Retrospective analysis of patients with SARS-CoV-2-infection or Covid-19 - Vascular Endothelium Growth Factor as potential prognostic biomarker

Einleitung: Das SARS-CoV-2-Virus löst Covid-19 aus. Als Pathomechanismus wird eine übersteuerte Immunantwort auf die virale Replikation, insbesondere mit entzündlicher Beteiligung von Endothel und konsekutiver mikrovaskulärer Dysfunktion in der Lungenstrombahn sowie Koagulopathie beobachtet. Das Spektrum der Erkrankungsschwere reicht von asyptomatischer Infektion bis hin zum schweren Lungenversagen (ARDS). Vascular Endothelial Growth Factor (VEGF) vermittelt proangiogene und endothelmodulierende Wirkungen und wird unter hypoxischen und proinflammatorischen Bedingungen verstärkt gebildet. Ziel dieser Arbeit ist, zu überprüfen, inwiefern sich das VEGF-Level bei verschiedenen Verlaufsformen von SARS-CoV-2-Infektionen unterscheidet und ob es zur Risikostratifizierung geeignet sein könnte. Methoden: Es erfolgte ein retrospektives Screening der im Unfallkrankenhaus Berlin behandelten Patient*innen mit dokumentierter SARS-CoV-2-Infektion im Jahr 2020. Eingeschlossen wurden diese, wenn mindestens eine VEGF-Messung vorlag. Zusätzlich hierzu wurden weitere Laboranalyte sowie klinische Parameter des Erkrankungsverlaufes inklusive Scores der Erkrankungsschwere, wie etwa APACHE-2, im Rahmen einer explorativen Datenanalyse mit den VEGF-Messwerten in Beziehung gesetzt. Ergebnis: Es wurden 167 SARS-CoV-2-positive Personen eingeschlossen, wovon 139 an Covid-19 erkrankt waren. Die VEGF-Konzentration war in der Covid-19-Gruppe signifikant höher als in der Gruppe der asymptomatischen Infizierten, während sich die Mortalität zwischen den Gruppen nicht signifikant unterschied. In multivariater Analyse zeigte sich die VEGF-Konzentration assoziiert mit geringer Sauerstoffsättigung bei Aufnahme sowie der Leukozytenzahl und der Neutrophilen-Lymphozyten-Ratio (NLR). VEGF war bei den intensivpflichtigen Covid-19-Patient*innen signifikant höher als bei Normalstationsfähigen. APACHE-2 eignete sich zur Vorhersage von Versterben. Patient*innen mit hohen Score-Werten wiesen signifikant höhere VEGF-Konzentrationen bei Aufnahme auf. Die ROC-Analytik ergab, dass insbesondere das Auftreten von Organinsuffizienzen wie ARDS, Schock oder Nierenversagen (nicht jedoch Delir) zuverlässiger durch VEGF als durch andere Laboranalyte vorhergesagt werden konnte. Verstorbene waren älter, öfter an Hypertonus und Diabetes vorerkrankt und wiesen niedrigere SpO2-Werte bei Aufnahme auf. VEGF war in dieser Gruppe signifikant höher als in der Gruppe der Überlebenden (637 vs. 389 pg/ml, p = 0,041) und sagte die Mortalität ähnlich gut wie etablierte Marker voraus. Diskussion: Trotz der Limitationen als retrospektive Arbeit kann VEGF einen guten Beitrag zur Risikostratifizierung bei COVID-19 Patient*innen etwa in der Vorhersage von Intensivpflichtigkeit, Mortalität, sowie der Entstehung bestimmter Organinsuffizienzen leisten und sollte als zusätzlicher prognostischer Parameter und in Bezug auf eine potentielle pathogenetische Rolle bei Covid-19 weiter untersucht werden.Introduction: SARS-CoV-2-virus spread worldwide and causes Covid-19 which mostly manifests as a lung disease. It is characterized by immunological responses to viral replication and coherent with endotheliitis, microvascular disturbance of lung vasculature and coagulopathy. Disease severity varies between asymptomatic infection and acute respiratory distress syndrome (ARDS). Vascular Endothelial Growth Factor (VEGF) is a proangiogenic mediator which regulates endothelial changes. It is induced by proinflammatory signaling and hypoxia. We sought to determine whether VEGF-levels are different in SARS-CoV-2-infections of different disease course or severity and whether VEGF might be useful in risk stratification. Methods: After retrospective screening of all SARS-CoV-2-positive patients in Unfallkrankenhaus Berlin in 2020 we included those with documented VEGF-measurement. We recorded further laboratory values and clinical parameter including intensive care severity scores like APACHE-2. An exploratory data analysis was performed to detect possible relations between VEGF-level and clinical disease features. Results: We included 167 SARS-CoV-2-positive patients of which 139 suffered from Covid-19. Between the groups of respiratorily asymptomatic vs symptomatic patients mortality did not differ but VEGF was significantly higher in the patient group with respiratory symptoms. Multivariant regression analysis revealed that VEGF was associated with lower oxygen saturation on admission and with white blood cell count and neutrophil-lymphocyte-ratio (NLR). 71 of the Covid-19-patients had to be treated in the intensive care unit (ICU). VEGF was significantly higher in the patient group treated in ICU than in those being admitted to normal wards. APACHE-2 correlated with mortality and patients with high score values showed higher VEGF-concentrations on admission. ROC-analytic revealed that the occurrence of organ dysfunctions like lung failure, shock or acute kidney injury (but not delirium) could be predicted by VEGF more precisely than other laboratory values. Patients who died were older, suffered more frequently from hypertension or diabetes and showed lower oxygen saturation on admission. VEGF was significantly higher in this group compared to survivors (637 vs. 389 pg/ml, p = 0,041) and predicted mortality with same accuracy as established markers. Discussion: Even though there are several limitations to this retrospective study it revealed that in Covid-19 patients VEGF can contribute to the prediction of necessity of intensive care, mortality and the prediction of ARDS, kidney injury or shock. Its use in risk stratification of Covid-19 and potential pathogenetic involvement should be further investigated

