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Data on the long-term persistence of HCV resistance-associated substitutions (RASs) after treatment with direct-acting antivirals (DAAs) are limited. This study evaluated the persistence of NS3, NS5A, and NS5B RASs for up to 5 years after the end of treatment (EOT).We included samples from 678 individuals with an HCV genotype (GT) 1 or 3 infection and virologic DAA treatment failure collected in the European Resistance Database. NS3, NS5A, and NS5B were sequenced, and clinical parameters were evaluated.A total of 242 individuals with HCV GT1a (36%), 237 with GT1b (35%), and 199 (29%) with GT3 and a DAA failure were included. After protease inhibitor failure, the frequencies of NS3 RASs were 40-90% after the EOT. NS3 RASs disappeared rapidly in GT1b and GT3 after follow-up month 3 but were stable (≥60%) in GT1a owing to Q80K. The SOF-resistant NS5B RAS S282T was only found in individuals with GT3a. Non-nucleoside NS5B RASs were frequent in GT1 (56-80%) and decreased to 30% in GT1a but persisted in GT1b. NS5A RASs were very common in all GTs after NS5A inhibitor failure (88-95%), and even after follow-up month 24, their frequency was 65% and higher. However, RASs in GT1b had a stable course, whereas RASs in GT1a and GT3 declined slightly after follow-up month 24 (GT1a, 68%; GT1b, 95%; and GT3, 65%), mainly because of the slow decline of high-level resistant Y93H.We found that low-to medium-level RASs persisted, whereas high-level resistant RASs disappeared over time. Different patterns of RAS persistence according to HCV subtype could have implications for retreatment with first-generation DAAs and for global HCV elimination goals.There are little data on the long-term persistence of HCV resistance-associated substitutions (RASs) after DAA treatment failure, and RASs could have an impact on the efficacy of a rescue treatment. Especially in countries with limited availability of VOX/VEL/SOF or G/P/SOF, different patterns of RAS persistence could have implications for retreatment with first-generation DAAs and for global HCV elimination goals. The different patterns of RAS persistence identified in this study can be used to derive general rules regarding the persistence of RASs after DAA failure that could be applied by physicians in less developed countries to plan individualized HCV retreatment.

International audience; Migration velocity analysis is a method devoted to the evaluation of both reflectivity and background velocity models, associated with the high and low wavenumber components of the model, respectively. Inversion velocity analysis is one of its improved versions, leading to more stable background velocity updates. Still, the impact of the user parameters should be understood for an optimal update of the background velocity. We show that a sign reversal of the background velocity gradient could occur when the selected surface offset range or the space lag range is too small. We derive the theoretical limits and check their consistency through simulations in a simple model with a single interface. These guidelines determine the necessary ranges of surface offsets and space lags for a proper update of the background velocity model. We discuss their applicability on the Marmousi model. Artefacts in the retrieved background velocity model are observed when the guidelines are not satisfied.

The Al-based nanoquasicrystalline alloys are modern light weight alloys that respond to a strategy to develop new Al-based alloys with excellent combination of properties over a large range of temperatures when compared with standard aluminium alloys. The review describes their historical development, the manufacturing processes used for the alloy production and the microstructure obtained. A summary of the different systems and alloying elements used in the development is presented and their stability is discussed. Several properties have been studied with particular focus on mechanical and structural applications, which are discussed together with their potential applications.

Hepatitis C virus infection is causing chronic liver disease, cirrhosis, and hepatocellular carcinoma. By combining direct-acting antivirals (DAAs), high sustained virologic response rates (SVRs) can be achieved. Resistance-associated substitutions (RASs) are commonly observed after DAA failure, and especially nonstructural protein 5A (NS5A) RASs may impact retreatment options.1-3 Data on retreatment of DAA failure patients using first-generation DAAs are limited.4-7 Recently, a second-generation protease- and NS5A-inhibitor plus sofosbuvir (voxilaprevir/velpatasvir/sofosbuvir [VOX/VEL/SOF]) was approved for retreatment after DAA failure.8 However, this and other second-generation regimens are not available in many resource-limited countries or are not reimbursed by regular insurance, and recommendations regarding the selection of retreatment regimens using first-generation DAAs are very important. This study aimed to analyze patients who were re-treated with first-generation DAAs after failure of a DAA combination therapy.

