von Ujwal Mukund Mahajan ; Bettina Oehrle ; Elisabetta Goni ; Oliver Strobel ; Jörg Kaiser ; Robert Grützmann ; Jens Werner ; Helmut Friess ; Thomas M Gress ; Thomas W Seufferlein ; Waldemar Uhl ; Uwe Will ; John P. Neoptolemos ; Uwe A Wittel ; Marlies Vornhülz ; Simon Sirtl ; Georg Beyer ; Ivonne Regel ; Stefan Boeck ; Volker Heinemann ; Fabian Frost ; Antje Steveling ; Henry Völzke ; Astrid Petersmann ; Matthias Nauck ; Eckhard Weber ; Beate Kamlage ; Markus M Lerch ; Julia Mayerle
Online verfügbar: 16. Mai 2025, Artikelversion: 4. Juni 2025 ; Gesehen am 21.01.2026
Background - Earlier diagnosis of pancreatic ductal adenocarcinoma is key to improving overall survival in patients with this hard-to-treat cancer. We independently validated two previously identified plasma-based metabolic signatures for exclusion of pancreatic ductal adenocarcinoma in cohorts with an increased annual risk. - Methods - The METAPAC study was a prospective, multicentre, investigator-masked, enrichment design, phase 4 trial done in 23 centres in Germany. Patients with pancreatic lesions identified by diagnostic imaging that required further diagnostic assessment were recruited and followed up for 24 months. Targeted quantitative plasma metabolite analysis was done on a liquid chromatography-tandem mass spectrometry platform. The improved metabolic (i-Metabolic) signature consisted of 12 analytes plus carbohydrate antigen (CA) 19-9, and the minimalistic metabolic (m-Metabolic) signature consisted of four analytes plus CA 19-9. The primary endpoint of the study was the exclusion of pancreatic ductal adenocarcinoma with an 85% specificity and the highest possible diagnostic accuracy. All statistical analyses were done per protocol. This study is registered with the German Clinical Trials Register (DRKS00010866). - Findings - Between Sept 9, 2016, and April 8, 2022, 1370 patients with CT-identified pancreatic lesions necessitating further diagnostic assessment were screened, of whom 1129 patients (489 with pancreatic ductal adenocarcinoma, 640 controls) were included in the primary analysis (median age 67 years [IQR 58-75]; 556 [49%] female, 572 [51%] male). The control group consisted of high-risk individuals with acute pancreatitis (11 [1%] of 1129 participants), chronic pancreatitis (113 [10%]), intraductal papillary mucinous neoplasms (232 [21%]), cystic lesions other than intraductal papillary mucinous neoplasms (271 [24%]), and metastases of extrapancreatic origin (13 [1%]). The i-Metabolic signature detected pancreatic ductal adenocarcinoma with an area under the curve (AUC) of 0·846 (95% CI 0·842-0·849), specificity of 90·4% (89·8-91·1), sensitivity of 67·5% (66·9-68·0), and balanced accuracy of 80·5% (80·2-80·8), compared with CA 19-9 alone (AUC 0·799 [0·797-0·802], p<0·0001; specificity 79·1% [78·7-79·4]; sensitivity 81·8% [81·5-82·0]; balanced accuracy 80·6% [80·4-80·9]). The m-Metabolic signature detected pancreatic ductal adenocarcinoma with an AUC of 0·846 (95% CI 0·842-0·849; p<0·0001 vs CA 19-9 alone), specificity of 93·6% (93·1-94·0), sensitivity of 59·9% (59·3-60·4), and accuracy of 79·0% (78·8-79·2). In a population of 242 individuals with new-onset diabetes (three cases of incident pancreatic ductal adenocarcinoma), the m-Metabolic signature (without CA 19-9) significantly discriminated patients with pancreatic ductal adenocarcinoma from those without (p=0·038). AUC, specificity, and sensitivity remained constant after random bootstrapping for a prevalence of pancreatic ductal adenocarcinoma between 1% and 20%. - Interpretation - Two plasma-based metabolic signatures showed significant improvement in performance compared with CA 19-9 alone in excluding pancreatic ductal adenocarcinoma in a prospective real-world cohort. These findings could offer a surveillance tool in patients with an annual risk of pancreatic ductal adenocarcinoma of 1% to reduce unnecessary invasive procedures and facilitate earlier detection of resectable disease. - Funding - Federal Ministry of Education and Research (BMBF, Germany).
