Intérêt de l'éthylglucuronide comme marqueur d'abus d'alcool, aspects analytiques, diagnostiques et médico-légaux

RESUMEUne consommation excessive et chronique d'alcool est associée à une augmentation significative de la morbidité et de la mortalité. L'identification de marqueurs biologiques fiables, permettant de mettre en évidence une consommation excessive et chronique, présente donc un intérêt certain pour prévenir les conséquences néfastes de l'abus d'alcool. L'approche couramment employée consiste à mesurer les marqueurs biologiques indirects dans le sang, tels que les marqueurs hépatiques dont l'augmentation peut résulter d'une consommation chronique et excessive d'alcool. Cependant, leur valeur diagnostique est souvent limitée par leur manque de sensibilité et/ou de spécificité et leur combinaison est généralement recommandée pour améliorer le diagnostic. A ce jour, il n'existe pas de marqueur biologique permettant le diagnostic fiable d'une consommation chronique et excessive d'alcool.L'objectif principal de cette thèse était d'évaluer la pertinence de l'éthylglucuronide (EtG), un métabolite direct de l'éthanol présentant la particularité d'être incorporé dans les cheveux, comme marqueur d'une consommation chronique et excessive d'alcool. Dans un premier temps, une revue de la littérature a permis de dresser un état des lieux de l'usage de l'EtG et d'identifier les axes de réflexion. L'EtG s'est révélé être un marqueur efficace pour identifier une consommation chronique et excessive d'alcool. Cependant, l'absence de seuil de positivité fiable et une méconnaissance des facteurs influençant l'incorporation de l'EtG dans les cheveux ont été mises en évidence. Afin d'investiguer ces différents points, deux études ont été conduites : (1) une étude chez le rat pour tenter de comprendre les facteurs influençant l'incorporation de l'EtG dans les cheveux et étudier la relation entre la quantité d'alcool administrée et la concentration d'EtG mesurée dans les cheveux; et (2) une étude clinique afin de déterminer les performances diagnostiques de l'EtG comme marqueur d'une consommation excessive et chronique d'alcool. Une méthode analytique sensible et sélective par chromatographic gazeuse couplée à la spectrométrie de masse en tandem a été développée et appliquée à l'analyse de l'EtG dans les cheveux.Le sang semblait jouer un rôle majeur dans l'incorporation de l'EtG dans les poils. Son incorporation n'était pas influencée par la pigmentation. La concentration d'EtG mesurée dans les poils de rats reflétait la dose d'éthanol administrée. De plus, la mesure de l'EtG dans les cheveux humains a démontré de très bonnes performances diagnostiques pour détecter une consommation excessive et chronique d'alcool. Les performances diagnostiques de l'EtG surpassaient celles des marqueurs hépatiques usuels seuls ou combinés. L'EtG n'était pas influencé par l'âge, le sexe ou l'indice de masse corporelle. Un seuil de positivité de 25 pg/mg permettait de détecter les consommateurs à usage nocif avec une grande fiabilité. Un seuil de positivité de 9 pg/mg permettait de détecter les consommateurs à risque.SUMMARYChronic and excessive alcohol consumption is associated with a significant increase of morbidity and mortality. The identification of a reliable biomarker to detect chronic and excessive alcohol consumers would be valuable to prevent alcohol's harmful effects. The combined analysis of 2 or more hepatic biomarkers, which are known to be increased following sustained alcohol consumption, is usually applied to enhance the diagnostic performance in identifying chronic and excessive alcohol consumers. However, their diagnostic value is often limited by their lack of sensitivity and / or specificity and their combination is generally recommended to improve diagnosis. To date, there are no reliable biomarkers available for diagnosing chronic and excessive alcohol consumption.The main objective of this research was to evaluate the relevance of EtG, a direct alcohol metabolite, as a biomarker of chronic and excessive alcohol consumption, thanks to its characteristic to incorporate into hair. First, a review of literature on the use of EtG was carried out. EtG demonstrated strong potential in detecting chronic and excessive alcohol consumption. However, the lack of reliable cutoff and the unawareness of factors that affect the EtG incorporation into hair were stressed. To investigate these points, two studies have been conducted: (1) a nonclinical study in rats to determine the factors affecting the incorporation of EtG into hair as well as to investigate the relationship between the amount of alcohol administered and the EtG concentration measured in hair; and (2) a clinical study to determine the diagnostic performance of EtG as a biomarker for the identification of chronic and excessive alcohol consumers. A sensitive and specific Gas Chromatography-Mass Spectrometry coupled to tandem Mass Spectrometry method has been developed and applied to hair EtG analysis.Bloodstream seemed to play a major role in the EtG incorporation into hair. EtG incorporation into rat hair was not affected by hair pigmentation. EtG concentration in rat hair appeared to reflect the EtG concentration in blood. Besides, EtG demonstrated strong diagnostic performance in detecting both heavy alcohol consumption and at-risk alcohol consumption, and clearly outperformed diagnostic performance of hepatic biomarkers. In contrast with hepatic biomarkers, EtG was not associated with age, gender or body mass index. A reliable cutoff value of 25 pg/mg allowed to detect heavy drinkers; a reliable cutoff value of 9 pg/mg allowed to detect at-risk drinkers

