Medien und Asyl - Methodenausbildung mit Anwendungsbezug als Chance und Herausforderung

Das Lehr-Lern-Projekt “Medien und Asyl” kombinierte Forschungs- und Anwendungsbezug in der universitären Hochschullehre. Der Beitrag diskutiert die didaktischen Herausforderungen eines solchen Lehrforschungsprojekts mit Service Learning- Orientierung, und wie diese adressiert wurden. In der Darstellung des Ablaufs wird der konsekutive Charakter des dreisemestrigen Projekts deutlich. Die finale Phase der Medienkonzeption wird dabei ausführlicher vorgestellt. Abschließend wird die Bedeutung fortlaufender Evaluation und Anpassung des Projektablaufs als methodischer Schlüssel zum Gelingen identifiziert

Minimal B Cell Extrinsic IgG Glycan Modifications of Pro- and Anti-Inflammatory IgG Preparations in vivo

Select residues in the biantennary sugar moiety attached to the fragment crystallizable of immunoglobulin G (IgG) antibodies can modulate IgG effector functions. Thus, afucosylated IgG glycovariants have enhanced cytotoxic activity, whereas IgG glycovariants rich in terminal sialic acid residues can trigger anti-inflammatory effects. More recent evidence suggests that terminal α2,6 linked sialic acids can be attached to antibodies post IgG secretion. These findings raise concerns for the use of therapeutic antibodies as they may change their glycosylation status in the patient and hence affect their activity. To investigate to what extent B cell extrinsic sialylation processes modify therapeutic IgG preparations in vivo, we analyzed changes in human intravenous IgG (IVIg) sialylation upon injection in mice deficient in B cells or in mice lacking the sialyltransferase 1, which catalyzes the addition of α2,6 linked sialic acid residues. By performing a time course of IgG glycan analysis with HILIC-UPLC-FLR (plus MS) and xCGE-LIF our study suggests that therapeutic IgG glycosylation is stable upon injection in vivo. Only a very small fraction of IgG molecules acquired sialic acid structures predominantly in the Fab- but not the Fc-portion upon injection in vivo, suggesting that therapeutic antibody glycosylation will remain stable upon injection in vivo

Presentation and medical management of peripheral arterial disease in general practice: rationale, aims, design and baseline results of the PACE-PAD Study

Background: Peripheral arterial disease (PAD) is highly prevalent among individuals of higher age or those with one or more cardiovascular risk factors. Screening for PAD is recommended, since it is often linked to atherothrombotic manifestations in the coronary or carotid circulation and associated with a substantial increase in all-cause and cardiovascular mortality. We aimed to assess patients with newly diagnosed, suspected and confirmed PAD in the primary care setting with regards to clinical characteristics, diagnostic and therapeutic management (including referral to specialists), and medium-term outcomes. Methods: This was a multicentre, prospective, observational cohort study with a cross-sectional and a longitudinal part. A total of 2,781 general practitioners across Germany were cluster randomised to document five consecutive patients each in one of the strata: (1) patients with intermittent claudication (IC) or other typical PAD-related complaints (group A) or (2) patients >55 years of age with one or more risk factors (group B) for PAD (current smoking, diabetes, previous myocardial infection and/or previous stroke). Patients with confirmed PAD will be followed up for diagnostic procedures, therapy and vascular events over 18 months. Results: In group A, a total of 2,131 patients with suspected PAD (80.1% confirmed, 75.9% with referral to specialists) and in group B 9,921 patients were included (44.6% confirmed, 54.6% referral). The ankle-brachial index was calculated in 41.3% and 33.5% only. Mean age was 66.6 years (group A) and 68.4 years (group B), respectively. Vascular risk factors were prevalent in both groups, in particular smoking (group A 44.6%, group B 44.4%), hypertension (73.2 and 78.1%), hypercholesterolaemia (64.6 and 70.6%) and diabetes mellitus (41.7 and 60.6%). Concomitant atherothrombotic morbidities were frequent in both groups. In patients with the respective diseases, antihypertensive, antidiabetic, lipid-lowering and antithrombotic therapies were prescribed in group A in 96.6, 96.0, 91.1 and 89.7% and in group B in 98.3, 97.4, 94.1 and 91.2%. Conclusion: The cross-sectional part of the study indicates a substantial burden of disease in PAD patients in primary care. Treatment rates appear to have improved compared to earlier surveys. In the follow-up period, outcomes of these patients and their association with disease stages, guideline-oriented treatment or patient compliance and disease-coping strategies, among other factors, will be determined

Outcomes of medical management of peripheral arterial disease in general practice: follow-up results of the PACE-PAD Study

