Community-wide plasmid gene mobilization and selection.

Plasmids have long been recognized as an important driver of DNA exchange and genetic innovation in prokaryotes. The success of plasmids has been attributed to their independent replication from the host's chromosome and their frequent self-transfer. It is thought that plasmids accumulate, rearrange and distribute nonessential genes, which may provide an advantage for host proliferation under selective conditions. In order to test this hypothesis independently of biases from culture selection, we study the plasmid metagenome from microbial communities in two activated sludge systems, one of which receives mostly household and the other chemical industry wastewater. We find that plasmids from activated sludge microbial communities carry among the largest proportion of unknown gene pools so far detected in metagenomic DNA, confirming their presumed role of DNA innovators. At a system level both plasmid metagenomes were dominated by functions associated with replication and transposition, and contained a wide variety of antibiotic and heavy metal resistances. Plasmid families were very different in the two metagenomes and grouped in deep-branching new families compared with known plasmid replicons. A number of abundant plasmid replicons could be completely assembled directly from the metagenome, providing insight in plasmid composition without culturing bias. Functionally, the two metagenomes strongly differed in several ways, including a greater abundance of genes for carbohydrate metabolism in the industrial and of general defense factors in the household activated sludge plasmid metagenome. This suggests that plasmids not only contribute to the adaptation of single individual prokaryotic species, but of the prokaryotic community as a whole under local selective conditions.

Scale-specific sex-biased dispersal in the Valais shrew unveiled by genetic variation on the Y chromosome, autosomes, and mitochondrial DNA.

We investigated sex specificities in the evolutionary processes shaping Y chromosome, autosomes, and mitochondrial DNA patterns of genetic structure in the Valais shrew (Sorex antinorii), a mountain dwelling species with a hierarchical distribution. Both hierarchical analyses of variance and isolation-by-distance analyses revealed patterns of population structure that were not consistent across maternal, paternal, and biparentally inherited markers. Differentiation on a Y microsatellite was lower than expected from the comparison with autosomal microsatellites and mtDNA, and it was mostly due to genetic variance among populations within valleys, whereas the opposite was observed on other markers. In addition, there was no pattern of isolation by distance for the Y, whereas there was strong isolation by distance on mtDNA and autosomes. We use a hierarchical island model of coancestry dynamics to discuss the relative roles of the microevolutionary forces that may induce such patterns. We conclude that sex-biased dispersal is the most important driver of the observed genetic structure, but with an intriguing twist: it seems that dispersal is strongly male biased at large spatial scale, whereas it is mildly biased in favor of females at local scale. These results add to recent reports of scale-specific sex-biased dispersal patterns, and emphasize the usefulness of the Y chromosome in conjunction with mtDNA and autosomes to infer sex specificities.

Compliance with the Swiss Society for Nutrition's dietary recommendations in the population of Geneva, Switzerland: a 10-year trend study (1999-2009).

The trends in compliance with the dietary recommendations of the Swiss Society for Nutrition in the Geneva population were assessed for the period from 1999 to 2009 using 10 cross-sectional, population-based surveys (Bus Santé study) with a total of 9,320 participants aged 35 to 75 years (50% women). Dietary intake was assessed using a self-administered, validated, semi-quantitative food frequency questionnaire. Trends were assessed by logistic regression adjusting for age, smoking status, education, and nationality using survey year as the independent variable. After excluding participants with extreme intakes, the percentage of participants with a cholesterol intake of <300 mg/day increased from 40.8% in 1999 to 43.6% in 2009 for men (multivariate-adjusted P for trend=0.04) and from 57.8% to 61.4% in women (multivariate-adjusted P for trend=0.06). Calcium intake >1 g/day decreased from 53.3% to 46% in men and from 47.6% to 40.7% in women (multivariate-adjusted P for trend<0.001). Adequate iron intake decreased from 68.3% to 65.3% in men and from 13.3% to 8.4% in women (multivariate-adjusted P for trend<0.001). Conversely, no significant changes were observed for carbohydrates, protein, total fat (including saturated, monounsaturated, and polyunsaturated fatty acids), fiber, and vitamins D and A. We conclude that the quality of the Swiss diet did not improve between 1999 and 2009 and that intakes deviate substantially from expert recommendations for health promotion and chronic disease risk reduction.

