Prognosis of patients with hepatocellular carcinoma. Validation and ranking of established staging-systems in a large western HCC-cohort.

HCC is diagnosed in approximately half a million people per year, worldwide. Staging is a more complex issue than in most other cancer entities and, mainly due to unique geographic characteristics of the disease, no universally accepted staging system exists to date. Focusing on survival rates we analyzed demographic, etiological, clinical, laboratory and tumor characteristics of HCC-patients in our institution and applied the common staging systems. Furthermore we aimed at identifying the most suitable of the current staging systems for predicting survival. Overall, 405 patients with HCC were identified from an electronic medical record database. The following seven staging systems were applied and ranked according to their ability to predict survival by using the Akaike information criterion (AIC) and the concordance-index (c-index): BCLC, CLIP, GETCH, JIS, Okuda, TNM and Child-Pugh. Separately, every single variable of each staging system was tested for prognostic meaning in uni- and multivariate analysis. Alcoholic cirrhosis (44.4%) was the leading etiological factor followed by viral hepatitis C (18.8%). Median survival was 18.1 months (95%-CI: 15.2-22.2). Ascites, bilirubin, alkaline phosphatase, AFP, number of tumor nodes and the BCLC tumor extension remained independent prognostic factors in multivariate analysis. Overall, all of the tested staging systems showed a reasonable discriminatory ability. CLIP (closely followed by JIS) was the top-ranked score in terms of prognostic capability with the best values of the AIC and c-index (AIC 2286, c-index 0.71), surpassing other established staging systems like BCLC (AIC 2343, c-index 0.66). The unidimensional scores TNM (AIC 2342, c-index 0.64) and Child-Pugh (AIC 2369, c-index 0.63) performed in an inferior fashion. Compared with six other staging systems, the CLIP-score was identified as the most suitable staging system for predicting prognosis in a large German cohort of predominantly non-surgical HCC-patients

Stability of general-relativistic accretion disks

Self-gravitating relativistic disks around black holes can form as transient structures in a number of astrophysical scenarios such as binary neutron star and black hole-neutron star coalescences, as well as the core-collapse of massive stars. We explore the stability of such disks against runaway and non-axisymmetric instabilities using three-dimensional hydrodynamics simulations in full general relativity using the THOR code. We model the disk matter using the ideal fluid approximation with a $\Gamma$-law equation of state with $\Gamma=4/3$. We explore three disk models around non-rotating black holes with disk-to-black hole mass ratios of 0.24, 0.17 and 0.11. Due to metric blending in our initial data, all of our initial models contain an initial axisymmetric perturbation which induces radial disk oscillations. Despite these oscillations, our models do not develop the runaway instability during the first several orbital periods. Instead, all of the models develop unstable non-axisymmetric modes on a dynamical timescale. We observe two distinct types of instabilities: the Papaloizou-Pringle and the so-called intermediate type instabilities. The development of the non-axisymmetric mode with azimuthal number m = 1 is accompanied by an outspiraling motion of the black hole, which significantly amplifies the growth rate of the m = 1 mode in some cases. Overall, our simulations show that the properties of the unstable non-axisymmetric modes in our disk models are qualitatively similar to those in Newtonian theory.Comment: 30 pages, 21 figure

Training Schrödinger’s cat: quantum optimal control

It is control that turns scientific knowledge into useful technology: in physics and engineering itprovides a systematic way for driving a dynamical system from a given initial state into a desired targetstate with minimized expenditure of energy and resources. As one of the cornerstones for enabling quantumtechnologies, optimal quantum control keeps evolving and expanding into areas as diverse as quantumenhancedsensing, manipulation of single spins, photons, or atoms, optical spectroscopy, photochemistry,magnetic resonance (spectroscopy as well as medical imaging), quantum information processing and quantumsimulation. In this communication, state-of-the-art quantum control techniques are reviewed and putinto perspective by a consortium of experts in optimal control theory and applications to spectroscopy,imaging, as well as quantum dynamics of closed and open systems. We address key challenges and sketcha roadmap for future developments

