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Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs.
Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel.
Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy.
Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
Ziele: Das Ziel dieser offiziellen Leitlinie, die von der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) und der Deutschen Krebsgesellschaft (DKG) publiziert und koordiniert wurde, ist es, die Früherkennung, Diagnostik, Therapie und Nachsorge des Mammakarzinoms zu optimieren.
Methoden: Der Aktualisierungsprozess der S3-Leitlinie aus 2012 basierte zum einen auf der Adaptation identifizierter Quellleitlinien und zum anderen auf Evidenzübersichten, die nach Entwicklung von PICO-(Patients/Interventions/Control/Outcome-)Fragen, systematischer Recherche in Literaturdatenbanken sowie Selektion und Bewertung der gefundenen Literatur angefertigt wurden. In den interdisziplinären Arbeitsgruppen wurden auf dieser Grundlage Vorschläge für Empfehlungen und Statements erarbeitet, die im Rahmen von strukturierten Konsensusverfahren modifiziert und graduiert wurden.
Empfehlungen: Der Teil 1 dieser Kurzversion der Leitlinie zeigt Empfehlungen zur Früherkennung, Diagnostik und Nachsorge des Mammakarzinoms: Der Stellenwert des Mammografie-Screenings wird in der aktualisierten Leitlinienversion bestätigt und bildet damit die Grundlage der Früherkennung. Neben den konventionellen Methoden der Karzinomdiagnostik wird die Computertomografie (CT) zum Staging bei höherem Rückfallrisiko empfohlen. Die Nachsorgekonzepte beinhalten Untersuchungsintervalle für die körperliche Untersuchung, Ultraschall und Mammografie, während weiterführende Gerätediagnostik und Tumormarkerbestimmungen bei der metastasierten Erkrankung Anwendung finden.
Purpose: The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer.
Methods: The process of updating the S3 guideline dating from 2012 was based on the adaptation of identified source guidelines which were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and the results of a systematic search of literature databases and the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point to develop recommendations and statements which were modified and graded in a structured consensus procedure.
Recommendations: Part 1 of this short version of the guideline presents recommendations for the screening, diagnosis and follow-up care of breast cancer. The importance of mammography for screening is confirmed in this updated version of the guideline and forms the basis for all screening. In addition to the conventional methods used to diagnose breast cancer, computed tomography (CT) is recommended for staging in women with a higher risk of recurrence. The follow-up concept includes suggested intervals between physical, ultrasound and mammography examinations, additional high-tech diagnostic procedures, and the determination of tumor markers for the evaluation of metastatic disease.
Fragestellung: Es existiert eine Vielzahl von Begriffen für Verhaltenssüchte, die Mängel in Operationalisierung, Bezug zum Verhalten, Kompatibilität mit internationalen Klassifikationen sowie nicht stigmatisierender Nutzung aufweisen. Daher werden einheitliche Begriffe für Verhaltenssüchte benötigt. Methode: Im Rahmen einer Leitlinie zur Diagnostik und Behandlung Internetbezogener Störungen wurden Lösungen in Form eines Expertenkonsens entwickelt. Ergebnisse: Als Grundlage wurde die Einteilung von Verhaltenssüchten in der 11. Revision der International Classification of Diseases (ICD-11) genutzt. Es wurden die Begriffe Computerspielstörung (CSS) und Glücksspielstörung (GSS) für die beiden in ICD-11 enthaltenen Verhaltenssüchte gewählt sowie drei weitere spezifizierte Verhaltenssüchte vorgeschlagen: Soziale-Netzwerke-Nutzungsstörung (SNS), Shoppingstörung (ShS) und Pornografie-Nutzungsstörung (PNS). Für CSS, GSS und ShS wird weiterhin zwischen vorwiegend online oder vorwiegend offline unterschieden. Als Oberbegriff wird Störungen aufgrund von Verhaltenssüchten vorgeschlagen. Für Störungen aufgrund von Verhaltenssüchten, die sich vorwiegend auf online ausgeübte Verhaltensweisen beziehen, kann alternativ der Oberbegriff Internetnutzungsstörungen verwendet werden. Schlussfolgerung: Die vorgeschlagenen Termini weisen Verbesserungen im Vergleich zu uneindeutigen oder aus anderen Gründen ungünstigen Begriffen dar. Gleichzeitig konnte eine Kompatibilität mit der ICD-11 ermöglicht werden.
