| 1. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 2. |
- Oddsson, Asmundur, et al.
(författare)
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Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
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| 3. |
- Bräuner, Elvira Vaclavik, et al.
(författare)
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Indoor particles affect vascular function in the aged: an air filtration-based intervention study.
- 2008
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Ingår i: American journal of respiratory and critical care medicine. - 1535-4970. ; 177:4, s. 419-25
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Exposure to particulate matter is associated with risk of cardiovascular events, possibly through endothelial dysfunction, and indoor air may be most important. OBJECTIVES: We investigated effects of controlled exposure to indoor air particles on microvascular function (MVF) as the primary endpoint and biomarkers of inflammation and oxidative stress as secondary endpoints in a healthy elderly population. METHODS: A total of 21 nonsmoking couples participated in a randomized, double-blind, crossover study with two consecutive 48-hour exposures to either particle-filtered or nonfiltered air (2,533-4,058 and 7,718-12,988 particles/cm(3), respectively) in their homes. MEASUREMENTS AND MAIN RESULTS: MVF was assessed noninvasively by measuring digital peripheral artery tone after arm ischemia. Secondary endpoints included hemoglobin, red blood cells, platelet count, coagulation factors, P-selectin, plasma amyloid A, C-reactive protein, fibrinogen, IL-6, tumor necrosis factor-alpha, protein oxidation measured as 2-aminoadipic semialdehyde in plasma, urinary 8-iso-prostaglandin F(2alpha), and blood pressure. Indoor air filtration significantly improved MVF by 8.1% (95% confidence interval, 0.4-16.3%), and the particulate matter (diameter < 2.5 mum) mass of the indoor particles was more important than the total number concentration (10-700 nm) for these effects. MVF was significantly associated with personal exposure to iron, potassium, copper, zinc, arsenic, and lead in the fine fraction. After Bonferroni correction, none of the secondary biomarkers changed significantly. CONCLUSIONS: Reduction of particle exposure by filtration of recirculated indoor air for only 48 hours improved MVF in healthy elderly citizens, suggesting that this may be a feasible way of reducing the risk of cardiovascular disease.
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| 4. |
- Erlström, Mikael, et al.
(författare)
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Stratigraphy and geothermal assessment of Mesozoic sandstone reservoirs in the Öresund Basin - exemplified by well data and seismic profiles
- 2018
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Ingår i: Bulletin of the Geological Society of Denmark. - 0011-6297. ; 66, s. 123-149
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Tidskriftsartikel (refereegranskat)abstract
- The Øresund Basin in the transnational area between Sweden and Denmark forms a marginal part of the Danish Basin. The structural outline and stratigraphy of the Mesozoic succession is described, and a novel interpretation and description of the subsurface geology and geothermal potential in the North Sjælland Half-graben is presented. The subsurface bedrock in the basin includes several Mesozoic intervals with potential geothermal sandstone reservoirs. Parts of the succession fulfill specific geological requirements about distribution, composition and quality of the sandstones. A characterisation of these is presently of great interest in the attempt to identify geothermal reservoirs suitable for district heating purposes. The results presented in this paper include for the first time a comprehensive description of the stratigraphic intervals as well as the characteristics of the potential Mesozoic geothermal reservoirs in the Øresund region, including their distribution, composition and physical properties. This is illustrated by seismic cross-sections and well sections. In addition, results from analyses and evaluations of porosity, permeability, formation fluids and temperature are presented. Six potential geothermal reservoirs in the Mesozoic succession are described and assessed. Primary focus is placed on the characteristics of the reservoirs in the Lower Triassic and Rhaetian–Lower Jurassic succession. The study shows that the Mesozoic reservoir sandstones vary considerably with respect to porosity and permeability. Values range between 5–25% for the pre-Rhaetian Triassic sandstones, but are commonly > 25% for the Rhaetian–Lower Jurassic and Lower Cretaceous sandstones. The corresponding permeability rarely reaches above 500 mD for the pre-Rhaetian Triassic reservoirs, but often reach >1 Darcy for the Rhaetian–Lower Jurassic and the Lower Cretaceous sandstones. The interpreted formation temperatures for the reservoirs in the Øresund Basin are: 45–50°C at 1500 m, 60–70°C at 2000 m and 70–90°C at 2500 m depth . The combined results provide a geological framework for making site specific predictions regarding appraisal of viable geothermal projects for district heating purposes in the region as well as reducing the risk of unsuccessful wells
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| 5. |
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| 6. |
- Gunst, Jesper D., et al.
