Geographic variation in the frequency of isolation and fluconazole and voriconazole susceptibilities of Candida glabrata: an assessment from the ARTEMIS DISK Global Antifungal Surveillance Program.

Geographic differences in frequency and azole resistance among Candida glabrata may impact empiric antifungal therapy choice. We examined geographic variation in isolation and azole susceptibility of C. glabrata. We examined 23 305 clinical isolates of C. glabrata during ARTEMIS DISK global surveillance. Susceptibility testing to fluconazole and voriconazole was assessed by disk diffusion, and the results were grouped by geographic location: North America (NA) (2470 isolates), Latin America (LA) (2039), Europe (EU) (12 439), Africa and the Middle East (AME) (728), and Asia-Pacific (AP) (5629). Overall, C. glabrata accounted for 11.6% of 201 653 isolates of Candida and varied as a proportion of all Candida isolated from 7.4% in LA to 21.1% in NA. Decreased susceptibility (S) to fluconazole was observed in all geographic regions and ranged from 62.8% in AME to 76.7% in LA. Variation in fluconazole susceptibility was observed within each region: AP (range, 50-100% S), AME (48-86.9%), EU (44.8-88%), LA (43-92%), and NA (74.5-91.6%). Voriconazole was more active than fluconazole (range, 82.3-84.2% S) with similar regional variation. Among 22 sentinel sites participating in ARTEMIS from 2001 through 2007 (84 140 total isolates, 8163 C. glabrata), the frequency of C. glabrata isolation increased in 14 sites and the frequency of fluconazole resistance (R) increased in 11 sites over the 7-year period of study. The sites with the highest cumulative rates of fluconazole R were in Poland (22% R), the Czech Republic (27% R), Venezuela (27% R), and Greece (33% R). C. glabrata was most often isolated from blood, normally sterile body fluids and urine. There is substantial geographic and institutional variation in both frequency of isolation and azole resistance among C. glabrata. Prompt species identification and fluconazole susceptibility testing are necessary to optimize therapy for invasive candidiasis.

Méthodes sismiques actives adaptées à l'étude de milieux hétérogènes : application aux glissements de terrain

