Untersuchung von HLA-Merkmalen bei Patienten mit Morbus Basedow mit und ohne autoimmune organspezifische Zweiterkrankungen sowie mit und ohne Immunorbitopahtie

Die vorgelegt Arbeit untersucht HLA-Merkmale bei Patienten mit Morbus Basedow unter besonderer Berücksichtigung der HLA-DQA1-Allele. Dabei wird im speziellen unterschieden zwischen Patienten mit und ohne Immunorbitopathie. Dabei wird nach Unterschieden in diesen Gruppen gesucht, die möglicherweise Rückschlüsse auf Ätiopathogenese ziehen lassen bzw. die den Einsatz von HLA-Merkmalen in der Diagnostik oder Risikomarker rechtfertigen

Digitalisation anxiety: development and validation of a new scale

<jats:title>Abstract</jats:title><jats:p>The increasing spread of digital technologies and respective consequences for the way we live, work, and communicate can evoke feelings of tension and discomfort. This so-called digitalisation anxiety is related to existing and future technologies, includes the process of digitalisation in everyday life, and refers to multiple levels (the individual, organisations, and society). Existing scales measuring technology-related fears due not adequately reflect these features. Therefore, we developed the German version of the Digitalisation Anxiety Scale (DAS). Having generated items based on a qualitative interview study (Study 1, n = 26), we demonstrated the DAS’s factor structure, internal consistency and construct validity in Study 2a (n = 109) and test-retest reliability in Study 2b (n = 30). In Study 3 (n = 223), the scale’s structure was confirmed and correlates of digitalisation anxiety were examined. The final version of the DAS consists of 35 items with a four-factor structure (societal triggers for digitalisation anxiety, triggers related to interaction and leadership, triggers within oneself and triggers resulting from the digitalisation implementation process). Digitalisation Anxiety had negative relationships with well-being and performance. The scale allows practitioners and researchers to measure and benchmark individuals’ levels of digitalisation anxiety, and to track changes over time. The scale can inform interventions aiming at reducing digitalisation anxiety and stress resulting from digitalisation. </jats:p&gt

Clinical and morphological phenotype of the filamin myopathy: a study of 31 German patients

Mutations in the filamin C gene (FLNC) cause a myofibrillar myopathy (MFM), morphologically characterized by focal myofibrillar destruction and abnormal accumulation of several proteins within skeletal muscle fibres. We studied 31 patients from four German families to evaluate the phenotype of filaminopathy. All patients harboured the same p.W2710X mutation in FLNC. Haplotype analysis suggested a founder mutation in these German filaminopathy families. The mean age at onset of clinical symptoms was 44 +/− 6 years (range, 24-57 years). Slowly progressive muscle weakness was mostly pronounced proximally, initially affecting the lower extremities and involving the upper extremities in the course of disease progression, similar to the distribution of weakness seen in limb-girdle muscular dystrophies (LGMD). Patients frequently developed respiratory muscle weakness. About one-third of the patients showed cardiac abnormalities comprising conduction blocks, tachycardia, diastolic dysfunction and left ventricular hypertrophy indicating a cardiac involvement in filaminopathy. Serum creatine kinase levels varied from normal up to 10-fold of the upper limit. Magnetic resonance imaging studies showed a rather homogenous pattern of muscle involvement in the lower extremities differing from that in other types of MFM. Myopathological features included perturbation of myofibrillar alignment, accumulation of granulofilamentous material similar to that seen in primary desminopathies and abnormal intracellular protein deposits typical of MFM. Decreased activities of oxidative enzymes and fibre hypertrophy seem to be early features, whereas dystrophic changes were present in advanced stages of filaminopathy. Rimmed vacuoles were detected in only a few cases. The intracellular aggregates were composed of a variety of proteins including filamin C, desmin, myotilin, Xin, dystrophin and sarcoglycans. Therapy is so far limited to symptomatic treatment. The German filaminopathy cohort, the largest group of patients studied so far, shares phenotypic features with LGMD and presents with characteristic histopathological findings of MF

Identification of novel Angiogenin (ANG) gene missense variants in German patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by the selective death of motor neurons in the motor cortex, brain stem and spinal cord. Recently, missense variants in the angiogenin gene (ANG), an angiogenic factor expressed in ventral horn motor neurons that is up-regulated by hypoxia, have been found in ALS patients of Irish/Scottish, North American, Italian, French and Dutch descent. To investigate the role of ANG in the German population, we screened for mutations by sequencing the entire coding region of the ANG gene in a large sample of 581 German ALS cases and 616 sex- and age-matched healthy controls. We identified two heterozygous missense variants, F(−13)L and K54E, in two German sporadic ALS cases but not in controls. Both missense variants are novel and have not been previously found in ALS cases. Our results suggest that missense variants in the ANG gene play a role in ALS in the German population and provide further evidence to support the hypothesis that angiogenic factors up-regulated by hypoxia are involved in the pathophysiology of ALS

