TY - JOUR A1 - Asare-Kyei, Daniel A1 - Forkuor, Gerald A1 - Venus, Valentijn T1 - Modeling Flood Hazard Zones at the Sub-District Level with the Rational Model Integrated with GIS and Remote Sensing Approaches JF - Water N2 - Robust risk assessment requires accurate flood intensity area mapping to allow for the identification of populations and elements at risk. However, available flood maps in West Africa lack spatial variability while global datasets have resolutions too coarse to be relevant for local scale risk assessment. Consequently, local disaster managers are forced to use traditional methods such as watermarks on buildings and media reports to identify flood hazard areas. In this study, remote sensing and Geographic Information System (GIS) techniques were combined with hydrological and statistical models to delineate the spatial limits of flood hazard zones in selected communities in Ghana, Burkina Faso and Benin. The approach involves estimating peak runoff concentrations at different elevations and then applying statistical methods to develop a Flood Hazard Index (FHI). Results show that about half of the study areas fall into high intensity flood zones. Empirical validation using statistical confusion matrix and the principles of Participatory GIS show that flood hazard areas could be mapped at an accuracy ranging from 77% to 81%. This was supported with local expert knowledge which accurately classified 79% of communities deemed to be highly susceptible to flood hazard. The results will assist disaster managers to reduce the risk to flood disasters at the community level where risk outcomes are first materialized. KW - climate change KW - rational model KW - community KW - flood hazard index KW - West Africa KW - GIS KW - vulnerability KW - performance KW - impact KW - risk KW - mapping KW - runoff Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151581 VL - 7 SP - 3531 EP - 3564 ER - TY - JOUR A1 - Brumberg, Joachim A1 - Schröter, Nils A1 - Blazhenets, Ganna A1 - Frings, Lars A1 - Volkmann, Jens A1 - Lapa, Constantin A1 - Jost, Wolfgang H. A1 - Isaias, Ioannis U. A1 - Meyer, Philipp T. T1 - Differential diagnosis of parkinsonism: a head-to-head comparison of FDG PET and MIBG scintigraphy JF - NPJ Parkinsons Disease N2 - [\(^{18}\)F]fluorodeoxyglucose (FDG) PET and [\(^{123}\)I]metaiodobenzylguanidine (MIBG) scintigraphy may contribute to the differential diagnosis of neurodegenerative parkinsonism. To identify the superior method, we retrospectively evaluated 54 patients with suspected neurodegenerative parkinsonism, who were referred for FDG PET and MIBG scintigraphy. Two investigators visually assessed FDG PET scans using an ordinal 6-step score for disease-specific patterns of Lewy body diseases (LBD) or atypical parkinsonism (APS) and assigned the latter to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal syndrome. Regions-of-interest analysis on anterior planar MIBG images served to calculate the heart-to-mediastinum ratio. Movement disorder specialists blinded to imaging results established clinical follow-up diagnosis by means of guideline-derived case vignettes. Clinical follow-up (1.7 +/- 2.3 years) revealed the following diagnoses: n = 19 LBD (n = 17 Parkinson's disease [PD], n = 1 PD dementia, and n = 1 dementia with Lewy bodies), n = 31 APS (n = 28 MSA, n = 3 PSP), n = 3 non-neurodegenerative parkinsonism; n = 1 patient could not be diagnosed and was excluded. Receiver operating characteristic analyses for discriminating LBD vs. non-LBD revealed a larger area under the curve for FDG PET than for MIBG scintigraphy at statistical trend level for consensus rating (0.82 vs. 0.69, p = 0.06; significant for investigator #1: 0.83 vs. 0.69, p = 0.04). The analysis of PD vs. MSA showed a similar difference (0.82 vs. 0.69, p = 0.11; rater #1: 0.83 vs. 0.69, p = 0.07). Albeit the notable differences in diagnostic performance did not attain statistical significance, the authors consider this finding clinically relevant and suggest that FDG PET, which also allows for subgrouping of APS, should be preferred. KW - clinical diagnosis KW - F-18-FDG PET KW - disease KW - dementia KW - accuracy KW - stimulation KW - guidelines KW - criteria KW - brain KW - risk Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230675 VL - 6 ER - TY - JOUR A1 - Drechsler, Christiane A1 - Kolleritz, Barbara A1 - Meinitzer, Andreas A1 - März, Winfried A1 - Ritz, Eberhard A1 - König, Paul A1 - Neyer, Ulrich A1 - Pilz, Stefan A1 - Wanner, Christoph A1 - Kronenberg, Florian T1 - Homoarginine and Progression of Chronic Kidney Disease: Results from the Mild to Moderate Kidney Disease Study JF - PLoS ONE N2 - Background: Homoarginine is an amino acid derivative mainly synthesized in the kidney. It is suggested to increase nitric oxide availability, enhance endothelial function and to protect against cardiovascular diseases. We aimed to investigate the relation between homoarginine, kidney function and progression of chronic kidney disease (CKD). Methods: We measured plasma homoarginine concentrations in baseline samples of the Mild to Moderate Kidney Disease (MMKD) Study, a prospective cohort study of 227 patients with CKD in Europe. Homoarginine concentrations were available in 182 of the baseline samples and in 139 of the prospectively-followed patients. We correlated homoarginine concentrations to parameters of kidney function. The association between homoarginine and progression of CKD was assessed during a follow-up of up to seven years (median 4.45 years, interquartile range 2.54-5.19) using Cox regression analysis. Progression of CKD was defined as doubling of baseline serum creatinine and/or end-stage renal disease. Results: Study participants were at baseline on average 47 \(\pm\)13 years old and 65% were male. Mean \(\pm\) standard deviation of homoarginine concentrations were \(2.5 \pm 1.1 \mu mol/L\) and concentrations were incrementally lower at lower levels of GFR with mean concentrations of \(2.90 \pm 1.02 \mu mol/L\) (GFR. 90 ml/min), \(2.64 \pm 1.06 \mu mol/L\) (GFR 60-90 ml/min), \(2.52 \pm 1.24 \mu mol/L\) (GFR 30-60 ml/min) and \(2.05 \pm 0.78 \mu mol/L\) (GFR, 30 ml/min), respectively (p = 0.002). The age-and sex-adjusted risk to reach the renal endpoint was significantly higher by 62% with each decrease by one standard deviation (\(1.1 \mu mol/L\)) of homoarginine (HR 1.62, 95% CI 1.16-2.27, p = 0.005). This association was independent of proteinuria (HR 1.56, 95% CI 1.11-2.20, p = 0.01), and was slightly attenuated when adjusting for GFR (HR 1.40 (95% CI 0.98-1.98, p = 0.06). Conclusions: