Exploration pathologique des souris transgéniques porteuses du gène VPU de VIH-1

L‟infection par le VIH-1, chez les patients, affecte principalement le système immunitaire et conduit à une destruction graduelle des lymphocytes T CD4 et, par conséquent, entraîne un état d‟immunodéficience. Cette immunodéficience permet l'établissement d‟infections opportunistes qui sont responsables de manifestations cliniques associées au Sida. Ces patients peuvent aussi développer des lymphomes, lésions du système nerveux central et une atteinte rénale. L'ampleur et la sévérité des conditions associées observées chez les patients infectés par le VIH-1 ne peuvent être imputées seulement au processus infectieux et à la déplétion des cellules T CD4+. Ceci suggère que les produits des gènes de régulation pourraient avoir des effets cytopathogènes. Cependant, les études sur la physiopathogenèse induite par le VIH ou ses différents gènes ont été difficiles à mener en raison de l'absence d'animaux de laboratoire infectés par ce virus. Ceux-ci auraient pu aider à disséquer le rôle des différents composants du génome viral et les mécanismes pathogénétiques impliqués. Pour pallier cette contrainte, nous avons produit le premier modèle de souris transgéniques pour le gène vpu. Vpu code pour une phosphoprotéine membranaire avec plusieurs fonctions connues. Elle participe au relargage des virions à la surface cellulaire, induit la dégradation des CD4, induit la régulation négative des CMH-1, augmente la susceptibilité à la mort cellulaire des lymphocytes T infectés par le VIH et favorise la réplication virale en empêchant les mécanismes antiviraux cellulaires. Dans ce travail, nous avons caractérisé pathologiquement un modèle de souris transgéniques porteuses du gène vpu du VIH-1. Nos résultats démontrent que l‟expression de vpu chez les souris transgéniques induit le développement spontané d‟une hyperplasie lymphoïde pansystémique, une splénomégalie avec une hyperplasie lymphoïde folliculaire évoluant en lésions prémalignes et malignes qui présentent certaines similarités avec la maladie de Castleman et une iv glomérulonéphrite mesangioproliférative qui rappelle certaines altérations de néphropathie associée au VIH chez les patients infectés. L‟ensemble des altérations démontre que les souris Tg/vpu développent une activation chronique et non spécifique du système immunitaire. Dans cette activation immunitaire, une dérégulation de l‟IL-6 et une hyperplasie du réseau de cellules métallophiliques pourraient être impliquées. D‟autres résultats obtenus sur les évaluations du fonctionnement du système immunitaire de la rate et du thymus mettent en évidence une susceptibilité augmentée des lymphocytes des tissus lymphoïdes aux effets apoptotiques de la dexaméthasone et des lipopolysaccharides et un retard dans le repeuplement par les cellules d‟organes lymphoïdes ainsi qu‟une réaction inflammatoire (Schwartzman) exacerbée et des anomalies dans la réaction d‟hypersensibilité retardée expérimentale. Ce modèle transgénique reproduit plusieurs anomalies rencontrées chez les patients infectés par le VIH et ouvre de nouvelles hypothèses sur la pathogenèse de l‟infection par le VIH.

Cell lines and animal model in the analysis of pharmacogenomics markers in childhood acute lymphoblastic leukemia

