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Large-scale flood risk assessments are crucial for decision making, especially with respect to new flood defense schemes, adaptation planning and estimating insurance premiums. We apply the process-based Regional Flood Model (RFM) to simulate a 5000-year flood event catalog for all major catchments in Germany and derive risk curves based on the losses per economic sector. The RFM uses a continuous process simulation including a multisite, multivariate weather generator, a hydrological model considering heterogeneous catchment processes, a coupled 1D-2D hydrodynamic model considering dike overtopping and hinterland storage, spatially explicit sector-wise exposure data and empirical multi-variable loss models calibrated for Germany. For all components, uncertainties in the data and models are estimated. We estimate the median Expected Annual Damage (EAD) and Value at Risk at 99.5% confidence for Germany to be euro0.529 bn and euro8.865 bn, respectively. The commercial sector dominates by making about 60% of the total risk, followed by the residential sector. The agriculture sector gets affected by small return period floods and only contributes to less than 3% to the total risk. The overall EAD is comparable to other large-scale estimates. However, the estimation of losses for specific return periods is substantially improved. The spatial consistency of the risk estimates avoids the large overestimation of losses for rare events that is common in other large-scale assessments with homogeneous return periods. Thus, the process-based, spatially consistent flood risk assessment by RFM is an important step forward and will serve as a benchmark for future German-wide flood risk assessments.
The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world(1). Here we describe the release of exome-sequence data for the first 49,960 study participants, revealing approximately 4 million coding variants (of which around 98.6% have a frequency of less than 1%). The data include 198,269 autosomal predicted loss-of-function (LOF) variants, a more than 14-fold increase compared to the imputed sequence. Nearly all genes (more than 97%) had at least one carrier with a LOF variant, and most genes (more than 69%) had at least ten carriers with a LOF variant. We illustrate the power of characterizing LOF variants in this population through association analyses across 1,730 phenotypes. In addition to replicating established associations, we found novel LOF variants with large effects on disease traits, includingPIEZO1on varicose veins,COL6A1on corneal resistance,MEPEon bone density, andIQGAP2andGMPRon blood cell traits. We further demonstrate the value of exome sequencing by surveying the prevalence of pathogenic variants of clinical importance, and show that 2% of this population has a medically actionable variant. Furthermore, we characterize the penetrance of cancer in carriers of pathogenicBRCA1andBRCA2variants. Exome sequences from the first 49,960 participants highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community. <br /> Exome sequences from the first 49,960 participants in the UK Biobank highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community.
Ziel ist die Überprüfung der kurz- und mittelfristigen Wirksamkeit einer vorschulischen Förderung des Mengen- und Zahlenverständnisses bei Kindern mit einem Risiko für die Entwicklung einer Rechenstörung. Es wurden 32 Risikokinder mit einer Kombination aus den Förderprogrammen Mathematik im Vorschulalter und Mengen, zählen, Zahlen im letzten Kindergartenjahr von den Erzieherinnen trainiert und mit 38 untrainierten Risikokindern verglichen. Hinsichtlich der kurzfristigen Wirksamkeit zeigten sich positive Trainingseffekte auf die numerischen Leistungen im letzten Kindergartenjahr. Es ließen sich keine signifikanten mittelfristigen Trainingseffekte auf die Rechenleistungen im zweiten Halbjahr der 1. Klasse finden. Das eingesetzte vorschulische Präventionsprogramm leistete danach einen wichtigen Beitrag zur kurzfristigen Verbesserung der mathematischen Basiskompetenzen.
Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length
(2020)
Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length
(2020)
Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
Der Verfasser beschäftigt sich mit der Frage des Glaubensübertritts in einem Asylverfahren. Dabei nimmt er Zeitpunkt, Art und Umstände des Religionswechsels in den Blick. Ferner untersucht er, wie die sogenannte Konversion von den zuständigen Behörden und Gerichten zu behandeln und zu bewerten ist. Einführend gibt er einen Überblick zum völkerrechtlichen Schutz der Religions- und Weltanschauungsfreiheit sowie typischen Gefährdungslagen. Überdies befasst er sich mit den Rechtsgrundlagen des Asyl- und Flüchtlingsschutzrechts und stellt Verbindungen zum Flucht- und Verfolgungsgrund der Religion her.
Schwerpunkt bildet die Untersuchung der Verfahrensstadien, in denen die Konversion relevant wird. Dabei berücksichtigt der Verfasser die nationale und europäische Rechtsprechung. Von besonderer Bedeutung sind die Ausführungen zum Zusammenspiel von staatlichen Ermittlungspflichten und Mitwirkungsgeboten von Asylantragstellenden, wobei den Besonderheiten des grund- und menschenrechtlichen Mehrebenensystems Rechnung getragen wird.
Zentral sind ferner die Ausführungen zum Umgang mit Taufurkunden und sonstigen Bescheinigungen über die religiöse Überzeugung. Besonderes Gewicht liegt auf der verfassungsrechtlichen Stellung der Religionsgemeinschaften und der Frage, ob die Entscheidung einer Religionsgemeinschaft, ein neues Mitglied aufzunehmen, die Behörde im Asylverfahren bindet. Diesem Problem widmet sich der Verfasser unter Heranziehung der relevanten Literaturstimmen und einschlägigen Rechtsprechung.