Homoarginine concentrations are directly correlated with kidney function and are significantly associated with the progression of CKD. Low homoarginine concentrations might be an early indicator of kidney failure and a potential target for the prevention of disease progression which needs further investigations. KW - risk KW - alkaline phosphatase KW - cardiovascular events KW - nictric-oxide KW - induced insulin-release KW - creatine synthesis KW - renal function KW - heart failure KW - rat kidney KW - L-arginine Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130979 VL - 8 IS - 5 ER - TY - JOUR A1 - Drozd, Valentina M. A1 - Saenko, Vladimir A. A1 - Brenner, Alina V. A1 - Drozdovitch, Vladimir A1 - Pashkevich, Vasilii I. A1 - Kudelsky, Anatoliy V. A1 - Demidchik, Yuri E. A1 - Branovan, Igor A1 - Shiglik, Nikolay T1 - Major Factors Affecting Incidence of Childhood Thyroid Cancer in Belarus after the Chernobyl Accident: Do Nitrates in Drinking Water Play a Role? JF - PLoS One N2 - One of the major health consequences of the Chernobyl Nuclear Power Plant accident in 1986 was a dramatic increase in incidence of thyroid cancer among those who were aged less than 18 years at the time of the accident. This increase has been directly linked in several analytic epidemiological studies to iodine-131 (I-131) thyroid doses received from the accident. However, there remains limited understanding of factors that modify the I-131-related risk. Focusing on post-Chernobyl pediatric thyroid cancer in Belarus, we reviewed evidence of the effects of radiation, thyroid screening, and iodine deficiency on regional differences in incidence rates of thyroid cancer. We also reviewed current evidence on content of nitrate in groundwater and thyroid cancer risk drawing attention to high levels of nitrates in open well water in several contaminated regions of Belarus, i.e. Gomel and Brest, related to the usage of nitrogen fertilizers. In this hypothesis generating study, based on ecological data and biological plausibility, we suggest that nitrate pollution may modify the radiation-related risk of thyroid cancer contributing to regional differences in rates of pediatric thyroid cancer in Belarus. Analytic epidemiological studies designed to evaluate joint effect of nitrate content in groundwater and radiation present a promising avenue of research and may provide useful insights into etiology of thyroid cancer. KW - analysis KW - areas KW - power-station accident KW - iodine nutrition KW - skin hemagioma KW - pooled KW - risk KW - children KW - radiation KW - exposure KW - radiotherapy Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141863 VL - 10 IS - 9 ER - TY - JOUR A1 - Grabenhenrich, Linus B. A1 - Reich, Andreas A1 - Fischer, Felix A1 - Zepp, Fred A1 - Forster, Johannes A1 - Schuster, Antje A1 - Bauer, Carl-Peter A1 - Bergmann, Renate L. A1 - Bergmann, Karl E. A1 - Wahn, Ulrich A1 - Keil, Thomas A1 - Lau, Susanne T1 - The Novel 10-Item Asthma Prediction Tool: External Validation in the German MAS Birth Cohort JF - PLOS ONE N2 - Background: A novel non-invasive asthma prediction tool from the Leicester Cohort, UK, forecasts asthma at age 8 years based on 10 predictors assessed in early childhood, including current respiratory symptoms, eczema, and parental history of asthma. Objective: We aimed to externally validate the proposed asthma prediction method in a German birth cohort. Methods: The MAS-90 study (Multicentre Allergy Study) recorded details on allergic diseases prospectively in about yearly follow-up assessments up to age 20 years in a cohort of 1,314 children born 1990. We replicated the scoring method from the Leicester cohort and assessed prediction, performance and discrimination. The primary outcome was defined as the combination of parent-reported wheeze and asthma drugs (both in last 12 months) at age 8. Sensitivity analyses assessed model performance for outcomes related to asthma up to age 20 years. Results: For 140 children parents reported current wheeze or cough at age 3 years. Score distribution and frequencies of later asthma resembled the Leicester cohort: 9% vs. 16% (MAS-90 vs. Leicester) of children at low risk at 3 years had asthma at 8 years, at medium risk 45% vs. 48%. Performance of the asthma prediction tool in the MAS-90 cohort was similar (Brier score 0.22 vs. 0.23) and discrimination slightly better than in the original cohort (area under the curve, AUC 0.83 vs. 0.78). Prediction and discrimination were robust against changes of inclusion criteria, scoring and outcome definitions. The secondary outcome 'physicians' diagnosed asthma at 20 years' showed the highest discrimination (AUC 0.89). Conclusion: The novel asthma prediction tool from the Leicester cohort, UK, performed well in another population, a German birth cohort, supporting its use and further development as a simple aid to predict asthma risk in clinical settings. KW - disease KW - models KW - symptoms KW - risk KW - early-life KW - young children KW - preschool children KW - sample KW - wheeze KW - age Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114202 SN - 1932-6203 VL - 9 IS - 12 ER - TY - JOUR A1 - Hardcastle, Nicholas A1 - Tomé, Wolfgang A. A1 - Cannon, Donald M. A1 - Brouwer, Charlotte L. A1 - Wittendorp, Paul W. H. A1 - Dogan, Nesrin A1 - Guckenberger, Matthias A1 - Allaire, Stéphane A1 - Mallya, Yogish A1 - Kumar, Prashant A1 - Oechsner, Markus A1 - Richter, Anne A1 - Song, Shiyu A1 - Myers, Michael A1 - Polat, Bülent A1 - Bzdusek, Karl T1 - A multi-institution evaluation of deformable image registration algorithms for automatic organ delineation in adaptive head and neck radiotherapy JF - Radiation Oncology N2 - Background: Adaptive Radiotherapy aims to identify anatomical deviations during a radiotherapy course and modify the treatment plan to maintain treatment objectives. This requires regions of interest (ROIs) to be defined using the most recent imaging data. This study investigates the clinical utility of using deformable image registration (DIR) to automatically propagate ROIs. Methods: Target (GTV) and organ-at-risk (OAR) ROIs were non-rigidly propagated from a planning CT scan to a per-treatment CT scan for 22 patients. Propagated ROIs were quantitatively compared with expert physician-drawn ROIs on the per-treatment scan using Dice scores and mean slicewise Hausdorff distances, and center of mass distances for GTVs. The propagated ROIs were qualitatively examined by experts and scored based on their clinical utility. Results: Good agreement between the DIR-propagated ROIs and expert-drawn ROIs