Bloodstream infections related to totally implantable venous access port: What is the situation in our hospital?

Port-a-Cath© (PAC) are totally implantable devices that offer an easy and long term access to venous circulation. They have been extensively used for intravenous therapy administration and are particularly well suited for chemotherapy in oncologic patients. Previous comparative studies have shown that these devices have the lowest catheter-related bloodstream infection rates among all intravascular access systems. However, bloodstream infection (BSI) still remains a major issue of port use and epidemiology data for PAC-associated BSI (PABSI) rates differ strongly depending on studies. Also, current literature about PABSI risk factors is scarce and sometimes controversial. Such heterogeneity may depend on type of studied population and local factors. Therefore, the aim of this study was to describe local epidemiology and risk factors for PABSI in adult patients in our tertiary- care university hospital. We conducted a retrospective cohort study in order to describe local epidemiology. We also performed a nested case-control study to identify local risk factors of PABSI. We analyzed medical files of adult patients who had a PAC implanted between January 1st, 2008 and December 31st, 2009 and looked for PABSI occurrence before May 1st, 2011 to define cases. Thirty nine PABSI occurred in this population with an attack rate of 5.8%. We estimated an incidence rate of 0.08/1000 PAC-days using the case-control study. PABSI causative agents were mainly Gram positive cocci (62%). We identified three predictive factors of PABSI by multivariate statistical analysis: neutropenia on outcome date (Odds Ratio [OR]: 4.05; 95% confidence interval [CI]:1.05- 15.66; p=0.042), diabetes (OR: 11.53; 95% CI: 1.07-124.70; p=0.044) and having another infection than PABSI on outcome date (OR: 6.35; 95% CI: 1.50-26.86; p=0.012). Patients suffering from acute or renal failure (OR: 4.26; 95% CI: 0.94-19.21; p=0.059) or wearing another invasive device (OR: 2.99; 95%CI:0.96-9.31; p=0.059) did not have a statistically increased risk for developing a PABSI according to classical threshold (p<0.05) but nevertheless remained close to significance. Our study demonstrated that local epidemiology and microbiology of PABSI in our institution was similar to previous reports. A larger prospective study is required to confirm our results or to test preventive measures.

The Exotic Palaeo-Thethys Terrane in Central Iran: New geological data from Anarak, Jandaq and Posht-e-Badam areas

