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.

A new green fluorescent protein-based bacterial biosensor for analysing phenanthrene fluxes.

The polycyclic aromatic hydrocarbon (PAH)-degrading strain Burkholderia sp. RP007 served as host strain for the design of a bacterial biosensor for the detection of phenanthrene. RP007 was transformed with a reporter plasmid containing a transcriptional fusion between the phnS putative promoter/operator region and the gene encoding the enhanced green fluorescent protein (GFP). The resulting bacterial biosensor--Burkholderia sp. strain RP037--produced significant amounts of GFP after batch incubation in the presence of phenanthrene crystals. Co-incubation with acetate did not disturb the phenanthrene-specific response but resulted in a homogenously responding population of cells. Active metabolism was required for induction with phenanthrene. The magnitude of GFP induction was influenced by physical parameters affecting the phenanthrene flux to the cells, such as the contact surface area between solid phenanthrene and the aqueous phase, addition of surfactant, and slow phenanthrene release from Model Polymer Release System beads or from a water-immiscible oil. These results strongly suggest that the bacterial biosensor can sense different phenanthrene fluxes while maintaining phenanthrene metabolism, thus acting as a genuine sensor for phenanthrene bioavailability. A relationship between GFP production and phenanthrene mass transfer is proposed.

Genome-wide analysis of Sphingomonas wittichii RW1 behaviour during inoculation and growth in contaminated sand.

The efficacy of inoculation of single pure bacterial cultures into complex microbiomes, for example, in order to achieve increased pollutant degradation rates in contaminated material (that is, bioaugmentation), has been frustrated by insufficient knowledge on the behaviour of the inoculated bacteria under the specific abiotic and biotic boundary conditions. Here we present a comprehensive analysis of genome-wide gene expression of the bacterium Sphingomonas wittichii RW1 in contaminated non-sterile sand, compared with regular suspended batch growth in liquid culture. RW1 is a well-known bacterium capable of mineralizing dibenzodioxins and dibenzofurans. We tested the reactions of the cells both during the immediate transition phase from liquid culture to sand with or without dibenzofuran, as well as during growth and stationary phase in sand. Cells during transition show stationary phase characteristics, evidence for stress and for nutrient scavenging, and adjust their primary metabolism if they were not precultured on the same contaminant as found in the soil. Cells growing and surviving in sand degrade dibenzofuran but display a very different transcriptome signature as in liquid or in liquid culture exposed to chemicals inducing drought stress, and we obtain evidence for numerous 'soil-specific' expressed genes. Studies focusing on inoculation efficacy should test behaviour under conditions as closely as possible mimicking the intended microbiome conditions.

Characterization of rapeseed (Brassica napus) oils by bulk C, O, H, and fatty acid C stable isotope analyses

Rapeseed (Brassica napus) oils differing in cultivar, sites of growth, and harvest year were characterized by fatty acid concentrations and carbon, hydrogen, and oxygen stable isotope analyses of bulk oils (delta(13)C(bulk), delta(2)H(bulk), delta(18)O(bulk) values) and individual fatty acids (delta(13)C(FA)). The delta(13)C(bulk), delta(2)H(bulk), and delta(18)O(bulk) values were determined by continuous flow combustion and high-temperature conversion elemental analyzer isotope ratio mass spectrometry (EA/IRMS, TC-EA/IRMS). The delta(13)C(FA) values were determined using gas chromatography-combustion isotope ratio mass spectrometry (GC/C/IRMS). For comparison, other C(3) vegetable oils rich in linolenic acid (flax and false flax oils) and rich in linoleic acid (poppy, sunflower, and safflower oils) were submitted to the same chemical and isotopic analyses. The bulk and molecular delta(13)C values were typical for C(3) plants. The delta(13)C value of palmitic acid (delta(13)C(16:0)) and n-3 alpha-linolenic acid (delta(13)C(18:3n-3)) differed (p < 0.001) between rape, flax, and poppy oils. Also within species, significant differences of delta(13)C(FA) were observed (p < 0.01). The hydrogen and oxygen isotope compositions of rape oil differed between cultivars (p < 0.05). Major differences in the individual delta(13)C(FA) values were found. A plant-specific carbon isotope fractionation occurs during the biosynthesis of the fatty acids and particularly during desaturation of C(18) acids in rape and flax. Bulk oil and specific fatty acid stable isotope analysis might be useful in tracing dietary lipids differing in their origin.

