Biological monitoring of exposure to solvents using the chemical itself in urine: application to toluene

Objective Biomonitoring of solvents using the unchanged substance in urine as exposure indicator is still relatively scarce due to some discrepancies between the results reported in the literature. Based on the assessment of toluene exposure, the aim of this work was to evaluate the effects of some steps likely to bias the results and to measure urinary toluene both in volunteers experimentally exposed and in workers of rotogravure factories. Methods Static headspace was used for toluene analysis. o-Cresol was also measured for comparison. Urine collection, storage and conservation conditions were studied to evaluate possible loss or contamination of toluene in controlled situations applied to six volunteers in an exposure chamber according to four scenarios with exposure at stable levels from 10 to 50 ppm. Kinetics of elimination of toluene were determined over 24 h. A field study was then carried out in a total of 29 workers from two rotogravure printing facilities. Results Potential contamination during urine collection in the field is confirmed to be a real problem but technical precautions for sampling, storage and analysis can be easily followed to control the situation. In the volunteers at rest, urinary toluene showed a rapid increase after 2 h with a steady level after about 3 h. At 47.1 ppm the mean cumulated excretion was about 0.005% of the amount of the toluene ventilated. Correlation between the toluene levels in air and in end of exposure urinary sample was excellent (r = 0.965). In the field study, the median personal exposure to toluene was 32 ppm (range 3.6-148). According to the correlations between environmental and biological monitoring data, the post-shift urinary toluene (r = 0.921) and o-cresol (r = 0.873) concentrations were, respectively, 75.6 mu g/l and 0.76 mg/g creatinine for 50 ppm toluene personal exposure. The corresponding urinary toluene concentration before the next shift was 11 mu g/l (r = 0.883). Conclusion Urinary toluene was shown once more time a very interesting surrogate to o-cresol and could be recommended as a biomarker of choice for solvent exposure. [Authors]

Méthodologie intégrée de microgravimétrie en milieu urbain : test d'application au génie civil sur le métro M2 de Lausanne

