Hepatitis C virus and non-Hodgkin's lymphomas: Meta-analysis of epidemiology data and therapy options.

Hepatitis C virus (HCV) is a global health problem affecting a large fraction of the world\u2019s population: This virus is able to determine both hepatic and extrahepatic diseases. Mixed cryoglobulinemia, a B-cell \u201cbenign\u201d lymphoproliferative disorders, represents the most closely related as well as the most investigated HCV-related extrahepatic disorder. Since this virus is able to determine extrahepatic [non-Hodgkin\u2019s lymphoma (NHL)] as well as hepatic malignancies (hepatocellular carcinoma), HCV has been included among human cancer viruses. The most common histological types of HCV-associated NHL are the marginal zone, the lymphoplasmacytic and diffuse large cell lymphomas. The role of the HCV in the pathogenesis of the B-cell lymphoproliferative disorders is confirmed also by the responsiveness of the NHL to antiviral therapy. The purpose of this review is to provide an overview of the recent literature and a meta analysis of the epidemiology data, to explain the role of HCV in the development of NHL\u2019s lymphoma. Furthermore, the possibility to treat these HCV-related NHL with the antiviral therapy or with other therapeutic options, like chemotherapy, is also discussed

Fixed-Parameter Tractable Distances to Sparse Graph Classes

We show that for various classes $\mathcal{C}$ of sparse graphs, and several measures of distance to such classes (such as edit distance and elimination distance), the problem of determining the distance of a given graph $\small{G}$ to $\mathcal{C}$ is fixed-parameter tractable. The results are based on two general techniques. The first of these, building on recent work of Grohe et al. establishes that any class of graphs that is slicewise nowhere dense and slicewise first-order definable is FPT. The second shows that determining the elimination distance of a graph $\small{G}$ to a minor-closed class $\mathcal{C}$ is FPT. We demonstrate that several prior results (of Golovach, Moser and Thilikos and Mathieson) on the fixed-parameter tractability of distance measures are special cases of our first method

CD49d Is the strongest flow cytometry–based predictor of overall survival in chronic lymphocytic leukemia

Purpose Although CD49d is an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL), definitive validation evidence is lacking. A worldwide multicenter analysis was performed using published and unpublished CLL series to evaluate the impact of CD49d as an overall (OS) and treatment-free survival (TFS) predictor. Patients and Methods A training/validation strategy was chosen to find the optimal CD49d cutoff. The hazard ratio (HR) for death and treatment imposed by CD49d was estimated by pooled analysis of 2,972 CLLs; Cox analysis stratified by center and stage was used to adjust for confounding variables. The importance of CD49d over other flow cytometry–based prognosticators (eg, CD38, ZAP-70) was ranked by recursive partitioning. Results Patients with ≥ 30% of neoplastic cells expressing CD49d were considered CD49d+. Decrease in OS at 5 and 10 years among CD49d+ patients was 7% and 23% (decrease in TFS, 26% and 25%, respectively). Pooled HR of CD49d for OS was 2.5 (2.3 for TFS) in univariate analysis. This HR remained significant and of similar magnitude (HR, 2.0) in a Cox model adjusted for clinical and biologic prognosticators. Hierarchic trees including all patients or restricted to those with early-stage disease or those age ≤ 65 years always selected CD49d as the most important flow cytometry–based biomarker, with negligible additional prognostic information added by CD38 or ZAP-70. Consistently, by bivariate analysis, CD49d reliably identified patient subsets with poorer outcome independent of CD38 and ZAP-70. Conclusion In this analysis of approximately 3,000 patients, CD49d emerged as the strongest flow cytometry–based predictor of OS and TFS in CLL

A search for TeV gamma-ray emission from SNRs, pulsars and unidentified GeV sources in the Galactic plane in the longitude range between -2 deg and 85 deg

Using the HEGRA system of imaging atmospheric Cherenkov telescopes, one quarter of the Galactic plane (-2 deg < l < 85 deg) was surveyed for TeV gamma-ray emission from point sources and moderately extended sources (diameter <= 0.8 deg). The region covered includes 86 known pulsars (PSR), 63 known supernova remnants (SNR) and nine GeV sources, representing a significant fraction of the known populations. No evidence for emission of TeV gamma radiation was detected, and upper limits range from 0.15 Crab units up to several Crab units, depending on the observation time and zenith angles covered. The ensemble sums over selected SNR and pulsar subsamples and over the GeV-sources yield no indication for emission from these potential sources. The upper limit for the SNR population is at the level of 6.7% of the Crab flux and for the pulsar ensemble at the level of 3.6% of the Crab flux.Comment: 10 pages, 5 figures, 4 tables, accepted for publication in A&

