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The optimal strength of compression needed to prevent post-thrombotic syndrome (PTS) after a proximal deep vein thrombosis (DVT) is debated. We aimed to assess whether 25 mm Hg elastic compression stockings (ECS) are non-inferior to 35 mm Hg ECS in preventing PTS after a DVT.In this multicentre, double-blind, non-inferiority, randomised controlled trial, we enrolled adults (≥18 years) with a first ipsilateral proximal DVT attending 46 French vascular medicine hospital departments or private practices. Participants were randomly allocated (1:1, stratified by centre, age, and sex; with varying block sizes of two and four) to wear 25 mm Hg or 35 mm Hg ECS for 2 years. The primary outcome was the cumulative rate of PTS 2 years after inclusion, defined by a Villalta scale (≥5). Efficacy was assessed by intention-to-treat and in eligible participants who had complete primary outcome data. A per-protocol analysis was also conducted among compliant patients as a secondary outcome measure. Safety was assessed in all participants who used ECS at least once, and for which we have at least some tolerance information during follow-up. The margin for non-inferiority was 12·5%. This study is registered with ClinicalTrials.gov, NCT01578122, and has been completed.Between June 28, 2012, and July 21, 2017, we enrolled 341 eligible participants who consented to randomisation. 233 (68%) were men and median age was 59 years (IQR 45-70). Collection of ethnicity and race as a routine research variable is not authorised in France. Median follow-up was 735 days (IQR 721-760). 249 (73%) had complete data at 2 years. For the primary analysis, 40 (31%) of 129 participants with complete data in the 25 mm Hg ECS group and 40 (33%) of 120 in the 35 mm Hg group had PTS (absolute difference -2·3% [90% CI -12·1 to 7·4], pAlthough we did not reach the prespecified sample size, our results suggest that 25 mm Hg ECS are non-inferior to 35 mm Hg ECS in preventing PTS. Larger more powerful studies are needed.Laboratoires Innothera, France.

Stage-1 Registered Report with in-principle acceptance for publication in Glossa Psycholinguistics

Periodic discharges are a rare peculiar electroencephalogram pattern, occasionally associated with motor or other clinical manifestations, usually observed in critically ill patients. Their underlying pathophysiology remains poorly understood. Epileptic spasms in clusters and periodic discharges with motor manifestations share similar electroencephalogram pattern and some aetiologies of unfavourable prognosis such as subacute sclerosing panencephalitis or herpes encephalitis. Arterial spin labelling magnetic resonance imaging identifies localizing ictal and inter-ictal changes in neurovascular coupling, therefore assumed able to reveal concerned cerebral structures. Here, we retrospectively analysed ictal and inter-ictal arterial spin labelling magnetic resonance imaging in patients aged 6 months to 15 years (median 3 years 4 months) with periodic discharges including epileptic spasms, and compared these findings with those of patients with drug-resistant focal epilepsy who never presented periodic discharges nor epileptic spasms as well as to those of age-matched healthy controls. Ictal electroencephalogram was recorded either simultaneously with arterial spin labelling magnetic resonance imaging or during the close time lapse of patients’ periodic discharges, whereas inter-ictal examinations were performed during the patients’ active epilepsy but without seizures during the arterial spin labelling magnetic resonance imaging. Ictal arterial spin labelling magnetic resonance imaging was acquired in five patients with periodic discharges [subacute sclerosing panencephalitis (1), stroke-like events (3), West syndrome with cortical malformation (1), two of them also had inter-ictal arterial spin labelling magnetic resonance imaging]. Inter-ictal group included patients with drug-resistant epileptic spasms of various aetiologies (14) and structural drug-resistant focal epilepsy (8). Cortex, striatum and thalamus were segmented and divided in six functional subregions: prefrontal, motor (rostral, caudal), parietal, occipital and temporal. Rest cerebral blood flow values, absolute and relative to whole brain, were compared with those of age-matched controls for each subregion. Main findings were diffuse striatal as well as cortical motor cerebral blood flow increase during ictal examinations in generalized periodic discharges with motor manifestations (subacute sclerosing panencephalitis) and focal cerebral blood flow increase in corresponding cortical-striatal-thalamic subdivisions in lateralized periodic discharges with or without motor manifestations (stroke-like events and asymmetrical epileptic spasms) with straight topographical correlation with the electroencephalogram focus. For inter-ictal examinations, patients with epileptic spasms disclosed cerebral blood flow changes in corresponding cortical-striatal-thalamic subdivisions (absolute-cerebral blood flow decrease and relative-cerebral blood flow increase), more frequently when compared with the group of drug-resistant focal epilepsies, and not related to Vigabatrin treatment. Our results suggest that corresponding cortical-striatal-thalamic circuits are involved in periodic discharges with and without motor manifestations, including epileptic spasms, opening new insights in their pathophysiology and new therapeutical perspectives. Based on these findings, we propose a model for the generation of periodic discharges and of epileptic spasms combining existing pathophysiological models of cortical-striatal-thalamic network dynamics.

