Identification of weakly coupled multiphysics problems. Application to the inverse problem of electrocardiography

This work addresses the inverse problem of electrocardiography from a new perspective, by combining electrical and mechanical measurements. Our strategy relies on the defini-tion of a model of the electromechanical contraction which is registered on ECG data but also on measured mechanical displacements of the heart tissue typically extracted from medical images. In this respect, we establish in this work the convergence of a sequential estimator which combines for such coupled problems various state of the art sequential data assimilation methods in a unified consistent and efficient framework. Indeed we ag-gregate a Luenberger observer for the mechanical state and a Reduced Order Unscented Kalman Filter applied on the parameters to be identified and a POD projection of the electrical state. Then using synthetic data we show the benefits of our approach for the estimation of the electrical state of the ventricles along the heart beat compared with more classical strategies which only consider an electrophysiological model with ECG measurements. Our numerical results actually show that the mechanical measurements improve the identifiability of the electrical problem allowing to reconstruct the electrical state of the coupled system more precisely. Therefore, this work is intended to be a first proof of concept, with theoretical justifications and numerical investigations, of the ad-vantage of using available multi-modal observations for the estimation and identification of an electromechanical model of the heart

Studio di vetri musivi della Basilica Alfa (VI secolo) di Nicopoli d’Epiro, Grecia