Résumé Le « terrane » d'Anarak-Jandak occupe une position géologique clé au nord-ouest du Microcontinent Centre-East Iranien (CE1M), connecté avec le Bloc du Grand Kavir et la ceinture métamorphique de Sanandaj-Sirjan. Nous discutons ici l'origine de ces différentes unités, reliées jusqu'à présent à des épisodes orogéniques d'âge Précambrien à Paléozoïque inférieur, pour conclure finalement de leur affinité paléotéthysienne. Leur histoire commence par un épisode de rifting d'âge Ordovicien supérieur-Dévonien inférieur, pour se terminer au Trias par la collision des blocs Cimmériens dérivé du Gondwana avec le Bloc du Turan d'affinité asiatique (événement Eocimmérien). La plus importante unité métamorphique affleurant au sud-ouest de la région de Jandak-Anarak-Kaboudan est une épaisse séquence silicoclastique à grains fins contenant des blocs ophiolitiques (marginal-sea-type), et des associations basalte-gabbro à signatures géochimiques de type supra-subduction. Dans la région de Nakhlak, nous avons daté ces gabbros par la méthode U-Pb à 387f0.11 Ma ; les roches métamorphiques pélitiques ont donné des âges de refroidissement Ar-Ar pour la muscovite de 320 à 333 Ma. Ce complexe d'accrétion "varisque" a été métamorphisé dans le faciès schiste vert-amphibolite au cours de l'accrétion de la ceinture granitique d'Airekan, d'âge Cambrien inférieur (549±15 Ma par la méthode U/Pb), qui affleure aujourd'hui à l'extrémité nord-ouest du terrane d'Anarak-Jandak . La subduction vers le nord de l'océan Paléotéthys depuis le Paléazoïque supérieur jusqu'au Trias, a permis l'accumulation de grandes quantités de matériel océanique dans la zone de subduction. Par exemple, une succession de guyots (Anarak, Kaboudan, et Meraji Seamounts) et de hauts sous-marins, entrés en collision oblique avec le prisme d'accrétion, est à l'origine d'un léger métamorphisme de type HP qui affecte ces séries {âges Ar-Ar de 280 à 230 Ma). De plus, le magmatisme bimodal de Chah Gorbeh est caractérisé d'une part par des roches de type trondjémite-gabbros (262 Ma), d'autre part par des laves en coussin de type basaltes alcalins-rhyolites; ces roches magmatiques ont recoupé l'ophiolite d'Anarak lors de la mise en place de cette dernière dans la fosse interne de subduction. Quant au prisme d'accrétion de Doshakh, d'âge essentiellement Permien supérieur, i1 a été accrété le long de la marge continentale et métamorphisé dans le faciès schiste vert. La fermeture de la Paléotéthys s'enregistre finalement par la sédimentation dans le bassin d'avant pays du flysch de Bayazeh, d'âge probable Triasique. Le matériel issu de l'arc magmatique de la Paléotéthys est très bien préservé dans les dépôts infra-arc Dévonien supérieur-Carbonifère de Godar-e-Siah, ainsi que dans la succession d'avant-arc de Nakhlak. Pendant l'intervalle Paléozoïque supérieur-Trias, la région de Jandak a été soumise à un régime extensif de type bassin d'arrière-arc, dont un témoin pourrait être la ceinture ophiolitique d'Arusan, elle-même comparable aux écailles ophiolitiques d'Aghdarband au nord-est de l'Iran. Cet ensemble métamorphique est recoupé par des granites d'arc à collisionnel datés à 215±15 Ma. Dans la région de Yazd, témoin de la marge passive Cimmérienne, la sédimentation syn-rift Silurienne à Dévonienne inférieure a été interrompue pendant l'intervalle Trias moyen-Trias supérieur; il en a été de même pour les dépôts de plate-forme Paléozoïque supérieur. L'érosion, qui dans ce dernier cas a atteint le Permien, pourrait être liée au bombement flexural de la marge passive. La collision finale n'a pas induit de déformations trop importantes, et se caractérise par la mise en place de nappes sur la marge passive. Cet événement est scellé par des dépôts molassique du Lias. D'un point de vue régional, la zone s'étendant actuellement de la Mer Noire au Pamir a été soumise à six épisodes d'extension-compression du Jurassique inférieur (début du l'ouverture en position arrière-arc de la Néotéthys) à l'Eocène moyen. Par exemple, le terrane d'AnarakJandak, probablement situé entre le Kopeh Dagh et la plate-forme nord Afghane, s'est complètement détaché de sa patrie d'origine au début du Crétacé supérieur. Des preuves de cet événement se retrouvent dans les séries de plate-forme de Khur (préservation de séries syn-rift puis de marge passive). Les ophiolites de Nain et de Sabzevar sont de plus interprétée comme un témoin de l'existence de ce bassin d'arrière-arc. Dans l'intervalle Eocène-Oligocène, l'indentation par la plaque indienne de l'Eurasie a été contemporaine de la rotation horaire de fragments de l'ancien microcontinent Iranien et de la formation du CEIM. Cette rotation est responsable du transport du terrane d'Anarak-Jandak vers sa position actuelle en Iran Central, et de la dislocation de Terranes de moindre importance, comme le bloc de Posht-e Badam. Depuis le Miocène supérieur, et à la suite de la collision entre l'Arabie et l'Iran, le ternane d'Anarak-Jandak a subi des déformations liées à l'activité d'une zone de cisaillement dextre parallèle à la suture du Zagros, à l'arrière de l'arc magmatique d'Uromieh-Dokhtar. Résumé large public Le Microcontinent Centre-Est Iranien occupe une position géologique clé au centre de l'Iran. Les différentes unités qui le composent, reliées jusqu'à présent à des épisodes orogéniques d'âge Précambrien à Paléozoïque inférieur, sont maintenant rajeunies et liés à la fermeture de l'océean Paléotéthys. Leur histoire commence par un épisode de rifting d'âge Ordovicien supérieur à Dévonien inférieur, pour se terminer au Trias par la collision des- blocs Cimmériens, dérivés du Gondwana, avec le Bloc du Turan d'affinité asiatique. Dans la marge active asiatique de la Paléotéthys, nous avons daté les restes d'un océan marginal à 387±0.11 Ma. Ce complexe d'accrétion a été métamorphisé au cours de la réaccrétion de la ceinture granitique d'Airekan, d'âge Cambrien inférieur (549±15 Ma), qui affleure aujourd'hui à l'extrémité nord-ouest du « terrane » d'Anarak-Jandak correspondant à la plus grande partie de la région étudiée. Le matériel issu de l'arc