The recognition of the prosodic focus position in German-learning infants from 4 to 14 months
(2007)
The aim of the present study was to elucidate in a study with 4-, 6-, 8-, and 14-month-old German-learning children, when and how they may acquire the regularities which underlie Focus-to-Stress Alignment (FSA) in the target language, that is, how prosody is associated with specific communicative functions. Our findings suggest, that 14-month-olds have already found out that German allows for variable focus positions, after having gone through a development which goes from a predominantly prosodically driven processing of the input to a processing where prosody interacts more and more with the growing lexical and syntactic knowledge of the child.
Die "Digitalisierung" ist ein gesamtgesellschaftlicher und globaler Trend, der nahezu alle Bereiche der Lebens- und Arbeitswelt durchzieht und insofern auch das Studieren an (allen) Hochschulen betrifft. Das Schlagwort "Digitalisierung" verweist auch auf alle Varianten der Nutzung von digitalen Technologien im Bereich Studium und Lehre. Lange Zeit stand vor allem das E-Learning im Vordergrund der Diskussion und damit die Nutzung von digitalen Technologien im engeren Lehr-Lernkontext zur Unterstützung der Interaktion von Lehrenden und Studierenden. Heute werden an den Hochschulen zunehmend die weiteren Möglichkeiten der digitalen Technik für Studium und Lehre erkannt und immer mehr in der Praxis an Hochschulen genutzt: Von der Werbung um Studierende bis hin zur Ansprache von Alumni können sie die Qualität, die Leistungsfähigkeit, die Öffnung, Vermarktung und Internationalisierung der Hochschullehre unterstützen (Kerres 2013, Bischof und von Stuckrad 2013); und einige Hochschulen nutzen die Digitalisierung von Lehre und Studium zur Profilbildung und zur besseren Positionierung im nationalen und internationalen Wettbewerb zwischen Hochschulen. ...
Simple Summary: Treatment of metastatic renal cell carcinoma (mRCC) remains a challenge due to the lack of biomarkers indicating the optimal drug for each patient. This study analyzed blood samples of patients with predominant clear cell mRCC who were treated with the mTOR inhibitor everolimus after failure of one prior tumor therapy. In an exploratory approach, predictive blood biomarkers were searched. We found lower levels of the protein thrombospondin-2 (TSP-2) at the start of the therapy and higher lactate dehydrogenase (LDH) levels in serum two weeks after therapy initiation to be associated with therapy response. Of note, these blood biomarkers had a higher predictive value than baseline patient parameters or risk classifications. Polymorphisms in the mTOR gene appeared to be associated with therapy response, but were not significant. To conclude, it seems feasible to identify patients showing longtime responses to everolimus and possible to increase tumor therapy response rates based on biomarkers for individual therapy selection.
