| 1. |
- Ekelund, Oskar, et al.
(författare)
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Rapid high-resolution detection of colistin resistance in Gram-negative bacteria using flowcytometry : a comparison with broth microdilution, a commercial screening test and WGS
- 2021
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press. - 0305-7453 .- 1460-2091. ; 76:12, s. 3183-3191
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Even though both EUCAST and CLSI consider broth microdilution (BMD) as the reference method for antimicrobial susceptibility testing (AST) of colistin, the method exhibits potential flaws related to properties of the colistin molecule.OBJECTIVES: To develop a flow cytometry method (FCM) for colistin AST and to validate it against BMD, a commercial screening test and WGS.METHODS: Colistin-mediated loss of membrane integrity in Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp. was detected with the fluorescent probe YoPro-1 by FCM. An international collection of 65 resistant and 109 susceptible isolates were analysed and the colistin concentration required to reach the EC50 was compared with the BMD MIC and the presence of genotypic resistance markers.RESULTS: The overall FCM sensitivity and specificity for colistin resistance was 89% and 94%, with E. coli > K. pneumoniae > P. aeruginosa, whereas the performance for Acinetobacter spp. was poor. All tested E. coli were correctly categorized. Three K. pneumoniae isolates with genotypic findings consistent with colistin resistance were detected by FCM but not BMD. Compared with BMD, FCM delivered AST results with a 75% reduction of time.CONCLUSIONS: Here, we present a rapid FCM-based AST assay for qualitative and quantitative testing of colistin resistance in E. coli and K. pneumoniae. The assay revealed probable chromosomal colistin resistance in K. pneumoniae that was not detected by BMD. If confirmed, these results question the reliability of BMD for colistin testing.
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| 2. |
- Knöös Franzén, Ludvig, 1990-, et al.
(författare)
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A System of Systems Approach for Search and Rescue Missions
- 2020
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Konferensbidrag (refereegranskat)abstract
- System-of-Systems Engineering (SoSE) has become a constantly growing field within product development for complex systems. Systems are becoming more and more connected with other systems and the operational environment in general. This takes the development process to new levels of complexity where high degrees of uncertainties are expected due to ever occurring changes in the operational environment, and other external factors such as politics, economy, and technology. This creates a need of being able to understand the influence of changes early in the development process and to facilitate the systems? perseverance. The focus of the development shifts from fulfilling specific requirements, to being able to meet needs and deliver capabilities over time. Additionally, modeling and simulation for complex systems and System-of-Systems (SoS) becomes a valued alternative to the economically prohibited and almost impossible prototype testing. In consideration of this problem, the presented work introduces a method for both modeling and simulation of a SoS. The method uses ontology with description logic reasoning to derive and narrow down a SoS design space which is further analyzed using Agent Based Simulation (ABS). A Search and Rescue (SAR) scenario is used as a case study to test the method. Measures of Effectiveness (MoE), based on the time it takes to find a rescue subject and the cost of doing so, are used to evaluate the SoS performances. The presented method is envisioned to be used early in the development of complex systems and SoS to increase the overall understanding of them.
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| 3. |
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| 4. |
- Schön, Sofia, et al.
(författare)
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Exploring the Impact of Model Fidelity Through Interactive Visualizations for System of Systems
- 2022
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Ingår i: AIAA SciTech 2022 Forum, January 3-7, 2022, San Diego, CA & Virtual. - USA : American Institute of Aeronautics and Astronautics.
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Konferensbidrag (refereegranskat)abstract
- Studying Systems of Systems (SoS) in relation to Measures of Effectiveness (MoE) is a difficult task. This is due to that SoSs include several system levels and operate in changing environments. There are also computational challenges related to modeling and simulation of SoSs and it is difficult to predict behaviors. Therefore, choosing model fidelity for system models and assessing their impact on MoE is of high relevance to the field. This paper illustrates an approach to modeling and simulation for SoSs that can be used to assess the impact of scenario parameters and to explore when level of fidelity on system level affects the MoE. This is made through a case study based on Search and Rescue (SAR) operations where a Design Of Experiments (DOE) of scenario parameters is performed and simulations of each scenario experiment is performed. The case study shows how Agent Based Simulations (ABS) can be used to obtain the MoE for different SAR missions and how the choice of model fidelity for one of the aircraft’s sensors has different effects for various scenarios. Additionally, a Visual Analytics (VA) approach is introduced and used to create a dashboard for visualizing the obtained simulation results in an interactive way. This allows users to make explorations on the resulting data and see how different scenarios influence the performance of each SoS. Furthermore, the results show that changes in scenario parameters impacts the MoE and that this is difficult to predict, at least using a quantitative method. The results point to the importance of exploration for both the scenario, using an interactive dashboard, but also to the importance of exploring the simulation model to study emerging phenomenon. The results of this approach have raised questions regarding if a more qualitative approach of studying SoSs could be beneficial to study MoE for SoSs and if inspiration could be transferred from a more scientific point of view of systems.
