The EU-ADR Web Platform: delivering advanced pharmacovigilance tools

PURPOSE: Pharmacovigilance methods have advanced greatly during the last decades, making post-market drug assessment an essential drug evaluation component. These methods mainly rely on the use of spontaneous reporting systems and health information databases to collect expertise from huge amounts of real-world reports. The EU-ADR Web Platform was built to further facilitate accessing, monitoring and exploring these data, enabling an in-depth analysis of adverse drug reactions risks.METHODS: The EU-ADR Web Platform exploits the wealth of data collected within a large-scale European initiative, the EU-ADR project. Millions of electronic health records, provided by national health agencies, are mined for specific drug events, which are correlated with literature, protein and pathway data, resulting in a rich drug-event dataset. Next, advanced distributed computing methods are tailored to coordinate the execution of data-mining and statistical analysis tasks. This permits obtaining a ranked drug-event list, removing spurious entries and highlighting relationships with high risk potential.RESULTS: The EU-ADR Web Platform is an open workspace for the integrated analysis of pharmacovigilance datasets. Using this software, researchers can access a variety of tools provided by distinct partners in a single centralized environment. Besides performing standalone drug-event assessments, they can also control the pipeline for an improved batch analysis of custom datasets. Drug-event pairs can be substantiated and statistically analysed within the platform's innovative working environment.CONCLUSIONS: A pioneering workspace that helps in explaining the biological path of adverse drug reactions was developed within the EU-ADR project consortium. This tool, targeted at the pharmacovigilance community, is available online at https://bioinformatics.ua.pt/euadr/. Copyright © 2012 John Wiley & Sons, Ltd.

Impact de la prophylaxie hormonale sur les fractures du fémur proximal des femmes postménopausiques: une étude de simulation. [Impact of hormonal prevention on fractures of the proximal femur in postmenopausal women: a simulation study].

A simulation model of the effects of hormone replacement therapy (HRT) on hip fractures and their consequences is based on a population of 100,000 post-menopausal women. This cohort is confronted with literature derived probabilities of cancers (endometrium or breast, which are contra-indications to HRT), hip fracture, disability requiring nursing home or home care, and death. Administration of HRT for life prevents 55,5% of hip fractures, 22,6% of years with home care and 4,4% of years in nursing homes. If HRT is administered for 15 years, these results are 15,5%, 10% and 2,2%, respectively. A slight gain in life expectancy is observed for both durations of HRT. The net financial loss in the simulated population is 222 million Swiss Francs (cost/benefit ratio 1.25) for lifelong administration of HRT, and 153 million Swiss Francs (cost/benefit ratio 1.42) if HRT is administered during 15 years.

Integrated application of geochemical and geophysical methods for hydrogeological impact assessment for tunneling in fractured rock

