[Bed capacity management in times of the COVID-19 pandemic : A simulation-based prognosis of normal and intensive care beds using the descriptive data of the University Hospital Augsburg]. / Bettenkapazitätssteuerung in Zeiten der COVID-19-Pandemie : Eine simulationsbasierte Prognose der Normal- und Intensivstationsbetten anhand der deskriptiven Daten des Universitätsklinikums Augsburg.

BACKGROUND: Following the regional outbreak in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread all over the world, presenting the healthcare systems with huge challenges worldwide. In Germany the coronavirus diseases 2019 (COVID-19) pandemic has resulted in a slowly growing demand for health care with a sudden occurrence of regional hotspots. This leads to an unpredictable situation for many hospitals, leaving the question of how many bed resources are needed to cope with the surge of COVID-19 patients. OBJECTIVE: In this study we created a simulation-based prognostic tool that provides the management of the University Hospital of Augsburg and the civil protection services with the necessary information to plan and guide the disaster response to the ongoing pandemic. Especially the number of beds needed on isolation wards and intensive care units (ICU) are the biggest concerns. The focus should lie not only on the confirmed cases as the patients with suspected COVID-19 are in need of the same resources. MATERIAL AND METHODS: For the input we used the latest information provided by governmental institutions about the spreading of the disease, with a special focus on the growth rate of the cumulative number of cases. Due to the dynamics of the current situation, these data can be highly variable. To minimize the influence of this variance, we designed distribution functions for the parameters growth rate, length of stay in hospital and the proportion of infected people who need to be hospitalized in our area of responsibility. Using this input, we started a Monte Carlo simulation with 10,000 runs to predict the range of the number of hospital beds needed within the coming days and compared it with the available resources. RESULTS: Since 2 February 2020 a total of 306 patients were treated with suspected or confirmed COVID-19 at this university hospital. Of these 84 needed treatment on the ICU. With the help of several simulation-based forecasts, the required ICU and normal bed capacity at Augsburg University Hospital and the Augsburg ambulance service in the period from 28 March 2020 to 8 June 2020 could be predicted with a high degree of reliability. Simulations that were run before the impact of the restrictions in daily life showed that we would have run out of ICU bed capacity within approximately 1 month. CONCLUSION: Our simulation-based prognosis of the health care capacities needed helps the management of the hospital and the civil protection service to make reasonable decisions and adapt the disaster response to the realistic needs. At the same time the forecasts create the possibility to plan the strategic response days and weeks in advance. The tool presented in this study is, as far as we know, the only one accounting not only for confirmed COVID-19 cases but also for suspected COVID-19 patients. Additionally, the few input parameters used are easy to access and can be easily adapted to other healthcare systems.

[Reembursing health-care service provider networks]. / Vergütungsstrukturen von Versorgungsnetzwerken.

Health-care service provider networks are regarded as an important instrument to overcome the widely criticised fragmentation and sectoral partition of the German health-care system. The first part of this paper incorporates health-care service provider networks in the field of health-care research. The system theoretical model and basic functions of health-care research are used for this purpose. Furthermore already established areas of health-care research with strong relations to health-care service provider networks are listed. The second part of this paper introduces some innovative options for reimbursing health-care service provider networks which can be regarded as some results of network-oriented health-care research. The origins are virtual budgets currently used in part to reimburse integrated care according to §§ 140a ff. SGB V. Describing and evaluating this model leads to real budgets (capitation) - a reimbursement scheme repeatedly demanded by SVR-Gesundheit (German governmental health-care advisory board), for example, however barely implemented. As a final step a direct reimbursement of networks by the German sickness fund is discussed. Advantages and challenges are shown. The development of the different reimbursement schemes is partially based on models from the USA.

[Memorandum 'Development of health services research in Bavaria from the perspective of the Bavarian State Working Group 'Health Services Research (LAGeV)': status quo - potential - strategies']. / Memorandum "Weiterentwicklung der Gesundheitsversorgungsforschung in Bayern aus Sicht der Landesarbeitsgemeinschaft Gesundheitsversorgungsforschung: Status quo - Entwicklungspotenziale - Strategien".

