Graphitized carbon black in quartz tubes for the sampling of indoor air nicotine and analysis by microwave thermal desorption-capillary gas chromatography

Nicotine in a smoky indoor air environment can be determined using graphitized carbon black as a solid sorbent in quartz tubes. The temperature stability, high purity, and heat absorption characteristics of the sorbent, as well as the permeability of the quartz tubes to microwaves, enable the thermal desorption by means of microwaves after active sampling. Permeation and dynamic dilution procedures for the generation of nicotine in the vapor phase at low and high concentrations are used to evaluate the performances of the sampler. Tube preparation is described and the microwave desorption temperature is measured. Breakthrough volume is determined to allow sampling at 0.1-1 L/min for definite periods of time. The procedure is tested for the determination of gas and paticulate phase nicotine in sidestream smoke produced in an experimental chamber.

Development of a 3D very high-resolution seismic reflection system for lacustrine settings - a case study over a thrust fault zone in Lake Geneva

Un système efficace de sismique tridimensionnelle (3-D) haute-résolution adapté à des cibles lacustres de petite échelle a été développé. Dans le Lac Léman, près de la ville de Lausanne, en Suisse, des investigations récentes en deux dimension (2-D) ont mis en évidence une zone de faille complexe qui a été choisie pour tester notre système. Les structures observées incluent une couche mince (<40 m) de sédiments quaternaires sub-horizontaux, discordants sur des couches tertiaires de molasse pentées vers le sud-est. On observe aussi la zone de faille de « La Paudèze » qui sépare les unités de la Molasse du Plateau de la Molasse Subalpine. Deux campagnes 3-D complètes, d?environ d?un kilomètre carré, ont été réalisées sur ce site de test. La campagne pilote (campagne I), effectuée en 1999 pendant 8 jours, a couvert 80 profils en utilisant une seule flûte. Pendant la campagne II (9 jours en 2001), le nouveau système trois-flûtes, bien paramétrés pour notre objectif, a permis l?acquisition de données de très haute qualité sur 180 lignes CMP. Les améliorations principales incluent un système de navigation et de déclenchement de tirs grâce à un nouveau logiciel. Celui-ci comprend un contrôle qualité de la navigation du bateau en temps réel utilisant un GPS différentiel (dGPS) à bord et une station de référence près du bord du lac. De cette façon, les tirs peuvent être déclenchés tous les 5 mètres avec une erreur maximale non-cumulative de 25 centimètres. Tandis que pour la campagne I la position des récepteurs de la flûte 48-traces a dû être déduite à partir des positions du bateau, pour la campagne II elle ont pu être calculées précisément (erreur <20 cm) grâce aux trois antennes dGPS supplémentaires placées sur des flotteurs attachés à l?extrémité de chaque flûte 24-traces. Il est maintenant possible de déterminer la dérive éventuelle de l?extrémité des flûtes (75 m) causée par des courants latéraux ou de petites variations de trajet du bateau. De plus, la construction de deux bras télescopiques maintenant les trois flûtes à une distance de 7.5 m les uns des autres, qui est la même distance que celle entre les lignes naviguées de la campagne II. En combinaison avec un espacement de récepteurs de 2.5 m, la dimension de chaque «bin» de données 3-D de la campagne II est de 1.25 m en ligne et 3.75 m latéralement. L?espacement plus grand en direction « in-line » par rapport à la direction «cross-line» est justifié par l?orientation structurale de la zone de faille perpendiculaire à la direction «in-line». L?incertitude sur la navigation et le positionnement pendant la campagne I et le «binning» imprécis qui en résulte, se retrouve dans les données sous forme d?une certaine discontinuité des réflecteurs. L?utilisation d?un canon à air à doublechambre (qui permet d?atténuer l?effet bulle) a pu réduire l?aliasing observé dans les sections migrées en 3-D. Celui-ci était dû à la combinaison du contenu relativement haute fréquence (<2000 Hz) du canon à eau (utilisé à 140 bars et à 0.3 m de profondeur) et d?un pas d?échantillonnage latéral insuffisant. Le Mini G.I 15/15 a été utilisé à 80 bars et à 1 m de profondeur, est mieux adapté à la complexité de la cible, une zone faillée ayant des réflecteurs pentés jusqu?à 30°. Bien que ses fréquences ne dépassent pas les 650 Hz, cette source combine une pénétration du signal non-aliasé jusqu?à 300 m dans le sol (par rapport au 145 m pour le canon à eau) pour une résolution verticale maximale de 1.1 m. Tandis que la campagne I a été acquise par groupes de plusieurs lignes de directions alternées, l?optimisation du temps d?acquisition du nouveau système à trois flûtes permet l?acquisition en géométrie parallèle, ce qui est préférable lorsqu?on utilise une configuration asymétrique (une source et un dispositif de récepteurs). Si on ne procède pas ainsi, les stacks sont différents selon la direction. Toutefois, la configuration de flûtes, plus courtes que pour la compagne I, a réduit la couverture nominale, la ramenant de 12 à 6. Une séquence classique de traitement 3-D a été adaptée à l?échantillonnage à haute fréquence et elle a été complétée par deux programmes qui transforment le format non-conventionnel de nos données de navigation en un format standard de l?industrie. Dans l?ordre, le traitement comprend l?incorporation de la géométrie, suivi de l?