High-Dimensional Single-Cell Mapping of Central Nervous System Immune Cells Reveals Distinct Myeloid Subsets in Health, Aging, and Disease

Individual reports suggest that the central nervous system (CNS) contains multiple immune cell types with diverse roles in tissue homeostasis, immune defense, and neurological diseases. It has been challenging to map leukocytes across the entire brain, and in particular in pathology, where phenotypic changes and influx of blood-derived cells prevent a clear distinction between reactive leukocyte populations. Here, we applied high-dimensional single-cell mass and fluorescence cytometry, in parallel with genetic fate mapping systems, to identify, locate, and characterize multiple distinct immune populations within the mammalian CNS. Using this approach, we revealed that microglia, several subsets of border-associated macrophages and dendritic cells coexist in the CNS at steady state and exhibit disease-specific transformations in the immune microenvironment during aging and in models of Alzheimer's disease and multiple sclerosis. Together, these data and the described framework provide a resource for the study of disease mechanisms, potential biomarkers, and therapeutic targets in CNS disease

Exile Vol. XX No. 1

ARTWORK by Sue Sartarelli cover, 24 by Chris Schulze 5, 24, 29 by Heather Richey 6 by Katheryn Riedl 7 by Jane Joldersma 10 by Jan Mosher 12 Pat Victory 15 Rona Rosen 20, 31 Arthur Ernst 21 Kim McMullen 24 FICTION First Time by Bud Foufos 3-4 Father\u27s Last Party by Vic Coccimiglio 11 untitled by Catherine Bader 16-17 God and Sergeant Mays by J. Frank Burkhard 22 Pages of a Story by Peter Porteous 27-31 POETRY The Rest by Ezra Pound (preface) In the Midst of an Echo by Phil Mercurio 4 Sierra Madre Prose by John Purcell 5 untitled by Sue Payne 6 untitled by Cathy Graff 6 untitled by Sharon Singleton 7 Big Al by Phil Mercurio 9-10 untitled by Sharon Singleton 12 Folksinger by Alison Orleans 13 Sweat Rebellion by S. Hunt 13 Blackgrey by Laurie Wharton 14 What is she to you? by Peter Porteous 18 Pojects by Mary Mueller 21 untitled by Dawn Patnode 25 The Barn by Mary Schloss 25 PHOTOGRAPHY by Bruce Andre 1, 18 by Jane Joldersma 4, 23, 26 by Breese Olander 8 by Pam Purcell 8 by Loree Ruman 13, 14 Foster Schmidt 19 Chip Andreae 19, 23 Nancy Pickenson 26 Nancy Chorpenning 32 Many thanks to the advertising agencie -2 Pgs. 25 and 26 are out of order in the published edition and can be found between pages 8 and 9

Transarterial chemoembolization for hepatocellular carcinoma: development and external validation of the Munich-TACE score

Background: Allocation of patients with hepatocellular carcinoma (HCC) to the adequate therapy is determined by both tumor burden and liver function. The Barcelona Clinic Liver Cancer (BCLC) staging system and therapeutic algorithm recommends transarterial chemoembolization (TACE) based on the best evidence available to patients with intermediate-stage HCC (BCLC-B). However, many centers also treat subgroups of patients outside these recommendations and with more advanced disease by TACE. The purpose of this study was to identify prognostic factors in a TACE cohort, including BCLC-B patients, as well as patients treated outside of BCLC-B, to test the prognostic capabilities of published staging systems and to optimize prognostication for TACE patients.Patients and Methods: A cohort of 186 first-line TACE patients was analyzed. Independent prognostic factors were identified and used to construct the Munich-TACE score (M-TACE). M-TACE was tested against established staging systems (including BCLC and two recently published TACE-specific scores) and a ranking using concordance index and Akaike Information Criterion was performed. Finally, an external validation in an independent TACE cohort (n=71) was conducted.Results: Bilirubin, Quick/international normalized ratio, C-reactive protein, creatinine, -feto protein, and tumor extension were identified as independent prognostic factors and used to construct M-TACE. M-TACE identifies three distinct subgroups (P<0.0001) with median survival times of 35.2, 16.9, and 8.6 months, respectively. Compared with established staging systems, M-TACE showed the best prognostic capabilities in both cohorts of patients (cohort 1: c-index, 0.71;Akaike Information Criterion: 1276;cohort 2: c-index, 0.754).Conclusion: We identified independent risk factors for patients treated with TACE. The newly constructed M-TACE score is superior to established staging systems and might prove helpful to identify patients who are most suitable for TACE

