211 research outputs found
HARMONIA: strategy of an integrated resilience assessment platform (IRAP) with available tools and geospatial services
The huge amount of the available data nowadays has raised some major challenges which are related to the storage, fusion, structure, streaming and processing of these data. In this paper, we present the development of a holistic framework, entitled HARMONIA, that encompasses State-of-The-Art solutions for the emerging issues related to Climate Change, natural and/or man-made hazards and urban/peri-urban risks. The Horizon 2020 HARMONIA project is developing an Integrated Resilience Assessment Platform (IRAP) which plans to provide targeted services for different groups of end-users. In particular, it will actively support urban decision-makers in strategic decisions and planning and citizens in facing daily effects and risks of Climate Change. Additionally, the platform will be a place to interconnect cities which end up facing similar Climate Change effects. HARMONIA IRAP leverages cuttingedge technologies (i.e., explainable Artificial Intelligence, Data Mining, multi-criteria analysis, dynamic programming) and services (ie., Virtual Machines, Containers) in order to provide solutions considering the complexity and diversity of extreme earth and non-earth data. In addition, this platform includes a Decision Support System providing early-warning feedback and recommendations to the end-users. In this way the HARMONIA IRAP design tends to address these challenges by offering the corresponding dynamic, scalable and robust mechanisms with the aim to provide useful integrated tools for the related users. Datacubes architecture, which is a major part of the IRAP, offers the opportunity to investigate more sophisticated correlations among the data and provide a more tangible representation of the extracted information
Pour une approche holistique des conditions de vie des populations du passé
International audienceDivers facteurs dâinĂ©galitĂ©, tels que le genre, la position sociale, la profession, ou l'origine gĂ©ographique, interagissent et influencent sur les conditions de vie des populations (approche intersectionnelle). Sây ajoutent des facteurs environnementaux, comme les famines, les guerres ou des problĂšmes climatiques, qui aggravent les inĂ©galitĂ©s sociales. La plupart des Ă©tudes comparatives portant sur lâĂ©tat sanitaire se font Ă partir des groupes dĂ©jĂ constituĂ©s (femme/homme, classe dâĂąge, site, pĂ©riode ou composition du mobilier funĂ©raire) (Polet, 2016 ; Scott & Hoppa, 2018 ; Ubelaker & Pap, 2009 ; Vercellotti et al., 2011). Elles supposent par lĂ -mĂȘme que ces groupes sont homogĂšnes, alors quâils sont composĂ©s dâindividus ayant vĂ©cu des expĂ©riences diffĂ©rentes.Pour contourner ce biais, nous proposons dâutiliser des mĂ©thodes statistiques qui permettent dâagrĂ©ger les individus prĂ©sentant des conditions de vie similaires (clustering). Pour cette analyse, nous considĂ©rons les variables suivantes : cribra orbitalia, hyperostose poreuse de la voĂ»te crĂąnienne, hypoplasie linĂ©aire de l'email dentaire et petite stature. La collection objet de cette analyse, les Capucins de FerriĂšres (Martigues, Bouches-du-RhĂŽne, 1720-21), prĂ©sente quelques avantages : elle est composĂ©e exclusivement des victimes de lâĂ©pidĂ©mie de peste dite « de Marseille », leur dĂ©cĂšs est survenu dans un temps trĂšs bref (quelques mois), et tous ces individus ont vĂ©cu ensemble, selon les mĂȘmes normes sociales et les mĂȘmes contraintes environnementales.Les rĂ©sultats obtenus montrent que les diffĂ©rences des conditions de vie sont moins en fonction du sexe ou de lâĂąge, que des facteurs socio-environnementaux et des caractĂ©ristiques socio-biologiques des individus qui leur confĂšrent une vulnĂ©rabilitĂ© (frailty) plus ou moins grande.Cette Ă©tude dĂ©montre quâune approche genrĂ©e des conditions de vie doit prendre en compte la diversitĂ© des comportements et des vĂ©cus des individus, et quâune analyse binaire (hommes versus femmes) rend impossible lâobservation de toutes ces nuances
OCT2013, an ischaemia-activated antiarrhythmic prodrug, devoid of the systemic side effects of lidocaine
Background and Purpose
Sudden cardiac death (SCD) caused by acute myocardial ischaemia and ventricular fibrillation (VF) is an unmet therapeutic need. Lidocaine suppresses ischaemia-induced VF, but its utility is limited by side effects and a narrow therapeutic index. Here, we characterise OCT2013, a putative ischaemia-activated prodrug of lidocaine.
