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Two different tensions can be defined for a fluid membrane: the internal tension, $\gamma$, conjugated to the real membrane area in the Hamiltonian, and the frame tension, $\tau$, conjugated to the projected (or frame) area. According to the standard statistical description of a membrane, the fluctuation spectrum is governed by $\gamma$. However, using rotational invariance arguments, several studies argued that fluctuation spectrum must be governed by the frame tension $\tau$ instead. These studies disagree on the origin of the result obtained with the standard description yet: either a miscounting of configurations, quantified with the integration measure, or the use of a quadratic approximation of the Helfrich Hamiltonian. Analyzing the simplest case of a one-dimensional membrane, for which arc length offers a natural parametrization, we give a new proof that the fluctuations are driven by $\tau$, and show that the origin of the issue with the standard description is a miscounting of membrane configurations. The origin itself of this miscounting depends on the thermodynamic ensemble in which calculations are made.

Coordination of cytoplasmic flows on large scales in space and time are at the root of many cellular processes, including growth, migration or division. These flows are driven by organized contractions of the actomyosin cortex. In order to elucidate the basic mechanisms at work in the self-organization of contractile activity, we investigate the dynamic patterns of cortex contraction in true slime mold Physarum polycephalum confined in ring-shaped chambers of controlled geometrical dimensions. We make an exhaustive inventory of the different stable contractile patterns in the absence of migration and growth. We show that the primary frequency of the oscillations is independent of the ring perimeter, while the wavelength scales linearly with it. We discuss the consistence of these results with the existing models, shedding light on the possible feedback mechanisms leading to coordinated contractile activity.

Analysis of thermal capillary waves on the surface of a liquid usually assumes incompressibility of the bulk fluid. However, for droplets or bubbles with submicronic size, or for epithelial cells whose out-of-plane elongation can be modeled by an effective 2D bulk modulus, compressibility of the internal fluid must be taken into account for the characterization of their shape fluctuations. We present a theoretical analysis of the fluctuations of a two-dimensional compressible droplet. Analytical expressions for area, perimeter and energy fluctuations are derived and compared with Cellular Potts Model (CPM) simulations. This comparison shows a very good agreement between theory and simulations, and offers a precise calibration method for CPM simulations.

Cell sorting, whereby a heterogeneous cell mixture segregates and forms distinct homogeneous tissues, is one of the main collective cell behaviors at work during development. Although differences in interfacial energies are recognized to be a possible driving source for cell sorting, no clear consensus has emerged on the kinetic law of cell sorting driven by differential adhesion. Using a modified Cellular Potts Model algorithm that allows for efficient simulations while preserving the connectivity of cells, we numerically explore cell-sorting dynamics over very large scales in space and time. For a binary mixture of cells surrounded by a medium, increase of domain size follows a power-law with exponent n = 1/4 independently of the mixture ratio, revealing that the kinetics is dominated by the diffusion and coalescence of rounded domains. We compare these results with recent numerical studies on cell sorting, and discuss the importance of algorithmic differences as well as boundary conditions on the observed scaling., Author summary Cell sorting describes the spontaneous segregation of identical cells in biological tissues. This phenomenon is observed during development or organ regeneration in a variety of biological systems. Minimization of the total surface energy of a tissue, in which adhesion strengh between homotypic and heterotypic cells are different, is one of the mechanisms that explain cell sorting. This mechanism is then similar to the one that drives demixing of two immiscible fluids. Because of the high sensibility of this process to finite-size and finite-time effects, no clear consensus has emerged on the scaling law of cell sorting driven by differential adhesion. Using an efficient numerical code, we were able to investigate this scaling law on very large binary mixtures of cells. We show that on long times, cell sorting obeys a universal power law, which is independent of the mixture ratio and boundary conditions.