Phosphorus and carbon burial during cretaceous oceanic anoxic events, links with climatic changes

According to Jenkyns (2010), oceanic anoxic events (OAE) record profound changes in the climatic and paleoceanographic state of the planet and represent major disturbances in the global carbon cycle. One of the most studied OAEs on a worldwide scale is the Cenomanian-Turonian OAE 2, which is characterized by a pronounced positive excursion in carbon-isotope records and the important accumulation of organic-rich sediments. The section at Gongzha (Tibet) and the sections at Barranca and Axaxacualco (Mexico) are located in remote parts of the Tethys, and show δ13C records, which are well correlated with those of classical Tethyan sections. Both sections, however, do not exhibit the presence of organic-rich sediments. Phosphorus Mass Accumulation Rates (PMAR) in Tibet show a pattern similar to that observed in the Tethys by Mort et al. (2007), which suggests enhanced Ρ regeneration during the OAE 2 time interval, though there is no evidence for anoxic conditions in Tibet. Ρ appears here to have been mainly driven by detrital influx and sea-level fluctuations. The sections at Barranca and Axaxacualco show that the Mexican carbonate platform persisted during this anoxic event, which allowed the evolution of platform fauna otherwise not present in Tethyan sections. The persistence of this carbonate platform close to the Caribbean Igneous Plateau, which is thought to have released bio-limiting metals, is explained by local uplift which delayed the drowning of the platform and a specific oceanic circulation that permitted the preservation of oligotrophic conditions in the area. The Coniacian-Santonian OAE (OAE3) appears to have been more dependent on local conditions than OAE2. The presence of black shales associated with OAE3 appear to have been restricted to shallow-water settings and epicontinental seas in areas located around the Atlantic Ocean. The sections at Olazagutia (Spain), and Ten Mile - Arbor Park (USA), two potential Global Boundary Stratotype Sections and Points (GSSP) sites, are devoid of organic-rich sediments and lack a δ13C positive excursion around the C-S boundary. The Gabal Ekma section (Sinai, Egypt) exhibits accumulations of organic-rich sediments, in addition to phosphorite bone beds layers, which may have been linked to an epicontinental upwelling zone and/or storm inputs. Our data suggest that OAE 3 is rarely expressed by truly anoxic conditions and seems to have been linked to local conditions rather than global paleoenvironmental change. The evidence for detrital-P being the likely cause of Ρ fluctuations during the OAEs studied here does not negate the idea that anoxia was the principal driver of these fluctuations in the western Tethys. However, an explanation is required as to why the Ρ accumulation signatures are mirrored in both oxic and anoxic sedimentary successions. 'Eustatic/climatic' and 'productivity/anoxic' models may have both operated simultaneously in different parts of the world depending on local conditions, both producing similar trends in Ρ accumulation. - Selon Jenkyns (2010), les événements anoxiques océaniques enregistrent de profonds changements dans le climat et la paléoceanographie de la planète et représente des perturbations majeures du cycle du carbone. L'un des plus étudiés à l'échelle mondiale est l'ΟΑΕ2 du Cénomanien-Turonien, qui est caractérisé par une très forte excursion positive des isotopes du carbone et une importante accumulation de sédiments riche en matière organique. La section de Gongzha (Tibet) et les sections de Barranca et Axaxcualco (Mexique) sont situées aux confins de la Téthys, et enregistrent une courbe isotopique en δ13C parfaitement corrélable avec les sections téthysiennes, mais ne montre pas d'accumulation de black shales. Le taux de phosphore en accumulation de masses (PMAR) au Tibet montre un pattern similaire observé également par Mort et al. (2007) dans la Téthys, suggérant un model de régénération du Ρ durant l'anoxie, cependant aucune conditions anoxiques régnent dans la région du Tibet. Ρ apparaît donc principalement guidé par le détritisme et les fluctuations du niveau marin. Les sections de Barranca et d'Axaxacualco montrent que la plateforme carbonatée mexicaine persiste durant cet événement anoxique, et permet le développement d'une faune de plateforme qui n'est pas présente dans les sections téthysiennes. La persistance de cette plateforme carbonatée si proche du plateau Caribéen, qui est connu pour le relâchement de métaux bio-limitant, peut être expliqué par un soulèvement tectonique local qui inhibe l'ennoiement de la plateforme et une circulation océanique spécifique qui permet la préservation de conditions oligotrophiques dans cette région. L'événement anoxique océanique du Coniacien-Santonien apparaît plus dépendant des conditions locales que pour l'ΟΑΕ2. Les black shales associés à POAE3 sont restreints aux zones situées autour de l'océan Atlantique et plus particulièrement aux eaux peu profondes et épicontinentales. Les sections d'Olazagutia (Espagne), Ten Mile Creek et Arbor Park (USA), qui sont deux potentielles sections GSSP (Sections de stratotype de limite globaux et de points), ne montre pas d'accumulation de black shales et pas de forte excursion positive en δ13C autour de la limite C-S. La section de Gabal Ekma (Sinai, Egypte) montre des accumulations de black shales, en plus des couches de phosphorites et d'accumulation d'os (« bone beds »), vraisemblablement lié à des zones active d'upwelling épicontinentale et/ou d'apport de tempêtes. Nos données suggèrent que l'OAE 3 est rarement exprimé par de vraies conditions anoxiques et semble être plus lié à des conditions plus locales que des changements paléo-environnementaux globaux, comme observés pour le Cénomanien- Turonien. Les arguments pour un modèle lié au phosphore détritique qui serait la cause des fluctuations du phosphore total durant les OAEs, n'écartent pas l'idée que l'anoxie est la principale cause de ces fluctuations dans les sections riches en matière organique de l'Ouest téthysien. Cependant une explication est nécessaire pour comprendre pourquoi la signature de l'accumulation du phosphore est semblable dans les successions sédimentaires déposées dans des conditions oxygénées et anoxiques. Les modèles « Eustatisme/Climat » et « Productivité/anoxie » ont simultanément opéré dans les différentes parties du monde dépendant de conditions locales, et ont produit des tendances similaires en accumulation de phosphore.