Experimental Approach
The rat Langendorff-perfused isolated heart, anaesthetised rat and rat ventricular myocyte preparations were utilised in a series of blinded and randomised studies to investigate the antiarrhythmic effectiveness, adverse effects and mechanism of action of OCT2013, compared with lidocaine.
Key Results
In isolated hearts, OCT2013 and lidocaine prevented ischaemia-induced VF equi-effectively, but OCT2013 did not share lidocaine's adverse effects (PR widening, bradycardia and negative inotropy). In anaesthetised rats, i.v. OCT2013 and lidocaine suppressed VF and increased survival equi-effectively; OCT2013 had no effect on cardiac output even at 64âmg·kgâ»Âč i.v., whereas lidocaine reduced it even at 1âmg·kgâ»Âč. In adult rat ventricular myocytes, OCT2013 had no effect on CaÂČâș handling, whereas lidocaine impaired it. In paced isolated hearts, lidocaine caused rate-dependent conduction slowing and block, whereas OCT2013 was inactive. However, during regional ischaemia, OCT2013 and lidocaine equi-effectively hastened conduction block. Chromatography and MS analysis revealed that OCT2013, detectable in normoxic OCT2013-perfused hearts, became undetectable during global ischaemia, with lidocaine becoming detectable.
Conclusions and Implications
OCT2013 is inactive but is bio-reduced locally in ischaemic myocardium to lidocaine, acting as an ischaemia-activated and ischaemia-selective antiarrhythmic prodrug with a large therapeutic index, mimicking lidocaine's benefit without adversity
The contrasted phytoplankton dynamics across a frontal system in the southwestern Mediterranean Sea
Numerical simulations have shown that finescale structures such as fronts are often suitable places for the generation of vertical velocities,
transporting subsurface nutrients to the euphotic zone and thus modulating phytoplankton abundance and community structure. In these structures,
direct in situ estimations of the phytoplankton growth rates are rare; although difficult to obtain, they provide precious information on the
ecosystem functioning. Here, we consider the case of a front separating two water masses characterized by several phytoplankton groups with
different abundances in the southwestern Mediterranean Sea. In order to estimate possible differences in growth rates, we measured the
phytoplankton diurnal cycle in these two water masses as identified by an adaptive and Lagrangian sampling strategy. A size-structured population
model was then applied to these data to estimate the growth and loss rates for each phytoplankton group identified by flow cytometry, showing that
these two population parameters are significantly different on the two sides of the front and consistent with the relative abundances. Our results
introduce a general method for estimating growth rates at frontal systems, paving the way for in situ exploration of finescale biophysical
interactions.</p
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Effects of orange juice formulation on prebiotic functionality using an in vitro colonic model sytem
A three-stage continuous fermentative colonic model system was used to monitor in vitro the effect of different orange juice formulations on prebiotic activity. Three different juices with and without Bimuno, a GOS mixture containing galactooligosaccharides (B-GOS) were assessed in terms of their ability to induce a bifidogenic microbiota. The recipe development was based on incorporating 2.75g B-GOS into a 250 ml serving of juice (65°Brix of concentrate juice). Alongside the production of B-GOS juice, a control juice - orange juice without any additional Bimuno and a positive control juice, containing all the components of Bimuno (glucose, galactose and lactose) in the same relative proportions with the exception of B-GOS were developed. Ion Exchange Chromotography analysis was used to test the maintenance of bimuno components after the production process. Data showed that sterilisation had no significant effect on concentration of B-GOS and simple sugars. The three juice formulations were digested under conditions resembling the gastric and small intestinal environments. Main bacterial groups of the faecal microbiota were evaluated