Résumé Les glissements de terrain représentent un des principaux risques naturels dans les régions montagneuses. En Suisse, chaque année les glissements de terrains causent des dégâts qui affectent les infrastructures et ont des coûts financiers importants. Une bonne compréhension des mécanismes des glissements peut permettre d'atténuer leur impact. Celle-ci passe notamment par la connaissance de la structure interne du glissement, la détermination de son volume et de son ou ses plans de glissement. Dans un glissement de terrain, la désorganisation et la présence de fractures dans le matériel déplacé engendre un changement des paramètres physiques et en particulier une diminution des vitesses de propagation des ondes sismiques ainsi que de la densité du matériel. Les méthodes sismiques sont de ce fait bien adaptées à l'étude des glissements de terrain. Parmi les méthodes sismiques, l'analyse de la dispersion des ondes de surface est une méthode simple à mettre en oeuvre. Elle présente l'avantage d'estimer les variations des vitesses de cisaillement avec la profondeur sans avoir spécifiquement recours à l'utilisation d'une source d'onde S et de géophones horizontaux. Sa mise en oeuvre en trois étapes implique la mesure de la dispersion des ondes de surface sur des réseaux étendus, la détermination des courbes de dispersion pour finir par l'inversion de ces courbes. Les modèles de vitesse obtenus à partir de cette procédure ne sont valides que lorsque les milieux explorés ne présentent pas de variations latérales. En pratique cette hypothèse est rarement vérifiée, notamment pour un glissement de terrain dans lequel les couches remaniées sont susceptibles de présenter de fortes hétérogénéités latérales. Pour évaluer la possibilité de déterminer des courbes de dispersion à partir de réseaux de faible extension des mesures testes ont été effectuées sur un site (Arnex, VD) équipé d'un forage. Un profil sismique de 190 m de long a été implanté dans une vallée creusée dans du calcaire et remplie par des dépôts glacio-lacustres d'une trentaine de mètres d'épaisseur. Les données acquises le long de ce profil ont confirmé que la présence de variations latérales sous le réseau de géophones affecte l'allure des courbes de dispersion jusqu'à parfois empêcher leur détermination. Pour utiliser l'analyse de la dispersion des ondes de surface sur des sites présentant des variations latérales, notre approche consiste à déterminer les courbes de dispersions pour une série de réseaux de faible extension, à inverser chacune des courbes et à interpoler les différents modèles de vitesse obtenus. Le choix de la position ainsi que de l'extension des différents réseaux de géophones est important. Il tient compte de la localisation des hétérogénéités détectées à partir de l'analyse de sismique réfraction, mais également d'anomalies d'amplitudes observées sur des cartes qui représentent dans le domaine position de tir - position du récepteur, l'amplitude mesurée pour différentes fréquences. La procédure proposée par Lin et Lin (2007) s'est avérée être une méthode efficace permettant de déterminer des courbes de dispersion à partir de réseaux de faible extension. Elle consiste à construire à partir d'un réseau de géophones et de plusieurs positions de tir un enregistrement temps-déports qui tient compte d'une large gamme de distances source-récepteur. Au moment d'assembler les différentes données une correction de phase est appliquée pour tenir compte des hétérogénéités situées entre les différents points de tir. Pour évaluer cette correction nous suggérons de calculer pour deux tir successif la densité spectrale croisée des traces de même offset: Sur le site d'Arnex, 22 courbes de dispersions ont été déterminées pour de réseaux de géophones de 10 m d'extension. Nous avons également profité du forage pour acquérir un profil de sismique verticale en ondes S. Le modèle de vitesse S déduit de l'interprétation du profil de sismique verticale est utilisé comme information à priori lors l'inversion des différentes courbes de dispersion. Finalement, le modèle en deux dimension qui a été établi grâce à l'analyse de la dispersion des ondes de surface met en évidence une structure tabulaire à trois couches dont les limites coïncident bien avec les limites lithologiques observées dans le forage. Dans celui-ci des argiles limoneuses associées à une vitesse de propagation des ondes S de l'ordre de 175 m/s surmontent vers 9 m de profondeur des dépôts de moraine argilo-sableuse caractérisés par des vitesses de propagation des ondes S de l'ordre de 300 m/s jusqu'à 14 m de profondeur et supérieur ou égal à 400 m/s entre 14 et 20 m de profondeur. Le glissement de la Grande Combe (Ballaigues, VD) se produit à l'intérieur du remplissage quaternaire d'une combe creusée dans des calcaires Portlandien. Comme dans le cas du site d'Arnex les dépôts quaternaires correspondent à des dépôts glacio-lacustres. Dans la partie supérieure la surface de glissement a été localisée à une vingtaine de mètres de profondeur au niveau de l'interface qui sépare des dépôts de moraine jurassienne et des dépôts glacio-lacustres. Au pied du glissement 14 courbes de dispersions ont été déterminées sur des réseaux de 10 m d'extension le long d'un profil de 144 m. Les courbes obtenues sont discontinues et définies pour un domaine de fréquence de 7 à 35 Hz. Grâce à l'utilisation de distances source-récepteur entre 8 et 72 m, 2 à 4 modes de propagation ont été identifiés pour chacune des courbes. Lors de l'inversion des courbes de dispersion la prise en compte des différents modes de propagation a permis d'étendre la profondeur d'investigation jusqu'à une vingtaine de mètres de profondeur. Le modèle en deux dimensions permet de distinguer 4 couches (Vs1 < 175 m/s, 175 m/s < Vs2 < 225 m/s, 225 m/s < Vs3 < 400 m/s et Vs4 >.400 m/s) qui présentent des variations d'épaisseur. Des profils de sismiques réflexion en ondes S acquis avec une source construite dans le cadre de ce travail, complètent et corroborent le modèle établi à partir de l'analyse de la dispersion des ondes de surface. Un réflecteur localisé entre 5 et 10 m de profondeur et associé à une vitesse de sommation de 180 m/s souligne notamment la géométrie de l'interface qui sépare la deuxième de la troisième couche du modèle établi à partir de l'analyse de la dispersion des ondes de surface. Abstract Landslides are one of the main natural hazards in mountainous regions. In Switzerland, landslides cause damages every year that impact infrastructures and have important financial costs. In depth understanding of sliding mechanisms may help limiting their impact. In particular, this can be achieved through a better knowledge of the internal structure of the landslide, the determination of its volume and its sliding surface or surfaces In a landslide, the disorganization and the presence of fractures in the displaced material generate a change of the physical parameters and in particular a decrease of the seismic velocities and of the material density. Therefoe, seismic methods are well adapted to the study of landslides. Among seismic methods, surface-wave dispersion analysis is a easy to implement. Through it, shearwave velocity variations with depth can be estimated without having to resort to an S-wave source and to horizontal geophones. Its 3-step implementation implies measurement of surface-wave dispersion with long arrays, determination of the dispersion curves and finally inversion of these curves. Velocity models obtained through this approach are only valid when the investigated medium does not include lateral variations. In practice, this assumption is seldom correct, in particular for landslides in which reshaped layers likely include strong lateral heterogeneities. To assess the possibility of determining dispersion curves from short array lengths we carried out tests measurements on a site (Arnex, VD) that includes a borehole. A 190 m long seismic profile was acquired in a valley carved into limestone and filled with 30 m of glacio-lacustrine sediments. The data acquired along this profile confirmed that the presence of lateral variations under the geophone array influences the dispersion-curve shape so much that it sometimes preventes the dispersion curves determination. Our approach to use the analysis of surface-wave dispersion on sites that include lateral variations consists in obtaining dispersion curves for a series of short length arrays; inverting each so obtained curve and interpolating the different obtained velocity model. The choice of the location as well as the geophone array length is important. It takes into account the location of the heterogeneities that are revealed by the seismic refraction interpretation of the data but also, the location of signal amplitude anomalies observed on maps that represent, for a given frequency, the measured amplitude in the shot position - receiver position domain. The procedure proposed by Lin and Lin (2007) turned out to be an efficient one to determine dispersion curves using short extension arrays. It consists in building a time-offset from an array of geophones with a wide offset range by gathering seismograms acquired with different source-to-receiver offsets. When assembling the different data, a phase correction is applied in order to reduce static phase error induced by lateral variation. To evaluate this correction, we suggest to calculate, for two successive shots, the cross power spectral density of common offset traces. On the Arnex site, 22 curves were determined with 10m in length geophone-arrays. We also took advantage of the borehole to acquire a S-wave vertical seismic profile. The S-wave velocity depth model derived from the vertical seismic profile interpretation is used as prior information in the inversion of the dispersion-curves. Finally a 2D velocity model was established from the analysis of the different dispersion curves. It reveals a 3-layer structure in good agreement with the observed lithologies in the borehole. In it a clay layer with a shear-wave of 175 m/s shear-wave velocity overlies a clayey-sandy till layer at 9 m depth that is characterized down to 14 m by a 300 m/s S-wave velocity; these deposits have a S-wave velocity of 400 m/s between depths of 14 to 20 m. The La Grand Combe landslide (Ballaigues, VD) occurs inside the Quaternary filling of a valley carved into Portlandien limestone. As at the Arnex site, the Quaternary deposits correspond to glaciolacustrine sediments. In the upper part of the landslide, the sliding surface is located at a depth of about 20 m that coincides with the discontinuity between Jurassian till and glacio-lacustrine deposits. At the toe of the landslide, we defined 14 dispersion curves along a 144 m long profile using 10 m long geophone arrays. The obtained curves are discontinuous and defined within a frequency range of 7 to 35 Hz. The use of a wide range of offsets (from 8 to 72 m) enabled us to determine 2 to 4 mode of propagation for each dispersion curve. Taking these higher modes into consideration for dispersion curve inversion allowed us to reach an investigation depth of about 20 m. A four layer 2D model was derived (Vs1< 175 m/s, 175 m/s <Vs2< 225 m/s, 225 m/s < Vs3 < 400 m/s, Vs4> 400 m/s) with variable layer thicknesses. S-wave seismic reflection profiles acquired with a source built as part of this work complete and the velocity model revealed by surface-wave analysis. In particular, reflector at a depth of 5 to 10 m associated with a 180 m/s stacking velocity image the geometry of the discontinuity between the second and third layer of the model derived from the surface-wave dispersion analysis.