Mast cells are key actors of innate immunity and Th2 adaptive immune response which counterbalance Th1 response, critical for anti-viral immunity. Clonal Mast Cells Activation Disorders (cMCADs) such as mastocytosis and clonal mast cells activation syndrome are characterized by an abnormal mast cells accumulation and/or activation. No data have been published on the anti-viral immune response of patients with cMCADs. The aims of the study were to collected, in a comprehensive way, outcomes of cMCADs patients who experienced a biologically-proven COVID-19 and to characterize both anti-endemic coronaviruses and specific anti-SARS-CoV-2 immune responses in these patients. Clinical follow-up and outcome data were collected prospectively for one year within the French rare disease network CEREMAST encompassing patients from all over the country. Anti-SARS-CoV-2 and anti-endemic coronaviruses specific T-cells were assessed with an enzyme-linked immunospot assay (EliSpot) and anti-SARS-CoV-2 humoral response with dosage of circulating levels of specific IgG, IgA and neutralizing antibodies. Overall, 32 cMCADs patients were identified. None of them required non-invasive or mechanical ventilation; two patients were hospitalized to receive oxygen and steroid therapy. In 21 patients, a characterization of the SARS-CoV-2-specific immune response has been performed. A majority of patients showed a high proportion of circulating SARS-CoV-2-specific interferon (IFN)-γ producing T-cells and high levels of anti-Spike IgG antibodies with neutralizing activity. In addition, no defects in anti-endemic coronaviruses responses were found in patients with cMCADs compared to non-cMCADs controls. Patients with cMCADs frequently showed a spontaneous IFN-γ T-cell production in absence of any stimulation that correlated with circulating basal tryptase levels, a marker of mast cells burden. These findings underscore that patients with cMCADs might be not at risk of severe COVID-19 and the spontaneous IFN-γ production might explain this observation.Author SummaryMast cells are immune cells involved in many biological processes including the anti-microbial response. However, previous studies suggest that mast cells may have a detrimental role in the response against viruses such as SARS-CoV-2, responsible for COVID-19. When a mutation occurs in mast cells, it can lead to a group of diseases called clonal mast cells activation disorders (cMCADs), characterized by deregulated activation of these cells. Hence, patients with cMCADs might be more susceptible to severe COVID-19 than general population.We therefore conducted a 1-year study in France to collect data from all cMCADs patients included in the CEREMAST rare disease French network and who experienced COVID-19. Interestingly, we did not find any severe COVID-19 (i.e. requiring non-invasive or mechanical ventilation) in spite of well-known risk factors for severe COVID-19 in a part of cMCADs patients.We then have studied the immune response against SARS-CoV-2 and other endemic coronaviruses in these patients. We did not observe any abnormalities in the immune response either at the level of T and B lymphocytes. These findings underscore that these patients might not be at risk of severe COVID-19 as one might have feared.

Soft cellular systems, such as foams or biological tissues, exhibit highly complex rheological properties, even in the quasistatic regime, that numerical modeling can help to apprehend. We present a numerical implementation of quasistatic strain within the widely used cellular Potts model (CPM). The accuracy of the method is tested by simulating the quasistatic strain of two-dimensional dry foams, both ordered and disordered. The implementation of quasistatic strain in CPM allows the investigation of sophisticated interplays between stress-strain relationship and structural changes that take place in cellular systems.

International audience; BackgroundMast cells are key players in innate immunity and the TH2 adaptive immune response. The latter counterbalances the TH1 response, which is critical for antiviral immunity. Clonal mast cell activation disorders (cMCADs, such as mastocytosis and clonal mast cell activation syndrome) are characterized by abnormal mast cell accumulation and/or activation. No data on the antiviral immune response in patients with MCADs have been published.ObjectiveTo study a comprehensive range of outcomes in patients with cMCAD with PCR- or serologically confirmed coronavirus disease 2019 and to characterize the specific anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune response in this setting.MethodsClinical follow-up and outcome data were collected prospectively over a 12-month period by members of the French Centre de Référence des Mastocytoses rare disease network. Anti–SARS-CoV-2–specific T-cell activity was measured with an ELISA, and humoral responses were evaluated by assaying circulating levels of specific IgG, IgA, and neutralizing antibodies.ResultsOverall, 32 patients with cMCAD were evaluated. None required noninvasive or mechanical ventilation. Two patients were admitted to hospital for oxygen and steroid therapy. The SARS-CoV-2–specific immune response was characterized in 21 of the 32 patients. Most had high counts of circulating SARS-CoV-2–specific, IFN-γ–producing T cells and high titers of neutralizing antispike IgGs. The patients frequently showed spontaneous T-cell IFN-γ production in the absence of stimulation; this production was correlated with basal circulating tryptase levels (a marker of the mast cell burden).ConclusionsPatients with cMCADs might not be at risk of severe coronavirus disease 2019, perhaps due to their spontaneous production of IFN-γ.