(författare)
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Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial
- 2021
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Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- Background: The trans-membrane protease serine 2 (TMPRSS2) is essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and infection. Efficacy and safety of TMPRSS2 inhibitors in patients with coronavirus disease 2019 (Covid-19) have not been evaluated in randomized trials.Methods: We conducted an investigator-initiated, double-blind, randomized, placebo-controlled multicenter trial in patients hospitalized with confirmed SARS-CoV-2 infection from April 4, to December 31, 2020. Within 48 h of admission, participants were randomly assigned in a 2:1 ratio to receive the TMPRSS2 inhibitor camostat mesilate 200 mg three times daily for 5 days or placebo. The primary outcome was time to discharge or clinical improvement measured as ≥2 points improvement on a 7-point ordinal scale. Other outcomes included 30-day mortality, safety and change in oropharyngeal viral load. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001,200-42.Findings: 137 patients were assigned to receive camostat mesilate and 68 to placebo. Median time to clinical improvement was 5 days (interquartile range [IQR], 3 to 7) in the camostat group and 5 days (IQR, 2 to 10) in the placebo group (P = 0·31). The hazard ratio for 30-day mortality in the camostat compared with the placebo group was 0·82 (95% confidence interval [CI], 0·24 to 2·79; P = 0·75). The frequency of adverse events was similar in the two groups. Median change in viral load from baseline to day 5 in the camostat group was -0·22 log10 copies/mL (p <0·05) and -0·82 log10 in the placebo group (P <0·05).Interpretation: Under this protocol, camostat mesilate treatment was not associated with increased adverse events during hospitalization for Covid-19 and did not affect time to clinical improvement, progression to ICU admission or mortality.
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| 7. |
- Vester, Mazen, et al.
(författare)
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Myocardial perfusion imaging by 15O-H2O positron emission tomography predicts clinical revascularization procedures in symptomatic patients with previous coronary artery bypass graft.
- 2023
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Ingår i: European Heart Journal Open. - 2752-4191. ; 3:3, s. oead044-
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: We wanted to assess if 15O-H2O myocardial perfusion imaging (MPI) in a clinical setting can predict referral to coronary artery catheterization [coronary angiography (CAG)], execution of percutaneous coronary intervention (PCI), and post-PCI angina relief for patients with angina and previous coronary artery bypass graft (CABG).METHODS AND RESULTS: We analysed 172 symptomatic CABG patients referred for 15O-H2O positron emission tomography (PET) MPI at Aarhus University Hospital Department of Nuclear Medicine & PET Centre, of which five did not complete the scan. In total, 145 (87%) enrolled patients had an abnormal MPI. Of these, 86/145 (59%) underwent CAG within 3 months; however, no PET parameters predicted referral to CAG. During the CAG, 25/86 (29%) patients were revascularized by PCI. Relative flow reserve (RFR) (0.49 vs. 0.54 P = 0.03), vessel-specific myocardial blood flow (MBF) (1.53 vs. 1.88 mL/g/min, P < 0.01), and vessel-specific myocardial flow reserve (MFR) (1.73 vs. 2.13, P < 0.01) were significantly lower in patients revascularized by PCI. Receiver operating characteristic analysis of the vessel-specific parameters yielded optimal cutoffs of 1.36 mL/g/min (MBF) and 1.28 (MFR) to predict PCI. Angina relief was experienced by 18/24 (75%) of the patients who underwent PCI. Myocardial blood flow was an excellent predictor of angina relief on both a global [area under the curve (AUC) = 0.85, P < 0.01] and vessel-specific (AUC = 0.90, P < 0.01) level with optimal cutoff levels of 1.99 mL/g/min and 1.85 mL/g/min, respectively.CONCLUSION: For CABG patients, RFR, vessel-specific MBF, and vessel-specific MFR measured by 15O-H2O PET MPI predict whether subsequent CAG will result in PCI. Additionally, global and vessel-specific MBF values predict post-PCI angina relief.
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| 8. |
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| 9. |
- Ahlberg, Erik, et al.
(författare)
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"Vi klimatforskare stödjer Greta och skolungdomarna"
- 2019
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Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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| 10. |
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| 11. |
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| 12. |
- Andersson, Per, et al.
(författare)
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Modelling and Architecture Examples of Model Based Engine Control
- 1999
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Konferensbidrag (refereegranskat)abstract
- Environmental regulations and drivability issues are driving forces in the development of control systems for automotive engines. Precise control of the air and fuel is fundamental for achieving the goals. Furthermore, the architecture for the controller plays a central role in how the goals are achieved.A comparison is made between two conventional controller structures and a model based structure. The performance of the different control structures is evaluated on a simulation model. To point out the differences the evaluation is concentrated to transient conditions where a step in throttle angle is used as input to the system. In addition, connections between controllers and the engine model is discussed.