The aim of the memorandum on the development of health services research (HSR) in Bavaria is to operationalise the global objectives of the State Working Group "Health Services Research" (LAGeV) and to collectively define future topics, specific implementation steps, methods as well as ways of working for the future course of the LAGeV. The LAGeV is an expert committee that integrates and links the competencies of different actors from science, politics and health care regarding HSR and facilitates their cooperation. The memorandum is based on an explorative survey among the LAGeV members, which identified the status quo of health services research in Bavaria, potential for development, important constraints, promoting factors, specific recommendations as well as future topics for the further development of HSR in Bavaria. From the perspective of the LAGeV members, the 12 most important future topics are: 1) Interface and networking research, 2) Innovative health care concepts, 3) Health care for multimorbid patients, 4)Health care for chronically ill patients, 5) Evaluation of innovations, processes and technologies, 6) Patient orientation and user focus, 7) Social and regional inequalities in health care, 8) Health care for mentally ill patients, 9) Indicators of health care quality, 10) Regional needs planning, 11) Practical effectiveness of HSR and 12) Scientific use of routine data. Potential for development of HSR in Bavaria lies a) in the promotion of networking and sustainable structures, b) the establishment of an HSR information platform that bundles information and results in regard to current topics and aims to facilitate cooperation as well as c) in the initiation of measures and projects. The latter ought to pinpoint health care challenges and make recommendations regarding the improvement of health care and its quality. The cooperation and networking structures that were established with the LAGeV should be continuously expanded and be used to work on priority topics in order to achieve the global objectives of the LAGeV.

Empty bed contact time: The key for micropollutant removal in activated carbon filters.

The removal of micropollutants from wastewater is an emerging issue that currently concerns the wastewater sector the most. Granular Activated Carbon (GAC) has gained recognition as a suitable technology for dealing with this problem. This study assesses the performance of six GAC-filters for the removal of micropollutants installed as final treatment step at a municipal wastewater treatment plant. The influence of the GAC-type and the Empty Bed Contact Time (EBCT) on the filter performance was evaluated. The breakthrough behaviour of 13 selected micropollutants as well as the removal of the Dissolved Organic Carbon (DOC) and UV absorption at 254 nm were investigated. Besides, the adsorbed DOC (qDOC) was introduced as assessment parameter (adsorbed and biodegraded DOC), instead of the commonly used treated bed volume. Finally, Size Exclusion Chromatography (SEC) with online DOC and UV254nm detection was applied for a better understanding of the influent and effluent characteristics. The results showed that the pore size distribution is a crucial feature of the activated carbon. A balanced proportion of macro-, meso­ and micropores may play a role in the better removal of micropollutants in presence of DOC. Regardless of the GAC-type, a minimum EBCT between 20 - 30 min was necessary. We proved that a short EBCT would not fully use the sorption capacity, whereas a long EBCT would increase the carbon demand without improving of the removal. Lastly, according to the SEC results, after a short operation time no difference between the influent and effluent chromatographable fractions (DOC and UV254nm) was observed.

Molecular and immunological characterization of hr44, a human ocular component immunologically cross-reactive with antigen Ov39 of Onchocerca volvulus.

Structural similarities between host self-antigens and infectious organisms may be involved in the expression of autoimmune reactivity and development of autoimmune disease. The unique eye pathology associated with Onchocerca volvulus infection, particularly the development of posterior segment lesions, may be promoted by such autoreactive responses. Ov39 is a parasite-derived antigen that has been shown previously to be antigenically cross-reactive with a 44,000-M(r) host ocular component. A clone, designated hr44, was isolated from a cDNA library of human retina by immunoscreen using serum to Ov39. A monoclonal antibody raised to Ov39 also reacted with hr44 and gave evidence for a shared conformational epitope. The primary structure analysis showed that identities between the antigens are limited and confined to small peptides. The cross-reactivity between the antigens appears to involve T cells, since Ov39-specific T cells can be stimulated by hr44, a neural-specific antigen. Based on secondary structure prediction, hr44 has the typical features of a membrane-associated type I antigen with an amino-terminal extracellular domain. mAbs and antisera localized the antigen in the optic nerve, neural retina, retinal pigment epithelium, as well as the epithelial layers of ciliary body and iris.