magmatique de la Paléotéthys est très bien préservé et daté du Dévonien supérieur-Carbonifère. Pendant l'intervalle Paléozoïque supérieur-Trias, la région a été soumise à un régime extensif de type bassin d'arrière-arc, dont un témoin pourrait être la ceinture ophiolitique d'Arusan, comparable aux écailles ophiolitiques d'Aghdarband au nord-est de l'Iran. Cet ensemble métamorphique est recoupé par des granites datés à 215±15 Ma. La subduction vers le nord de l'océan Paléotéthys depuis le Paléozoïque supérieur jusqu'au Trias, a permis l'accumulation de grandes quantités de matériel océanique dans la zone de subduction. Par exemple, une succession de volcans sous-marins, entrés en collision avec le prisme d'accrétion, est à l'origine d'un léger métamorphisme de type HP qui affecte ces séries (280 à 230 Ma). Quant au prisme d'accrétion de Doshakh, d'âge essentiellement Permien supérieur, il a été mis en place le long de la marge continentale et métamorphisé dans le faciès schiste vert. La fermeture de la Paléotéthys s'enregistre finalement par la sédimentation dans le bassin d'avant pays du flysch de Bayazeh, d'âge Triasique. Dans la région de Yazd, on trouve les témoins de la marge passive Cimmérienne, la sédimentation syn-rift Silurienne à Dévonienne inférieure a été interrompue pendant l'intervalle Trias moyen-Trias supérieur, marqué par la flexuration de la marge passive lorsqu'elle rentra en collision avec la marge active asiatique. Cet événement est scellé par des dépôts molassique à charbon du Lias. Le «terrane» d'Anarak-Jandak, probablement situé à l'origine entre le Kopeh Dagh et la plate-forme nord Afghane, s'est complètement détaché de cette région au début du Crétacé supérieur lors de l'ouverture d'un bassin d'arrière-arc, engendré, cette fois, par la subduction de l'océan Néotéthys situé au sud des blocs cimmériens. Des preuves de cet événement se retrouvent dans les séries syn-rift, puis de marge passive de Khour. Les ophiolites de Nain et de Sabzevar sont interprétées comme un témoin de l'existence de ce bassin d'arrière-arc. Dans l'intervalle Eocène-Oligocène, l'indentation de l'Eurasie par la plaque indienne a été contemporaine de la rotation horaire de fragments de l'ancien microcontinent centre-Iranien. Cette rotation de près de 90° est responsable du transport du « terrane » d'Anarak-Jandak vers sa position actuelle. Abstract The Anarak-Jandaq terrane occupies a strategic geological situation at the north-western part of the Central-East Iranian Microcontinent (CEIM) and in connection with the Great Kavir Block and Sanandaj-Sirjan metamorphic belt. Our recent findings redefine the origin of these mentioned areas so far attributed to the Precambrian-Early Palaeozoic orogenic episodes, to be now directly related to the tectonic evolution of the Palaeo-Tethys Ocean, commenced by Late Ordovician-Early Devonian rifting events and terminated in the Triassic by the Eocimmerian tectonic event due to the collision of the Cimmerian blocks with the Asiatic Turan block. The most distributed metamorphic unit that is exposed from the south-west of Jandaq to the Anarak and Kaboudan areas is a thick and fine grain siliciclastic sequence accompanied by marginal-sea-basin ophiolitic blocks including basalt-gabbro association with supra-subduction-geochemical signature. These gabbros in the Nakhlak area were dated by U/Pb method at 387.6 ± 0.11 Ma and the metamorphic pelitic rocks yielded a range of 320 to 333 Ma muscovite-cooling ages based on 40Ar/39 Ar method. This "Variscan" accretionary complex was metamorphosed in greenschist-amphibolite facies during accretion to the Lower Cambrian Airekan granitic belt (549 ± 15 Ma by U/Pb method) that crops out at the northwestern edge of the Anarak-Jandaq terrane. Continued northward subduction of the Palaeo-Tethys Ocean during the entire Late Palaeozoic-Middle Triassic brought huge amount of oceanic material to the subduction zone. One chain of Carboniferous-Triassic oceanic rises and seamounts (the Anarak, Kaboudan, and Meraji Seamounts) obliquely collided with the accretionary wedge and created a mild HP metamorphic event (280-230 Ma based on 40Ar/39Ar results). Bimodal magmatism of the Chah Gorbeh area is characterized by a 262 Ma trondjemite-gabbro as well as pillow alkalibasalts-rhyolites which intruded the Anarak ophiolite when it was being emplaced within the inner-wall trench. The mainly Late Permian-Triassic Doshakh wedge was accreted along the continent and metamorphosed under lower greenschist facies and the probable Triassic Bayazeh flysch filled the foreland basin during the final closure. The Palaeo-Tethys magmatic arc products have been well preserved in the Late Devonian-Carboniferous Godar-e-Siah intra-arc deposits and the Triassic Nakhlak fore-arc succession. During the Late Palaeozoic-Triassic times, the Jandaq area has been affected by back-arc extension and probably the Arusan ophiolitic belt is the remnant of this narrow basin comparable to the Aqdarband ophiolitic remnant in north-east Iran. This metamorphic belt was intruded by 215 ± 15 Ma arc to collisional granites. In the passive margin of the Cimmerian block, on the Yazd region, the Silurian-Early Devonian syn-rift succession as well as the nearly continuous Upper Palaeozoic platform-type deposition was interrupted during the Middle to Late Triassic time, local erosion down to Devonian levels may be related to flexural bulge erosion. The collision event was not so strong to generate intensive deformation but was accompanied by some nappe thrusting onto the passive margin. It is finally unconformably covered by Liassic continental molassic deposits. Related to the onset of Neo-Tethyan back-arc opening in Early Jurassic to Mid-Eocene times, six periods of extensional-compressional events have differently influenced an elongated area, extending from the West Black Sea to Pamir. The Anarak-Jandaq terrane which was situated somewhere in this affected area, probably between the Kopeh Dagh and North Afghan platform, was completely detached from its source at the beginning of the Late Cretaceous