Background & Aims Little is known about substitutions that mediate resistance of hepatitis C virus (HCV) to direct-acting antivirals (DAAs), due to the small number of patients with treatment failure in approval studies. It is important to identify resistance patterns to select effective salvage treatments. Methods We performed a comprehensive analysis for resistance-associated substitutions (RASs) in HCV genes (nonstructural protein [NS]3, NS5A, NS5B) targeted by DAAs. We compared NS3, NS5A, and NS5B sequences from 626 patients in Europe with DAA failure with sequences from 2322 DAA-naive patients, infected with HCV genotypes 1 to 4. We considered RASs to be relevant if they were associated with DAA failure in patients or conferred a greater than twofold change in susceptibility compared with a reference strain in in vitro replicon assays. Data were collected on pretreatment status, DAA regimen, the treatment initiation date and duration, and virologic response. Patients who received at least 4 weeks of antiviral treatment were included in the analysis. Results RASs in NS3 associated with simeprevir or paritaprevir failure include R155K and D168E/V. In addition, several RASs were specifically associated with failure of simeprevir (Q80K/R in patients with genotype 1a or 4) or paritaprevir (Y56H in combination with D168V in patients with genotype 1b). Y93H in NS5A was the RAS most frequently associated with failure of daclatasvir, ledipasvir, or ombitasvir in patients with genotype 1b infection, and L31M was associated with failure of daclatasvir or ledipasvir, but not ombitasvir. RASs in NS5A were heterogeneous among patients with HCV genotype 1a or genotype 4 infections. In patients with HCV genotype 3, Y93H was associated with resistance to daclatasvir, but no RASs were associated with ledipasvir failure, pointing to a limited efficacy of ledipasvir in patients with genotype 3. Among patients failed by sofosbuvir-containing regimens, L159F was enriched in patients with genotype 1b (together with C316N) or genotype 3 infection, whereas the RAS S282T was rarely observed. Conclusions We compared RASs in NS3, NS5A, and NS5B among patients failed by DAA therapy. Theses varied with the HCV genotype and subtype, and the different drug classes. These findings might be used to select salvage therapies.

A 63-year-old female was admitted to the hospital with leg and forearm paresthesias. We found progressive ataxia, dementia, and psychosocial deterioration. The clinical symptoms, the neurologic and psychiatric abnormalities together with the inflammatory cerebrospinal fluid alteration and the cerebral magnetic resonance imaging changes suggested a paraneoplastic etiology. It was confirmed by paraneoplastic antineuronal antibodies in the patient's serum and the histological diagnosis of a small cell bronchial carcinoma. The prognosis of patients with paraneoplastic symptoms is the better the earlier a diagnosis is established and antitumor therapy is initiated.

We have applied wave-equation tomography to both refraction and reflection data to retrieve the long-wavelength subsurface velocity model. To simulate reflection waves, especially, long- and short-wavelength structures are separated and mapped into velocity and density, respectively. To match the amplitude of the real reflection waves, full waveform inversion is applied to the near-offset data, where all the short-wavelength impedance contrasts are mapped into density. The short-wavelength density model is then converted into zero-offset travel time domain where it is independent of the long-wavelength velocity model. As velocity is updated using wave-equation tomography, density is converted back into depth domain for wave-field modeling. To alleviate the nonlinearity of the inversion problem, an offset continuation strategy is adapted that refraction waves are used first to provide vertical constrains on the velocity model, after which, reflection waves are included to provide lateral constrains. As wave-equation tomography has derived the satisfactory long-wavelength velocity model, FWI is initialized to invert all the data to retrieve the short-wavelength velocity structures. The strategy is applied to one marine real dataset example with 15-km-long streamer. Our results shows that one can recover detailed velocity information starting from a poorly constrained model with appropriate regularization.

