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The role of Human pegivirus (HPgV) in patients with encephalitis has been recently questioned. We present cases of 4 patients with similar clinical, biological, and radiological characteristics, including a past history of transplantation with long-term immunosuppression and a progressive course of severe and predominantly myelitis, associated in 3 cases with optic neuropathy causing blindness. Extensive workup was negative but analysis of the CSF by use of pan-microorganism DNA- and RNA-based shotgun metagenomics was positive for HPgV. This case series further supports the hypothesis of HPgV CNS infection and highlights the utility of metagenomic next-generation sequencing of CSF in immunocompromised patients.

Background and ObjectivesIt remains unknown to what extent ictal scalp EEG can accurately predict the localization of the intracerebral seizure onset in presurgical evaluation of drug-resistant epilepsies. In this study, we aimed to define homogeneous ictal scalp EEG profiles (based on their first ictal abnormality) and assess their localizing value using simultaneously recorded scalp EEG and stereo-EEG.MethodsWe retrospectively included consecutive patients with drug-resistant focal epilepsy who had simultaneous stereo-EEG and scalp EEG recordings of at least 1 seizure in the epileptology unit in Nancy, France. We analyzed 1 seizure per patient and used hierarchical cluster analysis to group similar seizure profiles on scalp EEG and then performed a descriptive analysis of their intracerebral correlates.ResultsWe enrolled 129 patients in this study. The hierarchical cluster analysis showed 6 profiles on scalp EEG first modification. None were specific to a single intracerebral localization. The “normal EEG” and “blurred EEG” clusters (early muscle artifacts) comprised only 5 patients each and corresponded to no preferential intracerebral localization. The “temporal discharge” cluster (n = 46) was characterized by theta or delta discharges on ipsilateral anterior temporal scalp electrodes and corresponded to a preferential mesial temporal intracerebral localization. The “posterior discharge” cluster (n = 42) was characterized by posterior ipsilateral or contralateral rhythmic alpha discharges or slow waves on scalp and corresponded to a preferential temporal localization. However, this profile was the statistically most frequent scalp EEG correlate of occipital and parietal seizures. The “diffuse suppression” cluster (n = 9) was characterized by a bilateral and diffuse background activity suppression on scalp and corresponded to mesial, and particularly insulo-opercular, localization. Finally, the “frontal discharge” cluster (n = 22) was characterized by bilateral frontal rhythmic fast activity or preictal spike on scalp and corresponded to preferential ventrodorsal frontal intracerebral localizations.DiscussionThe hierarchical cluster analysis identified 6 seizure profiles regarding the first abnormality on scalp EEG. None of them were specific of a single intracerebral localization. Nevertheless, the strong relationships between the “temporal,” “frontal,” “diffuse suppression,” and “posterior” profiles and intracerebral discharge localizations may contribute to hierarchize hypotheses derived from ictal scalp EEG analysis regarding intracerebral seizure onset.

Alors que la transition énergétique réactive le risque de black-out électrique, l’article montre que les leviers d’action disponibles (coupures, hausse de tarifs…) posent un problème aigu de justice sociale. Mais en analysant ce risque comme un péril commun, il devient possible d’élargir les choix possibles de réductions de consommation, tout en adoptant une nouvelle répartition des coûts, davantage cohérente avec une action de sauvetage au bénéfice de tous. L'article ouvre des perspectives sur des rôles nouveaux pour les gestionnaires de réseau à l’heure de la sobriété.

Surgery is an effective treatment for drug-resistant temporal-lobe epilepsy (TLE), but is still underutilized for older patients because of a perceived higher rate of perioperative complications, cognitive decline and worse seizure outcome.We retrospectively screened all patients operated on in our institution for drug-resistant TLE between 2007 and 2019. Data of patients aged ≥50 years versus50 years at surgery were compared. The primary endpoint was freedom from disabling seizure (Engel I) at 2 years postoperatively.In patients aged ≥50 years (n=19), mean age at surgery was 54.9 years and mean disease duration was 36.6 years. At 2 years postoperatively, rates of Engel I seizure outcome were not significantly different between the two groups (73.9% in the50 years group versus 94.4% in the ≥50 years group). Although surgical complications were significantly (47.4%) in the older patients, neurological deficit was permanent in only 5.3% of cases. At 1 year postoperatively, neuropsychological outcome did not significantly differ between the two groups.Patients aged ≥50 years had an excellent seizure outcome at 2 years postoperatively. Early postoperative complications were more frequent in patients aged ≥50 years but were mostly transient. Cognitive outcome was similar to that in younger patients. These findings strongly suggest that age ≥50 years should not be an exclusion criterion for resective epilepsy surgery in patients with drug-resistant TLE.

