13 research outputs found

    Age independent survival benefit for patients with hepatocellular carcinoma (HCC) without metastases at diagnosis: a population-based study

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    OBJECTIVE Hepatocellular carcinoma (HCC) is a major cause of death worldwide and its incidence is expected to increase globally. Aim of this study was to assess whether the implementation of screening policies and the improvement of treatment options translated into a real-world survival benefit in HCC patients. DESIGN 4078 patients diagnosed with HCC between 1998 and 2016 from the Munich Cancer Registry were analysed. Tumour characteristics and outcome were analysed by time period and according to age and presence of metastases at diagnosis. Overall survival (OS) was analysed using Kaplan-Meier method and relative survival (RS) was computed for cancer-specific survival. Cox proportional hazard models were conducted to control for prognostic variables. RESULTS While incidence of HCC remained substantially stable, tumours were diagnosed at increasingly earlier stages, although the median age at diagnosis increased. The 3 years RS in HCC improved from 19.8% in 1998-2002, 22.4% in 2003-2007, 30.6% in 2008-2012 up to 31.0% in 2013-2016. Median OS increased from 6 months in 1998-2002 to 12 months in 2008-2016. However, analysis according to the metastatic status showed that survival improved only in patients without metastases at diagnosis whereas the prognosis of patients with metastatic disease remained unchanged. CONCLUSION These real-world data show that, in contrast to the current assumptions, the incidence of HCC did not increase in a representative German region. Earlier diagnosis, likely related to the implementation of screening programmes, translated into an increasing employment of effective therapeutic options and a clear survival benefit in patients without metastases at diagnosis, irrespective of age

    A Combined Perceptual, Physico-Chemical, and Imaging Approach to ‘Odour-Distances’ Suggests a Categorizing Function of the Drosophila Antennal Lobe

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    How do physico-chemical stimulus features, perception, and physiology relate? Given the multi-layered and parallel architecture of brains, the question specifically is where physiological activity patterns correspond to stimulus features and/or perception. Perceived distances between six odour pairs are defined behaviourally from four independent odour recognition tasks. We find that, in register with the physico-chemical distances of these odours, perceived distances for 3-octanol and n-amylacetate are consistently smallest in all four tasks, while the other five odour pairs are about equally distinct. Optical imaging in the antennal lobe, using a calcium sensor transgenically expressed in only first-order sensory or only second-order olfactory projection neurons, reveals that 3-octanol and n-amylacetate are distinctly represented in sensory neurons, but appear merged in projection neurons. These results may suggest that within-antennal lobe processing funnels sensory signals into behaviourally meaningful categories, in register with the physico-chemical relatedness of the odours

    MIDAS - Maßnahmen und Instrumente des aktiven Schallschutzes beim FluglĂ€rm - wissenschaftlicher Abschlussbericht

