TRUSTING REVIEW MECHANISMS IN KNOWLEDGE MANAGEMENT SYSTEMS: ANTECEDENTS, OUTCOMES, AND THE ROLE OF PERCEIVED RISK

In recent years, the success of social media in the private realm has entailed an increasing awareness of opportunities that are linked to user-generated content in knowledge management systems. Alongside the benefits in terms of knowledge quantity, new quality risks arise from an unregulated knowledge contribution. Considering that, review mechanisms have been implemented to monitor the content and provide a basis to distinguish between good and poor quality knowledge assets. This paper proposes a model to uncover the role of trust in expert and peer reviews during the knowledge application process by considering its antecedents, its outcomes, and the influnce of perceived risk. The model suggests that trust in expert and peer reviews is based on the ability, benevolence, and integrity of the respective group and is positively influnced by a higher trustor´s propensity to trust. Perceived risk in a particular situation influnces the decision whether to apply knowledge based on trust in expert or in peer reviews. It is assumed that high-risk decisions are based on expert reviews more likely because the organizational and individual risk is perceived to be lowered, whereas peer reviews can only mitigate organizational risk

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

Verlaufsbeurteilung der Intima-Media-Dicke bei Patienten mit primärem Hyperaldosteronismus

In der vorliegenden Arbeit wurde die Intima-Media-Dicke und deren Verlauf über den Zeitraum eines Jahres unter spezifischer Therapie bei Patienten mit primärem Hyperaldosteronismus in den Untergruppen des Aldosteron produzierenden Adenoms sowie der bilateralen adrenalen Hyperplasie verglichen. Untersucht wurden verschiedene Einflussfaktoren und deren Auswirkung auf die Intima-Media-Dicke. Darüber hinaus wurde die Mirkoalbuminurie in Hinblick auf die Eignung als Surrogatmarker für den Therapieerfolg evaluiert. Die Kohorte bestand aus 60 Patienten mit gesichertem primärem Hyperaldosteronismus, welche sich über den Zeitraum von Oktober 2008 bis Februar 2013 im Rahmen des Conn-Registers in München vorstellten. Es konnte gezeigt werden, dass bezüglich der Hypertonie in beiden Untergruppen durch die spezifische Therapie innerhalb eines Jahres, in der Mehrzahl der Fälle, eine Normalisierung des Blutdrucks erreicht werden konnte. Bei der Untergruppe des Aldosteron produzierenden Adenoms konnte häufig auch eine biochemische Komplettremission erzielt werden. Nichtsdestotrotz nahm die Intima-Media-Dicke in der Gesamtkohorte im gleichen Zeitraum zu. Die Subtypen waren in Hinblick auf die kardiovaskulären Risikofaktoren homogen. Der Ausgangswert der Intima-Media-Dicke lag bei den Patienten mit einem Aldosteron produzierendem Adenom nicht signifikant höher. Jedoch konnte für die Untergruppen kein signifikanter Unterschied in der Zunahme der Intima-Media-Dicke, der Optimierung des Blutdrucks oder der Verringerung der Mikroalbuminurie aufgezeigt werden. Die Intima-Media-Dicke zeigte sich sehr abhängig von unbeeinflussbaren Faktoren wie Alter und auch Geschlecht. Die Mikroalbuminurie hingegen zeigte in beiden Kohorten im Vergleich zur Intima-Media-Dicke den Therapieerfolg hinsichtlich der Blutdruckeinstellung durch eine Normalisierung der Messwerte an. Auch präsentierte sie sich nicht so abhängig von Alter, Geschlecht sowie den üblichen kardiovaskulären Risikofaktoren. Aus diesem Grund könnte die Mikroalbuminurie als Surrogatmarker für das Therapieansprechen herangezogen werden. Eine Aussage über das kardiovaskuläre Langzeitergebnis erlaubt sie jedoch nicht

T Cell Phenotype and T Cell Receptor Repertoire in Patients with Major Depressive Disorder