A 53-year-old man presented with acute loss of vision, negative scotoma and dyschromatopsia in his left eye. He reported contact with people with severe respiratory syndrome - coronavirus-2 (SARS-CoV-2) 8 days prior symptoms. Funduscopic examination revealed several retinal hemorrhages. Spectral-domain optical coherence tomography showed lesions consistent with acute macular neuroretinopathy and paracentral acute middle maculopathy. Quickly after his presentation, SARSCov-2 was confirmed by chest computed tomography-scan and RT-PCR in this patient. Thrombotic complications associated with Covid-19 infection have high incidence and may involve the retina. We described a case of retinal involvement associated with Covid-19 infection.Funduscopic examination revealed retinal hemorrhages in a man with loss of vision. Optical coherence tomography showed an acute macular neuroretinopathy and paracentral acute middle maculopathy. Coronavirus disease was confirmed by chest computed tomography-scan and RT-PCR.

We described three clinical cases of pyogenic liver abscess caused by hypervirulent Klebsiella pneumoniae (hvKp) successfully treated by prolonged antibiotherapy, in which one case was complicated by endophthalmitis. Whole genome sequencing helped to confirm the diagnosis of these hvKp strains, which belong to clonal complexes CC86 and CC23 and carried hvKp-associated genes (magA and/or rmpA). This syndrome is increasingly reported in France and Europe and raises questions about the source of infection.

Cet article présente des principes de conception de films portant sur le travail à des fins de formation professionnelle, et les illustre par un cas pratique issu d’un partenariat avec les huissiers d’un Office cantonal suisse. Ces principes reposent sur une analyse préalable de leur activité, de ses contraintes et de ses effets à partir de l’observation et du filmage du travail. Le montage secondaire des films s’éloigne de la présentation fidèle du travail pour en restituer les éléments typiques implicites, révélés par l’analyse préalable. Montés sous forme de récits, ils sont censés perturber les visionneurs en provoquant chez eux un engagement mimétique par rapport aux scènes présentées et un re-enactement lors du visionnage, c’est à dire une expérience proche du vécu de travail. Ce visionnage est aussi censé déclencher des dynamiques d’appropriation des composantes typiques du travail, et de leur expropriation et partage avec d’autres professionnels, favorisant la constitution d’une communauté de pratique. This paper is about film editing for documentation of work practices and training purposes. It illustrates these principles by a practical case: the working activity of bailiffs in a Swiss cantonal office. Training situations designing is based on a prior analysis of bailiffs’ activity, its constraints and its effects, by the mean of observation and video recording of work practices. During films editing, we move away from the faithful presentation of work practice, to account of its typical implicit elements, revealed by the preliminary analysis. The films are built like stories. They are supposed to disturb the viewers by provoking a mimetic engagement at them when viewing the scenes, and a re-enactement – i.e. an experience close to the former working one –. Viewings are also supposed to trigger appropriation of the typical components of activity by the bailiffs, and an expropriation and sharing of them with other professionals, promoting the construction of a community of practice.

This chapter explores participants’ experiences in the Theater of Lived Experience (TLE), an educational dispositive for adults with life trajectories marked by severe traumatic episodes resulting in deadlock and states of collapse. Participants were accompanied as they created mini-plays: they prepared scripts about a problematic experience, staged them and directing the actors. We adopted a semiological approach to these experiences through in situ observations and ex post interviews to (a) identify the participants’ intentions, concerns, anticipations and knowledge and (b) reconstruct the salient features before and during TLE. Several months later, we again analysed the changes in their life experience. Results showed that TLE offered a break in the participants’ life courses and gained value as an event triggering resilience and dynamic vitality. TLE illustrates a developmental perspective in adult education that uses on artistic mediation and provides grounds for broader reflection on education and resilience.