Accès à la thrombolyse lors d'AVC: rôle des secours préhospitaliers et des médecins de premier recours [Access to thrombolysis in stroke: place of the rescue system and of the primary care physician].

Thrombolysis is the most effective treatment improving the outcome of patients suffering from acute stroke. Moreover, its effectiveness increases when administrated as quick as possible after the onset of the first symptoms. Prehospital selection of patients and their immediate transfer to stroke center are the principal factors allowing the practice of thrombolysis within the authorized time frame. On the basis of regional Swiss French data, it seems that patients evaluated by emergency physician and their direct transfer in an acute stroke unit reduces delays and allows for a higher thrombolysis rate.

The Anarak, Jandaq and Posht-e-Badam metamorphic complexes in central Iran: New geological data, relationships and tectonic implications

The Anarak, Jandaq and Posht-e-Badam metamorphic complexes occupy the NW part of the Central-East Iranian Microcontinent and are juxtaposed with the Great Kavir block and Sanandaj-Sirjan zone. Our recent findings redefine the origin of these complexes, so far attributed to the Precambrian-Early Paleozoic orogenic episodes, and now directly related to the tectonic evolution of the Paleo-Tethys Ocean. This tectonic evolution was initiated by Late Ordovician-Early Devonian rifting events and terminated in the Triassic by the Eocimmerian collision event due to the docking of the Cimmerian blocks with the Asiatic Turan block. The ``Variscan accretionary complex'' is a new name we proposed for the most widely distributed metamorphic rocks connected to the Anarak and Jandaq complexes. This accretionary complex exposed from SW of Jandaq to the Anarak and Kabudan areas is a thick and fine grain siliciclastic sequence accompanied by marginal-sea ophiolitic remnants, including gabbro-basalts with a supra-subduction-geochemical signature. New Ar-40/Ar-39 ages are obtained as 333-320 Ma for the metamorphism of this sequence under greenschist to amphibolite facies. Moreover, the limy intercalations in the volcano-sedimentary part of this complex in Godar-e-Siah yielded Upper Devonian-Tournaisian conodonts. The northeastern part of this complex in the Jandaq area was intruded by 215 +/- 15 Ma arc to collisional granite and pegmatites dated by ID-TIMS and its metamorphic rocks are characterized by Some Ar-40/Ar-39 radiometric ages of 163-156 Ma. The ``Variscan'' accretionary complex was northwardly accreted to the Airekan granitic terrane dated at 549 +/- 15 Ma. Later, from the Late Carboniferous to Triassic, huge amounts of oceanic material were accreted to its southern side and penetrated by several seamounts such as the Anarak and Kabudan. This new period of accretion is supported by the 280-230 Ma Ar-40/Ar-39 ages for the Anarak mild high-pressure metamorphic rocks and a 262 Ma U-Pb age for the trondhjemite-rhyolite association of that area. The Triassic Bayazeh flysch filled the foreland basin during the final closure of the Paleo-Tethys Ocean and was partly deposited and/or thrusted onto the Cimmerian Yazd block. The Paleo-Tethys magmatic arc products have been well-preserved in the Late Devonian-Carboniferous Godar-e-Siah intra-arc deposits and the Triassic Nakhlak fore-arc succession. On the passive margin of the Cimmerian block, in the Yazd region, the nearly continuous Upper Paleozoic platform-type deposition was totally interrupted during the Middle to Late Triassic. Local erosion, down to Lower Paleozoic levels, may be related to flexural bulge erosion. The platform was finally unconformably covered by Liassic continental molassic deposits of the Shemshak. One of the extensional periods related to Neo-Tethyan back-arc rifting in Late Cretaceous time finally separated parts of the Eocimmerian collisional domain from the Eurasian Turan domain. The opening and closing of this new ocean, characterized by the Nain and Sabzevar ophiolitic melanges, finally transported the Anarak-Jandaq composite terrane to Central Iran, accompanied by large scale rotation of the Central-East Iranian Microcontinent (CEIM). Due to many similarities between the Posht-e-Badam metamorphic complex and the Anarak-Jandaq composite terrane, the former could be part of the latter, if it was transported further south during Tertiary time. (C) 2007 Elsevier B.V. All rights reserved.