was observed based on the metrics used. 94% of all ROIs generated using DIR were scored as being clinically useful, requiring minimal or no edits. However, 27% (12/44) of the GTVs required major edits. Conclusion: DIR was successfully used on 22 patients to propagate target and OAR structures for ART with good anatomical agreement for OARs. It is recommended that propagated target structures be thoroughly reviewed by the treating physician. KW - intensity-modulated radiotherapy KW - megavoltage computed-tomography KW - cancer KW - variability KW - strategies KW - risk Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134756 VL - 7 IS - 90 ER - TY - JOUR A1 - Kohlhase, Sandra A1 - Bogdanova, Natalia V. A1 - Schürmann, Peter A1 - Bermisheva, Marina A1 - Khusnutdinova, Elza A1 - Antonenkova, Natalia A1 - Park-Simon, Tjoung-Won A1 - Hillemanns, Peter A1 - Meyer, Andreas A1 - Christiansen, Hans A1 - Schindler, Detlev A1 - Dörk, Thilo T1 - Mutation Analysis of the ERCC4/FANCQ Gene in Hereditary Breast Cancer JF - PLOS ONE N2 - The ERCC4 protein forms a structure-specific endonuclease involved in the DNA damage response. Different cancer syndromes such as a subtype of Xeroderma pigmentosum, XPF, and recently a subtype of Fanconi Anemia, FA-Q, have been attributed to biallelic ERCC4 gene mutations. To investigate whether monoallelic ERCC4 gene defects play some role in the inherited component of breast cancer susceptibility, we sequenced the whole ERCC4 coding region and flanking untranslated portions in a series of 101 Byelorussian and German breast cancer patients selected for familial disease (set 1, n = 63) or for the presence of the rs1800067 risk haplotype (set 2, n = 38). This study confirmed six known and one novel exonic variants, including four missense substitutions but no truncating mutation. Missense substitution p.R415Q (rs1800067), a previously postulated breast cancer susceptibility allele, was subsequently screened for in a total of 3,698 breast cancer cases and 2,868 controls from Germany, Belarus or Russia. The Gln415 allele appeared protective against breast cancer in the German series, with the strongest effect for ductal histology (OR 0.67; 95%CI 0.49; 0.92; p = 0.003), but this association was not confirmed in the other two series, with the combined analysis yielding an overall Mantel-Haenszel OR of 0.94 (95% CI 0.81; 1.08). There was no significant effect of p.R415Q on breast cancer survival in the German patient series. The other three detected ERCC4 missense mutations included two known rare variants as well as a novel substitution, p.E17V, that we identified on a p.R415Q haplotype background. The p.E17V mutation is predicted to be probably damaging but was present in just one heterozygous patient. We conclude that the contribution of ERCC4/FANCQ coding mutations to hereditary breast cancer in Central and Eastern Europe is likely to be small. KW - ERCC1-XPF KW - susceptibility loci KW - ERCC4 KW - genome-wide association KW - fanconi-anemia KW - ATM gene KW - endonuclease KW - risk KW - requency KW - variants Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117582 VL - 9 IS - 1 ER - TY - THES A1 - Lohr, Andreas T1 - Risikostratifikation grosszelliger B-Zell Non-Hodgkin Lymphome anhand immunhistochemischer Parameter T1 - Risk-stratification of diffuse large B-cell lymphomas by immunohistochemical parameters N2 - Die diffusen großzelligen B-Zell-Lymphome (DLBCL) stellen den häufigsten Typ aller Non-Hodgkin-Lymphome dar, sind aber morphologisch, immunologisch, genetisch und klinisch eine sehr heterogene Gruppe. Aufgrund dieser Heterogenität von DLBCL wurde in mehreren Studien untersucht, ob eine molekulare Heterogenität der Tumoren vorläge, bzw. versucht, eine molekulare Reklassifikation zu erreichen. Resultat dieser Bemühungen war eine Unterscheidung bzw. Definition einer Keimzentrums- ähnlichen (GCB-cell-like) Gruppe und einer aktivierten B-Zellen-ähnlichen (ABC-like) Gruppe, die sich in ihrem Ansprechen auf übliche Therapieschemata, mit einer deutlich besseren Prognose für die GCB-like-Gruppe, unterschieden. Die hierbei angewendete Microarray-Technologie hat den entscheidenden Nachteil, dass hierfür qualitativ hochwertige RNA zur Verfügung stehen muss. Neu ist der Ansatz, unterschiedliche Proteinexpressionsmuster am Paraffinmaterial zur Unterscheidung prognostisch relevanter Gruppen heranzuziehen. Die hierbei erzielten Daten sind allerdings in Ihren Aussagen hinsichtlich der prognostischen Wertigkeiten widersprüchlich. In der vorliegenden Arbeit wurden zunächst verschiedene biologische Parameter am Paraffinmaterial hinsichtlich ihrer prognostischen Wertigkeit in der Risikostratifikation von DLBCL untersucht. In einem ersten Schritt wurden klinische Daten von 99 de novo entstandenen großzelligen B-Zell-Lymphomen erhoben, bei denen es sich um 84 DLBCL und um elf DLBCL mit einer weiteren Komponente eines follikulären Lymphoms Grad 3B bzw. auch um vier Fälle mit ausschließlich follikulärem Wachstumsmuster handelte. Die Klassifikation der Fälle nach dem Internationalen Prognostischen Index (IPI) sowie der einzelnen klinischen Parameter des IPI zeigte eine deutliche prognostische Relevanz. In einem zweiten Schritt wurden immunhistochemische Färbungen mit verschiedenen Antikörpern durchgeführt und auf ihre prognostische Bedeutung überprüft. Als negative prognostische Parameter erwiesen sich die Negativität für CD10 sowie BCL-6, also Antigene, die mit einer Keimzentrumszell-Differenzierung assoziiert werden, sowie eine Überexpression von MUM-1, das mit einer postfollikulären Differenzierung assoziiert wird. Weiterhin konnte gezeigt werden, dass einer Expression von BCL-2 und einem Ki67-Index von unter 80 % eine negative prognostische Bedeutung zukommt. Die Stratifikation der Fälle in einen GCB- und einen ABC- Typ anhand des Hans-Klassifikators zeigte nur eine schwache Korrelation zur Überlebenswahrscheinlichkeit. In einem dritten Schritt wurde gezeigt, dass die kombinierte Analyse jeweils zweier Parameter eine relative Abhängigkeit ihrer Expression von der Expression weiterer Marker erkennen ließ. Aus diesem Grunde wurde ein Modell einer sequentiellen Addition negativer prognostischer Indikatoren entwickelt, in der bei Anwesenheit einer negativen Variable (CD10-Negativität, BCL-6 < 20%, BCL-2 positiv, MUM-1≥ 50% und Ki67 < 80%) ein negativer Faktor gewertet und die Summe dieser als Risiko-Score angegeben wurde. Die Stratifikation der Patienten anhand dieses „kombinierten immunhistochemischen Risiko-Scores“ zeigte drei prognostisch deutlich unterschiedliche Gruppen: In der Gruppe von Patienten