Quasicrystals are a new class of ordenated structures with metaestable characteristics at room temperature. Quasicrystalline phases can be obtained by rapid quenching from the melt of some alloys. In general, quasicrystals present properties which make these alloys promising for wear and corrosion resistant coatings applications. During the last years, the development of quasicrystalline coatings by means of thermal spray techniques has been impulsed. However, no references have been found of their application by means of laser techniques. In this work four claddings of quasicrystalline compositions formed over aluminum substrate, produced by a continuos CO2 laser using simultaneous powders mixture injection are presented. The claddings were characterized by X ray diffraction, scanning electron microscopy and Vickers microhardness.Los cuasicristales constituyen un nuevo tipo de estructuras ordenadas con características metaestables a temperatura ambiente. En general, en determinadas aleaciones, pueden obtenerse por enfriamiento rápido desde el estado líquido. Han demostrado poseer buenas propiedades para su aplicación como recubrimientos resistentes al desgaste y a la corrosión. En este sentido, desde hace unos años, se ha impulsado el desarrollo de su aplicación mediante técnicas de thermal spray, aunque no se han encontrado referencias de su aplicación mediante técnicas de láser. En este trabajo, se presenta la formación de cuatro recubrimientos de aleaciones con composiciones cuasicristalinas sobre un sustrato de aluminio, utilizando un láser continuo de CO2, con inyección simultánea del material en forma de mezcla de polvos. Los mismos fueron caracterizados por difracción de rayos X, microscopía electrónica de barrido y microdureza Vickers.

Common-image gathers (CIGs) in the angle domain contain important information for velocity analysis and subsurface attribute analysis; and they may also be used to improve stacked migration images. In this paper we propose a new approach to compute the angle-domain CIGs for RTM based on an inverse-scattering imaging condition, in which the reflection angle presents itself implicitly as weighting of the wave fields. Two images are generated with and without the implicit reflection angle factor. The reflection angle is computed by dividing one pre-stack image by the other. Then pre-stack images from all the shots are mapped and binned into angle domain to form CIGs. Since the angle gathers are extracted in a postmigration step, it adds little memory requirement to RTM; and the computation is very efficient, especially for isotropic media. We demonstrate the method with several synthetic examples.

We describe an enzyme-linked immunosorbent assay (ELISA) to quantitate venom antigens in human serum and urine, and thus to help evaluate the severity of envenomation due to viper bites. This assay, which is performed with commercially available polyclonal Fab'2s in a double-sandwich method, is rapid, simple, and specific for antigens of European vipers (Vipera aspis, Vipera berus, and Vipera ammodytes). No cross-reactivity was observed with other snake venoms or human serum proteins. It showed a good linear response over a wide range of concentrations of venom antigens (from 1 to 100 ng/mL). It was very sensitive, with detection limits of 7 and 2 ng/mL for Vipera aspis venom in serum and urine, respectively. This ELISA is also easily reproducible; the coefficients of variation determined at different concentrations of venom (50, 25, and 5 ng/mL) did not exceed 10% in serum and 14% in urine samples collected from different donors. This test was applied to determine the concentrations of venom in the serum of patients bitten by a viper in France and to follow its elimination as a function of time. The method is adaptable to other venoms by using other specific immunoglobulins.

Wave equation migration is suitable for imaging in complex structures. Ideally, its imaging capability should be matched by corresponding velocity model building tools. However, the tool of choice for velocity model building, ray-based tomography, at first sight seems weakly compatible with wave equation migration. To overcome this contradiction we propose several strategies. The first is to convert the wave equation migration image gathers, typically indexed by subsurface offset, into a format appropriate for tomography: local reflection angle or its tangent. In conjunction with this conversion, we employ a datuming procedure to restrict the tomography to a localized domain where it is compatible with the wave equation migration band-limited propagation. A second strategy, more expensive and not yet widely tested, is to replace ray-based tomography with wave-equation-based migration velocity analysis, assuring complete compatibility with the imaging. In all cases, we notice that having wide-azimuth data makes velocity model building easier, as any chosen subsurface azimuth contains specular information.

Bei einem 34-jährigen Mann mit chronischem Husten und Belastungsdyspnoe wurden im CT-Thorax zystische Veränderungen festgestellt. Mittels bronchoalveolärer Lavage (BAL) gelang der Nachweis von Mycobacterium kansasii. Trotz Behandlung mit Rifampicin und Ethambutol zeigte sich in den folgenden[for full text, please go to the a.m. URL], 10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010)

We report a case of primary infectious thoracic aortitis with contained rupture of the descending thoracic aorta caused by Staphylococcus aureus and successfully treated with a rifampicin-rinsed aortic stent graft.