édition des traces, de l?harmonisation des «bins» (pour compenser l?inhomogénéité de la couverture due à la dérive du bateau et de la flûte), de la correction de la divergence sphérique, du filtrage passe-bande, de l?analyse de vitesse, de la correction DMO en 3-D, du stack et enfin de la migration 3-D en temps. D?analyses de vitesse détaillées ont été effectuées sur les données de couverture 12, une ligne sur deux et tous les 50 CMP, soit un nombre total de 600 spectres de semblance. Selon cette analyse, les vitesses d?intervalles varient de 1450-1650 m/s dans les sédiments non-consolidés et de 1650-3000 m/s dans les sédiments consolidés. Le fait que l?on puisse interpréter plusieurs horizons et surfaces de faille dans le cube, montre le potentiel de cette technique pour une interprétation tectonique et géologique à petite échelle en trois dimensions. On distingue cinq faciès sismiques principaux et leurs géométries 3-D détaillées sur des sections verticales et horizontales: les sédiments lacustres (Holocène), les sédiments glacio-lacustres (Pléistocène), la Molasse du Plateau, la Molasse Subalpine de la zone de faille (chevauchement) et la Molasse Subalpine au sud de cette zone. Les couches de la Molasse du Plateau et de la Molasse Subalpine ont respectivement un pendage de ~8° et ~20°. La zone de faille comprend de nombreuses structures très déformées de pendage d?environ 30°. Des tests préliminaires avec un algorithme de migration 3-D en profondeur avant sommation et à amplitudes préservées démontrent que la qualité excellente des données de la campagne II permet l?application de telles techniques à des campagnes haute-résolution. La méthode de sismique marine 3-D était utilisée jusqu?à présent quasi-exclusivement par l?industrie pétrolière. Son adaptation à une échelle plus petite géographiquement mais aussi financièrement a ouvert la voie d?appliquer cette technique à des objectifs d?environnement et du génie civil.<br/><br/>An efficient high-resolution three-dimensional (3-D) seismic reflection system for small-scale targets in lacustrine settings was developed. In Lake Geneva, near the city of Lausanne, Switzerland, past high-resolution two-dimensional (2-D) investigations revealed a complex fault zone (the Paudèze thrust zone), which was subsequently chosen for testing our system. Observed structures include a thin (<40 m) layer of subhorizontal Quaternary sediments that unconformably overlie southeast-dipping Tertiary Molasse beds and the Paudèze thrust zone, which separates Plateau and Subalpine Molasse units. Two complete 3-D surveys have been conducted over this same test site, covering an area of about 1 km2. In 1999, a pilot survey (Survey I), comprising 80 profiles, was carried out in 8 days with a single-streamer configuration. In 2001, a second survey (Survey II) used a newly developed three-streamer system with optimized design parameters, which provided an exceptionally high-quality data set of 180 common midpoint (CMP) lines in 9 days. The main improvements include a navigation and shot-triggering system with in-house navigation software that automatically fires the gun in combination with real-time control on navigation quality using differential GPS (dGPS) onboard and a reference base near the lake shore. Shots were triggered at 5-m intervals with a maximum non-cumulative error of 25 cm. Whereas the single 48-channel streamer system of Survey I requires extrapolation of receiver positions from the boat position, for Survey II they could be accurately calculated (error <20 cm) with the aid of three additional dGPS antennas mounted on rafts attached to the end of each of the 24- channel streamers. Towed at a distance of 75 m behind the vessel, they allow the determination of feathering due to cross-line currents or small course variations. Furthermore, two retractable booms hold the three streamers at a distance of 7.5 m from each other, which is the same distance as the sail line interval for Survey I. With a receiver spacing of 2.5 m, the bin dimension of the 3-D data of Survey II is 1.25 m in in-line direction and 3.75 m in cross-line direction. The greater cross-line versus in-line spacing is justified by the known structural trend of the fault zone perpendicular to the in-line direction. The data from Survey I showed some reflection discontinuity as a result of insufficiently accurate navigation and positioning and subsequent binning errors. Observed aliasing in the 3-D migration was due to insufficient lateral sampling combined with the relatively high frequency (<2000 Hz) content of the water gun source (operated at 140 bars and 0.3 m depth). These results motivated the use of a double-chamber bubble-canceling air gun for Survey II. A 15 / 15 Mini G.I air gun operated at 80 bars and 1 m depth, proved to be better adapted for imaging the complexly faulted target area, which has reflectors dipping up to 30°. Although its frequencies do not exceed 650 Hz, this air gun combines a penetration of non-aliased signal to depths of 300 m below the water bottom (versus 145 m for the water gun) with a maximum vertical resolution of 1.1 m. While Survey I was shot in patches of alternating directions, the optimized surveying time of the new threestreamer system allowed acquisition in parallel geometry, which is preferable when using an asymmetric configuration (single source and receiver array). Otherwise, resulting stacks are different for the opposite directions. However, the shorter streamer configuration of Survey II reduced the nominal fold from 12 to 6. A 3-D conventional processing flow was adapted to the high sampling rates and was complemented by two computer programs that format