Occipital lobe seizure are underrepresented in epilepsy surgery cases series. This may reflect the fear for post-surgical functional deficits but also the doubt about the ability of anatomo-electro-clinical correlations to localize precisely the epileptogenic zone in occipital lobe seizure.In this expert opinion paper, we review first the general clinical characteristics of occipital lobe seizures, describe the repertoire of visual phenomena and oculo-motor signes in occipital seizures, describe inter-ictal and ictal EEG and finally the possible schemes of epileptogenic zone organization.Visual and oculo-motor semiology points towards occipital onset seizures but is neither pathognomonic nor constant. Eyes version and unilateral ictal discharge have a strong lateralizing value but inter-ictal spikes as well as eyes version can be falsely lateralizing.Although visual and oculo-motor phenomena are characteristic of occipital lobe seizures, they may be discrete, overlooked and should therefore be carefully assessed. There are no clear electro-clinical correlations of a sublobar organization of occipital seizures but the clinical pattern of propagation might help to differentiate complex occipito-temporal from occipito-parietal initial epileptogenic network.

Generalization of ocular myasthenia gravis (OMG) represents a pejorative evolution, and no validated generalization-prevention strategy exists. The study aimed to determine the percentage of patients with OMG generalization and identify factors predictive of it to establish a prediction score.This retrospective, observational study included 151 patients diagnosed with OMG after an initial work-up in our institution. The outcome measure was time to MG generalization. The explanatory variables were age at onset ( 55 years), sex, first-year anti-acetylcholine-receptor antibody-positivity, repetitive nerve stimulation showing electromyogram decrement and corticosteroid use. Kaplan-Meier estimations of the probability of risk of generalization, and descriptive and multivariate Cox model analyses were computed. A nomogram combining explanatory variables was used to establish a score to predict the probability of OMG generalization.Among 183 patients' charts identified, 151 had confirmed OMG. Their median follow-up was 5.7 years. Estimations (95% CI) of OMG-generalization risk at 1, 3 and 10 years post-symptom onset, respectively, were: 13.0% (7.3-18.2), 25.1% (17.5-32.0) and 37.8% (27.2-45.2). The p-value-based multivariate analysis associated generalization with female sex, electromyogram decrement and first-year anti-acetylcholine-receptor antibody positivity, and Akaike information criterion-based analysis retained those three parameters and corticosteroid use. A nomogram was built and validated with an optimism-corrected C-statistic of 0.68, and calibration plots showed good fit.Our population's percentage of OMG generalization is in line with recent publications. Using the identified prognostic factors, the nomogram provided a score to predict the probable risk of generalization in our cohort.

Climate change is projected to cause not only higher mean temperatures but also higher climate variability. Although elevated CO2 concentrations can potentially increase the productivity of some ecosystems, higher temperatures and more frequent droughts may lead to increased respiration and mortality, possibly negating these productivity gains. The capacity of global forests to adjust to climate change depends on their functional diversity and the ecosystem’s adaptive capacity.The Plant-FATE eco-evolutionary model describes vegetation responses to altered environmental conditions, including CO2 concentrations, temperatures, and droughts. It represents functional diversity by modelling species as points in trait space and incorporates ecosystem adaptations at three levels: 1) to model acclimation of plastic traits of individual plants, we leverage the power of eco-evolutionary optimality principles, 2) to model shifts in species composition via demographic changes and species immigration, we implement a trait-size-structured demographic vegetation model, and 3) to model the long-term genetic evolution of species, we have developed new evolutionary theory for trait-size-structured communities.First, we show that with just a few calibrated parameters, the Plant-FATE model accurately predicts the fluxes of CO2 and water, size distributions, and trait distributions for a tropical wet site in the Amazon Forest. Second, we show that under elevated CO2 conditions and in the absence of nutrient limitation, our model predictions are broadly consistent with observations, namely: an increase in leaf area, productivity and biomass, and a decrease in stomatal conductance and photosynthetic capacity. Third, we simulate the calibrated model with hypothetical future drought regimes to investigate three key features of ecosystem responses: 1) the change in species composition and ecosystem functioning in response to altered conditions, 2) the timescales of ecosystem response to new regimes, 3) the influence of functional diversity on the timescale of ecosystem adaptation and its consequences for ecosystem collapse.Our eco-evolutionary vegetation modelling strategy presents a powerful approach to leverage the power of natural selection to simulate ecosystem dynamics under novel conditions that plants may have never experienced before.

This case series estimates the annual incidence of pediatric eye injuries associated with recreational use of nonpowder guns at an ophthalmologic emergency department in France.