Evaluation of the Main CEOS Pseudo Calibration Sites Using MODIS BRDF/ALBEDO Products

This work describes our findings about an evaluation of the stability and the consistency of twenty primary PICSs (Pseudo-Invariant Calibration Sites). We present an analysis of 13 years of 8-daily MODIS products of BRDF parameters and white-sky-albedos (WSA) over the shortwave band. This time series of WSA and BRDFs shows the variation of the “stability” varies significantly from site to site. Using a 10x10 km window size over all the sites, the change in of WSA stability is around 4% but the isotropicity, which is an important element in inter-satellite calibration, can vary from 75% to 98%. Moreover, some PICS, especially, Libya-4 which is one of the PICS which is most employed, has significant and relatively fast changes in wintertime. PICS observations of BRDF/albedo shows that the Libya-4 PICS has the best performance but it is not too far from some sites such as Libya-1 and Mali. This study also reveals that Niger-3 PICS has the longest continuous period of high stability per year, and Sudan has the most isotropic surface. These observations have important implications for the use of these sites

Assessment of Satellite-Derived Surface Reflectances by NASA’s CAR Airborne Radiometer over Railroad Valley Playa

CAR (Cloud Absorption Radiometer) is a multi-angular and multi-spectral airborne radiometer instrument, whose radiometric and geometric characteristics are well calibrated and adjusted before and after each flight campaign. CAR was built by NASA (National Aeronautics and Space Administration) in 1984. On 16 May 2008, a CAR flight campaign took place over the well-known calibration and validation site of Railroad Valley in Nevada, USA (38.504°N, 115.692°W). The campaign coincided with the overpasses of several key EO (Earth Observation) satellites such as Landsat-7, Envisat and Terra. Thus, there are nearly simultaneous measurements from these satellites and the CAR airborne sensor over the same calibration site. The CAR spectral bands are close to those of most EO satellites. CAR has the ability to cover the whole range of azimuth view angles and a variety of zenith angles depending on altitude and, as a consequence, the biases seen between satellite and CAR measurements due to both unmatched spectral bands and unmatched angles can be significantly reduced. A comparison is presented here between CAR’s land surface reflectance (BRF or Bidirectional Reflectance Factor) with those derived from Terra/MODIS (MOD09 and MAIAC), Terra/MISR, Envisat/MERIS and Landsat-7. In this study, we utilized CAR data from low altitude flights (approx. 180 m above the surface) in order to minimize the effects of the atmosphere on these measurements and then obtain a valuable ground-truth data set of surface reflectance. Furthermore, this study shows that differences between measurements caused by surface heterogeneity can be tolerated, thanks to the high homogeneity of the study site on the one hand, and on the other hand, to the spatial sampling and the large number of CAR samples. These results demonstrate that satellite BRF measurements over this site are in good agreement with CAR with variable biases across different spectral bands. This is most likely due to residual aerosol effects in the EO derived reflectance

A new global fAPAR and LAI dataset derived from optimal albedo estimates: comparison with MODIS products