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| 13. |
- Andrikopoulos, Petros, et al.
(författare)
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Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
- 2023
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Batra, Gorav, et al.
(författare)
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Data standards for atrial fibrillation/flutter and catheter ablation : The European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart)
- 2023
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Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - : Oxford University Press. - 2058-5225 .- 2058-1742. ; 9:6, s. 609-620
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Standardized data definitions are essential for monitoring and assessment of care and outcomes in observational studies and randomized controlled trials (RCTs). The European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart) project of the European Society of Cardiology aimed to develop contemporary data standards for atrial fibrillation/flutter (AF/AFL) and catheter ablation.METHODS AND RESULTS: We used the EuroHeart methodology for development of data standards and formed a Working Group comprising 23 experts in AF/AFL and catheter ablation registries, as well as representatives from the European Heart Rhythm Association and EuroHeart. We conducted a systematic literature review of AF/AFL and catheter ablation registries and data standard documents to generate candidate variables. We used a modified Delphi method to reach consensus on a final variable set. For each variable, the Working Group developed permissible values and definitions, and agreed as to whether the variable was mandatory (Level 1) or additional (Level 2). In total, 70 Level 1 and 92 Level 2 variables were selected and reviewed by a wider Reference Group of 42 experts from 24 countries. The Level 1 variables were implemented into the EuroHeart IT platform as the basis for continuous registration of individual patient data.CONCLUSION: By means of a structured process and working with international stakeholders, harmonized data standards for AF/AFL and catheter ablation for AF/AFL were developed. In context of the EuroHeart project, this will facilitate country-level quality of care improvement, international observational research, registry-based RCTs and post-marketing surveillance of devices and pharmacotherapies.
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| 19. |
- Berg Hansen, Kristoffer, et al.
(författare)
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Myocardial efficiency in patients with different aetiologies and stages of heart failure
- 2022
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 23:3, s. 328-337
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Myocardial external efficiency (MEE) is the ratio of cardiac work in relation with energy expenditure. We studied MEE in patients with different aetiologies and stages of heart failure (HF) to discover the role and causes of deranged MEE. In addition, we explored the impact of patient characteristics such as sex, body mass index (BMI), and age on myocardial energetics.Methods and results: Cardiac energetic profiles were assessed with C-11-acetate positron emission tomography (PET) and left ventricular ejection fraction (LVEF) was acquired with echocardiography. MEE was studied in 121 participants: healthy controls (n = 20); HF patients with reduced (HFrEF; n = 25) and mildly reduced (HFmrEF; n = 23) LVEF; and patients with asymptomatic (AS-asymp; n = 38) and symptomatic (AS-symp; n = 15) aortic stenosis (AS). Reduced MEE coincided with symptoms of HF irrespective of aetiology and declined in tandem with deteriorating LVEF. Patients with AS-symp and HFmrEF had reduced MEE as compared with controls (22.2 +/- 4.9%, P = 0.041 and 20.0 +/- 4.2%, P < 0.001 vs. 26.1 +/- 5.8% in controls) and a further decline was observed in patients with HFrEF (14.7 +/- 6.3%, P < 0.001). Disproportionate left ventricular hypertrophy was a major cause of reduced MEE. Female sex (P < 0.001), a lower BMI (P = 0.001), and advanced age (P = 0.03) were associated with a lower MEE.Conclusion: MEE was reduced in patients with HFrEF, HFmrEF, and HF due to pressure overload and MEE may therefore constitute a treatment target in HF. Patients with LVH, advanced age, female sex, and low BMI had more pronounced reduction in MEE and personalized treatment within these patient subgroups could be relevant.
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| 20. |
- Brugård, Jan, et al.
(författare)
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Mean Value Engine Modeling of a Turbo Charged Spark Ignited Engine : A Principle Study
- 2001
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Object oriented modeling of physical systems is an interesting paradigm, which has the potential to offer reusable models and model components. The aim of this study i to investigate how to build mean value models for automotive engines. MathModelica, a modeling tool for the object oriented modeling language Modelica, is used in this study. Several sub models have been developed for the different parts of the engine. Th models cover the air filter, intercooler, throttle, base engien, exhaust system, compressor, turbine, turbine shaft, and volumes. It is shown how the components can be connected to form both turbo charged engines as well as a naturally aspirated engines, which shows that the paradigm is applicable for the modeling and confirms the modeling principle. One problem that has popped up att several occasions is the selection of initial conditions for the simulation. Especially when restrictions with low pressure drops are connected between two volumes, the simulation engine has problems finding initial conditions. The models have been compared to measured engine data collected at a test bench in Vehicular Systems laboratory at Linköping University. The agreement with measurement data is good and the models work as expected.