the unconventional navigation data to industry standards. Processing included trace editing, geometry assignment, bin harmonization (to compensate for uneven fold due to boat/streamer drift), spherical divergence correction, bandpass filtering, velocity analysis, 3-D DMO correction, stack and 3-D time migration. A detailed semblance velocity analysis was performed on the 12-fold data set for every second in-line and every 50th CMP, i.e. on a total of 600 spectra. According to this velocity analysis, interval velocities range from 1450-1650 m/s for the unconsolidated sediments and from 1650-3000 m/s for the consolidated sediments. Delineation of several horizons and fault surfaces reveal the potential for small-scale geologic and tectonic interpretation in three dimensions. Five major seismic facies and their detailed 3-D geometries can be distinguished in vertical and horizontal sections: lacustrine sediments (Holocene) , glaciolacustrine sediments (Pleistocene), Plateau Molasse, Subalpine Molasse and its thrust fault zone. Dips of beds within Plateau and Subalpine Molasse are ~8° and ~20°, respectively. Within the fault zone, many highly deformed structures with dips around 30° are visible. Preliminary tests with 3-D preserved-amplitude prestack depth migration demonstrate that the excellent data quality of Survey II allows application of such sophisticated techniques even to high-resolution seismic surveys. In general, the adaptation of the 3-D marine seismic reflection method, which to date has almost exclusively been used by the oil exploration industry, to a smaller geographical as well as financial scale has helped pave the way for applying this technique to environmental and engineering purposes.<br/><br/>La sismique réflexion est une méthode d?investigation du sous-sol avec un très grand pouvoir de résolution. Elle consiste à envoyer des vibrations dans le sol et à recueillir les ondes qui se réfléchissent sur les discontinuités géologiques à différentes profondeurs et remontent ensuite à la surface où elles sont enregistrées. Les signaux ainsi recueillis donnent non seulement des informations sur la nature des couches en présence et leur géométrie, mais ils permettent aussi de faire une interprétation géologique du sous-sol. Par exemple, dans le cas de roches sédimentaires, les profils de sismique réflexion permettent de déterminer leur mode de dépôt, leurs éventuelles déformations ou cassures et donc leur histoire tectonique. La sismique réflexion est la méthode principale de l?exploration pétrolière. Pendant longtemps on a réalisé des profils de sismique réflexion le long de profils qui fournissent une image du sous-sol en deux dimensions. Les images ainsi obtenues ne sont que partiellement exactes, puisqu?elles ne tiennent pas compte de l?aspect tridimensionnel des structures géologiques. Depuis quelques dizaines d?années, la sismique en trois dimensions (3-D) a apporté un souffle nouveau à l?étude du sous-sol. Si elle est aujourd?hui parfaitement maîtrisée pour l?imagerie des grandes structures géologiques tant dans le domaine terrestre que le domaine océanique, son adaptation à l?échelle lacustre ou fluviale n?a encore fait l?objet que de rares études. Ce travail de thèse a consisté à développer un système d?acquisition sismique similaire à celui utilisé pour la prospection pétrolière en mer, mais adapté aux lacs. Il est donc de dimension moindre, de mise en oeuvre plus légère et surtout d?une résolution des images finales beaucoup plus élevée. Alors que l?industrie pétrolière se limite souvent à une résolution de l?ordre de la dizaine de mètres, l?instrument qui a été mis au point dans le cadre de ce travail permet de voir des détails de l?ordre du mètre. Le nouveau système repose sur la possibilité d?enregistrer simultanément les réflexions sismiques sur trois câbles sismiques (ou flûtes) de 24 traces chacun. Pour obtenir des données 3-D, il est essentiel de positionner les instruments sur l?eau (source et récepteurs des ondes sismiques) avec une grande précision. Un logiciel a été spécialement développé pour le contrôle de la navigation et le déclenchement des tirs de la source sismique en utilisant des récepteurs GPS différentiel (dGPS) sur le bateau et à l?extrémité de chaque flûte. Ceci permet de positionner les instruments avec une précision de l?ordre de 20 cm. Pour tester notre système, nous avons choisi une zone sur le Lac Léman, près de la ville de Lausanne, où passe la faille de « La Paudèze » qui sépare les unités de la Molasse du Plateau et de la Molasse Subalpine. Deux campagnes de mesures de sismique 3-D y ont été réalisées sur une zone d?environ 1 km2. Les enregistrements sismiques ont ensuite été traités pour les transformer en images interprétables. Nous avons appliqué une séquence de traitement 3-D spécialement adaptée à nos données, notamment en ce qui concerne le positionnement. Après traitement, les données font apparaître différents faciès sismiques principaux correspondant notamment aux sédiments lacustres (Holocène), aux sédiments glacio-lacustres (Pléistocène), à la Molasse du Plateau, à la Molasse Subalpine de la zone de faille et la Molasse Subalpine au sud de cette zone. La géométrie 3-D détaillée des failles est visible sur les sections sismiques verticales et horizontales. L?excellente qualité des données et l?interprétation de plusieurs horizons et surfaces de faille montrent le potentiel de cette technique pour les investigations à petite échelle en trois dimensions ce qui ouvre des voies à son application dans les domaines de l?environnement et du génie civil.