We present the first comparison between new fAPAR and LAI products derived from the GlobAlbedo dataset and the widely-used MODIS fAPAR and LAI and products. The GlobAlbedo derived products are produced using a 1D two-stream radiative transfer (RT) scheme designed explicitly for global parameter retrieval from albedo, with consistency between RT model assumptions and observations, as well as with typical large-scale land surface model RT schemes. The approach does not require biome-specific structural assumptions (e.g. cover, clumping, understory), unlike more detailed 3D RT model approaches. GlobAlbedo-derived values of fAPAR and LAI are compared with MODIS values over 2002-2011 at multiple flux tower sites within selected biomes, over 1200 × 1200 km regions and globally. GlobAlbedo-derived fAPAR and LAI values are temporally more stable than the MODIS values due to (1) the smoothness of the underlying albedo, derived via optimal estimation (assimilation) using an a priori estimate of albedo derived from an albedo ‘climatology’ (composited multi-year albedo observations) and (2) space-time invariant prior information in the inversion of the two-stream RT scheme. Parameters agree closely in timing but with GlobAlbedo values consistently lower than MODIS, particularly for LAI. Larger differences occur in winter (when values are lower) and in the Southern hemisphere. Globally, we find that: GlobAlbedo-derived fAPAR is ~0.9- 1.01 × MODIS fAPAR with an offset of ~0.03; GlobAlbedo-derived LAI is ~0.6 × MODIS LAI with an offset of ~0.2. Differences arise due to the RT model assumptions underlying the products, meaning care is required in interpreting either set of values, particularly when comparing to finescale ground-based estimates. We present global calibrations between GlobAlbedo-derived and MODIS products.JRC.H.5-Land Resources Managemen

Sea Ice Albedo from MISR and MODIS: Production, Validation, and Trend Analysis

he Multi-angle Imaging SpectroRadiometer (MISR) sensor onboard the Terra satellite provides high accuracy albedo products. MISR deploys nine cameras each at different view angles, which allow a near-simultaneous angular sampling of the surface anisotropy. This is particularly important to measure the near-instantaneous albedo of dynamic surface features such as clouds or sea ice. However, MISR’s cloud mask over snow or sea ice is not yet sufficiently robust because MISR’s spectral bands are only located in the visible and the near infrared. To overcome this obstacle, we performed data fusion using a specially processed MISR sea ice albedo product (that was generated at Langley Research Center using Rayleigh correction) combining this with a cloud mask of a sea ice mask product, MOD29, which is derived from the MODerate Resolution Imaging Spectroradiometer (MODIS), which is also, like MISR, onboard the Terra satellite. The accuracy of the MOD29 cloud mask has been assessed as >90% due to the fact that MODIS has a much larger number of spectral bands and covers a much wider range of the solar spectrum. Four daily sea ice products have been created, each with a different averaging time window (24 h, 7 days, 15 days, 31 days). For each time window, the number of samples, mean and standard deviation of MISR cloud-free sea ice albedo is calculated. These products are publicly available on a predefined polar stereographic grid at three spatial resolutions (1 km, 5 km, 25 km). The time span of the generated sea ice albedo covers the months between March and September of each year from 2000 to 2016 inclusive. In addition to data production, an evaluation of the accuracy of sea ice albedo was performed through a comparison with a dataset generated from a tower based albedometer from NOAA/ESRL/GMD/GRAD. This comparison confirms the high accuracy and stability of MISR’s sea ice albedo since its launch in February 2000. We also performed an evaluation of the day-of-year trend of sea ice albedo between 2000 and 2016, which confirm the reduction of sea ice shortwave albedo with an order of 0.4–1%, depending on the day of year and the length of observed time window

Codeine accumulation and elimination in larvae, pupae, and imago of the blowfly Lucilia sericata and effects on its development

The aim of this study was to evaluate the reliability of insect larvae as samples for toxicological investigations. For this purpose, larvae of Lucilia sericata were reared on samples of minced pig liver treated with different concentrations of codeine: therapeutic, toxic, and potentially lethal doses. Codeine was detected in all tested larvae, confirming the reliability of these specimens for qualitative toxicology analysis. Furthermore, concentrations measured in larvae were correlated with levels in liver tissue. These observations bring new elements regarding the potential use of opiates concentrations in larvae for estimation of drug levels in human tissues. Morphine and norcodeine, two codeine metabolites, have been also detected at different concentrations depending on the concentration of codeine in pig liver and depending on the substance itself. The effects of codeine on the development of L. sericata were also investigated. Results showed that a 29-h interval bias on the evaluation of the larval stage duration calculated from the larvae weight has to be considered if codeine was present in the larvae substrate. Similarly, a 21-h interval bias on the total duration of development, from egg to imago, has to be considered if codeine was present in the larvae substrat