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| 21. |
- Bräuner, Elvira Vaclavik, et al.
(författare)
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Exposure to ambient concentrations of particulate air pollution does not influence vascular function or inflammatory pathways in young healthy individuals.
- 2008
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Ingår i: Particle and fibre toxicology. - : Springer Science and Business Media LLC. - 1743-8977. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Particulate air pollution is associated with increased risk of cardiovascular events although the involved mechanisms are poorly understood. The objective of the present study was to investigate the effects of controlled exposure to ambient air fine and ultrafine particles on microvascular function and biomarkers related to inflammation, haemostasis and lipid and protein oxidation. METHODS: Twenty-nine subjects participated in a randomized, two-factor crossover study with or without biking exercise for 180 minutes and with 24 hour exposure to particle rich (number concentrations, NC: 11600 +/- 5600 per cm3, mass concentrations: 13.8 +/- 7.4 mug/m3 and 10.5 +/- 4.8 mug/m3 for PM10-2.5 and PM2.5, respectively) or particle filtered (NC: 555 +/- 1053 per cm3) air collected above a busy street. Microvascular function was assessed non-invasively by measuring digital peripheral artery tone following arm ischemia. Biomarkers included haemoglobin, red blood cells, platelet count, coagulation factors, C-reactive protein, fibrinogen, interleukin-6, tumour necrosis factor alpha, lag time to copper-induced oxidation of plasma lipids and protein oxidation measured as 2-aminoadipic semialdehyde in plasma. RESULTS: No statistically significant differences were observed on microvascular function or the biomarkers after exposure to particle rich or particle filtered air. CONCLUSION: This study indicates that exposure to air pollution particles at outdoor concentrations is not associated with detectable systemic inflammation, lipid or protein oxidation, altered haemostasis or microvascular function in young healthy participants.
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| 22. |
- Christesen, Henrik Thybo, et al.
(författare)
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Tissue variations of mosaic genome-wide paternal uniparental disomy and phenotype of multi-syndromal congenital hyperinsulinism
- 2020
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Ingår i: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212 .- 1878-0849. ; 63:1
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Tidskriftsartikel (refereegranskat)abstract
- Mosaic genome-wide paternal uniparental disomy (GW-pUPD) is a rarely recognised disorder. The phenotypic manifestations of multilocus imprinting defects (MLIDs) remain unclear. We report of an apparently non-syndromic infant with severe congenital hyperinsulinism (CHI) and diffuse pancreatic labelling by 18F*-DOPA-PET/CT leading to near-total pancreatectomy. The histology was atypical with pronounced proliferation of endocrine cells comprising >70% of the pancreatic tissue and a small pancreatoblastoma. Routine genetic analysis for CHI was normal in the blood and resected pancreatic tissue. At two years’ age, Beckwith-Wiedemann Syndrome (BWS) stigmata emerged, and at five years a liver tumour with focal nodular hyperplasia and an adrenal tumour were resected. pUPD was detected in 11p15 and next in the entire chromosome 11 with microsatellite markers. Quantitative fluorescent PCR with amplification of chromosome-specific DNA sequences for chromosomes 13, 18, 21 and X indicated GW-pUPD. A next generation sequencing panel with 303 SNPs on 21 chromosomes showed pUPD in both blood and pancreatic tissue. The mosaic distribution of GW-pUPD ranged from 31 to 35% in blood and buccal swap to 74% in the resected pancreas, 80% in a non-tumour liver biopsy, and 100% in the liver focal nodular hyperplasia and adrenal tumour. MLID features included transient conjugated hyperbilirubinaemia and lack of macrosomia from BWS (pUPD6); and behavioural and psychomotor manifestations of Angelman Syndrome (pUPD15) on follow-up. In conclusion, atypical pancreatic histology in apparently non-syndromic severe CHI patients may be the first clue to BWS and multi-syndromal CHI from GW-pUPD. Variations in the degree of mosaicism between tissues explained the phenotype.
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| 23. |
- Dekkers, Koen, et al.
(författare)
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An online atlas of human plasma metabolite signatures of gut microbiome composition.
