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Institution

University of Duisburg-Essen

EducationEssen, Nordrhein-Westfalen, Germany
About: University of Duisburg-Essen is a education organization based out in Essen, Nordrhein-Westfalen, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 16072 authors who have published 39972 publications receiving 1109199 citations.


Papers
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Journal ArticleDOI
TL;DR: A consensus statement on the application of colchicine in children and adolescents with familial Mediterranean fever was developed by caregivers from Germany, Austria, and Turkey.
Abstract: The daily application of colchicine is the standard therapy for prophylaxis of attacks and amyloid deposition in familial Mediterranean fever. However, because of many issues (eg, dosage, time of introduction, etc), no standardized treatment recommendations have been established. In this work we review the available literature on colchicine use with respect to its indication, efficacy, mode of application, and safety in children and adolescents with familial Mediterranean fever. On the basis of this analysis, a consensus statement on the application of colchicine in children and adolescents with familial Mediterranean fever was developed by caregivers from Germany, Austria, and Turkey.

222 citations

Journal ArticleDOI
01 May 2005-Leukemia
TL;DR: Over-representation of high-risk genomic aberrations such as 17p deletion or 11q deletion and distribution of the IgVH mutation status in B-CLL discordant for ZAP-70/CD38 pointed toward a distinct biologic background of the observed disease subgroups.
Abstract: Prognostic predictions in B-cell chronic lymphocytic leukemia (B-CLL) at early clinical stage are based on biological disease parameters, such as ZAP-70 and CD38 protein levels, genomic aberrations as well as immunoglobulin variable heavy chain gene (IgV(H)) mutation status. In the current study, ZAP-70 and CD38 expressions were examined by flow cytometry in 252 patients with B-CLL. Cytoplasmic ZAP-70 expression in more than 20% (ZAP-70(+)) and surface CD38 expression on more than 30% (CD38(+)) of B-CLL cells were associated with an unfavorable clinical course. The levels of ZAP-70 and CD38 did not change over time in the majority of patients where sequential samples were available for analysis. Combined analysis of ZAP-70 and CD38 yielded discordant results in 73 patients (29.0%), whereas 120 patients (47.6%) were concordantly negative and 59 patients (23.4%) were concordantly positive for ZAP-70 and CD38 expression. Median treatment-free survival times in patients whose leukemic cells were ZAP-70(+)CD38(+) was 30 months as compared to 130 months in patients with a ZAP-70(-)CD38(-) status. In patients with discordant ZAP-70/CD38 results, the median treatment-free survival time was 43 months. Thus, ZAP-70 and CD38 expression analyses provided complementary prognostic information identifying three patient subgroups with good, intermediate and poor prognosis. Over-representation of high-risk genomic aberrations such as 17p deletion or 11q deletion and distribution of the IgV(H) mutation status in B-CLL discordant for ZAP-70/CD38 pointed toward a distinct biologic background of the observed disease subgroups. This finding was also supported by microarray-based gene expression profiling in a subset of 35 patients. The expression of 37 genes differed significantly between the three groups defined by their expression of ZAP-70 and CD38, including genes that are involved in regulation of cell survival and chemotherapy resistance.

