The Use of Social Media in Enterprises for Communication, Collaboration, and Knowledge Management

Der Erfolg von Social Media im Internet hat dazu geführt, dass diese Technologie zunehmend auch in Unternehmen eingesetzt, oder über deren Implementierung nachgedacht wird. Durch die erwartete Verbesserung der Kommunikation und Interaktion zwischen Mitarbeitern auf der einen Seite und des Wissensmanagements auf der anderen Seite er-hoffen sich Entscheidungsträger in Unternehmen einen erheblichen betriebswirtschaftlichen Nutzen. Obwohl es einige Beispiele erfolgreicher Enterprise-Social-Media(ESM)-Implementierungen gibt und mehr als 90% der Fortune 500 Unternehmen ESM eingeführt haben oder dies planen, verfehlen 80% der ESM-Projekte die eingangs definierten Ziele. Während die Entscheidung, die Software einzukaufen, zentral getroffen wird, hängt deren Erfolg von der aktiven Partizipation der Mitarbeiter ab – wie sich anhand der genannten Statistiken zeigt, ist beides nicht zwangsläufig korreliert. Im Gegensatz zu organischem Wachstum, wie es in Social-Media-Anwendungen im Internet in den vergangenen Jahren beobachtet werden konnte (z.B. bei Facebook), ist die Nutzungsrate von internen ESM oft zu gering, um den Fortbestand der Community zu sichern. Es zeigt sich dabei verstärkt, dass passive Roll-Out-Strategien, die darauf vertrauen, dass es ein vergleichbares organisches Wachstum auch bei ESM gibt, zum Scheitern verurteilt sind. Viel-mehr müssen Analysen im Vorhinein das für einen spezifischen Anwendungsbereich geeignete Tool identifizieren, und Strategien entwickelt werden, wie Mitarbeiter für die Interaktion über die neuen Anwendungen gewonnen werden können. Da Ausgaben für Informationstechnologien bei einem geringen Nutzungsgrad nicht zu-rechtfertigen sind, trägt die vorliegende Dissertation in acht Essays dazu bei, verschiedene Facetten der ESM-Nutzung näher beleuchten und so zu einem besseren Verständnis des Themas und damit einhergehend einer effektiveren und effizienteren Implementierung von ESM beitragen. Sowohl die Analyse von Einflussfaktoren auf verschiedene Nutzungstypen von ESM, die Optimierung von Enterprise-Suchalgorithmen als auch die Neuinterpretation von Online-Produkt-Ratings können dabei helfen, die Veränderungen der internen und externen Kommunikation, Kollaboration und des Wissensmanagements, die sich durch den Einsatz von ESM ergeben, besser zu erklären und bedarfs-gerechter einzusetzen. Die theoretischen und praktischen Implikationen, welche sich konkret aus den einzelnen Essays ergeben, werden in den entsprechenden Abschnitten der jeweiligen Papiere erläutert

HLA Ligand Atlas: a benign reference of HLA-presented peptides to improve T-cell-based cancer immunotherapy

BACKGROUND The human leucocyte antigen (HLA) complex controls adaptive immunity by presenting defined fractions of the intracellular and extracellular protein content to immune cells. Understanding the benign HLA ligand repertoire is a prerequisite to define safe T-cell-based immunotherapies against cancer. Due to the poor availability of benign tissues, if available, normal tissue adjacent to the tumor has been used as a benign surrogate when defining tumor-associated antigens. However, this comparison has proven to be insufficient and even resulted in lethal outcomes. In order to match the tumor immunopeptidome with an equivalent counterpart, we created the HLA Ligand Atlas, the first extensive collection of paired HLA-I and HLA-II immunopeptidomes from 227 benign human tissue samples. This dataset facilitates a balanced comparison between tumor and benign tissues on HLA ligand level. METHODS Human tissue samples were obtained from 16 subjects at autopsy, five thymus samples and two ovary samples originating from living donors. HLA ligands were isolated via immunoaffinity purification and analyzed in over 1200 liquid chromatography mass spectrometry runs. Experimentally and computationally reproducible protocols were employed for data acquisition and processing. RESULTS The initial release covers 51 HLA-I and 86 HLA-II allotypes presenting 90,428 HLA-I- and 142,625 HLA-II ligands. The HLA allotypes are representative for the world population. We observe that immunopeptidomes differ considerably between tissues and individuals on source protein and HLA-ligand level. Moreover, we discover 1407 HLA-I ligands from non-canonical genomic regions. Such peptides were previously described in tumors, peripheral blood mononuclear cells (PBMCs), healthy lung tissues and cell lines. In a case study in glioblastoma, we show that potential on-target off-tumor adverse events in immunotherapy can be avoided by comparing tumor immunopeptidomes to the provided multi-tissue reference. CONCLUSION Given that T-cell-based immunotherapies, such as CAR-T cells, affinity-enhanced T cell transfer, cancer vaccines and immune checkpoint inhibition, have significant side effects, the HLA Ligand Atlas is the first step toward defining tumor-associated targets with an improved safety profile. The resource provides insights into basic and applied immune-associated questions in the context of cancer immunotherapy, infection, transplantation, allergy and autoimmunity. It is publicly available and can be browsed in an easy-to-use web interface at https://hla-ligand-atlas.org