An ancient founder mutation in PROKR2 impairs human reproduction.

Congenital gonadotropin-releasing hormone (GnRH) deficiency manifests as absent or incomplete sexual maturation and infertility. Although the disease exhibits marked locus and allelic heterogeneity, with the causal mutations being both rare and private, one causal mutation in the prokineticin receptor, PROKR2 L173R, appears unusually prevalent among GnRH-deficient patients of diverse geographic and ethnic origins. To track the genetic ancestry of PROKR2 L173R, haplotype mapping was performed in 22 unrelated patients with GnRH deficiency carrying L173R and their 30 first-degree relatives. The mutation's age was estimated using a haplotype-decay model. Thirteen subjects were informative and in all of them the mutation was present on the same ~123 kb haplotype whose population frequency is ≤10%. Thus, PROKR2 L173R represents a founder mutation whose age is estimated at approximately 9000 years. Inheritance of PROKR2 L173R-associated GnRH deficiency was complex with highly variable penetrance among carriers, influenced by additional mutations in the other PROKR2 allele (recessive inheritance) or another gene (digenicity). The paradoxical identification of an ancient founder mutation that impairs reproduction has intriguing implications for the inheritance mechanisms of PROKR2 L173R-associated GnRH deficiency and for the relevant processes of evolutionary selection, including potential selective advantages of mutation carriers in genes affecting reproduction.

Wide-pulse-high-frequency neuromuscular stimulation of triceps surae induces greater muscle fatigue compared with conventional stimulation.