RESUME Dès le printemps 2004, la construction d'une 2ème ligne de métro est entreprise dans la ville de Lausanne en Suisse. En reliant Ouchy, au bord du lac Léman (alt. 373 m) à Epalinges (alt. 711 m), le nouveau métro "M2" traversera dès 2008 l'agglomération lausannoise du Sud au Nord sur une distance de 6 km. Depuis l'avant-projet, en 1999, une grande quantité de données géologiques a été récolté et de nombreux forages exécutés sur le site. Ceci nous a donné une occasion unique d'entreprendre une étude de microgravimétrique urbaine de détail. Le mode de creusement du tunnel dépend fortement des matériaux à excaver et il est classiquement du domaine du géologue, avec ses connaissances de la géologie régionale et de la stratigraphie des forages, de fournir à l'ingénieur un modèle géologique. Ce modèle indiquera dans ce cas l'épaisseur des terrains meubles qui recouvrent le soubassement rocheux. La représentativité spatiale d'une information très localisée, comme celle d'un forage, est d'autant plus compliquée que le détail recherché est petit. C'est à ce moment là que la prospection géophysique, plus spécialement gravimétrique, peut apporter des informations complémentaires déterminantes pour régionaliser les données ponctuelles des forages. La microgravimétrie en milieu urbain implique de corriger avec soin les perturbations gravifiques sur la mesure de la pesanteur dues aux effets de la topographie, des bâtiments et des caves afin d'isoler l'effet gravifique dû exclusivement à l'épaisseur du remplissage des terrains meubles. Tenant compte de l'intensité des corrections topographiques en milieu urbain, nous avons donné une grande importance aux sous-sols, leurs effets gravifiques pouvant atteindre l'ordre du dixième de mGal. Nous avons donc intégré ces corrections celle de topographie et traité les effets des bâtiments de manière indépendante. Nous avons inclus dans le modèle numérique de terrain (MNT) la chaussée et les sous-sols afin de construire un modèle numérique de terrain urbain. Nous utiliserons un nouvel acronyme « MNTU »pour décrire ce modèle. Nous proposons d'établir des cartes de corrections topographiques préalables, basées sur les données à disposition fournies par le cadastre en faisant des hypothèses sur la profondeur des sous-sols et la hauteur des bâtiments. Les deux zones de test choisies sont caractéristiques des différents types d'urbanisation présente à Lausanne et se révèlent par conséquent très intéressantes pour élaborer une méthodologie globale de la microgravimétrie urbaine. Le but était d'évaluer l'épaisseur du remplissage morainique sur un fond rocheux molassique se situant à une profondeur variable de quelques mètres à une trentaine de mètres et d'en établir une coupe dans l'axe du futur tracé du métro. Les résultats des modélisations se sont révélés très convaincants en détectant des zones qui diffèrent sensiblement du modèle géologique d'avant projet. Nous avons également démontré que l'application de cette méthode géophysique, non destructive, est à même de limiter le nombre de sondages mécaniques lors de l'avant-projet et du projet définitif, ce qui peut limiter à la fois les coûts et le dérangement engendré par ces travaux de surface. L'adaptabilité de la technique gravimétrique permet d'intervenir dans toutes les différentes phases d'un projet de génie civil comme celui de la construction d'un métro en souterrain. KURZFASSUNG Seit dem Frühling 2004 ist in der Stadt Lausanne (Schweiz) die neue U-Bahn "M2" in Konstruktion. Diese soll auf 6 km Länge die Lausanner Agglomeration von Süd nach Nord durchqueren. Die dem Projekt zu Grunde liegende technische Planung sieht vor, daß die Bahnlinie hauptsächlich in der Molasse angesiedelt sein wird. Seit dem Vorentwurf (1999) ist eine große Anzahl geologischer Angaben gesammelt worden. Daraus ergab sich die einmalige Gelegenheit, die Informationen aus den damit verbundenen zahlreichen Bohrungen zu einer detaillierten mikrogravimetrischen Studie der Stadt Lausanne zu erweitern und zu vervollständigen. Das Ziel bestand darin, die Mächtigkeit der die Molasseüberdeckenden Moräneablagerung abzuschätzen, um eine entsprechendes geologisches Profile entlang der künftigen Bahnlinie zu erstellen. Weiterhin sollte gezeigt werden, daß die Anwendung dieser nicht-invasiven geophysikalischen Methode es ermöglicht, die Anzahl der benötigten Bohrungen sowohl in der Pilotphase wie auch im endgültigen Projekt zu reduzieren, was zu wesentlichen finanziellen Einsparungen in der Ausführung des Werkes beitragen würde. Die beiden in dieser Studie bearbeiteten Testzonen befinden sich im Nordteil und im Stadtzentrum von Lausanne und sind durch eine unterschiedliche Urbanisierung charakterisiert. Das anstehende Gestein liegt in verschiedenen Tiefen: von einigen Metern bis zu etwa dreißig Metern. Diese Zonen weisen alle Schwierigkeiten einer urbanen Bebauung mit hoher Verkehrsdichte auf und waren daher massgebend bei der Ausarbeitung einer globalen mikrogravimetrischen Methodologie für die Stadt Lausanne. Die so entwickelte Technik ermöglicht, die störenden Auswirkungen der Topographie, der Gebäude, der Keller und der Öffentlichen Infrastrukturen sorgfältig zu korrigieren, um so die ausschließlich auf die Mächtigkeit des Lockergesteins zurückzuführenden Effekte zu isolieren. In Bezug auf die Intensität der Auswirkungen der topographischen Korrekturen im Stadtgebiet wurde den Untergeschossen eine besonders grosse Bedeutung zugemessen da die entsprechenden Schwerkrafteffekte eine Grösse von rund einem Zehntel mGal erreichen können. Wir schlagen deshalb vor, vorläufige Karten der topographischen Korrekturen zu erstellen. Diese Korrekturen basieren auf den uns vom Katasterplan gelieferten Daten und einigen Hypothesen bezüglich der Tiefe der Untergeschosse und der Höhe der Gebäude. Die Verfügbarkeit einer derartigen Karte vor der eigentlichen gravimetrischen Messkampagne würde uns erlauben, die Position der Meßstationen besser zu wählen. Wir sahen zudem, daß ein entsprechenden a priori Filter benutzt werden kann, wenn die Form und die Intensität der Anomalie offensichtlich dem entsprechenden Gebäude zugeordnet werden können. Diese Strategie muß jedoch mit Vorsicht angewandt werden, denn falls