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The renin-angiotensin system (RAS) within the brain is implicated in the control of fluid and electrolyte balance, autonomic functions, blood pressure, and energy expenditure. Mouse models are increasingly used to explore these mechanisms; however, sex and dose dependencies of effects elicited by chronic intracerebroventricular (ICV) angiotensin II (ANG II) infusion have not been carefully established in this species. To examine the interactions among sex, body mass, and ICV ANG II on ingestive behaviors and energy balance, young adult C57BL/6J mice of both sexes were studied in a multiplexed metabolic phenotyping system (Promethion) during chronic infusion of ANG II (0, 5, 20, or 50 ng/h). At these infusion rates, ANG II caused accelerating dose-dependent increases in drinking and total energy expenditure in male mice, but female mice exhibited a complex biphasic response with maximum responses at 5 ng/h. Body mass differences did not account for sex-dependent differences in drinking behavior or total energy expenditure. In contrast, resting metabolic rate was similarly increased by ICV ANG II in a dose-dependent manner in both sexes after correction for body mass. We conclude that chronic ICV ANG II stimulates water intake, resting, and total energy expenditure in male C57BL/6J mice following straightforward accelerating dose-dependent kinetics, but female C57BL/6J mice exhibit complex biphasic responses to ICV ANG II. Furthermore, control of resting metabolic rate by ANG II is dissociable from mechanisms controlling fluid intake and total energy expenditure. Future studies of the sex dependency of ANG II within the brain of mice must be designed to carefully consider the biphasic responses that occur in females.

Background: GPCRs (G protein–coupled receptors) are implicated in blood pressure (BP) and fluid intake regulation. There is a developing concept that these effects are mediated by both canonical G protein signaling and noncanonical β-arrestin mediated signaling, but the contributions of each remain largely unexplored. Here, we hypothesized that β-arrestin contributes to fluid homeostasis and blood pressure (BP) regulation in deoxycorticosterone acetate (DOCA) salt hypertension, a prototypical model of salt-sensitive hypertension. Methods: Global β-arrestin1 ( Arrb1 ) and β-arrestin2 ( Arrb2 ) knockout mice were employed to evaluate drinking behavior, and BP was evaluated in Arrb2 -knockout mice. Age- and sex-matched C57BL/6 mice served as controls. We measured intake of water and different sodium chloride solutions and BP employing a 2-bottle choice paradigm with and without DOCA. Results: Without DOCA (baseline), Arrb2 -knockout mice exhibited a significant elevation in saline intake with no change in water intake. With DOCA treatment, Arrb2 -knockout mice exhibited a significant increase in both saline and water intake. Although Arrb2 -knockout mice exhibited hypernatremia at baseline conditions, we did not find significant changes in total body sodium stores or sodium palatability. In a separate cohort, BP was measured via telemetry in Arrb2 -knockout and C57BL/6 mice with and without DOCA. Arrb2 -knockout did not exhibit significant differences in BP before DOCA treatment when provided water alone, or when provided a choice of water and saline. However, Arrb2 -knockout exhibited an increased pressor response to DOCA-salt. Conclusions: These findings suggest that in salt-sensitive hypertension, ARRB2, but not ARRB1 (β-arrestin 1), might counterbalance the canonical signaling of GPCRs.

Resumen La anorexia y la perdida de peso son sintomas comunes en geriatria, con graves consecuencias en terminos de morbimortalidad y de pronostico funcional. Las causas mas frecuentes son las etiologias oncologicas, los trastornos gastrointestinales benignos, los trastornos psiquiatricos y las enfermedades neurocognitivas. Sin embargo, muchos factores geriatricos predisponen a este riesgo y deben ser investigados. Para ello, la «regla de las 9D» ofrece una vision exhaustiva y rapida de estos factores: drugs (farmacos), depresion, demencia, disfagia, disgeusia, denticion, disfuncion (discapacidades funcionales), disease (enfermedades agudas o cronicas), diarrea. Se requiere una exploracion fisica rigurosa para tratar de identificar la etiologia. Algunas pruebas complementarias, guiados por la exploracion fisica, pueden ayudar en el diagnostico. Sin embargo, en el 25% de los casos no se encuentra la etiologia. El tratamiento consiste en tratar la causa, al tiempo que se implementa el soporte nutricional adecuado. Tambien es esencial una evaluacion geriatrica global para poner de manifiesto todos los factores que predisponen a la anorexia o a la perdida de peso con el fin de proponer medidas de apoyo multimodales.

