Identifiabilité structurelle et identification de systèmes couplés par les sorties

International audienceCet article s'intéressè a l'identification des syst emes de grande taille qui peuvent etre décomposés en une collection de sous-syst emes couplés par les sorties. Il est d'abord montré que si le syst eme global est structurellement identifiable, alors tous les sous-syst emes le sont egalement, en considérant les sorties comme de nouvelles entrées. Cette propriété est ensuite utilisée pour proposer une procédure d'identification décentralisée. L'efficacité de l'approche pro-posée est illustrée sur un exemple académique. Mots-clés— Identifiabilité structurelle, Identification décen-tralisée, Syst emes de grande taille. I. Introduction Les syst emes technologiques de grande taille tels que les syst emes de transport, les syst emes electriques, les syst emes de bâtiments. . .sont omniprésents dans notre vie moderne. La grande taille de ces syst emes a conduit au développement de diverses techniques pour réduire la complexité de leur etude. Une approche possible est de considérer le grand syst eme comme une collection de nom-breux sous-syst emes plus simples. L'identification [1] est un point crucial pour l'´ elaboration d'une stratégie de contrôle basée sur un mod ele. D'un point de vue pratique, leprobì eme de la taille des syst emes se posé egalement pour l'identification paramétrique. Pour simplifier l'identification des syst emes de grande taille, de nombreux auteurs ont essayé d'exploiter leur structure. Dans [5], le syst eme global est hiérarchisé et une méthode itérative est proposée pour l'identification. Dans [7], les auteurs s' intéressent aux syst emes circulants [3], et ils exploitent leurs propriétés pour définir une procédure originale d'identification. Une autre technique exploite la propriété de découplage en boucle fermée afin de définir une collection d'observateurs décentralisés pour les syst emes non linéaires interconnectés [12]. Dans cet article, nous supposons que le syst eme global est structurellement identifiable. L'identifiabilité structu-relle est une propriété importante quand il faut evaluer les param etres du syst eme, car elle garantit l'unicité des param etres [15]. Dans [13], l'auteur se concentre sur les syst emes compartimentaux pour etudier l'identifiabi-lité structurelle du syst eme global, et dans [4], l'identi-fiabilité pratique peut etre vérifiée pour des conditions suffisantes sur les signaux d'interaction entre les sous-syst emes. Dans ce document, on consid ere un ensemble de syst emes linéaires couplés par leurs sorties. Un exemple est représenté sur la figure 1. De nombreux processus peuvent etre modélisés sous cette forme, c'est le cas par exemple des syst emes thermiques dans les bâtiments [8]

Patient and Public Involvement in Research:Lessons for Inflammatory Bowel Disease

Participatory research, also referred to as patient and public involvement, is an approach that involves collaborating with patients affected by the focus of the research, on the design, development and delivery of research to improve outcomes. There are two broad justifications for this: first, that it enhances the quality and relevance of research, and second, that it satisfies the ethical argument for patient inclusion in decisions about them. This synergistic and collaborative effort, which bridges the divide between researchers and participants with the lived condition, is now a mainstream activity and widely accepted as best practice. Although there has been a substantial increase in the literature over the past two decades, little has been published on how participatory research has been used in inflammatory bowel disease [IBD] research and little guidance as to how researchers should go about this. With an increasing incidence and prevalence worldwide, combined with declining study enrolment in an era of perennial unmet need, there are a multitude of benefits of participatory research to IBD patients and investigators, including research output that is informed and relevant to the real world. A key example of participatory research in IBD is the I-CARE study, a large-scale, pan-European observational study assessing the safety of advanced therapies, which had significant patient involvement throughout the study. In this review, we provide a comprehensive overview of the benefits and challenges of participatory research and discuss opportunities of building strategic alliances between IBD patients, healthcare providers and academics to strengthen research outcomes.</p

A randomised cross-over trial in healthy adults indicating improved absorption of omega-3 fatty acids by pre-emulsification