Wave-Equation Migration has evolved towards a routine tool to generate final stack images but the computation of wave-equation image gathers has not yet spread out in the industry. Nevertheless, provided a good understanding of wave equation gathers’ typology, this prestack information proves to be useful to improve final wave-equation stack images and to build accurate velocity models. In this paper, we explore these new image-gathers, describe their behaviour in terms of true specular events as opposed to artefacts and propose solutions for the applications of these image-gathers in improved imaging and in velocity model building. We first describe what are the image-gathers produced by Wave-Equation Migration. Then we characterize the specular events and the acquisition and processing artefacts they exhibit. On analytical and synthetic image-gathers, we illustrate the artefacts linked with the acquisition truncation. Although feeding tomography with these gathers may require a sophisticated method to recover only the specular part, an adapted mute can prove to be a very efficient in a post-processing workflow. We illustrate on a real 3D subsalt dataset how the use of wave-equation image gathers significantly improves the seismic stack.

Viper bites are frequent in France but the evaluation of the severity of envenomings and consequently patient treatment has not yet been properly evaluated. The purpose of this study was to measure venom antigens in blood and/or urine of bitten patients and to establish a quantitative relationship with clinical observations. A prospective enquiry was conducted in 1990 in France to collect epidemiological, clinical and biological data from hospitals. Urine and blood samples were tested for their content of Vipera aspis venom antigens by a sandwich enzyme linked immunosorbent assay (ELISA). One hundred and two charts were analysed, from patients presenting documented viper bites. Oedema was the prominent local feature (81 cases). Systemic signs consisted of vomiting and/or diarrhoea (22 cases), slight or severe hypotension (15 cases), shock (2 cases) and bleeding (1 case). A relationship was observed between these systemic signs and the extent of the oedema, which permitted the establishment of a grading scale. Grade 0 (no envenoming) was identified by fang marks and absence of oedema and local reaction; grade 1 (mild envenoming) by local oedema and absence of systemic symptoms; grade 2 (moderate envenoming) by regional oedema and moderate systemic symptoms; and grade 3 (severe envenoming) by extensive oedema and severe systemic symptoms. Quantification of venom antigens in blood or urine of patients by ELISA revealed a significant correlation between clinical signs of envenoming and the level of venom antigens in blood or urine. This indicated that the ELISA test is a useful and predictive tool for clinically grading viper envenomings.

Wave Equation Migration, WEM, is suitable for imaging in complex structures. Nevertheless its imaging capability should be matched by correspondingly capable velocity model building tools. The tool of choice for velocity model building is ray-based tomogr

In this paper we describe the definition and applications of structurally conformable transversely isotropic (STI) velocity models in seismic imaging. After describing some geological aspects of STI media, we present the effects of this kind of anisotropy

C003 Subsalt Velocity Analysis by Combining Wave Equation Based Redatuming and Kirchhoff Based Migration Velocity Analysis B. Wang* (CGGVeritas) F. Audebert (CGGVeritas) V. Dirks (CGGVeritas) J. Liu (CGGVeritas) & P. Zhang (CGGVeritas) SUMMARY Due to the geometrical complexity of the typical Gulf of Mexico (GOM) velocity models with embedded salt bodies of any shapes wave equation migration is used preferentially over Kirchhoff methods for subsalt velocity model building. This preference is based on the ability of wave-equation based migrations to overcome the need for tracing complex ray paths through the salt bodies and for a better handling of multi-path arrivals

We have developed a new methodology to produce a best focused zero-offset image, even though the migration velocity model has errors. In this methodology, first we generate Common Focusing Error (CFE) images using wave equation based prestack migration and applying zero-time as well as non-zero-time imaging conditions. Then a semi-automatic procedure is applied to pick the focusing error (DT) field, and the picked DT field is used to select the best focused image from the CFE images. To produce an accurately positioned and well focused zero-offset image, we separate the prestack focusing effect from the poststack focusing effect, by performing poststack demigration followed by DT compensated poststack remigration.

