TY - JOUR A1 - Dumont, Martine A1 - Weber-Lassalle, Nana A1 - Joly-Beauparlant, Charles A1 - Ernst, Corinna A1 - Droit, Arnaud A1 - Feng, Bing-Jian A1 - Dubois, Stéphane A1 - Collin-Deschesnes, Annie-Claude A1 - Soucy, Penny A1 - Vallée, Maxime A1 - Fournier, Frédéric A1 - Lemaçon, Audrey A1 - Adank, Muriel A. A1 - Allen, Jamie A1 - Altmüller, Janine A1 - Arnold, Norbert A1 - Ausems, Margreet G. E. M. A1 - Berutti, Riccardo A1 - Bolla, Manjeet K. A1 - Bull, Shelley A1 - Carvalho, Sara A1 - Cornelissen, Sten A1 - Dufault, Michael R. A1 - Dunning, Alison M. A1 - Engel, Christoph A1 - Gehrig, Andrea A1 - Geurts-Giele, Willemina R. R. A1 - Gieger, Christian A1 - Green, Jessica A1 - Hackmann, Karl A1 - Helmy, Mohamed A1 - Hentschel, Julia A1 - Hogervorst, Frans B. L. A1 - Hollestelle, Antoinette A1 - Hooning, Maartje J. A1 - Horváth, Judit A1 - Ikram, M. Arfan A1 - Kaulfuß, Silke A1 - Keeman, Renske A1 - Kuang, Da A1 - Luccarini, Craig A1 - Maier, Wolfgang A1 - Martens, John W. M. A1 - Niederacher, Dieter A1 - Nürnberg, Peter A1 - Ott, Claus-Eric A1 - Peters, Annette A1 - Pharoah, Paul D. P. A1 - Ramirez, Alfredo A1 - Ramser, Juliane A1 - Riedel-Heller, Steffi A1 - Schmidt, Gunnar A1 - Shah, Mitul A1 - Scherer, Martin A1 - Stäbler, Antje A1 - Strom, Tim M. A1 - Sutter, Christian A1 - Thiele, Holger A1 - van Asperen, Christi J. A1 - van der Kolk, Lizet A1 - van der Luijt, Rob B. A1 - Volk, Alexander E. A1 - Wagner, Michael A1 - Waisfisz, Quinten A1 - Wang, Qin A1 - Wang-Gohrke, Shan A1 - Weber, Bernhard H. F. A1 - Devilee, Peter A1 - Tavtigian, Sean A1 - Bader, Gary D. A1 - Meindl, Alfons A1 - Goldgar, David E. A1 - Andrulis, Irene L. A1 - Schmutzler, Rita K. A1 - Easton, Douglas F. A1 - Schmidt, Marjanka K. A1 - Hahnen, Eric A1 - Simard, Jacques T1 - Uncovering the contribution of moderate-penetrance susceptibility genes to breast cancer by whole-exome sequencing and targeted enrichment sequencing of candidate genes in women of European ancestry JF - Cancers N2 - Rare variants in at least 10 genes, including BRCA1, BRCA2, PALB2, ATM, and CHEK2, are associated with increased risk of breast cancer; however, these variants, in combination with common variants identified through genome-wide association studies, explain only a fraction of the familial aggregation of the disease. To identify further susceptibility genes, we performed a two-stage whole-exome sequencing study. In the discovery stage, samples from 1528 breast cancer cases enriched for breast cancer susceptibility and 3733 geographically matched unaffected controls were sequenced. Using five different filtering and gene prioritization strategies, 198 genes were selected for further validation. These genes, and a panel of 32 known or suspected breast cancer susceptibility genes, were assessed in a validation set of 6211 cases and 6019 controls for their association with risk of breast cancer overall, and by estrogen receptor (ER) disease subtypes, using gene burden tests applied to loss-of-function and rare missense variants. Twenty genes showed nominal evidence of association (p-value < 0.05) with either overall or subtype-specific breast cancer. Our study had the statistical power to detect susceptibility genes with effect sizes similar to ATM, CHEK2, and PALB2, however, it was underpowered to identify genes in which susceptibility variants are rarer or confer smaller effect sizes. Larger sample sizes would be required in order to identify such genes. KW - breast cancer KW - genetic susceptibility KW - whole-exome sequencing KW - moderate-penetrance genes Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281768 SN - 2072-6694 VL - 14 IS - 14 ER - TY - JOUR A1 - Schoffer, Olaf A1 - Schülein, Stefanie A1 - Arand, Gerlinde A1 - Arnholdt, Hans A1 - Baaske, Dieter A1 - Bargou, Ralf C. A1 - Becker, Nikolaus A1 - Beckmann, Matthias W. A1 - Bodack, Yves A1 - Böhme, Beatrix A1 - Bozkurt, Tayfun A1 - Breitsprecher, Regine A1 - Buchali, Andre A1 - Burger, Elke A1 - Burger, Ulrike A1 - Dommisch, Klaus A1 - Elsner, Gudrun A1 - Fernschild, Karin A1 - Flintzer, Ulrike A1 - Funke, Uwe A1 - Gerken, Michael A1 - Göbel, Hubert A1 - Grobe, Norbert A1 - Gumpp, Vera A1 - Heinzerling, Lucie A1 - Kempfer, Lana Raffaela A1 - Kiani, Alexander A1 - Klinkhammer-Schalke, Monika A1 - Klöcking, Sabine A1 - Kreibich, Ute A1 - Knabner, Katrin A1 - Kuhn, Peter A1 - Lutze, Stine A1 - Mäder, Uwe A1 - Maisel, Tanja A1 - Maschke, Jan A1 - Middeke, Martin A1 - Neubauer, Andreas A1 - Niedostatek, Antje A1 - Opazo-Saez, Anabelle A1 - Peters, Christoph A1 - Schell, Beatrice A1 - Schenkirsch, Gerhard A1 - Schmalenberg, Harald A1 - Schmidt, Peter A1 - Schneider, Constanze A1 - Schubotz, Birgit A1 - Seide, Anika A1 - Strecker, Paul A1 - Taubenheim, Sabine A1 - Wackes, Matthias A1 - Weiß, Steffen A1 - Welke, Claudia A1 - Werner, Carmen A1 - Wittekind, Christian A1 - Wulff, Jörg A1 - Zettl, Heike A1 - Klug, Stefanie J. T1 - Tumour stage distribution and survival of malignant melanoma in Germany 2002-2011 JF - BMC Cancer N2 - Background Over the past two decades, there has been a rising trend in malignant melanoma incidence worldwide. In 2008, Germany introduced a nationwide skin cancer screening program starting at age 35. The aims of this study were to analyse the distribution of malignant melanoma tumour stages over time, as well as demographic and regional differences in stage distribution and survival of melanoma patients. Methods Pooled data from 61 895 malignant melanoma patients diagnosed between 2002 and 2011 and documented in 28 German population-based and hospital-based clinical cancer registries were analysed using descriptive methods, joinpoint regression, logistic regression and relative survival. Results The number of annually documented cases increased by 53.2% between 2002 (N = 4 779) and 2011 (N = 7 320). There was a statistically significant continuous positive trend in the proportion of stage UICC I cases diagnosed between 2002 and 2011, compared to a negative trend for stage UICC II. No trends were found for stages UICC III and IV respectively. Age (OR 0.97, 95% CI 0.97–0.97), sex (OR 1.18, 95% CI 1.11–1.25), date of diagnosis (OR 1.05, 95% CI 1.04–1.06), ‘diagnosis during screening’ (OR 3.24, 95% CI 2.50–4.19) and place of residence (OR 1.23, 95% CI 1.16–1.30) had a statistically significant influence on the tumour stage at diagnosis. The overall 5-year relative survival for invasive cases was 83.4% (95% CI 82.8–83.9%). Conclusions No distinct changes in the distribution of malignant melanoma tumour stages among those aged 35 and older were seen that could be directly attributed to the introduction of skin cancer screening in 2008. " KW - Malignant melanoma KW - TNM staging KW - Survival analysis KW - Skin cancer screening KW - Stage distribution Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164544 VL - 16 IS - 936 ER - TY - JOUR A1 - Hagg, Wilfried A1 - Mayr, Elisabeth A1 - Mannig, Birgit A1 - Reyers, Mark A1 - Schubert, David A1 - Pinto, Joaquim G. A1 - Peters, Juliane A1 - Pieczonka, Tino A1 - Juen, Martin A1 - Bolch, Tobias A1 - Paeth, Heiko A1 - Mayer, Christoph T1 - Future climate change and its impact on runoff generation from the debris-covered Inylchek glaciers, Central Tian Shan, Kyrgyzstan JF - Water N2 - The heavily debris-covered Inylchek glaciers in the central Tian Shan are the largest glacier system in the Tarim catchment. It is assumed that almost 50% of the discharge