Manuscripts As Sources of Linguistics and Cultural Studies. Current Issues – Methods – Problems. Proceedings of the post-graduate conference, Bamberg, 4.-5.12.2015

Der Tagungsband des Nachwuchskolloquiums „Handschriften als Quellen der Sprach- und Kulturwissenschaft. Aktuelle Fragestellungen – Methoden – Probleme“, das am 4. und 5. Dezember 2015 an der Universität Bamberg abgehalten wurde, vereint Beiträge aus nahezu allen dem Mittelalter zugewandten Disziplinen. Handschriftenbasierte Forschung aus der germanistischen Mediävistik, der historischen Sprachwissenschaft, Geschichte und Kunstgeschichte eröffnet eine breite Perspektive auf die mittelalterliche bis frühneuzeitliche Kultur und Gesellschaft, auf die sprachlichen Begebenheiten dieser Epoche, deren Manifestation durch Schreiber und die kodikologische und paläographische Analyse der Schreibumstände sowie die Chancen und Anforderungen einer zeitgemäßen Forschung durch die Nutzbarmachung informationstechnologischer Ressourcen und die Digital Humanities. Mit der vorliegenden Publikation werden Forschungsergebnisse von Nachwuchswissenschaftlerinnen und -wissenschaftlern, aber auch renommierten Fachvertreterinnen und -vertretern aus dem In- und Ausland dergestalt zusammengeführt, dass sich ein vielschichtiges Bild über die aktuelle Situation in der Forschung handschriftlicher Quellen ergibt.The proceedings of the postgraduate conference „Handschriften als Quellen der Sprach- und Kulturwissenschaft. Aktuelle Fragestellungen – Methoden – Probleme“, which was held on 4th and 5th of December 2015 at the University of Bamberg, unifies contributions from almost all medieval disciplines. Manuscript-based research from Germanic medieval studies, historical linguistics, history and art history opens up a broad perspective on medieval and early modern culture and society, on the linguistic characteristics of this period, their manifestation by scribes, the codicological and palaeographic analysis of their writing conditions and the opportunities as well as demands of contemporary research through the utilization of information technology resources and the Digital Humans. The present publication brings together the research results of junior scientists and renowned experts from Germany and abroad in such an extent, that a complex picture emerges of the status quo in research of manuscriptual sources

The EnMAP imaging spectroscopy mission towards operations

EnMAP (Environmental Mapping and Analysis Program) is a high-resolution imaging spectroscopy remote sensing mission that was successfully launched on April 1st, 2022. Equipped with a prism-based dual-spectrometer, EnMAP performs observations in the spectral range between 418.2nm and 2445.5nm with 224 bands and a high radiometric and spectral accuracy and stability. EnMAP products, with a ground instantaneous field-of-view of 30m×30m at a swath width of 30km, allow for the qualitative and quantitative analysis of surface variables from frequently and consistently acquired observations on a global scale. This article presents the EnMAP mission and details the activities and results of the Launch and Early Orbit and Commissioning Phases until November 1st, 2022. The mission capabilities and expected performances for the operational Routine Phase are provided for existing and future EnMAP users

The EnMAP imaging spectroscopy mission towards operations

EnMAP (Environmental Mapping and Analysis Program) is a high-resolution imaging spectroscopy remote sensing mission that was successfully launched on April 1st, 2022. Equipped with a prism-based dual-spectrometer, EnMAP performs observations in the spectral range between 418.2 nm and 2445.5 nm with 224 bands and a high radiometric and spectral accuracy and stability. EnMAP products, with a ground instantaneous field-of-view of 30 m x 30 m at a swath width of 30 km, allow for the qualitative and quantitative analysis of surface variables from frequently and consistently acquired observations on a global scale. This article presents the EnMAP mission and details the activities and results of the Launch and Early Orbit and Commissioning Phases until November 1st, 2022. The mission capabilities and expected performances for the operational Routine Phase are provided for existing and future EnMAP users