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| 5. |
- Schön, Sofia, 1993-, et al.
(författare)
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Integration of Multi-Fidelity Models with Agent-Based Simulation for System of Systems
- 2021
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Ingår i: Proceedings of the AIAA Aviation 2021 Forum, Virtual Event, 2nd - 6th August, 2021.. - Reston, Virginia : American Institute of Aeronautics and Astronautics.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- System of Systems (SoS) are everywhere, either created and directed by an organization or simply emerging to fulfill a need. SoS consist of many independent Constituent Systems (CS) with their own life cycles and behavior. One of the big challenges with studying SoS is building models to support the analysis of these large complex systems. For existent SoS, it may be tempting to use available models from subsequent levels and connect them in a common framework, rather than creating new models tailored for the SoS analysis. Typically, the already existing models often have a high level of fidelity and have been created from a certain point of view to best fit its purpose. This paper shows that a framework with higher fidelity models on Sub-Systems (SS) level will impact the performance on SoS level but also take longer time to converge and thus need more simulations in order for the results to be trusted. With an holistic approach to the development of SoS, we use hierarchical integration of CS and SS models to provide inputs to the simulation on SoS level. Using maritime Search and Rescue (SAR) as a case study, the mission performance of two aircraft searching for a lost life raft through Agent Based Simulation (ABS). Two cases are compared where one of them has a higher fidelity representation of the sensor model. Through the case study it is possible to investigate the impact of model fidelity on the SS level to the simulation results on SoS level. The two cases simulate the same scenario but still show a difference in mission performance. A convergence analysis show that with the the High Fidelity Models (HFM) the simulation takes slightly longer to converge. This paper is the beginning of a multi-fidelity model library that will be used to explore the impact of model fidelity on all the levels of SoS and from that find general methods for choosing model fidelity when analyzing SoS.
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| 6. |
- Schön, Sofia, 1993-
(författare)
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Model Fidelity in Mission Scenario Simulations for Systems of Systems : A Case Study of Maritime Search and Rescue
- 2023
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Systems of Systems (SoS) represent a view where individual, independent systems named Constituent System (CS) collaborate to achieve overarching capabilities not attainable by a single CS alone. In cyberphysical systems, CS can be engineered entities like boats or aircraft, when they collaborate in an environment it can be viewed as an SoS. There is a large interest in modeling and simulation of phenomena present at different scales of SoS, which requires choosing appropriate model fidelity and resolution for the study. This thesis delves into the intricacies of modeling and simulation of mission scenarios within SoS, with a keen focus on engineered CS operating in physical environments. At the heart of the thesis lies the concept of model fidelity, examined through philosophical, scientific, and engineering perspectives.A maritime search and rescue scenario by airborne search assets serves as case study, using Agent Based Simulation (ABS) to explore the Measures of Effectiveness (MoE) of the mission. Through a hierarchical viewpoint it is studied how the model fidelity on Sub-System (SS) level affects its performance and how it aggregates up to performance on the CS level and at last the MoE on SoS level. In the scenarios, manned assets utilize traditional search patterns that is used in present search and rescue operations. Concurrently, autonomous assets employ a belief map search strategy where the map is based on probability density functions underpinned by a Bayesian modeling approach to new observations as the search progresses.The study shows that increasing the model fidelity at the SS level, particularly by refining the representation of the search sensor, can impact the MoE of the mission at the SoS level. However, this influence shows to be notably scenario-dependent, emphasizing the intricate relationship between model fidelity and system performance. The findings indicate that the relevance of model fidelity is tied to how measures of performance at lower levels aggregate to influence overarching mission outcomes. The thesis concludes by discussing validation and verification of the case study and ties encountered modeling difficulties to resolution and model fidelity aspects. Future work is suggested to be a deeper dive into mission engineering, where the mission itself is viewed as the system of interest, and how it could be combined with modeling and simulation in product development.
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| 7. |
- Tobias, Deirdre K, et al.
(författare)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Forskningsöversikt (refereegranskat)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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