Autorégulation épistémique des systèmes sociaux de production de connaissance: le cas de la Banque du Canada

La littérature actuelle en philosophie de l’expertise accorde une plus grande attention aux aspects individuels du phénomène qu’à ses aspects sociaux. Le résultat est de rendre insatisfaisantes les méthodes dont dispose une personne profane afin évaluer le niveau de confiance à accorder à des regroupements d’experts (organisations expertes, centres de recherche nationaux, agences de financement, etc.). Le mémoire propose une ébauche de cadre conceptuel permettant d'évaluer rationnellement la confiance que l'on devrait accorder à de telles entités, appelées « systèmes socioépistémiques ». Il est suggéré d’utiliser la capacité d’un système social à contrôler et à corriger les croyances fausses tenues par ses membres, ou « autorégulation épistémique ». Au plan normatif, cette capacité générale se traduit par certaines caractéristiques bénéfiques qui devraient être retrouvées au sein d’un système socioépistémique. Ces caractéristiques sont intégrées au cadre conceptuel à partir de travaux en philosophie, en sociologie et en histoire des sciences. Afin de tester le cadre conceptuel « sur le terrain » et valider son utilité en pratique, il a été choisi de focaliser sur le cas de la Banque du Canada, l'organisation experte qui régule la politique monétaire au pays. Au plan empirique, une grille d’analyse a donc été développée pour opérationnaliser le cadre conceptuel, c’est-à-dire cumuler des observations concernant les pratiques épistémiques au sein de la Banque du Canada. Pour combler le besoin informationnel relatif à cette grille d’analyse, un corpus de documents officiels issus de la Banque du Canada a été moissonné du web, et des techniques de forage de textes ont été appliquées afin d’en extraire les documents pertinents. Bien qu’il faille, pour appuyer les conclusions tirées dans le mémoire, effectuer davantage de recherche avec des méthodes complémentaires, on peut avancer que des tensions semblent exister quant à la préservation de l’équilibre des intérêts cognitifs au sein du système. Celles-ci sont accentuées par des tendances de pilotage de la recherche visant la réalisation d’un agenda « officiel » de recherche pour l’organisation. Au final, bonifier progressivement le cadre conceptuel de l’autorégulation épistémique pourrait permettre d’en faire un guide pratique à l’évaluation, par procuration, du niveau de confiance à accorder à un regroupement expert

A role for IL-33-activated ILC2s in eosinophilic vasculitis

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare but serious disease with poorly understood mechanisms. Here, we report that patients with EGPA have elevated levels of TSLP, IL-25, and soluble ST2, which are well-characterized cytokine alarmins that activate or modulate type 2 innate lymphoid cells (ILC2s). Patients with active EGPA have a concurrent reduction in circulating ILC2s, suggesting a role for ILC2s in the pathogenesis of this disease. To explore the mechanism of these findings in patients, we established a model of EGPA in which active vasculitis and pulmonary hemorrhage were induced by IL-33 administration in predisposed, hypereosinophilic mice. In this model, induction of pulmonary hemorrhage and vasculitis was dependent on ILC2s and signaling through IL4Rα. In the absence of IL4Rα or STAT6, IL-33-treated mice had less vascular leak and pulmonary edema, less endothelial activation, and reduced eotaxin production, cumulatively leading to a reduction of pathologic eosinophil migration into the lung parenchyma. These results offer a mouse model for use in future mechanistic studies of EGPA, and they suggest that IL-33, ILC2s, and IL4Rα signaling may be potential targets for further study and therapeutic targeting in patients with EGPA

Immune checkpoint inhibitor-related acquired amegakaryocytosis thrombocytopenia: a case report and literature review

