VETESS : IDM, Test et SysML

Selected paper from the 7-th NEPTUNE WorkshopNational audienceIl apparaît souvent que les processus d'ingénierie système sont en fait décomposés en phases discontinues oùtrop peu d'informations sont partagées entre les différentes équipes, par exemple entre les équipes de design et de tests.Cette faiblesse peut être palliée par l’utilisation de modèles de spécifications qui jouent alors le rôle de référentiel pourl’ensemble des équipes participant au cycle de vie du logiciel. Ce type de modèle est couramment utilisé comme basedans les activités de conception, de vérification, ou encore de test. Le test basé sur les modèles est une approcheoriginale où sont automatiquement générés des cas de test et des scripts de test exécutables à partir d'une spécificationdu système sous test. Cette spécification prend la forme d'un modèle comportemental, permettant ainsi au générateur detests de déterminer, d'une part, quels sont les contextes d'exécution pertinents et, d'autre part, de prédire les effets sur lesystème de ces exécutions. Le but du projet VETESS est de rendre possible cette approche pour valider les systèmesembarqués automobiles. Il s’agit ainsi de mettre en œuvre et d’outiller un processus automatique permettant de dériver,d'un modèle de spécification décrit avec un sous-ensemble du langage de modélisation SysML, des cas de test, et deproduire ensuite les scripts de test correspondants à exécuter sur banc de test automobiles

The Solar Dynamics Observatory (SDO) Education and Outreach (E/PO) Program: Changing Perceptions One Program at a Time

We outline the context and overall philosophy for the combined Solar Dynamics Observatory (SDO) Education and Public Outreach (E/PO) program, present a brief overview of all SDO E/PO programs along with more detailed highlights of a few key programs, followed by a review of our results to date, conclude a summary of the successes, failures, and lessons learned, which future missions can use as a guide, while incorporating their own content to enhance the public's knowledge and appreciation of science and technology as well as its benefit to society

Real-world therapy with pembrolizumab: outcomes and surrogate endpoints for predicting survival in advanced melanoma patients in Germany

Knowledge on the real-world characteristics and outcomes of pembrolizumab-treated advanced melanoma patients in Germany and on the value of different real-world endpoints as surrogates for overall survival (OS) is limited. A sample of 664 pembrolizumab-treated patients with advanced melanoma from the German registry ADOReg was used. We examined OS, real-world progression-free survival (rwPFS), real-world time to next treatment (rwTtNT), and real-world time on treatment (rwToT). Spearman’s rank and iterative multiple imputation (IMI)-based correlation coefficients were computed between the OS and the rwPFS, rwTtNT, and rwToT and reported for the first line of therapy and the overall sample. The median OS was 30.5 (95%CI 25.0–35.4) months, the rwPFS was 3.9 months (95%CI 3.5–4.9), the rwTtNT was 10.7 months (95%CI 9.0–12.9), and the rwToT was 6.2 months (95%CI 5.1–6.8). The rwTtNT showed the highest correlation with the OS based on the IMI (rIMI = 0.83), Spearman rank correlations (rs = 0.74), followed by the rwToT (rIMI = 0.74 and rs = 0.65) and rwPFS (rIMI = 0.69 and rs = 0.56). The estimates for the outcomes and correlations were similar for the overall sample and those in first-line therapy. The median OS was higher compared to recent real-world studies, supporting the effectiveness of pembrolizumab in regular clinical practice. The rwTtNT may be a valuable OS surrogate, considering the highest correlation was observed with the OS among the investigated real-world endpoints

Real-World Therapy with Pembrolizumab: Outcomes and Surrogate Endpoints for Predicting Survival in Advanced Melanoma Patients in Germany

Knowledge on the real-world characteristics and outcomes of pembrolizumab-treated advanced melanoma patients in Germany and on the value of different real-world endpoints as surrogates for overall survival (OS) is limited. A sample of 664 pembrolizumab-treated patients with advanced melanoma from the German registry ADOReg was used. We examined OS, real-world progression-free survival (rwPFS), real-world time to next treatment (rwTtNT), and real-world time on treatment (rwToT). Spearman’s rank and iterative multiple imputation (IMI)-based correlation coefficients were computed between the OS and the rwPFS, rwTtNT, and rwToT and reported for the first line of therapy and the overall sample. The median OS was 30.5 (95%CI 25.0–35.4) months, the rwPFS was 3.9 months (95%CI 3.5–4.9), the rwTtNT was 10.7 months (95%CI 9.0–12.9), and the rwToT was 6.2 months (95%CI 5.1–6.8). The rwTtNT showed the highest correlation with the OS based on the IMI (rIMI = 0.83), Spearman rank correlations (rs = 0.74), followed by the rwToT (rIMI = 0.74 and rs = 0.65) and rwPFS (rIMI = 0.69 and rs = 0.56). The estimates for the outcomes and correlations were similar for the overall sample and those in first-line therapy. The median OS was higher compared to recent real-world studies, supporting the effectiveness of pembrolizumab in regular clinical practice. The rwTtNT may be a valuable OS surrogate, considering the highest correlation was observed with the OS among the investigated real-world endpoints