BACKGROUND: The health benefits of increased intakes of omega-3 fatty acids are well established but palatability often presents a problem. The process of emulsification is used in the food industry to provide a wider spectrum of use, often with the result of increased consumption. Moreover, as emulsification is an important step in the digestion and absorption of fats, the pre-emulsification process may enhance digestion and absorption. In this study the levels of plasma fatty acid and triacylglycerol (TAG) following the ingestion of either an oil mixture or an emulsified oil mixture have been compared. METHODS: In this randomised cross-over study, 13 volunteers received the oil mixture and 11 received the oil emulsion as part of an otherwise fat free meal. Blood samples were collected at 0, 1.5, 3, 4.5, 6, 7.5 and 9 hours after ingestion of oil, separated and stored at -20°C. Plasma triacylglycerols were assessed spectrophotometrically and fatty acids were determined by gas chromatography. Following a washout period of twenty days the procedure was repeated with the assignments reversed. RESULTS: The postprandial plasma TAG and the C18:3 (n-6), C18:3(n-3), C20:5(n-3) and C22:6 (n-3) polyunsaturated fatty acid (PUFA) levels for the emulsified oil group were increased significantly (P = 0.0182; P = 0.0493; P = 0.0137; P < 0.0001; P = 0.0355 respectively) compared with the non-emulsified oil group. The C16:0 and C18:0 saturated fatty acids, the C18:1 (n-9) monounsaturated fatty acid and the C18:2 PUFA were not significantly different for the oil and emulsified oil groups. CONCLUSION: Pre-emulsification of an oil mixture prior to ingestion increases the absorption of longer chain more highly unsaturated fatty acids (especially eicosapentaenoic acid and docosahexaenoic acid) but does not affect absorption of shorter chain less saturated fatty acids, suggesting that pre-emulsification of fish oils may be a useful means of boosting absorption of these beneficial fatty acids. Trial registration: Current Controlled Trials ISRCTN4320260

Effects of discontinuing or continuing ongoing statin therapy in severe sepsis and septic shock: a retrospective cohort study

International audienceABSTRACT: INTRODUCTION: Recent publications suggest potential benefits from statins as a preventive or adjuvant therapy in sepsis. Whether ongoing statin therapy should be continued or discontinued in patients admitted in the intensive care unit (ICU) for sepsis is open to question. METHODS: We retrospectively compared patients with severe sepsis and septic shock in whom statin therapy had been discontinued or continued. The primary endpoint was the number of organ failure-free days at day 14. Secondary end-points included hospital mortality and safety. The association of statin continuation with outcome was evaluated for crude analysis and after propensity score matching and adjustment. We also measured plasma atorvastatin concentrations in a separate set of ICU septic patients continuing the drug. RESULTS: Patients in whom statin therapy had been continued in the ICU (n = 44) had significantly more organ failure-free days (11 67891011121314 vs. 6 [0-12], mean difference of 2.34, 95%CI from 0.47 to 5.21, P = 0.03) as compared to others (n = 32). However, there were important imbalances between groups, with more hospital-acquired infections, more need for surgery before ICU admission, and a trend towards more septic shock at ICU admission in the discontinuation group. The significant association of statin continuation with organ failure free days found in the crude analysis did not persist after propensity-matching or multivariable adjustment: beta coefficients [95% CI] of 2.37 [-0.96 to 5.70] (P = 0.20) and 2.24 [-0.43 to 4.91] (P = 0.11) respectively. We found particularly high pre-dose and post-dose atorvastatin concentrations in ICU septic patients continuing the drug. CONCLUSIONS: Continuing statin therapy in ICU septic patients was not associated with reduction in the severity of organ failure after matching and adjustment. In addition, the very high plasma concentrations achieved during continuation of statin treatment advocates some caution

Airway Epithelial Cell Migration Dynamics: Mmp-9 Role in Cell–Extracellular Matrix Remodeling

