84 research outputs found
Gene expression profiling reveals consistent differences between clinical samples of human leukaemias and their model cell lines
Microarray gene expression profiles of fresh clinical samples of chronic myeloid leukaemia in chronic phase, acute promyelocytic leukaemia and acute monocytic leukaemia were compared with profiles from cell lines representing the corresponding types of leukaemia (K562, NB4, HL60). In a hierarchical clustering analysis, all clinical samples clustered separately from the cell lines, regardless of leukaemic subtype. Gene ontology analysis showed that cell lines chiefly overexpressed genes related to macromolecular metabolism, whereas in clinical samples genes related to the immune response were abundantly expressed. These findings must be taken into consideration when conclusions from cell line-based studies are extrapolated to patients
Effect of distance to specialist care for the diagnosis and disease outcome of inflammatory bowel disease in the Swiss inflammatory bowel disease cohort study
Background: Inflammatory bowel disease (IBD) needs early interventions and an individual specialist-patient relationship. Distance from a tertiary IBD center might affect patient's disease course and outcome. We investigated whether the patient-to-specialist distance has an impact on the disease course using the well-defined patient collective of the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS).
Methods: Patient's home address at diagnosis (postal zip code) was extracted from the SIBDCS database. Distance between each zip code and the nearest located IBD specialist center was calculated and classified into the following three sections based on proximity: 35 km (group 3).
Results: Our study included in total 408 IBD patients [234 Crohn's disease (CD), 154 ulcerative colitis (UC), 20 IBD unclassified (IBDU)]. Median age was lowest in group 2 at diagnosis (G1: 28 years; G2: 21 years, G3: 26 years, p < 0.01). The diagnostic delay did not differ between groups. CD patients in group 1 were treated more often with anti-tumor necrosis factor (TNF) agents (72% versus 56%, p = 0.04) and 5-aminosalicylates (44% versus 28%, p = 0.04) than in group 3. UC/IBDU patients in group 1 were treated more often with corticosteroids than patients in group 3 (83% versus 58%, p < 0.01). The occurrence of IBD-related surgeries did not differ between groups.
Conclusions: Patient-to-specialist distance might affect drug treatment. However, disease course and the need for IBD-related surgery does not seem to be associated with a longer distance to specialist care in Switzerland
Mutation Spectrum in Liquid Versus Solid Biopsies From Patients With Advanced Gastroenteropancreatic Neuroendocrine Carcinoma.
PURPOSE
Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are rare and have a poor prognosis. Most GEP-NEC are diagnosed with metastatic disease, with only minor biopsies available for molecular diagnostics. We assessed the applicability of liquid biopsies for molecular profiling of GEP-NEC.
MATERIALS AND METHODS
We performed massive parallel sequencing of 76 cancer-related genes in circulating tumor DNA from 50 patients with advanced GEP-NEC and compared findings to previous analyses of solid tumor biopsies from the same patients. Plasma samples were collected before therapy, and the median time span between blood and tissue sampling was 25 days.
RESULTS
We detected 178 somatic mutations in the liquid biopsies, 127 (71%) were also detected in the solid biopsies, whereas 51 (29%) were unique to the liquid biopsies. In the same 76 genes, we previously detected 199 somatic mutations (single nucleotide variants) in solid biopsies, of which 127 (64%) were also now detected in liquid biopsies. In exploratory subgroup assessments, concordance was higher in patients with liver metastases (P = 1.5 × 10-5) and increasing with level of liver involvement (P = 1.2 × 10-4). The concordance was similar between GEP-NEC with different primary sites, except being lower in esophageal cases (P = .001). Concordance was not associated with tumor mutation burden. Tumor tissue mutations also detected in liquid biopsies was lower for MSI (40%) versus MSS tumors (70%; P = 7.8 × 10-4). We identified potentially targetable mutations in plasma of 26 (52%) of patients with GEP-NEC; nine patients (18%) had potentially targetable mutation detected only in liquid biopsies.
