Liver surgery in cirrhosis and portal hypertension

The prevalence of hepatic cirrhosis in Europe and the United States, currently 250 patients per 100000 inhabitants, is steadily increasing. Thus, we observe a significant increase in patients with cirrhosis and portal hypertension needing liver resections for primary or metastatic lesions. However, extended liver resections in patients with underlying hepatic cirrhosis and portal hypertension still represent a medical challenge in regard to perioperative morbidity, surgical management and postoperative outcome. The Barcelona Clinic Liver Cancer classification recommends to restrict curative liver resections for hepatocellular carcinoma in cirrhotic patients to early tumor stages in patients with Child A cirrhosis not showing portal hypertension. However, during the last two decades, relevant improvements in preoperative diagnostic, perioperative hepatologic and intensive care management as well as in surgical techniques during hepatic resections have rendered even extended liver resections in higher-degree cirrhotic patients with portal hypertension possible. However, there are few standard indications for hepatic resections in cirrhotic patients and risk stratifications have to be performed in an interdisciplinary setting for each individual patient. We here review the indications, the preoperative risk-stratifications, the morbidity and the mortality of extended resections for primary and metastatic lesions in cirrhotic livers. Furthermore, we provide a review of literature on perioperative management in cirrhotic patients needing extrahepatic abdominal surgery and an overview of surgical options in the treatment of hepatic cirrhosis

Chronic viral infection promotes sustained Th1-derived immunoregulatory IL-10 via BLIMP-1

During the course of many chronic viral infections, the antiviral T cell response becomes attenuated through a process that is regulated in part by the host. While elevated expression of the immunosuppressive cytokine IL-10 is involved in the suppression of viral-specific T cell responses, the relevant cellular sources of IL-10, as well as the pathways responsible for IL-10 induction, remain unclear. In this study, we traced IL-10 production over the course of chronic lymphocytic choriomeningitis virus (LCMV) infection in an IL-10 reporter mouse line. Using this model, we demonstrated that virus-specific T cells with reduced inflammatory function, particularly Th1 cells, display elevated and sustained IL-10 expression during chronic LCMV infection. Furthermore, ablation of IL-10 from the T cell compartment partially restored T cell function and reduced viral loads in LCMV-infected animals. We found that viral persistence is needed for sustained IL-10 production by Th1 cells and that the transcription factor BLIMP-1 is required for IL-10 expression by Th1 cells. Restimulation of Th1 cells from LCMV-infected mice promoted BLIMP-1 and subsequent IL-10 expression, suggesting that constant antigen exposure likely induces the BLIMP-1/IL-10 pathway during chronic viral infection. Together, these data indicate that effector T cells self-limit their responsiveness during persistent viral infection via an IL-10-dependent negative feedback loop.This work was supported by an Australian NHMRC Overseas Biomedical Postdoctoral Fellowship (to I.A. Parish); a Yale School of Medicine Brown-Coxe Postdoctoral Fellowship (to I.A. Parish); the Alexander von Humboldt Foundation (SKA2010, to P.A. Lang); a CIHR grant (to P.S. Ohashi); and by the Howard Hughes Medical Institute and NIH grant RO1AI074699 (to S.M. Kaech). P.S. Ohashi holds a Canada Research Chair in Autoimmunity and Tumor immunity

HST/NICMOS Paschen-alpha Survey of the Galactic Center: Overview

We have recently carried out the first wide-field hydrogen Paschen-alpha line imaging survey of the Galactic Center (GC), using the NICMOS instrument aboard the Hubble Space Telescope. The survey maps out a region of 2253 pc^2 around the central supermassive black hole (Sgr A*) in the 1.87 and 1.90 Micron narrow bands with a spatial resolution of 0.01 pc at a distance of 8 kpc. Here we present an overview of the observations, data reduction, preliminary results, and potential scientific implications, as well as a description of the rationale and design of the survey. We have produced mosaic maps of the Paschen-alpha line and continuum emission, giving an unprecedentedly high resolution and high sensitivity panoramic view of stars and photo-ionized gas in the nuclear environment of the Galaxy. We detect a significant number of previously undetected stars with Paschen-alpha in emission. They are most likely massive stars with strong winds, as confirmed by our initial follow-up spectroscopic observations. About half of the newly detected massive stars are found outside the known clusters (Arches, Quintuplet, and Central). Many previously known diffuse thermal features are now resolved into arrays of intriguingly fine linear filaments indicating a profound role of magnetic fields in sculpting the gas. The bright spiral-like Paschen-alpha emission around Sgr A* is seen to be well confined within the known dusty torus. In the directions roughly perpendicular to it, we further detect faint, diffuse Paschen-alpha emission features, which, like earlier radio images, suggest an outflow from the structure. In addition, we detect various compact Paschen-alpha nebulae, probably tracing the accretion and/or ejection of stars at various evolutionary stages.Comment: accepted for publication in MNRAS; a version of higher resolution images may be found at http://www.astro.umass.edu/~wqd/papers/hst/paper1.pd

