Evaluation of ERA5 and WFDE5 forcing data for hydrological modelling and the impact of bias correction with regional climatologies: A case study in the Danube River Basin

Study region: The Danube River Basin. Study focus: Hydrological modelling of large, heterogeneous watersheds requires appropriate meteorological forcing data. The global meteorological reanalysis ERA5 and the global forcing dataset WFDE5 were evaluated for driving an uncalibrated setup of the mechanistic hydrological model PROMET (0.00833333 degrees/1 h resolution) for the period 1980-2016. Different climatologies were used for linear bias correction of ERA5: the global WorldClim 2 temperature and precipitation climatologies and the regional GLOWA and PRISM Alpine precipitation climatologies. Simulations driven with the uncorrected ERA5 reanalysis, the WFDE5 forcing dataset, ERA5 biascorrected with WorldClim 2 and ERA5 bias-corrected with a GLOWA-PRISM-WorldClim 2 mosaic were evaluated regarding percent bias of discharge and model efficiency. New hydrological insights for the region: Simulations yielded good model efficiencies and low percent biases of discharge at selected gauges. Uncalibrated model efficiencies corresponded with previous hydrological modelling studies. ERA5 and WFDE5 were well suited to drive PROMET in the hydrologically complex Danube basin, but bias correction of precipitation was essential for ERA5. The ERA5-driven simulation bias-corrected with a GLOWA-PRISM-WorldClim 2 mosaic performed best. Bias correction with GLOWA and PRISM outperformed WorldClim 2 in the Alps due to more realistic small-scale Alpine precipitation patterns resulting from higher station densities. In mountainous terrain, we emphasize the need for regional high-resolution precipitation climatologies and recommend them for bias correction of precipitation rather than global datasets

Statin-induced myopathic changes in primary human muscle cells and reversal by a prostaglandin F2 alpha analogue

Statin-related muscle side effects are a constant healthcare problem since patient compliance is dependent on side effects. Statins reduce plasma cholesterol levels and can prevent secondary cardiovascular diseases. Although statin-induced muscle damage has been studied, preventive or curative therapies are yet to be reported. We exposed primary human muscle cell populations (n = 22) to a lipophilic (simvastatin) and a hydrophilic (rosuvastatin) statin and analyzed their expressome. Data and pathway analyses included GOrilla, Reactome and DAVID. We measured mevalonate intracellularly and analyzed eicosanoid profiles secreted by human muscle cells. Functional assays included proliferation and differentiation quantification. More than 1800 transcripts and 900 proteins were differentially expressed after exposure to statins. Simvastatin had a stronger effect on the expressome than rosuvastatin, but both statins influenced cholesterol biosynthesis, fatty acid metabolism, eicosanoid synthesis, proliferation, and differentiation of human muscle cells. Cultured human muscle cells secreted ω-3 and ω-6 derived eicosanoids and prostaglandins. The ω-6 derived metabolites were found at higher levels secreted from simvastatin-treated primary human muscle cells. Eicosanoids rescued muscle cell differentiation. Our data suggest a new aspect on the role of skeletal muscle in cholesterol metabolism. For clinical practice, the addition of omega-n fatty acids might be suitable to prevent or treat statin-myopathy

Facile Synthesis of a Stable Side-on Phosphinyne Complex by Redox Driven Intramolecular Cyclisation

Alkyne complexes with vicinal substitution by a Lewis acid and a Lewis base at the coordinated alkyne are prospective frustrated Lewis pairs exhibiting a particular mutual distance and, hence, a specific activation potential. In this contribution, investigations on the generation of a WII alkyne complex bearing a phosphine as Lewis base and a carbenium group as Lewis acid are presented. Independently on potential substrates added, an intramolecular cyclisation product was always isolated. A subsequent deprotonation step led to an unprecedented side-on λ5-phosphinyne complex, which is interpreted as highly zwitterionic according to visible absorption spectroscopy supported by TD-DFT. Low-temperature 31P NMR and EPR spectroscopic measurements combined with time-dependent IR-spectroscopic monitoring provided insights in the mechanism of the cyclisation reaction. Decomposition of the multicomponent IR spectra by multivariate curve resolution and a kinetic hard-modelling approach allowed the derivation of kinetic parameters. Assignment of the individual IR spectra to potential intermediates was provided by DFT calculations. © 2020 The Authors. Published by Wiley-VCH Gmb

Ecological Sustainability Assessment of Water Distribution for the Maintenance of Ecosystems, their Services and Biodiversity

Water provision and distribution are subject to conflicts between users worldwide, with agriculture as a major driver of discords. Water sensitive ecosystems and their services are often impaired by man-made water shortage. Nevertheless, they are not sufficiently included in sustainability or risk assessments and neglected when it comes to distribution of available water resources. The herein presented contribution to the Sustainable Development Goals Clean Water and Sanitation (SDG 6) and Life on Land (SDG 15) is the Ecological Sustainability Assessment of Water distribution (ESAW-tool). The ESAW-tool introduces a watershed sustainability assessment that evaluates the sustainability of the water supply-demand ratio on basin level, where domestic water use and the water requirements of ecosystems are considered as most important water users. An ecological risk assessment estimates potential impacts of agricultural depletion of renewable water resources on (ground)water-dependent ecosystems. The ESAW-tool works in standard GIS applications and is applicable in basins worldwide with a set of broadly available input data. The ESAW-tool is tested in the Danube river basin through combination of high-resolution hydro-agroecological model data (hydrological land surface process model PROMET and groundwater model OpenGeoSys) and further freely available data (water use, biodiversity and wetlands maps). Based on the results, measures for more sustainable water management can be deduced, such as increase of rainfed agriculture near vulnerable ecosystems or change of certain crops. The tool can support decision making of authorities from local to national level as well as private enterprises who want to improve the sustainability of their supply chains. © 2022, The Author(s)