Old World megadroughts and pluvials during the Common Era

Climate model projections suggest widespread drying in the Mediterranean Basin and wetting in Fennoscandia in the coming decades largely as a consequence of greenhouse gas forcing of climate. To place these and other “Old World” climate projections into historical perspective based on more complete estimates of natural hydroclimatic variability, we have developed the “Old World Drought Atlas” (OWDA), a set of year-to-year maps of tree-ring reconstructed summer wetness and dryness over Europe and the Mediterranean Basin during the Common Era. The OWDA matches historical accounts of severe drought and wetness with a spatial completeness not previously available. In addition, megadroughts reconstructed over north-central Europe in the 11th and mid-15th centuries reinforce other evidence from North America and Asia that droughts were more severe, extensive, and prolonged over Northern Hemisphere land areas before the 20th century, with an inadequate understanding of their causes. The OWDA provides new data to determine the causes of Old World drought and wetness and attribute past climate variability to forced and/or internal variability

Skeletal Diversification via Heteroatom Linkage Control: Preparation of Bicyclic and Spirocyclic Scaffolds from NSubstituted Homopropargyl Alcohols

The discovery and application of a new branching pathway synthesis strategy that rapidly produces skeletally diverse scaffolds is described. Two different scaffold types, one a bicyclic iodo-vinylidene tertiary amine/tertiary alcohol and the other, a spirocyclic 3-furanone, are each obtained using a two-step sequence featuring a common first step. Both scaffold types lead to intermediates that can be orthogonally diversified using the same final components. One of the scaffold types was obtained in sufficiently high yield that it was immediately used to produce a 97-compound library

Blood glucose testing and primary prevention of diabetes mellitus type 2 - evaluation of the effect of evidence based patient information

<p>Abstract</p> <p>Background</p> <p>Evidence-based patient information (EBPI) has been recognised as important tool for informed choice in particular in the matter of preventive options. An objective, on the best scientific evidence-based consumer information about subthreshold elevated blood glucose levels (impaired fasting glucose and impaired glucose tolerance) and primary prevention of diabetes, is not available yet. Thus we developed a web-based EBPI and aim to evaluate its effects on informed decision making in people 50 years or older.</p> <p>Methods/Design</p> <p>We conduct a web-based randomised-controlled trial to evaluate the effect of information about elevated blood glucose levels and diabetes primary prevention on five specific outcomes: (i) knowledge of elevated blood glucose level-related issues (primary outcome); (ii) attitudes to a metabolic testing; (iii) intention to undergo a metabolic testing; (iv) decision conflict; (v) satisfaction with the information. The intervention group receives a specially developed EBPI about subthreshold elevated blood glucose levels and diabetes primary prevention, the control group information about this topic, available in the internet.</p> <p>The study population consists of people between 50 and 69 years of age without known diabetes. Participants will be recruited via the internet page of the cooperating health insurance company, Techniker Krankenkasse (TK), and the internet page of the German Diabetes Centre. Outcomes will be measured through online questionnaires. We expect better informed participants in the intervention group.</p> <p>Discussion</p> <p>The design of this study may be a prototype for other web-based prevention information and their evaluation.</p> <p>Trial registration</p> <p>Current Controlled Trial: ISRCTN22060616.</p