Federated Learning (FL) is a novel approach enabling several clients holding sensitive data to collaboratively train machine learning models, without centralizing data. The cross-silo FL setting corresponds to the case of few ($2$--$50$) reliable clients, each holding medium to large datasets, and is typically found in applications such as healthcare, finance, or industry. While previous works have proposed representative datasets for cross-device FL, few realistic healthcare cross-silo FL datasets exist, thereby slowing algorithmic research in this critical application. In this work, we propose a novel cross-silo dataset suite focused on healthcare, FLamby (Federated Learning AMple Benchmark of Your cross-silo strategies), to bridge the gap between theory and practice of cross-silo FL. FLamby encompasses 7 healthcare datasets with natural splits, covering multiple tasks, modalities, and data volumes, each accompanied with baseline training code. As an illustration, we additionally benchmark standard FL algorithms on all datasets. Our flexible and modular suite allows researchers to easily download datasets, reproduce results and re-use the different components for their research. FLamby is available at~\url{www.github.com/owkin/flamby}.

Decentralized optimization is increasingly popular in machine learning for its scalability and efficiency. Intuitively, it should also provide better privacy guarantees, as nodes only observe the messages sent by their neighbors in the network graph. But formalizing and quantifying this gain is challenging: existing results are typically limited to Local Differential Privacy (LDP) guarantees that overlook the advantages of decentralization. In this work, we introduce pairwise network differential privacy, a relaxation of LDP that captures the fact that the privacy leakage from a node $u$ to a node $v$ may depend on their relative position in the graph. We then analyze the combination of local noise injection with (simple or randomized) gossip averaging protocols on fixed and random communication graphs. We also derive a differentially private decentralized optimization algorithm that alternates between local gradient descent steps and gossip averaging. Our results show that our algorithms amplify privacy guarantees as a function of the distance between nodes in the graph, matching the privacy-utility trade-off of the trusted curator, up to factors that explicitly depend on the graph topology. Finally, we illustrate our privacy gains with experiments on synthetic and real-world datasets.

The brain renin angiotensin system (RAS) is known for its role in cardiovascular and metabolic regulation. Angiotensin II (Ang II) is the major active product of the RAS, exerting most of its physiological effects through the angiotensin type-1 receptor (AT 1 R). Canonical or G protein-mediated signaling of the AT 1 R within the brain is known to induce dipsogenic and pressor responses to Ang II stimulation. Non-canonical or β-arrestin mediated signaling is thought to counterbalance the detrimental effects of canonical signaling. However, the role of the non-canonical AT 1 R/β-arrestin pathway within the brain is understudied. Therefore, we hypothesized that β-Arrestin activation within the brain contributes to blood pressure (BP) regulation. Global β-arrestin1 ( Arrb 1) and β-arrestin2 ( Arrb 2) knockout (KO) mice were employed to evaluate BP upon treatment with 1) deoxycorticosterone acetate (DOCA)-salt and 2) Ang II. Age- and sex-matched C57BL/6J mice served as controls. First, mice were instrumented with radiotelemetry implants and BP was continuously recorded. At baseline, Arrb2 -KO mice exhibited similar BP when compared to WT (WT=128±5.5 vs Arrb 2-KO=131±5.4 mmHg; n=8 and 9, respectively). However. Arrb2-KO mice exhibited exacerbated responses to DOCA-salt compared to WT (WT=152±12 vs Arrb 2-KO=163±10 mmHg; n=8 and 9, respectively; p=0.03). Second, BP was evaluated upon acute intracerebroventricular (ICV) injection of Ang II (1ug). Arrb -2KO mice showed a higher BP response to Ang II compared to WT (WT=143±12 vs Arrb 2-KO=168±10 mmHg; n=5 and 6, respectively). These findings suggest that activation of β-arrestin2 might counterbalance the effects of canonical activation of the AT 1 R through G proteins. Overall, β-arrestin2 in the brain appears to protect against cardiovascular diseases since the genetic ablation of β-Arrestin2 resulted in an exacerbated BP, particularly with brain-specific injection of Ang II.