SummaryAfter collecting the essential historical, archaeological, and artistic information relative to the ancient town of Nikopolis in Epirus and its Alpha (or Doumetios) Basilica, built in the sixth century A.D., glass tesserae belonging to degraded and lost parts of the mosaic floors of the basilica were analysed, determining their chemical composition and the possible presence of crystalline phases. As in all glasses produced in the Mediterranean area in that epoch, they are soda-lime silicate glasses, in part with lead, obtained using natron as a flux. The typology of the glass corresponds to that of Roman glasses, of the first centuries A.D., and is the same as that employed for the basilicas of Ravenna in the fifth and sixth centuries; in particular, a comparison was made with the glass tesserae of the St Vitale Basilica. The technological base for producing coloured glasses is also practically the same as that of the mosaic glasses of Ravenna. In particular, antimony was used as an opacifying element and a fusion was carried out under reducing conditions to obtain red glass with microparticles of metallic copper. Thus, it can be supposed there was a common source of production of the mosaic glasses used in Nikopolis and Ravenna in the sixth century and that this source was in the Near Orient. RiassuntoDopo la raccolta delle informazioni essenziali di carattere storico, archeologico e artistico relative all’antica città di Nicopoli d’Epiro e alla sua Basilica Alfa (o Doumetios), costruita nel VI secolo d.C., sono state analizzate tessere vitree che appartenevano a parti dei pavimenti musivi della basilica degradate e andate perdute, determinando la loro composizione chimica e la eventuale presenza di fasi cristalline. Come tutti i vetri dell’epoca prodotti in area mediterranea si tratta di vetri silicatico-sodico-calcici, in parte piombici, ottenuti usando natron quale fondente. La tipologia del vetro corrisponde a quella dei vetri Romani, dei primi secoli d.C., ed è la stessa dei vetri musivi impiegati nelle basiliche ravennati del V e VI secolo; in particolare il confronto è stato effettuato con la composizione delle tessere vetrose della basilica di San Vitale. Anche la tecnologia alla base dell’ottenimento dei vetri colorati è praticamente la stessa dei vetri ravennati. In particolare, è stato usato antimonio come elemento opacizzante e condotta una fusione in ambiente riducente per ottenere vetro rosso con microparticelle di rame metallico. Si può, dunque, fare l’ipotesi di una fonte produttiva comune dei vetri musivi impiegati a Nicopoli e a Ravenna nel VI secolo e che tale fonte fosse nel Vicino Oriente. RésuméAprès la collecte des informations essentielles à caractère historique, archéologique et artistique concernant la ville antique de Nicopolis d’Épire et sa basilique Alpha (ou Doumetios), construite au VIe siècle apr. J.-C., il a été procédé à l’analyse des tesselles de verre qui appartenaient à des parties des pavements de mosaïque de la basilique qui ont été dégradés et perdus, à la définition de leur composition chimique et au relevé d’une éventuelle présence de phases cristallines. Comme tous les verres de l’époque fabriqués dans la région méditerranéenne, il s’agit de verres silico-sodiques-calciques, en partie plombiques, qui ont été obtenus en utilisant le natron comme fondant. La typologie du verre correspond à celle des verres romains des premiers siècles apr. J.-C., et c’est la même que celle des verres de mosaïque employés dans les basiliques de Ravenne des Ve et VIe siècles. Notamment, une comparaison a été effectuée sur la composition des tesselles de verre de la basilique de Saint-Vital. La technique permettant d’obtenir des verres colorés est pratiquement la même que celle des verres de Ravenne. En particulier, l’antimoine a été utilisé comme élément opacifiant, et une fusion en milieu réducteur a permis d’obtenir un verre rouge avec des microparticules de cuivre métallique. Nous pouvons donc émettre l’hypothèse d’une source commune de fabrication des verres de mosaïque utilisés à Nicopolis et à Ravenne au VIe siècle, et que cette source se trouvait au Proche Orient. ZusammenfassungNachdem die wesentlichen historischen, archäologischen und künstlerischen Informationen über die antike Stadt Nikopolis in Epirus und ihre im 6. Jahrhundert n. Chr. errichtete Basilika Alpha (auch Doumetios) eingeholt worden waren, wurden Glassteine analysiert, die zu zerstörten und verloren gegangenen Teilen des Mosaikbodens der Basilika gehörten, um ihre chemische Zusammensetzung und den eventuellen Gehalt an Kristallphasen zu bestimmen. Wie alle anderen Glassorten, die damals im Mittelmeergebiet hergestellt wurden, handelt es sich auch hier um silikat-, natrium- und kalkhaltiges, teils auch bleihaltiges Glas, das unter Verwendung von Natron als Schmelzmittel hergestellt wurde. Diese Glassorte entspricht derjenigen der Römischen Gläser aus den ersten Jahrhunderten n. Chr. und es ist die gleiche Glassorte, wie die der Glassteine, die in den Basiliken von Ravenna aus dem 5. und 6. Jahrhundert verwendet wurden.  