Al-based systems allow obtaining microstructures composed of different combination of several classes of phases: crystalline solid solutions, amorphous solid solutions, crystalline intermetallic compounds and quasicrystals. Many Al-Fe based systems are icosahedral phase former, but non icosahedral phase was reported in Al-Ni based systems. The strong hetero-atomic interaction in the liquid of Al-based alloys appears to have a big effect on the amorphous forming ability. In order to analyse the amorphous forming ability and the amorphous structure of Al-Fe and Al-Ni based alloys, series of samples were produced by melt spinning. The structure was characterized by means of X-ray diffraction, Mdssbauer spectroscopy and transmission electron microscopy. Clusters with medium range order in the Al-Fe based alloys were found and the icosahedral short range order in the amorphous structure is discussed. These alloys have a heterogeneous amorphous structure at nano-scale. The relationship among the different phases obtained by rapid solidification in the Al-Fe based systems is discussed considering the hetero-atomic interaction and the ability for clusters formation in the liquid.

A 63-year-old female was admitted to the hospital with leg and forearm paresthesias. We found progressive ataxia, dementia, and psychosocial deterioration. The clinical symptoms, the neurologic and psychiatric abnormalities together with the inflammatory cerebrospinal fluid alteration and the cerebral magnetic resonance imaging changes suggested a paraneoplastic etiology. It was confirmed by paraneoplastic antineuronal antibodies in the patient's serum and the histological diagnosis of a small cell bronchial carcinoma. The prognosis of patients with paraneoplastic symptoms is the better the earlier a diagnosis is established and antitumor therapy is initiated.

The purpose of imaging is 1) to focus the seismic data, 2) to position all seismic events correctly in space and 3) correct for amplitude and illumination effects.

E-02 MIGRATION IN THE ANGLE DOMAIN – AN INSIDE VIEW Migration in the angle domain. 1 FRANCOIS AUDEBERT 1 PASCAL FROIDEVAUX 2 LAURENCE NICOLETIS 2 and HERY RAKOTOARISOA 2 Migration in the angle domain comes as a recent development Xu et al. (1998) in the long-running story of true amplitude Kirchhoff migration. The classic approach in the offset domain for true amplitude migration uses the Beylkin determinant (Beylkin 1985) which is the Jacobian of the change of coordinates from the surface acquisition (source-receiver couple) to the illuminations vector at the depth point. The Beylkin Jacobian handles the irregularity of illumination

The morphogenesis and the distribution along the digestive tract of Trichostrongylus retortaeformis(Zeder, 1800) (Nematoda) were studied in detail in one of its natural hosts, Oryctolagus cuniculus. Worm-free rabbits were each infected with T. retortaeformis larvae and were killed at 12 h post-infection (HPI) and on each day from 1 to 15 days post-infection (DPI). The distribution of worm populations along the small intestine was assessed. At the different dates of infection, more than 80% of the population was recovered from the first third of the intestine with more than 50% occurring in the first 30 cm. For each date, morphological descriptions of the different stages of the life cycle were also provided. In addition, adult worms collected from naturally infected rabbits from France were redescribed.

Migration velocity analysis (MVA) should allow interpreters to check and improve the complex velocity models required for 3D pre-stack depth imaging

Antivenomous immunotherapy is still used empirically. To improve the efficacy and safety of immunotherapy, we studied the effects of administering antivenom antibodies (F(ab')2) on the pharmacokinetics of the Vipera aspis venom in rabbits. Free venom levels were measured by enzyme-linked immunosorbent assay and total concentrations were quantified by measuring the radioactivity of trichloroacetic acid-precipitable radioiodinated venom. The intravenous infusion of 125 mg of antivenom 7 h after intramuscular injection with 700 microg x kg(-1) of V. aspis venom produced a redistribution of the venom antigens from the extravascular to the vascular space. Moreover, anti-venom antibodies were able to neutralize the totality of venom antigens in the vascular space, because no free plasma venom was detectable by enzyme-linked immunosorbent assay within 15 min after antivenom injection. Similar effects were obtained after injection of 25 mg of antivenom; however, the venom was only partially neutralized with lower doses (5 and 2.5 mg). We further established that intravenous injection is the most efficient route for antivenom administration, and we examined the effects of early and late immunotherapy. Finally, the efficacy of Fab antibodies was compared with that of F(ab')2; the plasma redistribution and the immunoneutralization of the venom were lower than those induced after injection of the same dose of F(ab')2. The difference between the effects of F(ab')2 and Fab could be explained by the differential pharmacokinetics of the two fragments.

