34 research outputs found
Sequence-Based Hepatitis B Virus Antiviral Resistance Testing in Switzerland
No full textBACKGROUND: 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
Liver stiffness and platelet count for identifying patients with compensated liver disease at low risk of variceal bleeding
No full textBackground & Aims: The 2015 Baveno VI guidelines recommend against performing upper gastrointestinal endoscopy in patients with compensated cirrhosis who have a liver stiffness 150 000/mm³ because of a low prevalence of varices at risk of bleeding in this population. The aim was to synthesize the available evidence on the usefulness of the combined use of liver stiffness and platelet count to identify patients without oesophageal varices. Methods: Meta-analysis of trials evaluating the usefulness of a given cut-off for liver stiffness and platelet count to rule out the presence of oesophageal varices. Results: Fifteen studies were included. All studies excepting five used the Baveno VI criteria. Compared to patients with either high liver stiffness or low platelet count, those with low liver stiffness and normal platelet count had a lower risk of varices at risk of bleeding (OR=0.22, 95% CI=0.13-0.39, P<.001) with low heterogeneity between studies (I2=21%). They also had a lower risk of varices (OR=0.23, 95% CI=0.17-0.32, P<.001) with moderate heterogeneity between studies (I2=28%). In patients with low liver stiffness and normal platelet count, the pooled estimate rates for varices at risk of bleeding was 0.040 (95% CI=0.027-0.059) with low heterogeneity between studies (I2=3%). Conclusions: Patients with low liver stiffness and normal platelet count have a lower risk of varices than those with either high liver stiffness or low platelet count. Varices at risk of bleeding are found in no more than 4% of patients when liver stiffness is <20 kPa and platelet count is normal.SCOPUS: ar.jinfo:eu-repo/semantics/publishe
Self-expanding metal stent should be considered in patients with cirrhosis and uncontrolled variceal bleeding
No full textSCOPUS: le.jFLWINinfo:eu-repo/semantics/publishe
Beyond Bouma's window: How to explain global aspects of crowding?
No full textIn crowding, perception of an object deteriorates in the presence of nearby elements. Although crowding is a ubiquitous phenomenon, since elements are rarely seen in isolation, to date there exists no consensus on how to model it. Previous experiments showed that the global configuration of the entire stimulus must be taken into account. These findings rule out simple pooling or substitution models and favor models sensitive to global spatial aspects. In order to investigate how to incorporate global aspects into models, we tested a large number of models with a database of forty stimuli tailored for the global aspects of crowding. Our results show that incorporating grouping like components strongly improves model performance. Author summary Visual crowding highlights interactions between elements in the visual field. For example, an object is more difficult to recognize if it is presented in clutter. Crowding is one of the most fundamental aspects of vision, playing crucial roles in object recognition, reading and visual perception in general, and is therefore an essential tool to understand how the visual system encodes information based on its retinal input. Hence, classic models of crowding have focused only on local interactions between neighboring visual elements. However, abundant experimental evidence argues against local processing, suggesting that the global configuration of visual elements strongly modulates crowding. Here, we tested all available models of crowding that are able to capture global processing across the entire visual field. We tested 12 models including the Texture Tiling Model, a Deep Convolutional Neural Network and the LAMINART neural network with large scale computer simulations. We found that models incorporating a grouping component are best suited to explain the data. Our results suggest that in order to understand vision in general, mid-level, contextual processing is inevitable.LPS
Shrinking Bouma's window: How to model crowding in dense displays