The role of ADAM17 during liver damage

Abstract A disintegrin and metalloprotease (ADAM) 17 is a membrane bound protease, involved in the cleavage and thus regulation of various membrane proteins, which are critical during liver injury. Among ADAM17 substrates are tumor necrosis factor α (TNFα), tumor necrosis factor receptor 1 and 2 (TNFR1, TNFR2), the epidermal growth factor receptor (EGFR) ligands amphiregulin (AR) and heparin-binding-EGF-like growth factor (HB-EGF), the interleukin-6 receptor (IL-6R) and the receptor for a hepatocyte growth factor (HGF), c-Met. TNFα and its binding receptors can promote liver injury by inducing apoptosis and necroptosis in liver cells. Consistently, hepatocyte specific deletion of ADAM17 resulted in increased liver cell damage following CD95 stimulation. IL-6 trans-signaling is critical for liver regeneration and can alleviate liver damage. EGFR ligands can prevent liver damage and deletion of amphiregulin and HB-EGF can result in increased hepatocyte death and reduced proliferation. All of which indicates that ADAM17 has a central role in liver injury and recovery from it. Furthermore, inactive rhomboid proteins (iRhom) are involved in the trafficking and maturation of ADAM17 and have been linked to liver damage. Taken together, ADAM17 can contribute in a complex way to liver damage and injury

Science Models as Value-Added Services for Scholarly Information Systems

The paper introduces scholarly Information Retrieval (IR) as a further dimension that should be considered in the science modeling debate. The IR use case is seen as a validation model of the adequacy of science models in representing and predicting structure and dynamics in science. Particular conceptualizations of scholarly activity and structures in science are used as value-added search services to improve retrieval quality: a co-word model depicting the cognitive structure of a field (used for query expansion), the Bradford law of information concentration, and a model of co-authorship networks (both used for re-ranking search results). An evaluation of the retrieval quality when science model driven services are used turned out that the models proposed actually provide beneficial effects to retrieval quality. From an IR perspective, the models studied are therefore verified as expressive conceptualizations of central phenomena in science. Thus, it could be shown that the IR perspective can significantly contribute to a better understanding of scholarly structures and activities.Comment: 26 pages, to appear in Scientometric

PHANGS CO kinematics: disk orientations and rotation curves at 150 pc resolution

We present kinematic orientations and high resolution (150 pc) rotation curves for 67 main sequence star-forming galaxies surveyed in CO (2-1) emission by PHANGS-ALMA. Our measurements are based on the application of a new fitting method tailored to CO velocity fields. Our approach identifies an optimal global orientation as a way to reduce the impact of non-axisymmetric (bar and spiral) features and the uneven spatial sampling characteristic of CO emission in the inner regions of nearby galaxies. The method performs especially well when applied to the large number of independent lines-of-sight contained in the PHANGS CO velocity fields mapped at 1'' resolution. The high resolution rotation curves fitted to these data are sensitive probes of mass distribution in the inner regions of these galaxies. We use the inner slope as well as the amplitude of our fitted rotation curves to demonstrate that CO is a reliable global dynamical mass tracer. From the consistency between photometric orientations from the literature and kinematic orientations determined with our method, we infer that the shapes of stellar disks in the mass range of log($\rm M_{\star}(M_{\odot})$)=9.0-10.9 probed by our sample are very close to circular and have uniform thickness.Comment: 19 figures, 36 pages, accepted for publication in ApJ. Table of PHANGS rotation curves available from http://phangs.org/dat