La leucémie aiguë lymphoblastique (LAL) est le cancer pédiatrique le plus fréquent. Elle est la cause principale de mortalité liée au cancer chez les enfants due à un groupe de patient ne répondant pas au traitement. Les patients peuvent aussi souffrir de plusieurs toxicités associées à un traitement intensif de chimiothérapie. Les études en pharmacogénétique de notre groupe ont montré une corrélation tant individuelle que combinée entre les variants génétiques particuliers d’enzymes dépendantes du folate, particulièrement la dihydrofolate réductase (DHFR) ainsi que la thymidylate synthase (TS), principales cibles du méthotrexate (MTX) et le risque élevé de rechute chez les patients atteints de la LAL. En outre, des variations dans le gène ATF5 impliqué dans la régulation de l’asparagine synthetase (ASNS) sont associées à un risque plus élevé de rechute ou à une toxicité ASNase dépendante chez les patients ayant reçu de l’asparaginase d’E.coli (ASNase). Le but principal de mon projet de thèse est de comprendre davantage d’un point de vue fonctionnel, le rôle de variations génétiques dans la réponse thérapeutique chez les patients atteints de la LAL, en se concentrant sur deux composants majeurs du traitement de la LAL soit le MTX ainsi que l’ASNase. Mon objectif spécifique était d’analyser une association trouvée dans des paramètres cliniques par le biais d’essais de prolifération cellulaire de lignées cellulaires lymphoblastoïdes (LCLs, n=93) et d’un modèle murin de xénogreffe de la LAL. Une variation génétique dans le polymorphisme TS (homozygosité de l’allèle de la répétition triple 3R) ainsi que l’haplotype *1b de DHFR (défini par une combinaison particulière d’allèle dérivé de six sites polymorphiques dans le promoteur majeur et mineur de DHFR) et de leurs effets sur la sensibilité au MTX ont été évalués par le biais d’essais de prolifération cellulaire. Des essais in vitro similaires sur la réponse à l’ASNase de E. Coli ont permis d’évaluer l’effet de la variation T1562C de la région 5’UTR de ATF5 ainsi que des haplotypes particuliers du gène ASNS (définis par deux variations génétiques et arbitrairement appelés haplotype *1). Le modèle murin de xénogreffe ont été utilisé pour évaluer l’effet du génotype 3R3R du gène TS. L’analyse de polymorphismes additionnels dans le gène ASNS a révélé une diversification de l’haplotype *1 en 5 sous-types définis par deux polymorphismes (rs10486009 et rs6971012,) et corrélé avec la sensibilité in vitro à l’ASNase et l’un d’eux (rs10486009) semble particulièrement important dans la réduction de la sensibilité in vitro à l’ASNase, pouvant expliquer une sensibilité réduite de l’haplotype *1 dans des paramètres cliniques. Aucune association entre ATF5 T1562C et des essais de prolifération cellulaire en réponse à ASNase de E.Coli n’a été détectée. Nous n’avons pas détecté une association liée au génotype lors d’analyse in vitro de sensibilité au MTX. Par contre, des résultats in vivo issus de modèle murin de xénogreffe ont montré une relation entre le génotype TS 3R/3R et la résistance de manière dose-dépendante au traitement par MTX. Les résultats obtenus ont permis de fournir une explication concernant un haut risque significatif de rechute rencontré chez les patients au génotype TS 3R/3R et suggèrent que ces patients pourraient recevoir une augmentation de leur dose de MTX. À travers ces expériences, nous avons aussi démontré que les modèles murins de xénogreffe peuvent servir comme outil préclinique afin d’explorer l’option d’un traitement individualisé. En conclusion, la connaissance acquise à travers mon projet de thèse a permis de confirmer et/ou d’identifier quelques variants dans la voix d’action du MTX et de l’ASNase qui pourraient faciliter la mise en place de stratégies d’individualisation de la dose, permettant la sélection d’un traitement optimum ou moduler la thérapie basé sur la génétique individuelle.

Els recursos en l'aprenentatge de les Matemàtiques : un model per a l'EGB. 'El aprendizaje de las Matemáticas : un modelo para EGB'.