Widespread antimicrobial resistance generates an urgent need to develop better disease prophylaxis for intestinal bacterial pathogens. While the first phase of infection with any bacterial pathogen is typically colonization of the mucosal surfaces, current vaccine strategies typically target invasive stages of disease. Here we demonstrate the ability to specifically generate sterilizing immunity againstSalmonella entericasubspeciesentericaserovar Typhimurium (S.Tm) at the level of gut lumen colonization using a combination of oral vaccination and a rationally-designed niche competitor strain. This is based on the proven ability of specific secretory IgA to generate a fitness disadvantage for a targeted bacterium, allowing a non-targeted competitor to rapidly overtake its niche. By hugely decreasing the population size of an intestinal pathogen during the early stages of infection, this improves protection of gut tissue compared to standard licensed animal vaccines. We demonstrate that most effective protection is generated when the niche competitor is derived from the pathogen and therefore occupies an identical niche. However, as this is unrealistic in real-world infections, we further demonstrate that robust protection can also be generated with a more distantly related “probiotic” niche competitor from a distinct species. Interestingly, focusing prophylaxis on the gut lumen reveals an uncoupling of protective mechanisms required for protection in the gut and gut tissues and those required for protecting against colonization of the spleen and liver. Therefore, while there is still potential to improve this approach by adding systemic immune activation, we nevertheless believe this is a fundamental step forward in our ability to manipulate colonization of intestinal bacteria with potential application to a wide-range of entero-pathogens, as well as to manipulation of microbiota composition.

Electroencephalography (EEG) is the reference tool for the analysis of brain function, reflecting normal and pathological neuronal network activity. During the neonatal period, EEG patterns evolve weekly, according to gestational age. The first analytical criteria for the various maturational stages and standardized neonatal EEG terminology were published by a group of French neurophysiologists training in Paris (France) in 1999. These criteria, defined from analog EEG, were completed in 2010 with digital EEG analysis. Since then, this work has continued, aided by the technical progress in EEG acquisition, the improvement of knowledge on the maturating processes of neuronal networks, and the evolution of critical care. In this review, we present an exhaustive and didactic overview of EEG characteristics from extremely premature to full-term infants. This update is based on the scientific literature, enhanced by the study of normal EEGs of extremely premature infants by our group of neurophysiologists. For educational purposes, particular attention has been paid to illustrations using new digital tools.

Intestinal inflammation fuels the transmission of Salmonella Typhimurium (S.Tm). However, a substantial fitness cost is associated with virulence expression. Mutations inactivating transcriptional virulence regulators generate attenuated variants profiting from inflammation without enduring virulence cost. Such variants interfere with the transmission of fully virulent clones. Horizontal transfer of functional regulatory genes (HGT) into attenuated variants could nevertheless favor virulence evolution. To address this hypothesis, we cloned hilD, coding for the master regulator of virulence, into a conjugative plasmid that is highly transferrable during intestinal colonization. The resulting mobile hilD allele allows virulence to emerge from avirulent populations, and to be restored in attenuated mutants competing against virulent clones within-host. However, mutations inactivating the mobile hilD allele quickly arise. The stability of virulence mediated by HGT is strongly limited by its cost, which depends on the hilD expression level, and by the timing of transmission. We conclude that robust evolution of costly virulence expression requires additional selective forces such as narrow population bottlenecks during transmission., Nature Communications, 13, ISSN:2041-1723

Virulence gene expression can represent a substantial fitness cost to pathogenic bacteria. In the model entero-pathogen Salmonella Typhimurium (S.Tm), such cost favors emergence of attenuated variants during infections that harbor mutations in transcriptional activators of virulence genes (e.g., hilD and hilC). Therefore, understanding the cost of virulence and how it relates to virulence regulation could allow the identification and modulation of ecological factors to drive the evolution of S.Tm toward attenuation. In this study, investigations of membrane status and stress resistance demonstrate that the wild-type (WT) expression level of virulence factors embedded in the envelope increases membrane permeability and sensitizes S.Tm to membrane stress. This is independent from a previously described growth defect associated with virulence gene expression in S.Tm. Pretreating the bacteria with sublethal stress inhibited virulence expression and increased stress resistance. This trade-off between virulence and stress resistance could explain the repression of virulence expression in response to harsh environments in S.Tm. Moreover, we show that virulence-associated stress sensitivity is a burden during infection in mice, contributing to the inherent instability of S.Tm virulence. As most bacterial pathogens critically rely on deploying virulence factors in their membrane, our findings could have a broad impact toward the development of antivirulence strategies. ispartof: Plos Biology vol:20 issue:4 ispartof: location:United States status: published