The interaction of tunneling with groundwater is a problem both from an environmental and an engineering point of view. In fact, tunnel drilling may cause a drawdown of piezometric levels and water inflows into tunnels that may cause problems during excavation of the tunnel. While the influence of tunneling on the regional groundwater systems may be adequately predicted in porous media using analytical solutions, such an approach is difficult to apply in fractured rocks. Numerical solutions are preferable and various conceptual approaches have been proposed to describe and model groundwater flow through fractured rock masses, ranging from equivalent continuum models to discrete fracture network simulation models. However, their application needs many preliminary investigations on the behavior of the groundwater system based on hydrochemical and structural data. To study large scale flow systems in fractured rocks of mountainous terrains, a comprehensive study was conducted in southern Switzerland, using as case studies two infrastructures actually under construction: (i) the Monte Ceneri base railway tunnel (Ticino), and the (ii) San Fedele highway tunnel (Roveredo, Graubiinden). The chosen approach in this study combines the temporal and spatial variation of geochemical and geophysical measurements. About 60 localities from both surface and underlying tunnels were temporarily and spatially monitored during more than one year. At first, the project was focused on the collection of hydrochemical and structural data. A number of springs, selected in the area surrounding the infrastructures, were monitored for discharge, electric conductivity, pH, and temperature. Water samples (springs, tunnel inflows and rains) were taken for isotopic analysis; in particular the stable isotope composition (δ2Η, δ180 values) can reflect the origin of the water, because of spatial (recharge altitude, topography, etc.) and temporal (seasonal) effects on precipitation which in turn strongly influence the isotopic composition of groundwater. Tunnel inflows in the accessible parts of the tunnels were also sampled and, if possible, monitored with time. Noble-gas concentrations and their isotope ratios were used in selected locations to better understand the origin and the circulation of the groundwater. In addition, electrical resistivity and VLF-type electromagnetic surveys were performed to identify water bearing fractures and/or weathered areas that could be intersected at depth during tunnel construction. The main goal of this work was to demonstrate that these hydrogeological data and geophysical methods, combined with structural and hydrogeological information, can be successfully used in order to develop hydrogeological conceptual models of the groundwater flow in regions to be exploited for tunnels. The main results of the project are: (i) to have successfully tested the application of electrical resistivity and VLF-electromagnetic surveys to asses water-bearing zones during tunnel drilling; (ii) to have verified the usefulness of noble gas, major ion and stable isotope compositions as proxies for the detection of faults and to understand the origin of the groundwater and its flow regimes (direct rain water infiltration or groundwater of long residence time); and (iii) to have convincingly tested the combined application of a geochemical and geophysical approach to assess and predict the vulnerability of springs to tunnel drilling. - L'interférence entre eaux souterraines et des tunnels pose des problèmes environnementaux et de génie civile. En fait, la construction d'un tunnel peut faire abaisser le niveau des nappes piézométriques et faire infiltrer de l'eau dans le tunnel et ainsi créer des problème pendant l'excavation. Alors que l'influence de la construction d'un tunnel sur la circulation régionale de l'eau souterraine dans des milieux poreux peut être prédite relativement facilement par des solution analytiques de modèles, ceci devient difficile dans des milieux fissurés. Dans ce cas-là, des solutions numériques sont préférables et plusieurs approches conceptuelles ont été proposées pour décrire et modéliser la circulation d'eau souterraine à travers les roches fissurées, en allant de modèles d'équivalence continue à des modèles de simulation de réseaux de fissures discrètes. Par contre, leur application demande des investigations importantes concernant le comportement du système d'eau souterraine basées sur des données hydrochimiques et structurales. Dans le but d'étudier des grands systèmes de circulation d'eau souterraine dans une région de montagnes, une étude complète a été fait en Suisse italienne, basée sur deux grandes infrastructures actuellement en construction: (i) Le tunnel ferroviaire de base du Monte Ceneri (Tessin) et (ii) le tunnel routière de San Fedele (Roveredo, Grisons). L'approche choisie dans cette étude est la combinaison de variations temporelles et spatiales des mesures géochimiques et géophysiques. Environs 60 localités situées à la surface ainsi que dans les tunnels soujacents ont été suiviès du point de vue temporel et spatial pendant plus de un an. Dans un premier temps le projet se focalisait sur la collecte de données hydrochimiques et structurales. Un certain nombre de sources, sélectionnées dans les environs des infrastructures étudiées ont été suivies pour le