Crear un material de apoyo en el aula válido para el aprendizaje del tema 'los números enteros' de séptimo curso de EGB, que sea motivador para el alumno. 90 alumnos de la escuela pública de Sant Por de Mar, distribuidos a los tratamientos según un diseño de Solomón. Realiza una introducción teórica desde la psicología del niño, orientación, contenidos y tecnología educativa. Pasando a la elaboración de la metodología de trabajo y el material a utilizar. Realiza el diseño experimental (de Solomón) de la investigación realizando pretest y posttest, y extrayendo conclusiones del análisis de los datos sobre el material y el método. Creación de un (test de rendimiento) test de instrucción con 20 ítems. Encuesta basada en la técnica de observación directa y elaborada sobre la base de la prueba '¿qué opinas sobre tí mismo?' de la Universidad de Mariland. Comparación de medias entre grupos acorde con el diseño empleado. Estudio de la prueba: índice de dificultad y fiabilidad. Índices estadísticos y representaciones gráficas. Análisis de varianza. Respecto al material: el material gráfico impreso ofrece al maestro un medio de trabajo motivador en contenido y forma, es efectivo para el aprendizaje, y puede potenciar el cálculo mental rápido sin ocupar un tiempo excesivo, siendo además flexible y adaptable a cualquier metodología. Respecto al método: aporta material de trabajo numeroso, susceptible de ser utilizado total o parcialmente, y aceptado por el discente como útil y motivador.

El virus de l'hepatitis C i la ribonucleasa Phumana: aspectes biològics i terapèutics

