Klimafolgenabschätzungen in der Wasserwirtschaft und deren Nutzen für die Praxis

KlimafolgenClimate ImpactsDer globale Klimawandel kann regional unterschiedliche Auswirkungen haben. Während sich die wissenschaftliche Forschung vor allem mit der Analyse der Daten beschäftigt, ist die fachliche Praxis darum bemüht, die Ergebnisse zu interpretieren und Handlungsempfehlungen daraus abzuleiten. Im Zuge des Projektes KliBiW (Globaler Klimawandel – Wasserwirtschaftliche Folgenabschätzung für das Binnenland) wurden die Auswirkungen des Klimawandels auf die Hochwasser- und Niedrigwasserverhältnisse in Niedersachsen untersucht. Hierzu wurden die Daten von zwei regionalen Klimamodellen (WETTREG2006 und REMO), beide angetrieben durch das Globalmodell ECHAM5/MPI-OM, räumlich interpoliert und die Niederschläge zum Teil zeitlich disaggregiert, um hoch aufgelöste Klimainformationen bereitzuhalten. Anschließend erfolgte die Kopplung mit einem hydrologischen Modellsystem (PANTA RHEI), das bereits in der Hochwasservorhersagezentrale des NLWKN im Einsatz ist. Über Langzeitsimulationen wurden zukünftige Veränderungen in den Abflussverhältnissen räumlich und zeitlich differenziert für das Aller-Leine Gebiet identifiziert. Als Betrachtungszeiträume dienten eine nahe Zukunftsphase (2021 – 2050) und eine ferne Zukunftsphase (2071 – 2100). Die Veränderungen verschiedener hydrologischer Hoch- und Niedrigwasser-Kenngrößen wurden gegenüber einem Kontrollzeitraum (1971 – 2000) aufgezeigt. Die Auswertungen an 8 Pegeln in Einzugsgebieten >1.000 km² auf Tageswertbasis und an 6 Pegeln in Einzugsgebieten <1.000 km² auf Stundenwertbasis zeigten, dass sich die Hochwassersituation zukünftig verschärfen kann. Während kleinere Hochwässer häufiger auftreten können, nehmen die Scheitelabflüsse insbesondere in der fernen Zukunft zu. Aussagen zu größeren Ereignissen sind aufgrund der großen Bandbreite der Ergebnisse jedoch mit erheblichen Unsicherheiten behaftet. Die Niedrigwasserverhältnisse zeigten eine Abnahme der Abflüsse, speziell im Sommer, sowie eine Zunahme der Dauer undnder Volumendefizite bei Trockenperioden. Hierbei erschien die Variabilität und Ausprägung der Trockenheit in kleineren Einzugsgebieten etwas größer. Die Nutzung dieser Erkenntnisse stellt die fachliche Praxis vor die Herausforderung, die Ergebnisse zu interpretieren und zu kommunizieren. Unsicherheiten in den Modellketten müssen berücksichtigt und, wenn möglich, quantifiziert werden. Die abgeleiteten hydrologischen Konsequenzen des Klimawandels können z.B. Anwendung finden in der gesetzlich geforderten Berücksichtigung der Auswirkungen des Klimawandels auf die Risikogebiete entsprechend der Hochwasserrisikomanagement-Richtlinie (2007/60/EG). Dieser Beitrag gibt einen Überblick über wasserwirtschaftlich relevante Auswertungen von Klimamodelldaten auf unterschiedlichen räumlichen Skalen und zeigt anhand ausgewählter Beispiele auf, wie primär im wissenschaftlichen Kontext erhobene Ergebnisse effektiv für praxisrelevante Fragestellungen genutzt werden können

Combination of (M)DSC and surface analysis to study the phase behaviour and drug distribution of ternary solid dispersions

Purpose: Miscibility of the different compounds that make up a solid dispersion based formulation play a crucial role in the drug release profile and physical stability of the solid dispersion as it defines the phase behaviour of the dispersion. The standard technique to obtain information on phase behaviour of a sample is (modulated) differential scanning calorimetry ((M)DSC). However, for ternary mixtures (M)DSC alone is not sufficient to characterize their phase behaviour and to gain insight into the distribution of the active pharmaceutical ingredient (API) in a two-phased polymeric matrix. Methods: MDSC was combined with complementary surface analysis techniques, specifically time-of-flight secondary ion mass spectrometry (ToF-SIMS) and atomic force microscopy (AFM). Three spray-dried model formulations with varying API/PLGA/PVP ratios were analyzed. Results: The distribution of the API in the ternary solid dispersions depended on formulation parameters. The extent of API surface coverage and therefore the distribution of the API over both polymeric phases differed significantly for the three formulations. Conclusions: Combining (M)DSC and surface analysis rendered additional insights in the composition of mixed phases in complex systems, like ternary solid dispersions