Immunological crossreactivity between a cloned antigen of Onchocerca volvulus and a component of the retinal pigment epithelium.

Onchocerciasis (river blindness) is a major blinding disease in Africa, Central America, and South America. Loss of vision can be due to corneal change, optic atrophy, or chorioretinal disease. It has been suggested that autoimmunological reactions resulting from crossreactivity between parasite antigens and components of eye tissues contribute to development of ocular pathology. Using sera collected from onchocerciasis patients as a screening reagent, a cDNA clone (Ov39) has been isolated from a lambda gt11 expression library of Onchocerca volvulus. This antigen exhibits immunological crossreactivity with a component of retinal pigment epithelium cells (RPE). Antiserum raised against this recombinant peptide immunoprecipitates a 22,000 Mr antigen of adult O. volvulus and recognizes a 44,000 Mr component of bovine RPE by Western blotting. A 44,000 Mr antigen of cultured human RPE metabolically labeled with 35S-methionine can be immunoprecipitated with the same antiserum. An antigen of the same size is recognized by a rabbit antiserum raised against whole O. volvulus extract. Immunocytochemical studies on cryostat sections of the bovine eye using the antirecombinant sera localizes this antigen to the RPE.

X-ray spectromicroscopy in soil and environmental sciences.

X-ray microscopy is capable of imaging particles in the nanometer size range directly with sub-micrometer spatial resolution and can be combined with high spectral resolution for spectromicroscopy studies. Two types of microscopes are common in X-ray microscopy: the transmission X-ray microscope and the scanning transmission X-ray microscope; their set-ups are explained in this paper. While the former takes high-resolution images from an object with exposure times of seconds or faster, the latter is very well suited as an analytical instrument for spectromicroscopy. The morphology of clusters or particles from soil and sediment samples has been visualized using a transmission X-ray microscope. Images are shown from a cryo-tomography experiment based on X-ray microscopy images to obtain information about the three-dimensional structure of clusters of humic substances. The analysis of a stack of images taken with a scanning transmission X-ray microscope to combine morphology and chemistry within a soil sample is shown. X-ray fluorescence is a method ideally applicable to the study of elemental distributions and binding states of elements even on a trace level using X-ray energies above 1 keV.

[Hemoptysis and acute kidney injury in COVID-19]. / Hämoptysen und akutes Nierenversagen bei COVID-19.

The present case describes the diagnostic and therapy of the pulmorenal syndrome of a 40-year-old patient who presented in our clinic due to increasing respiratory insufficiency and hemoptysis with confirmed COVID-19 disease.

[Side effects of novel cancer immunotherapies]. / Nebenwirkungen neuer onkologischer Immuntherapien.

Systemic treatment with immune checkpoint inhibitors (ICI) has revolutionized the treatment of hematological and oncological diseases in recent years. The mechanism of action hinges on enhancing the natural ability of the immune system to eliminate malignant cells. The most important substances in this arena include inhibitors of PD­1, PD-L1 and CTLA­4. As a consequence, the spectrum of treatment-associated adverse reactions is shifting away from classical cytotoxic effects (e.g. pancytopenia and polyneuropathy) towards novel entities of immune-mediated complex diseases. These so-called immune-related adverse events (irAEs) can involve any organ system and mimic known classical autoimmune conditions. Timely recognition of irAEs is the key for rapid initiation of a suitable treatment and is especially challenging in the clinical routine as it requires an intensive interdisciplinary management. Nephrologists are particularly confronted with this kind of problem due to the highly interdisciplinary nature of their work. This article summarizes the broad spectrum of currently known renal and more frequently occuring non-renal forms of irAEs and aims to prime the reader on diagnostic and therapeutic options.

Dependence of maternal serum [AFP]/[hCG] median ratios on age of gestation: comparison of trisomy 21 to euploid pregnancies.