El virus de l'hepatitis C (VHC) provoca una hepatitis crònica que afecta a més de 170 milions de persones d'arreu del món. És un virus petit que es classifica dins de la família Flaviviridae i és un virus d'RNA de cadena positiva amb un genoma d'aproximadament 9.600 nucleòtids. A l'extrem 5' del genoma viral s'hi troba una regió no codificant (5'NCR) que comprèn els primers 341 nucleòtids i la seva funció està relaciona amb la traducció. Immediatament després hi ha una pauta de lectura oberta ORF que acaba en un únic codó d'aturada i codifica una poliproteïna de 3.010 aminoàcids. A continuació l'extrem 3' no codificant (3'NCR), que malgrat es desconeixen les seves funcions exactes, s'ha demostrat que és essencial per a la replicació vírica. La única poliproteïna generada és processada co- i postraduccionalment mitjançant proteases de l'hoste i víriques, donant lloc a les proteïnes estructurals (Core, E1 i E2-p7) i no estructurals (NS2-NS5B). Igual que la majoria de virus RNA, el VHC es caracteritza per tenir una taxa de mutació elevada. De fet, el genoma del virus no es pot definir com una única seqüència sinó per una població de variants molt relacionades entre sí. A aquesta manera d'organitzar la informació genètica se l'anomena quasiespècie viral i una de les seves implicacions principals és la facilitat amb què sorgeixen resistents al tractament. Els tractaments disponibles són llargs, cars, provoquen efectes secundaris considerables i només es resolen completament el 40% dels casos. Per aquesta raó es busquen altres solucions terapèutiques per combatre el virus entre les quals s'hi inclouen diferents estratègies. Una de les més innovadores i prometedores és la utilització de ribozims dirigits directament contra el genoma del virus. Aquest treball es centra en l'estudi de les noves estratègies terapèutiques basades en ribozims, concretament la ribonucleasa P. La ribonucleasa P és un ribozim que està present en tots els organismes ja que és l'enzim responsable de la maduració dels precursors d'RNA de transferència. El més interessant a nivell terapèutic és que s'ha demostrat que es pot dirigir la seva activitat cap a qualsevol RNA utilitzant una seqüència guia d'RNA que quan hibrida amb l'RNA diana, l'híbrid imita l'estructura secundària del substrat natural. En el cas del VHC, s'han estudiat ribozims dependents de seqüència (ribozims derivats d'RNAs satèl·lits i de viroides de plantes), sempre dirigits contra la regió més conservada del virus per evitar una disminució de l'eficiència del ribozim deguda a la variació de la diana. La ribonucleasa P és una endonucleasa d'activitat molt específica i es diferencia dels altres ribozims naturals en el sistema de reconeixement del substrat, reconeix elements estructurals i no de seqüència. L'objectiu final del treball és tallar in vitro l'RNA del VHC aprofitant la propietat que presenta aquest ribozim de reconèixer elements estructurals i no de seqüència ja que per a un mateix nombre de seqüències, el nombre d'estructures viables que pot adoptar l'RNA genòmic és molt més petit i per tant la variabilitat de la diana disminueix. S'han estudiat dos models d'RNasa P, la RNasa P humana guiada per seqüència guia externa (EGS) i l'RNA M1 de l'RNasa P d'E.coli unit a la seqüència guia per l'extrem 3' (ribozim M1GS). Abans però de dirigir el ribozim, s'han estudiat l'estructura i la variabilitat d'una regió del genoma del virus ja que s'ha descrit que són factors que poden limitar l'eficiència de qualsevol ribozim. Derivat d'aquests estudis s'aporten dades sobre accessibilitat i variabilitat d'una regió interna del genoma del virus de l'hepatitis C, la zona d'unió de la regió E2/NS2 (regió 2658-2869). L'estudi d'accessibilitat revela que la regió 2658-2869 del genoma del virus conté dominis oberts i tancats i que la transició entre uns i altres no és brusca si es compara amb altres regions d'estructura coneguda (regió 5' no codificant). Els resultats dels assajos in vitro amb els dos models de RNasa P mostren que s'ha aconseguit dirigir tant la ribonucleasa P humana com el ribozim M1GS cap a una zona, predeterminada segons l'estudi d'accessibilitat, com a poc estructurada i tallar l'RNA del virus. De l'anàlisi de mutacions, però, es dedueix que la regió estudiada és variable. Tot i dirigir el ribozim cap a la zona més accessible, la variació de la diana podria afectar la interacció amb la seqüència guia i per tant disminuir l'eficiència de tall. Si es proposés una estratègia terapèutica consistiria en un atac simultani de vàries dianes.D'altra banda i derivat d'un resultat inesperat on s'ha observat en els experiments control que l'extracte de RNasa P humana tallava l'RNA viral en absència de seqüències guia externes, s'ha caracteritzat una nova interacció entre l'RNA del VHC i la RNasa P humana. Per a la identificació de l'enzim responsable dels talls s'han aplicat diferents tècniques que es poden dividir en mètodes directes (RNA fingerprinting) i indirectes (immunoprecipitació i inhibicions competitives). Els resultats demostren que la ribonucleasa P humana, i no un altre enzim contaminant de l'extracte purificat, és la responsable dels dos talls específics observats i que es localitzen, un a l'entrada interna al ribosoma (IRES) i molt a prop del codó AUG d'inici de la traducció i l'altre entre la regió codificant estructural i no estructural. La ribonucleasa P és un dels enzims del metabolisme del tRNA que s'utilitza per identificar estructures similars al tRNA en substrats diferents del substrat natural. Així doncs, el fet que la ribonucleasa P reconegui i talli el genoma del VHC en dues posicions determinades suggereix que, a les zones de tall, el virus conté estructures semblants al substrat natural, és a dir estructures tipus tRNA. A més, tot i que el VHC és molt variable, els resultats indiquen que aquestes estructures poden ser importants per el virus, ja que es mantenen en totes les variants naturals analitzades. Creiem que la seva presència podria permetre al genoma interaccionar amb factors cel·lulars que intervenen en la biologia del tRNA,particularment en el cas de l'estructura tipus tRNA que es localitza a l'element IRES. Independentment però de la seva funció, es converteixen en unes noves dianes terapèutiques per a la RNasa P. S'ha de replantejar però l'estratègia inicial ja que la similitud amb el tRNA les fa susceptibles a l'atac de la ribonucleasa P, directament, en absència de seqüències guia externes.