Climate change and plant distribution: local models predict high-elevation persistence

Mountain ecosystems will likely be affected by global warming during the 21st century, with substantial biodiversity loss predicted by species distribution models (SDMs). Depending on the geographic extent, elevation range and spatial resolution of data used in making these models, different rates of habitat loss have been predicted, with associated risk of species extinction. Few coordinated across-scale comparisons have been made using data of different resolution and geographic extent. Here, we assess whether climate-change induced habitat losses predicted at the European scale (10x10' grid cells) are also predicted from local scale data and modeling (25x25m grid cells) in two regions of the Swiss Alps. We show that local-scale models predict persistence of suitable habitats in up to 100% of species that were predicted by a European-scale model to lose all their suitable habitats in the area. Proportion of habitat loss depends on climate change scenario and study area. We find good agreement between the mismatch in predictions between scales and the fine-grain elevation range within 10x10' cells. The greatest prediction discrepancy for alpine species occurs in the area with the largest nival zone. Our results suggest elevation range as the main driver for the observed prediction discrepancies. Local scale projections may better reflect the possibility for species to track their climatic requirement toward higher elevations.

Estimating traveltimes and groundwater flow patterns using 3D time-lapse crosshole ERT imaging of electrical resistivity fluctuations induced by infiltrating river water

The infiltration of river water into aquifers is of high relevance to drinking-water production and is a key driver of biogeochemical processes in the hyporheic and riparian zone, but the distribution and quantification of the infiltrating water are difficult to determine using conventional hydrological methods (e.g., borehole logging and tracer tests). By time-lapse inverting crosshole ERT (electrical resistivity tomography) monitoring data, we imaged groundwater flow patterns driven by river water infiltrating a perialpine gravel aquifer in northeastern Switzerland. This was possible because the electrical resistivity of the infiltrating water changed during rainfall-runoff events. Our time-lapse resistivity models indicated rather complex flow patterns as a result of spatially heterogeneous bank filtration and aquifer heterogeneity. The upper part of the aquifer was most affected by the river infiltrate, and the highest groundwater velocities and possible preferential flow occurred at shallow to intermediate depths. Time series of the reconstructed resistivity models matched groundwater electrical resistivity data recorded on borehole loggers in the upper and middle parts of the aquifer, whereas the resistivity models displayed smaller variations and delayed responses with respect to the logging data. in the lower part. This study demonstrated that crosshole ERT monitoring of natural electrical resistivity variations of river infiltrate could be used to image and quantify 3D bank filtration and aquifer dynamics at a high spatial resolution.

