Sequence-Based Hepatitis B Virus Antiviral Resistance Testing in Switzerland

BACKGROUND: A growing number of patients with chronic hepatitis B is being treated for extended periods with nucleoside and/or nucleotide analogs. In this context, antiviral resistance represents an increasingly common and complex issue. METHODS: Mutations in the hepatitis B virus (HBV) reverse transcriptase (rt) gene and viral genotypes were determined by direct sequencing of PCR products and alignment with reference sequences deposited in GenBank. RESULTS: Plasma samples from 60 patients with chronic hepatitis B were analyzed since March 2009. The predominant mutation pattern identified in patients with virological breakthrough was rtM204V/I ± different compensatory mutations, conferring resistance to L-nucleosides (lamivudine, telbivudine, emtricitabine) and predisposing to entecavir resistance (n = 18). Complex mutation patterns with a potential for multidrug resistance were identified in 2 patients. Selection of a fully entecavir resistant strain was observed in a patient exposed to lamivudine alone. Novel mutations were identified in 1 patient. Wild-type HBV was identified in 9 patients with suspected virological breakthrough, raising concerns about treatment adherence. No preexisting resistance mutations were identified in treatment-naïve patients (n = 13). Viral genome amplification and sequencing failed in 16 patients, of which only 2 had a documented HBV DNA > 1000 IU/ml. HBV genotypes were D in 28, A in 6, B in 4, C in 3 and E in 3 patients. Results will be updated in August 2010 and therapeutic implications discussed. CONCLUSIONS: With expanding treatment options and a growing number of patients exposed to nucleoside and/or nucleotide analogs, sequence-based HBV antiviral resistance testing is expected to become a cornerstone in the management of chronic hepatitis B.

Open Educational Resources : Experiences of use in a Latin-American context

This paper presents practical experiences using Open educational Resources (OER) for basic and elementary education (K12), educational research and research training on two inter-institutional projects with the collaboration of thirteen higher education institutions and with the support of the Corporación de Universidades para el Desarrollo del Internet (CUDI) and by the Consejo Nacional de Ciencia y Tecnología (CONACYT) of Mexico and hosted by the Tecnológico de Monterrey. The first initiative is titled "Knowledge Hub for K-12 Education" with the main goal of enrich a catalog of Open Educational Resources for basic and elementary education (K-12) for Mexico and Spanish speaking countries in Latin-America. The main goal of the second initiative is to build a collection of Open Educational Resources for Mobile Learning to address the issue of educational research and research training.

E-governança i atenció ciutadana : la Generalitat de Catalunya en el context internacional. Informe de recerca (Vol.II)

Aquest estudi té com a objectiu principal analitzar les transformacions que s'esdevenen al voltant de la incorporació d'innovacions tecnològiques de l'entorn de les TIC en els processos d'atenció al ciutadà per part de les administracions públiques. Les transformacions que hem analitzat tenen a veure amb tres dimensions que hem considerat bàsiques. D'una banda, ens hem centrat en els canvis que es produeixen en la forma en què els ciutadans (com a principals, tot i que no únics, usuaris) i l'administració es relacionen entre sí. De l'altra hem analitzat les transformacions que s'esdevenen en el funcionament intern i en la pròpia organització de l'administració arran de les transformacions dels canals de comunicació amb els usuaris. Per últim, hem considerat els canvis en la forma de gestionar (dissenyar, planificar, organitzar i dur a terme) el canvi i la innovació, tenint en compte especialment els rols dels diferents actors (no només públics) que hi participen. La recerca es recolza en un ampli estudi empíric sobre la Generalitat de Catalunya i en un estudi compartiu internacional sobre el Quebec, Emillia-Romagna i Escòcia.