Leber hereditary optic neuropathy (LHON) is an important example of mitochondrial blindness with the m.11778G>A mutation in the MT-ND4 gene being the most common disease-causing mtDNA variant worldwide. The REFLECT phase 3 pivotal study is a randomized, double-masked, placebo-controlled trial investigating the efficacy and safety of bilateral intravitreal injection of lenadogene nolparvovec in patients with a confirmed m.11778G>A mutation, using a recombinant adeno-associated virus vector 2, serotype 2 (rAAV2/2-ND4). The first-affected eye received gene therapy; the fellow (affected/not-yet-affected) eye was randomly injected with gene therapy or placebo. The primary end point was the difference in change from baseline of best-corrected visual acuity (BCVA) in second-affected/not-yet-affected eyes treated with lenadogene nolparvovec versus placebo at 1.5 years post-treatment, expressed in logarithm of the minimal angle of resolution (LogMAR). Forty-eight patients were treated bilaterally and 50 unilaterally. At 1.5 years, the change from baseline in BCVA was not statistically different between second-affected/not-yet-affected eyes receiving lenadogene nolparvovec and placebo (primary end point). A statistically significant improvement in BCVA was reported from baseline to 1.5 years in lenadogene nolparvovec-treated eyes: -0.23 LogMAR for the first-affected eyes of bilaterally treated patients (P < 0.01); and -0.15 LogMAR for second-affected/not-yet-affected eyes of bilaterally treated patients and the first-affected eyes of unilaterally treated patients (P < 0.05). The mean improvement in BCVA from nadir to 1.5 years was -0.38 (0.052) LogMAR and -0.33 (0.052) LogMAR in first-affected and second-affected/not-yet-affected eyes treated with lenadogene nolparvovec, respectively (bilateral treatment group). A mean improvement of -0.33 (0.051) LogMAR and -0.26 (0.051) LogMAR was observed in first-affected lenadogene nolparvovec-treated eyes and second-affected/not-yet-affected placebo-treated eyes, respectively (unilateral treatment group). The proportion of patients with one or both eyes on-chart at 1.5 years was 85.4% and 72.0% for bilaterally and unilaterally treated patients, respectively. The gene therapy was well tolerated, with no systemic issues. Intraocular inflammation, which was mostly mild and well controlled with topical corticosteroids, occurred in 70.7% of lenadogene nolparvovec-treated eyes versus 10.2% of placebo-treated eyes. Among eyes treated with lenadogene nolparvovec, there was no difference in the incidence of intraocular inflammation between bilaterally and unilaterally treated patients. Overall, the REFLECT trial demonstrated an improvement of BCVA in LHON eyes carrying the m.11778G>A mtDNA mutation treated with lenadogene nolparvovec or placebo to a degree not reported in natural history studies and supports an improved benefit/risk profile for bilateral injections of lenadogene nolparvovec relative to unilateral injections.

This study was undertaken to determine the role of optical coherence tomography (OCT) in predicting the final visual and structural outcome, and to evaluate the correlation between functional eye outcome and retinal changes, in patients with a first episode of optic neuritis (ON).In this prospective study, consecutive adult patients with acute ON underwent ophthalmological evaluation at baseline and at 1 and 12 months, including OCT measurements of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell and inner plexiform layer, and inner nuclear layer thicknesses; high- and low-contrast visual acuity; visual field assessment; and baseline brain magnetic resonance imaging. Univariate and multivariate linear regressions were used to assess predictive factors of outcome. Correlations between 12-month visual function and retinal structure were estimated by Spearman coefficients. Two groups of patients were analyzed, with or without multiple sclerosis (MS).Among 116 patients, 79 (68.1%) had MS, and 37 (31.9%) had ON not related to MS (including 19 idiopathic [i.e., isolated] ON, and 13 and five with myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies, respectively). We found no independent predictive factor of visual and retinal outcome. Analysis of the relationship between the visual field test (mean deviation) and pRNFL thickness demonstrated a threshold of 75.4 μm and 66.4 μm, below which the mean deviation was worse, for patients with MS (p = 0.007) and without MS (p lt; 0.001), respectively.We found that inner retinal layer measurements during the first month are not predictive of final outcome. The critical threshold of axonal integrity, below which visual function is damaged, is different between patients with and without MS.