International audience; Eye movement monitoring was used to explore the time course of orthographic learning in adult skilled readers while they read novel words presented in isolation one, three or five times. Off-line measures of spelling-to-dictation and orthographic decision were used to measure orthographic memorization. Further, the participants' visual attention span was estimated. Results showed better memorization of new words' orthography with additional exposures. An exposure-by-exposure in-depth analysis of eye movements revealed an early sharper decrease for the number of fixations and most measures of processing time. Participants with a higher visual attention span showed better performance in orthographic decision and processing times. The overall findings suggest that orthographic learning occurs from the first exposure and that top-down effects from the newly acquired orthographic knowledge would facilitate processing from the second exposure. Further, time needed for bottom-up information extraction appears to be modulated by visual attention span.

Resume Le secret professionnel, institue dans l’interet des patients, peut se retourner contre eux lors des actions en justice. Pour remedier a cela, le legislateur a prevu toute une serie de lois permettant a la fois de proteger le secret professionnel et l’interet des patients.

Purpose We aimed to identify prognostic factors for survival and long-term intellectual and developmental outcome in neonatal patients with early-onset urea cycle disorders (UCD) experiencing hyperammonaemic coma. Methods We retrospectively analysed ammonia (NH3) and glutamine levels, electroencephalogram and brain images obtained during neonatal coma of UCD patients born between 1995 and 2011 and managed at a single centre and correlated them to survival and intellectual and developmental outcome. Results We included 38 neonates suffering from deficiencies of argininosuccinate synthetase (ASSD, N = 12), ornithine transcarbamylase (OTCD, N = 10), carbamoylphosphate synthetase 1 (CPSD, N = 7), argininosuccinate lyase (ASLD, N = 7), N-acetylglutamate synthase (NAGS, N = 1) or arginase (ARGD, N = 1). Symptoms occurred earlier in mitochondrial than in cytosolic UCD. Sixty-eight percent of patients survived, with a mean (standard deviation-SD) follow-up of 10.4 (5.3) years. Mortality was mostly observed in OTCD (N = 7/10) and CPSD (N = 4/7) patients. Plasma NH3 level during the neonatal period, expressed as area under the curve, but not glutamine level was associated with mortality (p = .044 and p = .610). 62.1% of the patients had normal intellectual and developmental outcome. Intellectual and developmental outcome tended to correlate with UCD subtype (p = .052). No difference in plasma NH3 or glutamine level during the neonatal period among developmental outcomes was identified. EEG severity was linked to UCD subtypes (p = .004), ammonia levels (p = .037), duration of coma (p = .043), and mortality during the neonatal period (p = .020). Status epilepticus was recorded in 6 patients, 3 of whom died neonatally, 1 developed a severe intellectual disability while the 2 last patients had a normal development. Conclusion UCD subtypes differed by survival rate, intellectual and developmental outcome and EEG features in the neonatal period. Hyperammonaemia expressed as area under the curve was associated with survival but not with intellectual and developmental outcome whereas glutamine was not associated with one of these outcomes. Prognostic value of video-EEG monitoring and the association between status epilepticus and mortality should be assessed in neonatal hyperammonaemic coma in further studies.

Antibiotic treatment failure is of growing concern. Genetically encoded resistance is key in driving this process. However, there is increasing evidence that bacterial antibiotic persistence, a non-genetically encoded and reversible loss of antibiotic susceptibility, contributes to treatment failure and emergence of resistant strains as well. In this Review, we discuss the evolutionary forces that may drive the selection for antibiotic persistence. We review how some aspects of antibiotic persistence have been directly selected for whereas others result from indirect selection in disparate ecological contexts. We then discuss the consequences of antibiotic persistence on pathogen evolution. Persisters can facilitate the evolution of antibiotic resistance and virulence. Finally, we propose practical means to prevent persister formation and how this may help to slow down the evolution of virulence and resistance in pathogens. Antibiotic persistence is a threat to effective treatment of bacterial infections. In this Review, Bakkeren, Diard and Hardt discuss the evolutionary forces that have favoured the development of persisters in populations and the consequences for spread of resistance and virulence determinants.