weitere Anomalien dazukommen, können bedeutende Verschiebungen durch Übèrlagerungen der Schwerewirkung verschiedener Strukturen entstehen. Die Ergebnisse der Modellierung haben sich als sehr überzeugend erwiesen, da sie im Voraus unbekannte sensible Zonen korrekt identifiziert haben. Die Anwendbarkeit der in dieser Arbeit entwickelten gravimetrischen Technik ermöglicht es, während allen Phasen eines Grossbauprojekts, wie zum Beispiel bei der Konstruktion einer unterirdischen U-Bahn, einzugreifen. ABSTRACT Since Spring of 2004 a new metro line has been under construction in the city of Lausanne in Switzerland. The new line, the M2, will be 6 km long and will traverse the city from south to north. The civil engineering project determined that the line would be located primarily in the Molasse. Since the preparatory project in 1999, a great quantity of geological data has been collected, and the many drillings made on the site have proved to be a unique opportunity to undertake a study of urban microgravimetry. The goal was to evaluate the thickness of the morainic filling over the molassic bedrock, and to establish a section along the axis of the future line. It then had to be shown that the application of this nondestructive geophysical method could reduce the number of mechanical surveys required both for a preparatory and a definitive project, which would lead to real savings in the realization of a civil engineering project. The two test zones chosen, one in the northern part of the city and one in the city centre, are characterised by various types of urbanisation. Bedrock is at a depth varying from a few metres to about thirty metres. These zones well exemplify the various difficulties encountered in an urban environment and are therefore very interesting for the development of an overall methodology of urban microgravimetry. Microgravimetry in an urban environment requires careful corrections for gravific disturbances due to the effects of topography, buildings, cellars, and the infrastructure of distribution networks, in order to isolate the gravific effect due exclusively to the thickness of loose soil filling. Bearing in mind the intensity of the topographic corrections in an urban environment, we gave particular importance to basements. Their gravific effects can reach the order of one tenth of one meal, and can influence above all the precision of the Bouguer anomaly. We propose to establish preliminary topographic correction charts based on data provided to us by the land register, by making assumptions on the depths of basements and the heights of buildings. Availability of this chart previous to a gravimetry campaign would enable us to choose optimum measuring sites. We have also seen that an a priori filter can be used when the form and the intensity of the anomaly correspond visually to the corresponding building. This strategy must be used with caution because if other anomalies are to be associated, important shifts can be generated by the superposition of the effects of different structures. The results of the model have proved to be very convincing in detecting previously unknown sensitive zones. The adaptability of the gravimetry technique allows for application in all phases of a civil engineering project such as the construction of an underground metro line. RIASSUNTO Dalla primavera 2004 una nuova linea metropolitana é in costruzione nella città di Losanna in Svizzera. La nuova metropolitana "M2" traverserà per la lunghezza di 6 km il centro urbano di Losanna da sud a nord. II progetto d'ingegneria civile prevedeva un tracciato situato essenzialmente nel fondo roccioso arenaceo terziario (molassa). Dalla redazione del progetto preliminare, avvenuta nel 1999, una grande quantità di dati geologici sono stati raccolti e sono stati eseguiti numerosi sondaggi. Questo sì é presentato come un'occasione unica per mettere a punto uno studio microgravimetrico in ambiente urbano con lo scopo di valutare lo spessore dei terreni sciolti di origine glaciale che ricoprono il fondo roccioso di molassa e di mettere in evidenza come l'applicazione di questo metodo geofisico non distruttivo possa limitare il numero di sondaggi meccanici nella fase di progetto preliminare ed esecutivo con conseguente reale risparmio economico nella realizzazione di una tale opera. Le due zone di test sono situate una nella zona nord e la seconda nel centro storico di Losanna e sono caratterizzate da stili architettonici differenti. II fondo roccioso é situato ad una profondità variabile da qualche metro ad una trentina. Queste due zone sembrano ben rappresentare tutte le difficoltà di un ambiente urbano e ben si prestano per elaborare una metodologia globale per la microgravimetria in ambiente urbano. L'applicazione di questa tecnica nell'ambiente suddetto implica la correzione attenta delle perturbazioni sulla misura dell'accelerazione gravitazionale, causate dalla topografia, gli edifici, le cantine e le infrastrutture dei sottoservizi, per ben isolare il segnale esclusivamente causato dallo spessore dei terreni sciolti. Tenuto conto, dell'intensità delle correzioni topografiche, abbiamo dato grande importanza alle cantine, poiché il loro effetto sulle misure può raggiungere il decimo di mGal. Proponiamo quindi di redigere una carta delle correzioni topografiche preliminare all'acquisizione, facendo delle ipotesi sulla profondità delle cantine e sull'altezza degli edifici, sulla base delle planimetrie catastali. L'analisi di questa carta permetterà di scegliere le posizioni più adatte per le stazioni gravimetriche. Abbiamo anche osservato che un filtro a priori, qualora la forma e l'intensità dell'anomalia fosse facilmente riconducibile in maniera visuale ad un edificio, possa essere efficace. Tuttavia questa strategia deve essere utilizzata con precauzione, poiché può introdurre uno scarto, qualora più anomalie, dovute a differenti strutture, si sovrappongano. I risultati delle modellizzazioni si sono rivelati convincenti, evidenziando zone sensibili non conosciute preventivamente. L'adattabilità della tecnica gravimetrica ha mostrato di poter intervenire in differenti fasi di un progetto di ingegneria civile, quale è quella di un'opera in sotterraneo.