E-Governance and Citizen Information : The Generalitat of Catalonia in the International Context. Research report (synthesis document)

Aquest estudi té com a objectiu principal analitzar les transformacions que s'esdevenen al voltant de la incorporació d'innovacions tecnològiques de l'entorn de les TIC en els processos d'atenció al ciutadà per part de les administracions públiques. Les transformacions que hem analitzat tenen a veure amb tres dimensions que hem considerat bàsiques. D'una banda, ens hem centrat en els canvis que es produeixen en la forma en què els ciutadans (com a principals, tot i que no únics, usuaris) i l'administració es relacionen entre sí. De l'altra hem analitzat les transformacions que s'esdevenen en el funcionament intern i en la pròpia organització de l'administració arran de les transformacions dels canals de comunicació amb els usuaris. Per últim, hem considerat els canvis en la forma de gestionar (dissenyar, planificar, organitzar i dur a terme) el canvi i la innovació, tenint en compte especialment els rols dels diferents actors (no només públics) que hi participen. La recerca es recolza en un ampli estudi empíric sobre la Generalitat de Catalunya i en un estudi compartiu internacional sobre el Quebec, Emillia-Romagna i Escòcia.

Perspectives of auto-correcting lens distortions in mosaic-based underwater navigation

When unmanned underwater vehicles (UUVs) perform missions near the ocean floor, optical sensors can be used to improve local navigation. Video mosaics allow to efficiently process the images acquired by the vehicle, and also to obtain position estimates. We discuss in this paper the role of lens distortions in this context, proving that degenerate mosaics have their origin not only in the selected motion model or in registration errors, but also in the cumulative effect of radial distortion residuals. Additionally, we present results on the accuracy of different feature-based approaches for self-correction of lens distortions that may guide the choice of appropriate techniques for correcting distortions

Body context and posture affect mental imagery of hands.

Different visual stimuli have been shown to recruit different mental imagery strategies. However the role of specific visual stimuli properties related to body context and posture in mental imagery is still under debate. Aiming to dissociate the behavioural correlates of mental processing of visual stimuli characterized by different body context, in the present study we investigated whether the mental rotation of stimuli showing either hands as attached to a body (hands-on-body) or not (hands-only), would be based on different mechanisms. We further examined the effects of postural changes on the mental rotation of both stimuli. Thirty healthy volunteers verbally judged the laterality of rotated hands-only and hands-on-body stimuli presented from the dorsum- or the palm-view, while positioning their hands on their knees (front postural condition) or behind their back (back postural condition). Mental rotation of hands-only, but not of hands-on-body, was modulated by the stimulus view and orientation. Additionally, only the hands-only stimuli were mentally rotated at different speeds according to the postural conditions. This indicates that different stimulus-related mechanisms are recruited in mental rotation by changing the bodily context in which a particular body part is presented. The present data suggest that, with respect to hands-only, mental rotation of hands-on-body is less dependent on biomechanical constraints and proprioceptive input. We interpret our results as evidence for preferential processing of visual- rather than kinesthetic-based mechanisms during mental transformation of hands-on-body and hands-only, respectively.

Oxidants positively or negatively regulate nuclear factor kappaB in a context-dependent manner.

Redox-based mechanisms play critical roles in the regulation of multiple cellular functions. NF-kappaB, a master regulator of inflammation, is an inducible transcription factor generally considered to be redox-sensitive, but the modes of interactions between oxidant stress and NF-kappaB are incompletely defined. Here, we show that oxidants can either amplify or suppress NF-kappaB activation in vitro by interfering both with positive and negative signals in the NF-kappaB pathway. NF-kappaB activation was evaluated in lung A549 epithelial cells stimulated with tumor necrosis factor alpha (TNFalpha), either alone or in combination with various oxidant species, including hydrogen peroxide or peroxynitrite. Exposure to oxidants after TNFalpha stimulation produced a robust and long lasting hyperactivation of NF-kappaB by preventing resynthesis of the NF-kappaB inhibitor IkappaB, thereby abrogating the major negative feedback loop of NF-kappaB. This effect was related to continuous activation of inhibitor of kappaB kinase (IKK), due to persistent IKK phosphorylation consecutive to oxidant-mediated inactivation of protein phosphatase 2A. In contrast, exposure to oxidants before TNFalpha stimulation impaired IKK phosphorylation and activation, leading to complete prevention of NF-kappaB activation. Comparable effects were obtained when interleukin-1beta was used instead of TNFalpha as the NF-kappaB activator. This study demonstrates that the influence of oxidants on NF-kappaB is entirely context-dependent, and that the final outcome (activation versus inhibition) depends on a balanced inhibition of protein phosphatase 2A and IKK by oxidant species. Our findings provide a new conceptual framework to understand the role of oxidant stress during inflammatory processes.

