Molecular Biomarkers of Neovascular Age-Related Macular Degeneration With Incomplete Response to Anti-Vascular Endothelial Growth Factor Treatment.

The standard treatment for neovascular age-related macular degeneration (nAMD) consists of intravitreal anti-vascular endothelial growth factors (VEGF). However, for some patients, even maximal anti-VEGF treatment does not entirely suppress exudative activity. The goal of this study was to identify molecular biomarkers in nAMD with incomplete response to anti-VEGF treatment. Aqueous humor (AH) samples were collected from three groups of patients: 17 patients with nAMD responding incompletely to anti-VEGF (18 eyes), 17 patients affected by nAMD with normal treatment response (21 eyes), and 16 control patients without any retinopathy (16 eyes). Proteomic and multiplex analyses were performed on these samples. Proteomic analyses showed that nAMD patients with incomplete anti-VEGF response displayed an increased inflammatory response, complement activation, cytolysis, protein-lipid complex, and vasculature development pathways. Multiplex analyses revealed a significant increase of soluble vascular cell adhesion molecule-1 (sVCAM-1) [ p = 0.001], interleukin-6 (IL-6) [ p = 0.009], bioactive interleukin-12 (IL-12p40) [ p = 0.03], plasminogen activator inhibitor type 1 (PAI-1) [ p = 0.004], and hepatocyte growth factor (HGF) [ p = 0.004] levels in incomplete responders in comparison to normal responders. Interestingly, the same biomarkers showed a high intercorrelation with r2 values between 0.58 and 0.94. In addition, we confirmed by AlphaLISA the increase of sVCAM-1 [ p < 0.0001] and IL-6 [ p = 0.043] in the incomplete responder group. Incomplete responders in nAMD are associated with activated angiogenic and inflammatory pathways. The residual exudative activity of nAMD despite maximal anti-VEGF treatment may be related to both angiogenic and inflammatory responses requiring specific adjuvant therapy. Data are available via ProteomeXchange with identifier PXD02247

Arthrite juvénile idiopathique et agents biologiques : quels sont les risques de ces traitements

