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Dans une formulation abrupte contre l’esthétique de l’idéalisme allemand, Herbart exigea que l’on renonce à appréhender l’idée de la beauté de manière spéculative. La tâche la plus importante dans l’exploration du beau est bien plutôt de dégager les rapports originaires qui lui sont propres, et sur lesquels repose vraiment le plaisir esthétique. Hegel avait imprimé à l’intuition de l’idéalisme allemand sa dimension la plus partiale quand, dans ses Vorlesungen über Ästhetik qui parurent en 183...

Resume Introduction La vascularite a IgA est une vascularite leucocytoclasique des petits vaisseaux liee a des depots de complexes immuns d’IgA. Elle survient tres frequemment en contexte post-infectieux ; toutefois, le pathogene n’est que rarement mis en evidence. Observation Nous rapportons, pour la premiere fois, le cas d’un patient de 81 ans ayant developpe une vascularite a IgA a expression cutaneo-articulaire au decours immediat d’une pneumopathie abcedee a Klebsiella pneumoniae. La vascularite a regresse de maniere concomitante a l’instauration d’une antibiotherapie seule. Conclusion Cette observation nous rappelle l’interet de la recherche minutieuse d’un pathogene au cours des vascularites a IgA ainsi que d’un traitement causal.

Purpose To describe the characteristics and outcome of patients with giant-cell arteritis (GCA)-related ophthalmologic involvement at diagnosis. Methods In a retrospective single-center cohort of 409 consecutive patients with GCA, we retrieved 104 patients with visual symptoms at GCA diagnosis and we compared them to 104 age- and sex-matched controls without ophthalmologic involvement. Each visual symptom was associated to an ophthalmologic diagnosis that was centrally re-assessed by an ophthalmologist. Results Compared to controls, patients with visual symptoms showed less fever (p = 0.0006), less polymyalgia rheumatica (p = 0.02) and lower acute phase reactants (p = 0.004). Blurred vision (in 60% of patients), amaurosis fugax (in 18%), diplopia (in 13%) and permanent visual loss (in 9%) were the four visual symptoms described by patients before GCA diagnosis. Anterior ischemic optic neuropathy (AION) was found in 47 (45%) patients, followed by central retinal artery occlusion (CRAO) in 15 (15%). Two patients had both involvements. The delay of glucocorticoids initiation was not different between patients with and without visual symptoms (p = 0.06). Among the 60 patients with initial AION and/or CRAO, 39 (65%) kept definite blindness or important visual damage, although 45 (75%) had received intravenous (IV) pulses of methylprednisolone. A new ischemic event (AION in all cases) occurred in 4% of patients with visual symptoms despite the initiation of treatment. Conclusion Ophthalmologic involvement was observed in one-quarter of our GCA patients. AION is still associated with the worst visual prognosis, and IV methylprednisolone pulses did not reduce the risk of blindness in our study.

Background Nanopore technologies allow high-throughput sequencing of long strands of DNA at the cost of a relatively large error rate. This limits its use in the reading of amplicon libraries in which there are only a few mutations per variant and therefore they are easily confused with the sequencing noise. Consensus calling strategies reduce the error but sacrifice part of the throughput on reading typically 30 to 100 times each member of the library. Findings In this work, we introduce SINGLe (SNPs In Nanopore reads of Gene Libraries), an error correction method to reduce the noise in nanopore reads of amplicons containing point variations. SINGLe exploits that in an amplicon library, all reads are very similar to a wild-type sequence from which it is possible to experimentally characterize the position-specific systematic sequencing error pattern. Then, it uses this information to reweight the confidence given to nucleotides that do not match the wild-type in individual variant reads and incorporates it on the consensus calculation. Conclusions We tested SINGLe in a mutagenic library of the KlenTaq polymerase gene, where the true mutation rate was below the sequencing noise. We observed that contrary to other methods, SINGLe compensates for the systematic errors made by the basecallers. Consequently, SINGLe converges to the true sequence using as little as 5 reads per variant, fewer than the other available methods.