La fonction publique en Suisse : analyse géopolitique d'un fédéralisme à géométrie variable

Bien que présenté comme un modèle de stabilité, le fédéralisme est constamment remis en question. Le but de l'article est de présenter quelques-unes de ses caractéristiques lues à travers les effectifs de la fonction publique en Suisse. Pour ce faire, nous distinguerons quatre types d'employeurs : Confédération, cantons, communes et corporations de droit public, lesquels représentent 10,5 % du total des actifs en Suisse. Nous analyserons la densité administrative, la variation des emplois et le degré de décentralisation selon la culture, le territoire et la religion. Il ressort que la fonction publique intermédiaire, c'est-à-dire les cantons, joue le premier rôle avec ses 140'000 emplois en équivalents plein temps (EPT) sur un total de 328'000, en hausse de 10,3 % par rapport à 2001. Les communes comptent 38 % des agents publics (+3,6 % par rapport à 2001), loin devant la Confédération, 11 % du total (en perte de vitesse : -1,2 %) et les corporations de droit public, 9 % du total (+14,5 %). Le taux d'administration est plus élevé dans la partie francophone que dans la partie germanophone, ainsi que dans les centres économiques et les zones frontières. Les écarts entre les cantons peuvent varier du simple au triple. En fait, deux modèles politico-administratifs transparaissent : le premier « cantonaliste » et davantage étatiste dans la partie latine, l'autre « communaliste » et décentralisé, dominant dans la partie germanophone. Le quotient de décentralisation administrative montre de grandes différences entre l'est et l'ouest, qui s'estompent toutefois avec la modernisation des institutions et le repositionnement de la Suisse face à l'Europe.

Imaging of prolonged BOLD response in the somatosensory cortex of the rat.

Blood oxygenation level-dependent (BOLD) functional MRI is a widely employed methodology in experimental and clinical neuroscience, although its nature is not fully understood. To gain insights into BOLD mechanisms and take advantage of the new functional methods, it is of interest to investigate prolonged paradigms of activation suitable for long experimental protocols and to observe any long-term modifications induced by these functional challenges. While different types of sustained stimulation paradigm have been explored in human studies, the BOLD response is typically limited to a few minutes in animal models, due to fatigue, anesthesia effects and physiological instability. In the present study, the rat forepaw was electrically stimulated for 2 h, which resulted in a prolonged and localized cortical BOLD response over that period. The stimulation paradigm, including an inter-stimulus interval (ISI) of 10 s, that is 25% of the total time, was applied at constant or variable frequency over 2 h. The steady-state level of the BOLD response was reached after 15-20 min of stimulation and was maintained until the end of the stimulation. On average, no substantial loss in activated volume was observed at the end of the stimulation, but less variability in the fraction of remaining activated volume and higher steady-state BOLD amplitude were observed when stimulation frequency was varied between 2 and 3 Hz every 5 min. We conclude that the combination of ISI and variable stimulus frequency reproducibly results in robust, prolonged and localized BOLD activation. Copyright © 2015 John Wiley & Sons, Ltd.

Optimizing the Anti-VEGF Treatment Strategy for Neovascular Age-Related Macular Degeneration: From Clinical Trials to Real-Life Requirements.