Determination of extreme floods using a distributed hydrological model

Hydrological models developed for extreme precipitation of PMP type are difficult to calibrate because of the scarcity of available data for these events. This article presents the process and results of calibration for a distributed hydrological model at fine scale developed for the estimation of probable maximal floods in the case of a PMP. This calibration is done on two Swiss catchments for two events of summer storms. The calculation done is concentrated on the estimation of the parameters of the model, divided in two parts. The first is necessary for the computation of flow speeds while the second is required for the determination of the initial and final infiltration capacities for each terrain type. The results, validated with the Nash equation show a good correlation between the simulated and observed flows. We also apply this model on two Romanian catchments, showing the river network and estimated flow.

Centralised versus Decentralised Management of Patients's Medical Records

For more than 20 years, many countries have been trying to set up a standardised medical record at the regional or at the national level. Most of them have not reached this goal, essentially due to two main difficulties related to patient identification and medical records standardisation. Moreover, the issues raised by the centralisation of all gathered medical data have to be tackled particularly in terms of security and privacy. We discuss here the interest of a noncentralised management of medical records which would require a specific procedure that gives to the patient access to his/her distributed medical data, wherever he/she is located.

AssociationViewer: a scalable and integrated software tool for visualization of large-scale variation data in genomic context.

SUMMARY: We present a tool designed for visualization of large-scale genetic and genomic data exemplified by results from genome-wide association studies. This software provides an integrated framework to facilitate the interpretation of SNP association studies in genomic context. Gene annotations can be retrieved from Ensembl, linkage disequilibrium data downloaded from HapMap and custom data imported in BED or WIG format. AssociationViewer integrates functionalities that enable the aggregation or intersection of data tracks. It implements an efficient cache system and allows the display of several, very large-scale genomic datasets. AVAILABILITY: The Java code for AssociationViewer is distributed under the GNU General Public Licence and has been tested on Microsoft Windows XP, MacOSX and GNU/Linux operating systems. It is available from the SourceForge repository. This also includes Java webstart, documentation and example datafiles.

Novel methods improve prediction of species' distributions from occurrence data

Prediction of species' distributions is central to diverse applications in ecology, evolution and conservation science. There is increasing electronic access to vast sets of occurrence records in museums and herbaria, yet little effective guidance on how best to use this information in the context of numerous approaches for modelling distributions. To meet this need, we compared 16 modelling methods over 226 species from 6 regions of the world, creating the most comprehensive set of model comparisons to date. We used presence-only data to fit models, and independent presence-absence data to evaluate the predictions. Along with well-established modelling methods such as generalised additive models and GARP and BIOCLIM, we explored methods that either have been developed recently or have rarely been applied to modelling species' distributions. These include machine-learning methods and community models, both of which have features that may make them particularly well suited to noisy or sparse information, as is typical of species' occurrence data. Presence-only data were effective for modelling species' distributions for many species and regions. The novel methods consistently outperformed more established methods. The results of our analysis are promising for the use of data from museums and herbaria, especially as methods suited to the noise inherent in such data improve.

Networking the unemployed : Can policy interventions facilitate access to employment through informal channels ?