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for a detailed characterization of the gut microbiota and plasma metabolome, respectively, of 8583 participants invited at age 50 to 64 from the population-based Swedish CArdioPulmonary bioImage Study. Here, we find that the gut microbiota explain up to 58% of the variance of individual plasma metabolites and we present 997 associations between alpha diversity and plasma metabolites and 546,819 associations between specific gut metagenomic species and plasma metabolites in an online atlas ( https://gutsyatlas.serve.scilifelab.se/ ). We exemplify the potential of this resource by presenting novel associations between dietary factors and oral medication with the gut microbiome, and microbial species strongly associated with the uremic toxin p-cresol sulfate. This resource can be used as the basis for targeted studies of perturbation of specific metabolites and for identification of candidate plasma biomarkers of gut microbiota composition.
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| 24. |
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| 25. |
- Edlund, Simon, et al.
(författare)
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A Real-Time Platform for Collaboration Projects in Power Train Modeling and Control
- 1999
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Konferensbidrag (refereegranskat)abstract
- The requirements on research and development in automotive control are growing fast, and therefore convenient and efficient ways to make prototype experiments and demonstrations are sought for. Collaboration projects put some additional constraints on the experimental system used due to issues of safety and secrecy. These requirements are outlined, a real-time platform is developed, and experiences from some collaboration projects between industry and academia are discussed.
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| 26. |
- Egstrup, Kenneth, et al.
(författare)
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QT Response after a Test Dose and during Maintenance Therapy with AZD1305 in Patients with Atrial Fibrillation: A Double-Blind, Randomized, Placebo-Controlled Trial.
- 2011
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Ingår i: American journal of cardiovascular drugs : drugs, devices, and other interventions. - : Springer Science and Business Media LLC. - 1179-187X. ; 11:3, s. 199-208
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective: AZD1305 is an investigational antiarrhythmic agent that prolongs refractoriness through combined potassium and sodium channel inhibition. This study aimed to explore the utility of a test dose in predicting QT interval corrected according to Fridericia's formula (QTcF) during subsequent maintenance treatment with AZD1305. Methods: This was a randomized, double-blind, parallel-group, placebo-controlled trial carried out at multiple hospital cardiac facilities in Denmark, Norway, Poland, Slovakia, and Sweden. Patients with documented atrial fibrillation (AF) but currently in stable sinus rhythm for ≥2 hours and ≤90 days were eligible for inclusion. Patients were randomized in a 1:1:1 ratio to receive AZD1305 extended-release or matching placebo tablets as follows: group A - test dose 250mg, evening dose 125mg on day 1, maintenance dose 125mg twice daily; group B - test dose 500mg, placebo evening dose, maintenance dose 125mg twice daily; placebo group - placebo test and maintenance dose. Maintenance dosing was for 9 days. QTcF >550ms at any time during the in-patient phase or >500ms after discharge (day 4) were predefined study drug discontinuation criteria. The main outcome measure was the relationship between QTcF following the test dose and during maintenance treatment. Results: Sixty-five patients were randomized (n=21, 22, and 22 in group A, group B, and the placebo group, respectively). AZD1305 dose-dependently increased QTcF. There was a positive, linear correlation between the change in QTcF during the first 6 hours after the test dose and during the maintenance phase. Three patients, all from group B, discontinued treatment on day 1 due to QTcF >550ms. All other patients completed the study without events related to QT prolongation. There was a trend for reduced AF recurrence with AZD1305 compared with placebo. Conclusion: In this exploratory study a test dose predicted the QT response during maintenance treatment with AZD1305 and may thus be employed in further studies. [ClinicalTrials.gov Identifier: NCT00643448].
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| 27. |
- Eriksson, Lars, 1970-, et al.
(författare)
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Closed Loop Ignition Control by Ionization Current Interpretation
- 1998
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Ingår i: SAE technical paper series. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191. ; 106:SAE Technical Paper 970854, s. 1216-1223
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Tidskriftsartikel (refereegranskat)abstract
- The main result of this paper is a real-time closed loop demonstration of spark advance control by interpretation of ionization current signals. The advantages of such a system is quantified. The ionization current, obtained by using the spark plug as a sensor, is rich on information, but the signal is also complex. A key step in our method is to use parameterized functions to describe the ionization current. The results are validated on a SAAB 2.3 l, normally aspirated, production engine, showing that the placement of the pressure trace relative to TDC is controlled using only the ionization current for feedback.
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| 28. |
- Eriksson, Lars, 1970-, et al.
