Conception d'une micro-pompe sanguine

RÉSUMÉ L’objectif principal de ce mémoire est la conception d’une pompe sanguine d’assistance ventriculaire ayant un débit de 5L/min et un différentiel de pression de 100 mmHg, avec comme objectif secondaire l’évaluation de la possibilité de remplacer cette pompe par deux pompes identiques en parallèle ayant chacune un débit de 2.5L/min. Un second objectif secondaire était l’exploration de différents logiciels de conception et d’analyse de turbomachines. La conception de la pompe s’est faite à l’aide de CAESES, qui en plus d’être un logiciel de CAO donnant une grande liberté à l’utilisateur, permet également l’optimisation d’un design à l’aide de plusieurs algorithmes, dont un algorithme génétique. Quant aux logiciels Axial et Axcent, bien que testés, ils n’ont pas été utilisés dans la conception et l’analyse de la pompe. L’analyse de la pompe s’est faite principalement en CFD 3D à l’aide de CFX. Cependant d’autres logiciels de la suite Ansys ont été utilisés et testés, entre autres Turbogrid pour le maillage et Vista TF qui est un calculateur throughflow. À l’aide de ces outils, l’effet de plusieurs paramètres a été analysé, en particulier leur effet sur l’efficacité et le coefficient de charge de la pompe. Parmi les paramètres évalués, la variation du rayon au moyeu est le paramètre qui a le plus d’influence sur l’efficacité de la pompe. L’hémolyse et la puissance du design final ont également été évaluées à différents débits et différents différentiels de pression. Comme la pompe a été conçue dans le but d’être la plus efficace à un débit de 5L/min, il est normal que la puissance nécessaire par L/min soit la plus basse pour ce débit. Cependant, la véritable surprise est liée à l’hémolyse puisque contrairement à ce qui était anticipé, ce n’est pas avec le débit le plus bas que l’hémolyse est la plus basse, mais plutôt avec le débit de 5L/min. Finalement, il s’est avéré que ce n’est pas avantageux de placer deux pompes en parallèles avec un débit réduit puisque le rendement est moins bon et que l’index d’hémolyse est plus élevé.----------ABSTRACT The principal objective of this master’s thesis is the design and study of an axial blood pump with a volume flow of 5L/min and a pressure differential of 100 mmHg, with a secondary objective of evaluating the possibility of replacing this pump by two identical pumps in parallel with a volume flow of 2.5L/min. Another secondary objective is the exploration and testing of different design and turbomachinery analysis software. The design of the pump was made with CAESES, which is a CAD software that gives great liberty to the user, but also permit the use of different algorithm for the optimisation of a design. For the Axial and Axcent software, they were tested, but they were not used in the design or analysis of the pump. The pump analysis was made using 3D CFD with the CFX software. However, other softwares of the Ansys suite were used and tested: Turbogrid for the mesh creation and Vista TF which is a throughflow calculator. With those tools, it was possible to study the effect of different parameters of the pump. Amongst those parameters, it is the hub radius that has the biggest impact on the pump efficiency. The hemolysis and the power of the pump were also evaluated at different volume flow and delta pressure. Since the pump was designed for a flow of 5L/min, it is normal that the power per L/min is lower for this volume flow. However, the big surprise is that the lowest hemolysis was not found with the lowest volume flow, but the flow of 5L/min. So it is not an advantage to replace the pump at 5L/min by two identical pump in parallel

New Teachers’ Career Intentions: Factors Influencing New Teachers’ Decisions to Stay or to Leave the Profession