débit, la conductivité électrique, le pH et la température. De l'eau (sources, infiltration d'eau de tunnel et pluie) a été échantillonnés pour des analyses isotopiques; ce sont surtout les isotopes stables (δ2Η, δ180) qui peuvent indiquer l'origine d'une eaux, à cause de la dépendance d'effets spatiaux (altitude de recharge, topographie etc.) ainsi que temporels (saisonaux) sur les précipitations météoriques , qui de suite influencent ainsi la composition isotopique de l'eau souterraine. Les infiltrations d'eau dans les tunnels dans les parties accessibles ont également été échantillonnées et si possible suivies au cours du temps. La concentration de gaz nobles et leurs rapports isotopiques ont également été utilisées pour quelques localités pour mieux comprendre l'origine et la circulation de l'eau souterraine. En plus, des campagnes de mesures de la résistivité électrique et électromagnétique de type VLF ont été menées afin d'identifier des zone de fractures ou d'altération qui pourraient interférer avec les tunnels en profondeur pendant la construction. Le but principal de cette étude était de démontrer que ces données hydrogéologiques et géophysiques peuvent être utilisées avec succès pour développer des modèles hydrogéologiques conceptionels de tunnels. Les résultats principaux de ce travail sont : i) d'avoir testé avec succès l'application de méthodes de la tomographie électrique et des campagnes de mesures électromagnétiques de type VLF afin de trouver des zones riches en eau pendant l'excavation d'un tunnel ; ii) d'avoir prouvé l'utilité des gaz nobles, des analyses ioniques et d'isotopes stables pour déterminer l'origine de l'eau infiltrée (de la pluie par le haut ou ascendant de l'eau remontant des profondeurs) et leur flux et pour déterminer la position de failles ; et iii) d'avoir testé d'une manière convainquant l'application combinée de méthodes géochimiques et géophysiques pour juger et prédire la vulnérabilité de sources lors de la construction de tunnels. - L'interazione dei tunnel con il circuito idrico sotterraneo costituisce un problema sia dal punto di vista ambientale che ingegneristico. Lo scavo di un tunnel puô infatti causare abbassamenti dei livelli piezometrici, inoltre le venute d'acqua in galleria sono un notevole problema sia in fase costruttiva che di esercizio. Nel caso di acquiferi in materiale sciolto, l'influenza dello scavo di un tunnel sul circuito idrico sotterraneo, in genere, puô essere adeguatamente predetta attraverso l'applicazione di soluzioni analitiche; al contrario un approccio di questo tipo appare inadeguato nel caso di scavo in roccia. Per gli ammassi rocciosi fratturati sono piuttosto preferibili soluzioni numeriche e, a tal proposito, sono stati proposti diversi approcci concettuali; nella fattispecie l'ammasso roccioso puô essere modellato come un mezzo discreto ο continuo équivalente. Tuttavia, una corretta applicazione di qualsiasi modello numerico richiede necessariamente indagini preliminari sul comportamento del sistema idrico sotterraneo basate su dati idrogeochimici e geologico strutturali. Per approfondire il tema dell'idrogeologia in ammassi rocciosi fratturati tipici di ambienti montani, è stato condotto uno studio multidisciplinare nel sud della Svizzera sfruttando come casi studio due infrastrutture attualmente in costruzione: (i) il tunnel di base del Monte Ceneri (canton Ticino) e (ii) il tunnel autostradale di San Fedele (Roveredo, canton Grigioni). L'approccio di studio scelto ha cercato di integrare misure idrogeochimiche sulla qualité e quantité delle acque e indagini geofisiche. Nella fattispecie sono state campionate le acque in circa 60 punti spazialmente distribuiti sia in superficie che in sotterraneo; laddove possibile il monitoraggio si è temporalmente prolungato per più di un anno. In una prima fase, il progetto di ricerca si è concentrato sull'acquisizione dati. Diverse sorgenti, selezionate nelle aree di possibile influenza attorno allé infrastrutture esaminate, sono state monitorate per quel che concerne i parametri fisico-chimici: portata, conduttività elettrica, pH e temperatura. Campioni d'acqua sono stati prelevati mensilmente su sorgenti, venute d'acqua e precipitazioni, per analisi isotopiche; nella fattispecie, la composizione in isotopi stabili (δ2Η, δ180) tende a riflettere l'origine delle acque, in quanto, variazioni sia spaziali (altitudine di ricarica, topografia, etc.) che temporali (variazioni stagionali) della composizione isotopica delle precipitazioni influenzano anche le acque sotterranee. Laddove possibile, sono state campionate le venute d'acqua in galleria sia puntualmente che al variare del tempo. Le concentrazioni dei gas nobili disciolti nell'acqua e i loro rapporti isotopici sono stati altresi utilizzati in alcuni casi specifici per meglio spiegare l'origine delle acque e le tipologie di circuiti idrici sotterranei. Inoltre, diverse indagini geofisiche di resistività elettrica ed elettromagnetiche a bassissima frequenza (VLF) sono state condotte al fine di individuare le acque sotterranee circolanti attraverso fratture dell'ammasso roccioso. Principale obiettivo di questo lavoro è stato dimostrare come misure idrogeochimiche ed indagini geofisiche possano essere integrate alio scopo di sviluppare opportuni modelli idrogeologici concettuali utili per lo scavo di opere sotterranee. I