Application extraterritoriale du droit international des droits de l'homme

Les obligations de l'Etat en matière de droits de l'homme s'étendent-elles au-delà de ses frontières? Le sujet prend une importance considérable actuellement: interventions militaires à l'étranger, opérations de paix, occupation militaire, centres de détention à l'étranger, mouvements séparatistes soutenus par un Etat étranger, éloignement des étrangers, entraide judiciaire et administrative internationale, exequatur de décisions étrangères violant les droits de l'homme... Ces thèmes, et d'autres, sont abordés dans l'ouvrage sous l'angle du Pacte ONU II, de la CEDH, et de la Convention et la Déclaration américaines dans une approche comparative et systématique. L'ouvrage analyse en détail la jurisprudence et la pratique internationales relatives à ces instruments. L'auteur est avocat au Barreau du Canton de Vaud (Lausanne) et titulaire d'un LL.M. de l'Université de Cambridge.

Validation of an analytical method for nitrous oxide (N2O) laughing gas by headspace gas chromatography coupled to mass spectrometry (HS-GC-MS): Forensic application to a lethal intoxication.

Drug abuse is a widespread problem affecting both teenagers and adults. Nitrous oxide is becoming increasingly popular as an inhalation drug, causing harmful neurological and hematological effects. Some gas chromatography-mass spectrometry (GC-MS) methods for nitrous oxide measurement have been previously described. The main drawbacks of these methods include a lack of sensitivity for forensic applications; including an inability to quantitatively determine the concentration of gas present. The following study provides a validated method using HS-GC-MS which incorporates hydrogen sulfide as a suitable internal standard allowing the quantification of nitrous oxide. Upon analysis, sample and internal standard have similar retention times and are eluted quickly from the molecular sieve 5Å PLOT capillary column and the Porabond Q column therefore providing rapid data collection whilst preserving well defined peaks. After validation, the method has been applied to a real case of N2O intoxication indicating concentrations in a mono-intoxication.

Hydrogeophysical data integration at larger scales: Application of Bayesian sequential simulation for the characterization of heterogeneous alluvial aquifers

Knowledge of the spatial distribution of hydraulic conductivity (K) within an aquifer is critical for reliable predictions of solute transport and the development of effective groundwater management and/or remediation strategies. While core analyses and hydraulic logging can provide highly detailed information, such information is inherently localized around boreholes that tend to be sparsely distributed throughout the aquifer volume. Conversely, larger-scale hydraulic experiments like pumping and tracer tests provide relatively low-resolution estimates of K in the investigated subsurface region. As a result, traditional hydrogeological measurement techniques contain a gap in terms of spatial resolution and coverage, and they are often alone inadequate for characterizing heterogeneous aquifers. Geophysical methods have the potential to bridge this gap. The recent increased interest in the application of geophysical methods to hydrogeological problems is clearly evidenced by the formation and rapid growth of the domain of hydrogeophysics over the past decade (e.g., Rubin and Hubbard, 2005).