Safety of baricitinib for the treatment of atopic dermatitis over a median of 1.6 years and up to 3.9 years of treatment: an updated integrated analysis of eight clinical trials

Background Baricitinib, a selective Janus kinase (JAK)1/JAK2 inhibitor, is approved for treatment of moderate-to-severe atopic dermatitis (AD) in adults. Objectives We report integrated baricitinib safety data in patients with up to 3.9-years exposure. Methods Three datasets from the integrated AD clinical trial program were analyzed: placebo-controlled, 2-mg–4-mg extended, and All-bari. Data cutoffs were up to 21-December-2021 for long-term extension studies. Proportions of patients with events and incidence rates (IR)/100 patient years (PY) at risk were calculated. Results 2636 patients received baricitinib for 4628.4 PY. Discontinuation due to adverse events was low (IR = 3.4). IRs in All-bari were: serious adverse events, 5.2; infection, 67.2 (any infection), 6.7 (herpes simplex), 2.8 (herpes zoster), and 0.3 (opportunistic infections). Adverse events of special interest in All-bari included seven patients with positively adjudicated major adverse cardiovascular events (MACE) (IR = 0.15), three pulmonary emboli (PE) (IR = 0.06), 14 malignancies excluding nonmelanoma skin cancer (IR = 0.3), one gastrointestinal perforation (IR = 0.02), and four deaths (IR = 0.1). No deep vein thromboses (DVT) or tuberculosis were reported. Conclusion In this analysis, baricitinib maintained a similar safety profile to earlier analyses with no new safety signals. Rates of MACE, DVT/PE, malignancies, and serious infections were within ranges of background rates in patients with AD. Clinicaltrials.gov NCT02576938 (JAHG), NCT03334396 (JAHL; BREEZE-AD1), NCT03334422 (JAHM; BREEZE-AD2), NCT03334435 (JAHN; BREEZE-AD3), NCT03428100 (JAIN; BREEZE-AD4), NCT03435081 (JAIW; BREEZE-AD5), NCT03559270 (JAIX; BREEZE-AD6), NCT03733301 (JAIY; BREEZE-AD7

Two Phase 3 Trials of Baricitinib for Alopecia Areata

BACKGROUND & nbsp;Alopecia areata is an autoimmune condition characterized by rapid hair loss in the scalp, eyebrows, and eyelashes, for which treatments are limited. Baricitinib, an oral, selective, reversible inhibitor of Janus kinases 1 and 2, may interrupt cytokine signaling implicated in the pathogenesis of alopecia areata.& nbsp;METHODS & nbsp;We conducted two randomized, placebo-controlled, phase 3 trials (BRAVE-AA1 and BRAVE-AA2) involving adults with severe alopecia areata with a Severity of Alopecia Tool (SALT) score of 50 or higher (range, 0 [no scalp hair loss] to 100 [complete scalp hair loss]). Patients were randomly assigned in a 3:2:2 ratio to receive once-daily baricitinib at a dose of 4 mg, baricitinib at a dose of 2 mg, or placebo. The primary outcome was a SALT score of 20 or less at week 36.& nbsp;RESULTS & nbsp;We enrolled 654 patients in the BRAVE-AA1 trial and 546 in the BRAVE-AA2 trial. The estimated percentage of patients with a SALT score of 20 or less at week 36 was 38.8% with 4-mg baricitinib, 22.8% with 2-mg baricitinib, and 6.2% with placebo in BRAVE-AA1 and 35.9%, 19.4%, and 3.3%, respectively, in BRAVE-AA2. In BRAVE-AA1, the difference between 4-mg baricitinib and placebo was 32.6 percentage points (95% confidence interval [CI], 25.6 to 39.5), and the difference between 2-mg baricitinib and placebo was 16.6 percentage points (95% CI, 9.5 to 23.8) (P < 0.001 for each dose vs. placebo). In BRAVE-AA2, the corresponding values were 32.6 percentage points (95% CI, 25.6 to 39.6) and 16.1 percentage points (95% CI, 9.1 to 23.2) (P < 0.001 for each dose vs. placebo). Secondary outcomes for baricitinib at a dose of 4 mg but not at a dose of 2 mg generally favored baricitinib over placebo. Acne, elevated levels of creatine kinase, and increased levels of low- and high-density lipoprotein cholesterol were more common with baricitinib than with placebo.& nbsp;CONCLUSIONS & nbsp;In two phase 3 trials involving patients with severe alopecia areata, oral baricitinib was superior to placebo with respect to hair regrowth at 36 weeks. Longer trials are required to assess the efficacy and safety of baricitinib for alopecia areata. (Funded by Eli Lilly under license from Incyte; BRAVE-AA1 and BRAVE-AA2 .N

