Search

Background Garadacimab, a fully human IgG4 monoclonal antibody, inhibits the kallikrein-kinin pathway at a key initiator, activated coagulation factor XII (FXIIa), and may play a protective role in preventing the progression of COVID-19. This phase 2 study evaluated the efficacy and safety of garadacimab plus standard of care (SOC) versus placebo plus SOC in patients with severe COVID-19. Methods Patients hospitalised with COVID-19 were randomised (1:1) to a single intravenous dose of garadacimab (700 mg) plus SOC or placebo plus SOC. Co-primary endpoint was incidence of endotracheal intubation or death between randomisation and Day 28. All-cause mortality, safety and pharmacokinetic/pharmacodynamic parameters were assessed. Results No difference in incidence of tracheal intubation or death (p = 0.274) or all-cause mortality was observed (p = 0.382). Garadacimab was associated with a lower incidence of treatment-emergent adverse events (60.3% vs 67.8%) and fewer serious adverse events (34 vs 45 events) versus placebo. No garadacimab-related deaths or bleeding events were reported, including in the 45.9% (n = 28/61) of patients who received concomitant heparin. Prolonged activated partial thromboplastin time (aPTT), and increased coagulation factor XII (FXII) levels were observed with garadacimab versus placebo to Day 14, whilst FXIIa-mediated kallikrein activity (FXIIa-mKA) was suppressed to Day 28. Conclusion In patients with severe COVID-19, garadacimab did not confer a clinical benefit over placebo. Transient aPTT prolongation and suppressed FXIIa-mKA showed target engagement of garadacimab that was not associated with bleeding events even with concomitant anticoagulant use. The safety profile of garadacimab was consistent with previous studies in patients with hereditary angioedema. ClinicalTrials. gov Identifier NCT04409509. Date of registration: 28 May, 2020., Author(s): Alberto Papi [sup.1], Renee D. Stapleton [sup.2], Paul M. Shore [sup.3], Mihai Alexandru Bica [sup.4], Younan Chen [sup.5], Michael Larbig [sup.6], Tobias Welte [sup.7] Author Affiliations: (1) grid.8484.0, 0000 [...]

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1467-9809.2007.00587.x Byline: PAUL SHORE (1) Abstract: The past two decades have witnessed an important shift in the historiography of the Society of Jesus. The older style of Jesuit history, flavoured with confessional polemics, and so often dependent on the work of Jesuit scholars isolated from the more secularly oriented academic community, had already ceased to dominate when John O'Malley's magisterial The First Jesuits appeared in 1993. .sup.1 Since then, the partnering of Jesuit and non-Jesuit scholars has produced scholarship that is generally sympathetic to the Society's aims and methods while avoiding neither criticism of the Jesuits nor thorough, judicious use of archival materials. The significance of this trend is heightened by the declining numbers of Jesuits in North America and Europe, creating a situation where the advancement of Jesuit studies will, at least in these venues, increasingly become the responsibility of non-Jesuits. With the passing of the Jesuit scholar of Jesuits, something is lost and gained; potentially greater objectivity towards the Society is offset by the loss of insight into the individual and corporate experience of being a Jesuit. The four books reviewed here illustrate in varying degrees these developments in the field. Author Affiliation: (1)Saint Louis University, Missouri, USA

The ternary complex factor (TCF) subfamily of ETS-domain transcription factors bind with serum response factor (SRF) to the serum response element (SRE) and mediate increased gene expression. The TCF protein Elk-1 is phosphorylated by the JNK and ERK groups of mitogen-activated protein (MAP) kinases causing increased DNA binding, ternary complex formation, and transcriptional activation. Activated SRE-dependent gene expression is induced by JNK in cells treated with interleukin-1 and by ERK after treatment with phorbol ester. The Elk-1 transcription factor therefore integrates MAP kinase signaling pathways in vivoto coordinate biological responses to different extracellular stimuli., The SRE mediates increased immediate-early gene expression (for example, c-fos) in cells treated with growth factors or cytokines or subjected to environmental stress[1]. The SRF binds to the SRE along [...]

INTRODUCTION Nowhere is a reassessment of the Jesuit contribution to eighteenth century culture more overdue than in Bohemian studies.(1) The usual handicaps of confessional bias and political polemic are compounded [...]

Early Modern Religious Communities in East-Central Europe: Ethnic Diversity, Denominational Plurality and Comparative Politics in the Principality of Transylvania. By Istvan Keul. [Studies in Medieval and Reformation Traditions, Vol. 143.] [...]

To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1467-9809.2009.00818.x Byline: Paul Shore (1) Author Affiliation: (1)Department of HistorySt Louis University

Loyola's Bees: Ideology and Industry in Jesuit Latin Didactic Poetry. By Yasmin Annabel Haskell. A British Academy Postdoctoral Fellowship Monograph. (New York: Published for the British Academy by Oxford University [...]