Imazaquin sorption in surface and subsurface soil samples

The objective of this work was to study the sorption and desorption of imazaquin, in surface and subsurface soil samples from Brazil. Sorption and desorption steps were carried out using batch equilibration and high performance liquid chromatography analytical routines. The value of Kf,ads was positively correlated with clay content, and negatively correlated with pH of supernatant. Samples from Typic Haplustox, clayey soil profile having high clay content, provided higher Kf,ads values, and negative correlation with organic carbon, silt content, cation exchange capacity and pH.

Progress in front propagation research

We review the progress in the field of front propagation in recent years. We survey many physical, biophysical and cross-disciplinary applications, including reduced-variable models of combustion flames, Reid's paradox of rapid forest range expansions, the European colonization of North America during the 19th century, the Neolithic transition in Europe from 13 000 to 5000 years ago, the description of subsistence boundaries, the formation of cultural boundaries, the spread of genetic mutations, theory and experiments on virus infections, models of cancer tumors, etc. Recent theoretical advances are unified in a single framework, encompassing very diverse systems such as those with biased random walks, distributed delays, sequential reaction and dispersion, cohabitation models, age structure and systems with several interacting species. Directions for future progress are outlined

An Investigation of the Chemical Method of Determining the Cement Content of Hardened Concrete, MLR-71-01 and R-248, 1971

The Iowa State Highway Commission Laboratory is called upon to determine the cement content of hardened concrete when field problems relating to batch weights are encountered. The standard test for determining the cement content is ASTM C-85. An investigation of this method by the New Jersey State Highway Department involving duplicate samples and four cooperating laboratories produced very erratic results, however, the results obtained by this method have not been directly compared to known cement contents of concrete made with various cements and various aggregates used in Iowa.

Estudi experimental de la influència de l’angle d’inclinació de la mostra de combustible en la velocitat de propagació de la flama

El projecte estudia el comportament de la flama de forma experimental, ones recullen dades, es confeccionen taules, representen gràfiques i discuteixen resultats . Tot això, per arribar a aconseguir dades i resultats que permetin contrastar les prediccions de diferents models numèrics i aproximacions quasi analítiques. També s’han comparat i discutit críticament amb els estudis que ja s’havien publicat. Per tant, aquest projecte s’ha realitzat amb un combustible sòlid prim, anomenat cel•lulosa, del qual es coneix la composició, gramatge, etc. Amb aquest material, s’han tallat mostres de diferents mides, segons la característica de cada experiment a realitzar, ja que amb aquestes s’ha experimentat de dues maneres diferents: subjectant-les per les dues vores (vores inhibides) o amb una vora lliure. En qualsevol cas, totes les mostres s’han subjectat verticalment, i comencen a cremar des de la seva part superior on hi ha una resistència que s’escalfa i provoca la ignició, de manera que la combustió sigui descendent

Authentication of vegetable oils by bulk and molecular carbon isotope analyses with emphasis on olive oil and pumpkin seed oil

The authenticity of vegetable oils consumed in Slovenia and Croatia was investigated by carbon isotope analysis of the individual fatty acids by the use of gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS), and through carbon isotope analysis of the bulk oil. The fatty acids from samples of olive, pumpkin, sunflower, maize, rape, soybean, and sesame oils were separated by alkaline hydrolysis and derivatized to methyl esters for chemical characterization by capillary gas chromatography/mass spectrometry (GC/MS) prior to isotopic analysis. Enrichment in heavy carbon isotope (C-13) of th, bulk oil and of the individual fatty acids are related to (1) a thermally induced degradation during processing (deodorization, steam washing, or bleaching), (2) hydrolytic rancidity (lipolysis) and oxidative rancidity of the vegetable oils during storage, and (3) the potential blend with refined oil or other vegetable oils. The impurity or admixture of different oils may be assessed from the delta C-13(16:0) VS. delta C-13(18:1) covariations. The fatty acid compositions of Slovenian and Croatian olive oils are compared with those from the most important Mediterranean producer countries (Spain, Italy, Greece, and France).