ohne Risikofaktoren verstarb lediglich eine Patientin (die eine Behandlung abgelehnt hatte); in der Hochrisikogruppe (Score 5) verstarben alle Patienten innerhalb eines Jahres. Die multivariate Analyse des Scores ergab dabei eine Unabhängigkeit von den Parametern des IPI. In der intermediären Gruppe mit einem Risiko-Score von 1-4 zeigten sich der IPI sowie eine LDH-Erhöhung und das Vorhandensein einer B-Symptomatik als geeignete Parameter, um hier eine weitere Stratifizierung durchzuführen. Die vorliegende Arbeit stellt somit eine Erweiterung der publizierten Ansätze einer Erfassung prognostischer Indikatoren in kombinierten Algorithmen dar. Eine Verifizierung der gezeigten Ergebnisse in einer homogen behandelten Patientengruppe innerhalb einer klinischen Studie muss Ziel weiterer Untersuchungen sein. N2 - Diffuse large B-cell Lymphomas (DLBCL)are heterogeneous in morphologic, immunologic, genetic and clinical features. In different studies a molecular reclassification of this hetreogeneous group has been tried to establish, defining a germinal center B-cell-like group (GCB)and a activated B-cell-like group (ABC), with a better prognosis for the GCB-like group in responding to chemotherapy. Another way to differentiate prognostically relevant groups in DLBCL is by getting different protein expression patterns by using paraffin embedded material. In this study different biological parameters were analysed for their prognostic relevance. Clinical data of 99 de novo large B-cell lymphomas was collected, including 84 DLBCL, 11 DLBCL with a component of a follicular lymphoma grade 3B and 4 lamphomas with only a follicular growth pattern. Classification using the International Prognostic Index and its items in particular showed a significant clinical relevance. In a second step immunohistochemically revealed antibodies were examined for their prognostically relevance. As negative prognostic factors were found CD10-negativity and bcl-6, both beeing associated with a germinal center- differentiation. Another negative prognostic factor was MUM-1-overexpression, beeing associated with a postfollicular differentiation. Expression of bcl-2 und a Ki67-index below 80% indicated a negative prognosis as well. Stratification by using the Hans-Classificator showed a non-significant correlation of overall survival. In a third step a combined analysis of the parameters by looking for prognostic significance showed that the expression of one parameter was dependent of the expression of other parameters. Therefore a score was developed by using a sequentially addition of every negative prognostic factor (CD10-negativitiy, bcl-6 <20%, Bcl-2-positivity, MUM-1 >=50% and Ki67 <80%). Stratification of the patients using this "combined immunohistochemical risc score" showed three significantly different groups: In the group without any risc factor only one patient died (who had denied any treatment), in the high risk group (score 5) all patients died within one year. Multivariate analysis of the score showed independence of the IPI-parameters. In the intermediate risk group (score 1-4) the IPI-parameters as well as high LDH-levels and any B-symptoms were useful to make a further risk stratification. The present study extends the studies published trying to find prognostic indicators in combined algorithms. Verification of the presented results by a homogeneous treated patient group using a controlled clinical study has to be evaluated in further studies. KW - B-cell Lymphome KW - Überleben KW - immunhistochemisch KW - großzellige KW - Risiko KW - DLBCL KW - immunohistochemistry KW - risk KW - stratification KW - b-cell lymphomas Y1 - 2007 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-23654 ER - TY - CHAP A1 - Lutz, Werner K. T1 - Dose-response relationships in chemical carcinogenesis: from DNA adducts to tumor incidence N2 - Mechanistic possibilitles responsible for nonlinear shapes of the dose-response relationship in chemical carcinogenesis are discussed. (i) Induction and saturation of enzymatic activation and detoxification processes and of DNA repair affect the relationship between dose and steady-state DNA adduct Ievel; (ii) The fixation of DNA adducts in the form of mutations is accelerated by stimulation of the cell division, for Jnstance due to regenerative hyperplasia at cytotoxic dose Ievels; (iii) The rate of tumor formation results from a superposition of the rates of the individual steps. It can become exponential with dose if more than one step is accelerated by the DNA damage exerted by the genotoxic carcinogen. The strongly sigmoidal shapes often observed for dose-tumor incidence relationships in animal bioassays supports this analysis. A power of four for the dose in the su~linear part of the curve is the maximum observed (formaldehyde). In contrast to animal experiments, epidemiological data ln humans rarely show a slgnificant deviation from linearity. The discrepancy might be explained by the fact that a I arge nu mber of genes contribute to the overall sensitivity of an individual and to the respective heterogeneity within the human population. Mechanistic nonlinearities are flattened out in the presence of genetic and life-style factors which affect the sensitivity for the development of cancer. For a risk assessment, linear extrapolation from the high-dose lncidence to the spontaneaus rate can therefore be approprlate in a heterogeneous population even if the mechanism of action would result in a nonlinear shape of the dose-response curve in a homogeneaus population. KW - aflatoxin B1 KW - 2-acetylaminofluorene KW - DNA KW - adduct KW - covalent KW - binding KW - carcinogen KW - dose KW - extrapolation KW - individual KW - susceptibility KW - heterogeneous population KW - risk KW - tumour Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-71625 ER - TY - JOUR A1 - Marenholz, Ingo A1 - Esparza-Gordillo, Jorge A1 - Rüschendorf, Franz A1 - Bauerfeind, Anja A1 - Strachan, David P. A1 - Spycher, Ben D. A1 - Baurecht, Hansjörg A1 - Magaritte-Jeannin, Patricia A1 - Sääf, Annika A1 - Kerkhof, Marjan A1 - Ege, Markus A1 - Baltic, Svetlana A1 - Matheson, Melanie C. A1 - Li, Jin A1 - Michel, Sven A1 - Ang, Wei Q. A1 - McArdle, Wendy A1 - Arnold, Andreas A1 - Homuth, Georg A1 - Demenais, Florence A1 - Bouzigon, Emmanuelle A1 - Söderhäll, Cilla A1 - Pershagen, Göran A1 - de Jongste, Johan C. A1 - Postma, Dirkje S. A1 - Braun-Fahrländer, Charlotte A1 - Horak, Elisabeth A1 - Ogorodova, Ludmila M. A1 - Puzyrev, Valery P. A1 - Bragina, Elena Yu A1 - Hudson, Thomas J. A1 - Morin, Charles A1 - Duffy, David L. A1 - Marks, Guy B. A1 - Robertson, Colin F. A1 - Montgomery, Grant W. A1 - Musk, Bill A1 - Thompson, Philip J. A1 - Martin, Nicholas G. A1 - James, Alan A1 - Sleiman, Patrick A1 - Toskala, Elina A1 - Rodriguez, Elke A1 - Fölster-Holst, Regina A1 - Franke, Andre A1 - Lieb, Wolfgang A1 - Gieger, Christian A1 - Heinzmann, Andrea A1 - Rietschel, Ernst A1 - Keil, Thomas A1 - Cichon, Sven A1 - Nöthen, Markus M. A1 - Pennel, Craig E. A1 - Sly, Peter D. A1 - Schmidt, Carsten O. A1 - Matanovic, Anja A1 - Schneider, Valentin A1 - Heinig, Matthias A1 - Hübner, Norbert A1 - Holt, Patrick G. A1 - Lau, Susanne A1 - Kabesch, Michael A1 - Weidinger, Stefan A1 - Hakonarson, Hakon A1 - Ferreira, Manuel A. R. A1 - Laprise, Catherine A1 - Freidin, Maxim B. A1 - Genuneit, Jon A1 - Koppelman, Gerard H. A1 - Melén, Erik A1 - Dizier, Marie-Hélène A1 - Henderson, A. John A1 - Lee, Young Ae T1 - Meta-analysis identifies seven susceptibility loci involved in the atopic march JF - Nature Communications N2 - Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P = 2.1 x 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P = 5.3 x 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema. KW - chromosome 11Q13 KW - risk KW - genomewide association KW - hay fever KW - birth cohort KW - filaggrin mutations KW - food allergy KW - juvenile myoclonic epilepsy KW - childhood asthma KW - dermatitis Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139835 VL - 6 IS - 8804 ER - TY - THES A1 - Reeg, Johannes T1 - Empirical Studies of Contemporaneous Banking Research T1 - Empirische Studien aktueller Bankenforschung N2 - Banks perform important functions for the economy. Besides financial intermediation, banks provide information, liquidity, maturity- and risk-transformation (Fama, 1985). Banks ensure the transfer of liquidity from depositors to the most profitable investment projects. In addition, they perform important screening and monitoring services over investments hence contributing steadily to the efficient allocation of resources across the economy (Pathan and Faff, 2013). Since banks provide financial services all across the economy, this exposes banks (as opposed to non-banks) to systemic risk: the recent financial crisis revealed that banks can push economies into severe recessions. However, the crisis also revealed that certain bank types appear far more stable than others. For instance, cooperative banks performed better during the crisis than commercial banks. Different business models may reason these performance-differences: cooperative banks focus on relationship lending across their region, hence these banks suffered less from the collapse of the US housing market. Since cooperative banks performed better during the crisis than commercial banks, it is quite surprising that research concerning cooperative banks is highly underrepresented in the literature. For this reason, the following three studies aim to contribute to current literature by examining three independent contemporaneous research questions in the context of cooperative banks. Chapter 2 examines whether cooperative banks benefit from revenue diversification: Current banking literature reveals the recent trend in the overall banking industry that banks may opt for diversification by shifting their revenues to non-interest income. However, existing literature also shows that not every bank benefits from revenue diversification (Mercieca et al., 2007; Stiroh and Rumble, 2006; Goddard et al., 2008). Stiroh and Rumble (2006) find that large commercial banks (US Financial Holding Companies) perceive decreasing performance by shifting revenues towards non-interest income. Revenues from cooperative banks differ from those of commercial banks: commercial banks trade securities and derivatives, sell investment certificates and other trading assets. Concerning the lending business, commercial banks focus on providing loans for medium-sized and large companies rather than for small (private) customers. Cooperative banks rely on commission income (fees) from monetary transactions and selling insurances as a source of non-interest income. They generate most of their interest income by providing loans to small and medium-sized companies as well as to private customers in the region. These differences in revenues raise the question whether findings from Stiroh and Rumble (2006) apply to cooperative banks. For this reason, Chapter 2 evaluates a sample of German cooperative banks over the period 2005 to 2010 and aims to investigate the following research question: which cooperative banks benefit from revenue diversification? Results show that findings from Stiroh and Rumble (2006) do not apply to cooperative banks. Revenue concentration is positive related to risk-adjusted returns (indirect effect) for cooperative banks. At the same time, non-interest income is more profitable than interest income (direct effect). The evaluation of the underlying non-interest income share shows that banks who heavily focus on non-interest income benefit by shifting towards non-interest income. This finding arises due to the fact, that the positive direct effect dominates the negative indirect effect, leading in a positive (and significant) net effect. Furthermore, results reveal a negative net effect for banks who are heavily exposed to interest generating activities. This indicates that shifting to non-interest income decreases risk-adjusted returns for these banks. Consequently, these banks do better by focusing on the interest business. Overall, results show evidence that banks need time to build capabilities, expertise and experience before trading off return and risk efficiently with regard on revenue diversification. Chapter 3 deals with the relation between credit risk, liquidity risk, capital risk and bank efficiency: There has been rising competition in the European banking market due to technological development, deregulation and the introduction of the Euro as a common currency in recent decades. In order to remain competitive banks were forced to improve efficiency. That is, banks try to operate closer to a “best practice” production function in the sense that banks improve the input – output relation. The key question in this context is if banks improve efficiency at a cost of higher risk to compensate decreasing earnings. When it comes to bank risk, a large strand of literature discusses the issue of problem loans. Several studies identify that banks hold large shares of non-performing loans in their portfolio before becoming bankrupt (Barr and Siems, 1994; Demirgüc-Kunt, 1989). According