Dating of the oldest continental sediments from the Himalayan foreland basin

A detailed knowledge of Himalayan development is important for our wider understanding of several global processes, ranging from models of plateau uplift to changes in oceanic chemistry and climate(1-4). Continental sediments 55 Myr old found in a foreland basin in Pakistan(5) are, by more than 20 Myr, the oldest deposits thought to have been eroded from the Himalayan metamorphic mountain belt. This constraint on when erosion began has influenced models of the timing and diachrony of the India-Eurasia collision(6-8), timing and mechanisms of exhumation(9,10) and uplift(11), as well as our general understanding of foreland basin dynamics(12). But the depositional age of these basin sediments was based on biostratigraphy from four intercalated marl units(5). Here we present dates of 257 detrital grains of white mica from this succession, using the Ar-40-(39) Ar method, and find that the largest concentration of ages are at 36-40 Myr. These dates are incompatible with the biostratigraphy unless the mineral ages have been reset, a possibility that we reject on the basis of a number of lines of evidence. A more detailed mapping of this formation suggests that the marl units are structurally intercalated with the continental sediments and accordingly that biostratigraphy cannot be used to date the clastic succession. The oldest continental foreland basin sediments containing metamorphic detritus eroded from the Himalaya orogeny therefore seem to be at least 15-20 Myr younger than previously believed, and models based on the older age must be re-evaluated

Family outbreak of an infection with a recombinant Coxsackie A virus in eastern Switzerland

Purpose: We report on an unusual familial outbreak of a coxsackie virus infection in Switzerland in which five family members were affected. Most of the patients presented with signs of meningitis, and four were hospitalized. Methods: In three individuals, the virus was detected in the cerebrospinal fluid, pharynx, and stool, respectively. The genome was sequenced in specimens of two patients. Results: The nucleotide sequences of both virus strains were identical. Blast search revealed that the first half of the sequence was 88% homologous to Enterovirus 75 (EV-75), 87% with Echovirus 11 (E-11), and 84% homologous to Coxsackie virus A9 (CV-A9). The second half of the sequence was 77% homologous to EV-75, 75% to E-11, and 91% to CV-A9. Conclusion: We propose that the isolated virus strain is a recombinant strain with a 5′ untranslated region and with the start of the VP4 sequence originating from E-11/EV-75 and the rest of the genome originating from CV-A9. Interestingly, this novel virus strain showed an exceptional virulence and rapid spread. Twoweeks after the initial outbreak in this family, a similar outbreak was observed in a second geographic area roughly 100km distant to the primary identification site, and another 2months later this virus strain was found to circulate in the western part of Switzerland some 250km distant to the primary locus. These findings suggest that genetic recombination has resulted in a novel enterovirus with features of high virulence, contagiosity, and spreadin

Pore water chemistry of a Paleogene continental mudrock in Spain and a Jurassic marine mudrock in Switzerland: Sampling methods and geochemical interpretation

Este trabajo resume una serie de metodologías y aproximaciones desarrolladas en CIEMAT durante los últimos 10 años con el objetivo de obtener información del agua intersticial de dos formaciones arcillosas: la Opalinus Clay procedente de Suiza y una formación de edad Oligoceno Mioceno española. Ambas tienen características bastante diferentes tanto desde el punto de vista de la metodología aplicada para su estudio como del origen sedimentario en sí mismo de las dos formaciones. La arcilla Suiza se estudió a través de la participación en el experimento DI-B en el laboratorio subterráneo de Mont Terri, en Suiza, uno de cuyos objetivos fue el muestreo y análisis in situ del agua intersticial de la arcilla. Las muestras de agua se recogieron después de desarrollar equipos y metodologías para conseguir una alteración mínima de los parámetros críticos del agua de la arcilla: pH, Eh, pCO2, Fe(II) y alcalinidad. La modelización geoquímica se utilizó como herramienta para interpretar y entender los principales procesos geoquímicos que controlan la química del agua y el estado actual del sistema. En relación con la arcilla española, el artículo muestra el desarrollo de una metodología integrada para caracterizar el agua intersticial de la formación arcillosa a partir de muestras de testigos correspondientes a un sondeo, denominados S1. El estudio trata de integrar todos los datos disponibles sobre la composición del agua intersticial obtenida mediante la técnica de compresión bajo presión (squeezing) y mediante extractos acuosos, con la caracterización mineralógica y geoquímica de los testigos. La modelización geoquímica se utilizó con dos objetivos principales: para valorar la consistencia de los datos analíticos del agua intersticial y para determinar la importancia relativa de los principales procesos que gobiernan la química del agua intersticial. Específicamente, la modelización se utilizó para simular los procesos que controlan la evolución redox del sistema. Se consideró equilibrio para los minerales reactivos como la calcita, dolomita, yeso y ferrihidrita. Además, se trató la degradación de la materia orgánica y la disolución oxidativa de la pirita desde un punto de vista cinético

Chronic Norovirus Infection after Kidney Transplantation: Molecular Evidence for Immune-Driven Viral Evolution