Assessment of diesel exhaust particulate exposure and surface characteristics in association with levels of oxidative stress biomarkers

Exposure to PM10 and PM2.5 (particulate matter with aerodynamic diameter smaller than 10 μm and 2.5 μm, respectively) is associated with a range of adverse health effects, including cancer, pulmonary and cardiovascular diseases. Surface characteristics (chemical reactivity, surface area) are considered of prime importance to understand the mechanisms which lead to harmful effects. A hypothetical mechanism to explain these adverse effects is the ability of components (organics, metal ions) adsorbed on these particles to generate Reactive Oxygen Species (ROS), and thereby to cause oxidative stress in biological systems (Donaldson et al., 2003). ROS can attack almost any cellular structure, like DNA or cellular membrane, leading to the formation of a wide variety of degradation products which can be used as a biomarker of oxidative stress. The aim of the present research project is to test whether there is a correlation between the exposure to Diesel Exhaust Particulate (DEP) and the oxidative stress status. For that purpose, a survey has been conducted in real occupational situations where workers were exposed to DEP (bus depots). Different exposure variables have been considered: - particulate number, size distribution and surface area (SMPS); - particulate mass - PM2.5 and PM4 (gravimetry); - elemental and organic carbon (coulometry); - total adsorbed heavy metals - iron, copper, manganese (atomic adsorption); - surface functional groups present on aerosols (Knudsen flow reactor). Several biomarkers of oxidative stress (8-hydroxy-2'-deoxyguanosine and several aldehydes) have been determined either in urine or serum of volunteers. Results obtained during the sampling campaign in several bus depots indicated that the occupational exposure to particulates in these places was rather low (40-50 μg/m3 for PM4). Bimodal size distributions were generally observed (5 μm and <1 μm). Surface characteristics of PM4 varied strongly, depending on the bus depot. They were usually characterized by high carbonyl and low acidic sites content. Among the different biomarkers which have been analyzed within the framework of this study, mean urinary levels of 8-hydroxy-2'-deoxyguanosine increased significantly (p<0.05) during two consecutive days of exposure for non-smoker workers. On the other hand, no statistically significant differences were observed for serum levels of hexanal, nonanal and 4- hydroxy-nonenal (p>0.05). Biomarkers levels will be compared to exposure variables to gain a better understanding of the relation between the particulate characteristics and the formation of ROS by-products. This project is financed by the Swiss State Secretariat for Education and Research. It is conducted within the framework of the COST Action 633 "Particulate Matter - Properties Related to Health Effects".

ALK inhibitors in the treatment of advanced NSCLC.

Pharmacologic agents that target protein products of oncogenes in tumors are playing an increasing clinical role in the treatment of cancer. Currently, the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represent the standard of care for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring activating EGFR mutations. Subsequently other genetic abnormalities with "driver" characteristics - implying transforming and tumor maintenance capabilities have been extensively reported in several small distinct subsets of NSCLC. Among these rare genetic changes, anaplastic lymphoma kinase (ALK) gene rearrangements, most often consisting in a chromosome 2 inversion leading to a fusion with the echinoderm microtubule-associated protein like 4 (EML4) gene, results in the abnormal expression and activation of this tyrosine kinase in the cytoplasm of cancer cells. This rearrangement occurs in 2-5% of NSCLC, predominantly in young (50 years or younger), never- or former-smokers with adenocarcinoma. This aberration most commonly occurs a independently of EGFR and KRAS gene mutations. A fluorescent in situ hybridization assay was approved by the US Food and Drug Administration (FDA) as the standard method for the detection of ALK gene rearrangement in clinical practice and is considered the gold standard. Crizotinib, a first-in-class dual ALK and c-MET inhibitor, has been shown to be particularly effective against ALK positive NSCLC, showing dramatic and prolonged responses with low toxicity, predominantly restricted to the gastro-intestinal and visual systems, and generally self-limiting or easily managed. However, resistance to crizotinib inevitably emerges. The molecular mechanisms of resistance are currently under investigation, as are therapeutic approaches including crizotinib-based combination therapy and novel agents such as Hsp90 inhibitors. This review aims to present the current knowledge on this fusion gene, the clinic-pathological profile of ALK rearranged NSCLC, and to review the existing literature on ALK inhibitors, focusing on their role in the treatment of NSCLC.

Trends in dietary intake in Switzerland, 1999 to 2009.