NlmCategory="UNASSIGNED">This Perspective discusses the pertinence of variable dosing regimens with anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) with regard to real-life requirements. After the initial pivotal trials of anti-VEGF therapy, the variable dosing regimens pro re nata (PRN), Treat-and-Extend, and Observe-and-Plan, a recently introduced regimen, aimed to optimize the anti-VEGF treatment strategy for nAMD. The PRN regimen showed good visual results but requires monthly monitoring visits and can therefore be difficult to implement. Moreover, application of the PRN regimen revealed inferior results in real-life circumstances due to problems with resource allocation. The Treat-and-Extend regimen uses an interval based approach and has become widely accepted for its ease of preplanning and the reduced number of office visits required. The parallel development of the Observe-and-Plan regimen demonstrated that the future need for retreatment (interval) could be reliably predicted. Studies investigating the observe-and-plan regimen also showed that this could be used in individualized fixed treatment plans, allowing for dramatically reduced clinical burden and good outcomes, thus meeting the real life requirements. This progressive development of variable dosing regimens is a response to the real-life circumstances of limited human, technical, and financial resources. This includes an individualized treatment approach, optimization of the number of retreatments, a minimal number of monitoring visits, and ease of planning ahead. The Observe-and-Plan regimen achieves this goal with good functional results. Translational Relevance: This perspective reviews the process from the pivotal clinical trials to the development of treatment regimens which are adjusted to real life requirements. The article discusses this translational process which- although not the classical interpretation of translation from fundamental to clinical research, but a subsequent process after the pivotal clinical trials - represents an important translational step from the clinical proof of efficacy to optimization in terms of patients' and clinics' needs. The related scientific procedure includes the exploration of the concept, evaluation of security, and finally proof of efficacy.

Comment on reversal of hypogonadotropic hypogonadism in a Chinese cohort.

The reversal of congenital hypogonadotropic hypogonadism (CHH) is a relatively recent phenomenon that has gained increasing attention over the past 10 years. Yet to date, only one prospective study has been conducted estimating that 10% (95% confidence interval [CI]: 2%-18%) of cases undergo reversal. [1] Other retrospective studies have reported rates in the range of 5%-8% [2],[3] and a recent study showed 44/308 (14%, 95% CI: 11%-19%) CHH patients underwent reversal. [4] Moreover, a time-to-event analysis in this large cohort revealed a lifetime reversal incidence of 22%. The article by Mao and colleagues presented in this issue is a meaningful contribution to our understanding of reversal as it examines the largest retrospective cohort to date. [5] Interestingly, they report the rate of reversal as 5% (95% CI: 3%-8%) in this Chinese cohort. It is difficult to reconcile the discrepancies in rates of reversibility and direct comparisons are hampered by the variable definitions employed. Using a novel definition for reversal (i.e, either endogenous testosterone (T) >270 ng dl−1 , serum T gradually increasing above 150 ng dl−1 with increased testicular volume, or normal spontaneous sperm production/normal erectile function/ejaculation), Mao and colleagues posit that testicular size and triptorelin-stimulated LH levels are reliable predictive factors for reversal. However, these cannot be considered as hard and fast rules for predicting reversal as the groups intersect - akin to the overlap observed between CHH patients and those with delayed puberty. Indeed, the fact that approximately half (44%, 95% CI: 25%-66%) of the reversal patients in the study by Mao et al.[5] were diagnosed between 17 and 19 years of age, underscores the challenge in differentiating CHH from extreme normal variants of puberty. This study further lends credence the recently reported observations that reversals may relapse. [4],[6] The notion that reversal may not be lasting highlights the vulnerability of the reproductive axis among CHH patients. While the mechanism(s) for relapse are unclear, it seems plausible that environmental, metabolic or psychiatric stressors could contribute. The factors that Mao and colleagues identify as significantly different in cases of reversal, were not informative for identifying those cases that relapsed back to a hypogonadal state. Notably, reversal has been reported in probands harboring mutations in genes underlying CHH. [1],[3],[4],[6] Unfortunately, comprehensive genetic screening on the Chinese cohort is not available. The reversal phenomenon is fascinating for its glimpse into the plasticity of the neuroendocrine control of reproduction. Future directions will almost certainly include investigation of specific genetic signatures and novel biomarkers for predicting reversal (and relapse). Yet CHH is a rare condition and to fully elucidate the biology of reversible CHH, it will be important to harmonize definitions of what constitutes a reversal, carefully phenotype patients and chart the natural history of their CHH. In this way, this unique human disease model may offer further insights into the control of human reproduction and provide opportunities to translate discoveries into enhanced approaches to improve the care and quality of life for these patients.

Pulmonary metastasectomy in colorectal cancer patients with previously resected liver metastasis: pooled analysis.

BACKGROUND: Data addressing the outcomes and patterns of recurrence after pulmonary metastasectomy (PM) in patients with colorectal cancer (CRC) and previously resected liver metastasis are limited. METHODS: We searched the PubMed database for studies assessing PM in CRC and gathered individual data for patients who had PM and a previous curative liver resection. The influence of potential factors on overall survival (OS) was analyzed through univariate and multivariate analysis. RESULTS: Between 1983 and 2009, 146 patients from five studies underwent PM and had previous liver resection. The median interval from resection of liver metastasis until detection of lung metastasis and the median follow-up from PM were 23 and 48 months, respectively. Five-year OS and recurrence-free survival rates calculated from the date of PM were 54.4 and 29.3 %, respectively. Factors predicting inferior OS in univariate analysis included thoracic lymph node (LN) involvement and size of largest lung nodule ≥2 cm. Adjuvant chemotherapy and whether lung metastasis was detected synchronous or metachronous to liver metastasis had no influence on survival. In multivariate analysis, thoracic LN involvement emerged as the only independent factor (hazard ratio 4.86, 95 % confidence interval 1.56-15.14, p = 0.006). CONCLUSIONS: PM offers a chance for long-term survival in selected patients with CRC and previously resected liver metastasis. Thoracic LN involvement predicted poor prognosis; therefore, significant efforts should be undertaken for adequate staging of the mediastinum before PM. In addition, adequate intraoperative LN sampling allows proper prognostic stratification and enrollment in novel adjuvant therapy trials.