of Tarim River are provided by glaciers. For this reason, climatic changes, and thus changes in glacier mass balance and glacier discharge are of high impact for the whole region. In this study, a conceptual hydrological model able to incorporate discharge from debris-covered glacier areas is presented. To simulate glacier melt and subsequent runoff in the past (1970/1971–1999/2000) and future (2070/2071–2099/2100), meteorological input data were generated based on ECHAM5/MPI-OM1 global climate model projections. The hydrological model HBV-LMU was calibrated by an automatic calibration algorithm using runoff and snow cover information as objective functions. Manual fine-tuning was performed to avoid unrealistic results for glacier mass balance. The simulations show that annual runoff sums will increase significantly under future climate conditions. A sensitivity analysis revealed that total runoff does not decrease until the glacier area is reduced by 43%. Ice melt is the major runoff source in the recent past, and its contribution will even increase in the coming decades. Seasonal changes reveal a trend towards enhanced melt in spring, but a change from a glacial-nival to a nival-pluvial runoff regime will not be reached until the end of this century. KW - glaciers KW - debris-covered glaciers KW - hydrological modelling KW - climate scenarios KW - Tian Shan Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197592 SN - 2073-4441 VL - 10 IS - 11 ER - TY - JOUR A1 - Ziegler, Alice A1 - Meyer, Hanna A1 - Otte, Insa A1 - Peters, Marcell K. A1 - Appelhans, Tim A1 - Behler, Christina A1 - Böhning-Gaese, Katrin A1 - Classen, Alice A1 - Detsch, Florian A1 - Deckert, Jürgen A1 - Eardley, Connal D. A1 - Ferger, Stefan W. A1 - Fischer, Markus A1 - Gebert, Friederike A1 - Haas, Michael A1 - Helbig-Bonitz, Maria A1 - Hemp, Andreas A1 - Hemp, Claudia A1 - Kakengi, Victor A1 - Mayr, Antonia V. A1 - Ngereza, Christine A1 - Reudenbach, Christoph A1 - Röder, Juliane A1 - Rutten, Gemma A1 - Schellenberger Costa, David A1 - Schleuning, Matthias A1 - Ssymank, Axel A1 - Steffan-Dewenter, Ingolf A1 - Tardanico, Joseph A1 - Tschapka, Marco A1 - Vollstädt, Maximilian G. R. A1 - Wöllauer, Stephan A1 - Zhang, Jie A1 - Brandl, Roland A1 - Nauss, Thomas T1 - Potential of airborne LiDAR derived vegetation structure for the prediction of animal species richness at Mount Kilimanjaro JF - Remote Sensing N2 - The monitoring of species and functional diversity is of increasing relevance for the development of strategies for the conservation and management of biodiversity. Therefore, reliable estimates of the performance of monitoring techniques across taxa become important. Using a unique dataset, this study investigates the potential of airborne LiDAR-derived variables characterizing vegetation structure as predictors for animal species richness at the southern slopes of Mount Kilimanjaro. To disentangle the structural LiDAR information from co-factors related to elevational vegetation zones, LiDAR-based models were compared to the predictive power of elevation models. 17 taxa and 4 feeding guilds were modeled and the standardized study design allowed for a comparison across the assemblages. Results show that most taxa (14) and feeding guilds (3) can be predicted best by elevation with normalized RMSE values but only for three of those taxa and two of those feeding guilds the difference to other models is significant. Generally, modeling performances between different models vary only slightly for each assemblage. For the remaining, structural information at most showed little additional contribution to the performance. In summary, LiDAR observations can be used for animal species