Yellow fever impact on brown howler monkeys (Alouatta guariba clamitans) in Argentina: a metamodelling approach based on population viability analysis and epidemiological dynamics

In South America, yellow fever (YF) is an established infectious disease that has been identified outside of its traditional endemic areas, affecting human and nonhuman primate (NHP) populations. In the epidemics that occurred in Argentina between 2007-2009, several outbreaks affecting humans and howler monkeys (Alouatta spp) were reported, highlighting the importance of this disease in the context of conservation medicine and public health policies. Considering the lack of information about YF dynamics in New World NHP, our main goal was to apply modelling tools to better understand YF transmission dynamics among endangered brown howler monkey (Alouatta guariba clamitans) populations in northeastern Argentina. Two complementary modelling tools were used to evaluate brown howler population dynamics in the presence of the disease: Vortex, a stochastic demographic simulation model, and Outbreak, a stochastic disease epidemiology simulation. The baseline model of YF disease epidemiology predicted a very high probability of population decline over the next 100 years. We believe the modelling approach discussed here is a reasonable description of the disease and its effects on the howler monkey population and can be useful to support evidence-based decision-making to guide actions at a regional level.

Impact of inadequate empirical therapy on the mortality of patients with bloodstream infections: a propensity score-based analysis.

The impact of the adequacy of empirical therapy on outcome for patients with bloodstream infections (BSI) is key for determining whether adequate empirical coverage should be prioritized over other, more conservative approaches. Recent systematic reviews outlined the need for new studies in the field, using improved methodologies. We assessed the impact of inadequate empirical treatment on the mortality of patients with BSI in the present-day context, incorporating recent methodological recommendations. A prospective multicenter cohort including all BSI episodes in adult patients was performed in 15 hospitals in Andalucía, Spain, over a 2-month period in 2006 to 2007. The main outcome variables were 14- and 30-day mortality. Adjusted analyses were performed by multivariate analysis and propensity score-based matching. Eight hundred one episodes were included. Inadequate empirical therapy was administered in 199 (24.8%) episodes; mortality at days 14 and 30 was 18.55% and 22.6%, respectively. After controlling for age, Charlson index, Pitt score, neutropenia, source, etiology, and presentation with severe sepsis or shock, inadequate empirical treatment was associated with increased mortality at days 14 and 30 (odds ratios [ORs], 2.12 and 1.56; 95% confidence intervals [95% CI], 1.34 to 3.34 and 1.01 to 2.40, respectively). The adjusted ORs after a propensity score-based matched analysis were 3.03 and 1.70 (95% CI, 1.60 to 5.74 and 0.98 to 2.98, respectively). In conclusion, inadequate empirical therapy is independently associated with increased mortality in patients with BSI. Programs to improve the quality of empirical therapy in patients with suspicion of BSI and optimization of definitive therapy should be implemented.

iNKT/CD1d-antitumor immunotherapy significantly increases the efficacy of therapeutic CpG/peptide-based cancer vaccine.