Optimized venous return with a self-expanding cannula: from computational fluid dynamics to clinical application.

The Smart canula concept allows for collapsed cannula insertion, and self-expansion within a vein of the body. (A) Computational fluid dynamics, and (B) bovine experiments (76+/-3.8 kg) were performed for comparative analyses, prior to (C) the first clinical application. For an 18F access, a given flow of 4 l/min (A) resulted in a pressure drop of 49 mmHg for smart cannula versus 140 mmHg for control. The corresponding Reynolds numbers are 680 versus 1170, respectively. (B) For an access of 28F, the maximal flow for smart cannula was 5.8+/-0.5 l/min versus 4.0+/-0.1 l/min for standard (P<0.0001), for 24F 5.5+/-0.6 l/min versus 3.2+/-0.4 l/min (P<0.0001), and for 20F 4.1+/-0.3 l/min versus 1.6+/-0.3 l/min (P<0.0001). The flow obtained with the smart cannula was 270+/-45% (20F), 172+/-26% (24F), and 134+/-13% (28F) of standard (one-way ANOVA, P=0.014). (C) First clinical application (1.42 m2) with a smart cannula showed 3.55 l/min (100% predicted) without additional fluids. All three assessment steps confirm the superior performance of the smart cannula design.

Population Normalization with Ammonium in Wastewater-Based Epidemiology: Application to Illicit Drug Monitoring

Fluctuations in ammonium (NH4+), measured as NH4-N loads using an ion-selective electrode installed at the inlet of a sewage treatment plant, showed a distinctive pattern which was associated to weekly (i.e., commuters) and seasonal (i.e., holidays) fluctuations of the population. Moreover, population size estimates based on NH4-N loads were lower compared to census data. Diurnal profiles of benzoylecgonine (BE) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) were shown to be strongly correlated to NH4-N. Characteristic patterns, which reflect the prolonged nocturnal activity of people during the weekend, could be observed for BE, cocaine, and a major metabolite of MDMA (i.e., 4-hydroxy-3-methoxymethamphetamine). Additional 24 h composite samples were collected between February and September 2013. Per-capita loads (i.e., grams per day per 1000 inhabitants) were computed using census data and NH4-N measurements. Normalization with NH4-N did not modify the overall pattern, suggesting that the magnitude of fluctuations in the size of the population is negligible compared to those of illicit drug loads. Results show that fluctuations in the size of the population over longer periods of time or during major events can be monitored using NH4-N loads: either using raw NH4-N loads or population size estimates based on NH4-N loads, if information about site-specific NH4-N population equivalents is available.

Routine use of point-of-care tests: usefulness and application in clinical microbiology.

Point-of-care (POC) tests offer potentially substantial benefits for the management of infectious diseases, mainly by shortening the time to result and by making the test available at the bedside or at remote care centres. Commercial POC tests are already widely available for the diagnosis of bacterial and viral infections and for parasitic diseases, including malaria. Infectious diseases specialists and clinical microbiologists should be aware of the indications and limitations of each rapid test, so that they can use them appropriately and correctly interpret their results. The clinical applications and performance of the most relevant and commonly used POC tests are reviewed. Some of these tests exhibit insufficient sensitivity, and should therefore be coupled to confirmatory tests when the results are negative (e.g. Streptococcus pyogenes rapid antigen detection test), whereas the results of others need to be confirmed when positive (e.g. malaria). New molecular-based tests exhibit better sensitivity and specificity than former immunochromatographic assays (e.g. Streptococcus agalactiae detection). In the coming years, further evolution of POC tests may lead to new diagnostic approaches, such as panel testing, targeting not just a single pathogen, but all possible agents suspected in a specific clinical setting. To reach this goal, the development of serology-based and/or molecular-based microarrays/multiplexed tests will be needed. The availability of modern technology and new microfluidic devices will provide clinical microbiologists with the opportunity to be back at the bedside, proposing a large variety of POC tests that will allow quicker diagnosis and improved patient care.