It is widely known that informal contacts and networks constitute a major advantage when searching for a job. Unemployed people are likely to benefit from such informal contacts, but building and sustaining a network can be particularly difficult when out of employment. Interventions that allow unemployed people to effectively strengthen their networking capability could as a result be promising. Against this background, this article provides some hints in relation to the direction that such interventions could take. First, on the basis of data collected on a sample of 4,600 newly-unemployed people in the Swiss Canton of Vaud, it looks at the factors that influence jobseekers' decisions to turn to informal contacts for their job search. The article shows that many unemployed people are not making use of their network because they are unaware of the importance of this method. Second, it presents an impact analysis of an innovative intervention designed to raise awareness of the importance of networks which is tested in a randomized controlled trial setting.

ExpressionView--an interactive viewer for modules identified in gene expression data.

SUMMARY: ExpressionView is an R package that provides an interactive graphical environment to explore transcription modules identified in gene expression data. A sophisticated ordering algorithm is used to present the modules with the expression in a visually appealing layout that provides an intuitive summary of the results. From this overview, the user can select individual modules and access biologically relevant metadata associated with them. AVAILABILITY: http://www.unil.ch/cbg/ExpressionView. Screenshots, tutorials and sample data sets can be found on the ExpressionView web site.

BIO-INSPIRED COMPUTATIONAL TECHNIQUES APPLIED TO THE CLUSTERING AND VISUALIZATION OF SPATIO-TEMPORAL GEOSPATIAL DATA

The coverage and volume of geo-referenced datasets are extensive and incessantly¦growing. The systematic capture of geo-referenced information generates large volumes¦of spatio-temporal data to be analyzed. Clustering and visualization play a key¦role in the exploratory data analysis and the extraction of knowledge embedded in¦these data. However, new challenges in visualization and clustering are posed when¦dealing with the special characteristics of this data. For instance, its complex structures,¦large quantity of samples, variables involved in a temporal context, high dimensionality¦and large variability in cluster shapes.¦The central aim of my thesis is to propose new algorithms and methodologies for¦clustering and visualization, in order to assist the knowledge extraction from spatiotemporal¦geo-referenced data, thus improving making decision processes.¦I present two original algorithms, one for clustering: the Fuzzy Growing Hierarchical¦Self-Organizing Networks (FGHSON), and the second for exploratory visual data analysis:¦the Tree-structured Self-organizing Maps Component Planes. In addition, I present¦methodologies that combined with FGHSON and the Tree-structured SOM Component¦Planes allow the integration of space and time seamlessly and simultaneously in¦order to extract knowledge embedded in a temporal context.¦The originality of the FGHSON lies in its capability to reflect the underlying structure¦of a dataset in a hierarchical fuzzy way. A hierarchical fuzzy representation of¦clusters is crucial when data include complex structures with large variability of cluster¦shapes, variances, densities and number of clusters. The most important characteristics¦of the FGHSON include: (1) It does not require an a-priori setup of the number¦of clusters. (2) The algorithm executes several self-organizing processes in parallel.¦Hence, when dealing with large datasets the processes can be distributed reducing the¦computational cost. (3) Only three parameters are necessary to set up the algorithm.¦In the case of the Tree-structured SOM Component Planes, the novelty of this algorithm¦lies in its ability to create a structure that allows the visual exploratory data analysis¦of large high-dimensional datasets. This algorithm creates a hierarchical structure¦of Self-Organizing Map Component Planes, arranging similar variables' projections in¦the same branches of the tree. Hence, similarities on variables' behavior can be easily¦detected (e.g. local correlations, maximal and minimal values and outliers).¦Both FGHSON and the Tree-structured SOM Component Planes were applied in¦several agroecological problems proving to be very efficient in the exploratory analysis¦and clustering of spatio-temporal datasets.¦In this thesis I also tested three soft competitive learning algorithms. Two of them¦well-known non supervised soft competitive algorithms, namely the Self-Organizing¦Maps (SOMs) and the Growing Hierarchical Self-Organizing Maps (GHSOMs); and the¦third was our original contribution, the FGHSON. Although the algorithms presented¦here have been used in several areas, to my knowledge there is not any work applying¦and comparing the performance of those techniques when dealing with spatiotemporal¦geospatial data, as it is presented in this thesis.¦I propose original methodologies to explore spatio-temporal geo-referenced datasets¦through time. Our approach uses time windows to capture temporal similarities and¦variations by using the FGHSON clustering algorithm. The developed methodologies¦are used in two case studies. In the first, the objective was to find similar agroecozones¦through time and in the second one it was to find similar environmental patterns¦shifted in time.¦Several results presented in this thesis have led to new contributions to agroecological¦knowledge, for instance, in sugar cane, and blackberry production.¦Finally, in the framework of this thesis we developed several software tools: (1)¦a Matlab toolbox that implements the FGHSON algorithm, and (2) a program called¦BIS (Bio-inspired Identification of Similar agroecozones) an interactive graphical user¦interface tool which integrates the FGHSON algorithm with Google Earth in order to¦show zones with similar agroecological characteristics.