BACKGROUND: Therapeutic cancer vaccines aim to boost the natural immunity against transformed cancer cells, and a series of adjuvants and co-stimulatory molecules have been proposed to enhance the immune response against weak self-antigens expressed on cancer cells. For instance, a peptide/CpG-based cancer vaccine has been evaluated in several clinical trials and was shown in pre-clinical studies to favor the expansion of effector T versus Tregs cells, resulting in a potent antitumor activity, as compared to other TLR ligands. Alternatively, the adjuvant activity of CD1d-restricted invariant NKT cells (iNKT) on the innate and adaptive immunity is well demonstrated, and several CD1d glycolipid ligands are under pre-clinical and clinical evaluation. Importantly, additive or even synergistic effects have been shown upon combined CD1d/NKT agonists and TLR ligands. The aim of the present study is to combine the activation and tumor targeting of activated iNKT, NK and T cells. METHODS: Activation and tumor targeting of iNKT cells via recombinant α-galactosylceramide (αGC)-loaded CD1d-anti-HER2 fusion protein (CD1d-antitumor) is combined or not with OVA peptide/CpG vaccine. Circulating and intratumoral NK and H-2Kb/OVA-specific CD8 responses are monitored, as well as the state of activation of dendritic cells (DC) with regard to activation markers and IL-12 secretion. The resulting antitumor therapy is tested against established tumor grafts of B16 melanoma cells expressing human HER2 and ovalbumin. RESULTS: The combined CD1d/iNKT antitumor therapy and CpG/peptide-based immunization leads to optimized expansion of NK and OVA-specific CD8 T cells (CTLs), likely resulting from the maturation of highly pro-inflammatory DCs as seen by a synergistic increase in serum IL-12. The enhanced innate and adaptive immune responses result in higher tumor inhibition that correlates with increased numbers of OVA-specific CTLs at the tumor site. Antibody-mediated depletion experiments further demonstrate that in this context, CTLs rather than NK cells are essential for the enhanced tumor inhibition. CONCLUSIONS: Altogether, our study in mice demonstrates that αGC/CD1d-antitumor fusion protein greatly increases the efficacy of a therapeutic CpG-based cancer vaccine, first as an adjuvant during T cell priming and second, as a therapeutic agent to redirect immune responses to the tumor site.

Human cooperation based on punishment reputation.

The threat of punishment usually promotes cooperation. However, punishing itself is costly, rare in nonhuman animals, and humans who punish often finish with low payoffs in economic experiments. The evolution of punishment has therefore been unclear. Recent theoretical developments suggest that punishment has evolved in the context of reputation games. We tested this idea in a simple helping game with observers and with punishment and punishment reputation (experimentally controlling for other possible reputational effects). We show that punishers fully compensate their costs as they receive help more often. The more likely defection is punished within a group, the higher the level of within-group cooperation. These beneficial effects perish if the punishment reputation is removed. We conclude that reputation is key to the evolution of punishment.

Weighted Shape-based Averaging with Neighborhood Prior Model for Multiple Atlas Fusion-based Medical Image Segmentation

In medical imaging, merging automated segmentations obtained from multiple atlases has become a standard practice for improving the accuracy. In this letter, we propose two new fusion methods: "Global Weighted Shape-Based Averaging" (GWSBA) and "Local Weighted Shape-Based Averaging" (LWSBA). These methods extend the well known Shape-Based Averaging (SBA) by additionally incorporating the similarity information between the reference (i.e., atlas) images and the target image to be segmented. We also propose a new spatially-varying similarity-weighted neighborhood prior model, and an edge-preserving smoothness term that can be used with many of the existing fusion methods. We first present our new Markov Random Field (MRF) based fusion framework that models the above mentioned information. The proposed methods are evaluated in the context of segmentation of lymph nodes in the head and neck 3D CT images, and they resulted in more accurate segmentations compared to the existing SBA.

Instances d'aliénation: portrait du patient tiraillé 1. Individu et contexte [Instances of alienation: portrait of the torn patient. I. Individual and context].

While the past decades were marked by an increased interest for the existential situation of man suffering from disease, the mechanisms alienating the patient from himself and from his context have been poorly investigated. These mechanisms, though operating in a dynamic interaction, will be discussed here sequentially. The first part of this article focuses on individual mechanisms of alienation emerging from the relationship the patient establishes with his body and psyche and on those related to his relational context. The aim is not to comprehensively describe these phenomena, but to discuss--based on clinical vignettes--some examples and their implications. The second part of the article describes some mechanisms of alienation that are incorporated in the medical apparatus and the dominant discourses.