Im Einzelnen wurde der Vergleich mit den Mosaiksteinen aus Glas in der Basilika San Vitale vorgenommen. Auch die Technik der Herstellung farbigen Glases ist praktisch die gleiche, die in Ravenna zum Einsatz kam. Insbesondere wurde Antimon zur Opakisierung und ein Reduktions-Schmelzverfahren zur Herstellung roten Glases mit Mikropartikeln metallischen Kupfers verwendet. Es kann also angenommen werden, dass die Mosaik-Glassteine in Nikopolis und Ravenna im 6. Jahrhundert aus der gleichen Produktionsquelle stammten, und dass sich diese Quelle im Vorderen Orient befand. Resumen Tras haber recogido la información esencial desde el punto de vista histórico, arqueológico y artístico sobre la antigua ciudad de Nicópolis de Epiro y de su Basílica Alfa (o de Dumetios), construida en el siglo VI d.C., se han analizado las teselas de vidrio pertenecientes a partes del pavimento musivario de la basílica, las cuales han sufrido degrado o han desaparecido, para determinar su composición química y la eventual presencia de fases cristalinas. Al igual que los demás vidrios producidos en el área del Mediterráneo en aquella época, se trata de vidrios de silicato sódico cálcico, en parte plúmbicos, obtenidos utilizando natrón como fundente. El tipo de vidrio corresponde al de los vidrios romanos de los primeros siglos d.C. y es el mismo de los vidrios musivarios empleados en las basílicas de Rávena en los siglos V y VI; en particular, se ha realizado una comparación con la composición de las teselas de vidrio de la basílica de San Vital. Incluso la tecnología empleada para obtener vidrios de colores es prácticamente la misma que la de los vidrios de Rávena. En particular, se ha empleado antimonio como elemento opacador y se ha conducido una fusión en ambiente reductor para obtener vidrio rojo con micropartículas de cobre metálico. Por tanto, es posible plantear la hipótesis de que habría una fuente productiva común de los vidrios musivarios de Nicópolis y de Rávena en el siglo VI y que dicha fuente se habría encontrado en el Cercano Oriente. РезюмеПосле сбора существенных исторических, археологических и художественных сведений, связанных с древним городом Никополь Эпира и его Базиликой Альфа (или Doumetios), построенной в VI в. н. э., были проанализированы стеклянные тессеры, принадлежавшие частям разрушенных полов базилики, и установлен их химический состав и возможное присутствие кристаллических фаз. Как и все стекла той эпохи, сделанные в средиземноморской зоне, это кальциево-натриевые-силикатные стекла, частично свинцовые, полученные при использовании натрона в качестве расплавителя. Типология стекла соответствует типологии римского стекла первых веков нашей эры и такая же характеризует стеклянные мозаики, украшающие базилики Равенны V и VI веков; в частности было произведено сравнение с составом стеклянных тессер базилики Сан Витале. Технология для получения цветного стекла практически такая же как и у равеннских стекол. В частности  была применена сурьма как матирующий элемент и произведено плавление в восстановительной среде для получения красного стекла с микрочастицами металлической меди. Следовательно, возможна гипотеза об общем источнике производства стеклянных мозаик, использованных в Никополе и Равенне в VI веке, и что этот источник был на Ближнем Востоке. 摘要在古老城市伊庇鲁斯尼科波尔和它建于六世纪的第一神殿(或 Doumetios神殿)的相关历史、考古和艺术等特性的重要信息进行了收集之后，学者分析了属于大殿马赛克地板的玻璃镶嵌件并确定了它们的化学成分和结晶相的存在可能，该部分已退化和丢失了。正如地中海地区当时的所有玻璃产品都是钙 - 钠硅酸盐玻璃，一部分也含铅，都用泡碱作为熔剂。该玻璃类型与公元初几个世纪罗马的玻璃相对应，也和五、六世纪的拉文纳大教堂采用的马赛克玻璃一样；尤其是与圣维塔大教堂的玻化砖成分进行了对照。其实彩色玻璃的制造技术也跟拉文纳的相同。尤其当时先用了锑为不透明元素，然后在还原环境下进行了融合，就获得了金属铜微粒的红色玻璃。因此，可以猜想到六世纪拉文纳马赛克玻璃采用的生产来源和尼科波尔相同，并且这来源地是在近东。SummaryAfter collecting the essential historical, archaeological, and artistic information relative to the ancient town of Nikopolis in Epirus and its Alpha (or Doumetios) Basilica, built in the sixth century A.D., glass tesserae belonging to degraded and lost parts of the mosaic floors of the basilica were analysed, determining their chemical composition and the possible presence of crystalline phases. As in all glasses produced in the Mediterranean area in that epoch, they are soda-lime silicate glasses, in part with lead, obtained using natron as a flux. The typology of the glass corresponds to that of Roman glasses, of the first centuries A.D., and is the same as that employed for the basilicas of Ravenna in the fifth and sixth centuries; in particular, a comparison was made with the glass tesserae of the St Vitale Basilica. The technological base for producing coloured glasses is also practically the same as that of the mosaic glasses of Ravenna. In particular, antimony was used as an opacifying element and a fusion was carried out under reducing conditions to obtain red glass with microparticles of metallic copper. Thus, it can be supposed there was a common source of production of the mosaic glasses used in Nikopolis and Ravenna in the sixth century and that this source was in the Near Orient. RiassuntoDopo la raccolta delle informazioni essenziali di carattere storico, archeologico e artistico relative all’antica città di Nicopoli d’Epiro e alla sua Basilica Alfa (o Doumetios), costruita nel VI secolo d.C., sono state analizzate tessere vitree che appartenevano a parti dei pavimenti musivi della basilica degradate e andate perdute, determinando la loro composizione chimica e la eventuale presenza di fasi cristalline. Come tutti i vetri dell’epoca prodotti in area mediterranea si tratta di vetri silicatico-sodico-calcici, in parte piombici, ottenuti usando natron quale fondente. La tipologia del vetro corrisponde a quella dei vetri Romani, dei primi secoli d.C., ed è la stessa dei vetri musivi impiegati nelle basiliche ravennati del V e VI secolo; in particolare il confronto è stato effettuato con la composizione delle tessere vetrose della basilica di San Vitale. Anche la tecnologia alla base dell’ottenimento dei vetri colorati è praticamente la stessa dei vetri ravennati. In particolare, è stato usato antimonio come elemento opacizzante e condotta una fusione in ambiente riducente per ottenere vetro rosso con microparticelle di rame metallico. Si può, dunque, fare l’ipotesi di una fonte produttiva comune dei vetri musivi impiegati a Nicopoli e a Ravenna nel VI secolo e che tale fonte fosse nel Vicino Oriente.RésuméAprès la collecte des informations essentielles à caractère historique, archéologique et artistique concernant la ville antique de Nicopolis d’Épire et sa basilique Alpha (ou Doumetios), construite au VIe siècle apr. J.-C., il a été procédé à l’analyse des tesselles de verre qui appartenaient à des parties des pavements de mosaïque de la basilique qui ont été dégradés et perdus, à la définition de leur composition chimique et au relevé d’une éventuelle présence de phases cristallines. Comme tous les verres de l’époque fabriqués dans la région méditerranéenne, il s’agit de verres silico-sodiques-calciques, en partie plombiques, qui ont été obtenus en utilisant le natron comme fondant. La typologie du verre correspond à celle des verres romains des premiers siècles apr. J.-C., et c’est la même que celle des verres de mosaïque employés dans les basiliques de Ravenne des Ve et VIe siècles. Notamment, une comparaison a été effectuée sur la composition des tesselles de verre de la basilique de Saint-Vital. La technique permettant d’obtenir des verres colorés est pratiquement la même que celle des verres de Ravenne. En particulier, l’antimoine a été utilisé comme élément opacifiant, et une fusion en milieu réducteur a permis d’obtenir un verre rouge avec des microparticules de cuivre métallique. Nous pouvons donc émettre l’hypothèse d’une source commune de fabrication des verres de mosaïque utilisés à Nicopolis et à Ravenne au VIe siècle, et que cette source se trouvait au Proche Orient. ZusammenfassungNachdem die wesentlichen historischen, archäologischen und künstlerischen Informationen über die antike Stadt Nikopolis in Epirus und ihre im 6. Jahrhundert n. Chr. errichtete Basilika Alpha (auch Doumetios) eingeholt worden waren, wurden Glassteine analysiert, die zu zerstörten und verloren gegangenen Teilen des Mosaikbodens der Basilika gehörten, um ihre chemische Zusammensetzung und den eventuellen Gehalt an Kristallphasen zu bestimmen. Wie alle anderen Glassorten, die damals im Mittelmeergebiet hergestellt wurden, handelt es sich auch hier um silikat-, natrium- und kalkhaltiges, teils auch bleihaltiges Glas, das unter Verwendung von Natron als Schmelzmittel hergestellt wurde. Diese Glassorte entspricht derjenigen der Römischen Gläser aus den ersten Jahrhunderten n. Chr. und es ist die gleiche Glassorte, wie die der Glassteine, die in den Basiliken von Ravenna aus dem 5. und 6. Jahrhundert verwendet wurden.  Im Einzelnen wurde der Vergleich mit den Mosaiksteinen aus Glas in der Basilika San Vitale vorgenommen. Auch die Technik der Herstellung farbigen Glases ist praktisch die gleiche, die in Ravenna zum Einsatz kam. Insbesondere wurde Antimon zur Opakisierung und ein Reduktions-Schmelzverfahren zur Herstellung roten Glases mit Mikropartikeln metallischen Kupfers verwendet. Es kann also angenommen werden, dass die Mosaik-Glassteine in Nikopolis und Ravenna im 6. Jahrhundert aus der gleichen Produktionsquelle stammten, und dass sich diese Quelle im Vorderen Orient befand.ResumenTras haber recogido la información esencial desde el punto de vista histórico, arqueológico y artístico sobre la antigua ciudad de Nicópolis de Epiro y de su Basílica Alfa (o de Dumetios), construida en el siglo VI d.C., se han analizado las teselas de vidrio pertenecientes a partes del pavimento musivario de la basílica, las cuales han sufrido degrado o han desaparecido, para determinar su composición química y la eventual presencia de fases cristalinas. Al igual que los demás vidrios producidos en el área del Mediterráneo en aquella época, se trata de vidrios de silicato sódico cálcico, en parte plúmbicos, obtenidos utilizando natrón como fundente. El tipo de vidrio corresponde al de los vidrios romanos de los primeros siglos d.C. y es el mismo de los vidrios musivarios empleados en las basílicas de Rávena en los siglos V y VI; en particular, se ha realizado una comparación con la composición de las teselas de vidrio de la basílica de San Vital. Incluso la tecnología empleada para obtener vidrios de colores es prácticamente la misma que la de los vidrios de Rávena. En particular, se ha empleado antimonio como elemento opacador y se ha conducido una fusión en ambiente reductor para obtener vidrio rojo con micropartículas de cobre metálico. Por tanto, es posible plantear la hipótesis de que habría una fuente productiva común de los vidrios musivarios de Nicópolis y de Rávena en el siglo VI y que dicha fuente se habría encontrado en el Cercano Oriente. РезюмеПосле сбора существенных исторических, археологических и художественных сведений, связанных с древним городом Никополь Эпира и его Базиликой Альфа (или Doumetios), построенной в VI в. н. э., были проанализированы стеклянные тессеры, принадлежавшие частям разрушенных полов базилики, и установлен их химический состав и возможное присутствие кристаллических фаз. Как и все стекла той эпохи, сделанные в средиземноморской зоне, это кальциево-натриевые-силикатные стекла, частично свинцовые, полученные при использовании натрона в качестве расплавителя. Типология стекла соответствует типологии римского стекла первых веков нашей эры и такая же характеризует стеклянные мозаики, украшающие базилики Равенны V и VI веков; в частности было произведено сравнение с составом стеклянных тессер базилики Сан Витале. Технология для получения цветного стекла практически такая же как и у равеннских стекол. В частности  была применена сурьма как матирующий элемент и произведено плавление в восстановительной среде для получения красного стекла с микрочастицами металлической меди. Следовательно, возможна гипотеза об общем источнике производства стеклянных мозаик, использованных в Никополе и Равенне в VI веке, и что этот источник был на Ближнем Востоке. 摘要在古老城市伊庇鲁斯尼科波尔和它建于六世纪的第一神殿(或 Doumetios神殿)的相关历史、考古和艺术等特性的重要信息进行了收集之后，学者分析了属于大殿马赛克地板的玻璃镶嵌件并确定了它们的化学成分和结晶相的存在可能，该部分已退化和丢失了。正如地中海地区当时的所有玻璃产品都是钙 - 钠硅酸盐玻璃，一部分也含铅，都用泡碱作为熔剂。该玻璃类型与公元初几个世纪罗马的玻璃相对应，也和五、六世纪的拉文纳大教堂采用的马赛克玻璃一样；尤其是与圣维塔大教堂的玻化砖成分进行了对照。其实彩色玻璃的制造技术也跟拉文纳的相同。尤其当时先用了锑为不透明元素，然后在还原环境下进行了融合，就获得了金属铜微粒的红色玻璃。因此，可以猜想到六世纪拉文纳马赛克玻璃采用的生产来源和尼科波尔相同，并且这来源地是在近东。

A conduction velocity adapted eikonal model for electrophysiology problems with re-excitability evaluation

Computational models of heart electrophysiology achieved a great interest from the medical community since they represent a novel framework to study the mechanisms that underpin heart pathologies. The high demand of computational resources and the long computational times required to evaluate the model solution hamper the use of detailed computational models in clinical applications. In this paper, we propose a multi-front eikonal algorithm capable of adapting the conduction velocity (CV) to the activation frequency of the tissue substrate. We then couple the new eikonal model with a Mitchell-Schaeffer (MS) ionic model to determine the tissue electrical state. Compared to the standard eikonal model, this model introduces three novelties: first, the local value of the transmembrane potential and of the ionic variable are known from the solution of the ionic model; second, the action potential duration (AP D) and the diastolic interval (DI) are computed from the solution of the MS model and used to determine when a part of the tissue is re-excitable. Third, CV is locally adapted to the underpinning electrophysiological state through the analytical CV restitution expression and the computed local DI. We conduct series of simulations on a tissue slab and on 3D realistic heart geometry and compare results to the monodomain. Our results show that the new model is much more accurate than the standard eikonal model. This model enables the numerical simulation of the heart electrophysiology on a clinical time scale and thus constitutes a good model candidate for computer-guided cardiac therapy

Hypoxia sustains glioblastoma radioresistance through ERKs/DNA-PKcs/HIF-1α functional interplay

The molecular mechanisms by which glioblastoma multiforme (GBM) refracts and becomes resistant to radiotherapy treatment remains largely unknown. This radioresistance is partly due to the presence of hypoxic regions, which are frequently found in GBM tumors. We investigated the radiosensitizing effects of MEK/ERK inhibition on GBM cell lines under hypoxic conditions. Four human GBM cell lines, T98G, U87MG, U138MG and U251MG were treated with the MEK/ERK inhibitor U0126, the HIF-1α inhibitor FM19G11 or γ-irradiation either alone or in combination under hypoxic conditions. Immunoblot analysis of specific proteins was performed in order to define their anti‑oncogenic or radiosensitizing roles in the different experimental conditions. MEK/ERK inhibition by U0126 reverted the transformed phenotype and significantly enhanced the radiosensitivity of T98G, U87MG, U138MG cells but not of the U251MG cell line under hypoxic conditions. U0126 and ERK silencing by siRNA reduced the levels of DNA protein kinase catalytic subunit (DNA-PKcs), Ku70 and K80 proteins and clearly reduced HIF-1α activity and protein expression. Furthermore, DNA-PKcs siRNA-mediated silencing counteracted HIF-1α activity and downregulated protein expression suggesting that ERKs, DNA-PKcs and HIF-1α cooperate in radioprotection of GBM cells. Of note, HIF-1α inhibition under hypoxic conditions drastically radiosensitized all cell lines used. MEK/ERK signal transduction pathway, through the sustained expression of DNA-PKcs, positively regulates HIF-1α protein expression and activity, preserving GBM radioresistance in hypoxic condition

Deep learning methods to predict amyotrophic lateral sclerosis disease progression

Amyotrophic lateral sclerosis (ALS) is a highly complex and heterogeneous neurodegenerative disease that affects motor neurons. Since life expectancy is relatively low, it is essential to promptly understand the course of the disease to better target the patient’s treatment. Predictive models for disease progression are thus of great interest. One of the most extensive and well-studied open-access data resources for ALS is the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) repository. In 2015, the DREAM-Phil Bowen ALS Prediction Prize4Life Challenge was held on PRO-ACT data, where competitors were asked to develop machine learning algorithms to predict disease progression measured through the slope of the ALSFRS score between 3 and 12 months. However, although it has already been successfully applied in several studies on ALS patients, to the best of our knowledge deep learning approaches still remain unexplored on the ALSFRS slope prediction in PRO-ACT cohort. Here, we investigate how deep learning models perform in predicting ALS progression using the PRO-ACT data. We developed three models based on different architectures that showed comparable or better performance with respect to the state-of-the-art models, thus representing a valid alternative to predict ALS disease progression

The impact of anastomotic leak on long-term oncological outcomes after low anterior resection for mid-low rectal cancer: extended follow-up of a randomised controlled trial

The impact of anastomotic leaks (AL) on oncological outcomes after low anterior resection for mid-low rectal cancer is still debated. The aim of this study was to evaluate overall survival (OS), disease-free survival (DFS), and local and distant recurrence in patients with AL following low anterior resection