Auditory speech perception enables listeners to access phonological categories from speech sounds. During speech production and speech motor learning, speakers’ experience matched auditory and somatosensory input. Accordingly, access to phonetic units might also be provided by somatosensory information. The present study assessed whether humans can identify vowels using somatosensory feedback, without auditory feedback. A tongue-positioning task was used in which participants were required to achieve different tongue postures within the /e, [Formula: see text] , a/ articulatory range, in a procedure that was totally nonspeech like, involving distorted visual feedback of tongue shape. Tongue postures were measured using electromagnetic articulography. At the end of each tongue-positioning trial, subjects were required to whisper the corresponding vocal tract configuration with masked auditory feedback and to identify the vowel associated with the reached tongue posture. Masked auditory feedback ensured that vowel categorization was based on somatosensory feedback rather than auditory feedback. A separate group of subjects was required to auditorily classify the whispered sounds. In addition, we modeled the link between vowel categories and tongue postures in normal speech production with a Bayesian classifier based on the tongue postures recorded from the same speakers for several repetitions of the /e, [Formula: see text] , a/ vowels during a separate speech production task. Overall, our results indicate that vowel categorization is possible with somatosensory feedback alone, with an accuracy that is similar to the accuracy of the auditory perception of whispered sounds, and in congruence with normal speech articulation, as accounted for by the Bayesian classifier.

In the beginning it was simple: we injected a protein antigen and studied the immune responses against the purified protein. This elegant toolbox uncovered thousands of mechanisms via which immune cells are activated. However, when we consider immune responses against real infectious threats, this elegant simplification misses half of the story: the infectious agents are typically evolving orders-of-magnitude faster than we are. Nowhere is this more pronounced than in the mammalian large intestine. A bacterium representing only 0.1% of the human gut microbiota will have a population size of 10⁹ clones, each actively replicating. Moreover, the evolutionary pressure from other microbes is at least as profound as direct effects of the immune system. Therefore, to really understand intestinal immune mechanisms, we need to understand both the host response and how rapid microbial evolution alters the apparent outcome of the response. In this review we use the examples of intestinal inflammation and secretory immunoglobulin A (SIgA) to highlight what is already known (Fig. 1). Further, we will explore how these interactions can inform immunotherapy and prophylaxis. This has major implications for how we design effective mucosal vaccines against increasingly drug-resistant bacterial pathogens., Mucosal Immunology, 15 (6), ISSN:1933-0219, ISSN:1935-3456

A central component of the predictive coding theoretical framework concerns the comparison between predictions and sensory decoding. In the probabilistic setting, this takes the form of assessing the similarity or distance between probability distributions. However, such similarity or distance measures are not associated with explicit probabilistic models, making their assumptions implicit. In this paper, we explore an original variation on probabilistic coherence variables; we define a probabilistic component, that we call a "Bayesian comparator", that mathematically yields a particular similarity measure. A geometrical analogy suggests two variants of this measure. We apply these similarity measures to simulate the comparison of known, predicted patterns to patterns from sensory decoding, first in a simple, illustrative model, and second, in a previous model of visual word recognition. Experimental results suggest that the variant that is scaled by the norms of both predicted and perceived probability distributions yields better robustness and more desirable dynamics.

The probability of recognizing a word depends on the position of fixation during processing. In typical readers, the resulting word-recognition curves are asymmetrical, showing a left-of-centre optimal viewing position (OVP). First, we report behavioural results from dyslexic participants who show atypical word-recognition curves characterized by the OVP being right of centre with recognition probability being higher on the rightmost than on the leftmost letters. Second, we used BRAID, a Bayesian model of word recognition that implements gaze position, an acuity gradient, lateral interference and a visual attention component, to examine how variations in the deployment of visual attention would affect the OVP curves. We show that the atypical dyslexic curves are well simulated assuming a narrow distribution of visual attention and a shifting of visual attention towards the left visual field. These behavioural and modelling findings are discussed in light of current theories of visual attention deficits in developmental dyslexia.