Der rechtswissenschaftliche Beitrag bietet den beteiligten Akteuren nicht nur eine Einführung in das Themengebiet des Glaubensübertritts im Asylverfahren, sondern gibt den Lesenden auch eine praxistaugliche Handlungsunterstützung rund um die wichtigsten Fragen einer Konversion im Asylverfahren an die Hand. Praktische Bezüge entstehen beispielsweise dadurch, dass wichtige Impulse und Empfehlungen für eine gleichermaßen moderne, rechtsstaatliche und grundrechtsorientierte Verfahrensführung entwickelt werden.
Coronary artery disease is the most common cause of death globally and is linked to a number of risk factors including serum low density lipoprotein, high density lipoprotein, triglycerides and lipoprotein(a). Recently two proteins, angiopoietin-like protein 3 and 4, have emerged from genetic studies as being factors that significantly modulate plasma triglyceride levels and coronary artery disease. The exact function and mechanism of action of both proteins remains to be elucidated, however, mutations in these proteins results in up to 34% reduction in coronary artery disease and inhibition of function results in reduced plasma triglyceride levels. Here we report the crystal structures of the fibrinogen-like domains of both proteins. These structures offer new insights into the reported loss of function mutations, the mechanisms of action of the proteins and open up the possibility for the rational design of low molecular weight inhibitors for intervention in coronary artery disease.
Rivers have always flooded their floodplains. Over 2.5 billion people worldwide have been affected by flooding in recent decades. The economic damage is also considerable, averaging 100 billion US dollars per year. There is no doubt that damage and other negative effects of floods can be avoided. However, this has a price: financially and politically. Costs and benefits can be estimated through risk assessments. Questions about the location and frequency of floods, about the objects that could be affected and their vulnerability are of importance for flood risk managers, insurance companies and politicians. Thus, both variables and factors from the fields of hydrology and sociol-economics play a role with multi-layered connections. One example are dikes along a river, which on the one hand contain floods, but on the other hand, by narrowing the natural floodplains, accelerate the flood discharge and increase the danger of flooding for the residents downstream. Such larger connections must be included in the assessment of flood risk. However, in current procedures this is accompanied by simplifying assumptions. Risk assessments are therefore fuzzy and associated with uncertainties.
This thesis investigates the benefits and possibilities of new data sources for improving flood risk assessment. New methods and models are developed, which take the mentioned interrelations better into account and also quantify the existing uncertainties of the model results, and thus enable statements about the reliability of risk estimates. For this purpose, data on flood events from various sources are collected and evaluated. This includes precipitation and flow records at measuring stations as well as for instance images from social media, which can help to delineate the flooded areas and estimate flood damage with location information. Machine learning methods have been successfully used to recognize and understand correlations between floods and impacts from a wide range of data and to develop improved models.
Risk models help to develop and evaluate strategies to reduce flood risk. These tools also provide advanced insights into the interplay of various factors and on the expected consequences of flooding. This work shows progress in terms of an improved assessment of flood risks by using diverse data from different sources with innovative methods as well as by the further development of models. Flood risk is variable due to economic and climatic changes, and other drivers of risk. In order to keep the knowledge about flood risks up-to-date, robust, efficient and adaptable methods as proposed in this thesis are of increasing importance.
Ziel ist die Überprüfung der kurz- und mittelfristigen Wirksamkeit einer vorschulischen Förderung des Mengen- und Zahlenverständnisses bei Kindern mit einem Risiko für die Entwicklung einer Rechenstörung. Es wurden 32 Risikokinder mit einer Kombination aus den Förderprogrammen Mathematik im Vorschulalter und Mengen, zählen, Zahlen im letzten Kindergartenjahr von den Erzieherinnen trainiert und mit 38 untrainierten Risikokindern verglichen. Hinsichtlich der kurzfristigen Wirksamkeit zeigten sich positive Trainingseffekte auf die numerischen Leistungen im letzten Kindergartenjahr. Es ließen sich keine signifikanten mittelfristigen Trainingseffekte auf die Rechenleistungen im zweiten Halbjahr der 1. Klasse finden. Das eingesetzte vorschulische Präventionsprogramm leistete danach einen wichtigen Beitrag zur kurzfristigen Verbesserung der mathematischen Basiskompetenzen.
Objective: This study assesses the short-term and intermediate effects of preschool training stimulating phonological awareness and letter-sound correspondence for children at risk of developing dyslexia. Moreover, we examined whether training reduced the frequency of subsequent dyslexic problems. Method: 25 children at risk of developing dyslexia were trained with Horen, Lauschen, Lernen 1 und 2 (Kuspert & Schneider, 2008; Plume & Schneider, 2004) by their kindergarten teachers and were compared with 60 untrained at-risk children. Results:The training revealed a significant short-term effect: The phonological awareness of trained at-risk children increased significantly over that of untrained at-risk children. However, there were no differences in phonological awareness, spelling, and reading ability between the first-graders in the training and control group. Furthermore, reading problems were reduced in the training group. Conclusions: In the future, phonological awareness as well as additional predictors should be included when identifying children vulnerable to developing dyslexia. Moreover, in order to prevent dyslexia, additional prerequisite deficits need to be identified, alleviated, and their effects evaluated.