principali risultati ottenuti al termine di questa ricerca sono stati: (i) aver testato con successo indagini geofisiche (ERT e VLF-EM) per l'individuazione di acque sotterranee circolanti attraverso fratture dell'ammasso roccioso e che possano essere causa di venute d'acqua in galleria durante lo scavo di tunnel; (ii) aver provato l'utilità di analisi su gas nobili, ioni maggiori e isotopi stabili per l'individuazione di faglie e per comprendere l'origine delle acque sotterranee (acque di recente infiltrazione ο provenienti da circolazioni profonde); (iii) aver testato in maniera convincente l'integrazione delle indagini geofisiche e di misure geochimiche per la valutazione della vulnérabilité delle sorgenti durante lo scavo di nuovi tunnel. - "La NLFA (Nouvelle Ligne Ferroviaire à travers les Alpes) axe du Saint-Gothard est le plus important projet de construction de Suisse. En bâtissant la nouvelle ligne du Saint-Gothard, la Suisse réalise un des plus grands projets de protection de l'environnement d'Europe". Cette phrase, qu'on lit comme présentation du projet Alptransit est particulièrement éloquente pour expliquer l'utilité des nouvelles lignes ferroviaires transeuropéens pour le développement durable. Toutefois, comme toutes grandes infrastructures, la construction de nouveaux tunnels ont des impacts inévitables sur l'environnement. En particulier, le possible drainage des eaux souterraines réalisées par le tunnel peut provoquer un abaissement du niveau des nappes piézométriques. De plus, l'écoulement de l'eau à l'intérieur du tunnel, conduit souvent à des problèmes d'ingénierie. Par exemple, d'importantes infiltrations d'eau dans le tunnel peuvent compliquer les phases d'excavation, provoquant un retard dans l'avancement et dans le pire des cas, peuvent mettre en danger la sécurité des travailleurs. Enfin, l'infiltration d'eau peut être un gros problème pendant le fonctionnement du tunnel. Du point de vue de la science, avoir accès à des infrastructures souterraines représente une occasion unique d'obtenir des informations géologiques en profondeur et pour échantillonner des eaux autrement inaccessibles. Dans ce travail, nous avons utilisé une approche pluridisciplinaire qui intègre des mesures d'étude hydrogéochimiques effectués sur les eaux de surface et des investigations géophysiques indirects, tels que la tomographic de résistivité électrique (TRE) et les mesures électromagnétiques de type VLF. L'étude complète a été fait en Suisse italienne, basée sur deux grandes infrastructures actuellement en construction, qui sont le tunnel ferroviaire de base du Monte Ceneri, une partie du susmentionné projet Alptransit, situé entièrement dans le canton Tessin, et le tunnel routière de San Fedele, situé a Roveredo dans le canton des Grisons. Le principal objectif était de montrer comment il était possible d'intégrer les deux approches, géophysiques et géochimiques, afin de répondre à la question de ce que pourraient être les effets possibles dû au drainage causés par les travaux souterrains. L'accès aux galeries ci-dessus a permis une validation adéquate des enquêtes menées confirmant, dans chaque cas, les hypothèses proposées. A cette fin, nous avons fait environ 50 profils géophysiques (28 imageries électrique bidimensionnels et 23 électromagnétiques) dans les zones de possible influence par le tunnel, dans le but d'identifier les fractures et les discontinuités dans lesquelles l'eau souterraine peut circuler. De plus, des eaux ont été échantillonnés dans 60 localités situées la surface ainsi que dans les tunnels subjacents, le suivi mensuelle a duré plus d'un an. Nous avons mesurés tous les principaux paramètres physiques et chimiques: débit, conductivité électrique, pH et température. De plus, des échantillons d'eaux ont été prélevés pour l'analyse mensuelle des isotopes stables de l'hydrogène et de l'oxygène (δ2Η, δ180). Avec ces analyses, ainsi que par la mesure des concentrations des gaz rares dissous dans les eaux et de leurs rapports isotopiques que nous avons effectués dans certains cas spécifiques, il était possible d'expliquer l'origine des différents eaux souterraines, les divers modes de recharge des nappes souterraines, la présence de possible phénomènes de mélange et, en général, de mieux expliquer les circulations d'eaux dans le sous-sol. Le travail, même en constituant qu'une réponse partielle à une question très complexe, a permis d'atteindre certains importants objectifs. D'abord, nous avons testé avec succès l'applicabilité des méthodes géophysiques indirectes (TRE et électromagnétiques de type VLF) pour prédire la présence d'eaux souterraines dans le sous-sol des massifs rocheux. De plus, nous avons démontré l'utilité de l'analyse des gaz rares, des isotopes stables et de l'analyses des ions majeurs pour la détection de failles et pour comprendre l'origine des eaux souterraines (eau de pluie par le haut ou eau remontant des profondeurs). En conclusion, avec cette recherche, on a montré que l'intégration des ces informations (géophysiques et géochimiques) permet le développement de modèles conceptuels appropriés, qui permettant d'expliquer comment l'eau souterraine circule. Ces modèles permettent de prévoir les infiltrations d'eau dans les tunnels et de prédire la vulnérabilité de sources et des autres ressources en eau lors de construction de tunnels.