BACKGROUND: Current risk calculations for trisomy 21, which are based on multiples of median (MoM), do not take into account possible differences between euploid and trisomy 21 pregnancies that may develop with gestational age. In order to optimize the predictive value of screening tests, we calculated the ratio between maternal serum concentration of alpha-fetoprotein (AFP) and that of human chorionic gonadotropin (hCG) in euploid and in trisomy 21 pregnancies. METHODS: The medians of the concentration ratios, [AFP]/[hCG] at 16-21 weeks of gestation, were plotted as a function of gestational age for 307 cases of trisomy 21 and were compared with the medians of 30 549 normal karyotype cases. RESULTS: [AFP]/[hCG] ratio medians were independent of body weight and maternal age. There was a significant difference in the [AFP]/[hCG] ratio when comparing trisomy 21 and euploid pregnancies at each week. This difference became greater with advancing gestational age (P < 0.01). CONCLUSION: There is a significant difference in ratios of [AFP]/[hCG] between euploid and trisomy 21 pregnancies, which may be used to improve detection rates of Down syndrome screening.

Pesticides and antibiotics in permanent rice, alternating rice-shrimp and permanent shrimp systems of the coastal Mekong Delta, Vietnam.

BACKGROUND: Salinity intrusion into coastal regions is an increasing threat to agricultural production of salt sensitive crops like paddy rice. In the coastal Mekong Delta, farmers respond by shifting to more salinity tolerant agricultural production systems such as alternating rice-shrimp and permanent shrimp. While shrimps are sensitive to pesticide residues used on rice, the use of antibiotics in shrimp farming can cause contamination in rice crops. These patterns of cross-contamination are not well documented empirically in the rapidly changing agricultural landscape. OBJECTIVE AND METHODS: Our objective was to understand changing pollution patterns induced by shifts in agricultural land use system. We addressed this by i) documenting pesticide and antibiotic use in three different agriculture land use systems (permanent rice, alternating rice-shrimp and permanent shrimp), and by ii) determining residues of pesticides and antibiotics in top soil layers of these three land use systems. Samples were taken in Sóc Trang and Ben Tre province in the Mekong Delta, Vietnam. Chemical analyses comprised 12 of the most commonly used pesticides in rice paddies and six common antibiotics used in shrimp production. RESULTS: Results showed that residues of pesticides were present in all agricultural land use systems, including shrimp aquaculture. Active ingredients were mostly fungicides with a maximum concentration of 67 µg kg-1 found for isoprothiolane in permanent rice systems, followed by alternating rice-shrimp and permanent shrimp systems. Furthermore, antibiotics were present ubiquitously, with fluoroquinolones accumulating to larger amounts than sulfonamides and diaminopyrimidines. All concentrations were below critical lethal threshold values. CONCLUSION: Overall, farmers were most conscious of agrochemical use in alternating rice-shrimp systems to prevent harm to shrimps, which was reflected in overall lower concentrations of agrochemicals when compared to rice systems. Thus, alternating rice-shrimp systems present a low risk option in terms of food safety, which may bring additional benefits to this so far rather low-input system in brackish water transition zone.

[Acute-on-chronic liver failure: a diagnostic and therapeutic challenge for intensive care]. / Das akut-auf-chronische Leberversagen als diagnostische und therapeutische Herausforderung der Intensivmedizin.

Acute-on-chronic liver failure (ACLF) is an emerging clinical syndrome in patients with underlying liver disease that is usually triggered by one or multiple insults and characterized by progressive hepatic and nonhepatic organ failure, a significant risk of infections, and high short-term mortality rates. Despite our incomplete understanding of the underlying pathophysiology, ACLF requires timely diagnostic and therapeutic measures aiming at the identification and elimination of causative factors as well as the prevention of complications to improve the prognosis of affected patients.

Does sea-dyke construction affect the spatial distribution of pesticides in agricultural soils? - A case study from the Red River Delta, Vietnam.