Purpose The purpose of this study was to identify which combination of imaging modalities should be used to obtain the best diagnostic performance for the non-invasive diagnosis of giant cell arteritis (GCA). Materials and methods This IRB-approved prospective single-center study enrolled participants presenting with a suspected diagnosis of GCA from December 2014 to October 2017. Participants underwent high-resolution 3T magnetic resonance imaging (MRI), temporal and extra-cranial arteries ultrasound and retinal angiography (RA), prior to temporal artery biopsy (TAB). Diagnostic accuracy of each imaging modality alone, then a combination of several imaging modalities, was evaluated. Several algorithms were constructed to test optimal combinations using McNemar test. Results Forty-five participants (24 women, 21 men) with mean age of 75.4 ± 16 (SD) years (range: 59–94 years) were enrolled; of these 43/45 (96%) had ophthalmological symptoms. Diagnosis of GCA was confirmed in 25/45 (56%) patients. Sensitivity and specificity of MRI, ultrasound and RA alone were 100% (25/25; 95% CI: 86–100) and 86% (19/22; 95% CI: 65–97), 88% (22/25; 95% CI: 69–97) and 84% (16/19; 95% CI: 60–97), 94% (15/16; 95% CI: 70–100) and 74% (14/19; 95% CI: 49–91), respectively. Sensitivity, specificity, positive predictive and negative predictive values ranged from 95 to 100% (95% CI: 77–100), 67 to 100% (95% CI: 38–100), 81 to 100% (95% CI: 61–100) and 91 to 100% (95% CI: 59–100) when combining several imaging tests, respectively. The diagnostic algorithm with the overall best diagnostic performance was the one starting with MRI, followed either by ultrasound or RA, yielding 100% sensitivity (22/22; 95% CI: 85–100%) 100% (15/15; 95% CI: 78–100) and 100% accuracy (37/37; 95% CI: 91–100). Conclusion The use of MRI as the first imaging examination followed by either ultrasound or RA reaches high degrees of performance for the diagnosis of GCA and is recommended in daily practice.

Giant cell arteritis (GCA) is a vasculitis often revealed by visual signs. Diagnosis is challenging and urgent. Retinal angiography (RA) and MRI allow effective diagnosis. We compared those and proposed an imaging-based approach to diagnose GCA in ophthalmological practice.We conducted a retrospective study based on the data collected from patients suspected to have GCA on ophthalmological findings. Fluorescein (FA) and indocyanine green (ICG) RAs and MRI were performed and compared with final diagnosis.Among the 41 patients included, 25 were diagnosed with GCA. Sensitivities and specificities of FA and ICG were not different. MRI showed a higher sensitivity and specificity. The approach consisting in performing RA followed by MRI provided a better accuracy.Our study shows that RA can be supplemented by MRI in a specialized center to provide the most accurate diagnosis in GCA revealed by visual signs.

Summary Purpose In March 2020, the sudden rise in the number of SARS-CoV-2 infections in France led the government to impose a strict lockdown during which all non-urgent medical consultations were postponed. From March 17 to May 10, 2020, private medical practices were closed, and telemedicine was encouraged. The consequences on ophthalmic care were dramatic, with over 90% of scheduled consultations canceled. The goal of this study was to describe consultations during the 2-month strict lockdown in Paris and to analyze its impact on the visual outcomes of patients consulting in the ophthalmology emergency department (OED). Methods Data of patients who presented to the OED of the A. de Rothschild Foundation Hospital (RFH), a tertiary ophthalmology center in Paris, France, during the lockdown period and its immediate aftermath were analyzed. The results were compared to the same time periods in the years 2018 and 2019. Four time periods were defined and numbered chronologically: March 17 to May 10, 2018 (period 1);March 17 to May 10, 2019 (period 2);March 17 to May 10, 2020 (period 3, the lockdown period);May 11 to June 9, 2020 (period 4, the post-lockdown period). Results The number of consultations was reduced by more than 50% during the lockdown period (n=2909 patients) and by 30% during the post-lockdown period (n=2622) when compared to periods 1 (n=7125) and 2 (n=8058). Even though LP4 saw an increase in the number of patients consulting, there was no increase in the rate of severe diseases (12.8% during LP3 vs. 11.1% during LP4), and the proportion of patients who were admitted was statistically similar (4.3% vs. 3.6%). Neuro-ophthalmic diseases were the most common during LP3 and LP4. Neovascular glaucoma was twice as common during post-LP4 (P=0.08). We noted a significant increase in patients with graft rejection consulting in our OED during the post-LP4 (P

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The immediate social context at the time of drug consumption is critical at modulating it. The neurobiological substrate of such an influence is however poorly documented. The presence of a stranger peer, naïve to the drug, has been shown to reduce recreational cocaine intake in rats with similar results in human cocaine users. Here we assessed its influence in rats having previously lost their control over drug consumption. The subthalamic nucleus (STN) has been shown to play a critical role in cocaine motivation, escalation and re-escalation, as well as compulsive drug seeking. We show here that after escalation of cocaine intake, the presence of a stranger peer drastically reduced cocaine intake. The same effect was observed after both optogenetic inhibition and high-frequency stimulation of the STN in absence of a peer. We further show that the beneficial influence of social presence is mediated via the STN.One Sentence SummaryThe presence of a stranger peer drastically decreases cocaine intake after drug escalation, as does a subthalamic optogenetic modulation.