A new species of proteocephalid cestodes, provisionally assigned to the polyphyletic genus Ophiotaenia La Rue, 1911 (Cestoda: Proteocephalidae), is described from Compsophis infralineatus (Günther) (Serpentes: Pseudoxyrhophiidae) endemic to Madagascar. Ophiotaenia oreae n. sp. differs from all African and Asian species of Ophiotaenia by possessing more uterine diverticula (68-82 on one side). It is also characterised by the absence of an apical organ, the relative sizes of the cirrus-sac and ovary, the almost equatorial position of the gonopore, the diameter of the embryophore, and other biometric characteristics. Phylogenetic relationships of the new species indicate its relatedness to Indomalayan and Australasian proteocephalids from reptiles. Ophiotaenia oreae n. sp. formed a well-supported clade composed of species of Australophiotaenia de Chambrier, Beveridge and Scholz, 2018 from Australian snakes, Macrobothriotaenia ficta (Meggitt, 1931) from Xenopeltis unicolor Reinwardt in Boie from Vietnam, Ophiotaenia sp. from Trimeresurus flavomaculatus (Gray) from the Philippines, and Ophiotaenia bungari de Chambrier, Binh and Scholz, 2012 from Bungarus fasciatus (Schneider) from Vietnam. The only proteocephalid from Madagascan snakes sequenced so far, Ophiotaenia lapata Rambeloson, Ranaivoson and de Chambrier, 2012 from Madagascarophis colubrinus (Schlegel), does not form a monophyletic group with the new species. The actual species diversity of reptilian cestodes in Madagascar is undoubtedly underestimated. Because of the assumed strict (oioxenous) host specificity of reptilian proteocephalids and rich fauna of snakes occurring in Madagascar, it is plausible to expect the existence of dozens new species of proteocephalids on this island.

How is orthographic knowledge acquired? In line with the self-teaching hypothesis, most computational models assume that phonological recoding has a pivotal role in orthographic learning. However, these models make simplifying assumptions on the mechanisms involved in visuo-orthographic processing. Against evidence from eye movement data during orthographic learning, they assume that orthographic information on novel words is immediately available and accurately encoded after a single exposure. In this paper, we describe BRAID-Learn, a new computational model of orthographic learning. BRAID-Learn is a probabilistic and hierarchical model that incorporates the mechanisms of visual acuity, lateral interference, and visual attention involved in word recognition. Orthographic learning in the model rests on three main mechanisms: first, visual attention moves over the input string to optimize the gain of information on letter identity at each fixation; second, top-down lexical influence is modulated as a function of stimulus familiarity; third, after exploration, perceived information is used to create a new orthographic representation or stabilize a better-specified representation of the input word. BRAID-Learn was challenged on its capacity to simulate the eye movement patterns reported in humans during incidental orthographic learning. In line with the behavioral data, the model predicts a larger decline with exposures in number of fixations and processing time for novel words than for known words. For novel words, most changes occur between the first and second exposure, that is to say, after creation in memory of a new orthographic representation. Beyond phonological recoding, our results suggest that visuo-attentional exploration is an intrinsic portion of orthographic learning seldom taken into consideration by models or theoretical accounts.

Virulence gene expression can represent a substantial fitness cost to pathogenic bacteria. In the model entero-pathogen Salmonella Typhimurium (S.Tm), such cost favors emergence of attenuated variants during infections that harbor mutations in transcriptional activators of virulence genes (e.g., hilD and hilC). Therefore, understanding the cost of virulence and how it relates to virulence regulation could allow the identification and modulation of ecological factors to drive the evolution of S.Tm toward attenuation. In this study, investigations of membrane status and stress resistance demonstrate that the wild-type (WT) expression level of virulence factors embedded in the envelope increases membrane permeability and sensitizes S.Tm to membrane stress. This is independent from a previously described growth defect associated with virulence gene expression in S.Tm. Pretreating the bacteria with sublethal stress inhibited virulence expression and increased stress resistance. This trade-off between virulence and stress resistance could explain the repression of virulence expression in response to harsh environments in S.Tm. Moreover, we show that virulence-associated stress sensitivity is a burden during infection in mice, contributing to the inherent instability of S.Tm virulence. As most bacterial pathogens critically rely on deploying virulence factors in their membrane, our findings could have a broad impact toward the development of antivirulence strategies.

International audience; Recent neurocognitive models commonly consider speech perception as a hierarchy of processes, each corresponding to specific temporal scales of collective oscillatory processes in the cortex: 30–80 Hz gamma oscillations in charge of phonetic analysis, 4–9 Hz theta oscillations in charge of syllabic segmentation, 1–2 Hz delta oscillations processing prosodic/syntactic units and the 15–20 Hz beta channel possibly involved in top-down predictions. Several recent neuro-computational models thus feature theta oscillations, driven by the speech acoustic envelope, to achieve syllabic parsing before lexical access. However, it is unlikely that such syllabic parsing, performed in a purely bottom-up manner from envelope variations, would be totally efficient in all situations, especially in adverse sensory conditions. We present a new probabilistic model of spoken word recognition, called COSMO-Onset, in which syllabic parsing relies on fusion between top-down, lexical prediction of onset events and bottom-up onset detection from the acoustic envelope. We report preliminary simulations, analyzing how the model performs syllabic parsing and phone, syllable and word recognition. We show that, while purely bottom-up onset detection is sufficient for word recognition in nominal conditions, top-down prediction of syllabic onset events allows overcoming challenging adverse conditions, such as when the acoustic envelope is degraded, leading either to spurious or missing onset events in the sensory signal. This provides a proposal for a possible computational functional role of top-down, predictive processes during speech recognition, consistent with recent models of neuronal oscillatory processes.