Prediction of Childhood Asthma Using Conditional Probability and Discrete Event Simulation

Abstract: Asthma prevalence in children and adolescents in Spain is 10-17%. It is the most common chronic illness during childhood. Prevalence has been increasing over the last 40 years and there is considerable evidence that, among other factors, continued exposure to cigarette smoke results in asthma in children. No statistical or simulation model exist to forecast the evolution of childhood asthma in Europe. Such a model needs to incorporate the main risk factors that can be managed by medical authorities, such as tobacco (OR = 1.44), to establish how they affect the present generation of children. A simulation model using conditional probability and discrete event simulation for childhood asthma was developed and validated by simulating realistic scenario. The parameters used for the model (input data) were those found in the bibliography, especially those related to the incidence of smoking in Spain. We also used data from a panel of experts from the Hospital del Mar (Barcelona) related to actual evolution and asthma phenotypes. The results obtained from the simulation established a threshold of a 15-20% smoking population for a reduction in the prevalence of asthma. This is still far from the current level in Spain, where 24% of people smoke. We conclude that more effort must be made to combat smoking and other childhood asthma risk factors, in order to significantly reduce the number of cases. Once completed, this simulation methodology can realistically be used to forecast the evolution of childhood asthma as a function of variation in different risk factors.

Soluble MHC-peptide complexes: tools for the monitoring of T cell responses in clinical trials and basic research.

Soluble MHC-peptide complexes, commonly known as tetramers, allow the detection and isolation of antigen-specific T cells. Although other types of soluble MHC-peptide complexes have been introduced, the most commonly used MHC class I staining reagents are those originally described by Altman and Davis. As these reagents have become an essential tool for T cell analysis, it is important to have a large repertoire of such reagents to cover a broad range of applications in cancer research and clinical trials. Our tetramer collection currently comprises 228 human and 60 mouse tetramers and new reagents are continuously being added. For the MHC II tetramers, the list currently contains 21 human (HLA-DR, DQ and DP) and 5 mouse (I-A(b)) tetramers. Quantitative enumeration of antigen-specific T cells by tetramer staining, especially at low frequencies, critically depends on the quality of the tetramers and on the staining procedures. For conclusive longitudinal monitoring, standardized reagents and analysis protocols need to be used. This is especially true for the monitoring of antigen-specific CD4+ T cells, as there are large variations in the quality of MHC II tetramers and staining conditions. This commentary provides an overview of our tetramer collection and indications on how tetramers should be used to obtain optimal results.