IntroductionImmune checkpoint inhibitors (ICIs) are used in several advanced malignancies and may cause various immune-related adverse events (irAEs). Among them, hematological irAEs are less described. Acquired amegakaryocytic thrombocytopenia (AAT) is a rare immune hematologic disorder characterized by severe thrombocytopenia and complete absence of megakaryocytes in bone marrow.Case presentationHerein, we present the case of a patient in their 40s with metastatic melanoma who developed an AAT after 12 cycles of nivolumab (anti-PD1). His platelet count decreased by ≤5 × 109/l without other cytopenia. Bone marrow biopsy showed normal cellularity with a complete absence of megakaryocyte and T-CD8+ lymphocyte infiltration. Given the failure of systemic steroids, eltrombopag was started, an oral thrombopoietin receptor agonist (TPO-RA), and his platelet count subsequently increased with complete response.DiscussionFour other cases are described on literature with the same features than non-ICI-related AAT. All cases occurred after anti-PD/PD-L1 treatment with a median onset of 5 weeks. The presentation of our case is quite different with delayed cytopenia. Both ciclosporin and TPO-RA seem to be efficient therapies.ConclusionTPO-RA could be preferred in oncologic patients, but safety data are still missing to define clear guidelines for immune-related AAT management

Severe toxic rhabdomyolysis under combined palbociclib and simvastatin treatment: A case report

We report the fourth described case of severe toxic rhabdomyolysis occurring in an 81-year-old woman caused by the concomitant administration of palbociclib taken at the usual dosage (125 mg per day) and simvastatin. To the best of our knowledge, this is the first reported case successfully treated by plasma exchanges, with complete functional recovery within two months. The severity of this case justifies further consideration of pharmacokinetic interactions between palbociclib or other CDK-4-6 inhibitors and statins, which potentially increase the risk of an adverse event

Autorégulation épistémique des systèmes sociaux de production de connaissance: le cas de la Banque du Canada

La littérature actuelle en philosophie de l’expertise accorde une plus grande attention aux aspects individuels du phénomène qu’à ses aspects sociaux. Le résultat est de rendre insatisfaisantes les méthodes dont dispose une personne profane afin évaluer le niveau de confiance à accorder à des regroupements d’experts (organisations expertes, centres de recherche nationaux, agences de financement, etc.). Le mémoire propose une ébauche de cadre conceptuel permettant d'évaluer rationnellement la confiance que l'on devrait accorder à de telles entités, appelées « systèmes socioépistémiques ». Il est suggéré d’utiliser la capacité d’un système social à contrôler et à corriger les croyances fausses tenues par ses membres, ou « autorégulation épistémique ». Au plan normatif, cette capacité générale se traduit par certaines caractéristiques bénéfiques qui devraient être retrouvées au sein d’un système socioépistémique. Ces caractéristiques sont intégrées au cadre conceptuel à partir de travaux en philosophie, en sociologie et en histoire des sciences. Afin de tester le cadre conceptuel « sur le terrain » et valider son utilité en pratique, il a été choisi de focaliser sur le cas de la Banque du Canada, l'organisation experte qui régule la politique monétaire au pays. Au plan empirique, une grille d’analyse a donc été développée pour opérationnaliser le cadre conceptuel, c’est-à-dire cumuler des observations concernant les pratiques épistémiques au sein de la Banque du Canada. Pour combler le besoin informationnel relatif à cette grille d’analyse, un corpus de documents officiels issus de la Banque du Canada a été moissonné du web, et des techniques de forage de textes ont été appliquées afin d’en extraire les documents pertinents. Bien qu’il faille, pour appuyer les conclusions tirées dans le mémoire, effectuer davantage de recherche avec des méthodes complémentaires, on peut avancer que des tensions semblent exister quant à la préservation de l’équilibre des intérêts cognitifs au sein du système. Celles-ci sont accentuées par des tendances de pilotage de la recherche visant la réalisation d’un agenda « officiel » de recherche pour l’organisation. Au final, bonifier progressivement le cadre conceptuel de l’autorégulation épistémique pourrait permettre d’en faire un guide pratique à l’évaluation, par procuration, du niveau de confiance à accorder à un regroupement expert

Relapsing polychondritis can be characterized by three different clinical phenotypes: analysis of a recent series of 142 patients