Aim: Peripheral arterial disease (PAD), a marker of elevated vascular risk, is highly prevalent in general practice. We aimed to investigate patient characteristics and outcomes of PAD patients treated according to the guidelines versus those who were not. Methods: The Patient Care Evaluation-Peripheral Arterial Disease Study (PACE-PAD) was a multicenter, cluster randomized, prospective, longitudinal cohort study of patients with PAD in primary care, who were followed up for death or vascular events over 18 months. Guideline orientation was assumed if patients received anticoagulant/antiplatelet therapy, exercise training, and (if applicable) advice for smoking cessation and therapy of diabetes mellitus, hypertension, or hypercholesterolemia, respectively. Results: Of the 5,099 PAD patients (mean age 68.0 ± 9.0 years, 68.5% male subjects) who were followed up, 22.5, 34.6, 30.1, 7.8, and 3.5% (1.5% not specified) were in Fontaine stages I, IIa, IIb, III, and IV. Comprehensive guideline orientation was reported in 28.4% only; however, patients in lower Fontaine stages received guideline-oriented therapy more often (I: 30.3%, IIa: 31.6%, IIb: 29.1%, III: 9.8%, IV: 18.0%). During 18 months, 457 patients died (224 due to cerebrovascular or coronary deaths), 319 had unstable angina pectoris, 116 myocardial infarction, and 140 an ischemic stroke event. In total, 24% of patients had experienced any vascular event (19.1% a first event). Event rates did not differ between patients treated according to guidelines and those who were not. Conclusion: The present PAD cohort was a high-risk sample with an unexpectedly high rate of deaths and vascular events. While physicians appear to focus on the treatment of individual risk factors, rates of comprehensive PAD management in line with guideline recommendations are still suboptimal. Factors contributing to the lacking difference between outcomes in the guideline-oriented and non-guideline-oriented groups may comprise low treatment intensity or other reasons for unsatisfactory effect of treatment, misclassification of events, and patient’s noncompliance with therapy

E‐ARK Dissemination Information Package (DIP) Final Specification

The primary aim of this report is to present the final version of the E-ARK Dissemination Information Package (DIP) formats. The secondary aim is to describe the access scenarios in which these DIP formats will be rendered for use

Fc-engineering significantly improves the recruitment of immune effector cells by anti-ICAM-1 antibody MSH-TP15 for myeloma therapy

Despite several therapeutic advances, patients with multiple myeloma (MM) require additional treatment options since no curative therapy exists yet. In search of a novel therapeutic antibody, we previously applied phage display with myeloma cell screening and developed TP15, a scFv targeting intercellular adhesion molecule 1 (ICAM-1/CD54). To more precisely evaluate the antibody's modes of action, fully human IgG1 antibody variants were generated bearing wild-type (MSH-TP15) or mutated Fc to either enhance (MSH-TP15 Fc-eng.) or prevent (MSH-TP15 Fc k.o.) Fc gamma receptor binding. Especially MSH-TP15 Fc-eng. induced potent antibody-dependent cell-mediated cytotoxicity (ADCC) against malignant plasma cells by efficiently recruiting NK cells and engaged macrophages for antibody-dependent cellular phagocytosis (ADCP) of tumor cells. Binding studies with truncated ICAM-1 demonstrated MSH-TP15 binding to ICAM-1 domain 1-2. Importantly, MSH-TP15 and MSH-TP15 Fc-eng. both prevented myeloma cell engraftment and significantly prolonged survival of mice in an intraperitoneal xenograft model. In the subcutaneous model MSH-TP15 Fc-eng. was superior to MSH-TP15, whereas MSH-TP15 Fc k.o. was not effective in both models - reflecting the importance of Fc-dependent mechanisms of action also in vivo. The efficient recruitment of immune cells and the potent anti-tumor activity of the Fc-engineered MSH-TP15 antibody hold significant potential for myeloma immunotherapy

E‐ARK Search, Access and Display Interfaces

The aim of this report is to describe the “Search, Access and Display Interfaces” that have been developed in the Access component of the E-ARK project. The deliverable associated with this report is mainly a software deliverable and therefore this document provides only underpinning descriptions of and links to the software itself. The tools that are described and provided allow Consumers (ie. end-users and archivists) to: 1. Search and order records (primarily end-users, but also archivists) 2. Manage orders of records and manage the records themselves, including the AIP to DIP conversion (archivists only) 3. Access ordered records as DIPs (primarily end-users, but also archivists) In addition to the the introductory remarks in chapter 2, the functionality of the tools that allow the Consumers to search, manage, and access records is described in chapter 3. After the description of each tool, links are provided to code and documentation

E‐ARK Dissemination Information Package (DIP) Draft Specification

The primary aim of this report is to present the first version of the E-­‐ARK Dissemination Information Package (DIP) format. In order to do so the report describes the workflows and use cases of archival access services, and ultimately makes use of these these to present a set of requirements which should be followed when designing a DIP format. As access to archival records is largely dependent on the tools and environments used, the secondary aim of the deliverable is to go beyond the DIP format and look closely at the tools needed for preparing and using the DIP