Few comparative data exist on early infections secondary to remission-induction therapy (RIT) with rituximab (RTX) versus cyclophosphamide (CYC) in newly diagnosed anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients. We compared and analysed the rates and predictors of severe infection in such patients within the first 6 months following RIT. From the Caen University Hospital databases, we included all consecutive adults newly diagnosed with ANCA-positive granulomatosis with polyangiitis or microscopic polyangiitis between January 2006 and December 2019. We compared rates of survival without severe infection and survival without infections of any severity within 6 months of RIT and used a multivariate Cox analysis to identify predictors of infection. We included 145 patients, 27 in the RTX and 118 in the CYC group. Patients in the RTX group more frequently had pneumococcal vaccination (p < 0.01) and creatinine < 150 µmol/L; other characteristics were comparable between the two groups. Overall, 37 severe infections and 65 infections of any severity were recorded. Rates of survival without severe infection were similar in both groups (p = 0.69), but survival without infections of any severity was lower in the RTX group (p = 0.005). In multivariate analysis, risk factors at diagnosis for severe infections included chronic urinary tract disease, dialysis, and absence of trimethoprim–sulfamethoxazole prophylaxis (p < 0.01 each). Within 6 months of RIT, rates of survival without severe infection were similar in newly diagnosed ANCA-positive AAV patients treated with RTX or CYC, but survival rates without infections of any severity appeared to be lower with RTX treatment.

Objective To assess patients’ self-reported glucocorticoid (GC)-related adverse events (AEs) in a GCA population. Methods A questionnaire was sent to the 100 patients most recently diagnosed with GCA in a tertiary centre. This questionnaire included open- and close-ended questions on the disease and GC effects. Eight primary AE areas were analysed: cardiovascular, metabolic, muscle, cognitive and psychologic, bone, cutaneous and hairiness, infective and visual complications. Including derivative subitems from preceding areas, a total of 18 GC-related AEs were analysed separately and according to GC duration. Results Ninety patients were analysed and 89 (99%) reported at least one GC-related AE [median 6 (range 1–11)]. Cognitive and psychological changes, primarily insomnia (72%), affected 90% of patients. Cutaneous changes and muscle loss affected 70% of patients, with frequent impairment of physical autonomy (P = 0.007) associated with this event. Metabolic issues, especially weight gain (40%) and diabetes mellitus (20%), affected 49% of patients. Conversely, vision troubles and bone fractures were mentioned by 42% and 9% of patients, respectively, and more frequently in patients who received GCs for >18 months (P = 0.01 and P = 0.007, respectively). Cardiovascular changes and infections affected 30% and 26% of patients, respectively. Conclusion This real-life study of GC tolerance assessed using a self-evaluation provides pragmatic and updated data reminding us that GC tolerance remains more noteworthy than ever. This study suggests carefully monitoring GC-related AEs during follow-up and encourages GC-sparing strategies in some patients.

This paper questions the apparent silenc of Cassirer’s Philosophy of Symbolic Forms on the unconscious, in its double sense of the psychic structure and of the description of the imperceptible. Alt...

We perform detailed muon spin rotation (μSR) measurements in the classic antiferromagnet Fe2O3 and explain the spectra by considering dynamic population and dissociation of charge-neutral muon-polaron complexes. We show that charge-neutral muon states in Fe2O3, despite lacking the signatures typical of charge-neutral muonium centers in nonmagnetic materials, have a significant impact on the measured μSR frequencies and relaxation rates. Our identification of such polaronic muon centers in Fe2O3 suggests that isolated hydrogen (H) impurities form analogous complexes, and that H interstitials may be a source of charge carrier density in Fe2O3. ISSN:0031-9007 ISSN:1079-7114

We perform detailed muon spin rotation ($\ensuremath{\mu}\mathrm{SR}$) measurements in the classic antiferromagnet ${\mathrm{Fe}}_{2}{\mathrm{O}}_{3}$ and explain the spectra by considering dynamic population and dissociation of charge-neutral muon-polaron complexes. We show that charge-neutral muon states in ${\mathrm{Fe}}_{2}{\mathrm{O}}_{3}$, despite lacking the signatures typical of charge-neutral muonium centers in nonmagnetic materials, have a significant impact on the measured $\ensuremath{\mu}\mathrm{SR}$ frequencies and relaxation rates. Our identification of such polaronic muon centers in ${\mathrm{Fe}}_{2}{\mathrm{O}}_{3}$ suggests that isolated hydrogen (H) impurities form analogous complexes, and that H interstitials may be a source of charge carrier density in ${\mathrm{Fe}}_{2}{\mathrm{O}}_{3}$.

High-throughput directed evolution, implemented in well-controlled in vitro conditions, provides a powerful route for enzyme engineering. Most existing technologies are based on activity screening and require the sequential observation and sorting of each individual variant. By contrast, approaches based on autonomous feedback loops, linking phenotype to genotype replication, enable autonomous selection without screening. However, these approaches are only possible in vivo, or applicable to very specific activities, such as polymerases or ligases. Here, we leverage synthetic molecular networks to create a programmable in vitro feedback loop linking a target enzymatic activity to gene amplification. After encapsulation and lysis of up to 107 transformed variants, the genes present in each droplet are amplified according to the activity of the encoded enzyme, resulting in the autonomous enrichment of interesting sequences. Applied to a nicking enzyme with thermal or kinetic selection pressures, this method reveals detailed mutational landscapes and provides improved variants.