Differential susceptibilities of peach-potato aphid, Myzus persicae (Homoptera: Aphididae) and its parasitoid, Aphidius matricariae (Hymenoptera: Aphidiidae) to foliar insecticides on partially resistant and susceptible potato cultivars

In a field experiment the effects of Sumicidin (super) 5EC (fenitrothion), Metasystox EC25 (oxydemeton-methyl) and Tamaron SL600 (methamidophos), applied at different dosages, were evaluated against peach-potato aphid, Myzus persicae (Sulzer) and its parasitoid Aphidius matricariae Haliday on Cardinal and Desiree (respectively partially resistant and susceptible potato cultivars to M. persicae). Sumicidin (super) 5EC was found about 30% more effective in reducing aphid populations than the other insecticides tested. The highest doses of each insecticide caused maximum aphid mortality; in general aphid mortality appeared dose dependent. Almost all the higher and lower doses of the tested insecticides were about 19% more effective on Cardinal than on Desiree. The most significant result was the synergistic interaction at the lower doses with plant resistance, so that the same level of control was recorded with second highest dose on Cardinal as with the highest dose on Desiree. Also the same control level was achieved at the lowest dosage rate on Cardinal compared with the next higher dose on the Desiree. Sumicidin (super) 5EC was found least toxic to the parasitoid, A. matricariae in terms of percent parasitism, emergence of parasitoids and number of mature eggs in the emerging female parasitoids; increase of about 22, 67 and 47% respectively were found in parasitoid performance with Tamaron SL600 which was found comparatively highly toxic. The highest doses of all insecticides were found clearly toxic to the parasitoid. In general, effects on the parasitoid were dose dependent. Maximum yield was obtained from the second highest dose of Sumicidin (super) 5EC.

A predictive model for early-warning of Septoria leaf blotch on winter wheat

Disease-weather relationships influencing Septoria leaf blotch (SLB) preceding growth stage (GS) 31 were identified using data from 12 sites in the UK covering 8 years. Based on these relationships, an early-warning predictive model for SLB on winter wheat was formulated to predict the occurrence of a damaging epidemic (defined as disease severity of 5% or > 5% on the top three leaf layers). The final model was based on accumulated rain > 3 mm in the 80-day period preceding GS 31 (roughly from early-February to the end of April) and accumulated minimum temperature with a 0A degrees C base in the 50-day period starting from 120 days preceding GS 31 (approximately January and February). The model was validated on an independent data set on which the prediction accuracy was influenced by cultivar resistance. Over all observations, the model had a true positive proportion of 0.61, a true negative proportion of 0.73, a sensitivity of 0.83, and a specificity of 0.18. True negative proportion increased to 0.85 for resistant cultivars and decreased to 0.50 for susceptible cultivars. Potential fungicide savings are most likely to be made with resistant cultivars, but such benefits would need to be identified with an in-depth evaluation.

Epidemiological risk assessment using linked network and grid based modelling: Phytophthora ramorum and Phytophthora kernoviae in the UK

We developed a stochastic simulation model incorporating most processes likely to be important in the spread of Phytophthora ramorum and similar diseases across the British landscape (covering Rhododendron ponticum in woodland and nurseries, and Vaccinium myrtillus in heathland). The simulation allows for movements of diseased plants within a realistically modelled trade network and long-distance natural dispersal. A series of simulation experiments were run with the model, representing an experiment varying the epidemic pressure and linkage between natural vegetation and horticultural trade, with or without disease spread in commercial trade, and with or without inspections-with-eradication, to give a 2 x 2 x 2 x 2 factorial started at 10 arbitrary locations spread across England. Fifty replicate simulations were made at each set of parameter values. Individual epidemics varied dramatically in size due to stochastic effects throughout the model. Across a range of epidemic pressures, the size of the epidemic was 5-13 times larger when commercial movement of plants was included. A key unknown factor in the system is the area of susceptible habitat outside the nursery system. Inspections, with a probability of detection and efficiency of infected-plant removal of 80% and made at 90-day intervals, reduced the size of epidemics by about 60% across the three sectors with a density of 1% susceptible plants in broadleaf woodland and heathland. Reducing this density to 0.1% largely isolated the trade network, so that inspections reduced the final epidemic size by over 90%, and most epidemics ended without escape into nature. Even in this case, however, major wild epidemics developed in a few percent of cases. Provided the number of new introductions remains low, the current inspection policy will control most epidemics. However, as the rate of introduction increases, it can overwhelm any reasonable inspection regime, largely due to spread prior to detection. (C) 2009 Elsevier B.V. All rights reserved.