Kernel-based methods for change detection in remote sensing images

Nowadays, the joint exploitation of images acquired daily by remote sensing instruments and of images available from archives allows a detailed monitoring of the transitions occurring at the surface of the Earth. These modifications of the land cover generate spectral discrepancies that can be detected via the analysis of remote sensing images. Independently from the origin of the images and of type of surface change, a correct processing of such data implies the adoption of flexible, robust and possibly nonlinear method, to correctly account for the complex statistical relationships characterizing the pixels of the images. This Thesis deals with the development and the application of advanced statistical methods for multi-temporal optical remote sensing image processing tasks. Three different families of machine learning models have been explored and fundamental solutions for change detection problems are provided. In the first part, change detection with user supervision has been considered. In a first application, a nonlinear classifier has been applied with the intent of precisely delineating flooded regions from a pair of images. In a second case study, the spatial context of each pixel has been injected into another nonlinear classifier to obtain a precise mapping of new urban structures. In both cases, the user provides the classifier with examples of what he believes has changed or not. In the second part, a completely automatic and unsupervised method for precise binary detection of changes has been proposed. The technique allows a very accurate mapping without any user intervention, resulting particularly useful when readiness and reaction times of the system are a crucial constraint. In the third, the problem of statistical distributions shifting between acquisitions is studied. Two approaches to transform the couple of bi-temporal images and reduce their differences unrelated to changes in land cover are studied. The methods align the distributions of the images, so that the pixel-wise comparison could be carried out with higher accuracy. Furthermore, the second method can deal with images from different sensors, no matter the dimensionality of the data nor the spectral information content. This opens the doors to possible solutions for a crucial problem in the field: detecting changes when the images have been acquired by two different sensors.

Fills i fills de famílies immigrades als països rics. Informe 2010 sobre el cas de Catalunya al context de la Unió Europea

Aquest projecte ha consistit en la realització d'un informe actualitzat i ampli sobre la situació dels fills i filles de famílies immigrades a Catalunya en dos grups d’edat (0-17 i 18-29) i s'ha centrat en els àmbits socio-demogràfic, educatiu i jurídic, des d’una perspectiva comparativa internacional proporcionada pel projecte UNICEF Innocenti Children of Immigrant Families in 8 Affluent Countries (2009). S’ha treballat amb dades quantitatives, qualitatives i bibliogràfiques de diverses fonts primàries i secundàries. Per realitzar aquest informe, s’han ampliat els indicadors d’Innocenti en dos sentits: a) afegint, quan ha estat possible, els ja elaborats i experimentats per l’equip investigador al I i II Informes sobre Infància i Immigració a Catalunya en el marc del CIIMU els anys 2002 i 2005, així com els desenvolupats als capítols “Infancia e Inmigración” dels dos volums La Infancia en Cifras en España (Ministerio de Trabajo y Asuntos Sociales) els anys 2006 i el 2007 sobre una mostra del padró 2005 i amb projecció pel conjunt de l’estat; b) afegint una anàlisi jurídica transversal dels diferents marcs que regulen la situació dels fills i filles de famílies immigrades a la Unió Europea, Espanya, Catalunya i les cartes de drets internacionals, i s’ha contrastat aquestes regulacions amb l’anàlisi de casos obtinguts amb treball de camp etnogràfic a dues comarques (de Barcelona i Girona) que han permès il•lustrar les contradiccions de la seva aplicació. D’altra banda, seguint amb la perspectiva aplicada en estudis i informes precedents, l’abordatge ha permès analitzar comparativament la situació dels fills i filles de famílies immigrades amb els seus coetanis d’origen autòcton, pel que fa a les condicions de vida i les oportunitats socials en un sentit ampli. La Memòria que s’annexa consta de 4 grans apartats: 1) Sociodemografia, 2) Educació, 3) Marc jurídic, 4) Joves de famílies immigrades.