(författare)
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Ignition Control by Ionization Current Interpretation
- 1997
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Ingår i: SAE technical paper series. - 400 Commonwealth Drive, Warrendale, PA, United States : S A E Inc.. - 0148-7191. ; 105:SAE Technical Paper 960045, s. 165-171
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Tidskriftsartikel (refereegranskat)abstract
- Spark advance setting in spark-ignited engines is used to place the in-cylinder pressure curve relative to the top dead center. It is demonstrated that ionization current interpretation is feasible to use for spark advance control to optimize engine performance. A feedback scheme, not a calibration scheme, based on ionization current is proposed. It is thus related to pressure sensor feedback schemes, that have reported good results, but have not yet proven cost effective due to the cost of the pressure sensor. The method proposed here is very cost effective since it uses exactly the same hardware and instrumentation (already used in production cars) that is used to utilize the spark plug as a sensor to detect misfire and as a sensor for knock control. The only addition for ignition control is further signal interpretation in the electronic engine control unit. A key idea in our method is to use parameterized functions to describe the ionization current. These parameterized functions are used to separate out the different phases of the ionization current. Special emphasis is made to get a correct description of the pressure development. The results are validated on a SAAB 2.3 l production engine by direct comparison with an in-cylinder pressure sensor (used only for validation, not for control), but also by using a physical model relating the ionization current to the pressure.
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| 29. |
- Eriksson, Lars, et al.
(författare)
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Increasing the Efficiency of SI-Engines by Spark-Advance Control and Water Injection
- 1998
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Konferensbidrag (refereegranskat)abstract
- Engine efficiency can be maximized by directly measuring in-cylinder parameters and adjusting the spark advance, using a feedback scheme based on the ionization current as sensed variable. Water injection is shown to increase the engine efficiency, if at the same time the spark advance is also changed when water is injected to obtain maximum efficiency. A spark-advance control scheme, that takes the water injection into account, is thus necessary to increase the efficiency.
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| 30. |
- Eriksson, Lars, 1970-, et al.
(författare)
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Ionization Current Interpretation for Ignition Control in Internal Combustion Engines
- 1997
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Ingår i: Control Engineering Practice. - : Pergamon Press. - 0967-0661 .- 1873-6939. ; 5:8, s. 1107-1113
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Tidskriftsartikel (refereegranskat)abstract
- Spark advance setting in spark-ignited engines is used to place the in-cylinder pressure curve relative to the top dead center. A feedback scheme, not a calibration scheme, based on ionization current is proposed here. It is thus related to pressure sensor feedback schemes, that have reported good results, but have not yet been proved cost effective, due to the cost of the pressure sensor. The method proposed here is very cost-effective, since it uses exactly the same hardware and instrumentation (already used in production cars) that is used to utilize the spark plug as a sensor to detect misfire and as a sensor for knock control. A key idea in the method is to use parameterized functions to describe the ionization current. These parameterized functions are used to separate out the different phases of the ionization current. Special emphasis is laid on getting a correct description of the pressure development. The results are validated on a SAAB 2.3 l production engine by direct comparison with an in-cylinder pressure sensor (used only for validation, not for control), but also by using a physical model relating the ionization current to the pressure.
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| 31. |
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| 32. |
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| 33. |
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| 34. |
- Eriksson, Lars, et al.
(författare)
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Modeling of a turbocharged SI engine
- 2002
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Ingår i: Annual Reviews in Control. - 1367-5788 .- 1872-9088. ; 26 I, s. 129-137
-
Tidskriftsartikel (refereegranskat)abstract
- Turbocharged SI engines are a major possibility in the current trend of down-sized engines with preserved drivability performance. Considering control and supervision it is favorable to have a mean value model to be used e.g. in observer design. Such models of turbo engines are similar to those of naturally aspirated engines, but there are some special characteristics, e.g. the interconnected gas flows, the intercooler, the difference in relative sizes between the gas volumes (compared to naturally aspirated engines), the turbo, and the waste gate. Here, a model is developed with a strategy to find a model for each engine component (air filter, compressor, after cooler (or intercooler), throttle, engine, turbine, waste gate, and a lumped model for the catalyst and exhaust) as they behave in an engine setting. When investigating agreement with measured data and sensitivity of possible model structures, a number of interesting issues are raised. The experiments and the model validation have been performed on a Saab 2.3 1 production engine.
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| 35. |
- Eriksson, Lars, et al.
(författare)
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Non-linear Model-Based Throttle Control
- 2000
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Konferensbidrag (refereegranskat)abstract
- Spark ignited engines require accurate control of both air and fuel, and one important component in this system is the throttle servo. A non-linear throttle model is built and used for control design. It is shown that the non-linear model-based controller improves the performance compared to a conventional gain scheduled PI controller. Furthermore a method for estimating the load torque that the air flow produces on the throttle shaft is presented.
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| 36. |
- Eriksson, Lars, 1970-, et al.