The Ca(v)2.3 calcium channel antagonist SNX-482 reduces dorsal horn neuronal responses in a rat model of chronic neuropathic pain

Neuropathic pain is a difficult state to treat, characterized by alterations in sensory processing that can include allodynia (touch-evoked pain). Evidence exists for nerve damage-induced plasticity in both transmission and modulatory systems, including changes in voltage-dependent calcium channel (VDCC) expression and function; however, the role of Ca(v)2.3 calcium channels has not clearly been defined. Here, the effects of SNX-482, a selective Ca(v)2.3 antagonist, on sensory transmission at the spinal cord level have been investigated in the rat. The spinal nerve ligation (SNL) model of chronic neuropathic pain [Kim & Chung, (1992) Pain, 50, 355-363] was used to induce mechanical allodynia, as tested on the ipsilateral hindpaw. In vivo electrophysiological measurements of dorsal horn neuronal responses to innocuous and noxious electrical and natural stimuli were made after SNL and compared to sham-operated animals. Spinal SNX-482 (0.5-4 mu g/50 mu L) exerted dose-related inhibitions of noxious C-fibre- and A delta-fibre-mediated neuronal responses in conditions of neuropathy, but not in sham-operated animals. Measures of spinal cord hyperexcitability and nociception were most susceptible to SNX-482. In contrast, non-noxious A beta-mediated responses were not affected by SNX-482. Moreover, responses to innocuous mechanical and also thermal stimuli were more sensitive to SNX-482 in SNL than control animals. This study is the first to demonstrate an antinociceptive role for SNX-482-sensitive channels in dorsal horn neurons during neuropathy. These data are consistent with plasticity in Ca(V)2.3 calcium channel expression and suggest a potential selective target to reduce nociceptive transmission during conditions of nerve damage.

Profiling dehydrin gene sequence and physiological parameters in drought tolerant and susceptible spring wheat cultivars.

Physiological and yield traits such as stomatal conductance (mmol m-2s-1), Leaf relative water content (RWC %) and grain yield per plant were studied in a separate experiment. Results revealed that five out of sixteen cultivars viz. Anmol, Moomal, Sarsabz, Bhitai and Pavan, appeared to be relatively more drought tolerant. Based on morphophysiological results, studies were continued to look at these cultivars for drought tolerance at molecular level. Initially, four well recognized primers for dehydrin genes (DHNs) responsible for drought induction in T. durum L., T. aestivum L. and O. sativa L. were used for profiling gene sequence of sixteen wheat cultivars. The primers amplified the DHN genes variably like Primer WDHN13 (T. aestivum L.) amplified the DHN gene in only seven cultivars whereas primer TdDHN15 (T. durum L.) amplified all the sixteen cultivars with even different DNA banding patterns some showing second weaker DNA bands. Third primer TdDHN16 (T. durum L.) has shown entirely different PCR amplification prototype, specially showing two strong DNA bands while fourth primer RAB16C (O. sativa L.) failed to amplify DHN gene in any of the cultivars. Examination of DNA sequences revealed several interesting features. First, it identified the two exon/one intron structure of this gene (complete sequences were not shown), a feature not previously described in the two database cDNA sequences available from T. aestivum L. (gi|21850). Secondly, the analysis identified several single nucleotide polymorphisms (SNPs), positions in gene sequence. Although complete gene sequence was not obtained for all the cultivars, yet there were a total of 38 variable positions in exonic (coding region) sequence, from a total gene length of 453 nucleotides. Matrix of SNP shows these 37 positions with individual sequence at positions given for each of the 14 cultivars (sequence of two cultivars was not obtained) included in this analysis. It demonstrated a considerable diversity for this gene with only three cultivars i.e. TJ-83, Marvi and TD-1 being similar to the consensus sequence. All other cultivars showed a unique combination of SNPs. In order to prove a functional link between these polymorphisms and drought tolerance in wheat, it would be necessary to conduct a more detailed study involving directed mutation of this gene and DHN gene expression.