CONCLUSION
Liquid biopsy analyses may be an applicable alternative to solid biopsies in GEP-NEC. Liquid biopsies may add additional mutations compared with tumor biopsies alone and could be useful for biomarker assessment in clinical trials for these patients
Aleksandr Puškin and the Caucasus. Literature. History. Images
Der Band Aleksandr Puškin und der Kaukasus. Literatur. Geschichte. Bilder beleuchtet jene Phase der russischen Geschichte und Kultur, als im Zuge der Expansionspolitik des Zarenreiches neue, ferne Gebiete in den Blick gerieten. Gerade die Kaukasusregion bildete mit ihrer atemberaubenden Bergwelt und den dort seit alters her ansässigen Völkern mit unterschiedlichen Religionen, Sitten und Gebräuchen für die Konstituierung des Selbstverständnisses des Dichters Aleksandr Puškin (1799-1837) und der russischen Gesellschaft eine Herausforderung.
Die Beiträge von Rolf-Dietrich Keil, Elisabeth von Erdmann, Leonid Arinštejn, Wolfgang Stephan Kissel, Andreas Ebbinghaus, Thomas Grob, Ada Raev und Sebastian Kempgen bewegen sich räumlich, zeitlich und methodisch zwischen unterschiedlichen Polen. Die Zugangsweisen umfassen biographische, macht- und geopolitische, literaturwissenschaftliche, ideengeschichtliche, kulturwissenschaftliche, kunsthistorische und wissenschaftsgeschichtliche Fokussierungen.
In der Zusammenschau von unterschiedlichen Quellen, literarischen Werken und bildkünstlerischen Zeugnissen wird herausgearbeitet, dass der Kaukasus aus russischer Sicht im ersten Drittel des 19. Jahrhunderts viele Gesichter hatte: Er war gleichermaßen mythengesättigter „Mundus Imaginalis“, Ort romantischer Sehnsucht und orientalischer Phantasien, „imperiale Landschaft“ und vielgestaltige Kulturlandschaft. Darüber hinaus diente er als Inspirationsquelle für neue literarische und bild-künstlerische Genres, als Erkenntnisraum und Prüfstein für den Begriff der Zivilisation. Neben Besonderheiten des russischen Orientdiskurses wird abschließend der Umgang des modernen Georgien mit dem kulturellen Erbe der einstigen Besatzer thematisiert.The volume Aleksandr Puškin and the Caucasus. Literature. History. Images examines a period of Russian history and culture in which new distant territories came into view as a consequence of Russian expansionism. The Caucasus region with its stunning mountain landscapes and its ancient peoples of various religions, habits and customs posed a challenge both to the development of Aleksandr Puškin’s (1799-1837) self-concept as a poet as well as to the formation of the identity of the Russian society as a whole.
The articles written by Rolf-Dietrich Keil, Elisabeth von Erdmann, Leonid Arinštejn, Wolfgang Stephan Kissel, Andreas Ebbinghaus, Thomas Grob, Ada Raev and Sebastian Kempgen encompass different aspects of time, space and methodology. The theoretical approaches include biographical, power-political, geopolitical and literary focuses, as well as an emphasis on the history of ideas, cultural science, history of art and history of science.
In the synopsis of diverse source material, including works of literature and visual arts, it becomes apparent that from the Russian perspective in the first third of the 19th century, the Caucasus had many faces. It simultaneously was a mythological “Mundus Imaginalis”, a place of romantic longing and oriental phantasies, an “imperial landscape” and a territory with multifarious cultural landscapes. It served as a source of inspiration for new literary and artistic genres, a place of cognition and a touchstone for the concept of civilization. Apart from specific aspects of the Russian orientalist discourse, it is also discussed how modern Georgia deals with the cultural heritage of its former occupiers
The North Atlantic Waveguide and Downstream Impact Experiment
The North Atlantic Waveguide and Downstream Impact Experiment (NAWDEX) explored the impact of diabatic processes on disturbances of the jet stream and their influence on downstream high-impact weather through the deployment of four research aircraft, each with a sophisticated set of remote sensing and in situ instruments, and coordinated with a suite of ground-based measurements. A total of 49 research flights were performed, including, for the first time, coordinated flights of the four aircraft: the German High Altitude and Long Range Research Aircraft (HALO), the Deutsches Zentrum für Luft- und Raumfahrt (DLR) Dassault Falcon 20, the French Service des Avions Français Instrumentés pour la Recherche en Environnement (SAFIRE) Falcon 20, and the British