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  • 11
    Keywords: OPTIMIZATION ; AGENTS ; Germany ; MODEL ; PERFUSION ; CT ; imaging ; TISSUE ; computed tomography ; TIME ; QUALITY ; CONTRAST ; SIMULATION ; CONTRAST AGENT ; FLOW ; MRI ; MAGNETIC-RESONANCE ; magnetic resonance imaging ; HUMANS ; tomography ; COMPUTED-TOMOGRAPHY ; CONTRAST AGENTS ; MAGNETIC-RESONANCE ANGIOGRAPHY ; gadobenate dimeglumine ; ANGIOGRAPHY ; GD-DTPA ; dynamic MRI ; resonance imaging ; ENHANCEMENT ; computer simulation ; methods ; IMAGE QUALITY ; MULTIDETECTOR-ROW CT ; TIMES ; COMPUTED TOMOGRAPHIC ANGIOGRAPHY ; Lead ; BENEFIT ; RELAXIVITY ; 1.0 M GADOBUTROL ; bolus kinetics ; concentration ; DIFFERENT IODINE CONCENTRATIONS ; dose ; INJECTION RATES ; M GADOPENTETATE DIMEGLUMINE
    Abstract: Objectives: First pass contrast-enhanced magnetic resonance imaging (MRI) and computed tomography (CT) are influenced by parameters that characterize the injected bolus. The aim of this study was to assess the role of contrast agent concentration and the differences between MRI and CT. Material and Methods: We systematically evaluated the published literature to define the differences between MRI and CT with regards to the influence of contrast agent concentration and flow rate on signal enhancement and image quality. Subsequently, we used a simulation model to simulate bolus dispersion in the human body for contrast agents with different concentration. We performed this simulation for different injection times (3-25 seconds) as well as for single and double contrast agent dose, and calculated the effect of contrast agent concentration and dose on the increase of local contrast agent concentration. Results: Although CT studies have shown that even a moderate increase in contrast agent concentration leads to higher peak concentration in the tissue or artery of interest, MRI studies have failed to show a marked benefit of higher concentration. The simulation demonstrated that the use of high concentrated contrast agent leads to an increase in local contrast agent concentration within the tissue or artery of interest, only if injection time is long (in CT commonly 〉10 seconds) compared with the time constant of bolus dispersion (about 5 seconds in humans). If the injection time is shorter (in MRI commonly 1-4 seconds), the local contrast agent concentration is mainly affected by the injected dose. Conclusion: Contrast agent concentration is a key parameter for the optimization of dynamic imaging techniques such as angiography or perfusion in CT, whereas in dynamic MRI, contrast agent dose and relaxivities are the leading parameters
    Type of Publication: Journal article published
    PubMed ID: 20661143
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  • 12
  • 13
    Abstract: Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR), cetuximab and panitumumab, are a mainstay of metastatic colorectal cancer (mCRC) treatment. However, a significant number of patients suffer from primary or acquired resistance. RAS mutations are negative predictors of clinical efficacy of anti-EGFR antibodies in patients with mCRC. Oncogenic RAS activates the MAPK and PI3K/AKT pathways, which are considered the main effectors of resistance. However, the relative impact of these pathways in RAS-mutant CRC is less defined. A better mechanistic understanding of RAS-mediated resistance may guide development of rational intervention strategies. To this end we developed cancer models for functional dissection of resistance to anti-EGFR therapy in vitro and in vivo. To selectively activate MAPK- or AKT-signaling we expressed conditionally activatable RAF-1 and AKT in cancer cells. We found that either pathway independently protected sensitive cancer models against anti-EGFR antibody treatment in vitro and in vivo. RAF-1- and AKT-mediated resistance was associated with increased expression of anti-apoptotic BCL-2 proteins. Biomarkers of MAPK and PI3K/AKT pathway activation correlated with inferior outcome in a cohort of mCRC patients receiving cetuximab-based therapy. Dual pharmacologic inhibition of PI3K and MEK successfully sensitized primary resistant CRC models to anti-EGFR therapy. In conclusion, combined targeting of MAPK and PI3K/AKT signaling, but not single pathways, may be required to enhance the efficacy of anti-EGFR antibody therapy in patients with RAS-mutated CRC as well as in RAS wild type tumors with clinical resistance.
    Type of Publication: Journal article published
    PubMed ID: 28507280
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  • 14
    Abstract: PURPOSE: DNA damage-induced cell death is a major effector mechanism of radiotherapy. Aberrant expression of anti-apoptotic BCL-2 family proteins is frequently observed in lung cancers. Against this background, we studied radioresistance mediated by BCL-2 family proteins at the mechanistic level and its potential as target for radiochemotherapy. METHODS: Lung cancer models stably expressing BCL-xL or MCL-1 were irradiated to study cell death, clonogenic survival, and DNA repair kinetics in vitro, and growth suppression of established tumors in vivo. Additionally, endogenous BCL-xL and MCL-1 were targeted by shRNA or pharmacologic agents prior to irradiation. RESULTS: Radiation exposure induced apoptosis at negligible levels. Yet, anti-apoptotic BCL-xL and MCL-1 expression conferred short-term and long-term radioresistance in vitro and in vivo. Radioresistance correlated with pertubations in homologous recombination repair and repair of DNA double-strand breaks by error-prone, alternative end-joining. Notably, genetic or pharmacologic targeting of BCL-xL or MCL-1 effectively sensitized lung cancer cells to radiotherapy. CONCLUSIONS: In addition to directly suppressing apoptosis, BCL-2 family proteins confer long-term survival benefits to irradiated cancer cells associated with utilization of error-prone repair pathways. Targeting BCL-xL and MCL-1 is an attractive strategy for improving lung cancer radiotherapy.