Activation of central AT 1 Rs (angiotensin type 1 receptors) is required for the increased blood pressure, polydipsia, and salt intake in deoxycorticosterone acetate (DOCA)–salt hypertension. TRV120027 (TRV027) is an AT 1 R-biased agonist that selectively acts through β-arrestin. We hypothesized that intracerebroventricular administration of TRV027 would ameliorate the effects of DOCA-salt. In a neuronal cell line, TRV027 induced AT 1a R internalization through dynamin and clathrin-mediated endocytosis. We next evaluated the effect of chronic intracerebroventricular infusion of TRV027 on fluid intake. We measured the relative intake of water versus various saline solutions using a 2-bottle choice paradigm in mice subjected to DOCA with a concomitant intracerebroventricular infusion of either vehicle, TRV027, or losartan. Sham mice received intracerebroventricular vehicle without DOCA. TRV027 potentiated DOCA-induced water intake in the presence or absence of saline. TRV027 and losartan both increased the aversion for saline—an effect particularly pronounced for highly aversive saline solutions. Intracerebroventricular Ang (angiotensin) II, but not TRV027, increased water and saline intake in the absence of DOCA. In a separate cohort, blood pressure responses to acute intracerebroventricular injection of vehicle, TRV, or losartan were measured by radiotelemetry in mice with established DOCA-salt hypertension. Central administration of intracerebroventricular TRV027 or losartan each caused a significant and similar reduction of blood pressure and heart rate. We conclude that administration of TRV027 a selective β-arrestin biased agonist directly into the brain increases aversion to saline and lowers blood pressure in a model of salt-sensitive hypertension. These data suggest that selective activation of AT 1 R β-arrestin pathways may be exploitable therapeutically.

The brain renin-angiotensin system (RAS) is implicated in control of blood pressure (BP), fluid intake, and energy expenditure (EE). Angiotensin II (ANG II) within the arcuate nucleus of the hypothalamus contributes to control of resting metabolic rate (RMR) and thereby EE through its actions on Agouti-related peptide (AgRP) neurons, which also contribute to EE control by leptin. First, we determined that although leptin stimulates EE in control littermates, mice with transgenic activation of the brain RAS (sRA) exhibit increased EE and leptin has no additive effect to exaggerate EE in these mice. These findings led us to hypothesize that leptin and ANG II in the brain stimulate EE through a shared mechanism. Because AgRP signaling to the melanocortin MC4R receptor contributes to the metabolic effects of leptin, we performed a series of studies examining RMR, fluid intake, and BP responses to ANG II in mice rendered deficient for expression of MC4R via a transcriptional block ( Mc4r-TB). These mice were resistant to stimulation of RMR in response to activation of the endogenous brain RAS via chronic deoxycorticosterone acetate (DOCA)-salt treatment, whereas fluid and electrolyte effects remained intact. These mice were also resistant to stimulation of RMR via acute intracerebroventricular (ICV) injection of ANG II, whereas BP responses to ICV ANG II remained intact. Collectively, these data demonstrate that the effects of ANG II within the brain to control RMR and EE are dependent on MC4R signaling, whereas fluid homeostasis and BP responses are independent of MC4R signaling.

Background: Validated combined symptom-medication scores (CSMSs) are needed to investigate the effects of allergic rhinitis treatments. This study aimed to use real-life data from the MASK-air® app to generate and validate hypothesis- and data-driven CSMSs. Methods: We used MASK-air® data to assess the concurrent validity, test-retest reliability and responsiveness of one hypothesis-driven CSMS (modified CSMS: mCSMS), one mixed hypothesis- and data-driven score (mixed score), and several data-driven CSMSs. The latter were generated with MASK-air® data following cluster analysis and regression models or factor analysis. These CSMSs were compared with scales measuring (i) the impact of rhinitis on work productivity (visual analogue scale [VAS] of work of MASK-air®, and Work Productivity and Activity Impairment: Allergy Specific [WPAI-AS]), (ii) quality-of-life (EQ-5D VAS) and (iii) control of allergic diseases (Control of Allergic Rhinitis and Asthma Test [CARAT]). Results: We assessed 317,176 days of MASK-air® use from 17,780 users aged 16-90 years, in 25 countries. The mCSMS and the factor analyses-based CSMSs displayed poorer validity and responsiveness compared to the remaining CSMSs. The latter displayed moderate-to-strong correlations with the tested comparators, high test-retest reliability and moderate-to-large responsiveness. Among data-driven CSMSs, a better performance was observed for cluster analyses-based CSMSs. High accuracy (capacity of discriminating different levels of rhinitis control) was observed for the latter (AUC-ROC = 0.904) and for the mixed CSMS (AUC-ROC = 0.820). Conclusion: The mixed CSMS and the cluster-based CSMSs presented medium-high validity, reliability and accuracy, rendering them as candidates for primary endpoints in future rhinitis trials. © 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