Exchanging uncertainty: interoperable geostatistics?

Traditionally, geostatistical algorithms are contained within specialist GIS and spatial statistics software. Such packages are often expensive, with relatively complex user interfaces and steep learning curves, and cannot be easily integrated into more complex process chains. In contrast, Service Oriented Architectures (SOAs) promote interoperability and loose coupling within distributed systems, typically using XML (eXtensible Markup Language) and Web services. Web services provide a mechanism for a user to discover and consume a particular process, often as part of a larger process chain, with minimal knowledge of how it works. Wrapping current geostatistical algorithms with a Web service layer would thus increase their accessibility, but raises several complex issues. This paper discusses a solution to providing interoperable, automatic geostatistical processing through the use of Web services, developed in the INTAMAP project (INTeroperability and Automated MAPping). The project builds upon Open Geospatial Consortium standards for describing observations, typically used within sensor webs, and employs Geography Markup Language (GML) to describe the spatial aspect of the problem domain. Thus the interpolation service is extremely flexible, being able to support a range of observation types, and can cope with issues such as change of support and differing error characteristics of sensors (by utilising descriptions of the observation process provided by SensorML). XML is accepted as the de facto standard for describing Web services, due to its expressive capabilities which allow automatic discovery and consumption by ‘naive’ users. Any XML schema employed must therefore be capable of describing every aspect of a service and its processes. However, no schema currently exists that can define the complex uncertainties and modelling choices that are often present within geostatistical analysis. We show a solution to this problem, developing a family of XML schemata to enable the description of a full range of uncertainty types. These types will range from simple statistics, such as the kriging mean and variances, through to a range of probability distributions and non-parametric models, such as realisations from a conditional simulation. By employing these schemata within a Web Processing Service (WPS) we show a prototype moving towards a truly interoperable geostatistical software architecture

The potential of a confined closed greenhouse in terms of sustainable production, crop growth, yield and valuable plant compounds of tomatoes