Baricitinib in patients with moderate-to-severe atopic dermatitis: Results from a randomized monotherapy phase 3 trial in the United States and Canada (BREEZE-AD5)

Background: Baricitinib, an oral selective Janus kinase 1/Janus kinase 2 inhibitor, is being studied for moderate-to-severe atopic dermatitis (AD) in adults. Objective: To evaluate the efficacy and safety of baricitinib monotherapy in a North American phase 3 trial (BREEZE-AD5/NCT03435081) of adults with moderate-to-severe AD who responded inadequately or were intolerant to topical therapy. Methods: Patients (N = 440) were randomized 1:1:1 to once-daily placebo or baricitinib (1 mg or 2 mg). The primary endpoint was the proportion of patients achieving ≥75% reduction in the Eczema Area and Severity Index at week 16. A key secondary endpoint was the proportion of patients achieving a validated Investigator Global Assessment for AD score of 0 (clear)/1(almost clear) with ≥2-point improvement. Results: At week 16, the proportion of patients achieving Eczema Area and Severity Index was 8%, 13%, and 30% (P \u3c.001, 2 mg vs placebo) and those with a validated Investigator Global Assessment for AD score of 0/1 were 5%, 13%, and 24% (P \u3c.001, 2 mg vs placebo) for placebo, baricitinib 1 mg, and baricitinib 2 mg, respectively. Safety findings were similar to those of other baricitinib AD studies. Limitations: Short-term clinical trial results may not be generalizable to real-world settings. Conclusion: Baricitinib was efficacious for patients with moderate-to-severe AD with no new safety findings over 16 weeks

Wound-healing defect of CD18(−/−) mice due to a decrease in TGF-β(1) and myofibroblast differentiation

We studied the mechanisms underlying the severely impaired wound healing associated with human leukocyte-adhesion deficiency syndrome-1 (LAD1) using a murine disease model. In CD18(−/−) mice, healing of full-thickness wounds was severely delayed during granulation-tissue contraction, a phase where myofibroblasts play a major role. Interestingly, expression levels of myofibroblast markers α-smooth muscle actin and ED-A fibronectin were substantially reduced in wounds of CD18(−/−) mice, suggesting an impaired myofibroblast differentiation. TGF-β signalling was clearly involved since TGF-β(1) and TGF-β receptor type-II protein levels were decreased, while TGF-β(1) injections into wound margins fully re-established wound closure. Since, in CD18(−/−) mice, defective migration leads to a severe reduction of neutrophils in wounds, infiltrating macrophages might not phagocytose apoptotic CD18(−/−) neutrophils. Macrophages would thus be lacking their main stimulus to secrete TGF-β(1). Indeed, in neutrophil–macrophage cocultures, lack of CD18 on either cell type leads to dramatically reduced TGF-β(1) release by macrophages due to defective adhesion to, and subsequent impaired phagocytic clearance of, neutrophils. Our data demonstrates that the paracrine secretion of growth factors is essential for cellular differentiation in wound healing