Study question How should endometriosis management be improved from the patient’s point of view? Summary answer One thousand endometriosis patients proposed 2,587 ideas to improve the management of endometriosis that reflect three main themes: diagnosis, care, and information on the disease. What is known already Endometriosis is a gynecologic condition affecting 10% of reproductive-age women. The disease causes severe pelvic pain and has a dramatic impact on women’s quality of life. A mean delay of 7 years was described between onset of symptoms and diagnosis. There is an urgent need to reduce this delay and to rethink endometriosis care in order to adopt a more comprehensive and patient-centered approach, as women are often dissatisfied with the care they receive. Study design, size, duration This study was carried out in a random sample of endometriosis patients participating in ComPaRe (Community of Patients for Research), a prospective e-cohort of adult chronic disease patients who will be followed-up for 10 years. Participants complete monthly online questionnaires about their life with their disease(s). Recruitment began in January 2017 and is still ongoing, with currently 44,000 participants, including 10,000 endometriosis patients in the ComPaRe-Endometriosis sub-cohort. Participants/materials, setting, methods We selected a random sample of 1,000 participants in ComPaRe-Endometriosis, forming 3 equal groups of age (45 years old) and education (14 years). We conducted a qualitative study to gather their ideas for improving the management of their disease. Participants were asked: “If you had a magic wand, what would you change in your health care?”. One interviewer and two patients independently extracted ideas from the open-ended responses using thematic analysis. Main results and the role of chance Patients proposed a total of 2,587 ideas to improve the management of endometriosis, which we classified in three main themes: diagnosis, care, and information on the disease. To improve diagnosis, women proposed 724 ideas classified into 11 areas of improvement, including training of health professionals, taking symptoms seriously, improving the diagnosis process, and recognition of the disease by clinicians. To improve care, patients gave 1,677 ideas classified into 71 areas of improvement. For example, they asked for a better pain management, more listening from caregivers, the reimbursement of care or medical treatments, help in accessing clinicians that are expert in endometriosis, and reduced waiting times for medical appointments and exams. Finally, to improve information on the disease, participants suggested 186 ideas classified into 5 areas of improvement, covering more explanation about the disease, public recognition of endometriosis and general awareness, and more research and more explanation of research results. Limitations, reasons for caution The results were reviewed by three people in order to reduce the margin of interpretation in the analysis of this open-ended question, but some subjectivity remains. Generalizability may be difficult because the results are linked to the specificities of the French model of care. Wider implications of the findings: Through the many ideas proposed by patients, we identified a total of 87 areas for improvement in endometriosis diagnosis, care, and information. These results reflect patients’ expectations in terms of management of their disease and will be useful to design a better global care for endometriosis from the patients’ perspective. Trial registration number Not applicable

International audience; Immunology research in the last 50 years has made huge progress in understanding the mechanisms of anti-bacterial defense of deep, normally sterile, tissues such as blood, spleen and peripheral lymph nodes. In the intestine, with its dense commensal microbiota, it seems rare that this knowledge can be simply translated. Here we put forward the idea that perhaps it is not always the theory of immunology that is lacking to explain mucosal immunity, but rather that we have overlooked crucial parts of the mucosal immunological language required for its translation: namely intestinal and bacterial physiology. We will try to explain this in the context of intestinal secretory antibodies (mainly secretory IgA), which have been described to prevent, to alter, to not affect, or to promote colonization of the intestine and gut-draining lymphoid tissues, and where effector mechanisms have remained elusive. In fact, these apparently contradictory outcomes can be generated by combining the basic premises of bacterial agglutination with an understanding of bacterial growth (i.e. secretory IgA-driven enchained growth), fluid handling and bacterial competition in the gut lumen.

The microbiota confers colonization resistance, which blocks Salmonella gut colonization1. As diet affects microbiota composition, we studied whether food composition shifts enhance susceptibility to infection. Shifting mice to diets with reduced fibre or elevated fat content for 24 h boosted Salmonella Typhimurium or Escherichia coli gut colonization and plasmid transfer. Here, we studied the effect of dietary fat. Colonization resistance was restored within 48 h of return to maintenance diet. Salmonella gut colonization was also boosted by two oral doses of oleic acid or bile salts. These pathogen blooms required Salmonella’s AcrAB/TolC-dependent bile resistance. Our data indicate that fat-elicited bile promoted Salmonella gut colonization. Both E. coli and Salmonella show much higher bile resistance than the microbiota. Correspondingly, competitive E. coli can be protective in the fat-challenged gut. Diet shifts and fat-elicited bile promote S. Typhimurium gut infections in mice lacking E. coli in their microbiota. This mouse model may be useful for studying pathogen–microbiota–host interactions, the protective effect of E. coli, to analyse the spread of resistance plasmids and assess the impact of food components on the infection process. Short-term exposure to a high-fat diet reduces colonization resistance to Salmonella Typhimurium infection in mice and is associated with increase bile salts and plasmid transfer; however, E. coli can provide a protective effect under these conditions.