throughout the colonic model study using 16S rRNA-based fluorescence in situ hybridization (FISH). Potential effects of supplementation of the juices on microbial metabolism were studied measuring short chain fatty acids (SCFAs) using gas chromatography. Furthermore, B-GOS juices showed positive modulations of the microbiota composition and metabolic activity. In particular, numbers of faecal bifidobacteria and lactobacilli were significantly higher when B-GOS juice was fermented compared to controls. Furthermore, fermentation of B-GOS juice resulted in an increase in Roseburia subcluster and concomitantly increased butyrate production, which is of potential benefit to the host. In conclusion, this study has shown B-GOS within orange juice can have a beneficial effect on the fecal microbiota
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CLSM method for the dynamic observation of pH change within polymer matrices for oral delivery
If acid-sensitive drugs or cells are administered orally, there is often a reduction in efficacy associated with gastric passage. Formulation into a polymer matrix is a potential method to improve their stability. The visualization of pH within these materials may help better understand the action of these polymer systems and allow comparison of different formulations. We herein describe the development of a novel confocal laser-scanning microscopy (CLSM) method for visualizing pH changes within polymer matrices and demonstrate its applicability to an enteric formulation based on chitosan-coated alginate gels. The system in question is first shown to protect an acid-sensitive bacterial strain to low pH, before being studied by our technique. Prior to this study, it has been claimed that protection by these materials is a result of buffering, but this has not been demonstrated. The visualization of pH within these matrices during exposure to a pH 2.0 simulated gastric solution showed an encroachment of acid from the periphery of the capsule, and a persistence of pHs above 2.0 within the matrix. This implies that the protective effect of the alginate-chitosan matrices is most likely due to a combination of buffering of acid as it enters the polymer matrix and the slowing of acid penetration
Development of a pro-arrhythmic ex vivo intact human and porcine model: cardiac electrophysiological changes associated with cellular uncoupling
We describe a human and large animal Langendorff experimental apparatus for live electrophysiological studies and measure the electrophysiological changes due to gap junction uncoupling in human and porcine hearts. The resultant ex vivo intact human and porcine model can bridge the translational gap between smaller simple laboratory models and clinical research. In particular, electrophysiological models would benefit from the greater myocardial mass of a large heart due to its effects on far-field signal, electrode contact issues and motion artefacts, consequently more closely mimicking the clinical setting. Porcine (nâ=â9) and human (nâ=â4) donor hearts were perfused on a custom-designed Langendorff apparatus. Epicardial electrograms were collected at 16 sites across the left atrium and left ventricle. A total of 1 mM of carbenoxolone was administered at 5 ml/min to induce cellular uncoupling, and then recordings were repeated at the same sites. Changes in electrogram characteristics were analysed. We demonstrate the viability of a controlled ex vivo model of intact porcine and human hearts for electrophysiology with pharmacological modulation. Carbenoxolone reduces cellular coupling and changes contact electrogram features. The time from stimulus artefact to (-dV/dt)max increased between baseline and carbenoxolone (47.9â±â4.1â67.2â±â2.7 ms) indicating conduction slowing. The features with the largest percentage change between baseline and carbenoxolone were fractionation +â185.3%, endpoint amplitude ââ106.9%, S-endpoint gradient +â54.9%, S point ââ39.4%, RS ratio +â38.6% and (-dV/dt)max ââ20.9%. The physiological relevance of this methodological tool is that it provides a model to further investigate pharmacologically induced pro-arrhythmic substrates
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