OBJECTIVE: To assess nutrition trends of the Geneva population for the period 1999-2009. DESIGN: Bus Santé Geneva study, which conducts annual health surveys in random samples of the Geneva population. Dietary intake was assessed using a validated FFQ and trends were assessed by linear regression. SETTING: Population-based survey. SUBJECTS: Data from 9283 participants (50% women, mean age 51·5 (sd 10·8) years) were analysed. RESULTS: In both genders total energy intake decreased from 1999 to 2009, by 2·9% in men and by 6·3% in women (both trends P < 0·005). Vegetable protein and total carbohydrate intakes, expressed as a percentage of total energy intake, increased in women. MUFA intake increased while SFA, PUFA and alcohol intakes decreased in both genders. Intakes of Ca, Fe and carotene decreased in both genders. No changes in fibre, vitamin D and vitamin A intakes were found. Similar findings were obtained after excluding participants with extreme dietary intakes, except that the decreases in SFA, vegetable protein and carbohydrate were no longer significant in women. CONCLUSIONS: Between 1999 and 2009, a small decrease in total energy intake was noted in the Geneva population. Although the decrease in alcohol and SFA intakes is of interest, the decrease in Ca and Fe intakes may have adverse health effects in the future.

Étude des mécanismes de transfert des fibres en sciences forensiques

RESUME Les fibres textiles sont des produits de masse utilisés dans la fabrication de nombreux objets de notre quotidien. Le transfert de fibres lors d'une action délictueuse est dès lors extrêmement courant. Du fait de leur omniprésence dans notre environnement, il est capital que l'expert forensique évalue la valeur de l'indice fibres. L'interprétation de l'indice fibres passe par la connaissance d'un certain nombre de paramètres, comme la rareté des fibres, la probabilité de leur présence par hasard sur un certain support, ainsi que les mécanismes de transfert et de persistance des fibres. Les lacunes les plus importantes concernent les mécanismes de transfert des fibres. A ce jour, les nombreux auteurs qui se sont penchés sur le transfert de fibres ne sont pas parvenus à créer un modèle permettant de prédire le nombre de fibres que l'on s'attend à retrouver dans des circonstances de contact données, en fonction des différents paramètres caractérisant ce contact et les textiles mis en jeu. Le but principal de cette recherche est de démontrer que la création d'un modèle prédictif du nombre de fibres transférées lors d'un contact donné est possible. Dans le cadre de ce travail, le cas particulier du transfert de fibres d'un tricot en laine ou en acrylique d'un conducteur vers le dossier du siège de son véhicule a été étudié. Plusieurs caractéristiques des textiles mis en jeu lors de ces expériences ont été mesurées. Des outils statistiques (régression linéaire multiple) ont ensuite été utilisés sur ces données afin d'évaluer l'influence des caractéristiques des textiles donneurs sur le nombre de fibres transférées et d'élaborer un modèle permettant de prédire le nombre de fibres qui vont être transférées à l'aide des caractéristiques influençant significativement le transfert. Afin de faciliter la recherche et le comptage des fibres transférées lors des expériences de transfert, un appareil de recherche automatique des fibres (liber finder) a été utilisé dans le cadre de cette recherche. Les tests d'évaluation de l'efficacité de cet appareil pour la recherche de fibres montrent que la recherche automatique est globalement aussi efficace qu'une recherche visuelle pour les fibres fortement colorées. Par contre la recherche automatique perd de son efficacité pour les fibres très pâles ou très foncées. Une des caractéristiques des textiles donneurs à étudier est la longueur des fibres. Afin de pouvoir évaluer ce paramètre, une séquence d'algorithmes de traitement d'image a été implémentée. Cet outil permet la mesure de la longueur d'une fibre à partir de son image numérique à haute résolution (2'540 dpi). Les tests effectués montrent que les mesures ainsi obtenues présentent une erreur de l'ordre du dixième de millimètre, ce qui est largement suffisant pour son utilisation dans le cadre de cette recherche. Les résultats obtenus suite au traitement statistique des résultats des expériences de transfert ont permis d'aboutir à une modélisation du phénomène du transfert. Deux paramètres sont retenus dans le modèle: l'état de la surface du tissu donneur et la longueur des fibres composant le tissu donneur. L'état de la surface du tissu est un paramètre tenant compte de la quantité de fibres qui se sont détachées de la structure du tissu ou qui sont encore faiblement rattachées à celle-ci. En effet, ces fibres sont les premières à se transférer lors d'un contact, et plus la quantité de ces fibres par unité de surface est importante, plus le nombre de fibres transférées sera élevé. La longueur des fibres du tissu donneur est également un paramètre important : plus les fibres sont longues, mieux elles sont retenues dans la structure du tissu et moins elles se transféreront. SUMMARY Fibres are mass products used to produce numerous objects encountered everyday. The transfer of fibres during a criminal action is then very common. Because fibres are omnipresent in our environment, the forensic expert has to evaluate the value of the fibre evidence. To interpret fibre evidence, the expert has to know some parameters as frequency of fibres,' probability of finding extraneous fibres by chance on a given support, and transfer and persistence mechanisms. Fibre transfer is one of the most complex parameter. Many authors studied fibre transfer mechanisms but no model has been created to predict the number of fibres transferred expected in a given type of contact according to parameters as characteristics of the contact and characteristics of textiles. The main purpose of this research is to demonstrate that it is possible to create a model to predict the number of fibres transferred during a contact. In this work, the particular case of the transfer of fibres from a knitted textile in wool or in acrylic of a driver to the back of a carseat has been studied. Several characteristics of the textiles used for the experiments were measured. The data obtained were then treated with statistical tools (multiple linear regression) to evaluate the influence of the donor textile characteristics on the number of úbers transferred, and to create a model to predict this number of fibres transferred by an equation containing the characteristics having a significant influence on the transfer. To make easier the searching and the counting of fibres, an apparatus of automatic search. of fibers (fiber finder) was used. The tests realised to evaluate the efficiency of the fiber finder shows that the results obtained are generally as efficient as for visual search for well-coloured fibres. However, the efficiency of automatic search decreases for pales and dark fibres. One characteristic of the donor textile studied was the length of the fibres. To measure this parameter, a sequence of image processing algorithms was implemented. This tool allows to measure the length of a fibre from it high-resolution (2'540 dpi) numerical image. The tests done shows that the error of the measures obtained are about some tenths of millimetres. This precision is sufficient for this research. The statistical methods applied on the transfer experiment data allow to create a model of the transfer phenomenon. Two parameters are included in the model: the shedding capacity of the donor textile surface and the length of donor textile fibres. The shedding capacity of the donor textile surface is a parameter estimating the quantity of fibres that are not or slightly attached to the structure of the textile. These fibres are easily transferred during a contact, and the more this quantity of fibres is high, the more the number of fibres transferred during the contact is important. The length of fibres is also an important parameter: the more the fibres are long, the more they are attached in the structure of the textile and the less they are transferred during the contact.