International audience; The word length effect in Lexical Decision (LD) has been studied in many behavioral experiments but no computational models has yet simulated this effect. We use a new Bayesian model of visual word recognition, the BRAID model, that simulates expert readers performance. BRAID integrates an attentional component modeled by a Gaus-sian probability distribution, a mechanism of lateral interference between adjacent letters and an acuity gradient, but no phonological component. We explored the role of visual attention on the word length effect using 1,200 French words from 4 to 11 letters. A series of five simulations was carried out to assess (a) the impact of a single attentional focus versus multiple shifts of attention on the word length effect and (b) how this effect is modulated by variations in the distribution of attention. Results show that the model successfully simulates the word length effect reported for humans in the French Lexicon Project when allowing multiple shifts of attention for longer words. The magnitude and direction of the effect can be modulated depending on the use of a uniform or narrow distribution of attention. The present study provides evidence that visual attention is critical for the recognition of single words and that a narrowing of the attention distribution might account for the exaggerated length effect reported in some reading disorders.

International audience; No abstract available

Environmental cues modulate the expression of virulence in bacterial pathogens. However, while cues that upregulate virulence are often intuitive and mechanistically well understood, this is less so for cues that downregulate virulence. In this study, we noticed that upregulation of the HilD virulence regulon in Salmonella Typhimurium (S.Tm) sensitized cells to membrane stress mediated by cholate, Tris/EDTA or heat. Further monitoring of membrane status and stress resistance of S.Tm cells in relation to virulence expression, revealed that co-expressed virulence factors embedded in the envelope (including the Type Three Secretion System 1 and the flagella) increased permeability, and stress sensitivity of the membrane. Importantly, pretreating the bacteria by sublethal stress inhibited virulence expression and restored stress resistance. As such, these results demonstrate a trade-off between virulence and stress resistance, which explains the downregulation of virulence expression in response to harsh environments in S.Tm.

Objective We aimed to describe epilepsy and EEG patterns related to vigilance states and age, in chromosome15-long-arm-duplication-syndrome (dup15q) children with epilepsy, in both duplication types: interstitial (intdup15) and isodicentric (idic15). Methods Clinical data and 70 EEGs of 12 patients (5 intdup15, 7 idic15), followed from 4.5 m.o to 17y4m (median follow-up 8y3m), were retrospectively reviewed. EEGs were analyzed visually and using power spectrum analysis. Results Seventy video-EEGs were analyzed (1–16 per patient, median 6), follow-up lasting up to 8y10m (median 4y2m): 25 EEGs in intdup15 (8 m.o to 12y.o, median 4y6m) and 45 EEGs in idic15 (7 m.o to 12 y.o, median 15 m). Epilepsy: 6 West syndrome (WS) (2intdup15, 4idic15); 4 Lennox-Gastaut syndromes (LGS) (1 intdup15, 3 idic15), 2 evolving from WS; focal epilepsy (3 intdup15). In idic15, WS displayed additional myoclonic seizures (3), atypical (4) or no hypsarrhythmia (2) and posterior predominant spike and polyspike bursts (4). Beta-band rapid-rhythms (RR): present in 11 patients, power decreased during non-REM-sleep, localization shifted from diffuse to anterior, peak frequency increased with age. Conclusion WS with peculiar electro-clinical features and LGS, along with beta-band RR decreasing in non-REM-sleep and shifting from diffuse to anterior localization with age are recognizable features pointing towards dup15q diagnosis in children with autism spectrum disorder and developmental delay. Significance This study describes electroclinical features in both interstitial and isodicentric duplications of chromosome 15q, in epileptic children, including some recent extensions regarding sleep features; and illustrates how the temporo-spatial organization of beta oscillations can be of significant help in directing towards dup15q diagnosis hypothesis.