222 citations

Journal ArticleDOI
TL;DR: In this paper, an empirical study on an initial learning progression of energy, a concept of central importance to the understanding of science, is presented, which involves recurring cycles of empirical validation and theoretical refinement.
Abstract: This article presents an empirical study on an initial learning progression of energy, a concept of central importance to the understanding of science. Learning progressions have been suggested as one vehicle to support the systematic and successful teaching of core science concepts. Ideally, a learning progression will provide teachers with a framework to assess students' level of understanding of a core concept and to guide students towards a more sophisticated level of understanding. Taking existing research as a point of departure, developing a learning progression involves recurring cycles of empirical validation and theoretical refinement. In this article, we report about our efforts in working towards a learning progression of energy. First, we derived an initial learning progression by utilizing existing curriculum, research on students' understanding, and development of students' understanding of energy. Second, we used these sources of guidance to develop a robust measurement instrument, the Energy Concept Assessment (ECA), based on multiple choice questions. Third, we utilized this instrument to assess the understanding of N = 1,856 students from three different grade levels, Grades 6, 8, and 10. Findings provided evidence that students from Grade 6 mostly obtain an understanding of energy forms and energy sources. Students of Grade 8 additionally demonstrate an understanding of energy transfer and transformation, whereas only students of Grade 10, and then only some of these students, achieve a deeper understanding of energy conservation. We discuss the implications of our findings against the background of existing research on students understanding of energy. Finally, further steps in working towards a learning progression of energy are identified. Zusammenfassung: Der vorliegende Artikel beschreibt den ersten Schritt in der Entwicklung und Validierung einer Learning Progression fur das Energiekonzept; einem Konzept, das zentral fur die Entwicklung eines tiefergehenden Versta¨ndnisses der Naturwissenschaften ist. Learning Progressions sollen das das systematische und erfolgreiche Unterrichten zentraler naturwissenschaftlicher Konzepte unterstutzen. Idealerweise sollen Learning Progressions Lehrkraften eine Rahmen bieten, den Entwicklungsstand ihrer Schulerinnen und Schuler hinsichtlich des Verstandnisses zentraler naturwissenschaftlicher Konzepte einzuschatzen und Unterricht so zu gestalten, dass er die Entwicklung eines elaborierten Verstandnisses befordert. Die Entwicklung einer Learning Progression beginnt mit der theoretischen Begrundung einer vorlaufigen Learning Progression, gefolgt von iterativen Zyklen empirischer Validierung und Uberarbeitung. In diesem Artikel berichten wir uber unsere Arbeiten zur Entwicklung einer Learning Progression fur das Energiekonzept. Im Rahmen dieser Arbeiten wurde zunachst ausgehend von vorliegenden Befunden zum Verstandnis und der Entwicklung des Verstandnisses von Energie eine vorlaufige Learning Progression begrundet. Im zweiten Schritt wurde auf Grundlage der Learning Progression ein entsprechendes Instrument auf Basis von Multiple-Choice-Aufgaben entwickelt – das Energy Concept Assessment (ECA). Im dritten und letzten Schritt wurde das Instrument eingesetzt, um das Verstandnis von Energie bei N = 1856 Schulerinnen und Schulern der Jahrgange 6, 8 und 10 zu erfassen. Die Ergebnisse unserer Untersuchung legen nahe, dass Schulerinnen und Schuler aus Jahrgang 6 im Wesentlichen uber ein Verstandnis von Energieformen und –quellen verfugen. Schulerinnen und Schuler aus Jahrgang 8 zeigen daruber hinaus ein Verstandnis von Energieumwandlung und –transport. Ein Verstandnis von Energieerhaltung ist nur von Schulerinnen und Schuler aus Jahrgang 10 und dann auch nur von einem Teil dieser Schulerinnen und Schuler zu erwarten. Vor dem Hintergrund dieser Ergebnisse und der bisherigen Forschung zum Energieverstandnis, diskutiert der Artikel weitere Schritte fur die die Entwicklung einer Learning Progression fur das Energiekonzept. © 2012 Wiley Periodicals, Inc. J Res Sci Teach 50:162–188, 2013