Use of the dried blood spot sampling process coupled with fast gas chromatography and negative-ion chemical ionization tandem mass spectrometry: application to fluoxetine, norfluoxetine, reboxetine, and paroxetine analysis.

The objective of this work was to combine the advantages of the dried blood spot (DBS) sampling process with the highly sensitive and selective negative-ion chemical ionization tandem mass spectrometry (NICI-MS-MS) to analyze for recent antidepressants including fluoxetine, norfluoxetine, reboxetine, and paroxetine from micro whole blood samples (i.e., 10 microL). Before analysis, DBS samples were punched out, and antidepressants were simultaneously extracted and derivatized in a single step by use of pentafluoropropionic acid anhydride and 0.02% triethylamine in butyl chloride for 30 min at 60 degrees C under ultrasonication. Derivatives were then separated on a gas chromatograph coupled with a triple-quadrupole mass spectrometer operating in negative selected reaction monitoring mode for a total run time of 5 min. To establish the validity of the method, trueness, precision, and selectivity were determined on the basis of the guidelines of the "Société Française des Sciences et des Techniques Pharmaceutiques" (SFSTP). The assay was found to be linear in the concentration ranges 1 to 500 ng mL(-1) for fluoxetine and norfluoxetine and 20 to 500 ng mL(-1) for reboxetine and paroxetine. Despite the small sampling volume, the limit of detection was estimated at 20 pg mL(-1) for all the analytes. The stability of DBS was also evaluated at -20 degrees C, 4 degrees C, 25 degrees C, and 40 degrees C for up to 30 days. Furthermore, the method was successfully applied to a pharmacokinetic investigation performed on a healthy volunteer after oral administration of a single 40-mg dose of fluoxetine. Thus, this validated DBS method combines an extractive-derivative single step with a fast and sensitive GC-NICI-MS-MS technique. Using microliter blood samples, this procedure offers a patient-friendly tool in many biomedical fields such as checking treatment adherence, therapeutic drug monitoring, toxicological analyses, or pharmacokinetic studies.

Trace element monitoring in the ICU: quality and economic impact of a change in sampling practice.

BACKGROUND & AIMS: Trace elements (TE) are involved in the immune and antioxidant defences which are of particular importance during critical illness. Determining plasma TE levels is costly. The present quality control study aimed at assessing the economic impact of a computer reminded blood sampling versus a risk guided on-demand monitoring of plasma concentrations of selenium, copper, and zinc. METHODS: Retrospective analysis of 2 cohorts of patients admitted during 6 months periods in 2006 and 2009 to the ICU of a University hospital. INCLUSION CRITERIA: to receive intravenous micronutrient supplements and/or to have a TE sampling during ICU stay. The TE samplings were triggered by computerized reminder in 2006 versus guided by nutritionists in 2009. RESULTS: During the 2 periods 636 patients met the inclusion criteria out of 2406 consecutive admissions, representing 29.7% and 24.9% respectively of the periods' admissions. The 2009 patients had higher SAPS2 scores (p = 0.02) and lower BMI compared to 2006 (p = 0.007). The number of laboratory determinations was drastically reduced in 2009, particularly during the first week, despite the higher severity of the cohort, resulting in à 55% cost reduction. CONCLUSIONS: The monitoring of TE concentrations guided by a nutritionist resulted in a reduction of the sampling frequency, and targeting on the sickest high risk patients, requiring a nutritional prescription adaptation. This control leads to cost reduction compared to an automated sampling prescription.

L'exploitation des peintures en spray en criminalistique: mise en place d'une procédure de gestion et de comparaison des spectres infrarouges à l'aide des statistiques multivariées

