Fundamental principles of data assimilation underlying the Verdandi library: applications to biophysical model personalization within euHeart

International audienceWe present the fundamental principles of data assimilation underlying the Verdandi library, and how they are articulated with the modular architecture of the library. This translates -- in particular -- into the definition of standardized interfaces through which the data assimilation library interoperates with the model simulation software and the so-called observation manager. We also survey various examples of data assimilation applied to the personalization of biophysical models, in particular for cardiac modeling applications within the euHeart European project. This illustrates the power of data assimilation concepts in such novel applications, with tremendous potential in clinical diagnosis assistance

Interactions physiologie-outils thérapeutiques dans les constructions physiopathologiques du goitre exophtalmique (1860-1960) / Physiological interactions, as therapeutic tools in physiopathological constructions of the exophtalmic goiter (1860-1960)

SUMMARY. — This paper deals with the relationship between physiology and therapeutic tools in the construction of the concept of exophtalmic goiter, the commonest form of thyroid hyperfunction. The clinical symptoms consisting in thyroid enlargement (goiter), exophtalmos and heart palpitations were described between 1835 and 1840. In 1862, this clinical triad was widely discussed at the French Academy of medicine and interpreted as a nervous disease. In the 1880 's the development of thyroid surgery and the discovery of the thyroid gland function led to a profound change in the interpretation of the disease. Exophtalmic goiter was now looked upon as a thyroid disease with specific histological lesions. These lesions justified the surgical treatment of the disease. As early as 1900, exophtalmic goiter was reinterpreted in the light of thyroid chemistry and considered as being due to a vitiating thyroid secretion. Taking into account the physiological knowledge, several therapeutic schemata led to a dead end. At the beginning of the 1940's empirical observations brought about alternative medical treatments : the use of radioiodine and antithyroid compounds. From 1940 to 1960, the application of radioiodine shed a completely new light on thyroid physiopathology. This study shows that Claude Bernard's linear schema in the field of scientific medicine — 1) physiology ; 2) pathology ; 3) therapeutic — should be used with caution.RÉSUMÉ. — Cet article est consacré aux interactions entre savoir physiologique et outils thérapeutiques dans la construction du concept de goitre exophtalmique, forme la plus commune d'hyperfonctionnement thyroïdien. Dans les années 1830, la médecine clinique décrit cette nouvelle entité clinique dont la triade symptomatique (goitre, exophtalmie et palpitations) et son éventuelle origine nerveuse font l'objet d'un long débat à l'Académie de médecine en 1862. Vingt ans plus tard, le développement de la chirurgie thyroïdienne, qui permet l'émergence de la fonction du corps thyroïde, transforme le goitre exophtalmique en une maladie spécifique de la glande thyroïde avec l'identification de lésions histologiques justifiant son traitement par thyroïdectomie. Dès 1900, l'essor de la chimie thyroïdienne conduit à associer lésion histologique et viciation de la sécrétion thyroïdienne sur laquelle on s'efforce d'agir autrement que par la chirurgie. Plusieurs schémas thérapeutiques sont construits à partir de la physiologie thyroïdienne, qui débouchent sur des impasses. Au début des années 1940, des approches empiriques ont favorisé l'émergence de deux alternatives médicales au traitement chirurgical : l'iode radioactif et les antithyroïdiens de synthèse qui bloquent le métabolisme de l'iode intrathyroïdien. Ces deux outils ont permis un accroissement prodigieux des connaissances en physiologie thyroïdienne. Cette étude nuance ainsi le schéma linéaire proposé par Claude Bernard pour le développement de la médecine scientifique : physiologie, pathologie et thérapeutique.Fragu Philippe. Interactions physiologie-outils thérapeutiques dans les constructions physiopathologiques du goitre exophtalmique (1860-1960) / Physiological interactions, as therapeutic tools in physiopathological constructions of the exophtalmic goiter (1860-1960). In: Revue d'histoire des sciences, tome 53, n°1, 2000. pp. 107-132

Assessing intratumor distribution and uptake with MBBG versus MIBG imaging and targeting xenografted PC12-pheochromocytoma cell line

The heterogeneity of tumor uptake is likely to substantially limit the effectiveness of metaiodobenzylguanidine (MIBG) therapy. This study was done to establish whether metabromobenzyl-guanidine (MBBG) can target neuroendocrine tumors and to provide intratumor biodistribution and uptake information in comparison to MIBG. Methods: MBBG and MIBG tumor uptake and kinetic studies were performed in experimental PC-12 pheochromocytoma grown in nude mice. Intratumor distribution studies were performed using autoradiography and secondary ion mass spectrometry (SIMS) microscopy, because the latter technique can detect and potentially quantify both drugs concomitantly within the same tumor specimen. Results: MBBG uptake in PC12 tumors was early (2 hr) and intense (80% ID/g). Retention values were similar for both drugs 24 hr postinjection. At the cellular level, MBBG mostly accumulated in the cytosol. At the multicellular level, cells exhibited staining, but in many areas, SIMS images of both drugs were not spatially correlated. Conclusion: MBBG targeted experimental pheochromocytoma efficiently with high early uptake values. Bromine-76-MBBG is a promising means of imaging and quantifying tumor uptake with PET. Both drugs were localized in the cytosol, but the correlation between the two distributions, as assessed by the values of the standardized local concentrations, was weak although significant multicellularly

An European cooperative study on irradiation and thyroid disease

SCOPUS: le.jinfo:eu-repo/semantics/publishe

Cancer mortality after radiotherapy for a skin hemangioma during childhood.

International audienceBACKGROUND AND PURPOSE: A cohort study was performed as part of a European Radiation Protection Program to investigate the carcinogenic effect of treatment with ionizing radiation in early childhood. This paper presents mortality after radiotherapy in this cohort. PATIENTS AND METHODS: The cohort comprised 7037 patients under 15 years of age treated for a skin hemangioma between 1940 and 1973 at the Institut Gustave-Roussy, among whom 4940 received radiotherapy. The vital status and causes of death were obtained as well as the mortality rates in the general French population. External and internal analyses were performed. Standardized mortality ratio (SMR) and relative risk (RR) variations according to exposure to radiotherapy or not and the type of treatment were studied. RESULTS: During the 1969-1997 follow-up period, 16 cohort patients died of cancer, 14 after radiotherapy. A non-significant excess of cancer-related mortality was observed for irradiated patients as compared to the general population (SMR=1.53; 95% CI=0.86-2.48). Treatment with (226)Ra seemed to play a significant role (RR=2.53; 95% CI=0.84-7.07) compared to no radiotherapy. CONCLUSION: This study suggests an excess risk of cancer-related mortality in patients treated during early childhood with radiotherapy for skin hemangioma, and especially with (226)Ra. These patients need to be followed up in the future