The lancet. Gastroenterology & Hepatology London : Elsevier, 2016 10(2025), 7 vom: Juli, Seite 634-647 Online-Ressource
Die erneuerbaren Energien wie Solarenergie and Windenergie haben in den vergangenen Jahrzehnten eine enorme Bedeutung als Alternative zu den konventionellen fossilen Brennstoffen wie Kohle, Erdöl und Erdgas gewonnen. Diese alternativen Quellen sind sauber, umweltfreundlich und regenerativ. Jedoch sind sie auch sehr wetterabhängig und nicht direkt von Menschen kontrollierbar. Dadurch verursacht die großmaßstäbliche Integration der erneuerbare Energien eine Netzinstabilität, weil das traditionelle Stromnetz für eine vorhersagbare Last und eine abschaltbare Erzeugung ausgelegt ist. In dieser Arbeit werden die Variabilität der erneuerbaren Quellen und deren Einfluss auf den Ausgleichsbedarf für ein zukünftiges europäisches Energiesystem mit hohen Anteilen an Solar- und Windenergie untersucht. Der Schwerpunkt ist die Analyse der Auswirkungen unterschiedlich geneigter und unterschiedlich orientierter PV-Module auf den Ausgleichsbedarf für Europa. Darüber hinaus wird die Modelldomäne nach Nordafrika erweitert, um den Einfluss des konzentrierten Solarstromimports auf den europäischen Speicher- und Backup-Bedarf abzuschätzen. Es wurde gezeigt, dass die beste Wahl der Modulkonfiguration sehr empfindlich von den jeweiligen Solar- und Windanteilen am Strommix abhängt. Falls ein Speicher mit einer Kapazität von mindestens sechs durchschnittlichen Stundenbelastungen zur Verfügung steht, sollten steil aufgestellte Module mit gering ausgeprägten Jahresgängen bevorzugt werden. In einem winddominierten Szenario sind die niedrig geneigten Ost- und Westmodule am besten geeignet um den Ausgleichsbedarf zu reduzieren. Wenn kein Speicher vorhanden ist, reduziert ein Verbund von stark geneigten Ost- und Westmodulen den Ausgleichsbedarf, solange der Solaranteil hoch genug ist, um zwischen verschiedenen Konfigurationen zu unterscheiden. Einige dieser Modulkonfigurationen können in Bezug auf die installierte Kapazität ziemlich teuer sein. Aber der Umbau alter PV-Systeme zu Konfigurationen die für ein bestimmtes Szenario am besten geeignet sind, kann langfristig vorteilhaft sein. <dt.>
Over the past decades, renewable energy sources like solar and wind have gained enormous importance as alternative to the conventional fossil fuel based resources, such as coal, petroleum, and natural gas. These alternative sources are clean, environmental friendly, and naturally replenished. However, these renewable sources are largely weather-dependent and their output is not directly controllable by human beings. As a result, their large scale integration causes grid instability as the traditional power grid is designed for somewhat predictable load and dispatchable generation. In this thesis, this variable nature of renewable sources and their influence on balancing needs are studied for a future European power system with high shares of solar and wind generation. The main focus here is the analysis of the impact of differently inclined and differently oriented PV modules on balancing needs for Europe. Additionally, the model domain is expanded to North Africa to estimate the influence of concentrated solar power import on European storage and backup needs. The results show that the favorable choice of module configuration is very sensitive to the shares of solar and wind. For high solar shares, highly inclined modules with less pronounced annual courses are favorable, if a storage is available with a capacity to cover at least 6 hours of average load. In a wind-dominated scenario, lowly inclined East/West facing modules are most suitable to reduce balancing needs. When no storage is present, a combination of highly inclined East and West facing modules reduces the balancing needs as long as solar share is high enough to distinguish between different configurations. Some of these module configurations may be quite expensive in terms of installed capacity, but repowering old PV modules to configurations best suited for a specific scenario, can be advantageous in the long run. <engl.>
Auch als elektronisches Dokument verfügbar: http://www.energiemeteorologie.de/publications/solar/conference/2009/staffelstein/solarleistungsvorhersage_staffelstein09.pdf
Symposium Photovoltaische Solarenergie (24 : 2009 : Bad Staffelstein) 24. Symposium Photovoltaische Solarenergie Regensburg : OTTI, 2009 2009, insges. 6 S. 539, [18] S.