The clinical application of converting enzyme inhibitors.

Chronic blockade of the renin angiotensin system became possible when orally active inhibitors of angiotensin converting enzyme, the enzyme which catalyzes the transformation of angiotensin I into angiotensin II, were synthetized. Two compounds, captopril and enalapril, have been investigated in clinical studies. The decrease of the pressor response to exogenous angiotensin I and of the circulating levels of angiotensin II following administration of these inhibitors has been demonstrated to be directly related to the degree of suppression of plasma angiotensin converting enzyme activity. These inhibitors have been shown to normalize blood pressure alone in some hypertensive patients whereas in many others, satisfactory blood pressure control can be achieved only after the addition of a diuretic. Captopril and enalapril also markedly improve cardiac function of patients with chronic congestive heart failure. Chronic blockade of the renin angiotensin system has therefore provided an interesting new approach to the treatment of clinical hypertension and heart failure.

Recommandations de pratique clinique dans la schizophrénie : de la théorie à la mise en application

Résumé: Dans le cadre d'une étude rétrospective au sein d'une unité de réhabilitation ,nous avons cherché à examiner le degré de respect de recommandations de pratique clinique (RPC) abordant le traitement pharmacologique au long cours de la schizophrénie, par des médecins qui n'en ont qu'une connaissance indirecte. « The Expert Consensus Guideline for the treatment of schizophrenia » (« ECGTS ») a été retenu comme référence sur la base d'une comparaison avec cinq autres RPC principales. Sur un collectif de 20 patients, les recommandations de «l'ECGTS» sont totalement respectées dans 65 % des cas, partiellement respectées dans 10% et non respectées dans 25 %, démontrant ainsi que la pratique clinique est clairement perfectible (principalement dans le traitement des symptômes psychotiques et dépressifs). Cependant, le respect des RPC ne garantit pas forcément la résolution de tous les problèmes cliniques rencontrés : 12 patients sur 20 présentent des effets secondaires à l'évaluation clinique, et pour 8 d'entre eux, les recommandations à ce niveau sont respectées. Notre étude montre cependant que le choix et l'application d'une RPC n'est pas simple. Les RPC actuelles donnent peu ou pas d'instrument de mesure, ni de critère précis pour évaluer les problèmes cliniques auxquels elles font référence. L'avenir appartient donc à des RPC qui proposent, outre les recommandations cliniques elles-mêmes, les moyens de leur vérification et de leur application sur le terrain.

The application of chemometrics on Infrared and Raman spectra as a tool for the forensic analysis of paints

The aim of this work is to evaluate the capabilities and limitations of chemometric methods and other mathematical treatments applied on spectroscopic data and more specifically on paint samples. The uniqueness of the spectroscopic data comes from the fact that they are multivariate - a few thousands variables - and highly correlated. Statistical methods are used to study and discriminate samples. A collection of 34 red paint samples was measured by Infrared and Raman spectroscopy. Data pretreatment and variable selection demonstrated that the use of Standard Normal Variate (SNV), together with removal of the noisy variables by a selection of the wavelengths from 650 to 1830 cm−1 and 2730-3600 cm−1, provided the optimal results for infrared analysis. Principal component analysis (PCA) and hierarchical clusters analysis (HCA) were then used as exploratory techniques to provide evidence of structure in the data, cluster, or detect outliers. With the FTIR spectra, the Principal Components (PCs) correspond to binder types and the presence/absence of calcium carbonate. 83% of the total variance is explained by the four first PCs. As for the Raman spectra, we observe six different clusters corresponding to the different pigment compositions when plotting the first two PCs, which account for 37% and 20% respectively of the total variance. In conclusion, the use of chemometrics for the forensic analysis of paints provides a valuable tool for objective decision-making, a reduction of the possible classification errors, and a better efficiency, having robust results with time saving data treatments.