Migration velocity analysis allows the checking and improvement of the complex velocity models required for 3D pre-stack depth imaging. The new migration velocity method we propose is free from any assumptions regarding the migration velocity model. Our method is based on the classic CRP (Common Reflecting Point) gathers from common-offset migration, extended by a scan of homothetic velocity perturbations. The scan of velocity perturbations around the complex 3D velocity model is economically emulated by a scaling of the precomputed traveltimes. Optimal alignment is directly observed. If present, an alignment at depth Z and perturbation y gives directly a new depth location and a velocity perturbation. A table of siech new depth locations and velocity perturbations allows the product ion of an updated velocity model.

Snake bites are a major public health problem throughout the world, particularly in tropical countries where mortality and morbidity rates are very high. The specific treatment of ophidian envenomation is serotherapy. It consists in the empirical administration of large amounts of specific antivenoms. Although serotherapy has been discovered a century ago, the mechanism by which antibodies of antivenoms neutralize venom proteins in vivo is still poorly understood. In order to rationalize antivenom therapy, clinicians should be able to know as quickly as possible the severity of the envenomation, to assess the appropriateness of serotherapy and to adapt the dose of serum to inject to the gravity of envenoming. Moreover, some parameters of antivenom administration such as the delay in administration after snake bites, and the route of injection and the type of antibodies to be used, are dependent on the understanding of the kinetics of venom and antivenom. Such investigations have been performed in the case of envenomations by European vipers in France. An ELISA was developed to determine venom concentrations in biological samples of patients bitten by vipers in an attempt to establish a correlation between venom levels and clinical symptoms. The kinetics of Vipera aspis venom was studied using experimental envenomations in rabbits. The effect of antivenom administration on the toxicokinetics of venom was also determined.

The general problem of 3D pre-stack depth imaging is composed of two parts: 1) the definition of the velocity model necessary to properly image the area of interest (model building), and 2) the depth migration itself

Toxicokinetic studies of Vipera aspis venom were performed in rabbits after experimental envenomation. Venom proteins with a molecular weight greater than 6 kDa (high-molecular weight proteins) and which reacted in enzyme-linked immunosorbent assay with specific antiviper venom Fab'2, were also responsible for the lethal potency and the capillary permeability increasing activity of the venom. Conversely, low-molecular weight proteins were not detected by enzyme-linked immunosorbent assay and were pharmacologically inactive. The toxicokinetics of both classes of venom components were studied, using high-molecular weight and low-molecular weight radiolabeled proteins as well as enzyme-linked immunosorbent assay. After intravenous injection, Vipera aspis venom in plasma followed a biexponential decline with a distribution half-life of 0.7 hr and an elimination half-life of 12 hr. The distribution volume was 1.2 l.kg-1 and the systemic clearance was 84 ml.hr-1.kg-1. Venom levels in plasma after intramuscular injection of three doses (300, 500 and 700 micrograms/kg) of venom increased within the few hours after the venom administration to reach maximal values proportional to the injected doses. They subsequently followed a monoexponential decline, with an apparent terminal half-life of 32.5 hr. Absorption was a kinetically complex process, rapid during the first 24 hr and continued at a slower rate over the subsequent 72 hr. Bioavailability of venom was about 65%, regardless of the administered dose, and less than 5% of venom injected was excreted by the renal route.

We took advantage of the Mannousi model to exploreand check the possibilities of focusing analysis (resulting from S-G prestack depth migration, where S stands for shot and G for geophone), as a tool for determining a "background" velocity model. As the Marmousi model was unknown to us, we decided to use only the geological information in our possession, and the minimal processing necessary for the S-G prestack depth migration. Regarding the pre-processing, a correction of the time-lag of the wavelet is sufficient to ensure depth calibration. Further deconvolution and multiple-removal are desirabie (but not compulsory) for better legibility of focusing analyses. Regarding determination of velocities, focusing analyses perform very wen in areas of calm structure, allowing us to find depths, veloeities and smooth lateral velocity gradients. In areas of complex structures, information given by focusing analysis is harder to exploit, particularly in the case of sharp lateral velocity variations : where strong deviations of rays occur, no quantitative information is to be expected, but only a qualitative check of geological interpretation.