Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in severe COVID-19

The clinical course of the 2019 coronavirus disease (COVID-19) is variable and to a substantial degree still unpredictable, especially in persons who have neither been vaccinated nor recovered from previous infection. We hypothesized that disease progression and inflammatory responses were associated with alterations in the microbiome and metabolome. To test this, we integrated metagenome, metabolome, cytokine, and transcriptome profiles of longitudinally collected samples from hospitalized COVID-19 patients at the beginning of the pandemic (before vaccines or variants of concern) and non-infected controls, and leveraged detailed clinical information and post-hoc confounder analysis to identify robust within- and cross-omics associations. Severe COVID-19 was directly associated with a depletion of potentially beneficial intestinal microbes mainly belonging to Clostridiales, whereas oropharyngeal microbiota disturbance appeared to be mainly driven by antibiotic use. COVID-19 severity was also associated with enhanced plasma concentrations of kynurenine, and reduced levels of various other tryptophan metabolites, lysophosphatidylcholines, and secondary bile acids. Decreased abundance of Clostridiales potentially mediated the observed reduction in 5-hydroxytryptophan levels. Moreover, altered plasma levels of various tryptophan metabolites and lower abundances of Clostridiales explained significant increases in the production of IL-6, IFNγ and/or TNFα. Collectively, our study identifies correlated microbiome and metabolome alterations as a potential contributor to inflammatory dysregulation in severe COVID-19

Probabilistic safety assessment of fire hazards

An as far as possible exhaustive conceptual approach has been developed to systematically address all kinds of internal and external hazards and their potential combinations in Level 1 PSA in a comprehensive manner. The approach assumes a comprehensive generic compilation of hazards being available. By means of site-specific screening process it is decided which hazards need to be analysed in detail by means of probabilistic methods. The requested extension of the plant model is carried out by a systematic approach for those hazards to be analysed in detail. For this purpose, lists of hazard relevant structures, systems and components and their failure dependencies according to the hazards are derived. The comprehensive extension of Level 1 PSA by hazards is demonstrated at the example of plant internal fires

Approach to assess fire risk for nuclear power plants

The results of the first fire risk assessments on an international level have shown that fires are one major contributor to the risk of a nuclear power plant depending on the plant specific fire protection concept. Therefore, fire risk assessment has today become an integral part of the probabilistic safety assessment of nuclear power plants in addition to deterministic analyses. Based on existing guidance documents a state-ofthe-art approach for performing probabilistic fire risk assessment has also been developed in Germany. This approach has been exemplarily and completely applied to a German nuclear power plant with boiling water reactor for the full power states PSA. The general approach outlines the steps necessary for performing fire risk assessment and the prerequisites for a sound and traceable database

Development of a Library Based Tool for Screening External Hazards and Hazard Combinations

For a meaningful and efficient probabilistic risk analysis of external hazards and event combinations involving such hazards those hazards with significant risk potential need to be identified and considered for detailed anal-yses. Such a site and plant specific screening approach for external and internal hazards based on a hazards library covering all types of hazards is under development at GRS. The paper provides insights on the approach and first examples of application

Operating Experience with Hydrological External Hazards and Their Potential Safety Significance

The nuclear accidents of Fukushima in March 2011 have indicated the significance of external hazards for nuclear installations safety. One lesson learned from post-Fukushima investigations worldwide is that the operating experience from external hazards, even if these did not pose any significant harm to the affected plant, do represent important precursors, which should be taken into account in deterministic as well as probabilistic safety assessment. This paper provides an overview on the significance of events or event combinations involving hydrological external hazards. Some more recent examples of events from hydrological external hazards and their potential safety significance for nuclear power plants are discussed

Methods to assess effects of cable failures caused by fire

It is state-of-the-art that a Level 1 PSA also includes a fire PSA for all plant operational states. In performing Fire PSA not only the malfunction of the components has to be assessed but also all supply systems and cables have to be traced for a given component. In the past it was assumed in the case of a fire in a compartment that all components and cables in that compartment are not functional anymore. However, this is in many cases a too conservative approach and could lead to overestimated fire induced core damage frequencies. Therefore, a method is necessary to assess in a more realistic manner the effects of cables failures caused by fire. Such a procedure requires a sound data base on equipment, list of cables and their properties as well as cable routing. Two methods are described which are currently developed. One of them is a cable failure mode and effect analysis which is easier to apply in practice

Risk analysis of external hydrological hazards with flooding potential for a German nuclear reference site

Probabilistic Safety Analyses (PSA) are a supplementary analytical tool used worldwide more and more in order to quantitatively assess the effect of hazards on the overall result regarding the safety of industrial installations, in particular nuclear power plants. In that way PSA provides a reliable basis for decisions on the necessity and the benefits of safety improvements. In the recent past, the existing methods and tools with respect to determining the site-specific risk of nuclear power plants have been comprehensively extended and further enhanced. The focus of extending the existing PSA methods was on external hydrological hazards with flooding potential. For systematically considering hydrological hazards within PSA a systematic approach has been developed. The paper demonstrates the extended approach in the example of a nuclear power plant site with different flooding risks