Background. Norovirus infection is the most common cause of acute self-limiting gastroenteritis. Only 3 cases of chronic norovirus infection in adult solid organ transplant recipients have been reported thus far. Methods. This case series describes 9 consecutive kidney allograft recipients with chronic norovirus infection with persistent virus shedding and intermittent diarrhea for a duration of 97-898 days. The follow-up includes clinical course, type of immunosuppression, and polymerase chain reaction for norovirus. Detailed molecular analyses of virus isolates from stool specimens over time were performed. Results. The intensity of immunosuppression correlated with the diarrheal symptoms but not with viral shedding. Molecular analysis of virus strains from each patient revealed infection with different variants of GII.4 strains in 7 of 9 patients. Another 2 patients were infected with either the GII.7 or GII.17 strain. No molecular evidence for nosocomial transmission in our outpatient clinic was found. Capsid sequence alignments from follow-up specimens of 4 patients showed accumulation of mutations over time, resulting in amino acid changes predominantly in the P2 and P1-2 region. Up to 25 amino acids mutations were accumulated over a 683-day period in the patient with an 898-day shedding history. Conclusion. Norovirus infection may persist in adult renal allograft recipients with or without clinical symptoms. No evidence for nosocomial transmission in adult renal allograft recipients was found in our study. Molecular analysis suggests continuous viral evolution in immunocompromised patients who are unable to clear this infectio

Valley Bifurcation in an O(3)O(3) σ\sigma Model: Implications for High-Energy Baryon Number Violation

The valley method for computing the total high-energy anomalous cross section $S_{anom}$ is the extension of the optical theorem to the case of instanton-antiinstanton backgrounds. As a toy model for baryon number violation in Electroweak theory, we consider a version of the $O(3)$ $\sigma$ model in which the conformal invariance is broken perturbatively. We show that at a critical energy the saddle-point values of the instanton size and instanton-antiinstanton separation bifurcate into complex conjugate pairs. This nonanalytic behavior signals the breakdown of the valley method at an energy where $S_{anom}$ is still exponentially suppressed. (Figures replaced 5/3/93).Comment: (14 pages, Los Alamos Preprint LA-UR-93-811). 3 uuencoded figures include

A Functional Henipavirus Envelope Glycoprotein Pseudotyped Lentivirus Assay System

<p>Abstract</p> <p>Background</p> <p>Hendra virus (HeV) and Nipah virus (NiV) are newly emerged zoonotic paramyxoviruses discovered during outbreaks in Queensland, Australia in 1994 and peninsular Malaysia in 1998/9 respectively and classified within the new <it>Henipavirus </it>genus. Both viruses can infect a broad range of mammalian species causing severe and often-lethal disease in humans and animals, and repeated outbreaks continue to occur. Extensive laboratory studies on the host cell infection stage of HeV and NiV and the roles of their envelope glycoproteins have been hampered by their highly pathogenic nature and restriction to biosafety level-4 (BSL-4) containment. To circumvent this problem, we have developed a henipavirus envelope glycoprotein pseudotyped lentivirus assay system using either a luciferase gene or green fluorescent protein (GFP) gene encoding human immunodeficiency virus type-1 (HIV-1) genome in conjunction with the HeV and NiV fusion (F) and attachment (G) glycoproteins.</p> <p>Results</p> <p>Functional retrovirus particles pseudotyped with henipavirus F and G glycoproteins displayed proper target cell tropism and entry and infection was dependent on the presence of the HeV and NiV receptors ephrinB2 or B3 on target cells. The functional specificity of the assay was confirmed by the lack of reporter-gene signals when particles bearing either only the F or only G glycoprotein were prepared and assayed. Virus entry could be specifically blocked when infection was carried out in the presence of a fusion inhibiting C-terminal heptad (HR-2) peptide, a well-characterized, cross-reactive, neutralizing human mAb specific for the henipavirus G glycoprotein, and soluble ephrinB2 and B3 receptors. In addition, the utility of the assay was also demonstrated by an examination of the influence of the cytoplasmic tail of F in its fusion activity and incorporation into pseudotyped virus particles by generating and testing a panel of truncation mutants of NiV and HeV F.</p> <p>Conclusions</p> <p>Together, these results demonstrate that a specific henipavirus entry assay has been developed using NiV or HeV F and G glycoprotein pseudotyped reporter-gene encoding retrovirus particles. This assay can be conducted safely under BSL-2 conditions and will be a useful tool for measuring henipavirus entry and studying F and G glycoprotein function in the context of virus entry, as well as in assaying and characterizing neutralizing antibodies and virus entry inhibitors.</p

Detection of regular boundaries in noisy and textured images : a multiscale active contour approach

