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

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

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

The Trigger System of the H.E.S.S. Telescope Array

H.E.S.S. -- The High Energy Stereoscopic System-- is a new system of large atmospheric Cherenkov telescopes for GeV/TeV Gamma-ray astronomy. This paper describes the trigger system of H.E.S.S. with emphasis on the multi-telescope array level trigger. The system trigger requires the simultaneous detection of air-showers by several telescopes at the hardware level. This requirement allows a suppression of background events which in turn leads to a lower system energy threshold for the detection of Gamma-rays. The implementation of the H.E.S.S. trigger system is presented along with data taken to characterise its performance.Comment: 20 pages, 12 figures, Accepted for publication in Astroparticle Physic

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&

Mediterranean biodiversity gradient initiated by basin restriction

Physical connectivity between marine basins facilitates population exchange and hence controls biodiversity. The Mediterranean Sea is a semi-restricted basin with only a small two-way connection to the global ocean, and it is a region heavily impacted by climate change and biological invasions today. The massive migration of non-indigenous species into the basin through the Suez Canal, driven and enabled by climate warming, is drastically changing Mediterranean biodiversity. Understanding therefore the origin and cause(s) of pre-existing biodiversity patterns is crucial for predicting future impacts of climate change. Mediterranean biodiversity exhibits a west-to-east decreasing gradient in terms of species richness, but the processes that resulted in this gradient have only been hypothesized. By examining the fossil record, we provide evidence that this gradient developed 5.33 million years ago at the end of the Messinian Salinity Crisis, and it was therefore caused by the re-population of the basin by marine species with a dominating western source at the Mediterranean¿Atlantic gateway

Freshening of the Mediterranean Salt Giant: controversies and certainties around the terminal (Upper Gypsum and Lago-Mare) phases of the Messinian Salinity Crisis

The late Miocene evolution of the Mediterranean Basin is characterized by major changes in connectivity, climate and tectonic activity resulting in unprecedented environmental and ecological disruptions. During the Messinian Salinity Crisis (MSC, 5.97-5.33 Ma) this culminated in most scenarios first in the precipitation of gypsum around the Mediterranean margins (Stage 1, 5.97-5.60 Ma) and subsequently &gt; 2 km of halite on the basin floor, which formed the so-called Mediterranean Salt Giant (Stage 2, 5.60-5.55 Ma). The final MSC Stage 3, however, was characterized by a "low-salinity crisis", when a second calcium-sulfate unit (Upper Gypsum; substage 3.1, 5.55-5.42 Ma) showing (bio)geochemical evidence of substantial brine dilution and brackish biota-bearing terrigenous sediments (substage 3.2 or Lago-Mare phase, 5.42-5.33 Ma) deposited in a Mediterranean that received relatively large amounts of riverine and Paratethys-derived low-salinity waters. The transition from hypersaline evaporitic (halite) to brackish facies implies a major change in the Mediterranean’s hydrological regime. However, even after nearly 50 years of research, causes and modalities are poorly understood and the original scientific debate between a largely isolated and (partly) desiccated Mediterranean or a fully connected and filled basin is still vibrant. Here we present a comprehensive overview that brings together (chrono)stratigraphic, sedimentological, paleontological, geochemical and seismic data from all over the Mediterranean. We summarize the paleoenvironmental, paleohydrological and paleoconnectivity scenarios that arose from this cross-disciplinary dataset and we discuss arguments in favour of and against each scenario

IGHV gene mutational status and 17p deletion are independent molecular predictors in a comprehensive clinical-biological prognostic model for overall survival prediction in chronic lymphocytic leukemia

Prognostic index for survival estimation by clinical-demographic variables were previously proposed in chronic lymphocytic leukemia (CLL) patients. Our objective was to test in a large retrospective cohort of CLL patients the prognostic power of biological and clinical-demographic variable in a comprehensive multivariate model. A new prognostic index was proposed