Funder: GenSight Biologics, Funder: patients’ organizations MITOCON and IFOND, and patients’ donations, Funder: Fight for Sight UK; doi: http://dx.doi.org/10.13039/501100000615, Funder: Isaac Newton Trust; doi: http://dx.doi.org/10.13039/501100004815, Funder: Addenbrooke’s Charitable Trust, Funder: National Eye Research Centre, Funder: International Foundation for Optic Nerve Disease, Funder: NIHR as part of the Rare Diseases Translational Research Collaboration, Funder: National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology; doi: http://dx.doi.org/10.13039/501100012618, INTRODUCTION: Lenadogene nolparvovec is a promising novel gene therapy for patients with Leber hereditary optic neuropathy (LHON) carrying the m.11778G>A ND4 mutation (MT-ND4). A previous pooled analysis of phase 3 studies showed an improvement in visual acuity of patients injected with lenadogene nolparvovec compared to natural history. Here, we report updated results by incorporating data from the latest phase 3 trial REFLECT in the pool, increasing the number of treated patients from 76 to 174. METHODS: The visual acuity of 174 MT-ND4-carrying patients with LHON injected in one or both eyes with lenadogene nolparvovec from four pooled phase 3 studies (REVERSE, RESCUE and their long-term extension trial RESTORE; and REFLECT trial) was compared to the spontaneous evolution of an external control group of 208 matched patients from 11 natural history studies. RESULTS: Treated patients showed a clinically relevant and sustained improvement in their visual acuity when compared to natural history. Mean improvement versus natural history was - 0.30 logMAR (+ 15 ETDRS letters equivalent) at last observation (P < 0.01) with a maximal follow-up of 3.9 years after injection. Most treated eyes were on-chart as compared to less than half of natural history eyes at 48 months after vision loss (89.6% versus 48.1%; P < 0.01) and at last observation (76.1% versus 44.4%; P < 0.01). When we adjusted for covariates of interest (gender, age of onset, ethnicity, and duration of follow-up), the estimated mean gain was - 0.43 logMAR (+ 21.5 ETDRS letters equivalent) versus natural history at last observation (P < 0.0001). Treatment effect was consistent across all phase 3 clinical trials. Analyses from REFLECT suggest a larger treatment effect in patients receiving bilateral injection compared to unilateral injection. CONCLUSION: The efficacy of lenadogene nolparvovec in improving visual acuity in MT-ND4 LHON was confirmed in a large cohort of patients, compared to the spontaneous natural history decline. Bilateral injection of gene therapy may offer added benefits over unilateral injection. TRIAL REGISTRATION NUMBERS: NCT02652780 (REVERSE); NCT02652767 (RESCUE); NCT03406104 (RESTORE); NCT03293524 (REFLECT); NCT03295071 (REALITY).

Purpose: Evaluate the safety profile of lenadogene nolparvovec (Lumevoq®) in patients with Leber hereditary optic neuropathy. Design: Pooled analysis of safety data from 5 clinical studies. Methods: A total of 189 patients received single unilateral or bilateral intravitreal injections of a recombinant adeno-associated virus 2 (rAAV2/2) vector encoding the human wild-type ND4 gene. Adverse events (AEs) were collected throughout the studies, up to 5 years. Intraocular inflammation and increased intraocular pressure (IOP) were ocular AEs of special interest. Other assessments included ocular examinations, vector bio-dissemination and systemic immune responses against rAAV2/2. Results: Almost all patients (95.2%) received 9 × 1010 viral genomes and 87.8% had at least 2 years of follow-up. Most patients (75.1%) experienced at least one systemic AE, but systemic treatment-related AEs occurred in 3 patients, none was serious. Intraocular inflammation was reported in 75.6% of lenadogene nolparvovec-treated eyes. Almost all intraocular inflammations occurred in the anterior chamber (58.8%) or in the vitreous (40.3%) and was of mild (90.3%) or moderate (8.8%) intensity; most resolved with topical corticosteroids alone. All IOP increases were mild to moderate in intensity. No AE led to study discontinuation. Bio-dissemination of lenadogene nolparvovec and systemic immune response were limited. The safety profile was comparable for patients treated bilaterally and unilaterally. Conclusions: Lenadogene nolparvovec has a good overall safety profile with excellent systemic tolerability, consistent with limited bio-dissemination. The product is well tolerated, with mostly mild ocular side effects responsive to conventional ophthalmologic treatments.

