Unternehmensbewertung und Grundsätze ordnungsmäßiger Due Diligence

Gegenstand der Arbeit sind konzeptionelle Ansätze von Grundsätzen ordnungsmäßiger Due Diligence, die Ex-Post-Überraschungen als Folge von Informationsrisiken und die im Bereich des Unternehmenskaufs bestehende Rechtsunsicherheit verringern sollen. Leitlinie ist hierbei der Schutz des zu übertragenden Unternehmens und das gemeinsame Interesse von Verkäufer und Käufer an der Leichtigkeit und Sicherheit der Unternehmensübertragung. Die einzelnen Grundsätze, die an diesem Gedanken auszurichten sind, dienen der Planung und Durchführung sowie der Dokumentation und Berichterstattung über die Due Diligence. Diese Grundsätze sollten von der Abgrenzung des Kaufobjektes über die Identifikation, Aufbereitung und Handhabung von Risiken eine durchgängige Berücksichtigung der Risiken bis zur Kaufpreisvereinbarung und Vertragsausarbeitung sicherstellen

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Abstract: Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Variant annotation was supported by software resources provided via the Caché Campus program of the InterSystems GmbH to Alexander Teumer

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Publisher Copyright: © 2019, The Author(s).Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.Peer reviewe

QUIT EMR trial: a prospective, observational, multicentre study to evaluate quality and 24 hours post-transport morbidity of interhospital transportation of critically ill patients: study protocol

INTRODUCTION: It is widely accepted that transportation of critically ill patients is high risk. Unfortunately, however, there are currently no evidence-based criteria with which to determine the quality of various interhospital transport systems and their impact on the outcomes for patients. We aim to rectify this by assessing 2 scores which were developed in our hospital in a prospective, observational study. Primarily, we will be examining the Quality of interhospital critical care transportation in the Euregion Meuse-Rhine (QUIT EMR) score, which focuses on the quality of the transport system, and secondarily the SEMROS (Simplified EMR outcome score) which detects changes in the patient's clinical condition in the 24 hours following their transportation. METHODS AND ANALYSIS: A web-based application will be used to document around 150 pretransport, intratransport and post-transport items of each patient case.To be included, patients must be at least 18-years of age and should have been supervised by a physician during an interhospital transport which was started in the study region.The quality of the QUIT EMR score will be assessed by comparing 3 predefined levels of transport facilities: the high, medium and low standards. Subsequently, SEMROS will be used to determine the effect of transport quality on the morbidity 24 hours after transportation.It is estimated that there will be roughly 3000 appropriate cases suitable for inclusion in this study per year. Cases shall be collected from 1 April 2015 until 31 December 2017. ETHICS AND DISSEMINATION: This trial was approved by the Ethics committees of the university hospitals of Maastricht (Netherlands) and Aachen (Germany). The study results will be published in a peer reviewed journal. Results of this study will determine if a prospective randomised trial involving patients of various categories being randomly assigned to different levels of transportation system shall be conducted. TRIAL REGISTRATION NUMBER: NTR4937