Properties of dust in the Galactic center region probed by AKARI far-infrared spectral mapping - detection of a dust feature

We investigate the properties of interstellar dust in the Galactic center region toward the Arches and Quintuplet clusters. With the Fourier Transform Spectrometer of the AKARI/Far-Infrared Surveyor, we performed the far-infrared (60 - 140 cm^-1) spectral mapping of an area of about 10' x 10' which includes the two clusters to obtain a low-resolution (R = 1.2 cm^-1) spectrum at every spatial bin of 30" x 30". We derive the spatial variations of dust continuum emission at different wavenumbers, which are compared with those of the [O III] 88 micron (113 cm^-1) emission and the OH 119 micron (84 cm^-1) absorption. The spectral fitting shows that two dust modified blackbody components with temperatures of ~20 K and ~50 K can reproduce most of the continuum spectra. For some spectra, however, we find that there exists a significant excess on top of a modified blackbody continuum around 80 - 90 cm^-1 (110 - 130 microns). The warmer dust component is spatially correlated well with the [O III] emission and hence likely to be associated with the highly-ionized gas locally heated by intense radiation from the two clusters. The excess emission probably represents a dust feature, which is found to be spatially correlated with the OH absorption and a CO cloud. We find that a dust model including micron-sized graphite grains can reproduce the observed spectrum with the dust feature fairly well.Comment: 10 pages, 8 figures, accepted for publication in A&

Tumor Necrosis Factor-mediated survival of CD169⁺ cells promotes immune activation during vesicular stomatitis virus infection

Innate immune activation is essential to mount an effective antiviral response and to prime adaptive immunity. Although a crucial role of CD169+ cells during vesicular stomatitis virus (VSV) infections is increasingly recognized, factors regulating CD169+ cells during viral infections remain unclear. Here, we show that tumor necrosis factor is produced by CD11b+ Ly6C+ Ly6G+ cells following infection with VSV. The absence of TNF or TNF receptor 1 (TNFR1) resulted in reduced numbers of CD169+ cells and in reduced type I interferon (IFN-I) production during VSV infection, with a severe disease outcome. Specifically, TNF triggered RelA translocation into the nuclei of CD169+ cells; this translocation was inhibited when the paracaspase MALT-1 was absent. Consequently, MALT1 deficiency resulted in reduced VSV replication, defective innate immune activation, and development of severe disease. These findings indicate that TNF mediates the maintenance of CD169+ cells and innate and adaptive immune activation during VSV infection

A3COSMOS: the dust attenuation of star-forming galaxies at z=2.5-4.0 from the COSMOS-ALMA archive

We present an analysis of the dust attenuation of star-forming galaxies at z = 2.5-4.0 through the relationship between the UV spectral slope (β), stellar mass (M*), and the infrared excess (IRX = LIR/LUV) based on far-infrared continuum observations from the Atacama Large Millimeter/sub-millimeter Array (ALMA). Our study exploits the full ALMA archive over the COSMOS field processed by the A3COSMOS team, which includes an unprecedented sample of ∼1500 galaxies at z ∼ 3 as primary or secondary targets in ALMA band 6 or 7 observations with a median continuum sensitivity of 126 μJybeam−1 (1σ). The detection rate is highly mass dependent, decreasing drastically below log (M*/M⊙) = 10.5. The detected galaxies show that the IRX-β relationship of massive (log M*/M⊙ > 10) main-sequence galaxies at z = 2.5-4.0 is consistent with that of local galaxies, while starbursts are generally offset by ∼0.5dex to larger IRX values. At the low-mass end, we derive upper limits on the infrared luminosities through stacking of the ALMA data. The combined IRX-M* relation at log(M∗/M⊙)>9 exhibits a significantly steeper slope than reported in previous studies at similar redshifts, implying little dust obscuration at log M*/M⊙ < 10. However, our results are consistent with earlier measurements at z ∼ 5.5, indicating a potential redshift evolution between z ∼ 2 and z ∼ 6. Deeper observations targeting low-mass galaxies will be required to confirm this finding.PL, DL, and ES acknowledge funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 694343). SL acknowledge funding from SCHI 536/9-1. EFJA acknowledge support of the Collaborative Research Center 956, subproject A1, funded by the Deutsche Forschungsgemeinschaft (DFG)