We compared the extent and origin of muscle fatigue induced by short-pulse-low-frequency [conventional (CONV)] and wide-pulse-high-frequency (WPHF) neuromuscular electrical stimulation. We expected CONV contractions to mainly originate from depolarization of axonal terminal branches (spatially determined muscle fiber recruitment) and WPHF contractions to be partly produced via a central pathway (motor unit recruitment according to size principle). Greater neuromuscular fatigue was, therefore, expected following CONV compared with WPHF. Fourteen healthy subjects underwent 20 WPHF (1 ms-100 Hz) and CONV (50 μs-25 Hz) evoked isometric triceps surae contractions (work/rest periods 20:40 s) at an initial target of 10% of maximal voluntary contraction (MVC) force. Force-time integral of the 20 evoked contractions (FTI) was used as main index of muscle fatigue; MVC force loss was also quantified. Central and peripheral fatigue were assessed by voluntary activation level and paired stimulation amplitudes, respectively. FTI in WPHF was significantly lower than in CONV (21,717 ± 11,541 vs. 37,958 ± 9,898 N·s P<0,001). The reductions in MVC force (WPHF: -7.0 ± 2.7%; CONV: -6.2 ± 2.5%; P < 0.01) and paired stimulation amplitude (WPHF: -8.0 ± 4.0%; CONV: -7.4 ± 6.1%; P < 0.001) were similar between conditions, whereas no change was observed for voluntary activation level (P > 0.05). Overall, our results showed a different motor unit recruitment pattern between the two neuromuscular electrical stimulation modalities with a lower FTI indicating greater muscle fatigue for WPHF, possibly limiting the presumed benefits for rehabilitation programs.

Development and Validation of Decision Rules to Guide Frequency of Monitoring CD4 Cell Count in HIV-1 Infection before Starting Antiretroviral Therapy.

Background: Although CD4 cell count monitoring is used to decide when to start antiretroviral therapy in patients with HIV-1 infection, there are no evidence-based recommendations regarding its optimal frequency. It is common practice to monitor every 3 to 6 months, often coupled with viral load monitoring. We developed rules to guide frequency of CD4 cell count monitoring in HIV infection before starting antiretroviral therapy, which we validated retrospectively in patients from the Swiss HIV Cohort Study.Methodology/Principal Findings: We built up two prediction rules ("Snap-shot rule" for a single sample and "Track-shot rule" for multiple determinations) based on a systematic review of published longitudinal analyses of CD4 cell count trajectories. We applied the rules in 2608 untreated patients to classify their 18 061 CD4 counts as either justifiable or superfluous, according to their prior >= 5% or < 5% chance of meeting predetermined thresholds for starting treatment. The percentage of measurements that both rules falsely deemed superfluous never exceeded 5%. Superfluous CD4 determinations represented 4%, 11%, and 39% of all actual determinations for treatment thresholds of 500, 350, and 200x10(6)/L, respectively. The Track-shot rule was only marginally superior to the Snap-shot rule. Both rules lose usefulness for CD4 counts coming near to treatment threshold.Conclusions/Significance: Frequent CD4 count monitoring of patients with CD4 counts well above the threshold for initiating therapy is unlikely to identify patients who require therapy. It appears sufficient to measure CD4 cell count 1 year after a count > 650 for a threshold of 200, > 900 for 350, or > 1150 for 500x10(6)/L, respectively. When CD4 counts fall below these limits, increased monitoring frequency becomes advisable. These rules offer guidance for efficient CD4 monitoring, particularly in resource-limited settings.

An attempt to refine rockfall hazard zoning based on the kinetic energy, frequency and fragmentation degree

Rockfall hazard zoning is usually achieved using a qualitative estimate of hazard, and not an absolute scale. In Switzerland, danger maps, which correspond to a hazard zoning depending on the intensity of the considered phenomenon (e.g. kinetic energy for rockfalls), are replacing hazard maps. Basically, the danger grows with the mean frequency and with the intensity of the rockfall. This principle based on intensity thresholds may also be applied to other intensity threshold values than those used in Switzerland for rockfall hazard zoning method, i.e. danger mapping. In this paper, we explore the effect of slope geometry and rockfall frequency on the rockfall hazard zoning. First, the transition from 2D zoning to 3D zoning based on rockfall trajectory simulation is examined; then, its dependency on slope geometry is emphasized. The spatial extent of hazard zones is examined, showing that limits may vary widely depending on the rockfall frequency. This approach is especially dedicated to highly populated regions, because the hazard zoning has to be very fine in order to delineate the greatest possible territory containing acceptable risks.

16q24.1 microdeletion in a premature newborn: Usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn.