Facility for Airborne Atmospheric Measurements (FAAM) BAe 146. The observation period from 17 September to 22 October 2016 with frequently occurring extratropical and tropical cyclones was ideal for investigating midlatitude weather over the North Atlantic. NAWDEX featured three sequences of upstream triggers of waveguide disturbances, as well as their dynamic interaction with the jet stream, subsequent development, and eventual downstream weather impact on Europe. Examples are presented to highlight the wealth of phenomena that were sampled, the comprehensive coverage, and the multifaceted nature of the measurements. This unique dataset forms the basis for future case studies and detailed evaluations of weather and climate predictions to improve our understanding of diabatic influences on Rossby waves and the downstream impacts of weather systems affecting Europe
Structural evolution and disintegration of oceanic intraplate volcanoes: The Bathymetrists Seamounts and its relation to Sierra Leona Rise (eastern equatorial Atlantic) - Cruise No. M152/2, 03.01. – 12.02.2019, Las Palmas (Spain) – Walvis Bay (Namibia), SEDIS
Summary
The Bathymetrists Seamounts (BSM) are located north of the volcanic Sierra Leone Rise in the eastern Atlantic between 6° and 9°N. The three W-E, N-S and NE-SW striking directions of the seamounts indicate a clear structural control for the emplacement of these volcanoes. The origin of the melts, their relationship to the Sierra Leone Rise and the role of the faults in the formation of the melts are unknown as the BSM could be explained by plume related volcanism or decompression melting beneath deep (transform) faults. The SEDIS-cruise M152/2 of RV METEOR strove for a better understanding of the life cycle of submarine volcanoes and their effect on the oceanic lithosphere in the oceanic intraplate setting of the BSM and the relationship to the Sierra Leone Rise. The aims were: 1) to understand the interaction between crustal thickness, tectonics and volcanic phases, 2) to investigate the structural, chronological and petrological evolution of individual seamounts and seamount chains, 3) to review slope failures and resulting mass flow processes. We addressed these objectives by more than 4000 km highresolution reflection seismic and more than 5000 km of parametric echosounder, multi-beam, and gravity and magnetic profiles. Rock samples for ground truthing and geochemical research have been collected during 14 dredge stations. We further determined the concentrations in surface seawater and air and the state of air-sea exchange of a number of nowadays globally banned pesticides, polychlorinated biphenyls, brominated flame retardants, polycyclic aromatic hydrocarbons and their derivatives.
Zusammenfassung
Die Bathymetrists Seeberge liegen nördlich der Sierra Leone Schwelle, einer vulkanischen Plattform im östlichen Atlantik zwischen 6° und 9° N. Diese submarinen Vulkane gruppieren sich entlang W-E, N-S und NE-SW Trends, was eine strukturelle Kontrolle der Vulkanentstehung indiziert. Die Schmelzentstehung sind unbekannt und können mit PlumeVulkanismus oder Dekompressionsschmelzen unter bisher nicht untersuchten Störungen und tiefen Transformstörungen zusammenhängen. Der Bezug zur Sierra Leone Schwelle ist ebenfalls unbekannt. Im Zuge der SEDIS-Expedition M152/2 mit FS METEOR wurde der Lebenszyklus von Unterwasservulkanen und deren geochemischen Einfluss auf die ozeanische Lithosphäre der Bathymetrists Seeberge untersucht. Anhand der profilhaften geophysikalischer Messungen und Dredge-Proben wollen wir 1) die Wechselwirkung zwischen Krustenmächtigkeit, Tektonik und Vulkanismus verstehen, 2) die strukturelle, chronologische und petrologische Entwicklung von Vulkanen und Vulkanketten untersuchen, und 3) Auslösemechanismen, Transportprozesse und Volumina von Hangrutschungen studieren. Zur Bearbeitung der wissenschaftlichen Fragen sammelten wir mehr als 4000 km mehrkanal-reflexionsseismischer und mehr als 5000 km parametrische Sedimentecholot, Fächerlot, Schwere und Magnetik-Profile. Für die geochemischen Arbeiten sammelten wir an 14 Stationen Gesteinsproben unter Einsatz einer Dredge. Die regelmäßige Beprobung der Luft und des Oberflächenwassers diente der Bestimmung der Konzentration von heute weltweit verbotenen Pestiziden, polychlorierten Biphenylen, bromierten Flammschutzmitteln, polyzyklischen aromatischen Kohlenwasserstoffen und deren Derivaten und um den Austausch zwischen Luft und Meer weiter zu verstehen
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