Performance Analysis of Two Quantum Reaction Dynamics Codes: Time-Dependent and Time-Independent Strategies

The computer simulation of reaction dynamics has nowadays reached a remarkable degree of accuracy. Triatomic elementary reactions are rigorously studied with great detail on a straightforward basis using a considerable variety of Quantum Dynamics computational tools available to the scientific community. In our contribution we compare the performance of two quantum scattering codes in the computation of reaction cross sections of a triatomic benchmark reaction such as the gas phase reaction Ne + H2+ %12. NeH++ H. The computational codes are selected as representative of time-dependent (Real Wave Packet [ ]) and time-independent (ABC [ ]) methodologies. The main conclusion to be drawn from our study is that both strategies are, to a great extent, not competing but rather complementary. While time-dependent calculations advantages with respect to the energy range that can be covered in a single simulation, time-independent approaches offer much more detailed information from each single energy calculation. Further details such as the calculation of reactivity at very low collision energies or the computational effort related to account for the Coriolis couplings are analyzed in this paper.

Simulit, un modèle de simulation pour la planification hospitalière. [Simulit, a simulation model for hospital planning].

The aim of this computerized simulation model is to provide an estimate of the number of beds used by a population, taking into accounts important determining factors. These factors are demographic data of the deserved population, hospitalization rates, hospital case-mix and length of stay; these parameters can be taken either from observed data or from scenarii. As an example, the projected evolution of the number of beds in Canton Vaud for the period 1893-2010 is presented.

Simulation and Analysis of Arterial Traffic Operations Along the U.S. 61 Corridor in Burlington, Iowa, 1998

The Center for Transportation Research and Education (CTRE) used the traffic simulation model CORSIM to access proposed capacity and safety improvement strategies for the U.S. 61 corridor through Burlington, Iowa. The comparison between the base and alternative models allow for evaluation of the traffic flow performance under the existing conditions as well as other design scenarios. The models also provide visualization of performance for interpretation by technical staff, public policy makers, and the public. The objectives of this project are to evaluate the use of traffic simulation models for future use by the Iowa Department of Transportation (DOT) and to develop procedures for employing simulation modeling to conduct the analysis of alternative designs. This report presents both the findings of the U.S. 61 evaluation and an overview of model development procedures. The first part of the report includes the simulation modeling development procedures. The simulation analysis is illustrated through the Burlington U.S. 61 corridor case study application. Part I is not intended to be a user manual but simply introductory guidelines for traffic simulation modeling. Part II of the report evaluates the proposed improvement concepts in a side by side comparison of the base and alternative models.

Development of Self-Cleaning Box Culvert Designs, TR-545, 2009

The main function of a roadway culvert is to effectively convey drainage flow during normal and extreme hydrologic conditions. This function is often impaired due to the sedimentation blockage of the culvert. This research sought to understand the mechanics of sedimentation process at multi-box culverts, and develop self-cleaning systems that flush out sediment deposits using the power of drainage flows. The research entailed field observations, laboratory experiments, and numerical simulations. The specific role of each of these investigative tools is summarized below: a) The field observations were aimed at understanding typical sedimentation patterns and their dependence on culvert geometry and hydrodynamic conditions during normal and extreme hydrologic events. b) The laboratory experiments were used for modeling sedimentation process observed insitu and for testing alternative self-cleaning concepts applied to culverts. The major tasks for the initial laboratory model study were to accurately replicate the culvert performance curves and the dynamics of sedimentation process, and to provide benchmark data for numerical simulation validation. c) The numerical simulations enhanced the understanding of the sedimentation processes and aided in testing flow cases complementary to those conducted in the model reducing the number of (more expensive) tests to be conducted in the laboratory. Using the findings acquired from the laboratory and simulation works, self-cleaning culvert concepts were developed and tested for a range of flow conditions. The screening of the alternative concepts was made through experimental studies in a 1:20 scale model guided by numerical simulations. To ensure the designs are effective, performance studies were finally conducted in a 1:20 hydraulic model using the most promising design alternatives to make sure that the proposed systems operate satisfactory under closer to natural scale conditions.