Introduction Dix a 20 % des syndromes myelodysplasiques (SMD)/Leucemies myelomonocytaires chroniques (LMMC) pourraient etre associes a diverses pathologies extra-hematologiques telles que des dermatoses neutrophiles, des vascularites systemiques, des arthrites inflammatoires, des pseudo-maladies de Behcet ou des polychondrites [1] . La fievre, l’atteinte articulaire, le syndrome inflammatoire biologique marque, le rash evanescent sont des symptomes frequemment associes aux SMD et LMMC, mais ils peuvent egalement etre les signes cardinaux caracteristiques de la maladie de Still de l’adulte (MSA). Les MSA associees aux SMD/LMMC existent, principalement decrites dans les neoplasies solides mais aussi hematologiques [2] . L’identification recente du VEXAS syndrome (vacuoles, enzyme E1, lie a l’X, auto-inflammatoire, somatique) lie a une mutation somatique de UBA1 [3] nous amene a nous interroger sur l’existence de telles mutations chez les patients presentant des tableaux d’autoinflammation de type MSA ou pseudo Still associes a des SMD/LMMC. Dans cette etude nationale francaise, nous avons donc cherche a decrire les patients atteints de SMD/LMMC presentant une fievre recurrente inexpliquee avec des signes extra-hematologiques suggerant une MSA ainsi que leur pronostic/reponse therapeutique et recherche la presence d’une mutation UBA1 chez ces patients. Patients et methodes Les caracteristiques demographiques, cliniques et biologiques des 26 patients identifies avec cette association etaient collectees et analysees dans une etude retrospective multicentrique francaise. Le groupe temoin de SMD/LMMC etait compose de 104 patients du registre du Groupe francophone des myelodysplasies avec SMD/LMMC. La presence d’une mutation UBA1 etait realisee chez 15 patients. Resultats Les SMD avec exces de blastes (30,8 %) etaient les plus representes, le R-IPSS median etait de 3,7 [2–5]. Des traitements hematologiques specifiques etaient mis en place dans 17 cas (65 %), 0,5 an [0,1–1,2] apres le diagnostic de SMD, principalement par azacitidine (n = 15 ; 58 %). Les SMD/CMML de nos patients etaient plus precoces (71,4 [36–85] contre 78 ans (42-92) ; p = 0,0005) que ceux sans caracteristiques dysimmunitaires sans difference significative pour la survie globale et le delai d’evolution vers la leucemie myeloide aigue. Les patients identifies suspects de MSA presentaient tous une fievre recurrente inexpliquee et un syndrome inflammatoire biologique marque. Ils ont ete classes soit en MSA confirmee (n = 5) d’apres les criteres de Yamaguchi ou de Fautrel, soit en pseudoStill (n = 21) avec (n = 8) ou sans (n = 13) caracteristiques inhabituelles de MSA. Chez les pseudoStill, l’hyperleucocytose a polynucleaire neutrophile manquait pour 85 % des patients. Les diagnostics etaient concomitants chez 8 patients (32 %), celui de MSA precedait le SMD/CMML chez 12 patients (48 %) et survenait apres le diagnostic du SMD/CMML chez 5 patients (24 %) dans un delai median de 1,0 an [0,2–2]. L’âge median au diagnostic etait de 70,5 ans [64,3–78,9] et 76 % etaient des hommes. Des complications graves de MSA etaient constatees au moment du diagnostic ou au cours du suivi chez 9 patients (3 %) : des syndromes d’activation macrophagique (n = 5) ; des myopericardites (n = 3), des maladies pulmonaires interstitielles (n = 3) et un syndrome de detresse respiratoire aigue (n = 1). Parmi les 21 (91 %) patients ayant recu un traitement specifique pour la MSA, 16 (76 %) recevaient en 1ere ligne des corticostertiquedoides seuls ou en association avec de l’anakinra ou de l’infliximab. Les corticosteroides a forte dose conduisait a une reponse dans 12/15 des cas et les biotherapies dans 8/13 cas. Douze patients (57 %) necessitait un traitement de deuxieme ligne. L’azacitidine conduisait a une reponse de la MSA dans 11 (69 %) cas. Enfin, la mutation d’UBA1 etait recherchee chez 15 patients et revelait 5 (33 %) cas positifs. Conclusion Un tableau evocateur de MSA apres 65 ans chez un homme doit faire rechercher un SMD/LMMC en particulier devant l’absence d’hyperleucocytose ou d’atypies mais aussi l’existence de mutations somatiques dont celle d’UBA1. En cas de MSA refractaire associee a un SMD/LMMC, l’indication a un traitement hematologique specifique peut etre discute.