(författare)
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Towards On-Board Engine Calibration with Feedback Control Incorporating Combustion Models and Ion-sense
- 2003
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Ingår i: Automatisierungstechnik. - : De Gruyter Oldenbourg. - 0178-2312 .- 2196-677X. ; 51:5, s. 204-212
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Tidskriftsartikel (refereegranskat)abstract
- Die Technik der Ionenstrommessung dient der Untersuchung des Verbrennungsvorganges im Zylinder. Bei der Ionenstrommessung wird nach der Zündung eine Spannung zwischen der Mittel- und der Massenelektrode der Zündkerze angelegt. Anschliessend wird der Stromfluss zwischen diesen beiden Elektroden gemessen. Das Signal des Ionenstroms ist eine komplexe Funktion, die Informationüber den Zylinderdruck, die Zylindertemperatur und den Verbrennungsvorgang enth ält. Um diese Information zu erhalten, bedient man sich eines einfachen analytischen Ionenstrommodells. Das Modell besteht aus detaillierten Untermodellen zur Analyse des Drucks, der Temperatur, der thermischen Ionisierung und des Ionisierungsstroms innerhalb des Zylinders. Die Kalibrierung der Modellparameter erfolgt on-board durch eine Signalinterpretation. Experimentelle Untersuchungen zeigen eine gute Übereinstimmung mit dem Modell und ebnen damit den Weg hin zu einer Echtzeit-Kalibrierung des Motors. Ion-sense is a technique to probe the in-cylinder combustion by applying, after ignition, a sense voltage across the spark plug gap and measure the current through the gap. This current measurement is a complicated function that contains a lot of information about the in-cylinder pressure, temperature and combustion. To extract this information, a major contribution here is a simple analytical ionization current model that consists of explicit analytical submodels for in-cylinder pressure, temperature, thermal ionization, and ionization current. Since the model is analytical, the on-board signal interpretation is a simple adaptation of some model parameters. Experimental validation shows good agreement, and thus paves the way towards real-time on-board engine calibration.
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| 37. |
- Forslund, Sofia K., et al.
(författare)
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Combinatorial, additive and dose-dependent drug–microbiome associations
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505
-
Tidskriftsartikel (refereegranskat)abstract
- During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1–5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease.
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| 38. |
- Fröberg, Anders, et al.
(författare)
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Controlling Gear Engagement and disengagement on heavy trucks for minimization of fuel consumption
- 2005
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Ingår i: Proceedings of the 16th IFAC World Congress.
-
Konferensbidrag (refereegranskat)abstract
- There is a potential to save fuel for heavy trucks by storing kineticenergy in the vehicle when driving downhill, because the speed adds kinetic energyto the vehicle which can be used after the downhill slope to propell the vehicle.This behavior can be even more utilized by disengaging the gear to reduce thefriction in the driveline and thus increase the speed even more. Two differentcontrol strategies to choose when to disengage the gear is presented: One schemethat uses instantaneous inclination and one predictive control scheme that useslook ahead information of the road topology. Simulation results show that geardisengagement in downhills can reduce the fuel consumption about 3%.
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| 39. |
- Groen, Solveig Skovlund, et al.
(författare)
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A serological type II collagen neoepitope biomarker reflects cartilage breakdown in patients with osteoarthritis
- 2021
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Ingår i: Osteoarthritis and Cartilage Open. - : Elsevier BV. - 2665-9131. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: There is an unmet medical need for biomarkers in OA which can be applied in clinical drug development trials. The present study describes the development of a specific and robust assay measuring type II collagen degradation (T2CM) and discusses its potential as a noninvasive translational biomarker. Methods: A type II collagen specific neoepitope (T2CM) was identified by mass spectrometry and monoclonal antibodies were raised towards the epitope, employed in a chemiluminescence immunoassay. T2CM was assessed in bovine cartilage explants with or without MMP-13 inhibitor, and explant supernatants were analyzed by Western blot. T2CM was measured in plasma samples from one study (n = 48 patients) where OA patients were referred to total knee replacement (TKR). Additionally, T2CM was quantified in serum from OA patients receiving salmon calcitonin treatment (sCT) (n = 50) compared to placebo (n = 57). Results: The T2CM assay was technically robust (13/4 % inter/intra-variation) and specific for the type II collagen fragment cleaved by MMP-1 and -13. The MMP-13 inhibitor reduced the T2CM release from bovine cartilage explants receiving catabolic treatment. These results were confirmed by Western blot. In human end-stage OA patients (scheduled for TKR), the T2CM levels were elevated compared to moderate OA (p<0.004). The OA patients receiving sCT had lower levels of T2CM compared to placebo group after 1, 6, and 24 months of treatment (p = 0.0285, p = 0.0484, p = 0.0035). Conclusions: To our knowledge, T2CM is the first technically robust serological biomarker assay which has shown biological relevance in ex vivo models and OA cohorts. This suggests that T2CM may have potential as a translational biomarker for cartilage degradation.