Résumé Contexte L'arthrite juvénile idiopathique (AJI) est la maladie rhumatismale la plus fréquente chez l'enfant qui a longtemps été traitée uniquement par des antiinflammatoires non stéroïdiens (AINS) et des traitements de fond non biologique tels que le méthotrexate ou la sulfazalazine. Le développement et la mise sur le marché de plusieurs agents biologiques (AB) ont révolutionné la prise en charge des AJI. Actuellement, après plus de 15 ans d’expérience avec les AB, de nombreux Centres de rhumatologie pédiatrique, dont le Centre hospitalier universitaire vaudois à Lausanne (CHUV) et l’Hôpital Femme – Mère – Enfant (HFME) à Lyon s’intéressent à la tolérance et aux effets indésirables (EI) de ces traitements biologiques. Objectifs • Identifier les facteurs influençant le délai entre le diagnostic d'AJI et l'introduction d'un traitement par agent biologique. • Définir les effets indésirables des traitements par agents biologiques enregistrés dans les Centres de consultation de rhumatologie pédiatrique de l’HFME à Lyon et du CHUV à Lausanne. Méthode Les données utilisées sont issues de la JIR cohorte. Cette dernière est une base de données regroupant des patients atteints de maladies inflammatoires rhumatismales de plusieurs pays. Deux extractions de données ont été utilisées pour ce travail. La principale extraction inclut tous les patients atteints d'une AJI et traités par au minimum un AB des Centres de consultation de rhumatologie pédiatrique du CHUV et de l’HFME depuis la création de la JIR jusqu'en 2015. Cette extraction est utilisée afin de : • Documenter les EI reportés en fonction de la durée d’exposition à l’AB, du lien de causalité entre l’EI et l’AB, de la nature et l’intensité des EI en étudiant séparément le CHUV et l’HFME. • D’évaluer le délai entre le diagnostic d’AJI et l’introduction du 1er AB, en fonction du type d’AJI et de l’année où le diagnostic a été posé en étudiant conjointement les Centres du CHUV et de l’HFME. Pour ce faire, nous avons formé 4 périodes en corrélation avec le développement et la mise sur le marché des AB. La deuxième extraction utilisée inclut tous les patients avec un diagnostic d’AJI suivis à la Consultation de rhumatologie pédiatrique du CHUV entre le 01.01.2015 et le 01.01.2016. Cette 2ème base de données sera utilisée uniquement afin de calculer la répartition des différents types d’AJI. 4 Les données utilisées ont été récoltées à partir de dossiers médicaux de patients de façon rétrospective. Résultats Au total, 232 patients dont 103 et 129 patients au CHUV et à Lyon respectivement ont été inclus dans l’étude. La durée moyenne de suivi des patients dans les deux Centres est de 16 mois. Le délai d’utilisation des AB est plus court au fil du temps pour tous les types d’AJI. Durant la période de 2010 à 2014 les délais sont les suivants : enthésite en rapport avec une arthrite (320 jours), oligoarthrite extensive (223 jours), oligoarthrite persistante (310 jours), polyarthrite FR (facteur rhumatoïde) négatif (277 jours), polyarthrite FR positif (125 jours), arthrite psoriasique (527 jours), arthrite systémique (134 jours). Le nombre total d’EI reportés à l’HFME est de 35 dont 21 graves et 74 au CHUV dont 7 sont graves. Les infections représentent 51% et 65% des EI non graves au CHUV et à l’HFME respectivement. Concernant l’intensité des EI au CHUV : faible (68%), modérée (21%), nulle (4%), sévère (4%) et très sévère (3%). À l’HFME, l’intensité des EI se répartit comme suit : sévère (37%), faible (23%), modéré (21%), très sévère (10%) et nulle (3%). L’incidence des EI pour un patient-année au CHUV sont les suivantes : tocilizumab 0.63, canakinumab 0.24, adalimumab 0.24, infliximab 0.18, anakinra 0.17, etanercept 0.12, abatacept 0.05. A l’HFME, l’incidence des EI par patient-année pour chaque AB sont les suivantes : canakinumab 0.52, tocilizumab 0.28, infliximab 0.08, adalimumab 0.05, anakinra 0.05, etanercept 0.03, et aucun EI avec l’abatacept. Le lien de causalité entre l’EI et l’AB est possible ou peu probable dans 70% des cas au CHUV et 73% à l’HFME. Conclusion Le délai d’introduction des AB est plus court au fil des années d’une part en raison du recul et des évidences d’efficacité sur le pronostic fonctionnel à long terme des patients atteints d’AJI, et d’autre part de l’arrivée sur le marché de plusieurs nouveaux AB. L’incidence des EI reportée est 2 fois plus importante au CHUV qu’à l’HFME, ceci pouvant être expliqué, en partie, par une utilisation de la JIR cohorte différente

Fully-automated atrophy segmentation in dry age-related macular degeneration in optical coherence tomography.

Age-related macular degeneration (AMD) is a progressive retinal disease, causing vision loss. A more detailed characterization of its atrophic form became possible thanks to the introduction of Optical Coherence Tomography (OCT). However, manual atrophy quantification in 3D retinal scans is a tedious task and prevents taking full advantage of the accurate retina depiction. In this study we developed a fully automated algorithm segmenting Retinal Pigment Epithelial and Outer Retinal Atrophy (RORA) in dry AMD on macular OCT. 62 SD-OCT scans from eyes with atrophic AMD (57 patients) were collected and split into train and test sets. The training set was used to develop a Convolutional Neural Network (CNN). The performance of the algorithm was established by cross validation and comparison to the test set with ground-truth annotated by two graders. Additionally, the effect of using retinal layer segmentation during training was investigated. The algorithm achieved mean Dice scores of 0.881 and 0.844, sensitivity of 0.850 and 0.915 and precision of 0.928 and 0.799 in comparison with Expert 1 and Expert 2, respectively. Using retinal layer segmentation improved the model performance. The proposed model identified RORA with performance matching human experts. It has a potential to rapidly identify atrophy with high consistency