Phylogeographic patterning of mtDNA in the widely distributed harvest mouse (Micromys minutus) suggests dramatic cycles of range contraction and expansion during the mid- to late Pleistocene

We examined sequence variation in the mitochondrial cytochrome b gene (1140 bp, n = 73) and control region (842-851 bp, n = 74) in the Eurasian harvest mouse (Micromys minutus (Pallas, 1771)), with samples drawn from across its range, from Western Europe to Japan. Phylogeographic analyses revealed region-specific haplotype groupings combined with overall low levels of inter-regional genetic divergence. Despite the enormous intervening distance, European and East Asian samples showed a net nucleotide divergence of only 0.36%. Based on an evolutionary rate for the cytochrome b gene of 2.4%(.)(site(.)lineage(.)million years)(-1), the initial divergence time of these populations is estimated at around 80 000 years before present. Our findings are consistent with available fossil evidence that has recorded repeated cycles of extinction and recolonization of Europe by M. minutus through the Quaternary. The molecular data further suggest that recolonization occurred from refugia in the Central to East Asian region. Japanese haplotypes of M. minutus, with the exception of those from Tsushima Is., show limited nucleotide diversity (0.15%) compared with those found on the adjacent Korean Peninsula. This finding suggests recent colonization of the Japanese Archipelago, probably around the last glacial period, followed by rapid population growth.

A Confluence of Risks: Control and Compliance in the World of Unstructured Data, Big Data and the Cloud

The emergence of powerful new technologies, the existence of large quantities of data, and increasing demands for the extraction of added value from these technologies and data have created a number of significant challenges for those charged with both corporate and information technology management. The possibilities are great, the expectations high, and the risks significant. Organisations seeking to employ cloud technologies and exploit the value of the data to which they have access, be this in the form of "Big Data" available from different external sources or data held within the organisation, in structured or unstructured formats, need to understand the risks involved in such activities. Data owners have responsibilities towards the subjects of the data and must also, frequently, demonstrate that they are in compliance with current standards, laws and regulations. This thesis sets out to explore the nature of the technologies that organisations might utilise, identify the most pertinent constraints and risks, and propose a framework for the management of data from discovery to external hosting that will allow the most significant risks to be managed through the definition, implementation, and performance of appropriate internal control activities.

Insight into oversight : how information commissioners contribute to the achievement of access-to-information policy objectives

This thesis examines how oversight bodies, as part of an ATI policy, contribute to the achievement of the policy's objectives. The aim of the thesis is to see how oversight bodies and the work they do affects the implementation of their respective ATI policies and thereby contributes to the objectives of those policies using a comparative case study approach. The thesis investigates how federal/central government level information commissioners in four jurisdictions - Germany, India, Scotland, and Switzerland - enforce their respective ATI policies, which tasks they carry out in addition to their enforcement duties, the challenges they face in their work and the ways they overcome these. Qualitative data were gathered from primary and secondary documents as well as in 37 semi-structured interviews with staff of the commissioners' offices, administrative officials whose job entails complying with ATI, people who have made ATI requests and appealed to their respective oversight body, and external experts who have studied ATI implementation in their particular jurisdiction. The thesis finds that while the aspect of an oversight body's formal independence that has the greatest impact on its work is resource control and that although the powers granted by law set the framework for ensuring that the administration is properly complying with the policy, the commissioner's leadership style - a component of informal independence - has more influence than formal attributes of independence in setting out how resources are obtained and used as well as how staff set priorities and utilize the powers they are granted by law. The conclusion, therefore, is that an ATI oversight body's ability to contribute to the achievement of the policy's objectives is a function of three main factors: a. commissioner's leadership style; b. adequacy of resources and degree of control the organization has over them; c. powers and the exercise of discretion in using them. In effect, the thesis argues that it is difficult to pinpoint the value of the formal powers set out for the oversight body in the ATI law, and that their decisions on whether and how to use them are more important than the presumed strength of the powers. It also claims that the choices made by the commissioners and their staff regarding priorities and use of powers are determined to a large extent by the adequacy of resources and the degree of control the organization has over those resources. In turn, how the head of the organization leads and manages the oversight body is crucial to both the adequacy of the organization's resources and the decisions made about the use of powers. Together, these three factors have a significant impact on the body's effectiveness in contributing to ATI objectives.