Among immune cells, activated monocytes play a detrimental role in chronic and viral-induced inflammatory pathologies. The uncontrolled activation of monocytes and the subsequent excessive production of inflammatory factors damage bone-cartilage joints in Juvenile Idiopathic Arthritis (JIA), a childhood rheumatoid arthritis (RA) disease. Inflammatory monocytes also exert a critical role in the cytokine storm induced by SARS-CoV2 infection in severe COVID-19 patients. The moderate beneficial effect of current therapies and clinical trials highlights the need of alternative strategies targeting monocytes to treat RA and COVID-19 pathologies. Here, we show that targeting CXCR4 with small amino compound such as the histamine analogue clobenpropit (CB) inhibits spontaneous and induced-production of a set of key inflammatory cytokines by monocytes isolated from blood and synovial fluids of JIA patients. Moreover, daily intraperitoneal CB treatment of arthritic mice results in significant decrease in circulating inflammatory cytokine levels, immune cell infiltrates, joints erosion, and bone resorption leading to reduction of disease progression. Finally, we provide the prime evidence that the exposure of whole blood from hospitalized COVID-19 patients to CB significantly reduces levels of key cytokine-storm-associated factors including TNF-α, IL-6 and IL-1β. These overall data show that targeting CXCR4 with CB-like molecules may represent a promising therapeutic option for chronic and viral-induced inflammatory diseases.

The brain renin angiotensin system (RAS) regulates blood pressure (BP) and autonomic function. However, it remains unclear how and where angiotensin II (Ang II) is generated in conditions eliciting brain RAS overactivation including deoxycorticosterone acetate (DOCA)-salt hypertension (HT). In several tissues, the activation of prorenin requires its binding to the prorenin receptor (PRR). New evidence from this study indicates that prorenin and PRR are co-expressed in the proximity to the rostral ventrolateral nucleus (RVL), an anatomical brain region that controls sympathetic nerve activity. Therefore, we hypothesized that selective ablation of PRR targeting the RVL attenuates BP increase due to DOCA-salt. PRR ablation was targeted to the RVL by stereotactic microinjections of adeno-associated virus (AAV) expressing Cre recombinase-mCherry in PRR-flox mice (PRR RVL-KO ). AAV mCherry was used as control virus (WT). A pressor response to L-glutamate in the injection site served as confirmatory stereotactic target hit. RVL-targeted ablation of PRR resulted in lower BP responses to DOCA-salt in females (WT=115±3 vs KO=104±4 mmHg; p RVL-KO unexpectedly exhibited exaggerated increase in systolic BP (WT=149±3 vs KO=163±3 mmHg; p =0.004; n=8) and pulse pressure (WT=31±4 vs KO=45±4 mmHg; p =0.02; n=8) when compared to control. Next, mice were challenged with an intraperitoneal hypertonic saline injection equivalent to 10% of their body weight followed by 4 hours of urine collection. Urinary sodium excretion in female PRR RVL-KO was significantly lower when compared to WT ( p