Recapping of Varroa destructor-infested brood cells is a trait that has recently attracted interest in honey bee breeding to select mite-resistant Apis mellifera colonies. To investigate the genetic architecture of this trait, we evaluated a sample of A. mellifera mellifera colonies (N = 155) from Switzerland and France and performed a genome-wide association study, using a pool of 500 workers per colony for next-generation sequencing. The results revealed that two QTL were significantly (P < 0.05) associated with recapping of V. destructor-infested brood cells. The best-associated QTL is located on chromosome 5 in a region previously found to be associated with grooming behaviour, a resistance trait against V. destructor, in A. mellifera and Apis cerana. The second best-associated QTL is located on chromosome 4 in an intron of the Dscam gene, which is involved in neuronal wiring. Previous research demonstrated that genes involved in neuronal wiring are associated with recapping and varroa sensitive hygiene. Therefore, our study confirms the role of a gene region on chromosome 5 in social immunity and simultaneously provides novel insights into genetic interactions between common mite resistance traits in honey bees.

The urban environment is associated with a multitude of challenges and stressors for populations of wild species from the surrounding natural environment. Among those, habitat fragmentation and noise pollution are suspected to have negative effects on the behavior and physiology of free-living birds in urban areas. Exposure in early life and chronic exposure to anthropogenic noise could be particularly deleterious, with short-and long-term consequences. In this study, we investigated if noise levels in city parks affect the distribution and reproductive success of two common bird species in the urban environment, the great tit (Parus major) and the blue tit (Cyanistes caeruleus) and if vegetation cover could mitigate those effects. We predicted that high noise levels might correlate with a decreased nest-box occupancy rate, a delayed laying date or a decreased clutch size, hatching, and fledging success. On the contrary, vegetation cover was expected to correlate positively with nest occupancy rate, advanced laying date, increased clutch size, hatching, and fledging success. We used data from population monitoring collected between 2012 and 2019 in parks and green public spaces in the city center and suburbs of Paris, France, and did not find any correlation between nest occupancy rates and noise levels or vegetation cover for both species. Laying date was not significantly related to anthropogenic noise in any species but was delayed with increasing vegetation cover in the great tit, while we did not find any association with clutch size. Hatching success in blue tits negatively correlated with increasing noise levels, and positively with increasing vegetation coverage. Finally, we did not find any correlation between anthropogenic noise or vegetation cover and the clutch size or fledging success in both species. In this study, two closely related species that share a common environment show a different sensibility to environmental parameters during reproduction, a key period for population maintenance. It also highlights the importance of considering multiple parameters when studying wild populations living in the urban environment.

Background Nonarteritic anterior ischemic optic neuropathy (NAAION) is a major cause of blindness in individuals over 50 years of age, with no available effective treatment. The oral dual endothelin receptor antagonist, bosentan, increases retinal optic nerve head blood flow in healthy humans and glaucoma patients. The objective of this trial is to assess the efficacy of bosentan administered at the acute stage in improving outcomes in NAAION patients. Methods ENDOTHELION (ENDOTHELin antagonist receptor in Ischemic Optic Neuropathy) is a phase III, interventional, prospective, multicentre, placebo-controlled randomised double-blind clinical trial. The primary outcome is change in the visual field mean deviation (MD) at 3 months (Humphrey 30-2 SITA standard programme). Secondary outcomes include MD and visual acuity changes up to 24 months, changes in peripapillary retinal nerve fibre and macular ganglion cell layer thickness in the affected eye, as measured by optical coherence tomography, rate of NAAION bilateralisation at 2 years, and quality-of-life. Patients over 50 years of age presenting with typical NAAION of recent onset (less than 21 days) are randomly assigned to either 125 mg oral bosentan or placebo, twice a day, during 8 weeks. Besides visits during the treatment phase, patients attend follow-up visits at 2, 3, 6, 12 and 24 months. The inclusion of patients began in August 2015 at five French University hospital ophthalmology departments and two specialised ophthalmology centres. It is planned to include 86 patients in this trial. To date we have included 72 patients and 49 have completed the full follow-up process. Discussion An endothelin receptor antagonist is a potential approach to improving the anatomical and functional prognosis of patients with NAAION. This multicentre double-blind randomised controlled trial is an opportunity to assess (1) the effect of bosentan on the structure and function of the optic nerve in NAAION, at 3 months, (2) the effect of bosentan on the bilateralisation rate at 24 months and (3) the tolerance profile of bosentan in this population. Trial registration ClinicalTrials.gov NCT02377271. Registered on March 3, 2015.