Fouilles à Marseille : la ville médiévale et moderne

Les fouilles archéologiques conduites dans le centre de Marseille depuis quelques décennies ont transformé notre connaissance de la ville. Longtemps focalisée sur la période grecque, première ville de France oblige, l'attention des archéologues s'est portée également sur des vestiges plus récents à partir du début des années 1990, alors que se multipliaient les opérations d'aménagement soit en limite de la ville antique et médiévale, soit au coeur même de celle-ci. Ainsi, de la place Villeneuve-Bargemon à la bibliothèque de l'Alcazar ou au tunnel de la Major, ce sont autant de lieux de découvertes qui retracent l'histoire de Marseille depuis le début du Moyen Age jusqu'à la Révolution française. Après dix ans de réflexion, alimentée par de nombreux articles, une exposition et des échanges croisés sur Marseille médiévale et moderne, les auteurs de ce volume ont souhaité restituer l'histoire de ce port majeur de la Méditerranée qu'est Marseille à un public aussi bien spécialisé que simplement désireux de mieux connaître cette ville. Le lecteur pourra ainsi comprendre comment des vestiges archéologiques, soigneusement sortis de leur gangue de terre par des archéologues professionnels, attestent des heurs et malheurs d'une cité qui croît au rythme du développement de l'activité portuaire. A côté des archéologues, la contribution des historiens et des archivistes à cette redécouverte de Marseille est importante. Elle témoigne de la nécessité de multiplier les regards sur des périodes que l'on croit connaître parce que plus proches de nous. L'ancrage que donne la matérialité des vestiges permet de mieux comprendre les références topographiques des textes d'archives écrits à une époque où l'évidence des lieux pour leurs contemporains fait ressortir notre propre ignorance. Abondamment illustré, ce volume met en valeur également le développement d'une archéologie des Temps modernes à côté de celle, déjà acceptée, du Moyen Age. C'est le développement de l'archéologie dite "de sauvetage" puis "préventive" qui a incité à traiter de façon égale tous les vestiges, quelle que soit leur période. Et là encore la confrontation avec les textes, en particulier dans le domaine de la construction, montre tout l'intérêt de cette approche pour la connaissance de nos racines

Real-world effectiveness of pembrolizumab in advanced melanoma: analysis of a French national clinicobiological database

International audienceAim: To describe real-world pembrolizumab administration and outcomes for advanced melanoma in France. Materials & methods: Using the MelBase longitudinal database, this multicenter historical-prospective study examined treatment and outcomes of patients with nonuveal, unresectable stage III/IV melanoma initiating pembrolizumab from April 2016 to September 2017, with follow-up to September 2019. Kaplan–Meier time-to-event analyses were conducted. Results: Of 223 patients (median age 67; 51% men), 134 (60%), 36 (16%) and 53 (24%) initiated pembrolizumab in first-, second- and third-line, respectively. Median overall survival (months) was 32.6 (95% CI: 20.3–not reached [NR]), 14.4 (8.6–NR) and 9.3 (6.4–NR), respectively. Best real-world tumor response of complete or partial response was recorded for 49, 39 and 26% of patients, respectively. Conclusion: Study results support benefits of pembrolizumab therapy for advanced melanoma

Burden and Risk Factors of Brain Metastases in Melanoma: A Systematic Literature Review

Melanoma can frequently metastasize to the brain with severe consequences. However, variation of melanoma brain metastases (MBM) development among populations is not well studied, and underlying mechanisms and risk factors for MBM development are not consistently documented. We conducted a systematic literature review (SLR) including a total of 39 articles to evaluate the proportion of melanoma patients who are diagnosed with, or develop, brain metastases, and summarize the risk factors of MBM. The average proportion of MBM was calculated and weighted by the sample size of each study. Meta-analyses were conducted for the selected risk factors using a random-effects model. The proportion of MBM at diagnosis was 33% (975 with MBM out of 2948 patients) among patients with cutaneous melanoma (excluding acral) and 23% (651/2875) among patients with cutaneous mixed with other types of melanoma. The proportion at diagnosis was lower among populations with mucosal (9/96, 9%) or uveal (4/184, 2%) melanoma and among populations outside the United States and Europe. Meta-analysis demonstrated that male vs. female gender and left-sided tumors vs. right-sided were significantly associated with increased risk of melanoma brain metastases. These data may help clinicians to assess an individual patient’s risk of developing melanoma brain metastases