No full textIn crowding, perception of a target deteriorates in the presence of nearby flankers. Traditionally, it is thought that visual crowding obeys Bouma's law, i.e., all elements within a certain distance interfere with the target, and that adding more elements always leads to stronger crowding. Crowding is predominantly studied using sparse displays (a target surrounded by a few flankers). However, many studies have shown that this approach leads to wrong conclusions about human vision. Van der Burg and colleagues proposed a paradigm to measure crowding in dense displays using genetic algorithms. Displays were selected and combined over several generations to maximize human performance. In contrast to Bouma's law, only the target's nearest neighbours affected performance. Here, we tested various models to explain these results. We used the same genetic algorithm, but instead of selecting displays based on human performance we selected displays based on the model's outputs. We found that all models based on the traditional feedforward pooling framework of vision were unable to reproduce human behaviour. In contrast, all models involving a dedicated grouping stage explained the results successfully. We show how traditional models can be improved by adding a grouping stage. Author summary To understand human vision, psychophysical research usually focuses on simple stimuli. Vision is often described as a cascade of feed-forward computations in which local features detectors pool information along the processing hierarchy to form complex and abstract features. Crowding is can be modelled within this framework by the pooling of information from one processing stage to the next. This naturally explains Bouma's law, a hallmark of crowding according to which only elements within a certain region, often proposed to be half the target eccentricity, interfere with the target. However, pooling models are strongly challenged by recent experimental results, because Bouma's law does not hold for more complex stimuli. Visual elements far beyond Bouma's window can increase or alleviate crowding. In addition, Van der Burg and colleagues showed that only the nearest neighbours interfere with the target in dense displays. Hence, Bouma's window can shrink too. Here, we aimed at modelling the range of crowding in dense displays. From previous studies, we know that visual grouping cannot be explained without grouping and segmentation. We compared the performance of different models of vision to the human data of Van der Burg and colleagues. We found that all models based on the traditional pooling framework of vision failed to reproduce the human data, whereas all models that included grouping and segmentation processes were successful in this respect. We concluded that grouping and segmentation processes naturally and consistently explain the difference between simple and complex displays in vision paradigms.LPS
Systematic review with meta-analysis: self-expanding metal stents in patients with cirrhosis and severe or refractory oesophageal variceal bleeding.
No full textThe prognosis of patients with cirrhosis and acute variceal bleeding is very poor when the standard-of-care fails to control bleeding. New treatment modalities are needed in these patients.SCOPUS: re.jFLWINinfo:eu-repo/semantics/publishe
Signalome-wide assessment of host cell response to hepatitis C virus
No full textHost cell signalling during infection with intracellular pathogens remains poorly understood. Here we report on the use of antibody microarray technology to detect variations in the expression levels and phosphorylation status of host cell signalling proteins during hepatitis C virus (HCV) replication. Following transfection with HCV RNA, the JNK and NF-kappa B pathways are suppressed, while the JAK/STAT5 pathway is activated; furthermore, components of the apoptosis and cell cycle control machineries are affected in the expression and/or phosphorylation status. RNAi-based hit validation identifies components of the JAK/STAT, NF-kappa B, MAPK and calcium-induced pathways as modulators of HCV replication. Selective chemical inhibition of one of the identified targets, the JNK activator kinase MAP4K2, does impair HCV replication. Thus this study provides a comprehensive picture of host cell pathway mobilization by HCV and uncovers potential therapeutic targets. The strategy of identifying targets for anti-infective intervention within the host cell signalome can be applied to any intracellular pathogen.Australian Cancer Research Foundation (ACRF); Victorian Department of Industry, Innovation and Regional Development (DIIRD); Australian Phenomics Network (APN); Australian Government's Education Investment Fund through the Super Science Initiative; Australasian Genomics Technologies Association (AGTA); Brockhoff Foundation; Peter MacCallum Cancer Centre Foundation; EU (ERC HEPCAR); EU (H2020 HEPCENT); NIH [U19-AI123862]; Australian Centre for HIV and Hepatitis Virology Research (ACH2)SCI(E)ARTICLE
External validation of the nomogram for individualized prediction of hepatocellular carcinoma occurrence in patients with hepatitis C virus–related compensated cirrhosis
No full textSCOPUS: le.jinfo:eu-repo/semantics/publishe