prediction. However, the effort and cost of aerial surveys are not always in proportion with the prediction quality, especially when the species distribution follows zonal patterns, and elevation information yields similar results. KW - biodiversity KW - species richness KW - LiDAR KW - elevation KW - partial least square regression KW - arthropods KW - birds KW - bats KW - predictive modeling Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262251 SN - 2072-4292 VL - 14 IS - 3 ER - TY - JOUR A1 - Redlich, Sarah A1 - Zhang, Jie A1 - Benjamin, Caryl A1 - Dhillon, Maninder Singh A1 - Englmeier, Jana A1 - Ewald, Jörg A1 - Fricke, Ute A1 - Ganuza, Cristina A1 - Haensel, Maria A1 - Hovestadt, Thomas A1 - Kollmann, Johannes A1 - Koellner, Thomas A1 - Kübert‐Flock, Carina A1 - Kunstmann, Harald A1 - Menzel, Annette A1 - Moning, Christoph A1 - Peters, Wibke A1 - Riebl, Rebekka A1 - Rummler, Thomas A1 - Rojas‐Botero, Sandra A1 - Tobisch, Cynthia A1 - Uhler, Johannes A1 - Uphus, Lars A1 - Müller, Jörg A1 - Steffan‐Dewenter, Ingolf T1 - Disentangling effects of climate and land use on biodiversity and ecosystem services—A multi‐scale experimental design JF - Methods in Ecology and Evolution N2 - Climate and land-use change are key drivers of environmental degradation in the Anthropocene, but too little is known about their interactive effects on biodiversity and ecosystem services. Long-term data on biodiversity trends are currently lacking. Furthermore, previous ecological studies have rarely considered climate and land use in a joint design, did not achieve variable independence or lost statistical power by not covering the full range of environmental gradients. Here, we introduce a multi-scale space-for-time study design to disentangle effects of climate and land use on biodiversity and ecosystem services. The site selection approach coupled extensive GIS-based exploration (i.e. using a Geographic information system) and correlation heatmaps with a crossed and nested design covering regional, landscape and local scales. Its implementation in Bavaria (Germany) resulted in a set of study plots that maximise the potential range and independence of environmental variables at different spatial scales. Stratifying the state of Bavaria into five climate zones (reference period 1981–2010) and three prevailing land-use types, that is, near-natural, agriculture and urban, resulted in 60 study regions (5.8 × 5.8 km quadrants) covering a mean annual temperature gradient of 5.6–9.8°C and a spatial extent of ~310 × 310 km. Within these regions, we nested 180 study plots located in contrasting local land-use types, that is, forests, grasslands, arable land or settlement (local climate gradient 4.5–10°C). This approach achieved low correlations between climate and land use (proportional cover) at the regional and landscape scale with |r ≤ 0.33| and |r ≤ 0.29| respectively. Furthermore, using correlation heatmaps for local plot selection reduced potentially confounding relationships between landscape composition and configuration for plots located in forests, arable land and settlements. The suggested design expands upon previous research in covering a significant range of environmental gradients and including a diversity of dominant land-use types at different scales within different climatic contexts. It allows independent assessment of the relative contribution of multi-scale climate and land use on biodiversity and ecosystem services. Understanding potential interdependencies among global change drivers is essential to develop effective restoration and mitigation strategies against biodiversity decline, especially in expectation of future climatic changes. Importantly, this study also