Simulated-annealing-based conditional simulation for the local-scale characterization of heterogeneous aquifers

Simulated-annealing-based conditional simulations provide a flexible means of quantitatively integrating diverse types of subsurface data. Although such techniques are being increasingly used in hydrocarbon reservoir characterization studies, their potential in environmental, engineering and hydrological investigations is still largely unexploited. Here, we introduce a novel simulated annealing (SA) algorithm geared towards the integration of high-resolution geophysical and hydrological data which, compared to more conventional approaches, provides significant advancements in the way that large-scale structural information in the geophysical data is accounted for. Model perturbations in the annealing procedure are made by drawing from a probability distribution for the target parameter conditioned to the geophysical data. This is the only place where geophysical information is utilized in our algorithm, which is in marked contrast to other approaches where model perturbations are made through the swapping of values in the simulation grid and agreement with soft data is enforced through a correlation coefficient constraint. Another major feature of our algorithm is the way in which available geostatistical information is utilized. Instead of constraining realizations to match a parametric target covariance model over a wide range of spatial lags, we constrain the realizations only at smaller lags where the available geophysical data cannot provide enough information. Thus we allow the larger-scale subsurface features resolved by the geophysical data to have much more due control on the output realizations. Further, since the only component of the SA objective function required in our approach is a covariance constraint at small lags, our method has improved convergence and computational efficiency over more traditional methods. Here, we present the results of applying our algorithm to the integration of porosity log and tomographic crosshole georadar data to generate stochastic realizations of the local-scale porosity structure. Our procedure is first tested on a synthetic data set, and then applied to data collected at the Boise Hydrogeophysical Research Site.

Providing more informative projections of climate change impact on plant distribution in a mountain environment

