| 549881. |
- Lindgren, Petter, et al.
(författare)
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A likelihood ratio-based approach for improved source attribution in microbiological forensic investigations
- 2019
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Ingår i: Forensic Science International. - : Elsevier. - 0379-0738 .- 1872-6283. ; 302
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Tidskriftsartikel (refereegranskat)abstract
- A common objective in microbial forensic investigations is to identify the origin of a recovered pathogenic bacterium by DNA sequencing. However, there is currently no consensus about how degrees of belief in such origin hypotheses should be quantified, interpreted, and communicated to wider audiences. To fill this gap, we have developed a concept based on calculating probabilistic evidential values for microbial forensic hypotheses. The likelihood-ratio method underpinning this concept is widely used in other forensic fields, such as human DNA matching, where results are readily interpretable and have been successfully communicated in juridical hearings. The concept was applied to two case scenarios of interest in microbial forensics: (1) identifying source cultures among series of very similar cultures generated by parallel serial passage of the Tier 1 pathogen Francisella tularensis, and (2) finding the production facilities of strains isolated in a real disease outbreak caused by the human pathogen Listeria monocytogenes. Evidence values for the studied hypotheses were computed based on signatures derived from whole genome sequencing data, including deep-sequenced low-frequency variants and structural variants such as duplications and deletions acquired during serial passages. In the F. tularensis case study, we were able to correctly assign fictive evidence samples to the correct culture batches of origin on the basis of structural variant data. By setting up relevant hypotheses and using data on cultivated batch sources to define the reference populations under each hypothesis, evidential values could be calculated. The results show that extremely similar strains can be separated on the basis of amplified mutational patterns identified by high-throughput sequencing. In the L. monocytogenes scenario, analyses of whole genome sequence data conclusively assigned the clinical samples to specific sources of origin, and conclusions were formulated to facilitate communication of the findings. Taken together, these findings demonstrate the potential of using bacterial whole genome sequencing data, including data on both low frequency SNP signatures and structural variants, to calculate evidence values that facilitate interpretation and communication of the results. The concept could be applied in diverse scenarios, including both epidemiological and forensic source tracking of bacterial infectious disease outbreaks.
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| 549882. |
- Lindgren, Per, et al.
(författare)
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A Real-Time Semantics for the IEC 61499 standard
- 2015
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Ingår i: Proceedings of 2015 IEEE 20th International Conference on Emerging Technologies & Factory Automation (ETFA 2015). - Piscataway, NJ : IEEE Communications Society. - 9781467379298
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Konferensbidrag (refereegranskat)abstract
- The IEC 61499 standard provides an executable model for distributed control systems in terms of interacting function blocks. However, the current IEC 61499 standard lacks appropriate timing semantics for the specification of timing requirements, reasoning on timing properties at the model level, and for the timing verification of a specific deployment. In this paper we address this fundamental shortcoming by proposing Real-Time-4-FUN, a real-time semantics for IEC 61499. The key property is the preservation of non-determinism, allowing us to reason on (and verify) timing properties at the model level without assuming any specific scheduling policy or stipulating specific order of execution for the deployment. This provides for a clear separation of concerns, where the designer can focus on properties of the application prior to, and separately from, deployment verification. The proposed timing semantics is backwards compatible to the current standard, thus allow for reuse of existing designs. The transitional property allows timing requirements to propagate to downstream sub-systems, and can be utilized for scheduling both at device and network level. Based on a translation to RTFM-tasks and resources, IEC 61499 the models can be analyzed, compiled and executed. As a proof of concept the timing semantics has been experimentally implemented in the RTFM-core language and the accompanying (thread based) RTFM-RT run-time system.
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| 549883. |
- Lindgren, Per, et al.