provides a baseline for long-term ecological monitoring programs. KW - study design KW - biodiversity KW - climate change KW - ecosystem functioning KW - insect monitoring KW - land use KW - space-for-time approach KW - spatial scales Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258270 VL - 13 IS - 2 ER - TY - JOUR A1 - Meyer, Constantin A1 - Peters, Jan Christoph A1 - Thiel, Michael A1 - Rathmann, Joachim A1 - Job, Hubert T1 - Monitoring von Freiflächeninanspruchnahme und -versiegelung für eine nachhaltige Raumentwicklung in Bayern JF - Raumforschung und Raumordnung JF - Spatial Research and Planning N2 - Im Freistaat Bayern wird intensiv diskutiert, wie die nach wie vor hohe Freiflächeninanspruchnahme für Siedlungs- und Verkehrszwecke reduziert werden kann. Wissenschaftliche Grundlage für Steuerungsansätze in der Stadt- und Regionalentwicklung sollte ein verbessertes staatliches Flächenmonitoring sein, welches über die amtliche Statistik und deren Hauptindikator "Siedlungs- und Verkehrsfläche" hinaus auch die qualitative Dimension der Flächeninanspruchnahme einbezieht. Dafür stellt dieser Beitrag methodische Erweiterungsansätze für das Flächenmonitoring vor, welche kleinräumige Analysen der Zersiedelung, Freiraumstruktur, Flächenversiegelung und Ökosystemleistungen am Beispiel des Landkreises Rhön-Grabfeld aufzeigen. Diese werden im Kontext der Debatte zu Ursachen und Steuerung der Freiflächeninanspruchnahme sowie zu aktuellen Anforderungen an das Flächenmonitoring diskutiert. Betont wird deren Bedeutung für das Monitoring rechtlicher Vorgaben und politischer Ziele zur nachhaltigen Flächennutzung. N2 - In the federal state of Bavaria, there is currently intensive discussion on how land consumption for settlement and transport purposes can be reduced in the long term. In order to provide a solid scientific basis for steering instruments in urban and regional development, the official land use monitoring should be improved by including also the qualitative and structural dimension of land consumption in addition to existing official statistics and their main indicator ‘settlement and traffic area’. For this purpose, the paper presents methodological extensions, which show small-scale analyses of urban sprawl, open space structure, soil sealing and ecosystem services using the example of the district of Rhön-Grabfeld. These methodological extensions are discussed in the context of the relevant debates on the causes and steering of land consumption as well as on current requirements for land use monitoring, emphasising their importance for the monitoring of legal guidelines and political objectives on sustainable land use. T2 - Monitoring of land consumption and soil sealing as a contribution to sustainable spatial development in Bavaria KW - Bayern KW - Flächenmonitoring KW - Freiraumstruktur KW - Ökosystemleistungen KW - Siedlungs-und Verkehrsfläche KW - Zersiedelung KW - Bavaria KW - Ecosystem services KW - Land use monitoring KW - Open spaces KW - Settlement and traffic area KW - Urban sprawl Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261622 VL - 79 IS - 2 ER - TY - JOUR A1 - Peters, Sarah A1 - Frisch, Sabine A1 - Stock, Annika A1 - Merta, Julien A1 - Bäumer, Christian A1 - Blase, Christoph A1 - Schuermann, Eicke A1 - Tippelt, Stephan A1 - Bison, Brigitte A1 - Frühwald, Michael A1 - Rutkowski, Stefan A1 - Fleischhack, Gudrun A1 - Timmermann, Beate T1 - Proton beam therapy for pediatric tumors of the central nervous system — experiences of clinical outcome and feasibility from the KiProReg study JF - Cancers N2 - As radiotherapy is an important part of the treatment in a variety of pediatric tumors of the central nervous system (CNS), proton