Relapsing polychondritis (RP) is a rare condition characterized by recurrent inflammation of cartilaginous tissue and systemic manifestations. Data on this disease remain scarce. This study was undertaken to describe patient characteristics and disease evolution, identify prognostic factors, and define different clinical phenotypes of RP.METHODS:We performed a retrospective study of 142 patients with RP who were seen between 2000 and 2012 in a single center.RESULTS:Of the 142 patients, 86 (61%) were women. The mean ± SD age at first symptoms was 43.5 ± 15 years. Patients had the following chondritis types: auricular (89%; n = 127), nasal (63%; n = 89), laryngeal (43%; n = 61), tracheobronchial (22%; n = 32), and/orcostochondritis (40%; n = 57). The main other manifestations were articular (69%; n = 98), ophthalmologic (56%; n = 80), audiovestibular (34%; n = 48), cardiac (27%; n = 38), and cutaneous (28%; n = 40). At a mean ± SD followup of 13 ± 9 years, the 5- and 10-year survival rates were 95 ± 2% and 91 ± 3%, respectively. Factors associated with death on multivariable analysis were male sex (P = 0.01), cardiac abnormalities (P = 0.03), and concomitant myelodysplastic syndrome (MDS) (P = 0.004) or another hematologic malignancy (P = 0.01). Cluster analysis revealed that separating patients into 3 groups was clinically relevant, thereby separating patients with associated MDS, those with tracheobronchial involvement, and those without the 2 features in terms of clinical characteristics, therapeutic management, and prognosis.CONCLUSION:This large series of patients with definite RP revealed an improvement in survival as compared with previous studies. Factors associated with death were male sex, cardiac involvement, and concomitant hematologic malignancy. We identified 3 distinct phenotypes

Multiplane Image Restoration Using Multivariate Curve Resolution: An Alternative Approach to Deconvolution in Conventional Brightfield Microscopy

Three-dimensional reconstruction in brightfield microscopy is challenging since a 2D image includes from in-focus and out-of-focus light which removes the details of the specimen’s structures. To overcome this problem, many techniques exist, but these generally require an appropriate model of Point Spread Function (PSF). Here, we propose a new images restoration method based on the application of Multivariate Curve Resolution (MCR) algorithms to a stack of brightfield microscopy images to achieve 3D reconstruction without the need for PSF. The method is based on a statistical reconstruction approach using a self-modelling mixture analysis. The MCR-ALS (ALS for Alternating Least Square) algorithm under non-negativity constraints, Wiener, Richardson–Lucy, and blind deconvolution algorithms were applied to silica microbeads and red blood cells images. The MCR analysis produces restored images that show informative structures which are not noticeable in the initial images, and this demonstrates its capability for the multiplane reconstruction of the amplitude of 3D objects. In comparison with 3D deconvolution methods based on a set of No Reference Images Quality Metrics (NR-IQMs) that are Standard Deviation, ENTROPY Average Gradient, and Auto Correlation, our method presents better values of these metrics, showing that it can be used as an alternative to 3D deconvolution methods

Degradation Phenomena on “Homemade” Explanted Aortic Textile Endografts

International audienceObjectiveIn the 1990s, the concept of “homemade” endografts (EGs) using commercially available materials was proposed in clinical practice for endovascular abdominal aortic repair (EVAR). The aim of this study was to analyse the ageing phenomena of these EGs in light of explant analyses.MethodsThe study focused on five explanted homemade EGs collected from 2012 to 2014. The explants were assessed in accordance with the ISO 9001/13485 certified standard protocol, which included naked eye evaluation, organic remnant cleaning, and microscopic and endoscopic examinations and analysis (magnification range from 20% to 200%). The observations report followed a classification based on 12 features assessing the fabric cover, the stitch filament, and the stents.ResultsThe reasons for explantation were type 1 endoleak in three cases and aneurysm sac growth in two. The implantation duration ranged from 56 to 202 months. Sixty three per cent of the fabric surface lesions (holes and tears) were related to abrasion between the fabric and the stents. Up to 33% of the knots used to connect adjacent stents were broken on one EG. Other defects including running suture rupture and stent corrosion were also observed. The overall hole cumulated surface ranged from 0.377 mm2 (56 month of implantation) up to 3.21 mm2 (78 month of implantation).ConclusionIn this study, various ageing phenomena on homemade textile EGs were identified and classified. The main damaging mechanisms were related to abrasion stress leading to tears and holes in the fabric, stitch ruptures, and detachment of stent segments responsible for serious EG deformations and further degradation