Probing functional groups at the gas-aerosol interface using heterogeneous titration reactions: a tool for predicting aerosol health effects?

The complex chemical and physical nature of combustion and secondary organic aerosols (SOAs) in general precludes the complete characterization of both bulk and interfacial components. The bulk composition reveals the history of the growth process and therefore the source region, whereas the interface controls--to a large extent--the interaction with gases, biological membranes, and solid supports. We summarize the development of a soft interrogation technique, using heterogeneous chemistry, for the interfacial functional groups of selected probe gases [N(CH(3))(3), NH(2)OH, CF(3)COOH, HCl, O(3), NO(2)] of different reactivity. The technique reveals the identity and density of surface functional groups. Examples include acidic and basic sites, olefinic and polycyclic aromatic hydrocarbon (PAH) sites, and partially and completely oxidized surface sites. We report on the surface composition and oxidation states of laboratory-generated aerosols and of aerosols sampled in several bus depots. In the latter case, the biomarker 8-hydroxy-2'-deoxyguanosine, signaling oxidative stress caused by aerosol exposure, was isolated. The increase in biomarker levels over a working day is correlated with the surface density N(i)(O3) of olefinic and/or PAH sites obtained from O(3) uptakes as well as with the initial uptake coefficient, γ(0), of five probe gases used in the field. This correlation with γ(0) suggests the idea of competing pathways occurring at the interface of the aerosol particles between the generation of reactive oxygen species (ROS) responsible for oxidative stress and cellular antioxidants.