to efficiency, studies show that the average bank generates low profits and incorporates high costs compared to the “best practice” production frontier (Fiordelisi et al., 2011; Williams, 2004). At first glance, these two issues do not seem related. However, Berger and DeYoung (1997) show that banks with poor management are less able to handle their costs (low cost-efficiency) as well as to monitor their debtors in an appropriate manner to ensure loan quality. The negative relationship between cost efficiency and non-performing loans leads to declining capital. Existing studies (e.g. Williams, 2004; Berger and DeYoung, 1997) show that banks with a low level of capital tend to engage in moral hazard behavior, which in turn can push these banks into bankruptcy. However, the business model of cooperative banks is based on the interests of its commonly local customers (the cooperative act: § 1 GenG). This may imply that the common perception of banks engaging in moral hazard behavior may not apply to cooperative banks. Since short-term shareholder interests (as a potential factor for moral hazard behavior) play no role for cooperative banks this may support this notion. Furthermore, liquidity has been widely neglected in the existing literature, since the common perception has been that access to additional liquid funds is not an issue. However, the recent financial crisis revealed that liquidity dried up for many banks due to increased mistrust in the banking sector. Besides investigating moral hazard behavior, using data from 2005 to 2010 this study moves beyond current literature by employing a measure for liquidity risk in order to evaluate how liquidity risk relates to efficiency and capital. Results mostly apply to current literature in this field since the empirical evaluation reveals that lower cost and profit-efficiency Granger-cause increases in credit risk. At the same time, results indicate that credit risk negatively Granger-causes cost and profit-efficiency, hence revealing a bi-directional relationship between these measures. However, most importantly, results also show a positive relationship between capital and credit risk, thus displaying that moral hazard behavior does not apply to cooperative banks. Especially the business model of cooperative banks, which is based on the interests of its commonly local customers (the cooperative act: § 1 GenG) may reason this finding. Contrary to Fiordelisi et al. (2011), results also show a negative relationship between capital and cost-efficiency, indicating that struggling cooperative banks focus on managing their cost-exposure in following periods. Concerning the employed liquidity risk measure, the authors find that banks who hold a high level of liquidity are less active in market related investments and hold high shares of equity capital. This outcome clearly reflects risk-preferences from the management of a bank. Chapter 4 examines governance structures of cooperative banks: The financial crisis of 2007/08 led to huge distortions in the banking market. The failure of Lehman Brothers was the beginning of government interventions in various countries all over the world in order to prevent domestic economies from even further disruptions. In the aftermath of the crisis, politicians and regulators identified governance deficiencies as one major factor that contributed to the crisis. Besides existing studies in the banking literature (e.g. Beltratti and Stulz, 2012; Diamond and Rajan, 2009; Erkens et al., 2012) an OECD study from 2009 supports this notion (Kirkpatrick, 2009). Public debates increased awareness for the need of appropriate governance mechanisms at that time. Consequently, politicians and regulators called for more financial expertise on bank boards. Accordingly, the Basel Committee on Banking Supervision states in principle 2 that “board members should remain qualified, individually and collectively, for their positions. They should understand their oversight and corporate governance role and be able to exercise sound, objective judgement about the affairs of the bank.” (BCBS, 2015). Taking these perceptions into consideration the prevailing question is whether financial experts on bank boards do really foster bank stability? This chapter aims to investigate this question by referring to the study from Minton et al. (2014). In their study, the authors investigate US commercial bank holding companies between the period 2003 and 2008. The authors find that financial experts on the board of US commercial bank holding companies promote pro-cyclical bank performance. Accordingly, the authors question regulators view of more financial experts on the board leading to more banking stability. However, Minton et al. (2014) do not examine whether their findings accrue due to financial experts who act in the interests of shareholders or due to the issue that financial experts may have a more risk-taking attitude (due to a better understanding of financial instruments) than other board members. Supposed that their findings accrue due to financial experts who act in the interests of shareholders. Then financial experts on the board of banks where short-term shareholder interests play no role (cooperative banks) may prove beneficial with regard on bank performance during the crisis as well as in normal times. This would mean that they use their skills and expertise to contribute sustainable growth to the bank. Contrary, if this study reveals pro-cyclical bank performance related to financial experts on the board of cooperative banks, this finding may be addressed solely to the risk-taking attitude of financial experts (since short-term shareholder interests play no role). For this reason, this chapter aims to identify the channel for the relation of financial experts and bank performance by examining the following research question: Do financial experts on the board promote pro-cyclical bank performance in a setting where short-term shareholder interests play no role? Results show that financial experts on the board of cooperative banks (data from 2006 to 2011) do not promote pro-cyclical bank performance. Contrary, results show evidence that financial experts on the board of cooperative banks appear to foster long-term bank stability. This suggests that regulators should consider ownership structure (and hence business model of banks) when imposing new regulatory constraints for financial experts on the bank board. N2 - Banken nehmen wichtige Funktionen innerhalb einer Volkswirtschaft wahr. Innerhalb ihrer Rolle als Finanzintermediär stellen sie