Many textbooks dealing with surface tension favor the thermodynamic approach (minimization of some thermodynamic potential such as free energy) over the mechanical approach (balance of forces) to describe capillary phenomena, stating that the latter is flawed and misleading. Yet, mechanical approach is more intuitive for students than free energy minimization, and does not require any knowledge of thermodynamics. In this paper we show that capillary phenomena can be unmistakably described using the mechanical approach, as long as the system on which the forces act is properly defined. After reminding the microscopic origin of a tangential tensile force at the interface, we derive the Young-Dupr{\'e} equation, emphasizing that this relation should be interpreted as an interface condition at the contact line, rather than a force balance equation. This correct interpretation avoids misidentification of capillary forces acting on a given system. Moreover, we show that a reliable method to correctly identify the acting forces is to define a control volume that does not embed any contact line on its surface. Finally, as an illustration of this method, we apply the mechanical approach in a variety of ways on a classic example: the derivation of the equilibrium height of capillary rise (Jurin's law).

We derive general conditions for the design of two-dimensional stiffest elastic networks with tetrakis-like (or ‘Union Jack’-like) topology. Upon generalizing recent results for tetrakis structures composed of two different rod geometries (length and cross-sectional area), we derive the elasticity tensor of a lattice with generalized tetrakis architecture, which is composed of three kinds of rods and generally exhibits anisotropic response. This study is accompanied by an experimental verification of the theoretical prediction for the longitudinal modulus of the lattice. In addition, the introduction of a third rod geometry allows to extend considerably the possible lattice geometries for isotropic, stiffest elastic lattices with tetrakis-like topology. The potential of the analyzed structures as innovative metamaterials featuring extremely high elastic moduli vs. density ratios is highlighted.

Background Safety of HPV vaccines is still in question due to reports of autoimmune diseases (ADs) following HPV immunization. Objectives To assess the risk of ADs associated with HPV vaccination of female adolescents/young adults in France. Methods Systematic prospective case-referent study conducted to assess the risks associated with real-life use of HPV vaccines. Cases were female 11–25 years old with incident ADs [central demyelination/multiple sclerosis (CD/MS), connective tissue disease (CTD), Guillain-Barre syndrome (GBS), type-1 diabetes (T1D), autoimmune thyroiditis (AT), and idiopathic thrombocytopenic purpura (ITP)]. Cases were consecutively and prospectively identified at specialized centers across France (2008–2014) and individually matched by age and place of residence to referents recruited in general practice. Risk was computed using multivariate conditional logistic regression models adjusted for family history of ADs, living in France (north/south), co-medications and co-vaccinations. Results With a total of 478 definite cases matched to 1869 referents, all ADs combined were negatively associated to HPV vaccination with an adjusted odds ratio of 0.58 (95% confidence interval: 0.41–0.83). Similar results were obtained for CD/MS, AT, CT, and T1D, the last two not reaching statistical significance. No association was found for ITP and GBS. Sensitivity analyses combining definite and possible cases with secondary time window showed similar results. Conclusion Exposure to HPV vaccines was not associated with an increased risk of ADs within the time period studied. Results were robust to case definitions and time windows of exposure. Continued active surveillance is needed to confirm this finding for individual ADs.

The aim of our study was to investigate possible differences in nailfold videocapillaroscopy (NVC) features between patients with dermatomyositis (DM), overlap myositis (OM), antisynthetase syndrome (ASS), and immune-mediated necrotizing myopathy (IMNM).We performed a cross-sectional monocentric study. All patients with inflammatory myopathies (IMs) over a 6-month period were analyzed by NVC for giant and ramified capillaries, tortuosities, capillary density, disorganization, and scleroderma pattern. Clinical, biological, and pathological characteristics were retrospectively recorded. Patients were classified as having DM, OM, ASS, or IMNM for comparison. Patients were also compared with a group of patients with systemic sclerosis (SSc).NVC was analyzed in DM (n = 17), OM (n = 8), ASS (n = 12), and IMNM (n = 6). Vascular disorganization and avascular zones were observed only in DM (11.8%) and OM (62.5%). The percentage of patients with giant capillaries was higher in OM (n = 4/8) than in DM (n = 3/17) and absent in ASS and IMNM. Frequency of ramified capillaries, tortuosities, hemorrhages, or thrombosis was not different between subgroups. A scleroderma pattern was only observed in OM patients.In this limited series of patients, we observed that DM and OM NVC abnormalities are different from ASS and IMNM. We could not determine NVC specific patterns associated with myositis-specific antibody subtypes of DM because of the small number of patients.Key Points• Nailfold videocapillaroscopy abnormalities are different in subgroups of inflammatory myopathies.• Giant capillaries, disorganization, and major capillary loss are observed in overlap myositis and dermatomyositis but not in antisynthetase syndrome (ASS) or immune-mediated necrotizing myopathy.• Nailfold videocapillaroscopy abnormalities in overlap myositis (with the exclusion of ASS) are close to systemic sclerosis.