Zinc adsorption in highly weathered soils

The objective of this work was to assess the effects of pH and ionic strength upon zinc adsorption, in three highly weathered variable charge soils. Adsorption isotherms were elaborated from batch adsorption experiments, with increasing Zn concentrations (0-80 mg L-1), and adsorption envelopes were constructed through soil samples reactions with 0.01, 0.1 and 1 mol L-1 Ca(NO3)2 solutions containing 5 mg L-1 of Zn, with an increasing pH value from 3 to 8. Driving force of reaction was quantified by Gibbs free energy and separation factor. Isotherms were C-, H- and L-type and experimental results were fitted to nonlinear Langmuir model. Maximum adsorption ranged from 59-810 mg kg-1, and Zn affinity was greater in subsoil (0.13-0.81 L kg-1) than in the topsoil samples (0.01-0.34 L kg-1). Zinc adsorption was favorable and spontaneous, and showed sharply increase (20-90%) in the 4-6 pH range. No effect of ionic strength was observed at pH values below 5, because specific adsorption mechanisms predominated in the 3-5 pH range. Above pH 5, and in subsoil samples, Zn was adsorbed by electrostatic mechanisms, since ionic strength effect was observed. Despite depth and ionic strength effects, Zn adsorption depends mainly on the pH.

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".

Prévalence et facteurs associés à la consommation de tabac non fumé chez les jeunes hommes suisses

Introduction Le tabac non fumé (smokeless tobacco) comprend les formes de tabac qui ne sont pas consommées par combustion. Les deux principaux types de consommation sont le snus, par application sur la muqueuse orale, et le tabac à sniffer. Le premier se consomme surtout en Suède et les pays scandinaves ; la consommation du second a récemment fait son apparition en Suisse malgré son interdiction. Méthodes Nous avons utilisé la base de données de la Cohort on substance use risk factors (C-surf), une cohorte de jeunes hommes suisses se présentant à 3 centres de recrutement de l'Armée Suisse (Lausanne, Windisch et Mels). Un total de 13 245 jeunes hommes ont été invités à participer à cette enquête sur la consommation de substances. Le taux de réponses a été de 45.2%. Nous avons inclu 5720 participants pour cette analyse et utilisé une approche statistique par régression logistique pour identifier les déterminants de consommation de tabac non fumé. Résultats L'âge moyen des participants était de 19.5 ans. 8% des participants ont déclaré consommer régulièrement du tabac à sniffer et 3% consommer du snus au moins une fois par mois. La consommation de tabac à sniffer était associée à la consommation non quotidienne de cigarettes [odds ratio (OR) 2.41, 95% confidence interval (Cl) 1.90-3.05], ainsi qu'à celle d'alcool à risque (OR 3.93, 95% Cl 1.86-8.32) etépisodique (OR 7.41, 95% Cl 4.11-13.38). Un BMI élevé, un revenu familial au-dessus de la moyenne et un faible niveau de formation étaient également associés à la consommation de tabac à sniffer, alors que la consommation occasionnelle de cannabis l'était négativement. Les facteurs associés à la consommation de snus étaient similaires à ceux du tabac à sniffer. Conclusions Un jeune homme suisse sur 12 consomme du tabac à sniffer et 3% consomment du snus. La consommation de tabac non fumé est associée à d'autres comportements à risque, en particulier la consommation d'alcool à risque. Les résultats de la régression logistique multivariée montrent une association de la consommation de tabac non fumé à la consommation d'alcool à risque. Le rôle du tabac non fumé dans l'induction de la dépendance à la nicotine et dans l'initiation à d'autres comportements à risque, ainsi que ses effets sur la santé devront être analysés sur la base d'études longitudinales.

Progress in front propagation research

We review the progress in the field of front propagation in recent years. We survey many physical, biophysical and cross-disciplinary applications, including reduced-variable models of combustion flames, Reid's paradox of rapid forest range expansions, the European colonization of North America during the 19th century, the Neolithic transition in Europe from 13 000 to 5000 years ago, the description of subsistence boundaries, the formation of cultural boundaries, the spread of genetic mutations, theory and experiments on virus infections, models of cancer tumors, etc. Recent theoretical advances are unified in a single framework, encompassing very diverse systems such as those with biased random walks, distributed delays, sequential reaction and dispersion, cohabitation models, age structure and systems with several interacting species. Directions for future progress are outlined