Rabih Hage,1 Claire Alapetite,2 Hervé Brisse,3,4 Kevin Zuber,5 Augustin Lecler,6 Guillaume Lot,7 Caroline Le Guerinel,7 Catherine Vignal-Clermont,1 Herve Boissonnet7 1Neuro-ophthalmology Department, Hôpital Fondation A. de Rothschild, Paris, France; 2Radiation Oncology Department, and Proton Center Institut Curie, Paris-Orsay, France; 3Imaging Department, Institut Curie, Paris, France; 4Université des Sciences et Lettres, Paris, France; 5Department of Statistics and Clinical Research, Hôpital Fondation A. de Rothschild, Paris, France; 6Radiology Department, Hôpital Fondation A. de Rothschild, Paris, France; 7Neurosurgery Department, Hôpital Fondation A. de Rothschild, Paris, FranceCorrespondence: Rabih Hage Tel/Fax +33148036322Email rhage@for.parisPurpose: Management of optic nerve sheath meningiomas (ONSM) remains challenging. Photon radiation therapy (PhRT) is the most common treatment for sight-threatening ONSM. Proton beam therapy (PBT) is less commonly used because it is more expensive and because there are questions about its efficacy specifically in relation to ONSM. PBT has the theoretical advantage of reducing radiation exposure to adjacent structures. We report the visual outcome of patients with primary ONSM managed at the Fondation Ophtalmologique Adolphe de Rothschild, Paris, France, and treated with PBT at the Centre de Protonthérapie, Institut Curie, Orsay, France.Methods: We conducted a retrospective review of all patients with primary ONSM who received PBT (either by itself or following surgery) between January 2006 and January 2019. Neuro-ophthalmic examinations were performed at presentation and after radiotherapy, and, when applicable, after surgery. Meningiomas were measured at the time of diagnosis and at each follow-up MRI examination.Results: Sixty patients (50 women, 10 men; mean age, 45.2± 11.1y) were included, of whom 29 underwent surgery. At presentation, 52 (87%) of them had decreased vision (average visual acuity: 0.6 logMAR). Fundus examination showed optic disc swelling (n=27; 46.5%), optic disc pallor (n=22; 37.9%), optic disc cupping (n=2; 3.4%), opto-ciliary shunt (n=8; 13.8%), or choroidal folds (n=5; 8.6%). Otherwise, it was unremarkable (n=7; 12.1%). After treatment, visual function was stable overall. Fundus examination showed pallor (n=47; 83.9%), swelling (n=3; 5.4%), or cupping (n=2; 3.4%) of the optic disc, or was unremarkable (n=5; 8.9%). The visual field of 8 patients worsened, while 3 developed asymptomatic retinal hemorrhages. Tumor shrunk significantly in 8 patients at 1 year after PBT and remained stable in size in all others. Patients with opto-ciliary shunts had significantly worse visual outcome than other patients. Retinal abnormalities were observed in 11 patients during follow-up.Conclusion: PBT alone or in association with surgery appears to be a safe and efficient treatment for ONSM, reducing the tumor size and stabilizing visual function. The risk of developing radiation retinopathy seems to be higher when patients had upfront surgery.Keywords: optic nerve sheath meningioma, ONSM, proton beam therapy, PBT, compressive optic neuropathy, brain tumor, visual loss, opto-ciliary shunt, radiation retinopathy, RON

Peer reviewed: True, The freshwater snail Biomphalaria glabrata is an intermediate host of Schistosoma mansoni, the agent of human intestinal schistosomiasis. However, much is to be discovered about its innate immune system that appears as a complex black box, in which the immune cells (called hemocytes) play a major role in both cellular and humoral response towards pathogens. Until now, hemocyte classification has been based exclusively on cell morphology and ultrastructural description and depending on the authors considered from 2 to 5 hemocyte populations have been described. In this study, we proposed to evaluate the hemocyte heterogeneity at the transcriptomic level. To accomplish this objective, we used single cell RNA sequencing (scRNAseq) technology coupled to a droplet-based system to separate hemocytes and analyze their transcriptome at a unique cell level in naive Biomphalaria glabrata snails. We were able to demonstrate the presence of 7 hemocyte transcriptomic populations defined by the expression of specific marker genes. As a result, scRNAseq approach showed a high heterogeneity within hemocytes, but provides a detailed description of the different hemocyte transcriptomic populations in B. glabrata supported by distinct cellular functions and lineage trajectory. As a main result, scRNAseq revealed the 3 main population as a super-group of hemocyte diversity but, on the contrary, a great hemocytes plasticity with a probable capacity of hemocytes to engage to different activation pathways. This work opens a new field of research to understand the role of hemocytes particularly in response to pathogens, and towards S. mansoni parasites.

Ce chapitre s’intéresse aux aciers à haute tenue mécanique résistants à la corrosion humide, à l’oxydation et au fluage. Les effets liés à la composition, à la microstructure, aux défauts et aux procédés mis en œuvre sont discutés. En filigrane, il apparaît qu’il existe un compromis entre les propriétés mécaniques et le comportement qui découle des interactions avec l’environnement.