Summary Due to their conic shape and the reduction of area with increasing elevation, mountain ecosystems were early identified as potentially very sensitive to global warming. Moreover, mountain systems may experience unprecedented rates of warming during the next century, two or three times higher than that records of the 20th century. In this context, species distribution models (SDM) have become important tools for rapid assessment of the impact of accelerated land use and climate change on the distribution plant species. In my study, I developed and tested new predictor variables for species distribution models (SDM), specific to current and future geographic projections of plant species in a mountain system, using the Western Swiss Alps as model region. Since meso- and micro-topography are relevant to explain geographic patterns of plant species in mountain environments, I assessed the effect of scale on predictor variables and geographic projections of SDM. I also developed a methodological framework of space-for-time evaluation to test the robustness of SDM when projected in a future changing climate. Finally, I used a cellular automaton to run dynamic simulations of plant migration under climate change in a mountain landscape, including realistic distance of seed dispersal. Results of future projections for the 21st century were also discussed in perspective of vegetation changes monitored during the 20th century. Overall, I showed in this study that, based on the most severe A1 climate change scenario and realistic dispersal simulations of plant dispersal, species extinctions in the Western Swiss Alps could affect nearly one third (28.5%) of the 284 species modeled by 2100. With the less severe 61 scenario, only 4.6% of species are predicted to become extinct. However, even with B1, 54% (153 species) may still loose more than 80% of their initial surface. Results of monitoring of past vegetation changes suggested that plant species can react quickly to the warmer conditions as far as competition is low However, in subalpine grasslands, competition of already present species is probably important and limit establishment of newly arrived species. Results from future simulations also showed that heavy extinctions of alpine plants may start already in 2040, but the latest in 2080. My study also highlighted the importance of fine scale and regional. assessments of climate change impact on mountain vegetation, using more direct predictor variables. Indeed, predictions at the continental scale may fail to predict local refugees or local extinctions, as well as loss of connectivity between local populations. On the other hand, migrations of low-elevation species to higher altitude may be difficult to predict at the local scale. Résumé La forme conique des montagnes ainsi que la diminution de surface dans les hautes altitudes sont reconnues pour exposer plus sensiblement les écosystèmes de montagne au réchauffement global. En outre, les systèmes de montagne seront sans doute soumis durant le 21ème siècle à un réchauffement deux à trois fois plus rapide que celui mesuré durant le 20ème siècle. Dans ce contexte, les modèles prédictifs de distribution géographique de la végétation se sont imposés comme des outils puissants pour de rapides évaluations de l'impact des changements climatiques et de la transformation du paysage par l'homme sur la végétation. Dans mon étude, j'ai développé de nouvelles variables prédictives pour les modèles de distribution, spécifiques à la projection géographique présente et future des plantes dans un système de montagne, en utilisant les Préalpes vaudoises comme zone d'échantillonnage. La méso- et la microtopographie étant particulièrement adaptées pour expliquer les patrons de distribution géographique des plantes dans un environnement montagneux, j'ai testé les effets d'échelle sur les variables prédictives et sur les projections des modèles de distribution. J'ai aussi développé un cadre méthodologique pour tester la robustesse potentielle des modèles lors de projections pour le futur. Finalement, j'ai utilisé un automate cellulaire pour simuler de manière dynamique la migration future des plantes dans le paysage et dans quatre scénarios de changement climatique pour le 21ème siècle. J'ai intégré dans ces simulations des mécanismes et des distances plus réalistes de dispersion de graines. J'ai pu montrer, avec les simulations les plus réalistes, que près du tiers des 284 espèces considérées (28.5%) pourraient être menacées d'extinction en 2100 dans le cas du plus sévère scénario de changement climatique A1. Pour le moins sévère des scénarios B1, seulement 4.6% des espèces sont menacées d'extinctions, mais 54% (153 espèces) risquent de perdre plus 80% de leur habitat initial. Les résultats de monitoring des changements de végétation dans le passé montrent que les plantes peuvent réagir rapidement au réchauffement climatique si la compétition est faible. Dans les prairies subalpines, les espèces déjà présentes limitent certainement l'arrivée de nouvelles espèces par effet de compétition. Les résultats de simulation pour le futur prédisent le début d'extinctions massives dans les Préalpes à partir de 2040, au plus tard en 2080. Mon travail démontre aussi l'importance d'études régionales à échelle fine pour évaluer l'impact des changements climatiques sur la végétation, en intégrant des variables plus directes. En effet, les études à échelle continentale ne tiennent pas compte des micro-refuges, des extinctions locales ni des pertes de connectivité entre populations locales. Malgré cela, la migration des plantes de basses altitudes reste difficile à prédire à l'échelle locale sans modélisation plus globale.

Natural genetic variation in Arabidopsis: tools, traits and prospects for evolutionary ecology.

BACKGROUND: The model plant Arabidopsis thaliana (Arabidopsis) shows a wide range of genetic and trait variation among wild accessions. Because of its unparalleled biological and genomic resources, the potential of Arabidopsis for molecular genetic analysis of this natural variation has increased dramatically in recent years. SCOPE: Advanced genomics has accelerated molecular phylogenetic analysis and gene identification by quantitative trait loci (QTL) mapping and/or association mapping in Arabidopsis. In particular, QTL mapping utilizing natural accessions is now becoming a major strategy of gene isolation, offering an alternative to artificial mutant lines. Furthermore, the genomic information is used by researchers to uncover the signature of natural selection acting on the genes that contribute to phenotypic variation. The evolutionary significance of such genes has been evaluated in traits such as disease resistance and flowering time. However, although molecular hallmarks of selection have been found for the genes in question, a corresponding ecological scenario of adaptive evolution has been difficult to prove. Ecological strategies, including reciprocal transplant experiments and competition experiments, and utilizing near-isogenic lines of alleles of interest will be a powerful tool to measure the relative fitness of phenotypic and/or allelic variants. CONCLUSIONS: As the plant model organism, Arabidopsis provides a wealth of molecular background information for evolutionary genetics. Because genetic diversity between and within Arabidopsis populations is much higher than anticipated, combining this background information with ecological approaches might well establish Arabidopsis as a model organism for plant evolutionary ecology.