OBJECTIVE:: Report of a 16q24.1 deletion in a premature newborn, demonstrating the usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn and multiple congenital malformations. DESIGN:: Descriptive case report. SETTING:: Genetic department and neonatal intensive care unit of a tertiary care children's hospital. INTERVENTIONS:: None. PATIENT:: We report the case of a preterm male infant, born at 26 wks of gestation. A cardiac malformation and bilateral hydronephrosis were diagnosed at 19 wks of gestation. Karyotype analysis was normal, and a 22q11.2 microdeletion was excluded by fluorescence in situ hybridization analysis. A cesarean section was performed due to fetal distress. The patient developed persistent pulmonary hypertension unresponsive to mechanical ventilation and nitric oxide treatment and expired at 16 hrs of life. MEASUREMENTS AND MAIN RESULTS:: An autopsy revealed partial atrioventricular canal malformation and showed bilateral dilation of the renal pelvocaliceal system with bilateral ureteral stenosis and annular pancreas. Array-based comparative genomic hybridization analysis (Agilent oligoNT 44K, Agilent Technologies, Santa Clara, CA) showed an interstitial microdeletion encompassing the forkhead box gene cluster in 16q24.1. Review of the pulmonary microscopic examination showed the characteristic features of alveolar capillary dysplasia with misalignment of pulmonary veins. Some features were less prominent due to the gestational age. CONCLUSIONS:: Our review of the literature shows that alveolar capillary dysplasia with misalignment of pulmonary veins is rare but probably underreported. Prematurity is not a usual presentation, and histologic features are difficult to interpret. In our case, array-based comparative genomic hybridization revealed a 16q24.1 deletion, leading to the final diagnosis of alveolar capillary dysplasia with misalignment of pulmonary veins. It emphasizes the usefulness of array-based comparative genomic hybridization analysis as a diagnostic tool with implications for both prognosis and management decisions in newborns with refractory persistent pulmonary hypertension and multiple congenital malformations.

The HSR on chromosome 1 of the house mouse, Mus domesticus: distribution and frequency in Switzerland.

A total of 357 house mice (Mus domesticus) from 83 localities uniformly distributed throughout Switzerland were screened for the presence of a homogenously staining region (HSR) on chromosome 1. Altogether 47 mice from 11 localities were HSR/+ or HSR/HSR. One sample of 11 individuals all had an HSR/HSR karyotype. Almost all mice with the variant were collected from the Rhone valley (HSR frequency: 61%) and Val Bregaglia (HSR frequency: 81%). For samples from most of the area of Switzerland, the HSR was absent. There was no strong association between the geographic distribution of the HSR and the areas of occurrence of metacentrics. However, at Chiggiogna the HSR was found on Rb (1.3). Possible explanations for the HSR polymorphism are discussed.

Use of high-frequency jet ventilation for percutaneous tumor ablation.

PURPOSE: To report feasibility and potential benefits of high-frequency jet ventilation (HFJV) in tumor ablations techniques in liver, kidney, and lung lesions. METHODS: This prospective study included 51 patients (14 women, mean age 66 years) bearing 66 tumors (56 hepatic, 5 pulmonary, 5 renal tumors) with a median size of 16 ± 8.7 mm, referred for tumor ablation in an intention-to-treat fashion before preoperative anesthesiology visit. Cancellation and complications of HFJV were prospectively recorded. Anesthesia and procedure duration, as well as mean CO2 capnea, were recorded. When computed tomography guidance was used, 3D spacial coordinates of an anatomical target <2 mm in diameter on 8 slabs of 4 slices of 3.75-mm slice thickness were registered. RESULTS: HFJV was used in 41 of 51 patients. Of the ten patients who were not candidate for HFJV, two patients had contraindication to HFJV (severe COPD), three had lesions invisible under HFJV requiring deep inspiration apnea for tumor targeting, and five patients could not have HFJV because of unavailability of a trained anesthetic team. No specific complication or hypercapnia related to HFJV were observed despite a mean anesthetic duration of 2 h and ventilation performed in procubitus (n = 4) or lateral decubitus (n = 6). Measured internal target movement was 0.3 mm in x- and y-axis and below the slice thickness of 3.75 mm in the z-axis in 11 patients. CONCLUSIONS: HFJV is feasible in 80 % of patients allowing for near immobility of internal organs during liver, kidney, and lung tumor ablation.

Estudo de caso: o uso da língua portuguesa por jovens provindos de outros países no domínio privado, público e educativo