This article deals with the detection of edges in noisy and textured images . After an overview of the shortcomings of local operators, we assess active contour models, which constrain the detection using a priori information . The implementation of active contours is difficult due to several problems . We suggest two methods which make this global approach more robust and easier to use . On one hand, the parameters are set using a calibration algorithm which relies on geometrical a priori . The value of the parameters depends upon the maximum curvature . On the other hand, a multiscale strategy reduces the need for an accurate initialization of active contours . The convergence is robust at coarse scales and the localization of edges is enhanced at fine scales . Several efficient algorithms are proposed to track contours over decreasing scale, using a prediction on the distorsion of boundaries caused by gaussian blurring . The experiments show the validity of our approach and the relevance of a cooperation between segmentation processes, especially to solve the initialization problem .Cet article traite de la détection de contours dans des images fortement bruitées et texturées. Après avoir exposé les limitations des opérateurs locaux, nous suggérons de contraindre la détection grâce aux modèles de contours actifs, qui introduisent des informations a priori sur la géométrie et la régularité des objets cherchés. La mise en oeuvre des contours actifs est difficile en raison de nombreux problèmes pratiques. Nous proposons deux techniques rendant cette approche globale plus robuste et plus facile d'emploi. D'une part, nous facilitons le choix des paramètres en adaptant un algorithme de calibrage ayant une explication géométrique : les paramètres dépendent de la valeur de la courbure maximale. L'association des contours actifs et d'une représentation multiéchelle permet d'autre part de réduire la dépendance vis-à-vis de l'initialisation. Après une convergence robuste vers une solution grossière, la localisation des contours est améliorée en diminuant progressivement l'échelle d'analyse. Nous proposons alors plusieurs techniques efficaces de suivi des contours dans l'espace-échelle, s'appuyant sur une prédiction du déplacement des frontières sous l'effet du lissage gaussien. Les résultats expérimentaux montrent la validité de notre approche, et mettent en évidence l'apport d'une collaboration entre processus de segmentation, en particulier pour automatiser l'initialisation

Optimized patient transfer using an innovative multidisciplinary assessment in the Kanton Aargau (OPTIMA I): an observational survey in lower respiratory tract infections

BACKGROUND: Current medical scores have limited efficiency and safety profiles to enable assignment to the most appropriate treatment site in patients with lower respiratory tract infections (LRTIs). We describe our current triage practice and assess the potential of a combination of CURB65 with proadrenomedullin (ProADM) levels for triage decisions. METHODS: Consecutive patients with LRTIs presenting to our emergency department were prospectively followed and retrospectively classified according to CURB65 and ProADM levels (CURB65-A). Low medical risk patients were further subgrouped according to biopsychosocial and functional risks. We compared the proportion of patients virtually allocated to triage sites with actual triage decisions and assessed the added impact of ProADM in a subgroup. RESULTS: Overall, 93% of 146 patients were hospitalised. Among the 138 patients with available CURB65-A, 17.4% had a low medical risk indicating possible treatment in an outpatient or non-acute medical setting; 34.1% had an intermediate medical risk (short-hospitalisation); and 48.6% had a high medical risk (hospitalisation). Fewer patients were in a low CURB65-A class (I) than a low CURB65 class (0,1) (17.4% vs. 46.3%, p >0.001). Mean length of hospitalisation was 9.8 days including 3.6 days after reaching medical stability. In 60.3% of patients, hospitalisation was prolonged after medical stability mainly for medical reasons. CONCLUSIONS: Current rates of hospitalisation are high in patients with LRTI and length of stay frequently extended beyond time of medical stabilization. The lower proportion of patients reclassified as low risk by adding ProADM to the CURB65 score might improve confidence in the triage algorithm

Development of an Acute and Highly Pathogenic Nonhuman Primate Model of Nipah Virus Infection

Nipah virus (NiV) is an enigmatic emerging pathogen that causes severe and often fatal neurologic and/or respiratory disease in both animals and humans. Amongst people, case fatality rates range between 40 and 75 percent and there are no vaccines or treatments approved for human use. Guinea pigs, hamsters, cats, ferrets, pigs and most recently squirrel monkeys (New World monkey) have been evaluated as animal models of human NiV infection, and with the exception of the ferret, no model recapitulates all aspects of NiV-mediated disease seen in humans. To identify a more viable nonhuman primate (NHP) model, we examined the pathogenesis of NiV in African green monkeys (AGM). Exposure of eight monkeys to NiV produced a severe systemic infection in all eight animals with seven of the animals succumbing to infection. Viral RNA was detected in the plasma of challenged animals and occurred in two of three subjects as a peak between days 7 and 21, providing the first clear demonstration of plasma-associated viremia in NiV experimentally infected animals and suggested a progressive infection that seeded multiple organs simultaneously from the initial site of virus replication. Unlike the cat, hamster and squirrel monkey models of NiV infection, severe respiratory pathology, neurological disease and generalized vasculitis all manifested in NiV-infected AGMs, providing an accurate reflection of what is observed in NiV-infected humans. Our findings demonstrate the first consistent and highly pathogenic NHP model of NiV infection, providing a new and critical platform in the evaluation and licensure of either passive and active immunization or therapeutic strategies for human use