While a link between inflammation and the development of neuropsychiatric disorders, including major depressive disorder (MDD) is supported by a growing body of evidence, little is known about the contribution of aberrant adaptive immunity in this context. Here, we conducted in-depth characterization of T cell phenotype and T cell receptor (TCR) repertoire in MDD. For this cross- sectional case–control study, we recruited antidepressant-free patients with MDD without any somatic or psychiatric comorbidities (n = 20), who were individually matched for sex, age, body mass index, and smoking status to a non-depressed control subject (n = 20). T cell phenotype and repertoire were interrogated using a combination of flow cytometry, gene expression analysis, and next generation sequencing. T cells from MDD patients showed significantly lower surface expression of the chemokine receptors CXCR3 and CCR6, which are known to be central to T cell differentiation and trafficking. In addition, we observed a shift within the CD4+ T cell compartment characterized by a higher frequency of CD4+CD25highCD127low/− cells and higher FOXP3 mRNA expression in purified CD4+ T cells obtained from patients with MDD. Finally, flow cytometry-based TCR Vβ repertoire analysis indicated a less diverse CD4+ T cell repertoire in MDD, which was corroborated by next generation sequencing of the TCR β chain CDR3 region. Overall, these results suggest that T cell phenotype and TCR utilization are skewed on several levels in patients with MDD. Our study identifies putative cellular and molecular signatures of dysregulated adaptive immunity and reinforces the notion that T cells are a pathophysiologically relevant cell population in this disorder

Association of Variants at UMOD with Chronic Kidney Disease and Kidney Stones—Role of Age and Comorbid Diseases

Chronic kidney disease (CKD) is a worldwide public health problem that is associated with substantial morbidity and mortality. To search for sequence variants that associate with CKD, we conducted a genome-wide association study (GWAS) that included a total of 3,203 Icelandic cases and 38,782 controls. We observed an association between CKD and a variant with 80% population frequency, rs4293393-T, positioned next to the UMOD gene (GeneID: 7369) on chromosome 16p12 (OR = 1.25, P = 4.1×10−10). This gene encodes uromodulin (Tamm-Horsfall protein), the most abundant protein in mammalian urine. The variant also associates significantly with serum creatinine concentration (SCr) in Icelandic subjects (N = 24,635, P = 1.3×10−23) but not in a smaller set of healthy Dutch controls (N = 1,819, P = 0.39). Our findings validate the association between the UMOD variant and both CKD and SCr recently discovered in a large GWAS. In the Icelandic dataset, we demonstrate that the effect on SCr increases substantially with both age (P = 3.0×10−17) and number of comorbid diseases (P = 0.008). The association with CKD is also stronger in the older age groups. These results suggest that the UMOD variant may influence the adaptation of the kidney to age-related risk factors of kidney disease such as hypertension and diabetes. The variant also associates with serum urea (P = 1.0×10−6), uric acid (P = 0.0064), and suggestively with gout. In contrast to CKD, the UMOD variant confers protection against kidney stones when studied in 3,617 Icelandic and Dutch kidney stone cases and 43,201 controls (OR = 0.88, P = 5.7×10−5)

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

Using polymeric materials to control stem cell behavior for tissue regeneration

Patients with organ failure often suffer from increased morbidity and decreased quality of life. Current strategies of treating organ failure have limitations, including shortage of donor organs, low efficiency of grafts, and immunological problems. Tissue engineering emerged about two decades ago as a strategy to restore organ function with a living, functional engineered substitute. However, the ability to engineer a functional organ is limited by a limited understanding of the interactions between materials and cells that are required to yield functional tissue equivalents. Polymeric materials are one of the most promising classes of materials for use in tissue engineering, due to their biodegradability, flexibility in processing and property design, and the potential to use polymer properties to control cell function. Stem cells offer potential in tissue engineering because of their unique capacity to self‐renew and differentiate into neurogenic, osteogenic, chondrogenic, and myogenic lineages under appropriate stimuli from extracellular components. This review examines recent advances in stem cell–polymer interactions for tissue regeneration, specifically highlighting control of polymer properties to direct adhesion, proliferation, and differentiation of stem cells, and how biomaterials can be designed to provide some of the stimuli to cells that the natural extracellular matrix does. (Part C) 96:63–81, 2012. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90582/1/21003_ftp.pd