A afluência de imigrantes a Portugal, nas últimas três décadas transformou radicalmente todo o tecido social português, caracterizando-se hoje pela sua heterogeneidade. Até ao início da década de 90 do século XX, os fluxos migratórios provinham essencialmente dos Países de Língua Oficial Portuguesa, com maior incidência de Cabo Verde, Brasil e Angola. É nessa década que se registam movimentos bastante significativos de imigrantes provenientes da Europa Central e Oriental, principalmente da Ucrânia, Rússia, Roménia e Moldávia, assim como da Ásia, destacando-se os naturais da China, Índia, Paquistão e das antigas repúblicas soviéticas. De acordo com a análise apresentada pelo Instituto Nacional de Estatística em Dezembro de 2006, residiam de forma legal em Portugal 329 898 cidadãos de nacionalidade estrangeira, sendo as maiores comunidades de Cabo Verde (57 349), Brasil (41 728) e Angola (28 854). A sociedade portuguesa do século XXI, distancia-se cada vez mais do conceito de monolinguismo, tal como se evidencia no Projecto Gulbenkian “Diversidade Linguística na Escola Portuguesa”, que, segundo o estudo feito, onze por cento dos alunos residentes na área da Grande Lisboa nasceram fora de Portugal e têm como línguas maternas cinquenta e oito idiomas. É urgente uma intervenção diferente no que corresponde a esta nova realidade linguística em Portugal e sobretudo no que concerne à integração do “outro”, reconhecendo e respeitando as várias línguas maternas e culturas, como também a sua preservação a fim de possibilitar o desenvolvimento íntegro e harmonioso da identidade. A heterogeneidade da actual sociedade portuguesa impõe um olhar atento para com esta nova realidade no país, sobretudo em muitas das escolas onde a par do uso da língua portuguesa outras línguas são também usadas como forma de comunicação entre os mesmos pares, situação esta perfeitamente desajustada da realidade escolar madeirense Estudo de caso: O uso da Língua Portuguesa por jovens oriundos de outros países nos domínios privado, público e educativo. 10 de inícios da década de 90 do século XX, à excepção dos alunos provenientes da Venezuela, os denominados luso-descendentes. A escola mudara, tudo se alterara, havia que tentar perceber o que estava a ocorrer, um novo Mundo “invadira” as turmas, prontas a aprender, a saber, a descobrir. Era preciso preencher o silêncio expectante. Aprender uma nova língua, a portuguesa, decorrente da obrigatoriedade implícita de tratar-se da língua oficial, obrigava a repensar o ensino, a continuamente desvendar novos caminhos possibilitadores de encontro entre a língua materna e a segunda, de reencontro com a identidade linguística e cultural que não se quer perdidas, só tornado possível na diferença. A par de uma escola que se apresentava de forma diferente, cuja intervenção teria de ser oposta à de então, uma vez que a aprendizagem do português era feita como língua segunda (L2), muitas foram e são as inquietações, um turbilhão de interrogações decorriam deste contacto constante de uma língua que se diz minha, fonte de partilha com outros jovens. O uso da língua portuguesa confinar-se-á unicamente à escola com os professores e colegas ou despoletará curiosidades, vontades, interesses, motivados por objectivos confinados ao percurso e à história humana? Muitas são as interrogações que ocorrem, muitos são também os momentos de sabedoria mútua de línguas e países a desvendar num contínuo ininterrupto e é essa constante procura que determina a busca de respostas. Entre muitas interrogações uma afigurava-se de forma latente, quiçá fonte de resposta para outras interrogações inerentes à língua portuguesa como língua segunda. A sua utilização por parte dos alunos de outras nacionalidades nos domínios privado, público e educativo engloba domínios diversos capazes de informar acerca do uso dessa mesma língua. Importa no entanto reforçar que estes alunos constituem um grupo heterogéneo sob diversos pontos de vista: etário, linguístico e cultural. Do ponto de vista linguístico a população que tem o português como língua segunda abrange alunos falantes de diferentes línguas maternas, umas mais próximas, outras mais afastadas do português, propiciando diferentes graus de transferência de conhecimentos linguísticos e de experiências comunicativas, como também em diferentes estádios de aquisição e que fora da escola o usam em maior ou menor número de contextos e com um grau de frequência desigual. Estudo de caso: O uso da Língua Portuguesa por jovens oriundos de outros países nos domínios privado, público e educativo. 11 Dispõem também de diferentes capacidades individuais para discriminar, segmentar e produzir sequências linguísticas. Já do ponto de vista cultural apresentam diferentes hábitos de aprendizagem, bem como diferentes representações e expectativas face à escola. Todos estes factores determinarão ritmos de progressão distintos no que respeita à aprendizagem do português como língua segunda. As oportunidades de aprendizagem e de uso que cada indivíduo tem ao longo da vida, determinantes no processo de aquisição, desenvolvimento e aprendizagem de uma língua, variam bastante de indivíduo para indivíduo. Os alunos podem viver num mesmo contexto no entanto razões variadíssimas determinarão diferentes oportunidades de aprendizagem e de uso. Viver-se num contexto de imersão não é suficiente para que todos tenham o mesmo grau de exposição a material linguístico rico e variado da L2. Essas oportunidades também se relacionam com a distância linguística entre língua primeira (L1) e a língua segunda, quanto mais afastadas são as duas línguas mais os falantes da L2 se refugiam na sua língua materna, assim como também se associam aos hábitos culturais da comunidade e da família.

Introducing a first AIDS vaccine in Switzerland: a Policy Delphi analysis.