Politique fédérale des agglomérations dans les domaines des transports et de l'urbanisation

La croissance de la population, de l'économie et des transports individuels motorisés, particulièrement depuis la seconde moitié du 20ème siècle, ont notamment comme corollaire le développement urbanistique hors des frontières de la ville-centre et la formation des agglomérations. Ces zones urbaines sont stratégiques puisqu'elles accueillent une part toujours plus importante de la population et représentent le moteur de l'économie nationale. Toutefois, le développement des agglomérations et de la mobilité individuelle motorisée ne va pas sans poser de nombreux problèmes, dont la résolution nécessite de les aborder à l'échelle de l'agglomération, en coordonnant les transports et l'urbanisation. Notre système politique fédéral se définit notamment par une répartition des compétences dans une multitude de domaines entre les trois niveaux institutionnels de la Confédération, des cantons et des communes. Cette réalité est particulièrement vraie en matière d'aménagement du territoire. Il est à noter que les plus petites unités institutionnelles (les communes) conservent encore aujourd'hui des prérogatives importantes dans ce domaine. Au début des années 2000, la Confédération a développé une politique publique en faveur de ces zones stratégiques. Au moyen du fonds d'infrastructure, la politique fédérale des agglomérations dans les domaines des transports et de l'urbanisation est une politique publique incitative. Le dépôt, par les agglomérations, d'un projet respectant un cahier des charges précis et proposant des mesures de coordination entre les transports et l'urbanisation, permet d'obtenir un cofinancement fédéral du transport d'agglomération. Parmi les projets d'agglomération de première génération présentés à la Confédération, certains ont obtenu le cofinancement, d'autres pas. Le dimensionnement trop généreux des surfaces à bâtir fut notamment un facteur d'échec du projet d'agglomération de Fribourg, alors que la capacité à développer l'urbanisation à l'intérieur de l'agglomération fut un facteur de succès du projet Lausanne-Morges. L'analyse des projets d'agglomération Riviera et Monthey-Aigle, qui sont des projets de deuxième génération, confrontée à des entretiens avec des urbanistes et des responsables politiques, permet d'identifier leurs faiblesses et leurs atouts. Le projet d'agglomération Riviera présente une complémentarité des territoires et un grand potentiel de développement, mais aussi un manque de cohésion des partenaires du projet. Quant au projet Monthey-Aigle, il existe une réelle volonté politique de trouver des solutions aux conflits, mais les possibilités de développer les transports publics sont faibles. Dans le cadre de l'examen fédéral de ces deux projets d'agglomération, les éléments précités pourraient être des facteurs d'échec ou de succès. La politique publique fédérale invite les agglomérations à penser le développement de leurs transports et de leur urbanisation à un niveau global. La prise de hauteur et la coordination politique que cela suppose sont à même d'améliorer le lieu de vie des trois-quarts de la population suisse et de préserver le moteur de l'économie nationale. The growth of population, economy and personal motorised transportation, most particularly since the second half of the 20th century, has, as a consequence, induced an expansion of urban areas outside the borders of cities and encouraged the formation of urban agglomerations. These urban zones are of strategic importance as they attract an increasingly large population and represent a real driver of the national economy. However, the development of these agglomerations and the motorised mobility of their inhabitants cause numerous problems which require solutions to be adopted at the level of the agglomeration involving the interconnection of transport and urbanisation. Our federal political system is characterised by a distribution of responsibilities in many domains among the three institutional levels, namely the Confederation, the cantons and the communes. This is particularly the case of territorial developments. It should be noted that the smallest institutional units, the communes, still hold today important responsibilities in this area. At the beginning of the years 2000, the Confederation has developed a public policy in favour of these strategic zones. Through the establishment of an infrastructure fund, the federal policy in favour of urban agglomerations in the areas of transport and urbanisation aims at providing incentives to agglomerations. The submission by the agglomeration of a project containing a clear description of tasks and measures to integrate transport and urbanisation can result in a cofinancing participation by the Confederation in this project. Among the projects of first generation which had been submitted to the Confederation, some have received the cofinancing, others have not. The too generous dimension of the building areas in the project submitted by the agglomeration of Fribourg was a factor of its failure, while the capacity to develop urbanisation within the agglomeration was a factor of success for the Lausanne-Morges project. The analysis of the projects of the agglomerations Riviera and Monthey-Aigle which are projects of the second generation, as well as the interviews of urbanists and concerned officials have allowed us to identify their strengths and weaknesses. The Riviera project provides a complementary approach and a high potential of territorial developments, but at the same time denotes a lack of cohesion among partners of the project. With respect to the project Monthey-Aigle, there is a real political willingness to resolve conflicts, but the potential for the development of public transports is small. In the consideration by the Confederation of these two projects, the factors mentioned above may bring success or failure. The federal public policy incites the agglomerations to conceive the development of their transportation and urbanisation plans at a global level. The elevation of interests and the political coordination that this requires can improve the place of living of ¾ of the Swiss population and preserve the engine of growth of the national economy.