Cell spreading and migration associated with the expression of the 92-kD gelatinase (matrix metalloproteinase 9 or MMP-9) are important mechanisms involved in the repair of the respiratory epithelium. We investigated the location of MMP-9 and its potential role in migrating human bronchial epithelial cells (HBEC). In vivo and in vitro, MMP-9 accumulated in migrating HBEC located at the leading edge of a wound and MMP-9 expression paralleled cell migration speed. MMP-9 accumulated through an actin-dependent pathway in the advancing lamellipodia of migrating cells and was subsequently found active in the extracellular matrix (ECM). Lamellipodia became anchored through primordial contacts established with type IV collagen. MMP-9 became amassed behind collagen IV where there were fewer cell–ECM contacts. Both collagen IV and MMP-9 were involved in cell migration because when cell–collagen IV interaction was blocked, cells spread slightly but did not migrate; and when MMP-9 activation was prevented, cells remained fixed on primordial contacts and did not advance at all. These observations suggest that MMP-9 controls the migration of repairing HBEC by remodeling the provisional ECM implicated in primordial contacts

Flare-IBD: development and validation of a questionnaire based on patients’ messages on an internet forum for early detection of flare in inflammatory bowel disease: study protocol

International audienceIntroduction: Crohn’s disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD), are chronic disabling conditions characterised by flares followed by periods of remission. However, patients with IBD are seen every 3–6 months in the outpatient clinic, and the occurrence of a flare between two outpatient visits is not captured. To our knowledge, there is no validated patient-reported outcome (PRO) tool to measure the phenomenon of flare in IBD. This study aimed to use an innovative methodology to collect messages posted by patients in an internet forum for developing and validating a PRO measuring flare in IBD.Methods and analysis: The design involves (1) computer engineering sciences for scraping extraction of messages posted in an internet forum and for identification of messages related to flare; (2) qualitative methods for thematic content analyse of the messages posted, for candidate items generation, for items selection (Delphi process) and for items adjustment (‘think-aloud’ interviews) and (3) quantitative methods for psychometricvalidation of the PRO.Ethics and dissemination: Ethical approval was obtained from the Comité de Protection des Personnes (CPP) CPP Nord-Ouest I (19.07.15.44139) in November 2019. The project aims to provide a tool to evaluate IBD flare in current medical practice that is constructed with patients’ perspectives. Items generation from a source corresponding to exchanges in an internet forum is an innovative method in this field and provides awider coverage of qualitative data. If such a forum can result in interesting material, then this could be a new methodological perspective for generating items for questionnaires. Findings will be reported and disseminated widely through international peer-reviewed journal publications, oral and poster presentations at scientific conference

MRI Findings in 77 Children with Non-Syndromic Autistic Disorder

International audienceBACKGROUND: The clinical relevance of MR scanning in children with autism is still an open question and must be considered in light of the evolution of this technology. MRI was judged to be of insufficient value to be included in the standard clinical evaluation of autism according to the guidelines of the American Academy of Neurology and Child Neurology Society in 2000. However, this statement was based on results obtained from small samples of patients and, more importantly, included mostly insufficient MRI sequences. Our main objective was to evaluate the prevalence of brain abnormalities in a large group of children with a non-syndromic autistic disorder (AD) using T1, T2 and FLAIR MRI sequences. METHODOLOGY: MRI inspection of 77 children and adolescents with non-syndromic AD (mean age 7.4+/-3.6) was performed. All met the DSM-IV and ADI -R criteria for autism. Based on recommended clinical and biological screenings, we excluded patients with infectious, metabolic or genetic diseases, seizures or any other neurological symptoms. Identical MRI inspections of 77 children (mean age 7.0+/-4.2) without AD, developmental or neurological disorders were also performed. All MRIs were acquired with a 1.5-T Signa GE (3-D T1-FSPGR, T2, FLAIR coronal and axial sequences). Two neuroradiologists independently inspected cortical and sub-cortical regions. MRIs were reported to be normal, abnormal or uninterpretable. PRINCIPAL FINDINGS: MRIs were judged as uninterpretable in 10% (8/77) of the cases. In 48% of the children (33/69 patients), abnormalities were reported. Three predominant abnormalities were observed, including white matter signal abnormalities (19/69), major dilated Virchow-Robin spaces (12/69) and temporal lobe abnormalities (20/69). In all, 52% of the MRIs were interpreted as normal (36/69 patients). CONCLUSIONS: An unexpectedly high rate of MRI abnormalities was found in the first large series of clinical MRI investigations in non-syndromic autism. These results could contribute to further etiopathogenetic research into autism

Exon skipping as a therapeutic strategy applied to an RYR1 mutation with pseudo-exon inclusion causing a severe core myopathy.