The Red River Delta is a major agricultural production area of Vietnam with year-round use of pesticides for paddy rice cultivation and other production systems. The delta is protected from flooding, storm surges and saline water intrusion by a sophisticated river and sea-dyke system. Little is known about the effects of such a dyke system on pesticide pollution in the enclosed landscape. Our aim was to address this gap by i) determining pesticide prevalence in soils and sediments within a dyked agricultural area, and by ii) assessing whether and to which degree this dyke system might affect the spatial distribution of pesticides. After sampling paddy rice fields (topsoil) and irrigation ditches (sediment) perpendicular to the dyke in Giao Thuy district, we analysed 12 of the most commonly used pesticides in this area. In soils, we detected most frequently isoprothiolane (100% detection frequency), chlorpyrifos (85%) and propiconazole (41%) while in sediments isoprothiolane (71%) and propiconazole (71%) were most frequently found. Maximum concentrations reached 42.6 µg isoprotiolane kg-1 in soil, and 35.1 µg azoxystrobin kg-1 in sediment. Our results supported the assumption that the dyke system influenced residue distribution of selected pesticides. More polar substances increasingly accumulated in fields closer to the sea-dyke (R2 = 0.92 for chlorpyrifos and 0.51 for isoprothiolane). We can thus support initiatives from local authorities to use the distance to dykes as a mean for deliniating zones of different environmental pollution; yet, the degree at which dykes influence pesticide accumulation appear to be compound specific.

A feasible approach to all-electronic digital labeling and readout for cell identification.

We present two critical innovations that enable a unique, purely electronic approach to microfluidic whole-cell analysis, focusing on the problem of cell identification and sorting. We used fully-scalable lithographic techniques to microfabricate digital barcodes, providing a means for low-cost, large volume production. We have demonstrated molecular functionalization of the barcodes, using biotin-streptavidin, as well as human CD4 antibody, and we have successfully linked the barcodes to polystyrene beads using the biotin-streptavidin complex. This functionalization allows unique barcodes to be attached to specific cell types, based on phenotype. We have also implemented an electronic barcode readout scheme, using a radio frequency microsensor integrated in an elastomeric microfluidic channel, that can read individual barcodes at rates in excess of 1000 labels s(-1). The barcodes are biologically compatible, and coupled with the electronic sensing technology, provide a route to compact, inexpensive, disposable cell identification, sorting and purification.

Fluorescence microscopic visualization and quantification of initial bacterial colonization on enamel in situ.

OBJECTIVE: The acquired salivary pellicle has been defined as proteinaceous film free of bacteria. However, due to the large numbers of microorganisms existent in the oral fluids, it is conceivable that adherent bacteria are already present in the initial pellicle. The aim of this in situ study was to visualize and to quantify these bacteria. DESIGN: Initial biofilm formation was performed on bovine enamel slabs mounted buccally on individual splints and carried in situ by six subjects for 3, 30 and 120 min, respectively. After intraoral exposure, the slabs were rinsed with saline solution and the adherent bacteria were investigated with the following fluorescence microscopic methods: staining with 4',6-diamidino-2-phenylindole (DAPI), staining of vital and nonvital bacteria with fluoresceinediacetate and ethidiumbromide (live/dead staining) and fluorescence in situ hybridization (FISH) of eubacteria and streptococci, respectively. In addition, determination of colony forming units after ultrasonically induced detachment of bacteria was performed. RESULTS: With all the methods, bacteria were detected in the initial in situ biofilm irrespective of the formation time. The numbers of bacteria revealed high intraindividual and interindividual variability and the microorganisms were distributed randomly in small aggregates. The results of the epifluorescence microscopic techniques corresponded well. The mean number of adherent bacteria detected was in the range of 10-20x10(4)cm(-2). CONCLUSION: Already after 3 min, adherent bacteria are present in the initial pellicle. For the first time, DAPI-staining as well as FISH have proven success for visualization of initial intraoral colonization of enamel specimens.

[Extracorporeal therapies in hepatic diseases]. / Extrakorporale Therapien bei Lebererkrankungen.