Integrated methodologies to study human transcriptional regulation from functional genomics data

Abstract : The human body is composed of a huge number of cells acting together in a concerted manner. The current understanding is that proteins perform most of the necessary activities in keeping a cell alive. The DNA, on the other hand, stores the information on how to produce the different proteins in the genome. Regulating gene transcription is the first important step that can thus affect the life of a cell, modify its functions and its responses to the environment. Regulation is a complex operation that involves specialized proteins, the transcription factors. Transcription factors (TFs) can bind to DNA and activate the processes leading to the expression of genes into new proteins. Errors in this process may lead to diseases. In particular, some transcription factors have been associated with a lethal pathological state, commonly known as cancer, associated with uncontrolled cellular proliferation, invasiveness of healthy tissues and abnormal responses to stimuli. Understanding cancer-related regulatory programs is a difficult task, often involving several TFs interacting together and influencing each other's activity. This Thesis presents new computational methodologies to study gene regulation. In addition we present applications of our methods to the understanding of cancer-related regulatory programs. The understanding of transcriptional regulation is a major challenge. We address this difficult question combining computational approaches with large collections of heterogeneous experimental data. In detail, we design signal processing tools to recover transcription factors binding sites on the DNA from genome-wide surveys like chromatin immunoprecipitation assays on tiling arrays (ChIP-chip). We then use the localization about the binding of TFs to explain expression levels of regulated genes. In this way we identify a regulatory synergy between two TFs, the oncogene C-MYC and SP1. C-MYC and SP1 bind preferentially at promoters and when SP1 binds next to C-NIYC on the DNA, the nearby gene is strongly expressed. The association between the two TFs at promoters is reflected by the binding sites conservation across mammals, by the permissive underlying chromatin states 'it represents an important control mechanism involved in cellular proliferation, thereby involved in cancer. Secondly, we identify the characteristics of TF estrogen receptor alpha (hERa) target genes and we study the influence of hERa in regulating transcription. hERa, upon hormone estrogen signaling, binds to DNA to regulate transcription of its targets in concert with its co-factors. To overcome the scarce experimental data about the binding sites of other TFs that may interact with hERa, we conduct in silico analysis of the sequences underlying the ChIP sites using the collection of position weight matrices (PWMs) of hERa partners, TFs FOXA1 and SP1. We combine ChIP-chip and ChIP-paired-end-diTags (ChIP-pet) data about hERa binding on DNA with the sequence information to explain gene expression levels in a large collection of cancer tissue samples and also on studies about the response of cells to estrogen. We confirm that hERa binding sites are distributed anywhere on the genome. However, we distinguish between binding sites near promoters and binding sites along the transcripts. The first group shows weak binding of hERa and high occurrence of SP1 motifs, in particular near estrogen responsive genes. The second group shows strong binding of hERa and significant correlation between the number of binding sites along a gene and the strength of gene induction in presence of estrogen. Some binding sites of the second group also show presence of FOXA1, but the role of this TF still needs to be investigated. Different mechanisms have been proposed to explain hERa-mediated induction of gene expression. Our work supports the model of hERa activating gene expression from distal binding sites by interacting with promoter bound TFs, like SP1. hERa has been associated with survival rates of breast cancer patients, though explanatory models are still incomplete: this result is important to better understand how hERa can control gene expression. Thirdly, we address the difficult question of regulatory network inference. We tackle this problem analyzing time-series of biological measurements such as quantification of mRNA levels or protein concentrations. Our approach uses the well-established penalized linear regression models where we impose sparseness on the connectivity of the regulatory network. We extend this method enforcing the coherence of the regulatory dependencies: a TF must coherently behave as an activator, or a repressor on all its targets. This requirement is implemented as constraints on the signs of the regressed coefficients in the penalized linear regression model. Our approach is better at reconstructing meaningful biological networks than previous methods based on penalized regression. The method is tested on the DREAM2 challenge of reconstructing a five-genes/TFs regulatory network obtaining the best performance in the "undirected signed excitatory" category. Thus, these bioinformatics methods, which are reliable, interpretable and fast enough to cover large biological dataset, have enabled us to better understand gene regulation in humans.