Adjuvant Radiotherapy in Patients with Squamous Cell Carcinoma of the Oral Cavity or Oropharynx and Solitary Ipsilateral Lymph Node Metastasis (pN1) : A Prospective Multicentric Cohort Study

(1) Background: Evaluation of impact of adjuvant radiation therapy (RT) in patients with oral squamous cell carcinoma of the oral cavity/oropharynx (OSCC) of up to 4 cm (pT1/pT2) and solitary ipsilateral lymph node metastasis (pN1). A non-irradiated group with clinical follow-up was chosen for control, and survival and quality of life (QL) were compared; (2) Methods: This prospective multicentric comprehensive cohort study included patients with resected OSCC (pT1/pT2, pN1, and cM0) who were allocated into adjuvant radiation therapy (RT) or observation. The primary endpoint was overall survival. Secondary endpoints were progression-free survival and QL after surgery; (3) Results: Out of 27 centers, 209 patients were enrolled with a median follow-up of 3.4 years. An amount of 137 patients were in the observation arm, and 72 received adjuvant irradiation. Overall survival did not differ between groups (hazard ratio (HR) 0.98 [0.55–1.73], p = 0.94). There were fewer neck metastases (HR 0.34 [0.15–0.77]; p = 0.01), as well as fewer local recurrences (HR 0.41 [0.19–0.89]; p = 0.02) under adjuvant RT. For QL, irradiated patients showed higher values for the symptom scale pain after 0.5, two, and three years (all p < 0.05). After six months and three years, irradiated patients reported higher symptom burdens (impaired swallowing, speech, as well as teeth-related problems (all p < 0.05)). Patients in the RT group had significantly more problems with mouth opening after six months, one, and two years (p < 0.05); (4) Conclusions: Adjuvant RT in patients with early SCC of the oral cavity and oropharynx does not seem to influence overall survival, but it positively affects progression-free survival. However, irradiated patients report a significantly decreased QL up to three years after therapy compared to the observation group

Impact of the first COVID lockdown on accident- and injury-related pediatric intensive care admissions in Germany - a multicenter study

Children’s and adolescents’ lives drastically changed during COVID lockdowns worldwide. To compare accident- and injury-related admissions to pediatric intensive care units (PICU) during the first German COVID lockdown with previous years, we conducted a retrospective multicenter study among 37 PICUs (21.5% of German PICU capacities). A total of 1444 admissions after accidents or injuries during the first lockdown period and matched periods of 2017–2019 were reported and standardized morbidity ratios (SMR) were calculated. Total PICU admissions due to accidents/injuries declined from an average of 366 to 346 (SMR 0.95 (CI 0.85–1.05)). Admissions with trauma increased from 196 to 212 (1.07 (0.93–1.23). Traffic accidents and school/kindergarten accidents decreased (0.77 (0.57–1.02 and 0.26 (0.05–0.75)), whereas household and leisure accidents increased (1.33 (1.06–1.66) and 1.34 (1.06–1.67)). Less neurosurgeries and more visceral surgeries were performed (0.69 (0.38–1.16) and 2.09 (1.19–3.39)). Non-accidental non-suicidal injuries declined (0.73 (0.42–1.17)). Suicide attempts increased in adolescent boys (1.38 (0.51–3.02)), but decreased in adolescent girls (0.56 (0.32–0.79)). In summary, changed trauma mechanisms entailed different surgeries compared to previous years. We found no evidence for an increase in child abuse cases requiring intensive care. The increase in suicide attempts among boys demands investigation