Autoantibodies versus Skin Fibrosis Extent in Systemic Sclerosis: A Case-Control Study of Inverted Phenotypes

Objective: to describe the prevalences, characteristics, and survivals of patients with anti-topoisomerase 1 antibodies (ATA) and limited cutaneous systemic sclerosis (lSSc) and anti-centromere antibodies (ACA) and diffuse cutaneous systemic sclerosis (dSSc). Methods: patients with ATA lSSc or with ACA dSSc were included in a case-control retrospective study. Results: In our cohort of scleroderma, the prevalence of ACA dSSc and ATA lSSc was 1.1% (12/1040) and 8.9% (93/1040), respectively. ACA dSSc patients had less interstitial lung disease (ILD) (5 (41.7) vs. 74 (79.6); p p = 0.03 and 4 (33.3) vs. 4 (7.5); p = 0.02,) than ATA dSSc patients. ATA lSSc patients had a higher modified Rodnan skin score than ACA lSSc patients (4 [2–7.5] vs. 2 [0–5]; p p p p < 0.0001). Conclusion: ATA lSSc and ACA dSSc have specific characteristics when compared to ATA dSSc or ACA lSSc. ATA lSSc patients have more ILD than ACA lSSc patients, and ATA dSSc patients have the worst prognosis. Overall, inverted phenotypes show the value of a patient assessment combining antibody and skin subset and should be considered as a separate group

Escherichia coli Genomic Diversity within Extraintestinal Acute Infections Argues for Adaptive Evolution at Play

International audienceAdaptive processes in chronic bacterial infections are well described, but much less is known about the processes at play during acute infections. Here, by sequencing seven randomly selected isolates per patient, we analyzed Escherichia coli populations from three acute extraintestinal infections in adults (meningitis, pyelonephritis, and peritonitis), in which a high-mutation-rate isolate or mutator isolate was found. The isolates of single patients displayed between a few dozen and more than 200 independent mutations, with up to half being specific to the mutator isolate. Multiple signs of positive selection were evidenced: a high ratio of nonsynonymous to synonymous mutations (Ka /Ks ratio) and strong mutational convergence within and between patients, some of them at loci well known for their adaptive potential, such as rpoS, rbsR, fimH, and fliC For all patients, the mutator isolate was likely due to a large deletion of a methyl-directed mismatch repair gene, and in two instances, the deletion extended to genes involved in some genetic convergence, suggesting potential coselection. Intrinsic extraintestinal virulence assessed in a mouse model of sepsis showed variable patterns of virulence ranging from non-mouse killer to mouse killer for the isolates from single patients. However, genomic signature and gene inactivation experiments did not establish a link between a single gene and the capacity to kill mice, highlighting the complex and multifactorial nature of the virulence. Altogether, these data indicate that E. coli isolates are adapting under strong selective pressure when colonizing an extraintestinal site.IMPORTANCE Little is known about the dynamics of adaptation in acute bacterial infections. By sequencing multiple isolates from monoclonal extraintestinal Escherichia coli infections in several patients, we were able to uncover traces of selection taking place at short time scales compared to chronic infection. High genomic diversity was observed in the patient isolates, with an excess of nonsynonymous mutations, and the comparison within and between different infections showed patterns of convergence at the gene level, both constituting strong signs of adaptation. The genes targeted were coding mostly for proteins involved in global regulation, metabolism, and adhesion/motility. Moreover, virulence assessed in a mouse model of sepsis was variable among the isolates of single patients, but this difference was left unexplained at the molecular level. This work gives us clues about the E. coli lifestyle transition between commensalism and pathogenicity