International audienceCentral core disease is a myopathy often arising from mutations in the type 1 ryanodine receptor (RYR1) gene, encoding the sarcoplasmic reticulum calcium release channel RyR1. No treatment is currently available for this disease. We studied the pathological situation of a severely affected child with two recessive mutations, which resulted in a massive reduction in the amount of RyR1. The paternal mutation induced the inclusion of a new in-frame pseudo-exon in RyR1 mRNA that resulted in the insertion of additional amino acids leading to the instability of the protein. We hypothesized that skipping this additional exon would be sufficient to restore RyR1 expression and to normalize calcium releases. We therefore developed U7-AON lentiviral vectors to force exon skipping on affected primary muscle cells. The efficiency of the exon skipping was evaluated at the mRNA level, at the protein level, and at the functional level using calcium imaging. In these affected cells, we observed a decreased inclusion of the pseudo-exon, an increased RyR1 protein expression, and a restoration of calcium releases of normal amplitude either upon direct RyR1 stimulation or in response to membrane depolarization. This study is the first demonstration of the potential of exon-skipping strategy for the therapy of central core disease, from the molecular to the functional level

MESures et SImulation pour une GEstion Optimisée des systèmes de transports

The stakes that were targeted by this collaboration are linked to the rarefaction of resources used to build new transportation infrastructures and to the higher attention paid to the environmental impacts of mobilities. Indeed, transportation network managers have a real need for tools and methods to master the increase of movement demand while reducing the impacts of these moves. On these topics, the research done in the Ifsttar allied to the expertise of the Cerema gave birth to a form of integrative research that contributed to broaden the horizons of both partners. The main results of this collaboration are presented in this final report. They comprise: •Better understanding of flows propagation inside the transportation system;•Quantification tools for assessing the impacts of this flow in terms of travel time and accessibility as well as pollutants levels;•Offer of new simulation and modelling tools, that can be used in more situations; (because their calculation time is smaller and they include the effects of regulations);•Strengthening of the methodologies to assess the regulation of suburban motorways. In addition to the presentation of those results, the report includes a list of the productions of the collaboration, the most significant productions, the presentations made during the final seminar and directions for future research.Les enjeux que cette collaboration a permis de traiter sont liés à la raréfaction des ressources permettant de construire des nouvelles infrastructures de transports et à la montée de la prise en compte des impacts environnementaux des mobilités. Ceci génère un réel besoin, de la part des gestionnaires de réseaux de transports, d’outils et de méthodes leur permettant de maîtriser la croissance de la demande de déplacements tout en diminuant les impacts de ces déplacements. Sur ces sujets, l’articulation des recherches conduites à l’IFSTTAR et de l’expertise que possède le CEREMA a donné lieu à une recherche intégrative qui a contribué à élargir les horizons de chacun des deux partenaires. Les principaux résultats de Messigéo, présentés dans ce rapport final, concernent : •Amélioration de la compréhension de la propagation des flux dans le système de transport ;•Quantification des impacts du fonctionnement du système de transports en termes de temps de parcours et d’accessibilité, tout comme sur les niveaux de polluants ;•Proposition de nouveaux outils de modélisation et de simulation, utilisables dans plus de cas (car ils sont de temps de calcul faible et qu’ils intègrent les effets des régulations) ;•Consolidation des méthodologies d’évaluation des régulations des autoroutes périurbaines.Outre une synthèse de ces résultats, ce rapport contient également la liste des publications, les productions les plus significatives, les présentations faites au cours du séminaire de restitution, et des pistes de recherche future