VETESS : IDM, Test et SysML

Selected paper from the 7-th NEPTUNE WorkshopNational audienceIl apparaît souvent que les processus d'ingénierie système sont en fait décomposés en phases discontinues oùtrop peu d'informations sont partagées entre les différentes équipes, par exemple entre les équipes de design et de tests.Cette faiblesse peut être palliée par l’utilisation de modèles de spécifications qui jouent alors le rôle de référentiel pourl’ensemble des équipes participant au cycle de vie du logiciel. Ce type de modèle est couramment utilisé comme basedans les activités de conception, de vérification, ou encore de test. Le test basé sur les modèles est une approcheoriginale où sont automatiquement générés des cas de test et des scripts de test exécutables à partir d'une spécificationdu système sous test. Cette spécification prend la forme d'un modèle comportemental, permettant ainsi au générateur detests de déterminer, d'une part, quels sont les contextes d'exécution pertinents et, d'autre part, de prédire les effets sur lesystème de ces exécutions. Le but du projet VETESS est de rendre possible cette approche pour valider les systèmesembarqués automobiles. Il s’agit ainsi de mettre en œuvre et d’outiller un processus automatique permettant de dériver,d'un modèle de spécification décrit avec un sous-ensemble du langage de modélisation SysML, des cas de test, et deproduire ensuite les scripts de test correspondants à exécuter sur banc de test automobiles

Impaired Glucose Homeostasis in a Tau Knock-In Mouse Model

International audienceAlzheimer’s disease (AD) is the leading cause of dementia. While impaired glucose homeostasis has been shown to increase AD risk and pathological loss of tau function, the latter has been suggested to contribute to the emergence of the glucose homeostasis alterations observed in AD patients. However, the links between tau impairments and glucose homeostasis, remain unclear. In this context, the present study aimed at investigating the metabolic phenotype of a new tau knock-in (KI) mouse model, expressing, at a physiological level, a human tau protein bearing the P301L mutation under the control of the endogenous mouse Mapt promoter. Metabolic investigations revealed that, while under chow diet tau KI mice do not exhibit significant metabolic impairments, male but not female tau KI animals under High-Fat Diet (HFD) exhibited higher insulinemia as well as glucose intolerance as compared to control littermates. Using immunofluorescence, tau protein was found colocalized with insulin in the β cells of pancreatic islets in both mouse (WT, KI) and human pancreas. Isolated islets from tau KI and tau knock-out mice exhibited impaired glucose-stimulated insulin secretion (GSIS), an effect recapitulated in the mouse pancreatic β-cell line (MIN6) following tau knock-down. Altogether, our data indicate that loss of tau function in tau KI mice and, particularly, dysfunction of pancreatic β cells might promote glucose homeostasis impairments and contribute to metabolic changes observed in AD

DataSheet_1_Systematic literature review and meta-analysis of clinical outcomes and prognostic factors for melanoma brain metastases.docx

BackgroundMore than 60% of all stage IV melanoma patients develop brain metastases, while melanoma brain metastases (MBM) is historically difficult to treat with poor prognosis.ObjectivesTo summarize clinical outcomes and prognostic factors in MBM patients.MethodsA systematic review with meta-analysis was conducted, and a literature search for relevant studies was performed on November 1, 2020. Weighted average of median overall survival (OS) was calculated by treatments. The random-effects model in conducting meta-analyses was applied.ResultsA total of 41 observational studies and 12 clinical trials with our clinical outcomes of interest, and 31 observational studies addressing prognostic factors were selected. The most common treatments for MBM were immunotherapy (IO), MAP kinase inhibitor (MAPKi), stereotactic radiosurgery (SRS), SRS+MAPKi, and SRS+IO, with median OS from treatment start of 7.2, 8.6, 7.3, 7.3, and 14.1 months, respectively. Improved OS was observed for IO and SRS with the addition of IO and/or MAPKi, compared to no IO and SRS alone, respectively. Several prognostic factors were found to be significantly associated with OS in MBM.ConclusionThis study summarizes pertinent information regarding clinical outcomes and the association between patient characteristics and MBM prognosis.</p