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Platelet adhesion and spreading at the sites of vascular injury is vital to hemostasis. As an integral part of the innate immune system, platelets interact with opsonized bacterial pathogens through FcγRIIA and contribute to host defense. As mechanoscavangers, platelets actively migrate and capture bacteria via cytoskeleton-rich, dynamic structures, such as filopodia and lamellipodia. However, the role of human platelet FcγRIIA in cytoskeleton-dependent interaction with opsonized bacteria is not well understood. To decipher this, we used a reductionist approach with well-defined micropatterns functionalized with immunoglobulins mimicking immune complexes at planar interfaces and bacteriamimetic microbeads. By specifically blocking of FcγRIIA and selective disruption of the platelet cytoskeleton, we show that both functional FcγRIIA and cytoskeleton are necessary for human platelet adhesion and haptotaxis. The direct link between FcγRIIA and the cytoskeleton is further explored by single-particle tracking. We then demonstrate the relevance of cytoskeleton-dependent differential mobilities of FcγRIIA on bacteria opsonized with the chemokine platelet factor 4 (PF4) and patient-derived anti-PF4/polyanion IgG. Our data suggest that efficient capture of opsonized bacteria during host-defense is governed by mobility dynamics of FcγRIIA on filopodia and lamellipodia, and the cytoskeleton plays an essential role in platelet morphodynamics at biological interfaces that display immune complexes.
A Brief History of APIs
(2021)
Online platforms such as Facebook, YouTube and Twitter offer a wide range of data for scientific research. Since many of the social media providers have set up application programming interfaces (APIs), extensive volumes of data can be collected automatically (Jünger, 2018; Keyling & Jünger, 2016). Social media data are attractive, inter alia, because they not only include already available communication, such as that from public media, but they also make organisational and interpersonal communication visible (Ledford, 2020). In addition, these data are process-generated (Baur, 2011, p. 1234), meaning that they are generated independently of scientific research and thus promise an authentic insight into human behaviour. 1 A wide range of studies in the social sciences exploit APIs for data collection and analysis. Thus, the establishment and development of APIs has significant implications for science.
Einführung in die Ethik
(2021)
Das Open Access-Lehrbuch bietet eine allgemeinverständliche, aber wissenschaftlichen Ansprüchen genügende Einführung in die philosophische Ethik. Es erläutert den Begriff der Ethik, ihre zentralen Probleme, ihre geschichtliche Entwicklung, die einflussreichsten ethischen Grundpositionen und ihre aktuelle Relevanz in verschiedenen Praxisfeldern. Dabei erleichtert der historisch-systematische Zugang das Verständnis des Zusammenhangs von ethischer Theorie und gesellschaftlicher Praxis.
Soziale Eingebundenheit
(2021)
Der Schul- und Unterrichtsalltag wird maßgeblich durch soziale Interaktionen geprägt. Sowohl Beziehungen mit Lehrer*innen als auch mit Schülern und Schülerinnen (Peers) tragen zentral zu Lehr-/Lernprozessen und persönlicher Entwicklung der Heranwachsenden bei. Bei Lehrkräften entscheiden sie über Erfolg und Misserfolg beruflichen Handelns und finden dementsprechend zunehmend auch in der Lehrer*innenbildung Berücksichtigung. Was lange Zeit als „Kuschelpädagogik“ belächelt wurde, entpuppt sich – auch durch aktuelle Befunde aus der Hirnforschung – als einer der wichtigsten Bausteine für erfolgreiche Lehr-Lernprozesse: die Qualität der sozialen Beziehungen – subsumiert unter dem Begriff der sozialen Eingebundenheit.
In diesem Band werden sowohl theoretische Beiträge als auch aktuelle empirische Befunde zu Lehrer*innen-Schüler*innen-Beziehungen, Schüler*innen-Schüler*innen-Beziehungen und Beziehungen in der Lehrer*innenbildung vereint.
Der Band richtet sich an Personen, die sich mit sozialen Beziehungen im Bereich Schule und Lehrer*innenbildung beschäftigen, sei es durch eigene Forschungstätigkeiten, das Studium oder eine Tätigkeit in ebendieser Praxis.