The Use of Social Media in Enterprises for Communication, Collaboration, and Knowledge Management

Der Erfolg von Social Media im Internet hat dazu geführt, dass diese Technologie zunehmend auch in Unternehmen eingesetzt, oder über deren Implementierung nachgedacht wird. Durch die erwartete Verbesserung der Kommunikation und Interaktion zwischen Mitarbeitern auf der einen Seite und des Wissensmanagements auf der anderen Seite er-hoffen sich Entscheidungsträger in Unternehmen einen erheblichen betriebswirtschaftlichen Nutzen. Obwohl es einige Beispiele erfolgreicher Enterprise-Social-Media(ESM)-Implementierungen gibt und mehr als 90% der Fortune 500 Unternehmen ESM eingeführt haben oder dies planen, verfehlen 80% der ESM-Projekte die eingangs definierten Ziele. Während die Entscheidung, die Software einzukaufen, zentral getroffen wird, hängt deren Erfolg von der aktiven Partizipation der Mitarbeiter ab – wie sich anhand der genannten Statistiken zeigt, ist beides nicht zwangsläufig korreliert. Im Gegensatz zu organischem Wachstum, wie es in Social-Media-Anwendungen im Internet in den vergangenen Jahren beobachtet werden konnte (z.B. bei Facebook), ist die Nutzungsrate von internen ESM oft zu gering, um den Fortbestand der Community zu sichern. Es zeigt sich dabei verstärkt, dass passive Roll-Out-Strategien, die darauf vertrauen, dass es ein vergleichbares organisches Wachstum auch bei ESM gibt, zum Scheitern verurteilt sind. Viel-mehr müssen Analysen im Vorhinein das für einen spezifischen Anwendungsbereich geeignete Tool identifizieren, und Strategien entwickelt werden, wie Mitarbeiter für die Interaktion über die neuen Anwendungen gewonnen werden können. Da Ausgaben für Informationstechnologien bei einem geringen Nutzungsgrad nicht zu-rechtfertigen sind, trägt die vorliegende Dissertation in acht Essays dazu bei, verschiedene Facetten der ESM-Nutzung näher beleuchten und so zu einem besseren Verständnis des Themas und damit einhergehend einer effektiveren und effizienteren Implementierung von ESM beitragen. Sowohl die Analyse von Einflussfaktoren auf verschiedene Nutzungstypen von ESM, die Optimierung von Enterprise-Suchalgorithmen als auch die Neuinterpretation von Online-Produkt-Ratings können dabei helfen, die Veränderungen der internen und externen Kommunikation, Kollaboration und des Wissensmanagements, die sich durch den Einsatz von ESM ergeben, besser zu erklären und bedarfs-gerechter einzusetzen. Die theoretischen und praktischen Implikationen, welche sich konkret aus den einzelnen Essays ergeben, werden in den entsprechenden Abschnitten der jeweiligen Papiere erläutert

Guidelines for the coordinated enhancement of the maritime position, navigation and time data system 

Reliable knowledge of a ship’s position and movement in relation to other traffic participants and obstacles is a fundamental requirement for navigation and avoiding collisions and groundings. Consequently, the onboard provision of resilient position, navigation and time data (PNT) is emphasized by the International Maritime Organization’s (IMO) e-navigation strategy, solution S3 “Improved reliability, resilience and integrity of bridge equipment and navigation information” and by the assigned risk control option RCO5 “Improved reliability and resilience of onboard PNT systems”. An initial step towards resilient PNT has been realized by the maritime community with the development of the performance standards for shipborne multi-system radionavigation receiver equipment (MRR). This MRR performance standard (PS) supports the full use of data coming from current and future radionavigation systems and services. Consequently, the combined use of several global navigation satellite systems (GNSS) and the additional use of space based augmentation systems (SBAS) as well as optional terrestrial radionavigation systems (e.g. eLoran or R-Mode) will be supported to increase the performance of positioning and timing. As a second step, the development of guidelines for an onboard PNT (data processing) unit has been identified as supplementary and necessary. The starting point is the onboard use of a combination of GNSS receivers and autarkic systems (e.g. radar, gyro, echosounders with bathymetric data) for a comprehensive provision of required PNT data. Redundancy in the available data enables the application of integrity monitoring functions to evaluate the current usability of safety-critical data and components. The aim of the guidelines is the specification of data processing rules towards the resilient provision of standardized PNT data and integrity information. For this purpose, a modular architecture for an onboard PNT system is introduced and scaled to the need for data input as well as the performance of data output

