Characterization of particle distribution in a black carbon-filled elastomer via nanoindentation

A new method to characterize the distribution of hard particles dispersed into a soft elastomer matrix is developed using nanoindentation. It is based on the measurement of the contact stiffness from the continuous stiffness measurement module (CSM). Theoretically, for a homogeneous material, the contact stiffness is directly proportional to the contact depth. However, when indenting a carbon black-filled fluoroelastomer (FKM) this relation is no longer valid and abnormal contact stiffness evolutions are measured (jumps). The tip-particle model developed in this work is simply based on the hypothesis that all the deformation is supported by the elastomer matrix and that black carbon aggregates play the role of hard extensions of the diamond tip, when touching it (grey particles 1,2 & 3, Fig. 1a). As a result, each abnormal variation of contact stiffness is related to a new aggregate in contact with the tip. By knowing the stiffness amplitude of a jump and the relative stiffness where it appeared , the equivalent projected area of a particle can be calculated (Fig. 1d). From this calculation, one can extract the distribution of particles surface density from nanoindentation measurements only. Ten experimental indentation tests have been performed and the results are displayed in Fig. 1e. The distribution of particles surface density extracted from experiments is compared to measurements performed by image analysis of a 100 nm thick slide of the material observed by Transmission Electron Microscopy (TEM) (black squares). Furthermore, the tip-particle model is simulated numerically on the same image analysis (down pointing triangles). The results obtained from this model are in excellent agreement with the TEM observation which is really promising. Indeed, this model is an alternative to microscopy characterization which can be complicated to implement. Please click Additional Files below to see the full abstract

Brief Communication External globus pallidus stimulation modulates brain connectivity in Huntington's disease

Positron emission tomography with O-15-labeled water was used to study at rest the neurophysiological effects of bilateral external globus pallidus (GPe) deep brain stimulation in patients with Huntington's disease (HD). Five patients were compared with a control group in the on and off states of the stimulator. External globus pallidus stimulation decreased neuronal activity and modulated cerebral connectivity within the basal ganglia-thalamocortical circuitry, the sensorimotor, and the default-mode networks. These data indicate that GPe stimulation modulates functional integration in HD patients in accordance with the basal ganglia-thalamocortical circuit model

Caractérisation des effets indésirables en relation avec le système nerveux central des céphalosporines : analyse des cas graves enregistrés dans la Base Nationale Française de Pharmacovigilance

Introduction : les céphalosporines peuvent induire des effets indésirables relatifs au SNC, sous-suspectés et peu caractérisés. Notre objectif a été de les caractériser plus finement.Méthode : Analyse des cas graves rapportés dans la Base Nationale de Pharmacovigilance (1987- 2017).Résultats : 511 cas graves, 31 décès. Les patients étaient majoritairement des hommes (52,5%), d’âge moyen 67,1 ans, la clairance à la créatinine moyenne était de 32,9 ml/min. Les molécules les plus impliquées : céfépime (33,1%), ceftriaxone (29,7%), ceftazidime (19,6%), céfotaxime (9%) et céfazoline (2,9%), pour la plupart administrées par voie IV (87,3%). Des antécédents de maladies du SNC ont été rapportés pour 25% des patients. Les patients ont présenté : encéphalopathie (30,3%), état confusionnel (19,4%), convulsion (15,1%), myoclonie (9,4%), épilepsie (9,2%), coma (6,3%) et hallucination (4,3%). Le délai moyen d’apparition était de 7,7 jours et la durée en moyenne de 6 jours. Les dosages plasmatiques en céphalosporine ont été rapportés pour 153 patients (29,9%) et 107 étaient au-dessus des valeurs de référence, dont 62 (57,9%) avaient également une altération de la fonction rénale. La réalisation d’EEG a été rapportée pour 38,2% des patients (n=195), il était anormal dans 81% des cas (n=158).Conclusion : cette étude caractérise l’effet off-target des céphalosporines relatifs au SNC. La ceftriaxone est impliquée dans un nombre important de cas rapportés, aux côtés du céfépime. Cette nouvelle information est capitale pour les professionnels de santé. En effet, aucune communication concernant la ceftriaxone et ce type d’effet indésirable n’a encore été émise par les autorités sanitaires

Adverse drug reaction monitoring: Doing it the French way – Act II

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Patients’ organizations in rare diseases and involvement in drug information: Illustrations with LMC France, the French Association of Chronic Myeloid leukemia

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Angiotensin-converting enzyme and dipeptidyl peptidase-4 inhibitor–induced angioedema: A disproportionality analysis of the WHO pharmacovigilance database

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Pharmacovigilance and Drug-Induced Rare Diseases: Strengths of the French Network of Regional Pharmacovigilance Centres

International audienceThe French-style organization in the field of rare diseases allows a close contact between reference centres and regional pharmacovigilance centres thanks to their implementation within the French university hospital. This collaboration leads to highlight more and more drug-induced rare diseases. Through several historical examples (eosinophilia-myalgia syndrome due to L-tryptophan, type 1 narcolepsy with H1N1 pandemic influenza vaccine, capillary leak syndrome, acquired von Willebrand syndrome), it remains clear that pharmacovigilance is the cornerstone of the alert system. Clinicians from the rare disease reference centres can easily report adverse drug reactions (ADRs) to pharmacologists from their regional pharmacovigilance centre. Through experience, collaboration between countries, large database, and sometimes pharmacoepidemiological studies, an alert can then be raised. This collaboration underlines also similarities between the two disciplines, through the frequency of ADRs and diseases, the difficulty of the diagnosis in front of scarce data, and through the unusual worsening symptoms. Patients and associations of patients play also a proactive role as research partners at different steps, to quantify and qualify symptoms and ADRs, and also to develop orphan drugs. These several collaborations are a precious tool to improve patients' outcomes. These close contacts between the different actors are important to make earlier diagnosis of rare diseases and severe ADRs. Rare disease does not have to mean overlooked diseases

Some cautions when applying nanoindentation tests on a fluoroelastomer: Experimental researches and application

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Study of the Fatigue of an Elastomer by Using Instrumented Indentation

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Contributions on instrumented indentation of elastomers : practical case : Influence of thermal aging on local properties

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