This study examines the relationship between the reported career intentions and perceptions of preparedness of graduating secondary teachers in Quebec, across a two- year period, in an effort to identify factors which contribute to growing attrition rates among beginning teachers. The study reveals that those beginning teachers most concerned with their lack of preparation in the areas of classroom management and assessment of students’ learning are more likely to consider leaving the profession. While evidence suggests that beginning teachers do develop increasing confidence in terms of classroom management in their second year of teaching, their challenges with effectively assessing student learning endure through the first two years of teaching. Findings from this mixed method study suggest that both initial teacher education and employers have a shared responsibility to give greater attention to the ways in which teachers are introduced to and have experience with strategies for the assessment of student learning. Cette étude porte sur le rapport entre les intentions de carrière et les perceptions qu’ont les finissants en enseignement secondaire au Québec quant à leur niveau de préparation. La recherche s’est étalée sur deux ans et visait à identifier les facteurs qui contribuent au taux grandissant d’attrition chez les enseignants débutants. L’étude a révélé que les enseignants débutants qui sont les plus préoccupés par leur manque de préparation en matière de gestion de classe et en évaluation des apprentissages sont également susceptibles de penser à quitter la profession. Bien que les résultats montrent que les enseignants débutants tendent à devenir plus confiants en gestion de classe pendant leur deuxième année d’enseignement, leur défis quant à l’évaluation des apprentissages persistent tout au long de leur deuxième année d’enseignement. Les résultats de cette étude qui reposent sur une méthode mixte indiquent également que, tant la formation initiale des enseignants que les employeurs, doivent porter attention à la présentation des notions relatives à l’évaluation des apprentissages et aux expériences qui sont offertes aux enseignants en début de carrière

Influence of N- methylation and conformation on almiramide anti-leishmanial activity

The almiramide N-methylated lipopeptides exhibit promising activity against trypanosomatid parasites. A structure–activity relationship study has been performed to examine the influences of N-methylation and conformation on activity against various strains of leishmaniasis protozoan and on cytotoxicity. The synthesis and biological analysis of twenty-five analogs demonstrated that derivatives with a single methyl group on either the first or fifth residue amide nitrogen exhibited greater activity than the permethylated peptides and relatively high potency against resistant strains. Replacement of amino amide residues in the peptide, by turn inducing α‑amino γ‑lactam (Agl) and N-aminoimidazalone (Nai) counterparts, reduced typically anti-parasitic activity; however, peptide amides possessing Agl residues at the second residue retained significant potency in the unmethylated and permethylated series. Systematic study of the effects of methylation and turn geometry on anti-parasitic activity indicated the relevance of an extended conformer about the central residues, and conformational mobility by tertiary amide isomerization and turn geometry at the extremities of the active peptides

Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance

3D segmentation of abdominal aorta from CT-scan and MR images

International audienceWe designed a generic method for segmenting the aneurismal sac of an abdominal aortic aneurysm (AAA) both from multi-slice MR and CT-scan examinations. It is a semi-automatic method requiring little human intervention and based on graph cut theory to segment the lumen interface and the aortic wall of AAAs. Our segmentation method works independently on MRI and CT-scan volumes and has been tested on a 44 patient dataset and 10 synthetic images. Segmentation and maximum diameter estimation were compared to manual tracing from 4 experts. An inter-observer study was performed in order to measure the variability range of a human observer. Based on three metrics (the maximum aortic diameter, the volume overlap and the Hausdorff distance) the variability of the results obtained by our method is shown to be similar to that of a human operator, both for the lumen interface and the aortic wall. As will be shown, the average distance obtained with our method is less than one standard deviation away from each expert, both for healthy subjects and for patients with AAA. Our semi-automatic method provides reliable contours of the abdominal aorta from CT-scan or MRI, allowing rapid and reproducible evaluations of AAA

Sulcal Polymorphisms of the IFC and ACC Contribute to Inhibitory Control Variability in Children and Adults