The brain renin angiotensin system (RAS) is known for its role in cardiovascular and metabolic regulation. Angiotensin II (Ang II) is the major active product of the RAS, exerting most of its physiological effects through the angiotensin type-1 receptor (AT 1 R). Canonical or G-protein-mediated signaling of the AT 1 R within the brain has long been known to induce a dipsogenic and pressor response upon Ang II stimulation. Non-canonical or β-Arrestin mediated signaling is thought to counterbalance the detrimental effects of canonical signaling. However, the non-canonical AT 1 R/β-Arrestin pathway within the brain is understudied. Therefore, it is hypothesized that β-Arrestin activation contributes to fluid homeostasis and blood pressure (BP) regulation. Global β-Arrestin1 ( Arrb 1) and β-Arrestin2 ( Arrb 2) knockout (KO) mice were employed to evaluate drinking behavior and BP with and without deoxycorticosterone acetate (DOCA). Age- and sex-matched C57BL/6J mice served as controls. Mice were subjected to the two-bottle choice paradigm, in which the animals were presented with two bottles, one containing water and one containing 0.15M saline. In the absence of DOCA, mice lacking β-Arrestin2 had increased saline intake when compared to β-Arrestin1-KO and wildtype (WT=2.2±0.2 and Arrb 1-KO=2±0.4 vs Arrb 2-KO=5±0.7 mL/day; pArrb 1-KO=6.5±0.8 vs Arrb 2-KO=16.6±2 mL/day; pArrb 2-KO=124±6 mmHg; n=2), which was exacerbated in response to DOCA (WT=122±6 vs Arrb 2-KO=140±5 mmHg; n=2). These findings suggest that β-Arrestin2 might counterbalance effects of canonical activation of the AT 1 R through G proteins. Overall, β-Arrestin2 appears to protect against cardiovascular diseases since the genetic ablation of β-Arrestin2 resulted in an increase in saline intake and exacerbated BP.

OBJECTIVES: HIV-coinfected patients experience higher incidences of non-liver-related cancers than HCV-monoinfected patients. Chronic inflammation, immunosuppression, but also higher tobacco or alcohol consumption and metabolic dysregulation could explain this higher risk. We aimed to estimate the direct, indirect and total effects of HIV coinfection on the risk of non-liver-related cancers in HCV participants treated with direct-acting antivirals (DAAs). METHODS: Up to four HCV-monoinfected participants from the ANRS CO22 HEPATHER cohort were matched by age and sex to HIV/HCV-coinfected participants from the ANRS CO13 HEPAVIH cohort. Participants were followed from DAA initiation until the occurrence of a non-liver-related cancer. Counterfactual mediation analysis was carried out to estimate the direct (chronic inflammation and immunosuppression), indirect (tobacco and alcohol consumption and metabolic syndrome) and total effect of HIV coinfection on the risk of non-liver-related cancers. RESULTS: 548 HIV/HCV-coinfected and 2016 monoinfected participants were included. Overall, HIV coinfection was associated with a 3.7-fold [95% confidence interval (CI): 1.7-7.0] higher risk of non-liver-related cancers in HCV participants. This increased risk was explained by significant direct effect [hazard ratio (HR) = 3.4, 95% CI: 1.7-6.6] but not indirect effect (HR = 1.1, 95% CI: 0.8-1.5) of HIV coinfection. CONCLUSIONS: In HCV participants treated with DAAs, the direct effect of HIV coinfection, reflecting chronic inflammation and immunosuppression, was associated with a 3.7-fold higher risk of non-liver-related cancer. By contrast, the indirect effect of HIV coinfection, reflecting higher tobacco and alcohol consumption and metabolic dysregulation, was not significantly associated with the risk of non-liver-related cancers.

https://www.ices.dk/sites/pub/Publication%20Reports/Expert%20Group%20Report/Fisheries%20Resources%20Steering%20Group/2021/WGMIXFISH-ADVICE_2020.pdf, SI

The Working Group on Nephrops Surveys (WGNEPS) is the international coordination group for Nephrops underwater television and trawl surveys within ICES. This report summarizes the na-tional contributions on the results of the surveys conducted in 2020 together with time series covering all survey years, problems encountered, data quality checks and technological improve-ments as well as the planning for survey activities for 2021., WGNEPS, ICES