(författare)
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A SOA approach to delay and jitter tolerant distributed real-time complex event processing
- 2013
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Ingår i: 2013 IEEE International Symposium on Industrial Electronics (ISIE 2013). - Piscataway, NJ : IEEE Communications Society. - 9781467351935
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Konferensbidrag (refereegranskat)abstract
- The combination of Service Oriented Architectures (SOAs) and Complex Event Processing (CEP) is gaining momen- tum for event centric management and processing of informa- tion in complex distributed systems (e.g., business automation). Whereas systems for factory automation have traditionally been deployed using dedicated buses and proprietary (often scan based) protocols, a recent trend in process automation is towards adopting open internet based technologies and event based communication. This trend is driven by the increasing number and capabilities of devices used for monitoring and control, and the increased flexibility, maintainability and price/performance gains expected from IP (potentially SOA/CEP) enabled systems.In this paper we discuss the challenges involved to apply SOA and CEP to the field of factory automation. In particular, real- time aspects are highlighted, both w.r.t. to accurate time-stamping of physical events in a distributed system, as well as end-to-end timing including communication and CEP processing.We approach the challenges by an architecture combining state-of-the-art synchronisation mechanisms for wired and wire- less networks together with real-time communication and dis- tributed query processing based on the notion of time constrained reactions. We discuss the impact of synchronisation inaccuracies and delays introduced by processing and communication, and present a method for implementation of safe potential- and certain matches.
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| 549884. |
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| 549885. |
- Lindgren, Per, et al.
(författare)
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Abstract Timers and their Implementation onto the ARM Cortex-M family of MCUs
- 2016
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Ingår i: SIGBED Review. - : Association for Computing Machinery (ACM). - 1551-3688. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Real-Time For the Masses (RTFM) is a set of languages andtools being developed to facilitate embedded software developmentand provide highly ecient implementations gearedto static verication. The RTFM-kernel is an architecturedesigned to provide highly ecient and predicable Stack ResourcePolicy based scheduling, targeting bare metal (singlecore)platforms.We contribute by introducing a platform independent timerabstraction that relies on existing RTFM-kernel primitives.We develop two alternative implementations for the ARMCortex-M family of MCUs: a generic implementation, usingthe ARM dened SysTick/DWT hardware; and a targetspecic implementation, using the match compare/free runningtimers. While sacricing generality, the latter is moreexible and may reduce overall overhead. Invariants for correctnessare presented, and methods to static and run-timeverication are discussed. Overhead is bound and characterized.In both cases the critical section from release timeto dispatch is less than 2us on a 100MHz MCU. Queue andtimer mechanisms are directly implemented in the RTFMcorelanguage (-core in the following) and can be includedin system-wide scheduling analysis.
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| 549886. |
- Lindgren, Peter, et al.
(författare)
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Association between achieving treatment goals for lipid-lowering and cardiovascular events in real clinical practice
- 2005
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Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - : Oxford University Press (OUP). - 1741-8267 .- 1741-8275. ; 12:6, s. 530-534
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is substantial evidence that treatment with lipid-lowering agents can decrease cardiovascular morbidity and total mortality in patients with elevated serum lipid values and/or prior ischaemic heart disease. However, only a minority of these high-risk patients are believed to receive treatment, and among those who do receive pharmaceutical treatment the majority do not reach the therapeutic goal. Our goal was to investigate if this translates to a higher risk of cardiovascular events in real clinical practice. DESIGN: A retrospective cohort study using linkage of electronic medical records, the Swedish national inpatient registry and cause of death registry was performed, enrolling a total of 4976 patients who received treatment with a lipid-lowering agent at any time between 1 January 1993 and 1 December 2001. METHODS: Cox proportional hazards regression was used to evaluate the impact of goal attainment along with potential confounding factors. RESULTS: Patients who reached treatment goals were 24% less likely to suffer a cardiovascular event (relative risk: 0.76, 95% confidence interval: 0.60-0.96) than patients who did not reach treatment goals. A substantial proportion of patients treated with lipid-lowering agents do not achieve the treatment goals. CONCLUSIONS: Failure to reach treatment goals translates into a higher risk of cardiovascular events, and it is thus of importance to ensure that patients reach goals.
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| 549887. |
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| 549888. |
- Lindgren, Per, et al.