beam therapy (PBT) plays an evolving role due to its potential benefits attributable to the unique dose distribution, with the possibility to deliver high doses to the target volume while sparing surrounding tissue. Children receiving PBT for an intracranial tumor between August 2013 and October 2017 were enrolled in the prospective registry study KiProReg. Patient’s clinical data including treatment, outcome, and follow-up were analyzed using descriptive statistics, Kaplan–Meier, and Cox regression analysis. Adverse events were scored according to the Common Terminology Criteria for Adverse Events (CTCAE) 4.0 before, during, and after PBT. Written reports of follow-up imaging were screened for newly emerged evidence of imaging changes, according to a list of predefined keywords for the first 14 months after PBT. Two hundred and ninety-four patients were enrolled in this study. The 3-year overall survival of the whole cohort was 82.7%, 3-year progression-free survival was 67.3%, and 3-year local control was 79.5%. Seventeen patients developed grade 3 adverse events of the CNS during long-term follow-up (new adverse event n = 7; deterioration n = 10). Two patients developed vision loss (CTCAE 4°). This analysis demonstrates good general outcomes after PBT. KW - proton beam therapy KW - childhood cancer KW - brain cancer KW - adverse events KW - imaging changes Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297489 SN - 2072-6694 VL - 14 IS - 23 ER - TY - JOUR A1 - Lenz, Dominic A1 - Pahl, Jens A1 - Hauck, Fabian A1 - Alameer, Seham A1 - Balasubramanian, Meena A1 - Baric, Ivo A1 - Boy, Nikolas A1 - Church, Joseph A. A1 - Crushell, Ellen A1 - Dick, Anke A1 - Distelmaier, Felix A1 - Gujar, Jidnyasa A1 - Indolfi, Giuseppe A1 - Lurz, Eberhard A1 - Peters, Bianca A1 - Schwerd, Tobias A1 - Serranti, Daniele A1 - Kölker, Stefan A1 - Klein, Christoph A1 - Hoffmann, Georg F. A1 - Prokisch, Holger A1 - Greil, Johann A1 - Cerwenka, Adelheid A1 - Giese, Thomas A1 - Staufner, Christian T1 - NBAS Variants Are Associated with Quantitative and Qualitative NK and B Cell Deficiency JF - Journal of Clinical Immunology N2 - Purpose Biallelic pathogenic NBAS variants manifest as a multisystem disorder with heterogeneous clinical phenotypes such as recurrent acute liver failure, growth retardation, and susceptibility to infections. This study explores how NBAS-associated disease affects cells of the innate and adaptive immune system. Methods Clinical and laboratory parameters were combined with functional multi-parametric immunophenotyping methods in fifteen NBAS-deficient patients to discover possible alterations in their immune system. Results Our study revealed reduced absolute numbers of mature CD56dim natural killer (NK) cells. Notably, the residual NK cell population in NBAS-deficient patients exerted a lower potential for activation and degranulation in response to K562 target cells, suggesting an NK cell–intrinsic role for NBAS in the release of cytotoxic granules. NBAS-deficient NK cell activation and degranulation was normalized upon pre-activation by IL-2 in vitro, suggesting that functional impairment was reversible. In addition, we observed a reduced number of naïve B cells in the peripheral blood associated with hypogammaglobulinemia. Conclusion In summary, we demonstrate that pathogenic biallelic variants in NBAS are associated with dysfunctional NK cells as well as impaired adaptive humoral immunity. KW - NBAS KW - inborn error of immunity KW - NK cell deficiency KW - B cell deficiency KW - vesicle trafficking KW - familial hemophagocytic lymphohistiocytosis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308362 SN - 0271-9142 SN - 1573-2592 VL - 41 IS - 8 ER -