International audienceInhibitory control (IC) is a core executive function that enables humans to resist habits, temptations, or distractions. IC efficiency in childhood is a strong predictor of academic and professional success later in life. Based on analysis of the sulcal pattern, a qualitative feature of cortex anatomy determined during fetal life and stable during development, we searched for evidence that interindividual differences in IC partly trace back to prenatal processes. Using anatomical magnetic resonance imaging (MRI), we analyzed the sulcal pattern of two key regions of the IC neural network, the dorsal anterior cingulate cortex (ACC) and the inferior frontal cortex (IFC), which limits the inferior frontal gyrus. We found that the sulcal pattern asymmetry of both the ACC and IFC contributes to IC (Stroop score) in children and adults: participants with asymmetrical ACC or IFC sulcal patterns had better IC efficiency than participants with symmetrical ACC or IFC sulcal patterns. Such additive effects of IFC and ACC sulcal patterns on IC efficiency suggest that distinct early neurodevelopmental mechanisms targeting different brain regions likely contribute to IC efficiency. This view shares some analogies with the " common variant–small effect " model in genetics, which states that frequent genetic polymorphisms have small effects but collectively account for a large portion of the variance. Similarly, each sulcal polymorphism has a small but additive effect: IFC and ACC sulcal patterns, respectively, explained 3% and 14% of the variance of the Stroop interference scores. Significance Statement Inhibitory control (IC) is a cognitive function that plays a critical role in the pathophysiology of several psychiatric conditions and in academic and professional success. Using anatomical magnetic resonance imaging (MRI) of healthy children and adults, we found that IC efficiency is constrained by the morphology (sulcal pattern) of two key regions of the neural network underlying IC. Because the sulcal pattern is a morphologic feature of cortical anatomy that is determined during fetal life and stable during development, our findings provide evidence that interindividual differences in IC partly trace back to prenatal processes and that distinct early neurodevelopmental mechanisms targeting different brain regions likely contribute to IC efficiency

The IL‐27/IL‐27R axis is altered in CD4 + and CD8 + T lymphocytes from multiple sclerosis patients

International audienceObjectives: Pro- and anti-inflammatory properties have been attributed to interleukin-27 (IL-27). Nevertheless, the impact of this cytokine on chronic inflammatory diseases such as multiple sclerosis (MS) remains ill-defined. We investigated the biology of IL-27 and its specific receptor IL-27Rα in MS patients.Methods: Levels of IL-27 and its natural antagonist (IL-27-Rα) were measured by ELISA in biological fluids. CD4+ and CD8+ T lymphocytes were isolated from untreated relapsing-remitting MS patients and healthy donors. Transcriptome-wide analysis compared T-cell subsets stimulated or not with IL-27. Expression of the IL-27Rα, key immune factors, STAT phosphorylation and cytokine production was assessed by flow cytometry.Results: We observed elevated levels of IL-27 in the serum and cerebrospinal fluid of MS patients compared with controls. Moreover, we show that specific IL-27-mediated effects on T lymphocytes are reduced in MS patients including the induction of PD-L1. IL-27-triggered STAT3 signalling pathway is enhanced in CD4+ and CD8+ T lymphocytes from MS patients. Elevated IL-27Rα levels in serum from MS patients are sufficient to impair the capacity of IL-27 to act on immune cells. We demonstrate that shedding of IL-27Rα by activated CD4+ T lymphocytes from MS patients contributes to the increased IL-27Rα peripheral levels and consequently can dampen the IL-27 responsiveness.Conclusion: Our work identifies several mechanisms that are altered in the IL-27/IL-27R axis in MS patients, especially in T lymphocytes. Our results underline the importance of characterising the biology of cytokines in human patients prior to design new therapeutics

Determinants of Therapeutic Lag in Multiple Sclerosis

International audienceBackground: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups.Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation.Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants.Results: High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2-34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3-36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5-65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2-61.5).Conclusions: Pre-treatment EDSS and ARR are the most important determinants of therapeutic la

The effectiveness of natalizumab vs fingolimod–A comparison of international registry studies

International audienceBackground: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening.Methods: By re-analyzing original published results from MSBase, France, and Denmark using uniform methodologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/exclusion criteria and statistical methods with Inverse Probability Treatment Weighting.Results: The pooled analyses comprised 968 natalizumab- and 1479 fingolimod treated patients. The on-treatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod.Conclusion: The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed