Learning from Objects: the use of advanced numerical methods to exploit a complete set of information from experimental data, for the Mona Lisa’s Digital-Twin

International audienceThe approach to wooden artefacts of historical importance, and panel paintings in particular, is a task that requires a multidisciplinary approach based on experimental observation of the artwork and advanced techniques to make these data actually useful for the knowledge and preservation of the object. This study illustrates how a series of scientific observations and instrumental analyses can be used to construct a numerical simulation that allows a deeper understanding of the physical structure and behaviour of the object itself, namely to construct a hygro-mechanical predictive model (a “Digital-Twin”) of Leonardo da Vinci's Mona Lisa panel. Based on specific request from the Louvre Museum, a group of experts with different and complementary skills cooperated and are still cooperating to construct a complete set of experimental observation and non-invasive tests; so, the integration of the collected data made the construction possible of the panel’s Digital-Twin. This paper also specifically examines how the Digital-Twin can be used to compare two framing conditions of the panel; although the two experimental configurations are not inherently comparable, the comparison is made possible by the introduction of a technique of projection of the fields obtained as results of the two analyses, named the Projected Model Comparison (PMC), which has been developed specifically for this research

Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart.

Macrophages are components of the innate immune system with key roles in tissue inflammation and repair. It is now evident that macrophages also support organogenesis, but few studies have characterized their identity, ontogeny and function during heart development. Here, we show that the distribution and prevalence of resident macrophages in the subepicardial compartment of the developing heart coincides with the emergence of new lymphatics, and that macrophages interact closely with the nascent lymphatic capillaries. Consequently, global macrophage deficiency led to extensive vessel disruption, with mutant hearts exhibiting shortened and mis-patterned lymphatics. The origin of cardiac macrophages was linked to the yolk sac and foetal liver. Moreover, the Cx3cr1 + myeloid lineage was found to play essential functions in the remodelling of the lymphatic endothelium. Mechanistically, macrophage hyaluronan was required for lymphatic sprouting by mediating direct macrophage-lymphatic endothelial cell interactions. Together, these findings reveal insight into the role of macrophages as indispensable mediators of lymphatic growth during the development of the mammalian cardiac vasculature.This work was funded by the British Heart Foundation (chair award CH/11/1/28798 and programme grant RG/08/003/25264 to PRR) and supported by the BHF Oxbridge Centre of Regenerative Medicine (RM/13/3/30159); a Wellcome Trust Doctoral Training Fellowship 106334/Z/14/Z to TJC; a Wellcome Trust Four year PhD Studentship 215103/Z/18/Z to KK; a BHF Intermediate Basic Science Research Fellowship FS/19/31/34158 to JMV; a British Israel Research and Academic Exchange Partnership (BIRAX) Grant 13BX14PRET; a Leducq Foundation Transatlantic Network of Excellence Program 14CVD04 and MRC Unit funding to DGJ.S

Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair

Canonical roles for macrophages in mediating the fibrotic response after a heart attack include extracellular matrix turnover and activation of cardiac fibroblasts to initiate collagen deposition. Here we reveal that macrophages directly contribute collagen to the forming post-injury scar. Unbiased transcriptomics shows an upregulation of collagens in both zebrafish and mouse macrophages following heart injury. Adoptive transfer of macrophages, from either collagen-tagged zebrafish or adult mouse GFPtpz-collagen donors, enhances scar formation via cell autonomous production of collagen. In zebrafish, the majority of tagged collagen localises proximal to the injury, within the overlying epicardial region, suggesting a possible distinction between macrophage-deposited collagen and that predominantly laid-down by myofibroblasts. Macrophage-specific targeting of col4a3bpa and cognate col4a1 in zebrafish significantly reduces scarring in cryoinjured hosts. Our findings contrast with the current model of scarring, whereby collagen deposition is exclusively attributed to myofibroblasts, and implicate macrophages as direct contributors to fibrosis during heart repair

Agreement among Health Care Professionals in Diagnosing Case Vignette-Based Surgical Site Infections

OBJECTIVE: To assess agreement in diagnosing surgical site infection (SSI) among healthcare professionals involved in SSI surveillance. METHODS: Case-vignette study done in 2009 in 140 healthcare professionals from seven specialties (20 in each specialty, Anesthesiologists, Surgeons, Public health specialists, Infection control physicians, Infection control nurses, Infectious diseases specialists, Microbiologists) in 29 University and 36 non-University hospitals in France. We developed 40 case-vignettes based on cardiac and gastrointestinal surgery patients with suspected SSI. Each participant scored six randomly assigned case-vignettes before and after reading the SSI definition on an online secure relational database. The intraclass correlation coefficient (ICC) was used to assess agreement regarding SSI diagnosis on a seven-point Likert scale and the kappa coefficient to assess agreement for superficial or deep SSI on a three-point scale. RESULTS: Based on a consensus, SSI was present in 21 of 40 vignettes (52.5%). Intraspecialty agreement for SSI diagnosis ranged across specialties from 0.15 (95% confidence interval, 0.00-0.59) (anesthesiologists and infection control nurses) to 0.73 (0.32-0.90) (infectious diseases specialists). Reading the SSI definition improved agreement in the specialties with poor initial agreement. Intraspecialty agreement for superficial or deep SSI ranged from 0.10 (-0.19-0.38) to 0.54 (0.25-0.83) (surgeons) and increased after reading the SSI definition only among the infection control nurses from 0.10 (-0.19-0.38) to 0.41 (-0.09-0.72). Interspecialty agreement for SSI diagnosis was 0.36 (0.22-0.54) and increased to 0.47 (0.31-0.64) after reading the SSI definition. CONCLUSION: Among healthcare professionals evaluating case-vignettes for possible surgical site infection, there was large disagreement in diagnosis that varied both between and within specialties

Pourquoi la thérapie HAART remanie-t-elle les différents sites du tissu adipeux de manière hétérogène ? : importance de l’origine des dépôts, modélisation et mécanismes moléculaires

The adipose tissue (AT) is distributed throughout the body in different depots. There are two distinct types with specific functions: the white adipose tissue is used as an energetic reservoir and stores the lipids whereas the brown adipose tissue allows the thermogenesis. By its functionalities and its endocrinal capacity, the AT ensures the energetic homeostasis maintenance. Severe metabolic disorders result from an excess found during obesity or a remodelling in the lipodystrophies. Some of them have a genetic origin, the others are induced by drugs such as the HIV-protease inhibitors (PI) administered in the antiretroviral therapy against HIV. The adipose progenitor (AP) pool present in each depot is necessary for the maintenance of this tissue because it allows to renew the adipocyte stock. We characterized and identified new genes involved in the autocrine/paracrine Activin A loop which is responsible for AP pool self-renewal of whom is IER3. Its expression increases in obese patients and decreases under PI treatment. The modelling of the different depots shows that PI inhibit preferentially PA self-renewal or adipose differentiation depending on their localisation. Thus, lipodystrophies induced by antiretroviral therapy would have multifactorial causes. Finally, our results reveal PI dramatically and selectively reduce the brown adipocyte production. These effects should be considered in the context of inappropriate brown adipose tissue development in order to correct metabolic disorders associated to some pathologies.Le tissu adipeux (TA) est réparti dans tout le corps en différents dépôts. Il existe deux types distincts aux fonctions biens spécifiques : le tissu adipeux blanc sert de réservoir énergétique et stocke les lipides et le tissu adipeux brun permet la thermogénèse. Par ses fonctionnalités et son pouvoir endocrine, le TA assure le maintien de l’homéostasie énergétique. De graves désordres métaboliques résultent d’une surabondance retrouvée au cours de l’obésité ou lors d’un remodelage dans les lipodystrophies. Certaines ont une origine génétique, d’autres sont induites par des médicaments comme les inhibiteurs de la protéase (IP) du VIH administrés dans la thérapie antirétrovirale. Le pool de progéniteur adipeux (PA) présent dans chaque dépôt est essentiel au maintien de ce tissu car il permet de renouveler le stock d’adipocytes. Nous avons caractérisé et identifié de nouveaux gènes impliqués dans la boucle autocrine/paracrine de l’activineA qui est responsable de l’auto-renouvellement du pool de PA dont IER3. Son expression augmente chez les patients obèses et diminue sous traitement par les IP. La modélisation des différents dépôts montre que les IP inhibent préférentiellement l’auto-renouvellement ou la différenciation adipocytaire des PA en fonction de leur localisation. Les lipodystrophies induites par la thérapie antirétrovirale auraient des causes multifactorielles. Enfin, nos résultats révèlent que les IP diminuent drastiquement et sélectivement la production d’adipocytes bruns. Ces effets doivent être considérés dans un contexte de développement inopportun du tissu adipeux brun afin de corriger des désordres métaboliques associés à certaines pathologies

Study of the heterogeneous effects of the HAART therapy on the adipose tissue : importance of the depots origins, modelling and molecular mechanism

Le tissu adipeux (TA) est réparti dans tout le corps en différents dépôts. Il existe deux types distincts aux fonctions biens spécifiques : le tissu adipeux blanc sert de réservoir énergétique et stocke les lipides et le tissu adipeux brun permet la thermogénèse. Par ses fonctionnalités et son pouvoir endocrine, le TA assure le maintien de l’homéostasie énergétique. De graves désordres métaboliques résultent d’une surabondance retrouvée au cours de l’obésité ou lors d’un remodelage dans les lipodystrophies. Certaines ont une origine génétique, d’autres sont induites par des médicaments comme les inhibiteurs de la protéase (IP) du VIH administrés dans la thérapie antirétrovirale. Le pool de progéniteur adipeux (PA) présent dans chaque dépôt est essentiel au maintien de ce tissu car il permet de renouveler le stock d’adipocytes. Nous avons caractérisé et identifié de nouveaux gènes impliqués dans la boucle autocrine/paracrine de l’activineA qui est responsable de l’auto-renouvellement du pool de PA dont IER3. Son expression augmente chez les patients obèses et diminue sous traitement par les IP. La modélisation des différents dépôts montre que les IP inhibent préférentiellement l’auto-renouvellement ou la différenciation adipocytaire des PA en fonction de leur localisation. Les lipodystrophies induites par la thérapie antirétrovirale auraient des causes multifactorielles. Enfin, nos résultats révèlent que les IP diminuent drastiquement et sélectivement la production d’adipocytes bruns. Ces effets doivent être considérés dans un contexte de développement inopportun du tissu adipeux brun afin de corriger des désordres métaboliques associés à certaines pathologies.The adipose tissue (AT) is distributed throughout the body in different depots. There are two distinct types with specific functions: the white adipose tissue is used as an energetic reservoir and stores the lipids whereas the brown adipose tissue allows the thermogenesis. By its functionalities and its endocrinal capacity, the AT ensures the energetic homeostasis maintenance. Severe metabolic disorders result from an excess found during obesity or a remodelling in the lipodystrophies. Some of them have a genetic origin, the others are induced by drugs such as the HIV-protease inhibitors (PI) administered in the antiretroviral therapy against HIV. The adipose progenitor (AP) pool present in each depot is necessary for the maintenance of this tissue because it allows to renew the adipocyte stock. We characterized and identified new genes involved in the autocrine/paracrine Activin A loop which is responsible for AP pool self-renewal of whom is IER3. Its expression increases in obese patients and decreases under PI treatment. The modelling of the different depots shows that PI inhibit preferentially PA self-renewal or adipose differentiation depending on their localisation. Thus, lipodystrophies induced by antiretroviral therapy would have multifactorial causes. Finally, our results reveal PI dramatically and selectively reduce the brown adipocyte production. These effects should be considered in the context of inappropriate brown adipose tissue development in order to correct metabolic disorders associated to some pathologies

EMULSION ADSORBEE SECHE (EAS) (ETUDE DE L'INFLUENCE DE L'UTILISATION D'UN ADSORBANT UNIQUE ET D'UNE NOUVELLE PHASE GRASSE SUR LA CINETIQUE DE LIBERATION D'UN PRINCIPE ACTIF HYDROSOLUBLE)

LYON1-BU Santé (693882101) / SudocSudocFranceF

Assessment of surgical site infection (SSI) diagnosis for 40 vignettes (20 cardiac surgery cases and 20 gastrointestinal surgery cases) developed based on real patients in three French university hospitals.

*<p>Number of vignettes scored (for intraspecialty 20 vignettes were scored twice and for interspecialty 34 vignettes were scored 7 times).</p>**<p>missing values due a computer assignment glitch.</p