Adverse drug reactions following nonresponse in a depressed patient with CYP2D6 deficiency and low CYP 3A4/5 activity

A 47-year-old male taxi driver experienced multiple adverse drug reactions during therapy with clomipramine (CMI) and quetiapine for major depressive disorder, after having been unsuccessfully treated with adequate doses of mirtazapine and venlafaxine. Drug serum concentrations of CMI and quetiapine were significantly increased and pharmacogenetic testing showed a poor metabolizer status for CYP2D6, low CYP3A4/5 activity and normal CYP2C19 genotype. After reduction of the CMI dose and discontinuation of quetiapine, all ADR subsided except for the increase in liver enzymes. The latter improved but did not normalize completely, even months later, possibly due to concomitant cholelithiasis.

The micro-architecture estimation by TBS discriminate women with and without osteoporotic fracture independently of age, BMI and BMD: The Osteo-Mobile Vaud cohort study.

Introduction: « Osteo-Mobile Vaud » is a mobile osteoporosis (OP) screening program. The women > 60 years living in the region Vaud will be offered OP screening with new equipment installed in a bus. The main goal is to evaluate the fracture risk with the combination of clinical risk factors (CRF) and informations extracted by a single DXA: bone mineral density (BMD), vertebral fracture assessment (VFA), and micro-architecture (MA) evaluation. MA is yet evaluable in daily practice by the Trabecular Bone Score (TBS) measure. TBS is a novel grey-level texture measurement reflecting bone MA based on the use of experimental variograms of 2D projection images. TBS is very simple to obtain, by reanalyzing a lumbar DXA-scan. TBS has proven to have diagnosis and prognosis value, partially independent of CRF and BMD. A 55-years follow- up is planned. Method: The Osteo-Mobile Vaud cohort (1500 women, > 60 years, living in the region Vaud) started in July 2010. CRF for OP, lumbar spine and hip BMD, VFA by DXA and MA evaluation by TBS are recorded. Preliminary results are reported. Results: In July 31th, we evaluated 510 women: mean age 67 years, BMI 26 kg/m². 72 women had one or more fragility fractures, 39 had vertebral fracture (VFx) grade 2/3. TBS decreases with age (-0.005 / year, p<0.001), and with BMI (-0.011 per kg/m², p<0.001). Correlation between BMD and site matched TBS is low (r=0.4, p<0.001). For the lowest T-score BMD, odds ratio (OR, 95% CI) for VFx grade 2/3 and clinical OP Fx are 1.8 (1.1-2.9) and 2.3 (1.5-3.4). For TBS, age-, BMI- and BMD adjusted ORs (per SD decrease) for VFx grade 2/3 and clinical OP Fx are 1.9 (1.2-3.0) and 1.8 (1.2-2.7). The TBS added value was independent of lumbar spine BMD or the lowest T-score (femoral neck, total hip or lumbar spine). Conclusion: As in the already published studies, these preliminary results confirm the partial independence between BMD and TBS. More importantly, a combination of TBS and BMD may increase significantly the identification of women with prevalent OP Fx. For the first time we are able to have complementary information about fracture (VFA), density (BMD), and micro-architecture (TBS) from a simple, low ionizing radiation and cheap device: DXA. The value of such informations in a screening program will be evaluated.

Dynamic drag modeling of submerged aquatic vegetation canopy flows

Vegetation has a profound effect on flow and sediment transport processes in natural rivers, by increasing both skin friction and form drag. The increase in drag introduces a drag discontinuity between the in-canopy flow and the flow above, which leads to the development of an inflection point in the velocity profile, resembling a free shear layer. Therefore, drag acts as the primary driver for the entire canopy system. Most current numerical hydraulic models which incorporate vegetation rely either on simple, static plant forms, or canopy-scaled drag terms. However, it is suggested that these are insufficient as vegetation canopies represent complex, dynamic, porous blockages within the flow, which are subject to spatially and temporally dynamic drag forces. Here we present a dynamic drag methodology within a CFD framework. Preliminary results for a benchmark cylinder case highlight the accuracy of the method, and suggest its applicability to more complex cases.