Coordinated Enhancement of the maritime PNT System: �Road Map and Guidelines

A reliable knowledge of ship’s position and movement in relation to other traffic participants is necessary for safe navigation at sea. A prerequisite to avoid collisions and groundings is the resilient onboard provision of position, navigation, and time data. This is emphasized by e-navigation solution S3 “Improved reliability, resilience and integrity of bridge equipment and navigation information” and assigned risk control option RCO5 “Improved reliability and resilience of onboard PNT systems” (NCSR1/9). In recent years the modular and open concept of an integrated PNT system has been developed as framework for the coordinated enhancement of the maritime PNT system (NAV58/6/1, NAV58/INF5, NCSR1/9/2). The Performance Standard for multi-system shipborne radionavigation receiver equipment, highlighted in this concept and currently under development (NCSR1/10), provides the basis to enable the full use of data coming from current/future radionavigation systems/services (e.g. range measurements, system parameters and variables such as orbit, correction and augmentation data). Furthermore the concept recognises the demand of an onboard PNT Unit as a synonym for a shipborne data processing tool to facilitate the application of multi-system-/multi-sensor-based techniques for resilient provision of all PNT data and reliable monitoring of data and system integrity (NAV58/6/1, NAV58/INF5, NCSR1/9/2). The combined use of PVT relevant sensors (e.g. GNSS Receiver, DGNSS corrections, Multi-Radionavigation Receiver) and onboard systems (e.g. Radar, Gyro, Echosounder with bathymetric data) establishes the needed redundancy to enable the monitoring of data and system integrity and to improve the performance of provided PNT data. This enables the protection of the onboard process of PNT data generation (cybersecurity) against intrusions by malicious actors. Therefore the drafting of a Guideline for the PNT Unit is considered as a supplementary but necessary step in the overall PNT system development for e-navigation solution S3 and associated risk control option RCO5. Reliability, integrity and resilience are fundamental requirements on nautical onboard equipment/systems identified as user needs and addressed as high-priority solution in the frame of e-navigation. If the PNT data provision meets these fundamental requirements or not can only be evaluated with respect to specific sets of technical requirements. To determine the achieved degree of reliability it is necessary to specify the tasks/functions to be performed by the equipment/system, the nominal operating conditions incl. dependencies on external systems/services and the required interruption free period of time. To achieve standardized results for integrity evaluation it is necessary to specify the methods of integrity monitoring in an unambiguous manner. And to ensure resilience it is necessary to identify the demand on intrasystem error compensation in relation to specified tasks, functions and performance requirements. The development of a guideline for the onboard PNT Unit is an appropriate measure to point out and clarify the dependencies between available/usable system modules (e.g. sensors, services, data sources) the applicability/feasibility of system operation (tasks, functions) and the achievable quality of data products

The immunopeptidomic landscape of ovarian carcinomas

Immunotherapies, particularly checkpoint inhibitors, have set off a revolution in cancer therapy by releasing the power of the immune system. However, only little is known about the antigens that are essentially presented on cancer cells, capable of exposing them to immune cells. Large-scale HLA ligandome analysis has enabled us to exhaustively characterize the immunopeptidomic landscape of epithelial ovarian cancers (EOCs). Additional comparative profiling with the immunopeptidome of a variety of benign sources has unveiled a multitude of ovarian cancer antigens (MUC16, MSLN, LGALS1, IDO1, KLK10) to be presented by HLA class I and class II molecules exclusively on ovarian cancer cells. Most strikingly, ligands derived from mucin 16 and mesothelin, a molecular axis of prognostic importance in EOC, are prominent in a majority of patients. Differential gene-expression analysis has allowed us to confirm the relevance of these targets for EOC and further provided important insights into the relationship between gene transcript levels and HLA ligand presentation