222 citations

Journal ArticleDOI
TL;DR: Reduced-intensity conditioning results in a similar incidence of non-relapse mortality and reduced toxic effects compared with standard conditioning without affecting survival outcomes, and thus could be preferentially used in patients younger than 60 years with acute myeloid leukaemia transplanted in first complete remission.
Abstract: Summary Background Reduced-intensity conditioning regimens have been developed to minimise early toxic effects and deaths after allogeneic haemopoietic cell transplantation. However, the efficacy of these regimens before this procedure has not been investigated in a randomised trial. In this prospective, open-label randomised phase 3 trial we compared a reduced-intensity fludarabine-based conditioning regimen with a standard regimen in patients with acute myeloid leukaemia in first complete remission. Methods Patients were aged 18–60 years and had intermediate-risk or high-risk acute myeloid leukaemia (defined by cytogenetics) in first complete remission; an available HLA-matched sibling donor or an unrelated donor with at least nine of ten HLA alleles; and adequate renal, cardiac, pulmonary, and neurological function. Between Nov 15, 2004, and Dec 31, 2009, patients were randomly assigned (1:1, by a computer-based minimisation procedure that balanced patients for age, cytogenetic risk, induction therapy, and donor type) to receive either reduced-intensity conditioning of four doses of 2 Gy of total-body irradiation and 150 mg/m 2 fludarabine or standard conditioning of six doses of 2 Gy of total-body irradiation and 120 mg/kg cyclophosphamide. All patients were given ciclosporin and methotrexate as prophylaxis against graft-versus-host disease. Neither investigators nor patients were blinded to study treatment. Our primary endpoint was the incidence of non-relapse mortality, analysed in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT00150878. Findings The trial was stopped early on Dec 31, 2009, because of slow accrual of patients. 99 patients were randomly assigned to receive reduced-intensity conditioning and 96 to receive standard conditioning. The incidence of non-relapse mortality did not differ between the reduced-intensity and standard conditioning groups (cumulative incidence at 3 years 13% [95% CI 6–21] vs 18% [10–26]; HR 0·62 [95% CI 0·30–1·31]). Relapse incidence (cumulative incidence 3 years 28% [95% CI 19–38] vs 26% [17–36]; HR 1·10 [95% CI 0·63–1·90]), disease-free survival (3 year disease-free survival 58% [95% CI 49–70] vs 56% [46–67]; HR 0·85 [95% CI 0·55–1·32]), and overall survival (3 year overall survival 61% [95% CI 50–74] vs 58% [47–70]; HR 0·77 [95% CI 0·48–1·25]) did not differ significantly between groups. Grade 3–4 of oral mucositis was less common in the reduced-intensity group than in the standard conditioning group (50 patients in the reduced-intensity conditioning group vs 73 patients in the standard conditioning group); the frequency of other side-effects such as graft-versus-host disease and increased concentrations of bilirubin and creatinine did not differ significantly between groups. Interpretation Reduced-intensity conditioning results in a similar incidence of non-relapse mortality and reduced toxic effects compared with standard conditioning without affecting survival outcomes, and thus could be preferentially used in patients younger than 60 years with acute myeloid leukaemia transplanted in first complete remission. Funding Medical Faculty of Dresden University.

221 citations

Journal ArticleDOI
TL;DR: Differences in Treg-mediated suppression contribute to the clinical response to cetuximab treatment, suggesting its improvement by adding ipilimumab or other strategies of Treg ablation to promote antitumor immunity.
Abstract: The EGFR-targeted antibody cetuximab is effective against head and neck cancer (HNSCC), but in only 15% to 20% of patients, and the variability and extent of cetuximab-mediated cellular immunity is not fully understood. We hypothesized that regulatory T cells (Treg) may exert a functional and clinical impact on antitumor immunity in cetuximab-treated individuals. The frequency, immunosuppressive phenotype, and activation status of Treg and natural killer (NK) cells were analyzed in the circulation and tumor microenvironment of cetuximab-treated patients with HNSCC enrolled in a novel neoadjuvant, single-agent cetuximab clinical trial. Notably, cetuximab treatment increased the frequency of CD4(+)FOXP3(+) intratumoral Treg expressing CTLA-4, CD39, and TGFβ. These Treg suppressed cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) and their presence correlated with poor clinical outcome in two prospective clinical trial cohorts. Cetuximab expanded CTLA-4(+)FOXP3(+) Treg in vitro, in part, by inducing dendritic cell maturation, in combination with TGFβ and T-cell receptor triggering. Importantly, cetuximab-activated NK cells selectively eliminated intratumoral Treg but preserved effector T cells. In ex vivo assays, ipilimumab targeted CTLA-4(+) Treg and restored cytolytic functions of NK cells mediating ADCC. Taken together, our results argue that differences in Treg-mediated suppression contribute to the clinical response to cetuximab treatment, suggesting its improvement by adding ipilimumab or other strategies of Treg ablation to promote antitumor immunity.

221 citations


Authors

Showing all 16364 results

NameH-indexPapersCitations
Rui Zhang1512625107917
Olli T. Raitakari1421232103487
Anders Hamsten13961188144
Robert Huber13967173557
Christopher T. Walsh13981974314
Patrick D. McGorry137109772092
Stanley Nattel13277865700
Luis M. Liz-Marzán13261661684
Dirk Schadendorf1271017105777
William Wijns12775295517
Raimund Erbel125136474179
Khalil Amine11865250111
Hans-Christoph Diener118102591710
Bruce A.J. Ponder11640354796
Andre Franke11568255481
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023117
2022496
20213,694
20203,449
20193,155
20182,761