Because of insufficient data about their benefit–risk ratio in real life, drugs used for Alzheimer’s disease (AD; cholinesterase inhibitors and memantine) were withdrawn from the list of reimbursable drugs in France on 1 August 2018. In this context, this study aimed to investigate the effects of the removal of AD drugs from the list of reimbursed drugs among patients followed in memory centres in France, in terms of prevalence and factors associated with drug discontinuation and evolution of disease management and cognition after drug discontinuation. This is an observational study based on data from the National Alzheimer Data Bank (‘Banque Nationale Alzheimer’ [BNA]), which centralizes information about patients consulting in memory centres. The drug discontinuation rate was estimated among patients receiving AD drugs at the last visit before the end of reimbursement. Factors associated with drug discontinuation were investigated among sociodemographic and disease characteristics, as well as among the use of healthcare resources before the end of reimbursement. We compared the evolution of disease management (psychotropic drugs and non-pharmacological interventions) and Mini-Mental State Examination (MMSE) score during the year following the end of reimbursement among patients with a diagnosis of AD. Among the 19,380 patients of the study sample (62.5% females, mean age 81 years, 86.8% with a diagnosis of AD), 19.5% discontinued their treatment after the end of reimbursement. The main factors associated with drug discontinuation were the type of dementia and lower MMSE level. Compared with patients with a diagnosis of AD, those with vascular dementia were more likely to stop their treatment, whereas those with dementia with Lewy bodies were less likely to discontinue. Among patients with a diagnosis of AD, drug discontinuation was associated with increased use of psychotropic medications, especially antidepressants, and non-pharmacological interventions afterwards, but there was no difference regarding the evolution of MMSE score. This study provides real-life information about the use of AD drugs after they were withdrawn from reimbursement in France and shows that drug discontinuation was limited among patients followed in memory centres and accompanied by increased use of other healthcare resources.

Venous insufficiency is a very common disease affecting about 25% of the French population (if we combine all stages of its progression). It is a complex disease and its aetiology has not yet been fully elucidated. Some of its causes are well known, such as valvular dysfunction, vein wall defect, and the suctioning effect common to all varicose veins. These factors are generally associated and together lead to dysfunction of one or more of the saphenous veins. Saphenous vein dysfunction is revealed by ultrasound scan, a reflux lasting more than 0.5 seconds indicating venous incompetence. The potential consequences of saphenous vein dysfunction over time include: symptoms (heaviness, swellings, restlessness, cramps, itching of the lower limbs), acute complications (superficial venous thrombosis, varicose bleeding), chronic complications (changes in skin texture and colour, stasis dermatitis, eczema, vein atresia, leg ulcer), and appearance of unaesthetic varicose veins. It is not possible to repair an incompetent saphenous vein. The only therapeutic options at present are ultrasound-guided foam sclerotherapy, physical removal of the vein (saphenous stripping), or its thermal ablation (by laser or radiofrequency treatment), the latter strategy having now become the gold standard as recommended by international guidelines. Recommendations concerning thermal ablation of saphenous veins were published in 2014 by the Societe francaise de medecine vasculaire. Our society has now decided to update these recommendations, taking this opportunity to discuss unresolved issues and issues not addressed in the original guidelines. Thermal ablation of an incompetent saphenous vein consists in destroying this by means of a heating element introduced via ultrasound-guided venous puncture. The heating element comprises either a laser fibre or a radiofrequency catheter. The practitioner must provide the patient with full information about the procedure and obtain his/her consent prior to its implementation. The checklist concerning the interventional procedure issued by the HAS should be validated for each patient (see the appended document).

Background and purpose Multinodular and vacuolating neuronal tumor (MVNT) of the cerebrum is a rare brain lesion with suggestive imaging features. The aim of our study was to report the largest series of MVNTs so far and to evaluate the utility of advanced multiparametric magnetic resonance (MR) techniques. Methods This multicenter retrospective study was approved by our institutional research ethics board. From July 2014 to May 2019, two radiologists read in consensus the MR examinations of patients presenting with a lesion suggestive of an MVNT. They analyzed the lesions' MR characteristics on structural images and advanced multiparametric MR imaging. Results A total of 64 patients (29 women and 35 men, mean age 44.2 ± 15.1 years) from 25 centers were included. Lesions were all hyperintense on fluid-attenuated inversion recovery and T2-weighted imaging without post-contrast enhancement. The median relative apparent diffusion coefficient on diffusion-weighted imaging was 1.13 [interquartile range (IQR), 0.2]. Perfusion-weighted imaging showed no increase in perfusion, with a relative cerebral blood volume of 1.02 (IQR, 0.05) and a relative cerebral blood flow of 1.01 (IQR, 0.08). MR spectroscopy showed no abnormal peaks. Median follow-up was 2 (IQR, 1.2) years, without any changes in size. Conclusions A comprehensive characterization protocol including advanced multiparametric magnetic resonance imaging sequences showed no imaging patterns suggestive of malignancy in MVNTs. It might be useful to better characterize MVNTs.