Abstract: There is an unmet need for predictive biomarkers in metastatic renal cell carcinoma (mRCC) therapy. The phase IV MARC-2 trial searched for predictive blood biomarkers in patients with predominant clear cell mRCC who benefit from second-line treatment with everolimus. In an exploratory approach, potential biomarkers were assessed employing proteomics, ELISA, and polymorphism analyses. Lower levels of angiogenesis-related protein thrombospondin-2 (TSP-2) at baseline (≤665 parts per billion, ppb) identified therapy responders with longer median progression-free survival (PFS; ≤665 ppb at baseline: 6.9 months vs. 1.8, p = 0.005). Responders had higher lactate dehydrogenase (LDH) levels in serum two weeks after therapy initiation (>27.14 nmol/L), associated with a longer median PFS (3.8 months vs. 2.2, p = 0.013) and improved overall survival (OS; 31.0 months vs. 14.0 months, p < 0.001). Baseline TSP-2 levels had a stronger relation to PFS (HR 0.36, p = 0.008) than baseline patient parameters, including IMDC score. Increased serum LDH levels two weeks after therapy initiation were the best predictor for OS (HR 0.21, p < 0.001). mTOR polymorphisms appeared to be associated with therapy response but were not significant. Hence, we identified TSP-2 and LDH as promising predictive biomarkers for therapy response on everolimus after failure of one VEGF-targeted therapy in patients with clear cell mRCC.
The following mission statements by linguists and literary scholars working in different institutional and cultural contexts and at different stages of their careers are intended to map out the terrain covered by this journal. They tell similar stories about how these scholars came to cross the disciplinary boundary that too often divides their two fields, and they reveal a number of shared interests and emphases. But they also highlight the diversity of methodologies to which this journal is open – from metrics and stylistics to the cognitive sciences and Systemic Functional Grammar. The hopes and expectations voiced by the authors are partly pragmatic, expressing the wish that the journal’s Open Access format will have a broader reach than a journal published in the "traditional" way would, notably to colleagues outside of Western Europe. They also, however, emphasise the journal’s potential to shape our conception of "literary linguistics" and, therefore, to make an innovative contribution to shaping what continues to be a contested and often misunderstood "field".
Editorial
(2013)
The aim of this two-part special issue of The International Journal of Literary Linguistics is to probe the implications of the cognitive turn in literary linguistics that has gone hand in hand with the field’s growing appreciation of pragmatics at the end of the twentieth century (as illustrated e.g. by MacMahon, Mey, Verdonk and Weber). The view, increasingly shared by literary linguists, that literature is a communicative endeavour between text (author) and reader has resulted in a heightened interest in the cognitive abilities that ultimately make this communication possible. Yet the ease with which the buzzword ‘cognition’ sometimes is applied to explain these abilities and processes (which are often only assumed to exist rather than substantiated with empirical evidence) seems to be at odds not least with the fact that the cognitive sciences are far from a uniform field yielding fixed and finite results. Indeed, whether or not all language phenomena are underpinned by innate cognitive rules is an issue that remains a bone of contention amongst scholars, as does the nature of these cognitive rules themselves. Even a cognitive grammarian like Ronald Langacker warns against jumping to premature conclusions about the natural foundations of language (14) and avoids making such claims in his own work. ...
Flightless-I governs cell fate by recruiting the SUMO isopeptidase SENP3 to distinct HOX genes
(2017)
Background: Despite recent studies on the role of ubiquitin-related SUMO modifier in cell fate decisions, our understanding on precise molecular mechanisms of these processes is limited. Previously, we established that the SUMO isopeptidase SENP3 regulates chromatin assembly of the MLL1/2 histone methyltransferase complex at distinct HOX genes, including the osteogenic master regulator DLX3. A comprehensive mechanism that regulates SENP3 transcriptional function was not understood.
Results: Here, we identified flightless-I homolog (FLII), a member of the gelsolin family of actin-remodeling proteins, as a novel regulator of SENP3. We demonstrate that FLII is associated with SENP3 and the MLL1/2 complex. We further show that FLII determines SENP3 recruitment and MLL1/2 complex assembly on the DLX3 gene. Consequently, FLII is indispensible for H3K4 methylation and proper loading of active RNA polymerase II at this gene locus. Most importantly, FLII-mediated SENP3 regulation governs osteogenic differentiation of human mesenchymal stem cells.
Conclusion: Altogether, these data reveal a crucial functional interconnection of FLII with the sumoylation machinery that converges on epigenetic regulation and cell fate determination.