(författare)
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Contract Based Verification of IEC 61499
- 2017
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Ingår i: IEEE International Conference on Industrial Informatics (INDIN). - Piscataway, NJ : Institute of Electrical and Electronics Engineers (IEEE). - 9781509028702 ; , s. 132-141
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Konferensbidrag (refereegranskat)abstract
- The IEC 61499 standard proposes an event drivenexecution model for component based (in terms of FunctionBlocks), distributed industrial automation applications. However,the standard provides only an informal execution semantics, thusin consequence behavior and correctness relies on the designdecisions made by the tool vendor. In this paper we presentthe formalization of a subset of the IEC 61499 standard inorder to provide an underpinning for the static verification ofFunction Block models by means of deductive reasoning. Specifically,we contribute by addressing verification at the component,algorithm, and ECC levels. From Function Block descriptions, enrichedwith formal contracts, we show that correctness of componentcompositions, as well as functional and transitional behaviorcan be ensured. Feasibility of the approach is demonstrated bymanually encoding a set of representative use-cases in WhyML,for which the verification conditions are automatically derived(through the Why3 platform) and discharged (using automaticSMT-based solvers). Furthermore, we discuss opportunities andchallenges towards deriving certified executables for IEC 61499models.
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| 549889. |
- Lindgren, Peter, et al.
(författare)
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Cost-effectiveness analysis of exemestane compared with megestrol in advanced breast cancer: A model for Europe and Australia
- 2002
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Ingår i: PharmacoEconomics. - : Adis International. - 1179-2027 .- 1170-7690. ; 20:2, s. 101-108
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the cost effectiveness of exemestane compared to megestrol in post-menopausal women after tamoxifen failure. Design and setting: A modelling study from the third-party payer perspective in Australia, Belgium, France, Germany, Italy, The Netherlands, Spain and the United Kingdom. Methods:Amodelwas constructed, based on and driven by data on survival from a clinical study of these agents, including costs for exemestane and megestrol and costs for other treatments.Data from an observational study were used to calculate a country-specific daily cost for the other treatments. Life-years gained was used as the measure of effectiveness. Simulations were performed for 1080 days (‘within trial analysis’) and for a life-time perspective, in which survival after the end of the trial was assumed to be the same as the trend during follow up. Costs were presented in 1999 values. Main outcome measures and results: When running the model for 1080 days, the cost effectiveness of exemestane compared to megestrol varied between about EUR5000 and EUR13 000 per life-year gained. In Germany it was much lower (EUR1353) due to a higher cost of megestrol. The total expected cost effectiveness (model running until no survivors left) ranged from EUR3700 (Germany) to EUR9100 (The Netherlands). The estimated cost per life-year gained is well within limits generally considered cost effective. Conclusions: Exemestane is cost effective compared with megestrol for postmenopausal women with progressive advanced breast cancer after therapy with tamoxifen.
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| 549890. |
- Lindgren, P., et al.
(författare)
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Cost-effectiveness of atorvastatin for the prevention of coronary and stroke events: an economic analysis of the Anglo-Scandinavian Cardiac Outcomes Trial--lipid-lowering arm (ASCOT-LLA)
- 2005
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Ingår i: Eur J Cardiovasc Prev Rehabil. - : Oxford University Press (OUP). - 1741-8267. ; 12:1, s. 29-36
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study is to assess the cost-effectiveness of the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LLA) where patients from seven countries with hypertension and no history of coronary heart disease (CHD) were randomized to receive 10 mg atorvastatin or placebo. DESIGN: Economic analysis of a randomized controlled trial. METHODS: Data on resource use were aggregated for all patients during the entire trial period (median 3.3 years) and multiplied with unit costs for Sweden and the UK. The total number of cardiovascular events and procedures avoided was used as the measure of effectiveness. RESULTS: Patients treated with atorvastatin had an additional net costs of 449 euro (4114 SEK) in Sweden and 414 euro (260 pounds sterling) in the UK, but fewer events per patient (0.097 compared to 0.132). The incremental cost-effectiveness ratios were 12673 euro (116119 SEK) and 11693 euro (7349 pounds sterling) per event avoided. CONCLUSION: Based on comparisons with the WOSCOPS and 4S studies, atorvastatin at 10 mg to treat patients as in the ASCOT study, appears to be a cost-effective strategy.
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