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    Im DLR-Projekt MIDAS wurden im Rahmen einer Feldstudie am Flughafen Köln/Bonn die Akutwirkungen von NachtfluglĂ€rm auf den Schlaf sowie die daraus resultierenden psychologischen SekundĂ€rwirkungen bei N=51 Kindern (8-10 Jahre) erforscht. Jedes Kind wurde zu Hause in seinem gewohnten Umfeld in vier aufeinanderfolgenden NĂ€chten untersucht. In allen MessnĂ€chten wurden wĂ€hrend der gesamten Bettliegezeit der Schalldruckpegel und die GerĂ€uschdateien kontinuierlich am Ohr der schlafenden Kinder gemessen. Damit konnte die reale FluglĂ€rmbelastung abgebildet und zu den resultierenden akuten LĂ€rmwirkungen in Beziehung gesetzt werden. Gleichzeitig wurden in Bezug auf die Messung des Schlafs Effekte durch eine ungewohnte Umgebung (wie etwa in einem Schlaflabor) ausgeschlossen. FĂŒr Anflugverfahren wurde untersucht, wie die LĂ€rmbelastung durch horizontale Optimierung minimiert werden kann. Diese Minimierung beruht darauf, den FluglĂ€rm im Anflug dort einwirken zu lassen, wo er möglichst wenige Bewohner am Boden stört. An vier nicht realen BeispielflughĂ€fen wurde das Potenzial der horizontalen Optimierung aufgezeigt. DarĂŒber hinaus wurde fĂŒr Anflugverfahren auch untersucht, wie durch verbesserte Verfahren in der Vertikalen die LĂ€rmbelastung minimiert werden kann. Als Basis wurde zunĂ€chst eine Analyse der derzeit geflogenen Anflugprofile durchgefĂŒhrt. Darauf aufbauend wurde das Pilotenassistenzsystem Low Noise Augmentation System(LNAS) entwickelt. Es unterstĂŒtzt den Piloten dabei, ein energieoptimales Anflugprofil des LDLP-Verfahren zu fliegen. Diese Anflugprofile und die zugehörigen Handlungsempfehlungen basieren auf einer Flugzeugmodellsimulation, die auch eine Echtzeitkorrektur durchfĂŒhrt. Zur Erprobung von LNAS fanden am Flughafen Frankfurt Flugversuche vom 26. bis 28. September 2016 statt. Es ist eine Methode entwickelt und diese in ein Computerprogramm umgesetzt worden, das die an FlughĂ€fen mit Radar erfassten zeitlichen Positionsdaten von Start und Landungen automatisch aufbereitet, sodass diese anschließend fĂŒr Belange der FluglĂ€rmberechnung und-prognose nutzbar sind. Die Formulierung erfolgte anhand experimenteller und numerischer Daten aus den Bereichen Akustik und Aerodynamik. Im Projekt wurde das zusĂ€tzliche Hauptarbeitspaket "Ordnungspolitische Maßnahmen zur FluglĂ€rmreduzierung und ihre Kommunikation" bearbeitet. Als Grundlage hierfĂŒr wurden die Wirkungsketten ordnungspolitischer Maßnahmen beschrieben. DarĂŒber hinaus wurde die Kommunikation der Luftfahrtverkehrsindustrie mit der Bevölkerung untersucht und Leitlinien fĂŒr die FluglĂ€rmkommunikation abgeleitet

    Atezolizumab and bevacizumab with transarterial chemoembolization in hepatocellular carcinoma: the DEMAND trial protocol

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    The combination of the anti-PD-L1 antibody atezolizumab and the anti-VEGF bevacizumab is the first approved immunotherapeutic regimen for first-line therapy in patients with unresectable hepatocellular carcinoma (HCC), currently approved in more than 80 countries. The efficacy and tolerability of this regimen suggest that the use of atezolizumab bevacizumab could be extended to the treatment of patients with intermediate-stage HCC in combination with transarterial chemoembolization (TACE). The authors describe the rationale and design of the DEMAND study. This investigator-initiated, multicenter, randomized phase 2 study is the first trial to evaluate the safety and efficacy of atezolizumab bevacizumab prior to or in combination with TACE in patients with intermediate-stage HCC. The primary end point is the 24-month survival rate; secondary end points include objective response rate, progression-free survival, safety and quality of life

    A conditional piggyBac transposition system for genetic screening in mice identifies oncogenic networks in pancreatic cancer

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    © 2015 Nature America, Inc. All rights reserved. Here we describe a conditional piggyBac transposition system in mice and report the discovery of large sets of new cancer genes through a pancreatic insertional mutagenesis screen. We identify Foxp1 as an oncogenic transcription factor that drives pancreatic cancer invasion and spread in a mouse model and correlates with lymph node metastasis in human patients with pancreatic cancer. The propensity of piggyBac for open chromatin also enabled genome-wide screening for cancer-relevant noncoding DNA, which pinpointed a Cdkn2a cis-regulatory region. Histologically, we observed different tumor subentities and discovered associated genetic events, including Fign insertions in hepatoid pancreatic cancer. Our studies demonstrate the power of genetic screening to discover cancer drivers that are difficult to identify by other approaches to cancer genome analysis, such as downstream targets of commonly mutated human cancer genes. These piggyBac resources are universally applicable in any tissue context and provide unique experimental access to the genetic complexity of cancer.Link_to_subscribed_fulltex
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