Chaotic Transport in Three-Dimensional Reactors Operating in Open Flows for Continuous Biodiesel Production from Rapeseed Oil: Numerical and Experimental Comparative Study

International audienceThe present study aims to investigate a suitable biodiesel production process. Two reactors called serpentin-3D (S-3D) and New-Serpentin-3D (NS-3D), operating in continuous mode, are used to produce biodiesel. The thermal and dynamic characterizations of both reactors are numerically examined for several Reynolds number values. In addition, the conversion of the rapeseed oil to biodiesel is experimentally performed by the transesterification reaction. Numerical results showed a better quality of thermal mixing using NS-3D geometry where the degree of mixing is close to 1 for miscible and immiscible fluids. The experimental study illustrates that the conversion rate, using the reactor based on NS-3D geometry, is about 99%. Moreover, the properties of the biodiesel are in compliance with the required standard EN14214 (MG = 0.7 20 % m/m, DG = TG = 0.2 % m/m). Therefore, the NS-3D geometry could present a better alternative for the continuous production of biodiesel

Personalized Atrophy Risk Mapping in Age-Related Macular Degeneration.

To develop and validate an automatic retinal pigment epithelial and outer retinal atrophy (RORA) progression prediction model for nonexudative age-related macular degeneration (AMD) cases in optical coherence tomography (OCT) scans. Longitudinal OCT data from 129 eyes/119 patients with RORA was collected and separated into training and testing groups. RORA was automatically segmented in all scans and additionally manually annotated in the test scans. OCT-based features such as layers thicknesses, mean reflectivity, and a drusen height map served as an input to the deep neural network. Based on the baseline OCT scan or the previous visit OCT, en face RORA predictions were calculated for future patient visits. The performance was quantified over time with the means of Dice scores and square root area errors. The average Dice score for segmentations at baseline was 0.85. When predicting progression from baseline OCTs, the Dice scores ranged from 0.73 to 0.80 for total RORA area and from 0.46 to 0.72 for RORA growth region. The square root area error ranged from 0.13 mm to 0.33 mm. By providing continuous time output, the model enabled creation of a patient-specific atrophy risk map. We developed a machine learning method for RORA progression prediction, which provides continuous-time output. It was used to compute atrophy risk maps, which indicate time-to-RORA-conversion, a novel and clinically relevant way of representing disease progression. Application of recent advances in artificial intelligence to predict patient-specific progression of atrophic AMD

Near-Infrared Lasing in Four-Zigzag Edged Nanographenes by 1D versus 2D Electronic π-Conjugation

The search of compounds emitting in the near-infrared (NIR) has been accelerated owing to their use in biomedical and telecommunications applications. In this regard, nanographenes (NGs) are attractive materials adequate for integration with other technologies, which have recently demonstrated amplified spontaneous emission (ASE) and lasing across the visible spectrum. Here, the optical and ASE properties of four-zigzag edged NGs of the [m,n]peri-acenoacene family are reported, whose size is increased through conjugation extension by varying n (from 3 to 5) while keeping m = 2. Results show that such 1D conjugation extension method is more efficient in terms of shifting the photoluminescence (PL) to the infrared (PL at 710 nm in the larger compound, PP-Ar) than through 2D conjugation extension as in previously reported NGs (PL at 676 nm with the largest compound FZ3, with n = 3 and m = 4). Additionally, PP-Ar shows dual-ASE (at 726 and 787 nm), whose origin is elucidated through Raman and transient absorption spectroscopies. These compounds’ potential for red and NIR lasing is demonstrated through the fabrication of distributed feedback lasers with top-layer resonators. This study paves the way towards the development of stable low-cost all-plastic NIR lasers

Numerical study of heat transfer from a wall incorporating a phase change material

A numerical study of the thermal behavior of walls made up of construction materials used in Algeria and walls containing a phase change materials is presented. The model, based on the enthalpy formulation, is described by an equation of heat transfer. This equation is solved by an implicit method of finite differences and algorithm of Thomas. We analyzed the influence of the wall’s thickness and its composition on the evolution during the time of the temperature of the inside face of thewall