The technical performance of the HEGRA system of imaging air Cherenkov telescopes

Between early 1997 and late 2002, the HEGRA collaboration operated a stereoscopic system of 4 (later 5) imaging atmospheric Cherenkov telescopes. In this paper we present the calibration schemes which were developed for the system, and report on the performance of the detector over the years. In general, the telescope system was very well understood, regarding both the absolute calibration and the slight changes in performance over the years. The system had an energy threshold of 500 GeV for observations at zenith and under optimum detector conditions. With the corresponding calibration schemes, a systematic accuracy of 15 percent on the absolute energy scale has been achieved. The continuous sensitivity monitoring provided a relative accuracy of a few percent, and showed that the threshold did not exceed 600 GeV throughout the entire operation time. The readout electronics and the imaging quality of the dishes were well monitored and stable. The absolute pointing had an accuracy of at least 25 arcsec; this number was guaranteed throughout the whole lifetime of the experiment.G. Puhlhofer ... G. P. Rowell.. and W. Wittek...et al., the HEGRA Collaboratio

Tumour-infiltrating lymphocytes bear the 75 kDa tumour necrosis factor receptor.

Tumour necrosis factor alpha (TNF-alpha) is a cytokine with a variety of immunological properties. The identification of two receptors for this molecule, i.e. the 75 kDa and the 55 kDa TNF receptors (TNF-R), recently clarified the mechanisms through which this cytokine provides its wide range of immunomodulatory activities. In this study we have investigated the expression and the functional properties of these receptors on tumour-infiltrating lymphocytes (TILs) recovered from 17 patients with solid cancers (melanoma, colorectal carcinoma and lung cancer). To this end, TIL lines and freshly isolated TILs were evaluated for (a) the expression and the functional role of TNF receptors following culture in the presence of interleukin 2 (IL-2) and (b) the production of TNF-alpha following culture with IL-2 and the role of this cytokine in IL-2-driven TIL proliferation. Flow cytometry analysis demonstrated that TILs bear the 75 kDa TNF-R. Moreover, TIL lines express detectable messages for TNF-alpha and release this cytokine. Functional in vitro studies have shown that anti-TNF-alpha, as well as anti-75 kDa TNF-R antibodies, are able to inhibit the IL-2-induced TIL proliferation. These data demonstrate that TILs are equipped with a fully functional TNF-R system and suggest a putative role for this receptor and its ligand in the activation and expression of TILs following immunotherapy with IL-2

The MIS 5 marine terraces on the Tyrrhenian Sea coast of central Italy between Civitavecchia and the Fiora River

We reconstruct the marine terraces of the Marine Isotope Stage (MIS) 5 and the landscape evolution of the Tyrrhenian Sea coastal area between the Fiora River and Civitavecchia (central Italy), based on extensive fieldwork, biostratigraphical, palaeoecological, and geomorphological analyses, and 40Ar/39Ar dating. Our geomorphological mapping approach uses object-based image analysis, guided by field observations, to identify and map marine terraces using metrics calculated from a LiDAR-based digital terrain model. A suite of three marine terraces at elevations around 40 m, 20 m, and 6 m a.s.l. is recognized through this combined approach in the southwestern sector of the investigated area between Civitavecchia and Marina Velca. Geochronologic constraints based on 40Ar/39Ar dating of detrital sanidine extracted from the sedimentary deposits set a terminus post quem for the marine terraces, suggesting their correlation with MIS 5e, MIS 5c and MIS 5a.We have reconstructed an extensive paleosurface in this portion of the coastal area, marked by a CaCO3-rich, cemented, Thetystrombus latus-bearing biodetrital conglomerate that gently dips seaward from ca. 20 m to the present sea level and represents a range of environments from coastal to shelf. Despite the occurrence of the mollusc species considered distinctive for the MIS 5e highstand, combined geochronologic constraints and paleoecological reconstructions support its attribution to MIS 5c. The lowest terrace forms a narrow strip along the coastline and comprises near shore deposits, including a second, distinct biodetrital platform, at 2–3 m a.s.l. which, assuming a staircase geometry for the suite of terraces, is correlated with MIS 5a. Such geomorphological setting coincides with that reconstructed in the adjacent coastal sector between Civitavecchia and the Tiber delta, pointing at a significant late Quaternary regional uplift.</p