MMB & DFT 2014 : Proceedings of the International Workshops ; Modeling, Analysis and Management of Social Networks and their Applications (SOCNET 2014) & Demand Modeling and Quantitative Analysis of Future Generation Energy Networks and Energy-Efficient Systems (FGENET 2014)

At present, a comprehensive set of measurement, modeling, analysis, simulation, and performance evaluation techniques are employed to investigate complex networks. A direct transfer of the developed engineering methodologies to related analysis and design tasks in next-generation energy networks, energy-efficient systems and social networks is enabled by a common mathematical foundation. The International Workshop on "Demand Modeling and Quantitative Analysis of Future Generation Energy Networks and Energy-Efficient Systems" (FGENET 2014) and the International Workshop on "Modeling, Analysis and Management of Social Networks and their Applications" (SOCNET 2014) were held on March 19, 2014, at University of Bamberg in Germany as satellite symposia of the 17th International GI/ITG Conference on "Measurement, Modelling and Evaluation of Computing Systems" and "Dependability and Fault-Tolerance" (MMB & DFT 2014). They dealt with current research issues in next-generation energy networks, smart grid communication architectures, energy-efficient systems, social networks and social media. The Proceedings of MMB & DFT 2014 International Workshops summarizes the contributions of 3 invited talks and 13 reviewed papers and intends to stimulate the readers’ future research in these vital areas of modern information societies.Gegenwärtig wird eine reichhaltige Klasse von Verfahren zur Messung, Modellierung, Analyse, Simulation und Leistungsbewertung komplexer Netze eingesetzt. Die unmittelbare Übertragung entwickelter Ingenieurmethoden auf verwandte Analyse- und Entwurfsaufgaben in Energienetzen der nächsten Generation, energieeffizienten Systemen und sozialen Netzwerken wird durch eine gemeinsame mathematische Basis ermöglicht. Die Internationalen Workshops "Demand Modeling and Quantitative Analysis of Future Generation Energy Net-works and Energy-Efficient Systems" (FGENET 2014) und "Modeling, Analysis and Management of Social Networks and their Applications" (SOCNET 2014) wurden am 19. März 2014 als angegliederte Symposien der 17. Internationalen GI/ITG Konferenz "Measurement, Modelling and Evaluation of Computing Systems" und "Dependability and Fault-Tolerance" (MMB & DFT 2014) an der Otto-Friedrich-Universität Bamberg in Deutschland veranstaltet. Es wurden aktuelle Forschungsfragen in Energienetzen der nächsten Generation, Smart Grid Kommunikationsarchitekturen, energieeffizienten Systemen, sozialen Netzwerken und sozialen Medien diskutiert. Der Tagungsband der Internationalen Workshops MMB & DFT 2014 fasst die Inhalte von 3 eingeladenen Vorträgen und 13 begutachteten Beiträgen zusammen und beabsichtigt, den Lesern Anregungen für ihre eigenen Forschungen auf diesen lebenswichtigen Gebieten moderner Informationsgesellschaften zu vermitteln

The Crowdsourced Replication Initiative: Investigating Immigration and Social Policy Preferences. Executive Report.

In an era of mass migration, social scientists, populist parties and social movements raise concerns over the future of immigration-destination societies. What impacts does this have on policy and social solidarity? Comparative cross-national research, relying mostly on secondary data, has findings in different directions. There is a threat of selective model reporting and lack of replicability. The heterogeneity of countries obscures attempts to clearly define data-generating models. P-hacking and HARKing lurk among standard research practices in this area.This project employs crowdsourcing to address these issues. It draws on replication, deliberation, meta-analysis and harnessing the power of many minds at once. The Crowdsourced Replication Initiative carries two main goals, (a) to better investigate the linkage between immigration and social policy preferences across countries, and (b) to develop crowdsourcing as a social science method. The Executive Report provides short reviews of the area of social policy preferences and immigration, and the methods and impetus behind crowdsourcing plus a description of the entire project. Three main areas of findings will appear in three papers, that are registered as PAPs or in process