    Type of Publication: Journal article published
    PubMed ID: 28432456
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  • 15
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  53. Kongress der Deutschen Gesellschaft für Handchirurgie; 20121011-20121013; Lübeck; DOC12dgh71 /20121009/
    Publication Date: 2012-10-10
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 16
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  16. Deutscher Kongress für Versorgungsforschung (DKVF); 20171004-20171006; Berlin; DOCV156 /20170926/
    Publication Date: 2017-09-26
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 17
    Publication Date: 2017-11-15
    Description: Aim: This article focuses on the gender-specific career differences of residents in their postgraduate medical education in Germany. In particular the structural obstacles female physicians have to overcome during residency are investigated. Moreover, the study examines the position preferences of male and female physicians in the hospital and in how far occupational self-efficacy corresponds to the interest in a hospital leading position.Methods: The KarMed-Study's database consists of annual postal surveys throughout the entire residency of medical students, who were in their "Practical Year" in 2008/2009. Descriptive statistics and regression models were used in the analysis.Results: Male and female physicians differ in terms of their preferred work place (hospital, ambulatory care, others), hospital position and working hours. Female physicians prefer part-time work and rarely assume leading positions compared to male physicians. In addition, female physicians, especially those with children, need more time to complete their postgraduate training. Female physicians with children are burdened and disadvantaged more often than their female colleagues without children as well as male physicians in general (e.g. belated start and completion of residency, lower rate of doctorate titles, higher quota of part-time contracts, short-term employment contracts, and higher rates of residency interruption or termination). Besides gender and doctorate title, the occupational self-efficacy expectation has an influence on the preference of leading positions in hospitals. Respondents with a low occupational self-efficacy score are less likely to strive for leading positions with more responsibilities than those with a high score. Conclusion: The results demonstrate clear gender disparities in postgraduate training. Female physicians, especially those with children, are disadvantaged in various areas when compared with their male colleagues. In particular, the low rate of doctorate titles and the low score of self-efficacy expectation are associated negatively with the willingness to aim at leading positions in hospitals. Special measures and programmes should be developed for female physicians to counteract these differences.
    Description: Zielsetzung: Der Artikel befasst sich mit den geschlechtsspezifischen Karriereunterschieden von Ärztinnen und Ärzten in der fachärztlichen Weiterbildung. Untersucht wird, welche strukturellen Hindernisse insbesondere die Ärztinnen in der Weiterbildung erleben. Zudem soll nach Unterschieden zwischen den Geschlechtern bezüglich der Positionspräferenz im Krankenhaus gesucht werden. Ferner wird geprüft, inwiefern die berufliche Selbstwirksamkeit mit dem Interesse an einer leitenden Position im Krankenhaus nach der Weiterbildung korrespondiert.Methodik: Datenbasis der Studie sind die jährlichen postalischen Befragungen einer Kohorte von PJ-Studierenden des Jahrgangs 2008/09, die während der gesamten Weiterbildungsdauer verfolgt wird. Für die Auswertung wurden deskriptive Statistiken und Regressionen angewandt.Ergebnisse: Ärztinnen und Ärzte unterscheiden sich hinsichtlich ihrer Präferenzen für Versorgungssektor, Position und Arbeitszeit nach der fachärztlichen Weiterbildung: Ärztinnen präferieren weit öfter als Ärzte eine Arbeit in Teilzeit und möchten weniger oft Leitungspositionen im Krankenhaus übernehmen. Zudem brauchen Ärztinnen meist länger für die Weiterbildung, insbesondere dann, wenn sie Mutter sind. Ärztinnen mit Kind sind auch in anderen Bereichen stärker belastet und benachteiligt als ihre Kolleginnen ohne Kind sowie männlichen Kollegen generell (verspäteter Weiterbildungsbeginn und -abschluss; geringere Promotionsrate; höhere Quote an Teilzeitverträgen, kürzere Arbeitsverträge, Unterbrechungs- und Abbruchraten). Neben Geschlecht und Promotion hat die berufliche Selbstwirksamkeitserwartung (BSWE) einen Einfluss auf die Präferenz von Leitungspositionen im Krankenhaus - Befragte mit einem geringen BSWE-Score streben seltener Leitungspositionen an als jene mit hoher BSWE.Schlussfolgerung: Die Ergebnisse zeigen klare geschlechterspezifische Unterschiede in der fachärztlichen Weiterbildung. Ärztinnen sind in verschiedenen Bereichen stärker belastet als Ärzte, insbesondere Ärztinnen mit Kind. Speziell die geringere Promotionsrate und der BSWE-Score der Ärztinnen sind negativ mit der Bereitschaft assoziiert, eine Leitungsposition im Krankenhaus zu übernehmen. Um diesen Differenzen zu begegnen, sollten spezifische Maßnahmen und Programme für Ärztinnen entwickelt werden.
    Keywords: Postgraduate medical education ; gender roles ; hospital ; working time ; self-efficacy ; Fachärztliche Weiterbildung ; Berufswahl ; Krankenhaus ; Arbeitszeiten ; Selbstwirksamkeit ; ddc: 610
    Language: English
    Type: article
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  • 18
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Bad Honnef-Symposium 2015; 20150330-20150331; Königswinter; DOC15bhs23 /20150320/
    Publication Date: 2015-03-21
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 19
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  53. Kongress der Deutschen Gesellschaft für Handchirurgie; 20121011-20121013; Lübeck; DOC12dgh72 /20121009/
    Publication Date: 2012-10-10
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 20
    ISSN: 0168-583X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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