Rôles de K-RAS et de ERCC1 dans le traitement des carcinomes épidermoïdes avancés de la tête et du cou traités par chimioradiothérapie concomitante

Introduction: Les mutations du gène RAS sont présentes dans plusieurs types de cancers et ont une influence sur la réponse à la chimiothérapie. Excision repair cross- complementation group 1 (ERCC1) est un gène impliqué dans la réparation de l’acide désoxyribonucléique (ADN), et son polymorphisme au codon 118 est également associé à la réponse au traitement. Le peu d’études pronostiques portant sur ces deux gènes dans les cancers oto-rhino-laryngologiques (ORL) ne permet de tirer des conclusions claires. Objectifs: Déterminer l’influence des mutations de K-RAS codons 12 et 13 et du polymorphisme de ERCC1 codon 118 dans le traitement des cancers épidermoïdes avancés tête et cou traités par chimioradiothérapie concomitante à base de sels de platine. Méthode: Extraction de l’ADN provenant de spécimens de biopsie de patients traités par chimioradiothérapie concomitante pour des cancers avancés tête et cou, et ayant un suivi prospectif d’au moins deux ans. Identification des mutations de K-RAS codons 12 et 13 et du polymorphisme de ERCC1 au codon 118 dans les spécimens et corrélation de ces marqueurs avec la réponse au traitement. Résultats: Les mutations de K-RAS codon 12 sont associées à un moins bon contrôle loco-régional par rapport aux tumeurs ne démontrant pas la mutation (32% vs 83% p=0.03), sans affecter pour autant la survie globale. Aucune mutation de K-RAS codon 13 n’a été identifiée. Les différents polymorphismes de ERCC1 n’ont pas eu d’impact sur la réponse au traitement. Conclusion: Les mutations de K-RAS codons 12 et 13 et le polymorphisme de ERCC1 au codon 118 ne semblent pas mettre en évidence les patients qui bénéficieraient d’une autre modalité thérapeutique.Background: RAS gene mutations have been shown to occur in certain malignancies and have an impact treatment response and overall prognosis. Excision repair cross- complementation group 1 (ERCC1) is a gene implicated in deoxyribonucleic acid (DNA) repair, whose polymorphism at codon 118 has been linked to treatment response. Studies of these two genes in head and neck oncology literature have shown inconsistent results. Objectives: Determine the influence of K-RAS mutations (codons 12 and 13) and the polymorphism of ERCC1 codon 118 in patients with locally advanced head and neck cancer treated with concomitant platinum-based chemoradiation therapy. Methods: DNA extraction from paraffin-embedded biopsy specimens of patients with advanced head and neck squamous cell carcinoma treated with concomitant chemoradiation and followed prospectively for at least two years. Identification of K- RAS mutations (codons 12 and 13) and ERCC1 codon 118 polymorphism in the extracted DNA. Correlation of these markers with treatment response. Results: K-RAS codon 12 mutations were associated with a worse locoregional control than tumors without any mutations (32% vs 83% p=0.03); however, mutational status did not influence overall survival. No K-RAS codon 13 mutation was identified in our specimens. The different ERCC1 polymorphisms did not have an impact on treatment response. Conclusion: K-RAS mutational status (codon 12 and 13) and ERCC1 codon 118 polymorphism does not seem to discriminate between patients for whom another treatment option should be sought in patients with locally advanced head and neck squamous cell carcinoma

Dating and localizing an invasion from post-introduction data and a coupled reaction-diffusion-absorption model

Invasion of new territories by alien organisms is of primary concern for environmental and health agencies and has been a core topic in mathematical modeling, in particular in the intents of reconstructing the past dynamics of the alien organisms and predicting their future spatial extents. Partial differential equations offer a rich and flexible modeling framework that has been applied to a large number of invasions. In this article, we are specifically interested in dating and localizing the introduction that led to an invasion using mathematical modeling, post-introduction data and an adequate statistical inference procedure. We adopt a mechanistic-statistical approach grounded on a coupled reaction-diffusion-absorption model representing the dynamics of an organism in an heterogeneous domain with respect to growth. Initial conditions (including the date and site of the introduction) and model parameters related to diffusion, reproduction and mortality are jointly estimated in the Bayesian framework by using an adaptive importance sampling algorithm. This framework is applied to the invasion of \textit{Xylella fastidiosa}, a phytopathogenic bacterium detected in South Corsica in 2015, France