This preliminary exploration was limited by a number of factors. The format of the study has necessarily induced some form of selection bias of the panelists, because of the complexity of some questions, and the time required to complete the questionnaires. Several issues have not been addressed. One example could be the response to HIV infection occurring in a vaccinee. The study also did not address the difficulties related to the licensing of the vaccine. Indeed, the proposed scenario assumed that the vaccine had been registered as a starting point for the analysis. Finally, it has not been possible to conduct a sensitivity analysis, in order to evaluate how the responses would have been modified if some important characteristics of the vaccine had been modified.Very diverse evaluations were given in response to questions related with attitudes and perception of AIDS and AIDS vaccine. The possibility that vaccine availability or usage can be associated with an increased frequency in risky behaviors was spontaneously mentioned by half of the panelists. The estimation of the proportion of persons at highest risk who would choose to use this vaccine also indicated a high degree of uncertainty. This study offers important lessons. According to a broad and diverse panel of individuals, an incompletely effective AIDS vaccine would result in an additional level of complexity for the AIDS prevention strategy, rather than a simplification. The use of such a vaccine would have to be coupled with counselling. This implies a sustained emphasis on the recommendations which have been central to the STOP AIDS campaigns until now. In addition, consensual issues, as well as other issues more likely to be controversial have been identified. This should greatly help focusing the work of any committee designated to develop and implement a vaccination policy if an AIDS vaccine became available. Finally, our experience with the Policy Delphi indicates that this mode of structured communication could be usefully applied to other public health issues presenting a high visibility as well as a complex relationship with public perception.

Estudo de caso : o uso da língua portuguesa por jovens provindos de outros países no domínio privado, público e educativo

A afluência de imigrantes a Portugal, nas últimas três décadas transformou radicalmente todo o tecido social português, caracterizando-se hoje pela sua heterogeneidade. Até ao início da década de 90 do século XX, os fluxos migratórios provinham essencialmente dos Países de Língua Oficial Portuguesa, com maior incidência de Cabo Verde, Brasil e Angola. É nessa década que se registam movimentos bastante significativos de imigrantes provenientes da Europa Central e Oriental, principalmente da Ucrânia, Rússia, Roménia e Moldávia, assim como da Ásia, destacando-se os naturais da China, Índia, Paquistão e das antigas repúblicas soviéticas. De acordo com a análise apresentada pelo Instituto Nacional de Estatística em Dezembro de 2006, residiam de forma legal em Portugal 329 898 cidadãos de nacionalidade estrangeira, sendo as maiores comunidades de Cabo Verde (57 349), Brasil (41 728) e Angola (28 854). A sociedade portuguesa do século XXI, distancia-se cada vez mais do conceito de monolinguismo, tal como se evidencia no Projecto Gulbenkian “Diversidade Linguística na Escola Portuguesa”, que, segundo o estudo feito, onze por cento dos alunos residentes na área da Grande Lisboa nasceram fora de Portugal e têm como línguas maternas cinquenta e oito idiomas. É urgente uma intervenção diferente no que corresponde a esta nova realidade linguística em Portugal e sobretudo no que concerne à integração do “outro”, reconhecendo e respeitando as várias línguas maternas e culturas, como também a sua preservação a fim de possibilitar o desenvolvimento íntegro e harmonioso da identidade. A heterogeneidade da actual sociedade portuguesa impõe um olhar atento para com esta nova realidade no país, sobretudo em muitas das escolas onde a par do uso da língua portuguesa outras línguas são também usadas como forma de comunicação entre os mesmos pares, situação esta perfeitamente desajustada da realidade escolar madeirense Estudo de caso: O uso da Língua Portuguesa por jovens oriundos de outros países nos domínios privado, público e educativo. 10 de inícios da década de 90 do século XX, à excepção dos alunos provenientes da Venezuela, os denominados luso-descendentes. A escola mudara, tudo se alterara, havia que tentar perceber o que estava a ocorrer, um novo Mundo “invadira” as turmas, prontas a aprender, a saber, a descobrir. Era preciso preencher o silêncio expectante. Aprender uma nova língua, a portuguesa, decorrente da obrigatoriedade implícita de tratar-se da língua oficial, obrigava a repensar o ensino, a continuamente desvendar novos caminhos possibilitadores de encontro entre a língua materna e a segunda, de reencontro com a identidade linguística e cultural que não se quer perdidas, só tornado possível na diferença. A par de uma escola que se apresentava de forma diferente, cuja intervenção teria de ser oposta à de então, uma vez que a aprendizagem do português era feita como língua segunda (L2), muitas foram e são as inquietações, um turbilhão de interrogações decorriam deste contacto constante de uma língua que se diz minha, fonte de partilha com outros jovens. O uso da língua portuguesa confinar-se-á unicamente à escola com os professores e colegas ou despoletará curiosidades, vontades, interesses, motivados por objectivos confinados ao percurso e à história humana? Muitas são as interrogações que ocorrem, muitos são também os momentos de sabedoria mútua de línguas e países a desvendar num contínuo ininterrupto e é essa constante procura que determina a busca de respostas. Entre muitas interrogações uma afigurava-se de forma latente, quiçá fonte de resposta para outras interrogações inerentes à língua portuguesa como língua segunda. A sua utilização por parte dos alunos de outras nacionalidades nos domínios privado, público e educativo engloba domínios diversos capazes de informar acerca do uso dessa mesma língua. Importa no entanto reforçar que estes alunos constituem um grupo heterogéneo sob diversos pontos de vista: etário, linguístico e cultural. Do ponto de vista linguístico a população que tem o português como língua segunda abrange alunos falantes de diferentes línguas maternas, umas mais próximas, outras mais afastadas do português, propiciando diferentes graus de transferência de conhecimentos linguísticos e de experiências comunicativas, como também em diferentes estádios de aquisição e que fora da escola o usam em maior ou menor número de contextos e com um grau de frequência desigual. Estudo de caso: O uso da Língua Portuguesa por jovens oriundos de outros países nos domínios privado, público e educativo. 11 Dispõem também de diferentes capacidades individuais para discriminar, segmentar e produzir sequências linguísticas. Já do ponto de vista cultural apresentam diferentes hábitos de aprendizagem, bem como diferentes representações e expectativas face à escola. Todos estes factores determinarão ritmos de progressão distintos no que respeita à aprendizagem do português como língua segunda. As oportunidades de aprendizagem e de uso que cada indivíduo tem ao longo da vida, determinantes no processo de aquisição, desenvolvimento e aprendizagem de uma língua, variam bastante de indivíduo para indivíduo. Os alunos podem viver num mesmo contexto no entanto razões variadíssimas determinarão diferentes oportunidades de aprendizagem e de uso. Viver-se num contexto de imersão não é suficiente para que todos tenham o mesmo grau de exposição a material linguístico rico e variado da L2. Essas oportunidades também se relacionam com a distância linguística entre língua primeira (L1) e a língua segunda, quanto mais afastadas são as duas línguas mais os falantes da L2 se refugiam na sua língua materna, assim como também se associam aos hábitos culturais da comunidade e da família.