Integrated care priorities at a national level

AIMS AND OBJECTIVES: To identify and prioritise diseases which can be managed by an integrated care model. To develop an adequate methodology therefore. To develop a list of indicators for the design of integrated care models. To research and analyse international experience and evidence. METHODS: Identification and prioritisation of the diseases through means of a literature review, a questionnaire for health professionals and a workshop with scientific and professional experts. Cooperation between the Medical University Vienna and the Competence Centre Integrated Care of the Viennese Sickness Fund. RESULTS: A report with a priority list of diseases relevant for the Austrian health care system for which integrated care models should be developed over the next years. A role model for other health care systems wanting to develop a national priority list and strategy for integrated care models. CONCLUSIONS: Integrated Care is an adequate model to face the challenges of today's health care systems and can be utilised to restructure health care provision on a national level

Cold Temperature Encoding by Cutaneous TRPA1 and TRPM8-Carrying Fibers in the Mouse

Previous research identified TRPM8 and TRPA1 cold transducers with separate functions, one being functional in the non-noxious range and the second one being a nociceptive transducer. TRPM8-deficient mice present overt deficits in the detection of environmental cool, but not a lack of cold avoidance and TRPA1-deficient mice show clear deficits in some cold nocifensive assays. The extent of TRPA1's contribution to cold sensing in vivo is still unclear, because mice lacking both TRPM8 and TRPA1 (DKO) were described with unchanged cold avoidance from TRPM8−/− based on a two-temperature-choice assay and by c-fos measurement. The present study was designed to differentiate how much TRPM8 alone and combined TRPA1 and TRPM8 contribute to cold sensing. We analyzed behavior in the thermal ring track assay adjusted between 30 and 5°C and found a large reduction in cold avoidance of the double knockout mice as compared to the TRPM8-deficient mice. We also revisited skin-nerve recordings from saphenous-nerve skin preparations with regard to nociceptors and thermoreceptors. We compared the frequency and characteristics of the cold responses of TRPM8-expressing and TRPM8-negative C-fiber nociceptors in C57BL/6J mice with nociceptors of TRPM8-deficient and DKO mice and found that TRPM8 enables nociceptors to encode cold temperatures with higher firing rates and larger responses with sustained, static component. In TRPM8−/−, C-fiber cold nociceptors were markedly reduced and appeared further reduced in DKO. Nevertheless, the remaining cold responses in both knockout strains were similar in their characteristics and they were indifferent from the TRPM8-negative cold responses found in C57BL/6J mice. TRPM8 had a comparably essential role for encoding cold in thermoreceptors and lack of TRPM8 reduced response magnitude, peak and mean firing rates and the incidence of thermoreceptors. The encoding deficits were similar in the DKO strain. Our data illustrate that lack of TRPA1 in TRPM8-deficient mice results in a disproportionately large reduction in cold avoidance behavior and also affects the incidence of cold encoding fiber types. Presumably TRPA1 compensates for lack of TRPM8 to a certain extent and both channels cooperate to cover the entire cold temperature range, making cold-temperature encoding by TRPA1—although less powerful—synergistic to TRPM8

Hypervirulent Klebsiella pneumoniae Sequence Type 420 with a Chromosomally Inserted Virulence Plasmid

Background: Klebsiella pneumoniae causes severe diseases including sepsis, pneumonia and wound infections and is differentiated into hypervirulent (hvKp) and classic (cKp) pathotypes. hvKp isolates are characterized clinically by invasive and multiple site infection and phenotypically in particular through hypermucoviscosity and increased siderophore production, enabled by the presence of the respective virulence genes, which are partly carried on plasmids. Methods: Here, we analyzed two K. pneumoniae isolates of a human patient that caused severe multiple site infection. By applying both genomic and phenotypic experiments and combining basic science with clinical approaches, we aimed at characterizing the clinical background as well as the two isolates in-depth. This also included bioinformatics analysis of a chromosomal virulence plasmid integration event. Results: Our genomic analysis revealed that the two isolates were clonal and belonged to sequence type 420, which is not only the first description of this K. pneumoniae subtype in Germany but also suggests belonging to the hvKp pathotype. The latter was supported by the clinical appearance and our phenotypic findings revealing increased siderophore production and hypermucoviscosity similar to an archetypical, hypervirulent K. pneumoniae strain. In addition, our in-depth bioinformatics analysis suggested the insertion of a hypervirulence plasmid in the bacterial chromosome, mediated by a new IS5 family sub-group IS903 insertion sequence designated ISKpn74. Conclusion: Our study contributes not only to the understanding of hvKp and the association between hypervirulence and clinical outcomes but reveals the chromosomal integration of a virulence plasmid, which might lead to tremendous public health implications