We assessed the effect of different hepatic conditions such as fibrosis, steatosis and necroinflammatory activity on liver stiffness as measured by transient elastography in HIV/HCV‐coinfected ...patients. We studied all consecutive HIV/HCV‐coinfected patients who underwent liver biopsy and elastography between January 2007 and December 2008. Liver fibrosis was staged following METAVIR Cooperative Study Group criteria. Steatosis was categorized according to the percentage of affected hepatocytes as low (≤10%), moderate (<25%) and severe (≥25%). A total of 110 patients were included. Fibrosis was distributed by stage as follows: F0, n = 13; F1, n = 47; F2, n = 29; F3, n = 18; and F4, n = 3. Liver biopsy revealed the presence of hepatic steatosis in 68 patients (low to moderate, n = 53; and severe n = 15). By univariate regression analysis, fibrosis, necroinflammatory activity, and the degree of steatosis were correlated with liver stiffness. However, in a multiple regression analysis, steatosis and fibrosis were the only independent variables significantly associated with liver stiffness. With a cut‐off of 9.5 kPa to distinguish patients with F ≤ 2 from F ≥ 3, elastography led to a significantly higher number of misclassification errors (25%vs 5%; P = 0.014), most of which were false positives for F ≥ 3. Our study suggests that the correlation between liver stiffness and fibrosis as estimated by transient elastography may be affected by the presence of hepatic steatosis in HIV/HCV‐coinfected patients.
Abstract Background Epidemiological surveys have revealed outbreaks of pandemic influenza A (H1N1) 2009 in several different contexts. Molecular characterization of the influenza virus could help to ...provide a more accurate description of these outbreaks. Objective To genotype pandemic influenza A (H1N1) 2009 isolates from an epidemiologically defined nosocomial outbreak. Study design We sequenced the neuraminidase (NA) and hemagglutinin (HA) influenza A (H1N1) 2009 genes from ten HIV-positive patients involved in an epidemiologically defined outbreak in the Clinical Microbiology and Infectious Diseases (CMID) Department. Sequences were aligned to search for specific genetic features of the involved strain. We also analyzed 37 unrelated influenza A (H1N1) 2009 cases from other hospital departments. All the sequences were used to obtain phylogenetic trees. Results Identical genotypic features were shared by nine of the 10 cases initially considered to be involved in the outbreak, but not by the remaining case. These features involved two silent mutations at N385 and V407 in the NA gene and three amino acid substitutions in the HA gene (D225E, A189T, and P300S). Searching for these substitutions in patients with influenza A (H1N1) 2009 hospitalized in other departments during the same period allowed us to identify an additional unsuspected immunocompetent case. The five outbreak-specific substitutions were absent in the remaining 36 unrelated controls. One of the substitutions (P300S) rendered detection of this variant by the CDC protocol inefficient. The other outbreak-specific substitutions (D225E and A189T) were identified at codons that have been analyzed in the context of virulence. Conclusions Genotyping is essential to ensure a more accurate description of pandemic influenza A (H1N1) 2009 outbreaks.
We study the density profiles of collapsed galaxy-size dark matter halos with masses 10 super(11) to 5 x 10 super(12) M sub( )focusing mostly on the halo outer regions from the formal virial radius R ...sub(vir) up to 5R sub(vir)-7R sub(vir). We find that isolated halos in this mass range extend well beyond R sub(vir) exhibiting all properties of virialized objects up to 2R sub(vir)-3R sub(vir): relatively smooth density profiles and no systematic infall velocities. The dark matter halos in this mass range do not grow as one naively may expect through a steady accretion of satellites; i.e., on average there is no mass infall. This is strikingly different from more massive halos, which have large infall velocities outside the virial radius. We provide an accurate fit for the density profile of these isolated galaxy-size halos. For a wide range 0.01 R sub(vir)-2R sub(vir) of radii the halo density profiles are fitted with the approximation P = P sub(s) exp -2n (x super(1/n) - 1) + < P sub(m) >, where x = r/r sub(s),< P sub(m) > is the mean matter density of the universe, and the index n is in the range n = 6-7.5. These profiles do not show a sudden change of behavior beyond the virial radius. For larger radii we combine the statistics of the initial fluctuations with the spherical collapse model to obtain predictions for the mean and most probable density profiles for halos of several masses. The model gives excellent results beyond 2-3 formal virial radii for the most probable profile and qualitatively correct predictions for the mean profile.
We constructed noninvasive models to predict significant fibrosis (F ≥ 2) and advanced fibrosis (F ≥ 3) among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)‐coinfected patients, naïve for ...anti‐HCV treatment. A total of 296 patients with liver biopsy were randomly assigned to an estimation group (EG = 226; 70%) and a validation group (VG = 70; 30%). We developed the Hospital Gregorio Marañón (HGM)‐1 index, based on platelet count, aspartate aminotransferase (AST) and glucose, to predict F ≥ 2 and the HGM‐2 index, based on platelet count, international normalized ratio, alkaline phosphatase and AST to predict F ≥ 3. The area under the receiver operating characteristic curves (AUROCs) of the HGM‐1 index for the EG and the VG were 0.807 and 0.712 respectively. The AUROCs of the HGM‐2 index for the EG and the VG were 0.844 and 0.815 respectively. With the HGM‐1 index applied to the VG, using best cutoff scores, the negative predictive value (NPV) to exclude F ≥ 2 was 54.5% and the positive predictive value (PPV) to confirm F ≥ 2 was 93.3%. With the HGM‐2 index applied to the VG, using best cutoff scores, the NPV to exclude F ≥ 3 was 92.3, and the PPV to confirm F ≥ 3 was 64.3%. Thus, HGM‐2 accurately predicted F ≥ 3 among HIV/HCV‐coinfected patients. HGM‐1 was less accurate at predicting F ≥ 2.