Cette thèse étudie l'optimisation bi-niveau, certaines variantes et une application à la tarification dans les réseaux électriques intelligents.Les problèmes d'optimisation bi-niveaux sont une sous-catégorie de problèmes d'optimisation mathématique contrainte où un deuxième problème ou deuxième niveau estprésent dans les contraintes.Nous étudions leur application à un tariff variable en temps et en niveau de consommation, permettant à un fournisseur d'énergie d'exploiter la flexibilité de consommateurs par des incitations économiques.Une généralisation des problèmes bi-niveaux est également proposée, dans laquelle le deuxième niveau peut sélectionner une solution qui n'est pas optimale contrairement au modèle bi-niveau classique mais quasi-optimale.Résoudre cette variante de problèmes bi-niveaux demande l'anticipation de cette déviation de la solution de deuxième niveau de l'optimalité et garantit qu'une solution au problème bi-niveau sera réalisable malgré cette déviation. This thesis focuses on bilevel optimization, some variants, and an application to optimal price-setting in smart power grids.Bilevel optimization problems are a special subclass of constrained mathematical optimization problems where another problem, the lower level is embedded in the constraints.We consider their application to the optimal pricing of a Time-and-Level-of-Use Demand Response program, allowing an electricity supplier to leverage the flexibility of users through an economic incentive.A generalized form of bilevel optimization is also proposed where the lower level may pick a solution that is not optimal as typically assumed but near-optimal, that is feasible and within a fixed tolerance from an optimal solution.Solving this variant of bilevel optimization requires anticipation of the deviation from optimality and a guarantee that a solution remains feasible even with this deviation.

Activation of central AT

Resume Quels sont les enjeux ethiques lies a l’accompagnement des personnes les plus vulnerables dans un contexte de crise sanitaire, obligeant au confinement ? Parce que le concept de vulnerabilite est large et complexe, l’Espace ethique PACA-Corse s’est interesse plus particulierement a la prise en charge des enfants porteurs de handicaps, des enfants confies a l’aide sociale a l’enfance et des personnes atteintes de troubles psychiatriques. Le confinement a engendre une reorganisation de l‘offre de soin et de l’accompagnement medico-social, pouvant reveler ou aggraver certaines situations de vulnerabilites, voire meme laisser pour compte certaines personnes. Les plus isolees ou a risque de maltraitance ont pu vivre un double confinement. Comment reperer et repondre aux besoins des personnes deja en situation de vulnerabilite avant le confinement qui, isolees dans le contexte epidemique, ont vu leurs vulnerabilites s’accroitre ? Si de nouvelles facons de travailler ont ete mises en place en periode de confinement, certaines ont montre leur interet, d’autres leurs limites. L’enjeu etait de trouver la juste mesure pour aborder la particularite de chaque situation, activer des reseaux de prise en charge de maniere effective et solidaire, et ce, malgre la limitation des moyens et le contexte d’urgence. Toute la difficulte etait de faire coexister protocoles et valeurs du soin, en agissant de maniere reactive et creative. Tout en revelant des vulnerabilites, cette periode a oblige a faire preuve a la fois d’humilite face a l’incertitude, ainsi qu’a un devoir de responsabilite pour prendre soin de ceux qui en avaient le plus besoin.

A 56-year-old man presented a particularly severe and multisystemic case of coronavirus disease 2019 (COVID-19). In addition to the common lung and quite common pulmonary embolism and kidney injuries, he presented ocular and intestinal injuries that, to our knowledge, have not been described in COVID-19 patients. Although it is difficult to make pathophysiological hypotheses about a single case, the multiplicity of injured organs argues for a systemic response to pulmonary infection. A better understanding of physiopathology should feed the discussion about therapeutic options in this type of multifocal damage related to severe acute respiratory syndrome coronavirus 2.