Histogrammes spatiaux couleur optimisés pour l'indexation d'images par le contenu

- Dans cet article, nous présentons une méthode qui augmente l'efficacité et la précision des systèmes d'indexation et de recherche d'images couleur par le contenu basés sur les histogrammes spatiaux. Cette technique consiste essentiellement à extraire les informations spatiales de l'image en la divisant en plusieurs sous-images rectangulaires interférées (grille des histogrammes). La méthodologie proposée optimise, via une combinaison linéaire, le découpage horizontal et vertical de l'image pour le calcul des histogrammes spatiaux. Nous augmentons ainsi la performance de la recherche en réduisant en même temps le coût de stockage et le temps de calcul par rapport aux méthodes classiques dont le choix concernant le découpage reste arbitraire

Intercomparison of Surface Albedo Retrievals from MISR, MODIS, CGLS Using Tower and Upscaled Tower Measurements

Surface albedo is of crucial interest in land–climate interaction studies, since it is a key parameter that affects the Earth’s radiation budget. The temporal and spatial variation of surface albedo can be retrieved from conventional satellite observations after a series of processes, including atmospheric correction to surface spectral bi-directional reflectance factor (BRF), bi-directional reflectance distribution function (BRDF) modelling using these BRFs, and, where required, narrow-to-broadband albedo conversions. This processing chain introduces errors that can be accumulated and then affect the accuracy of the retrieved albedo products. In this study, the albedo products derived from the multi-angle imaging spectroradiometer (MISR), moderate resolution imaging spectroradiometer (MODIS) and the Copernicus Global Land Service (CGLS), based on the VEGETATION and now the PROBA-V sensors, are compared with albedometer and upscaled in situ measurements from 19 tower sites from the FLUXNET network, surface radiation budget network (SURFRAD) and Baseline Surface Radiation Network (BSRN) networks. The MISR sensor onboard the Terra satellite has 9 cameras at different view angles, which allows a near-simultaneous retrieval of surface albedo. Using a 16-day retrieval algorithm, the MODIS generates the daily albedo products (MCD43A) at a 500-m resolution. The CGLS albedo products are derived from the VEGETATION and PROBA-V, and updated every 10 days using a weighted 30-day window. We describe a newly developed method to derive the two types of albedo, which are directional hemispherical reflectance (DHR) and bi-hemispherical reflectance (BHR), directly from three tower-measured variables of shortwave radiation: downwelling, upwelling and diffuse shortwave radiation. In the validation process, the MISR, MODIS and CGLS-derived albedos (DHR and BHR) are first compared with tower measured albedos, using pixel-to-point analysis, between 2012 to 2016. The tower measured point albedos are then upscaled to coarse-resolution albedos, based on atmospherically corrected BRFs from high-resolution Earth observation (HR-EO) data, alongside MODIS BRDF climatology from a larger area. Then a pixel-to-pixel comparison is performed between DHR and BHR retrieved from coarse-resolution satellite observations and DHR and BHR upscaled from accurate tower measurements. The experimental results are presented on exploring the parameter space associated with land cover type, heterogeneous vs. homogeneous and instantaneous vs. time composite retrievals of surface albedo

Codeine accumulation and elimination in larvae, pupae, and imago of the blowfly Lucilia sericata and effects on its development.

The aim of this study was to evaluate the reliability of insect larvae as samples for toxicological investigations. For this purpose, larvae of Lucilia sericata were reared on samples of minced pig liver treated with different concentrations of codeine: therapeutic, toxic, and potentially lethal doses. Codeine was detected in all tested larvae, confirming the reliability of these specimens for qualitative toxicology analysis. Furthermore, concentrations measured in larvae were correlated with levels in liver tissue. These observations bring new elements regarding the potential use of opiates concentrations in larvae for estimation of drug levels in human tissues. Morphine and norcodeine, two codeine metabolites, have been also detected at different concentrations depending on the concentration of codeine in pig liver and depending on the substance itself. The effects of codeine on the development of L. sericata were also investigated. Results showed that a 29-h interval bias on the evaluation of the larval stage duration calculated from the larvae weight has to be considered if codeine was present in the larvae substrate. Similarly, a 21-h interval bias on the total duration of development, from egg to imago, has to be considered if codeine was present in the larvae substrate