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This study aimed at determining the recommended dose of the mammalian target of rapamycin inhibitor everolimus in combination with mitomycin C (MMC) in patients with previously treated metastatic esophagogastric cancer. In this phase I trial, patients received escalated doses of oral everolimus (5, 7.5, and 10 mg/day) in combination with intravenous MMC 5 mg/m2 every 3 weeks. Endpoints were the dose-limiting toxicity (DLT), safety, and response rates. Tumor tissues were tested for HER2-status and mutations in the PTEN, PIK3CA, AKT1, CTNNB1, and E-cadherin type 1 genes. Sixteen patients (12 male, four female) with gastric/gastroesophageal junction cancer were included. All patients were previously treated with a platinum-based chemotherapy. Treatment cohorts were: 5 mg/day, three patients; 7.5 mg/day, three patients; and 10 mg/day, 10 patients. No DLTs occurred during dose escalation. Most frequent grade 3 toxicities were leukopenia (18.8%) and neutropenia (18.8%). All other grade 3 toxicities were below 10%. No grade 4 toxicities occurred. Three (18.8%) patients experienced partial responses and four patients had stable disease (SD). Antitumor activity according to Response Evaluation Criteria In Solid Tumors (RECIST)-criteria was highest in the 10 mg/day cohort. No associations between HER2-status or detected mutations and response were observed. The recommended dose of everolimus combined with MMC is 10 mg/day. Encouraging signs of antitumor activity were seen (http://www.ClinicalTrials.gov; Clinical trial registration number: NCT01042782).
Hintergrund: Ab Frühjahr 2020 kam es zur weltweiten Verbreitung von SARS-CoV‑2 mit der heute als erste Welle der Pandemie bezeichneten Phase ab März 2020. Diese resultierte an vielen Kliniken in Umstrukturierungen und Ressourcenverschiebungen. Ziel unserer Arbeit war die Erfassung der Auswirkungen der Pandemie auf die universitäre Hals-Nasen-Ohren(HNO)-Heilkunde für die Forschung, Lehre und Weiterbildung. Material und Methoden: Die Direktorinnen und Direktoren der 39 Universitäts-HNO-Kliniken in Deutschland wurden mithilfe einer strukturierten Online-Befragung zu den Auswirkungen der Pandemie im Zeitraum von März bis April 2020 auf die Forschung, Lehre und die Weiterbildung befragt. Ergebnisse: Alle 39 Direktorinnen und Direktoren beteiligten sich an der Umfrage. Hiervon gaben 74,4 % (29/39) an, dass es zu einer Verschlechterung ihrer Forschungstätigkeit infolge der Pandemie gekommen sei. Von 61,5 % (24/39) wurde berichtet, dass pandemiebezogene Forschungsaspekte aufgegriffen wurden. Von allen Kliniken wurde eine Einschränkung der Präsenzlehre berichtet und 97,5 % (38/39) führten neue digitale Lehrformate ein. Im Beobachtungszeitraum sahen 74,4 % der Klinikdirektoren die Weiterbildung der Assistenten nicht gefährdet. Schlussfolgerung: Die Ergebnisse geben einen Einblick in die heterogenen Auswirkungen der Pandemie. Die kurzfristige Bearbeitung pandemiebezogener Forschungsthemen und die Einführung innovativer digitaler Konzepte für die studentische Lehre belegt eindrücklich das große innovative Potenzial und die schnelle Reaktionsfähigkeit der HNO-Universitätskliniken, um auch während der Pandemie ihre Aufgaben in der Forschung, Lehre und Weiterbildung bestmöglich zu erfüllen.
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n this paper we report on the investigation of baryonic resonance production in proton-proton collisions at the kinetic energies of 1.25 GeV and 3.5 GeV, based on data measured with HADES. Exclusive channels npπ+ and ppπ0 as well as ppe+e− were studied simultaneously in the framework of a one-boson exchange model. The resonance cross sections were determined from the one-pion channels for Δ(1232) and N(1440) (1.25 GeV) as well as further Δ and N* resonances up to 2 GeV/c2 for the 3.5 GeV data. The data at 1.25 GeV energy were also analysed within the framework of the partial wave analysis together with the set of several other measurements at lower energies. The obtained solutions provided the evolution of resonance production with the beam energy, showing a sizeable non-resonant contribution but with still dominating contribution of Δ(1232)P33. In the case of 3.5 GeV data, the study of the ppe+e− channel gave the insight on the Dalitz decays of the baryon resonances and, in particular, on the electromagnetic transition form-factors in the time-like region. We show that the assumption of a constant electromagnetic transition form-factors leads to underestimation of the yield in the dielectron invariant mass spectrum below the vector mesons pole. On the other hand, a comparison with various transport models shows the important role of intermediate ρ production, though with a large model dependency. The exclusive channels analysis done by the HADES collaboration provides new stringent restrictions on the parameterizations used in the models.