Frequency and Type of Side Effects of Immunomodulating Medication in the Swiss Inflammatory Bowel Disease Cohort

Background: Medical treatment of inflammatory bowel disease (IBD) is becoming more and more complex, as several classes of immuno-modulating drugs (IMD) are often used simultaneously. Thus, the probability of adverse effects is greatly increased. Most studies reporting on adverse effects focus on single therapy, and studies providing a global survey of side effects for multiple treatments are lacking. Aim: To assess the type and frequency of adverse events in IBD patients treated with single and multiple IMD therapy. Methods: Analysis of data from the Swiss IBD Cohort Study (SIBDCS) that collects data on a large sample of IBD patients from hospitals and private practices across Switzerland. The following IMD categories were analyzed: 5-ASA, azathioprine (Aza), 6-mercaptopurine (6-MP), methotrexate (MTX), anti-TNF (infliximab, adalimumab, certolizumab-pegol), cyclosporine, tacrolimus, and steroids. The following side effects were assessed: hepatitis, pancreatitis, leucopenia, thrombopenia, nephritis, allergic reaction, pneumonitis, infections (including tuberculosis), osteoporosis, abdominal pain/diarrhea (unrelated to IBD activity), cataract, diabetes, exanthema, hirsutism, lupus-like syndrome, myalgias, depression/psychosis, tumor development. Results: A total of 1,961 patients were analyzed (977 [50%] female, mean age 42.1 ± 14.4 years): 1,119 with Crohn's disease (CD), 800 with ulcerative colitis (UC), and 42 with indeterminate colitis (IC). Three-hundred eighteen (16.2%) patients were not treated with any of the above-mentioned medications, while 650 (33.2%), 569 (29%) and 424 (21.6%) patients had one-, two-, and three- or more- IMD therapy, respectively. Of the 1,643 patients treated with IMD, 535 (32.6%) patients reported at least one side effect. We found a significant correlation between the number of drugs used by a patient and the frequency of side effects (17.4% side effects for one drug, 29% for 2 drugs, and 60.6% for three or more drugs, p < 0.001). The frequency of side effects for the different IMD classes were as follows: 5-ASA (n = 980 treated patients) 10.8%, Aza/6-MP (n = 636) 51.9% (pancreatitis in 57 = 9%, hepatitis in 17 = 2.7% of treated patients), MTX (n = 146) 42.5% (hepatitis in 4 = 2.7% of treated patients), anti-TNF (n = 255) 23.1%, cyclosporine (n = 49) 10.2%, tacrolimus (n = 5) 20%, steroids (systemic or topical, n = 1,150) 9.6%. Conclusion: IBD treatment is associated with a significant number of side effects. A direct correlation between the number of IMD used simultaneously and the frequency of side effects was observed. The results of this study indicate that treating physicians should be vigilant for the occurrence of side effects in IBD patients under single and/or multiple drug therapy.