cloud explosion (UVCE) and a sulfur dioxide release have been assessed. The resulting safety distance of about 100 m for the UVCE is fairly acceptable in terms of performance (head loss and thermal loss) of the coupling system. However, the longer safety distance (about 1.5 km) calculated for a SO 2 release implies to foresee a long distance to settle the control room of the site or to foresee provisions able to stop very fast the SO 2 leak.