The interdisciplinary study investigates the relationship between Norse and Saami peoples in the medieval period and focuses on the multifaceted portrayal of Saami peoples in medieval texts. The investigative analysis is anchored in postcolonial methodologies and argues for the inherent need to decolonise the medieval source-material as well as recent historiography. This is achieved by presenting the historiographic and political background of research into Norse-Saami relations, before introducing an overview of textual sources discussing Saami peoples from the classical period to the late 1400s, an analysis of the textual motifs associated with the Saami in medieval literature (their relevance and prevalence), geo-political affairs, trading relations, personal relations and Saami presence in the south. By using decolonising tools to read Norse-Saami relations in medieval texts, influenced by archaeological material and postcolonial frameworks, the study challenges lingering colonial assumptions about the role of the Saami in Norse society. The current research episteme is re-adjusted to offer alternative readings of Saami characters and emphasis is put on agency, fluidity and the dynamic realities of the Saami medieval pasts.
Bei einem Herz-Kreislauf-Stillstand können Leitstellendisponenten mit Hilfe eines Telefonreanimationsprotokolls medizinische Laien in Wiederbelebungsmaßnahmen anleiten. Durch die Anwendung von Automatisierten Externen Defibrillatoren (AED) durch hinzukommende qualifizierte Ersthelfer (Community-First-Responder) kann die Überlebenswahrscheinlichkeit weiter gesteigert werden. Im Rahmen des Pilotprojektes MVLIFEDRONE wurde die Umsetzung eines Telefonreanimationsprotokolls, sowie die Reanimationsqualität und AED-Anwendung von Laienhelfenden und Community-First-Respondern in 48 Simulationsszenarien untersucht. Die Datenanalyse basierte auf Videoaufzeichnungen der Simulationen und Daten des Reanimationssimulators.
Die Forschungshypothese, dass bei dem aktuell in der Untersuchungsregion angewendeten Telefonreanimationsprotokolls Teilschritte in der Umsetzung durch die Laienhelfende nicht korrekt erfolgen, konnte nachgewiesen werden. Nur 64% der Laienhelfenden führten eine suffiziente Atemkontrolle durch. Bei Verwendung einer konkretisierten Atemkontrollanweisung mit Handlungsbeschreibung führten signifikant mehr Laienhelfende (92%) eine leitlinienkonforme Atemkontrolle durch, p <0,05. Verglichen zu Laienhelfenden (99 bpm), führten Community-First-Responder die Reanimation mit einer leitlinienkonformen Frequenz (109 bpm) und korrekter Handposition durch, wobei das Erreichen der Kompressionstiefe für beide Gruppen keine Herausforderung darstellte. Lautes Mitzählen der Laienhelfenden kann die Frequenz der Thoraxkompressionen verbessern. Eine Aufforderung zur Nutzung dieser Methode im Protokoll wird empfohlen. Andere Aufforderungen, wie Bewusstseinskontrolle, Entkleidung oder die Aktivierung der Freisprechfunktion, wurden von fast 100% der Laienhelfenden suffizient umgesetzt. Damit zeigen sich diese Formulierungen als verständlich und gut umsetzbar. Die vollständige Entlastung des Thoraxes wurde von beiden Helfergruppen unzureichend durchgeführt und sollte in der Ausbildung der Community-First-Responder explizit behandelt werden. In der AED-Anwendung fand sich kein signifikanter qualitativer Unterschied zwischen den Helfergruppen, wenngleich die Community-First-Responder im Mittel 20 Sekunden schneller waren. Die Hypothese der höheren Reanimationsqualität und schnelleren AED-Anwendung der Community-First-Respondern konnte bestätigt werden. Abschließend lässt sich feststellen, dass jedes Telefonreanimationsprotokoll auf seine Umsetzbarkeit und Qualität evaluiert werden sollte.
In diesem Open-Access-Buch wird die Aussteuerung von Zielkonflikten bei der Gestaltung des Luftrettungssystems in Deutschland erarbeitet, indem ein Modell zur Bewertung von Luftrettungsleistungen entwickelt wird. Der hubschraubergestützten Luftrettung kommt seit Jahren eine zunehmende Bedeutung in der notfallmedizinischen Versorgung zu. Als auffälliges und leistungsfähiges, aber auch teures Rettungsmittel unterliegt die Luftrettung äußerst vielen Ansprüchen, die von unterschiedlichsten Interessensgruppen an das Luftrettungssystem gestellt werden. Diese Partikularinteressen implizieren Zielkonflikte bei der Gestaltung des Luftrettungssystems.
Mit dem Kostenmodell werden verschiedene Szenarien modelliert, welche auf einem exemplarischen Erfahrungsobjekt basieren. Abgebildet werden unter anderem der Status Quo, Kritikpunkte am deutschen Luftrettungssystem sowie verschiedene Innovationen, die sich auch aus einem Vergleich ausgewählter internationaler Luftrettungssysteme ergeben. Die Ergebnisse der Arbeit werden genutzt, um Handlungsempfehlungen zur Gestaltung von Luftrettungssystemen auszuarbeiten.