General practitioner care in nursing homes during the first wave of the COVID-19 pandemic in Germany: a retrospective survey among nursing home managers

Background: Though evidence on the detrimental impact of the COVID-19 pandemic in nursing homes is vast, research focusing on general practitioners' (GP) care during the pandemic in nursing homes is still scarce. Methods: A retrospective online survey among 1,010 nursing home managers in Germany was conducted during the first wave of the COVID-19 pandemic between November 2020 and February 2021. Associations between perceived deficits in GP care (routine and acute visits) and both general and COVID-19-related characteristics of nursing homes were analysed using multiple logistic regression analyses. Results: The majority of nursing home managers reported no deficits in GP care (routine visits, 84.3%; acute visits, 92.9%). Logistic regression analyses revealed that deficits in GP care (routine visits) were significantly associated with visiting restrictions for GPs and nursing home size. Small nursing homes (1-50 residents) were significantly more likely to report deficits in GP care (routine visits) compared to medium (51-100 residents) and large nursing homes (> 100 residents). Further, deficits in GP care (acute visits) were significantly associated with dementia as a focus of care and the burden of insufficient testing for SARS-CoV-2 among residents. Moreover, visiting restrictions for GPs were significantly associated with dementia as the focus of care and the COVID-19 incidence at the federal state level. Finally, COVID-19 cases in nursing homes were significantly associated with size of nursing homes, COVID-19-incidence on the federal state level and the burden of insufficient testing capacities for SARS-CoV-2 among residents. Conclusion: We found structural factors associated with GP care deficits during the pandemic. New concepts for GP care should be implemented in pandemic preparedness plans to ensure high quality, consistent, and reliable GP care as well as effective infection prevention measures in nursing homes

Impaired Autonomic Responses to Emotional Stimuli in Autoimmune Limbic Encephalitis

Limbic encephalitis (LE) is an autoimmune-mediated disorder that affects structures of the limbic system, in particular the amygdala. The amygdala constitutes a brain area substantial for processing of emotional, especially fear-related signals. The amygdala is also involved in neuroendocrine and autonomic functions, including skin conductance responses (SCRs) to emotionally arousing stimuli. This study investigates behavioral and autonomic responses to discrete emotion-evoking and neutral film clips in a patient suffering from LE associated with contactin-associated protein-2 (CASPR2)-antibodies as compared to a healthy control group. Results show a lack of SCRs in the patient while watching the film clips, with significant differences compared to healthy controls in the case of fear-inducing videos. There was no comparable impairment in behavioral data (emotion report, valence and arousal ratings). The results point to a defective modulation of sympathetic responses during emotional stimulation in patients with LE, probably due to impaired functioning of the amygdala

Explaining global surface aerosol number concentrations in terms of primary emissions and particle formation

We use observations of total particle number concentration at 36 worldwide sites and a global aerosol model to quantify the primary and secondary sources of particle number. We show that emissions of primary particles can reasonably reproduce the spatial pattern of observed condensation nuclei (CN) (R2=0.51) but fail to explain the observed seasonal cycle at many sites (R2=0.1). The modeled CN concentration in the free troposphere is biased low (normalised mean bias, NMB=−88%) unless a secondary source of particles is included, for example from binary homogeneous nucleation of sulfuric acid and water (NMB=−25%). Simulated CN concentrations in the continental boundary layer (BL) are also biased low (NMB=−74%) unless the number emission of anthropogenic primary particles is increased or an empirical BL particle formation mechanism based on sulfuric acid is used. We find that the seasonal CN cycle observed at continental BL sites is better simulated by including a BL particle formation mechanism (R2=0.3) than by increasing the number emission from primary anthropogenic sources (R2=0.18). Using sensitivity tests we derive optimum rate coefficients for this nucleation mechanism, which agree with values derived from detailed case studies at individual sites

Managing spatial sustainability trade-offs: The case of wind power

The deployment of onshore wind power involves spatial sustainability trade-offs, e.g., between the minimization of energy system costs, the mitigation of impacts on humans and biodiversity, and equity concerns. We analyze challenges arising for decision-making if wind power generation capacity has to be allocated spatially in the presence of such trade-offs. The analysis is based on a game developed for and played by stakeholders in Germany. The results of the game illustrate that there is no unanimously agreed ranking of sustainability criteria among the participating stakeholders. They disagreed not only on the weights of different criteria but also their definition and measurement. Group discussions further revealed that equity concerns mattered for spatial allocation. Yet, stakeholders used quite different concepts of equity. The results support the importance of transparent, multi-level and participatory approaches to take decisions on the spatial allocation of wind power generation capacity

Large-scale physical mapping within the region 22q12.3-13.1 in meningioma

The lack of physical mapping data strongly restricts the analysis of the meningioma chromosomal region that was assigned to the bands 22q12.3-qter. Recently, we reported a new marker D22S16 for chromosome 22 that was assigned to the region 22q13-qter by in situ hybridization. Utilizing somatic cell hybrids we now sublocalized the marker D22S16 within the band region 22q12-13.1, thus placing it in the vicinity of the gene for the platelet derived growth factor (PDGFB). A physical map was established for the regions surrounding the PDGFB gene and the D22S16 marker. By means of pulsed-field gel electrophoresis (PFGE) D22S16 and PDGFB were found to be physically linked within 900 kb. We also identified two CpG clusters bordering the PDGFB gene. For the enzyme NotI, a variation of the PDGFB restriction pattern was found between different individuals. PFGE analysis of the two loci (PDFGB and D22S16) failed to identify major rearrangements in meningioma.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29218/1/0000273.pd