Mit der Color-Infrarot-Luftbildbefliegung in den Jahren 1992/1993 (siehe auch GÜNTHER; LANGE; NAGEL 1994) und der anschließenden Aufbereitung der Daten (Herstellung von Originalfilm und Kontaktkopie, Interpretation und Digitalisierung der Auswertungsergebnisse) nutzte das Land Sachsen-Anhalt bereits frühzeitig die Möglichkeit, mit Fernerkundungsdaten wichtige Informationen für den Naturschutz zu gewinnen . In dem von Mai 1997 bis April 2000 laufenden Forschungsprojekt "Der kombinierte Einsatz von multispektralen, hochauflösenden und stereoskopischen MOMS-2P-Daten zur Optimierung eines Landschaftsinformationssystems und zum Landschaftsmonitoring (MOMSIS)" wurde untersucht, inwieweit Biotop- und Nutzungstypenstrukturen auch im Satellitenbild erkannt werden können, um diese Informationen ergänzend zu den Ergebnissen aus der CIR-Luftbildbefliegung einsetzen zu können.
Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease) caused by mutations in the CLN3 gene is the most prevalent inherited neurodegenerative disease in childhood resulting in widespread central nervous system dysfunction and premature death. The consequences of CLN3 mutation on the progression of the disease, on neuronal transmission, and on central nervous network dysfunction are poorly understood. We used Cln3 knockout (Cln3Δex1-6) mice and found increased anxiety-related behavior and impaired aversive learning as well as markedly affected motor function including disordered coordination. Patch-clamp and loose-patch recordings revealed severely affected inhibitory and excitatory synaptic transmission in the amygdala, hippocampus, and cerebellar networks. Changes in presynaptic release properties may result from dysfunction of CLN3 protein. Furthermore, loss of calbindin, neuropeptide Y, parvalbumin, and GAD65-positive interneurons in central networks collectively support the hypothesis that degeneration of GABAergic interneurons may be the cause of supraspinal GABAergic disinhibition.
his contribution aims to give a basic overview of the latest results regarding the production of resonances in different collision systems. The results were extracted from experimental data collected with HADES that is a multipurpose detector located at the GSI Helmholtzzentrum, Darmstadt. The main points discussed here are: the properties of the strange resonances Λ(1405) and Σ(1385), the role of Δ’s as a source of pions in the final state, the production dynamics reflected in form of differential cross sections, and the role of the ϕ meson as a source for K− particles.
The Education Against Tobacco (EAT) network delivers smoking prevention advice in secondary schools, typically using the mirroring approach (i.e., a "selfie" altered with a face-aging app and shared with a class). In November 2017, however, the German assembly of EAT opted to expand its remit to include nursing students. To assess the transferability of the existing approach, we implemented it with the self-developed face-aging app "Smokerface" (=mixed − methods approach) in six nursing schools. Anonymous questionnaires were used to assess the perceptions of 197 students (age 18–40 years; 83.8% female; 26.4% smokers; 23.3% daily smokers) collecting qualitative and quantitative data for our cross-sectional study. Most students perceived the intervention to be fun (73.3%), but a minority disagreed that their own animated selfie (25.9%) or the reaction of their peers (29.5%) had motivated them to stop smoking. The impact on motivation not to smoke was considerably lower than experienced with seventh graders (63.2% vs. 42.0%; notably, more smokers also disagreed (45.1%) than agreed (23.5%) with this statement. Agreement rates on the motivation not to smoke item were higher in females than in males and in year 2–3 than in year 1 students. Potential improvements included greater focus on pathology (29%) and discussing external factors (26%). Overall, the intervention seemed to be appealing for nursing students