La spectroscopie infrarouge (FTIR) est une technique de choix dans l'analyse des peintures en spray (traces ou bonbonnes de référence), grâce à son fort pouvoir discriminant, sa sensibilité, et ses nombreuses possibilités d'échantillonnage. La comparaison des spectres obtenus est aujourd'hui principalement faite visuellement, mais cette procédure présente des limitations telles que la subjectivité de la prise de décision car celle-ci dépend de l'expérience et de la formation suivie par l'expert. De ce fait, de faibles différences d'intensités relatives entre deux pics peuvent être perçues différemment par des experts, même au sein d'un même laboratoire. Lorsqu'il s'agit de justifier ces différences, certains les expliqueront par la méthode analytique utilisée, alors que d'autres estimeront plutôt qu'il s'agit d'une variabilité intrinsèque à la peinture et/ou à son vécu (par exemple homogénéité, sprayage, ou dégradation). Ce travail propose d'étudier statistiquement les différentes sources de variabilité observables dans les spectres infrarouges, de les identifier, de les comprendre et tenter de les minimiser. Le deuxième objectif principal est de proposer une procédure de comparaison des spectres qui soit davantage transparente et permette d'obtenir des réponses reproductibles indépendamment des experts interrogés. La première partie du travail traite de l'optimisation de la mesure infrarouge et des principaux paramètres analytiques. Les conditions nécessaires afin d'obtenir des spectres reproductibles et minimisant la variation au sein d'un même échantillon (intra-variabilité) sont présentées. Par la suite une procédure de correction des spectres est proposée au moyen de prétraitements et de sélections de variables, afin de minimiser les erreurs systématiques et aléatoires restantes, et de maximiser l'information chimique pertinente. La seconde partie présente une étude de marché effectuée sur 74 bonbonnes de peintures en spray représentatives du marché suisse. Les capacités de discrimination de la méthode FTIR au niveau de la marque et du modèle sont évaluées au moyen d'une procédure visuelle, et comparées à diverses procédures statistiques. Les limites inférieures de discrimination sont testées sur des peintures de marques et modèles identiques mais provenant de différents lots de production. Les résultats ont montré que la composition en pigments était particulièrement discriminante, à cause des étapes de corrections et d'ajustement de la couleur subies lors de la production. Les particularités associées aux peintures en spray présentes sous forme de traces (graffitis, gouttelettes) ont également été testées. Trois éléments sont mis en évidence et leur influence sur le spectre infrarouge résultant testée : 1) le temps minimum de secouage nécessaire afin d'obtenir une homogénéité suffisante de la peinture et, en conséquence, de la surface peinte, 2) la dégradation initiée par le rayonnement ultra- violet en extérieur, et 3) la contamination provenant du support lors du prélèvement. Finalement une étude de population a été réalisée sur 35 graffitis de la région lausannoise et les résultats comparés à l'étude de marché des bonbonnes en spray. La dernière partie de ce travail s'est concentrée sur l'étape de prise de décision lors de la comparaison de spectres deux-à-deux, en essayant premièrement de comprendre la pratique actuelle au sein des laboratoires au moyen d'un questionnaire, puis de proposer une méthode statistique de comparaison permettant d'améliorer l'objectivité et la transparence lors de la prise de décision. Une méthode de comparaison basée sur la corrélation entre les spectres est proposée, et ensuite combinée à une évaluation Bayesienne de l'élément de preuve au niveau de la source et au niveau de l'activité. Finalement des exemples pratiques sont présentés et la méthodologie est discutée afin de définir le rôle précis de l'expert et des statistiques dans la procédure globale d'analyse des peintures. -- Infrared spectroscopy (FTIR) is a technique of choice for analyzing spray paint speciments (i.e. traces) and reference samples (i.e. cans seized from suspects) due to its high discriminating power, sensitivity and sampling possibilities. The comparison of the spectra is currently carried out visually, but this procedure has limitations such as the subjectivity in the decision due to its dependency on the experience and training of the expert. This implies that small differences in the relative intensity of two peaks can be perceived differently by experts, even between analysts working in the same laboratory. When it comes to justifying these differences, some will explain them by the analytical technique, while others will estimate that the observed differences are mostly due to an intrinsic variability from the paint sample and/or its acquired characteristics (for example homogeneity, spraying, or degradation). This work proposes to statistically study the different sources of variability observed in infrared spectra, to identify them, understand them and try to minimize them. The second goal is to propose a procedure for spectra comparison that is more transparent, and allows obtaining reproducible answers being independent from the expert. The first part of the manuscript focuses on the optimization of infrared measurement and on the main analytical parameters. The necessary conditions to obtain reproducible spectra with a minimized variation within a sample (intra-variability) are presented. Following that a procedure of spectral correction is then proposed using pretreatments and variable selection methods, in order to minimize systematic and random errors, and increase simultaneously relevant chemical information. The second part presents a market study of 74 spray paints representative of the Swiss market. The discrimination capabilities of FTIR at the brand and model level are evaluated by means of visual and statistical procedures. The inferior limits of discrimination are tested on paints coming from the same brand and model, but from different production batches. The results showed that the pigment composition was particularly discriminatory, because of the corrections and adjustments made to the paint color during its manufacturing process. The features associated with spray paint traces (graffitis, droplets) were also tested. Three elements were identified and their influence on the resulting infrared spectra were tested: 1) the minimum shaking time necessary to obtain a sufficient homogeneity of the paint and subsequently of the painted surface, 2) the degradation initiated by ultraviolet radiation in an exterior environment, and 3) the contamination from the support when paint is recovered. Finally a population study was performed on 35 graffitis coming from the city of Lausanne and surroundings areas, and the results were compared to the previous market study of spray cans. The last part concentrated on the decision process during the pairwise comparison of spectra. First, an understanding of the actual practice among laboratories was initiated by submitting a questionnaire. Then, a proposition for a statistical method of comparison was advanced to improve the objectivity and transparency during the decision process. A method of comparison based on the correlation between spectra is proposed, followed by the integration into a Bayesian framework at both source and activity levels. Finally, some case examples are presented and the recommended methodology is discussed in order to define the role of the expert as well as the contribution of the tested statistical approach within a global analytical sequence for paint examinations.