Galleria mellonella as an infection model for Campylobacter jejuni virulence

Larvae of Galleria mellonella (Greater Wax Moth) have been shown to be susceptible to Campylobacter jejuni infection and our study characterizes this infection model. Following infection with C. jejuni human isolates, bacteria were visible in the haemocoel and gut of challenged larvae, and there was extensive damage to the gut. Bacteria were found in the extracellular and cell-associated fraction in the haemocoel, and it was shown that C. jejuni can survive in insect cells. Finally, we have used the model to screen a further 67 C. jejuni isolates belonging to different MLST types. Isolates belonging to ST257 were the most virulent in the Galleria model, whereas those belonging to ST21 were the least virulent.

Insect infection model for campylobacter jejuni reveals that O-methyl phosphoramidate has insecticidal activity

Galleria mellonella (wax moth) larvae have elsewhere been shown to be susceptible to pathogens such as Francisella tularensis, Burkholderia mallei, and Pseudomonas aeruginosa. We report that the larvae are rapidly killed by Campylobacter jejuni at 37 degrees C. Three strains of C. jejuni tested, 11168H (human diarrheal isolate), G1 (human Guillain-Barre syndrome isolate), and 81-176 (human diarrheal isolate), were equally effective at killing G. mellonella larvae. A panel of defined mutants of C. jejuni 11168H, in known or putative virulence genes, showed different degrees of attenuation in G. mellonella larvae. A mutant lacking the O-methyl phosphoramidate (MeOPN) capsule side group was attenuated, clearly demonstrating that MeOPN has a role in virulence. This new model of C. jejuni infection should facilitate the identification of novel virulence genes.

To what extent are EU steel companies susceptible to competitive loss due to climate policy?

In recognition of their competitive vulnerability, a set of special rules have been devised for managing sectors such as steel and cement within the EU ETS. These rules basically seek to set sector specific performance benchmarks and reward top performers. However, the steel sector as a whole will receive the vast majority of its allowances for free in Phase III. Perceptions of competitive vulnerability have been largely based on inherently hypothetical analyses which rely heavily on counterfactual scenario and abatement cost estimates often provided by firms themselves. This paper diverges from these approaches by providing a qualitative assessment of the two key reasons underpinning the competitive vulnerability argument of the EU Steel Companies based on interviews and case study involving the three largest producers of steel within the EU – AcerlorMittal, Corus, and ThyssenKrupp. We find that these arguments provide only partial and weak justifications for competitive loss and discriminatory treatment in the EUETS. This strategy is difficult to counter by governments due to information asymmetry; and it appears to have proved very successful insofar as it has helped the industry to achieve free allocation in Phases I-III of EU ETS by playing up the risk of carbon leakage.