Cet article analyse le comportement paradoxal des expatriés de retour frustrés mais fidèles à leur organisation à partir d’une théorie encore émergente en sciences de gestion, celle du don/contre-don de Marcel Mauss. En considérant une expérience d’expatriation comme un « fait social total » qui inclut le passé, le présent et le futur de l’individu et articule l’ensemble des dimensions personnelles et professionnelles, nous proposons une perspective renouvelée sur la période du retour d’expatriation et formulons des préconisations managériales qui prennent en compte les mécanismes nouveaux mis en évidence., This article analyzes the paradoxical behaviour of repatriates who are frustrated yet remain loyal to their organization, using Marcel Mauss’s gift/countergift theory, which is a still-emerging in management science. Considering an expatriation experience as a “total social fact” that includes an individual’s past, present and future and connects all their personal and professional dimensions, we set forth a renewed perspective on the period of repatriation and offer managerial recommendations that take into account the new mechanisms brought to light., Este artículo analiza el paradójico comportamiento de los repatriados frustrados pero fieles a su organización, a partir de una teoría aún emergente en las Ciencias de Gestión, la del “don/contra-don”, de Marcel Mauss. Considerando una experiencia de expatriación como un “hecho social total” que incluye el pasado, el presente y el futuro del individuo y articula el conjunto de las dimensiones personales y profesionales, proponemos una perspectiva renovada sobre el periodo de regreso de la expatriación y formulamos preconizaciones que toman en cuenta los nuevos mecanismos puestos en evidencia.

BACKGROUND AND OBJECTIVE The prognosis in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a matter of debate. Our aim was to assess the long-term outcomes of patients with MOGAD. METHODS We retrospectively analysed the clinical and paraclinical data of patients from the French nationwide observatory study NOMADMUS who tested positive for MOG antibodies (MOG-IgG) and who had clinical follow-up of at least 8 years from their first episode. RESULTS Sixty-one patients (median [range] age at onset 27 [3-69] years), with a median (mean; range) follow-up of 177 (212.8; 98-657) months, were included. Among 58 patients with a relapsing course, 26.3% relapsed in the first year after onset. Of the 61 patients, 90.2% experienced at least one episode of optic neuritis. At last visit, the median (mean; range) Expanded Disability Status Scale (EDSS) score was 1 (2.12; 0-7.5), 12.5% had an EDSS score ≥6 and 37.5% had an EDSS score ≥3. Of 51 patients with final visual acuity (VA) data available, 15.7% had VA ≤0.1 in at least one eye and 25.5% had VA ≤0.5 in at least one eye. Bilateral blindness (VA ≤0.1) was present in 5.9% of patients. Finally, 12.5% of patients presented bladder dysfunction requiring long-term urinary catheterization. No factor associated significantly with a final EDSS score ≥3 or with final VA ≤0.1 was found. CONCLUSION Overall long-term favourable outcomes were achieved in a majority of our patients, but severe impairment, in particular visual damage, was not uncommon.

Cette table ronde a été organisée par Jean-Yves Authier autour de deux numéros d’Espaces et sociétés : « L’espace des classes moyennes » (no 148-149, 2012) et « Où est passé le peuple ? » (no 156-157, 2014) – et plus secondairement autour de deux autres numéros plus anciens : « Usages populaires de l’espace » (no 144-145, 2011) et « La gentrification urbaine » (no 132-133, 2008). Son enjeu était double : discuter du contenu de ces numéros et de leur réception ; débattre plus largement de l’approche matérielle et spatiale des classes sociales, de ses intérêts et de ses limites.Elle a réuni, à Paris, le 22 mai 2019, autour de Jean-Yves Authier, quatre intervenant·es :Deux contributrices aux numéros cités : Anaïs Collet, maîtresse de conférences en sociologie à la faculté des sciences sociales de l’université de Strasbourg et membre du laboratoire SAGE, auteure dans « L’espace des classes moyennes » de l’article intitulé « Le loft : habitat atypique et innovation sociale pour deux générations de “nouvelles classes moyennes” » ; et Cécile Vignal, maîtresse de conférences en sociologie à l’université de Lille, rattachée au laboratoire Clersé, coauteure dans le numéro « Où est passé le peuple » de l’article intitulé « Comment étudier les classes populaires aujourd’hui ? Une démarche d’ethnographie comparée ».Deux personnalités extérieures à ces deux numéros et à Espaces et sociétés : Marie-Christine Jaillet, géographe spécialisée dans les études urbaines, directrice de recherche au CNRS, rattachée au laboratoire LISST, qui a mené de nombreux travaux sur le lien entre périurbanisation et couches moyennes ; et Olivier Schwartz, sociologue, professeur émérite à l’université Paris Descartes, qui a consacré ses travaux de recherche au monde ouvrier et aux classes dites populaires.La table ronde a été structurée en trois temps : un premier consacré à la production des deux numéros ; un deuxième centré sur leur contenu et leur réception ; et un troisième, enfin, sur les intérêts et limites d’une approche des classes sociales par l’espace.