Serum Vitamin D Concentrations Are Not Associated with Insulin Resistance in Swiss Adults.

BACKGROUND: Low vitamin D status has been associated with an increased risk of developing type 2 diabetes and insulin resistance (IR), although this has been recently questioned. OBJECTIVE: We examined the association between serum vitamin D metabolites and incident IR. METHODS: This was a prospective, population-based study derived from the CoLaus (Cohorte Lausannoise) study including 3856 participants (aged 51.2 ± 10.4 y; 2217 women) free from diabetes or IR at baseline. IR was defined as a homeostasis model assessment (HOMA) index >2.6. Fasting plasma insulin and glucose were measured at baseline and at follow-up to calculate the HOMA index. The association of vitamin D metabolites with incident IR was analyzed by logistic regression, and the results were expressed for each independent variable as ORs and 95% CIs. RESULTS: During the 5.5-y follow-up, 649 (16.9%) incident cases of IR were identified. Participants who developed IR had lower baseline serum concentrations of 25-hydroxyvitamin D3 [25(OH)D3 (25-hydroxycholecalciferol); 45.9 ± 22.8 vs. 49.9 ± 22.6 nmol/L; P < 0.001], total 25(OH)D3 (25(OH)D3 + epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3]; 49.1 ± 24.3 vs. 53.3 ± 24.1 nmol/L; P < 0.001), and 3-epi-25(OH)D3 (4.2 ± 2.9 vs. 4.3 ± 2.5 nmol/L; P = 0.01) but a higher 3-epi- to total 25(OH)D3 ratio (0.09 ± 0.05 vs. 0.08 ± 0.04; P = 0.007). Multivariable analysis adjusting for month of sampling, age, and sex showed an inverse association between 25(OH)D3 and the likelihood of developing IR [ORs (95% CIs): 0.86 (0.68, 1.09), 0.60 (0.46, 0.78), and 0.57 (0.43, 0.75) for the second, third, and fourth quartiles compared with the first 25(OH)D3 quartile; P-trend < 0.001]. Similar associations were found between total 25(OH)D3 and incident IR. There was no significant association between 3-epi-25(OH)D3 and IR, yet a positive association was observed between the 3-epi- to total 25(OH)D3 ratio and incident IR. Further adjustment for body mass index, sedentary status, and smoking attenuated the association between 25(OH)D3, total 25(OH)D3, and the 3-epi- to total 25(OH)D3 ratio and the likelihood of developing IR. CONCLUSION: In the CoLaus study in healthy adults, the risk of incident IR is not associated with serum concentrations of 25(OH)D3 and total 25(OH)D3.

Prenatal Risk Factors and Outcomes in Gastroschisis: A Meta-Analysis.

BACKGROUND AND OBJECTIVE: Gastroschisis is a congenital anomaly with increasing incidence, easy prenatal diagnosis and extremely variable postnatal outcomes. Our objective was to systematically review the evidence regarding the association between prenatal ultrasound signs (intraabdominal bowel dilatation [IABD], extraabdominal bowel dilatation, gastric dilatation [GD], bowel wall thickness, polyhydramnios, and small for gestational age) and perinatal outcomes in gastroschisis (bowel atresia, intra uterine death, neonatal death, time to full enteral feeding, length of total parenteral nutrition and length of in hospital stay). METHODS: Medline, Embase, and Cochrane databases were searched electronically. Studies exploring the association between antenatal ultrasound signs and outcomes in gastroschisis were considered suitable for inclusion. Two reviewers independently extracted relevant data regarding study characteristics and pregnancy outcome. All meta-analyses were computed using individual data random-effect logistic regression, with single study as the cluster unit. RESULTS: Twenty-six studies, including 2023 fetuses, were included. We found significant positive associations between IABD and bowel atresia (odds ratio [OR]: 5.48, 95% confidence interval [CI] 3.1-9.8), polyhydramnios and bowel atresia (OR: 3.76, 95% CI 1.7-8.3), and GD and neonatal death (OR: 5.58, 95% CI 1.3-24.1). No other ultrasound sign was significantly related to any other outcome. CONCLUSIONS: IABD, polyhydramnios, and GD can be used to an extent to identify a subgroup of neonates with a prenatal diagnosis of gastroschisis at higher risk to develop postnatal complications. Data are still inconclusive on the predictive ability of several signs combined, and large prospective studies are needed to improve the quality of prenatal counseling and the neonatal care for this condition.