Impact of the modal aerosol scheme GLOMAP-mode on aerosol forcing in the Hadley Centre Global Environmental Model

The Hadley Centre Global Environmental Model (HadGEM) includes two aerosol schemes: the Coupled Large-scale Aerosol Simulator for Studies in Climate (CLASSIC), and the new Global Model of Aerosol Processes (GLOMAP-mode). GLOMAP-mode is a modal aerosol microphysics scheme that simulates not only aerosol mass but also aerosol number, represents internally-mixed particles, and includes aerosol microphysical processes such as nucleation. In this study, both schemes provide hindcast simulations of natural and anthropogenic aerosol species for the period 2000–2006. HadGEM simulations of the aerosol optical depth using GLOMAP-mode compare better than CLASSIC against a data-assimilated aerosol re-analysis and aerosol ground-based observations. Because of differences in wet deposition rates, GLOMAP-mode sulphate aerosol residence time is two days longer than CLASSIC sulphate aerosols, whereas black carbon residence time is much shorter. As a result, CLASSIC underestimates aerosol optical depths in continental regions of the Northern Hemisphere and likely overestimates absorption in remote regions. Aerosol direct and first indirect radiative forcings are computed from simulations of aerosols with emissions for the year 1850 and 2000. In 1850, GLOMAP-mode predicts lower aerosol optical depths and higher cloud droplet number concentrations than CLASSIC. Consequently, simulated clouds are much less susceptible to natural and anthropogenic aerosol changes when the microphysical scheme is used. In particular, the response of cloud condensation nuclei to an increase in dimethyl sulphide emissions becomes a factor of four smaller. The combined effect of different 1850 baselines, residence times, and abilities to affect cloud droplet number, leads to substantial differences in the aerosol forcings simulated by the two schemes. GLOMAP-mode finds a presentday direct aerosol forcing of −0.49Wm−2 on a global average, 72% stronger than the corresponding forcing from CLASSIC. This difference is compensated by changes in first indirect aerosol forcing: the forcing of −1.17Wm−2 obtained with GLOMAP-mode is 20% weaker than with CLASSIC. Results suggest that mass-based schemes such as CLASSIC lack the necessary sophistication to provide realistic input to aerosol-cloud interaction schemes. Furthermore, the importance of the 1850 baseline highlights how model skill in predicting present-day aerosol does not guarantee reliable forcing estimates. Those findings suggest that the more complex representation of aerosol processes in microphysical schemes improves the fidelity of simulated aerosol forcings.

Multilevel analysis of hepatitis A infection in children and adolescents: a household survey in the Northeast and Central-west regions of Brazil

Background The objectives were to estimate the prevalence of hepatitis A among children and adolescents from the Northeast and Midwest regions and the Federal District of Brazil and to identify individual-, household- and area-levels factors associated with hepatitis A infection. Methods This population-based survey was conducted in 20042005 and covered individuals aged between 5 and 19 years. A stratified multistage cluster sampling technique with probability proportional to size was used to select 1937 individuals aged between 5 and 19 years living in the Federal capital and in the State capitals of 12 states in the study regions. The sample was stratified according to age (59 and 10- to 19-years-old) and capital within each region. Individual- and household-level data were collected by interview at the home of the individual. Variables related to the area were retrieved from census tract data. The outcome was total antibodies to hepatitis A virus detected using commercial EIA. The age distribution of the susceptible population was estimated using a simple catalytic model. The associations between HAV infection and independent variables were assessed using the odds ratio and corrected for the random design effect and sampling weight. Multilevel analysis was performed by GLLAMM using Stata 9.2. Results The prevalence of hepatitis A infection in the 59 and 1019 age-group was 41.5 and 57.4, respectively for the Northeast, 32.3 and 56.0, respectively for the Midwest and 33.8 and 65.1 for the Federal District. A trend for the prevalence of HAV infection to increase according to age was detected in all sites. By the age of 5, 31.5 of the children had already been infected with HAV in the Northeast region compared with 20.0 in the other sites. By the age of 19 years, seropositivity was 70 in all areas. The curves of susceptible populations differed from one area to another. Multilevel modeling showed that variables relating to different levels of education were associated with HAV infection in all sites. Conclusion The study sites were classified as areas with intermediate endemicity area for hepatitis A infection. Differences in age trends of infection were detected among settings. This multilevel model allowed for quantification of contextual predictors of hepatitis A infection in urban areas.