International audience; PURPOSE: Immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) are associated in the definition of Evans syndrome (ES). The occurrence of neurological involvement in this population is poorly described and suggests an underlying primary immunodeficiency (PID). We aimed to describe the clinical manifestations, evolution, and PID profiles of these patients.METHODS: OBS'CEREVANCE is a French, nationwide prospective cohort that includes children with chronic ITP, AIHA, and ES. Patients with a neurological involvement were described. Centralized radiological and pathological reviews and genetic analyses were performed.RESULTS: On October 2016, eight patients (7/181 ES, 1/371 AIHA, and 0/615 ITP) were identified, all male, with a median age (range) at cytopenia onset of 11.5 years (1.6-15.8). Neurological symptoms appeared with a median delay of 6 years (2.5-18) after cytopenia and were polymorphic: seizures (n = 4), cranial nerve palsy (n = 2), Brown-Sequard syndrome (n = 2), intracranial pressure (n = 2), vertigo (n = 1), and/or sensory neuropathy (n = 1). Magnetic resonance imaging (MRI) showed inflammatory lesions, confirmed by pathology for five patients with macrophagic or lymphoplasmocytic infiltrates. All patients had other relevant immunopathological manifestations: pulmonary nodules (n = 6), lymphoproliferation (n = 4), abnormal immunophenotype (n = 8), and hypogammaglobulinemia (n = 7). Treatment consisted of steroids that improved symptomatology and MRI. Five patients relapsed and three had an asymptomatic radiological progression. A PID was identified in 3/8 patients: 22q11.2 microdeletion (n = 1) and CTLA deficiency (n = 2).CONCLUSION: Neurological involvement is a rare and severe late event in the course of childhood ES, which can reveal an underlying PID. Imaging and pathology examination highlight a causative immune dysregulation that may guide targeted therapeutic strategies.

International audience; We describe the clinical, hematologic and genetic characteristics of a retrospective series of 126 subjects from 64 families with hereditary xerocytosis. Twelve patients from six families carried a KCNN4 mutation, five had the recurrent p.Arg352His mutation and one had a new deletion at the exon 7-intron 7 junction. Forty-nine families carried a PIEZO1 mutation, which was a known recurrent mutation in only one-third of the cases and private sequence variation in others; 12 new probably pathogenic missense mutations were identified. The two dominant features leading to diagnosis were hemolysis that persisted after splenectomy and hyperferritinemia, with an inconstant correlation with liver iron content assessed by magnetic resonance imaging. PIEZO1-hereditary xerocytosis was characterized by compensated hemolysis in most cases, perinatal edema of heterogeneous severity in more than 20% of families and a major risk of post-splenectomy thrombotic events, including a high frequency of portal thrombosis. In KCNN4-related disease, the main symptoms were more severe anemia, hemolysis and iron overload, with no clear sign of red cell dehydration; therefore, this disorder would be better described as a ‘Gardos channelopathy’. These data on the largest series to date indicate that PIEZO1-hereditary xerocytosis and Gardos channelopathy are not the same disease although they share hemolysis, a high rate of iron overload and inefficient splenectomy. They demonstrate the high variability in clinical expression as well as genetic bases of PIEZO1-hereditary xerocytosis. These results will help to improve the diagnosis of hereditary xerocytosis and to provide recommendations on the clinical management in terms of splenectomy, iron overload and pregnancy follow-up.