A confined closed greenhouse (CGH) was applied to save energy and to investigate how tomatoes respond to specific microclimatic conditions. As such, new dynamic set-points for precise climate control were used in the CGH compared to those applied in a conventional greenhouse. Based on the reduced ventilation frequency in the CGH, the results showed that higher levels of mean temperature, CO2 concentration and relative humidity were achieved. Although the light interception was increased in the CGH, these changing microclimatic conditions resulted in higher rates of photosynthesis and an associated faster crop growth. This means that the mean plant height was increased by 1.5 m, which was the decisive factor to increase the total yield by 21.4% in relation to that produced in the conventional greenhouse. The new microclimatic environment caused by the CGH promoted the accumulation of primary and secondary plant compounds in tomatoes such as soluble solids (by 9%), lycopene (by 22%), ß-carotene (by 21%), phenolics (by 8%) and L-ascorbic acid (by 26%) compared to conventional produced tomatoes. Compared to existing greenhouse systems, the results suggested that a CGH can be used to produce tomatoes in a sustainable way, where the water use and the energy use efficiency can be improved by 71% and 43%, respectively

Mashups: An Approach to Overcoming the Business/IT Gap in Service-Oriented Architectures

For quite a long time already, great importance has been attached to the concept of Service-Oriented Architectures for future IT-architectures. However, a major challenge in implementing this concept lies in the gap between the functional department and IT department. Mashups, an architecture also based on services, try to avoid this gap by letting the user himself integrate the services. The following article analyzes similarities and differences between both architecture approaches, and explains to what extent and in which cases Mashups could complement a Service-Oriented Architecture

Religious revelation, secrecy and the limits of visual representation

This article seeks to contribute to a more adequate understanding of the adoption of modern audiovisual mass media by contemporary religious groups. It does so by examining Pentecostal-charismatic churches as well as the Christian mass culture instigated by its popularity, and so-called traditional religion in Ghana, which develop markedly different attitudes towards audiovisual mass media and assume different positions in the public sphere. Taking into account the complicated entanglement of traditional religion and Pentecostalism, approaching both religions from a perspective of mediation which regards media as intrinsic to religion, and seeking to avoid the pitfall of overestimating the power of modern mass media to determine the world, this article seeks to move beyond an unproductive recurrence to oppositions such as tradition and modernity, or religion and technology. It is argued that instead of taking as a point of departure more or less set ideas about the nexus of vision and modernity, the adoption of new mass media by religious groups needs to be analyzed by a detailed ethnographic investigation of how these new media transform existing practices of religious mediation. Special emphasis is placed on the tension between the possibilities of gaining public presence through new media, and the difficulty in authorizing these media, and the experiences they induce, as authentic. Copyright © 2006 SAGE Publications

Cyberinfrastructure for the digital brain:spatial standards for integrating rodent brain atlases

Biomedical research entails capture and analysis of massive data volumes and new discoveries arise from data-integration and mining. This is only possible if data can be mapped onto a common framework such as the genome for genomic data. In neuroscience, the framework is intrinsically spatial and based on a number of paper atlases. This cannot meet today’s data-intensive analysis and integration challenges. A scalable and extensible software infrastructure that is standards based but open for novel data and resources, is required for integrating information such as signal distributions, gene-expression, neuronal connectivity, electrophysiology, anatomy, and developmental processes. Therefore, the International Neuroinformatics Coordinating Facility (INCF) initiated the development of a spatial framework for neuroscience data integration with an associated Digital Atlasing Infrastructure (DAI). A prototype implementation of this infrastructure for the rodent brain is reported here. The infrastructure is based on a collection of reference spaces to which data is mapped at the required resolution, such as the Waxholm Space (WHS), a 3D reconstruction of the brain generated using high-resolution, multi-channel microMRI. The core standards of the digital atlasing service-oriented infrastructure include Waxholm Markup Language (WaxML): XML schema expressing a uniform information model for key elements such as coordinate systems, transformations, points of interest (POI)s, labels, and annotations; and Atlas Web Services: interfaces for querying and updating atlas data. The services return WaxML-encoded documents with information about capabilities, spatial reference systems and structures, and execute coordinate transformations and POI-based requests. Key elements of INCF-DAI cyberinfrastructure have been prototyped for both mouse and rat brain atlas sources, including the Allen Mouse Brain Atlas, UCSD Cell-Centered Database, and Edinburgh Mouse Atlas Project