Der interdisziplinäre Band postuliert eine Macht des Kontextes und erklärt, was darunter verstanden wird. Die Beiträge beleuchten und hinterfragen die Macht des Kontextes in dessen Relationen zu Sprache(n), Gesellschaft(en) und Medien. Dies geschieht teils aus philologischem, teils aus sozialwissenschaftlich-kommunikationswissenschaftlichem Blickwinkel und schließt jeweils mit Thesen zur Macht des Kontextes. Der Fokus in den Beiträgen lässt sich entlang der sozialwissenschaftlichen Ebenen (Mikroebene, Mesoebene, Makroebene) differenzieren. Mit Blick auf die gewonnenen Erkenntnisse eröffnet sich die Perspektive einer breit verstandenen Kontextlinguistik, und es werden Impulse und Anknüpfungspunkte für weitere Forschung in den Einzeldisziplinen sowie für disziplinenverbindende Forschung geboten.
Kragl, Angelique ; Hannemann, Anke ; Nauck, Matthias ; Völker, Uwe ; Siggelkow, Heide ; Teumer, Alexander ; Tzvetkov, Mladen V.
Osteoporosis, a complex chronic disease with increasing prevalence, is characterised by reduced bone mineral density (BMD) and increased fracture risk. The high heritability of BMD suggests substantial impact of the individual genetic disposition on bone phenotypes and the development of osteoporosis. In the past years, genome-wide association studies (GWAS) identified hundreds of genetic variants associated with BMD or osteoporosis. Here, we analysed 1103 single nucleotide polymorphisms (SNPs), previously identified as associated with estimated BMD (eBMD) in the UK Biobank. We assessed whether these SNPs are related to heel stiffness index obtained by quantitative ultrasound in 5665 adult participants of the Study of Health in Pomerania (SHIP). We confirmed 45 significant associations after correction for multiple testing. Next, we analysed six selected SNPs in 631 patients evaluated for osteoporosis [rs2707518 (CPED1/WNT16), rs3779381 (WNT16), rs115242848 (LOC101927709/EN1), rs10239787 (JAZF1), rs603424 (PKD2L1) and rs6968704 (JAZF1)]. Differences in minor allele frequencies (MAF) of rs2707518 and rs3779381 between SHIP participants (higher MAF) and patients evaluated for osteoporosis (lower MAF) indicated a protective effect of the minor allele on bone integrity. In contrast, differences in MAF of rs603424 indicated a harmful effect. Co-localisation analyses indicated that the rs603424 effect may be mediated via stearoyl-CoA desaturase (SCD) expression, an enzyme highly expressed in adipose tissue with a crucial role in lipogenesis. Taken together, our results support the role of the WNT16 pathway in the regulation of bone properties and indicate a novel causal role of SCD expression in adipose tissue on bone integrity.
Lode, Holger N. ; Ehlert, Karoline ; Huber, Stephanie ; Troschke-Meurer, Sascha ; Siebert, Nikolai ; Zumpe, Maxi ; Loibner, Hans ; Ladenstein, Ruth
Background
Short-term infusions of dinutuximab beta plus isotretinoin and cytokines administered in previous immunotherapy studies in neuroblastoma were associated with severe pain. Here, long-term, continuous infusion of single-agent dinutuximab beta was evaluated in patients with relapsed/refractory neuroblastoma.
Methods
In this open-label, single-arm, Phase 2 study, patients with either refractory or relapsed high-risk neuroblastoma received dinutuximab beta by continuous infusion over 10 days of each cycle, for up to five cycles. The primary endpoint was objective response rate 24 weeks after the end of cycle 5. Secondary endpoints included adverse events, intravenous morphine use, best response, duration of response, and three-year progression-free and overall survival.
Results
Of the 40 patients included, 38 had evaluable response. Objective response rate was 26% and best response rate 37%. Median duration of response was 238 days (IQR 108–290). Three-year progression-free and overall survival rates were 31% (95% CI 17–47) and 66% (95% CI 47–79), respectively. Prophylactic intravenous morphine use and duration of use decreased with increasing cycles. The most common grade 3 treatment-related adverse events were pain, diarrhea, and hypokalemia.
Conclusion
Long-term continuous infusion of single-agent dinutuximab beta is tolerable and associated with clinically meaningful responses in patients with relapsed/refractory high-risk neuroblastoma.
Clinical trial registration
The study is registered with ClinicalTrials.gov (NCT02743429) and EudraCT (2014-000588-42).