International audience; BackgroundBrain MRI parenchymal signal abnormalities have been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).PurposeTo describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe coronavirus disease 2019 (COVID-19) infection.Materials and MethodsThis was a retrospective study of patients evaluated from March 23, 2020, to April 27, 2020, at 16 hospitals. Inclusion criteria were (a) positive nasopharyngeal or lower respiratory tract reverse transcriptase polymerase chain reaction assays, (b) severe COVID-19 infection defined as a requirement for hospitalization and oxygen therapy, (c) neurologic manifestations, and (d) abnormal brain MRI findings. Exclusion criteria were patients with missing or noncontributory data regarding brain MRI or brain MRI showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. Categorical data were compared using the Fisher exact test. Quantitative data were compared using the Student t test or Wilcoxon test. P < .05 represented a significant difference.ResultsThirty men (81%) and seven women (19%) met the inclusion criteria, with a mean age of 61 years ± 12 (standard deviation) (age range, 8–78 years). The most common neurologic manifestations were alteration of consciousness (27 of 37, 73%), abnormal wakefulness when sedation was stopped (15 of 37, 41%), confusion (12 of 37, 32%), and agitation (seven of 37, 19%). The most frequent MRI findings were signal abnormalities located in the medial temporal lobe in 16 of 37 patients (43%; 95% confidence interval [CI]: 27%, 59%), nonconfluent multifocal white matter hyperintense lesions seen with fluid-attenuated inversion recovery and diffusion-weighted sequences with variable enhancement, with associated hemorrhagic lesions in 11 of 37 patients (30%; 95% CI: 15%, 45%), and extensive and isolated white matter microhemorrhages in nine of 37 patients (24%; 95% CI: 10%, 38%). A majority of patients (20 of 37, 54%) had intracerebral hemorrhagic lesions with a more severe clinical presentation and a higher admission rate in intensive care units (20 of 20 patients [100%] vs 12 of 17 patients without hemorrhage [71%], P = .01) and development of the acute respiratory distress syndrome (20 of 20 patients [100%] vs 11 of 17 patients [65%], P = .005). Only one patient had SARS-CoV-2 RNA in the cerebrospinal fluid.ConclusionPatients with severe coronavirus disease 2019 and without ischemic infarcts had a wide range of neurologic manifestations that were associated with abnormal brain MRI scans. Eight distinctive neuroradiologic patterns were described.

Etude réalisée dans le cadre du M2 Droit public général et contentieux publics, en liaison avec le rapport sur Les justiciables de la QPC (QPC2020) remis au Conseil constitutionnel le 15 janvier 2020, dirigé par le professeur Emmanuel Cartier (Université de Lille). Study carried out as part of the Master 2 General Public Law and Public Litigation, in connection with the report on "Les justiciables de la QPC" (QPC2020) submitted to the Constitutional Council on 15 January 2020, managed by professor Emmanuel Cartier (University of Lille)

he Working Group on Acoustic and Egg Surveys (WGACEGG) coordinates pelagic surveys for a number of stocks and provides monitoring for the two major sardine and anchovy stocks in ICES areas 6, 7, 8, and 9. The group evaluated small pelagic fish biomass indices derived from acoustic and Daily Egg Production Method (DEPM) surveys in ICES areas 6, 7, 8 and 9. These indices have been provided to the ICES Working Group on Southern Horse Mackerel, Anchovy and Sardine (WGHANSA), the Working Group on Widely Distributed Stocks (WGWIDE) and the Herring Assessment Working Group for the Area South of 62ºN (HAWG) stock assessment group, to serve as fishery-independent input for analytical assessment purposes. DEPM and acoustic indices were derived based on data collected using independent methods. Acoustic- and DEPM-derived biomass indices from quasi-synoptic surveys conducted in the Bay of Biscay in spring were compared, to assess the presence of potential bias and to improve the precision of fish stock biomass estimates. The DEPM-based anchovy biomass index was 22% higher than the acoustic index in 2019. Unusual concentrations of anchovy in Eastern Cantabrian Sea, an area not covered by the acoustic survey, and the presence near the sea surface of actively spawning individuals possibly under-sampled by acoustics in central Bay of Bay had been postulated as potential causes of this discrepancy. No significant difference was found between sardine biomass indices derived from DEPM and acoustics in 2019. The group has updated its database of standard gridded maps covering the European Atlantic area. This initiative continues to inform on the spatial dynamics of various parameters collected during the surveys coordinated under the auspices of the group (fish acoustic densities, anchovy and sardine egg abundance, surface temperature and salinity). Results of an analysis of the time series of gridded maps (anchovy and sardine acoustic density, surface salinity and temperature) showed quantitative changes in the spatial and temporal distribution of anchovy and sardine over the last 15 years, and further define their habitats in European Atlantic waters in spring. The timing and spatial coverage of DEPM and acoustic surveys that will be conducted by group members in 2020 were planned to optimise the monitoring of anchovy and sardine populations and their pelagic environment in the European Atlantic area. The synoptic nature of the survey components has been assessed for each target species. A manual describing the protocols used during the DEPM surveys coordinated by the WGACEGG group was reviewed, and writing of a manual of WGACEGG acoustic surveys continued. Both manuals will be available in 2020. The final results of the 2017 sardine DEPM assessment were endorsed by the group.