A new colorimetric method based on the bleaching of the iodoplatinate ion has been developed for fast and easy determination of γ-glutamyl-
S-ethenyl-cysteine (GEC) in narbon vetch (
Vicia ...narbonensis L.) seeds. The calibration curve showed a good correlation (
r
2
=
0.9959) between absorbance and GEC amounts from 5.5 to 33
μg (10–59.78
μmol/L). The limits of detection and quantification were 1.16 and 3.55
μmol/L, respectively, and no significant interferences from other sulfur-containing compounds were observed. The method showed excellent repeatability (relative standard deviation RSD
=
0.28%), reproducibility (RSD
=
4.4%), and accuracy (94%). Determination of GEC in 20 narbon vetch accessions yielded values that were in agreement with those reported previously using capillary electrophoresis and high-performance liquid chromatography methods. The method could be especially valuable for determination of GEC during the process of production of new low-GEC narbon vetch varieties.
Copy number analysis can be useful for assessing prognosis in diffuse large B cell lymphoma (DLBCL). We analyzed copy number data from tumor samples of 60 patients diagnosed with DLBCL de novo and ...their matched normal samples. We detected 63 recurrent copy number alterations (CNAs), including 33 gains, 30 losses, and nine recurrent acquired copy number neutral loss of heterozygosity (CNN-LOH). Interestingly, 20 % of cases acquired CNN-LOH of 6p21 locus, which involves the HLA region. In normal cells, there were no CNAs but we observed CNN-LOH involving some key lymphoma regions such as 6p21 and 9p24.1 (5 %) and 17p13.1 (2.5 %) in DLBCL patients. Furthermore, a model with some specific CNA was able to predict the subtype of DLBCL, 1p36.32 and 10q23.31 losses being restricted to germinal center B cell-like (GCB) DLBCL. In contrast, 8p23.3 losses and 11q24.3 gains were strongly associated with the non-GCB subtype. A poor prognosis was associated with biallelic inactivation of
TP53
or 18p11.32 losses, while prognosis was better in cases carrying 11q24.3 gains. In summary, CNA abnormalities identify specific DLBCL groups, and we describe CNN-LOH in germline cells from DLBCL patients that are associated with genes that probably play a key role in DLBCL development.
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•Crystallization of methane hydrate confined in a silica pore is described using MD.•Hydrate crystallizes occupying all the accessible volume, but presents many defects.•As in the ...case of ice, an interfacial liquid layer is observed between the hydrate and the confining silica walls.
The growth of a methane hydrate seed within a silica slit pore of fixed width has been studied using All-Atom Molecular Dynamics (AA-MD). An AA force field has been used to describe the molecules of the solid silica substrate, with α-quartz crystalline structure. The crystallisation of hydrates in confined geometries is not well understood yet, and the objective of this work is to study the hydrate growth inside a silica pore using molecular simulation. Both NVT and NpT ensembles were used in the AA-MD simulations to analyse the hydrate growth from an initial seed. Results showed that the boundary conditions imposed by the nanometric slit pore yielded a hydrate with structural defects, filling the accessible space between the silica walls. The water molecules which were not incorporated to the initial seed hydrate formed a high density water layer trapped between the silica walls and the crystallised hydrate. These results provide an interesting insight into the hydrate crystallisation process in confined geometries, resembling those found in natural hydrate deposits.
We present all-sky simulated Fermi maps of Delta *g-rays from dark matter (DM) decay and annihilation in the local universe. The DM distribution is obtained from a constrained cosmological simulation ...of the neighboring large-scale structure provided by the CLUES project. The DM fields of density and density squared are then taken as an input for the Fermi observation simulation tool to predict the Delta *g-ray photon counts that Fermi would detect in 5 years of an all-sky survey for given DM models. Signal-to-noise ratio (S/N) sky maps have also been obtained by adopting the current Galactic and isotropic diffuse background models released by the Fermi Collaboration. We point out the possibility for Fermi to detect a DM Delta *g-ray signal in local extragalactic structures. In particular, we conclude here that Fermi observations of nearby clusters (e.g., Virgo and Coma) and filaments are expected to give stronger constraints on decaying DM compared to previous studies. As an example, we find a significant S/N in DM models with a decay rate fitting the positron excess as measured by PAMELA. This is the first time that DM filaments are shown to be promising targets for indirect detection of DM. On the other hand, the prospects for detectability of annihilating DM in local extragalactic structures are less optimistic even with extreme cross-sections. We make the DM density and density squared maps publicly available online.
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