Liquidität bereit und übernehmen elementare Aufgaben der Fristen- und Risikotransformation (Fama ,1985). Sie stellen sicher, dass die Liquidität der Depotinhaber den profitabelsten Investitionsprojekten zukommt. Darüber hinaus übernehmen Banken wichtige Prüfungs- und Überwachungsfunktionen über ihre Investitionsprojekte und sorgen damit für eine stetig effiziente Ressourcenallokation innerhalb einer Volkswirtschaft (Pathan and Faff, 2013). Da jedoch Banken ihre Finanzdienstleistungen der gesamten Volkswirtschaft zur Verfügung stellen, erzeugen sie damit auch (im Gegensatz zu Firmen) ein gewisses Systemrisiko: die Finanzkrise 2007 – 2008 hat gezeigt, dass Banken ganze Staaten in eine Rezession ziehen können. Gleichzeitig hat die Krise allerdings auch gezeigt, dass bestimmte Banktypen deutlich stabiler sind als andere. So sind beispielsweise die genossenschaftlichen Volks- und Raiffeisenbanken deutlich besser durch die Krise gekommen als nahezu alle Universalbanken. Genossenschaftsbanken existieren in allen größeren westlichen Volkswirtschaften und nehmen innerhalb dieser oft eine bedeutende Rolle ein. Aufgrund der einerseits hohen Bedeutung von Genossenschaftsbanken in den genannten Volkswirtschaften und der andererseits vergleichsweise geringen Beachtung in der Literatur, ist es das Ziel dieser Dissertation mit den folgenden drei empirischen Studien die bestehende Forschung der Genossenschaftsbanken voranzutreiben. Die drei empirischen Studien beschäftigen sich mit jeweils unabhängigen Forschungsfragen, die für den Bankensektor in jüngster Zeit von hoher Relevanz sind. Kapitel 2 beschäftigt sich mit der Frage, welche Genossenschaftsbanken von einer Einnahmendiversifikation profitieren können: bestehende Literatur offenbart den Trend innerhalb des Bankensektors, wonach Banken nach Diversifikation streben, indem sie ihre Einnahmen immer stärker im zinsunabhängigen Geschäft generieren. Jedoch zeigt sich in der Literatur ebenfalls, dass längst nicht alle Banken durch die Einnahmendiversifikation profitieren (Mercieca et al., 2007; Stiroh and Rumble, 2006; Goddard et al., 2008). Bei der Untersuchung von Genossenschaftsbanken ergibt sich folgendes Bild: es profitieren diejenigen Banken von einer weiteren Einnahmendiversifikation, welche bereits einen hohen Anteil ihrer Einnahmen durch das zinsunabhängige Geschäft generieren. Des Weiteren zeigt die Untersuchung einen negativen Nettoeffekt für diejenigen Banken, welche den Großteil ihrer Einnahmen durch das Zinsgeschäft generieren. Insgesamt deuten die Hinweise der empirischen Untersuchung darauf hin, dass Banken eine gewisse Zeit benötigen um entsprechende Expertise und Erfahrung aufzubauen damit eine Einnahmendiversifikation eine konkurrenzfähige risikoadjustierte Rendite erzeugt. Kapitel 3 beschäftigt sich mit der Beziehung zwischen dem Risiko, der Kapitalausstattung und der Effizienz einer Bank. Das Geschäftsmodell von Genossenschaftsbanken beruht auf der Förderung der Interessen der Mitglieder (§ 1 GenG). Das legt die Vermutung nahe, dass die in der Literatur weit verbreitete Ansicht des moralischen Risikoverhaltens nicht auf Genossenschaftsbanken zutrifft. Darüber hinaus könnten die besonderen Governance-Strukturen von Genossenschaftsbanken diese These stützen: kurzfristige Eigentümerinteressen als mögliche Ursache für moralisches Risikoverhalten spielen bei Genossenschaftsbanken keine Rolle. Die Ergebnisse der empirischen Untersuchung von Genossenschaftsbanken zeigen, dass eine niedrigere Kosten- und Gewinneffizienz zu einem höheren Kreditrisiko führt. Gleichzeitig bestätigen die Ergebnisse, dass ein negativer Zusammenhang zwischen dem Kreditrisiko von Banken und deren Kosten- und Gewinneffizienz besteht. Als zentraler Unterschied zu bestehenden Studien zeigt sich jedoch, dass ein positiver Zusammenhang zwischen der Eigenkapitalposition und dem Kreditrisiko besteht. Das bedeutet, dass moralisches Risikoverhalten („moral hazard“) bei Genossenschaftsbanken, wie bereits vermutet, nicht stattfindet. Insbesondere der Zweck der Genossenschaftsbanken (§ 1 GenG) und die damit einhergehenden besonderen Governance-Strukturen sind nach Ansicht der Autoren die wesentliche Begründung für diese Erkenntnis. Kapitel 4 widmet sich den Governance-Strukturen von Genossenschaftsbanken. Speziell wird in diesem Kapitel die Forschungsfrage behandelt, ob Finanzexperten im Aufsichtsrat von Genossenschaftsbanken zu einer prozyklischen Bankperformance führen. Dieser Zusammenhang wurde in der Studie von Minton, Taillard und Williamson (2014) bei kapitalmarktorientierten Banken aufgezeigt. Die Ergebnisse der Genossenschaftsbanken hingegen zeigen, dass Finanzexperten in den Aufsichtsräten von Genossenschaftsbanken im Zeitraum von 2006 bis 2011 keine prozyklische Bankperformance erzeugen. Im Gegenteil, die Ergebnisse weisen darauf hin, dass Finanzexperten in den Aufsichtsräten von Genossenschaftsbanken eine langfristige Stabilität der Banken gewährleisten. In der Konsequenz bedeutet das, dass Regulatoren die Eigentümerstrukturen (und damit das Geschäftsmodell) von Banken berücksichtigen sollten, wenn sie neue regulatorische Anforderungen hinsichtlich Finanzexperten in den Aufsichtsräten von Banken einführen. KW - cooperative diversification KW - Genossenschaftsbanken KW - performance KW - banksrevenue KW - risk KW - profitability KW - efficiency KW - Aufsichtsrat KW - Diversifikation KW - Risiko Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-153581 ER - TY - JOUR A1 - Steppuhn, Henriette A1 - Langen, Ute A1 - Scheidt-Nave, Christa A1 - Keil, Thomas T1 - Major comorbid conditions in asthma and association with asthma-related hospitalizations and emergency department admissions in adults: results from the German national health telephone interview survey (GEDA) 2010 JF - BMC Pulmonary Medicine N2 - Background: It remains unclear to what extent asthma in adults is linked to allergic rhinitis (AR), gastroesophageal reflux disease (GERD), and acetylsalicylic acid exacerbated respiratory disease (AERD), and how these comorbidities may affect asthma outcomes in the general population. We therefore aimed to assess the prevalence of these major comorbidities among adults with asthma and examine their impact on asthma exacerbations requiring hospital care. Methods: A total of 22,050 adults 18 years and older were surveyed in the German National Health Telephone Interview Survey (GEDA) 2010 using a highly standardized computer-assisted interview technique. The study population comprised participants with self-reported physician-diagnosed asthma, among which the current (last 12 months) prevalence of AR and GERD-like symptoms (GERS), and life-time prevalence of AERD was estimated. Weighted bivariate analyses and logistic regression models were applied to assess the association of each comorbid condition with the asthma outcome (any self-reported asthma-related hospitalization and/or emergency department (ED) admission in the past year). Results: Out of 1,136 adults with asthma, 49.6% had GERS and 42.3% had AR within the past 12 months; 14.0% met the criteria of AERD, and 75.7% had at least one out of the three conditions. Overall, the prevalence of at least one exacerbation requiring emergency room or hospital admission within the past year was 9.0%. Exacerbation prevalence was higher among participants with comorbidities than among those without (9.8% vs. 8.2% for GERS; 11.2% vs. 7.6% for AR, and 22.2% vs. 7.0% for AERD), but only differences in association with AERD were statistically significant. A strong association between asthma exacerbation and AERD persisted in multivariable logistic regression analyses adjusting for sex, age group, level of body mass index, smoking status, educational attainment, and duration of asthma: odds ratio (OR) = 4.5, 95% confidence interval (CI) = 2.5-8.2. Conclusions: Data from this large nation-wide study provide evidence that GERS, AR and AERD are all common comorbidities among adults with asthma. Our data underline the public health and clinical impact of asthma with complicating AERD, contributing considerably to disease-specific hospitalization and/or ED admission in a defined asthma population, and emphasize the importance of its recognition in asthma care. KW - management KW - update KW - impact KW - risk KW - severity KW - prevalence KW - clinical-practice KW - aspirin sensitivity KW - allergic rhinitis KW - exacebrated respiratory-disease KW - gastroesophageal reflux disease KW - gastroesophageal reflux KW - hospitalization KW - national health survey KW - acetylsalicylic acid exacerbated respiratory disease KW - adult KW - aspirin-induced asthma KW - asthma Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122121 VL - 13 IS - 46 ER - TY - THES A1 - Weis, Claudia T1 - Berechnungen der Lebenserkrankungswahrscheinlichkeit bei familiärem Brustkrebs - Vergleich von Methoden T1 - Lifetime risk calculation for familial breast cancer - comparison of methods N2 - Diese Arbeit vergleicht verschiedene Methoden zur Berechung der Lebenserkrankungswahrscheinlichkeit bei familiärem Brustkrebs. Dabei handelt es sich um Tabellen von Chang-Claude und die Computerprogramme Cyrillic Version 2.1 sowie IBIS Breast Cancer Risk Evaluation Tool. Es stellte sich heraus, dass sich die Ergebnisse der Modelle nicht wesentlich voneinander unterscheiden. N2 - This paper compares different models of lifetime risk calculation for familial breast cancer. These were tables of Chang-Claude and the computer programmes Cyrillic Version 2.1 and IBIS Breast Cancer Risk Evaluation Tool. It is shown that there is no distinct difference between the results of calculated risks. KW - Brustkrebs KW - Risiko KW - Berechnung KW - breast cancer KW - risk KW - calculation Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-74027 ER - TY - JOUR A1 - Wischnewsky, Manfred A1 - Schwentner, Lukas A1 - Diessner, Joachim A1 - De Gregorio, Amelie A1 - Joukhadar, Ralf A1 - Davut, Dayan A1 - Salmen, Jessica A1 - Bekes, Inga A1 - Kiesel, Matthias A1 - Müller-Reiter, Max A1 - Blettner, Maria A1 - Wolters, Regine A1 - Janni, Wolfgang A1 - Kreienberg, Rolf A1 - Wöckel, Achim A1 - Ebner, Florian T1 - BRENDA-Score, a hghly significant, internally and externally validated prognostic marker for metastatic recurrence: analysis of 10,449 primary breast cancer patients JF - Cancers N2 - Background Current research in breast cancer focuses on individualization of local and systemic therapies with adequate escalation or de-escalation strategies. As a result, about two-thirds of breast cancer patients can be cured, but up to one-third eventually develop metastatic disease, which is considered incurable with currently available treatment options. This underscores the importance to develop a metastatic recurrence score to escalate or de-escalate treatment strategies. Patients and methods Data from 10,499 patients were available from 17 clinical cancer registries (BRENDA-project. In total, 8566 were used to develop the BRENDA-Index. This index was calculated from the regression coefficients of a Cox regression model for metastasis-free survival (MFS). Based on this index, patients were categorized into very high, high, intermediate, low, and very low risk groups forming the BRENDA-Score. Bootstrapping was used for internal validation and an independent dataset of 1883 patients for external validation. The predictive accuracy was checked by Harrell's c-index. In addition, the BRENDA-Score was analyzed as a marker for overall survival (OS) and compared to the Nottingham prognostic score (NPS). Results: Intrinsic subtypes, tumour size, grading, and nodal status were identified as statistically significant prognostic factors in the multivariate analysis. The five prognostic groups of the BRENDA-Score showed highly significant (p < 0.001) differences regarding MFS:low risk: hazard ratio (HR) = 2.4, 95%CI (1.7–3.3); intermediate risk: HR = 5.0, 95%CI.(3.6–6.9); high risk: HR = 10.3, 95%CI (7.4–14.3) and very high risk: HR = 18.1, 95%CI (13.2–24.9). The external validation showed congruent results. A multivariate Cox regression model for OS with BRENDA-Score and NPS as covariates showed that of these two scores only the BRENDA-Score is significant (BRENDA-Score p < 0.001; NPS p = 0.447). Therefore, the BRENDA-Score is also a good prognostic marker for OS. Conclusion: The BRENDA-Score is an internally and externally validated robust predictive tool for metastatic recurrence in breast cancer patients. It is based on routine parameters easily accessible in daily clinical care. In addition, the BRENDA-Score is a good prognostic marker for overall survival. Highlights: The BRENDA-Score is a highly significant predictive tool for metastatic recurrence of breast cancer patients. The BRENDA-Score is stable for at least the first five years after primary diagnosis, i.e., the sensitivities and specificities of this predicting system is rather similar to the NPI with AUCs between 0.76 and 0.81 the BRENDA-Score is a good prognostic marker for overall survival. KW - breast cancer KW - risk KW - prediction KW - BRENDA KW - score KW - follow up Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241064 SN - 2072-6694 VL - 13 IS - 13 ER -