Uncertainties and robustness with regard to the safety of a repository for high-level radioactive waste: introduction of a research initiative

The Federal Company for Radioactive Waste Disposal (BGE mbH) is tasked with the selection of a site for a high-level radioactive waste repository in Germany in accordance with the Repository Site Selection Act. In September 2020, 90 areas with favorable geological conditions were identified as part of step 1 in phase 1 of the Site Selection Act. Representative preliminary safety analyses are to be carried out next to support decisions on the question, which siting regions should undergo surface-based exploration. These safety analyses are supported by numerical simulations building on geoscientific and technical data. The models that are taken into account are associated with various sources of uncertainties. Addressing these uncertainties and the robustness of the decisions pertaining to sites and design choices is a central component of the site selection process. In that context, important research objectives are associated with the question of how uncertainty should be treated through the various data collection, modeling and decision-making processes of the site selection procedure, and how the robustness of the repository system should be improved. BGE, therefore, established an interdisciplinary research cluster to identify open questions and to address the gaps in knowledge in six complementary research projects. In this paper, we introduce the overall purpose and the five thematic groups that constitute this research cluster. We discuss the specific questions addressed as well as the proposed methodologies in the context of the challenges of the site selection process in Germany. Finally, some conclusions are drawn on the potential benefits of a large method-centered research cluster in terms of simulation data management

Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single cell transcriptomics

For COVID-19, effective and well-understood treatment options are still scarce. Since vaccine efficacy is challenged by novel variants, short-lasting immunity and vaccine hesitancy, understanding and optimizing therapeutic options remains essential. We aimed at better understanding the effects of two standard-of-care drugs, dexamethasone and anti-SARS-CoV-2 antibodies, on infection and host responses. By using two COVID-19 hamster models, pulmonary immune responses were analyzed to characterize effects of single or combinatorial treatments. Pulmonary viral burden was reduced by anti-SARS-CoV-2 antibody treatment, and similar or increased by dexamethasone alone. Dexamethasone exhibited strong anti-inflammatory effects and prevented fulminant disease in a severe disease model. Combination therapy showed additive benefits with both anti-viral and anti-inflammatory potency. Bulk and single-cell transcriptomic analyses confirmed dampened inflammatory cell recruitment into lungs upon dexamethasone treatment, and identified a specifically responsive subpopulation of neutrophils, thereby indicating a potential mechanism of action. Our analyses confirm the anti-inflammatory properties of dexamethasone and suggest possible mechanisms, validate anti-viral effects of anti-SARS-CoV-2 antibody treatment, and reveal synergistic effects of a combination therapy, thus informing more effective COVID-19 therapies

SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies

SARS-CoV-2 Beta variant of concern (VOC) resists neutralization by major classes of antibodies from COVID-19 patients and vaccinated individuals. Here, serum of Beta-infected patients revealed reduced cross-neutralization of wildtype virus. From these patients, we isolated Beta-specific and cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results from recruitment of VOC-specific clonotypes and accommodation of mutations present in Beta and Omicron into a major antibody class that is normally sensitive to these mutations. The Beta-elicited cross-reactive antibodies share genetic and structural features with wildtype-elicited antibodies, including a public VH1-58 clonotype targeting the RBD ridge. These findings advance our understanding of the antibody response to SARS-CoV-2 shaped by antigenic drift with implications for design of next-generation vaccines and therapeutics

Development and Characterisation of Gastroretentive Solid Dosage Form Based on Melt Foaming

Dosage forms with increased gastric residence time are promising tools to increase bioavailability of drugs with narrow absorption window. Low-density floating formulations could avoid gastric emptying; therefore, sustained drug release can be achieved. Our aim was to develop a new technology to produce low-density floating formulations by melt foaming. Excipients were selected carefully, with the criteria of low gastric irritation, melting range below 70°C and well-known use in oral drug formulations. PEG 4000, Labrasol and stearic acid type 50 were used to create metronidazole dispersion which was foamed by air on atmospheric pressure using in-house developed apparatus at 53°C. Stearic acid was necessary to improve the foamability of the molten dispersion. Additionally, it reduced matrix erosion, thus prolonging drug dissolution and preserving hardness of the moulded foam. Labrasol as a liquid solubiliser can be used to increase drug release rate and drug solubility. Based on the SEM images, metronidazole in the molten foam remained in crystalline form. MicroCT scans with the electron microscopic images revealed that the foam has a closed-cell structure, where spherical voids have smooth inner wall, they are randomly dispersed, while adjacent voids often interconnected with each other. Drug release from all compositions followed Korsmeyer-Peppas kinetic model. Erosion of the matrix was the main mechanism of the release of metronidazole. Texture analysis confirmed that stearic acid plays a key role in preserving the integrity of the matrix during dissolution in acidic buffer. The technology creates low density and solid matrix system with micronsized air-filled voids