Acute and acute-on-chronic liver failure have different underlying causes and are associated with hepatic or extrahepatic organ failure. Depending on etiology, up to 20% of critically ill patients suffer from hepatic dysfunction, which contributes to increased morbidity and mortality. A variety of extracorporeal procedures including renal replacement therapies, artificial and bioartificial liver support, and plasma exchange are used in the management of patients with liver diseases. Several randomized controlled studies of artificial liver support and plasma exchange proved the safety of these procedures and demonstrated improvement of hepatic encephalopathy and hemodynamics. A survival benefit could be observed in some of the randomized, controlled trials. In contrast, renal replacement therapy in critically ill patients with liver diseases has been assessed in retrospective case series and was associated with high mortality rates in liver cirrhosis. In summary, extracorporeal therapies are a cornerstone of therapeutic options in critically ill patients with hepatic failure. In addition to the comparison of different procedures, future studies should assess the timing of initiation as well as duration, and identify criteria of therapeutic futility of extracorporeal therapies in this population.

The initial stage of uranium oxidation: mechanism of UO(2) scale formation in the presence of a native lateral stress field.

In this work, an oxidation model for alpha-uranium is presented. It describes the internally lateral stress field built in the oxide scale during the reaction. The thickness of the elastic, stress-preserving oxide (UO(2+x)) scale is less than 0.5 microm. A lateral, 6.5 GPa stress field has been calculated from strains derived from line shifts (delta(2theta)) as measured by the X-ray diffraction of UO(2). It is shown that in the elastic growth domain, (110) is the main UO(2) growth plane for gas-solid oxidation. The diffusion-limited oxidation mechanism discussed here is based on the known "2:2:2" cluster theory which describes the mechanism of fluorite-based hyperstoichiometric oxides. In this study, it is adapted to describe oxygen-anion hopping. Anion hopping toward the oxide-metal interface proceeds at high rates in the [110] direction, hence making this pipeline route the principal growth direction in UO(2) formation. It is further argued that growth in the pure elastic domain of the oxide scale should be attributed entirely to anion hopping in 110. Anions, diffusing isotropically via grain boundaries and cracks, are shown to have a significant impact on the overall oxidation rate in relatively thick (>0.35 microm) oxide scales if followed by an avalanche break off in the postelastic regime. Stress affects oxidation in the elastic domain by controlling the hopping rate directly. In the postelastic regime, stress weakens hopping, indirectly, by enhancing isotropic diffusion. Surface roughness presents an additional hindering factor for the anion hopping. In comparison to anisotropic hopping, diffusion of isotropic hopping has a lower activation energy barrier. Therefore, a relatively stronger impact at lower temperatures due to isotropic diffusion is displayed.

Effect of cholesterol on Ca2+-induced aggregation and fusion of sonicated phosphatidylserine/cholesterol vesicles.

Small unilamellar vesicles composed of phosphatidylserine (PS) and cholesterol at various ratios were employed in studying the effect of cholesterol on Ca2+-induced vesicle aggregation and fusion using the Tb/dipicolinic acid assay. The leakage of preencapsulated Tb3+ was also measured. The analysis of the data provided estimates for the rate of aggregation C11, and the rate of fusion per se, f11. An increase in cholesterol contents results in a decrease in C11 values. Similarly, aggregation of PS/cholesterol vesicles is slower than that of PS vesicles in the presence of 650 mM NaCl. With 100 or 200 mM NaCl, the overall fusion rate of PS/cholesterol vesicles is slower than that of PS vesicles; the rate being reduced by an increase in cholesterol contents. With 600 mM NaCl, the overall fusion rate of PS/cholesterol 9:1 vesicles is faster than that of PS vesicles, and results are well-simulated by assuming no delay in vesicle aggregation up to dimers. Emerging f11 values are larger in PS/cholesterol than in PS vesicles. An analysis of fusion kinetics of several lipid concentrations shows that f11 values of PS/cholesterol 3:1 vesicles are 5-times larger than those of PS vesicles, when fusion occurs in a medium containing 200 mM NaCl and 1.5 mM Ca2+. The increase in Na+ concentration from 100 to 200 mM, or 600 mM results in a 50- or 150-fold reduction in f11 values of PS vesicles. It is suggested that incorporation of cholesterol in PS vesicles results in enhancement of Ca2+-induced fusogenic capacity.