Integral Formulations for the EEG Problem

The forward electro-encephalography (EEG) problem involves finding a potential V from the Poisson equation (V)=f, in which f represents electrical sources in the brain, and the conductivity of the head tissues. In the piecewise constant conductivity head model, this can be accomplished by the Boundary Element Method (BEM) using a suitable integral formulation. Most previous work is based on the same integral formulation, based on a double-lay- er potential. In this article we detail several alternative possibilities. We present a dual approach which involves a single-layer potential. Finally, we propose a symmetric formulation, which combines single and double-layer potentials, and which is new to the field of EEG, although it has been applied to other problems in electromagnetism. The three methods have been evaluated numerically using a semi-realistic geometry with known analytical solution, and the symmetric method achieves a significantly higher accuracy

Suicide inhibition of alpha-oxamine synthases:structures of the covalent adducts of 8-amino-7-oxononanoate synthase with trifluoroalanine

The suicide inhibition of the α-oxamine synthases by the substrate analog, L-trifluoroalanine was investigated. The inhibition resulted in the formation of a complex with loss of all three fluorine atoms. Decarboxylation and loss of fluoride occurred immediately after aldimine formation. The inherent flexibility could allow the difluorinated intermediate complex to adopt a suitable conformation. Decarboxylation in the normal mechanism occurs after formation of the ketoacid intermediate.link_to_subscribed_fulltex

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Efficacité et tolérance d'une dose de charge de morphine aux urgences (0,1 mg kg-1 +- titrations) (étude multicentrique prospective à propos de 354 patients)

Objectif : Evaluer la tolérance et le temps nécessaire pour obtenir une analgésie efficace (EN<3) après une dose de charge de morphine à 0.1 mg kg-1 +- titration dans un service d'urgences pour les douleurs sévères. Méthode : C est une étude multicentrique, descriptive, prospective. Après évaluation de la douleur par l'EN, la morphine est injectée à la dose de 0.1 mg kg-1 en IVL diluée pour les douleurs sévères en association au Perfalgan +- Kétoprofene en dehors des contre-indications. Après 5 minutes, des doses supplémentaires de 2 mg/5min sont injectées tant que l'EN 3. L'EN, la fréquence respiratoire (FR), la fréquence cardiaque (FC), la pression sanguine artérielle (PSA), l'échelle de sédation (ES) et les effets indésirables (EI) sont évalués avant l'administration de la morphine et toutes les 5 minutes. Résultats : 43% de femmes, 57% d'hommes. Age moyen : 46.97 +- 20.97 ans (15-97). 71% de douleurs post traumatiques. EN à l'arrivée: 7.43 +- 2.2. La dose de morphine nécessaire pour atteindre le seuil analgésique est de 0.129 +- 0.37 mg kg-1 . Ce seuil n'est obtenu qu'au bout de 30 minutes. Pas de différence significative en fonction du sexe, de l'âge, de motif de recours (traumatique ou médicochirurgicale). Les douleurs les plus sévères (EN 9-10) ont les besoins les plus élevées (0.15 mg kg-1).TOULOUSE3-BU Santé-Centrale (315552105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Computation of dynamic transmission error for gear transmission systems using modal decomposition and Fourier series

In this paper, a method for computing the dynamics of a geared system excited by its static transmission error is proposed. The method is based on the iterative spectral method (ISM) and on the harmonic balance method (HBM). It is shown that the dynamic transmission error (DTE) can be obtained in the frequency domain by solving a linear system of equations, which in turn allows the computation of the modal and physical coordinates of the system

Estimation of Secondary Phytoplankton Pigments From Satellite Observations Using Self‐Organizing Maps (SOMs)

International audienceThis study presents a method for estimating secondary phytoplankton pigments from satellite ocean color observations. We first compiled a large training data set composed of 12,000 samples; each sample is composed of 10 in situ phytoplankton high-performance liquid chromatography (HPLC)-measured pigment concentrations, GlobColour products of chlorophyll-a concentration, and remote sensing reflectance (Rrs()) data at different wavelengths, in addition to advanced very high resolution radiometer sea surface temperature measurements. The resulting data set regroups a large variety of encountered situations between 1997 and 2014. The nonlinear relationship between the in situ and satellite components was identified using a self-organizing map, which is a neural network classifier. As a major result, the self-organizing map enabled reliable estimations of the concentration of chlorophyll-a and of nine different pigments from satellite observations. A cross-validation procedure showed that the estimations were robust for all pigments (R-2>0.75 and an average root-mean-square error=0.016mg/m(3)). A consistent association of several phytoplankton pigments indicating phytoplankton group specific dynamic was shown at a global scale. We also showed the uncertainties for the estimation of each pigment