International audience; Many systems, including biological tissues and foams, are made of highly packed units having high deformability but low compressibility. At two dimensions, these systems offer natural tesselations of plane with fixed density, in which transitions from ordered to disordered patterns are often observed, in both directions. Using a modified Cellular Potts Model algorithm that allows rapid thermalization of extensive systems, we numerically explore the order-disorder transition of monodisperse, two-dimensional cellular systems driven by thermal agitation. We show that the transition follows most of the predictions of Kosterlitz-Thouless-Halperin-Nelson-Young (KTHNY) theory developed for melting of 2D solids, extending the validity of this theory to systems with many-body interactions. In particular, we show the existence of an intermediate hexatic phase, which preserves the orientational order of the regular hexagonal tiling, but looses its positional order. In addition to shedding light on the structural changes observed in experimental systems, our study shows that soft cellular systems offer macroscopic systems in which KTHNY melting scenario can be explored, in the continuation of Bragg's experiments on bubble rafts.

International audience; We consider the hydrodynamics of lipid bilayers containing transmembrane proteins of arbitrary shape. This biologically-motivated problem is relevant to the cell membrane, whose fluctuating dynamics play a key role in phenomena ranging from cell migration, intercellular transport, and cell communication. Using Onsager's variational principle, we derive the equations that govern the relaxation dynamics of the membrane shape, of the mass densities of the bilayer leaflets, and of the diffusing proteins' concentration. With our generic formalism, we obtain several results on membrane dynamics. We find that proteins that span the bilayer increase the intermonolayer friction coefficient. The renormalization, which can be significant, is in inverse proportion to the protein's mobility. Second, we find that asymmetric proteins couple to the membrane curvature and to the difference in monolayer densities. For practically all accessible membrane tensions (σ > 10 −8 N/m) we show that the protein density is the slowest relaxing variable. Furthermore, its relaxation rate decreases at small wavelengths due to the coupling to curvature. We apply our formalism to the large-scale diffusion of a concentrated protein patch. We find that the diffusion profile is not self-similar, owing to the wavevector dependence of the effective diffusion coefficient.

Pourquoi Angela Merkel se voit contrainte de changer son fusil d’epaule en matiere de politique europeenne et accepte une solidarite qu’elle a energiquement refusee pendant la crise des subprimes ? Habermas repond en soulignant la percee politique de l’Alternative pour l’Allemagne et le retour qu’elle impose sur l’histoire de l'Allemagne dans son rapport au nazisme, a l'Est et a l'Ouest, avant et apres la reunification.

Background We conducted a monocentric retrospective study of patients with myelodysplastic syndromes (MDS) and autoimmune or inflammatory disorders (AIMs) and a literature review. We analyzed the association with subgroups of the WHO 2016 MDS classification and patient's survival in a case control study. Risk factors associated with survival were analyzed by uni- and multivariate analysis. Results From all MDS patients 11% presented with AIMs. These were heterogeneous and the most frequent where polyarthritis (25%) and autoimmune cytopenias (17%). No difference for frequency and type of AIMs was observed for the WHO 2016 MDS subgroups (p = .3). In the case control study WHO classification, karyotype abnormalities, IPSS-R and IPSS were similar in both groups. The overall survival from MDS diagnosis was better in the group with AIMs [10.3 ± 0.6 (IC95% 6.2–12.9) versus 4.8 ± 1.1 years (IC95% 4.2–8.7), p = .04]. The better survival was restricted to MDS with low or intermediate-1 IPSS [11.1 ± 1.5 (IC95% 9.9-NR) versus 8.7 ± 1.3 years (IC95% 4.8–10.3), p = .006]. The better survival was only observed when AIMs diagnosis was timely associated or appeared after MDS diagnosis (p = .04). Factors associated with a better overall survival and survival without AML were steroid dependence [respectively HR = 0.042, p = .003, (IC95% 0.005–0.33) and HR = 0.07, p = .002, (IC95% 0.013–0.39)], a diagnosis of AIMs and MDS timely associated [respectively HR = 0.05, p = .009, (IC95% 0.006–0.478) and HR = 0.1, p = .008, (IC95% 0.018–0.54)] or a diagnosis of AIMs after MDS [respectively HR = 0.024, p = .009, (IC95% 0.001–0.39) and HR = 0.04, p = .008, (IC95% 0.003–0.43)]. Conclusion Autoimmune and inflammatory diseases associated to MDS are heterogeneous. AIMs diagnosed after or concomitantly to MDS seems associated with a better survival. Prospective studies are necessary to demonstrate that autoimmunity is associated to a better control of the MDS clone.