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| 40. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 41. |
- Jacobsen, Carsten Suhr, et al.
(författare)
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Inter-laboratory testing of the effect of DNA blocking reagent G2 on DNA extraction from low-biomass clay samples
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Here we show that a commercial blocking reagent (G2) based on modified eukaryotic DNA significantly improved DNA extraction efficiency. We subjected G2 to an inter-laboratory testing, where DNA was extracted from the same clay subsoil using the same batch of kits. The inter-laboratory extraction campaign revealed large variation among the participating laboratories, but the reagent increased the number of PCR-amplified16S rRNA genes recovered from biomass naturally present in the soils by one log unit. An extensive sequencing approach demonstrated that the blocking reagent was free of contaminating DNA, and may therefore also be used in metagenomics studies that require direct sequencing.
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| 42. |
- Kammann, Janina, et al.
(författare)
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Deep onshore reflection seismic imaging of the chalk group strata using a 45 kg accelerated weight-drop and combined recording systems with dense receiver spacing
- 2019
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Ingår i: Geophysics. - : SOC EXPLORATION GEOPHYSICISTS. - 0016-8033 .- 1942-2156. ; 84:4, s. B259-B268
-
Tidskriftsartikel (refereegranskat)abstract
- The Chalk Group forms important hydrocarbon reservoirs offshore and water aquifers onshore Denmark. Within a day of fieldwork, a 450 m long reflection seismic profile was acquired onshore in an area in southeast Denmark, where the Chalk Group extends almost to the surface and is approximately 900 m thick. The main objective of the study was to image the complete Chalk Group in high resolution and to study the origin of reflectivity within the different chalk units. A 45 kg accelerated weight- drop source, in combination with dense receiver spacing using microelectromechanical sensors mounted on a streamer and 48 planted geophones, was used for data acquisition. The profile runs subparallel to the cliffs of Stevns, and the recorded signal reaches the base of the Chalk Group at approximately 600 ms. The fully cored 443 m-deep Stevns-1 borehole, which is located at the recorded seismic line, provides excellent control on lithologic and facies changes. Comparison with the borehole data demonstrates that our seismic data set provides a high-resolution image of the internal layering of the Chalk Group. We find that the internal reflection coefficients of the Chalk Group are, in general, small based on wireline-log data. However, the reflected amplitudes are just big enough to be recorded with the receiver setup used, even from the pure chalk beds of the Chalk Group. The reflectivity seen on the high-resolution seismic profile is influenced by occurrences of clay-enriched chalk layers. Flint bands consisting of numerous flint nodules are a characteristic of the uppermost part of the Chalk Group at Stevns. The flint nodules appear to produce significant scattering of the seismic signals, and flint-rich layers appear with diffuse internal reflectivity characteristics. Outcrop-scale mound structures in Danian and Upper Cretaceous outcrops are for the first time seismically resolved.
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| 43. |
- Klein, Markus, 1974-
(författare)
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Single-Zone Cylinder Pressure Modeling and Estimation for Heat Release Analysis of SI Engines
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cylinder pressure modeling and heat release analysis are today important and standard tools for engineers and researchers, when developing and tuning new engines. Being able to accurately model and extract information from the cylinder pressure is important for the interpretation and validity of the result.The first part of the thesis treats single-zone cylinder pressure modeling, where the specific heat ratio model constitutes a key part. This model component is therefore investigated more thoroughly. For the purpose of reference, the specific heat ratio is calculated for burned and unburned gases, assuming that the unburned mixture is frozen and that the burned mixture is at chemical equilibrium. Use of the reference model in heat release analysis is too time consuming and therefore a set of simpler models, both existing and newly developed, are compared to the reference model.A two-zone mean temperature model and the Vibe function are used to parameterize the mass fraction burned. The mass fraction burned is used to interpolate the specific heats for the unburned and burned mixture, and to form the specific heat ratio, which renders a cylinder pressure modeling error in the same order as the measurement noise, and fifteen times smaller than the model originally suggested in Gatowski et al. (1984). The computational time is increased with 40 % compared to the original setting, but reduced by a factor 70 compared to precomputed tables from the full equilibrium program. The specific heats for the unburned mixture are captured within 0.2 % by linear functions, and the specific heats for the burned mixture are captured within 1 % by higher-order polynomials for the major operating range of a spark ignited (SI) engine.In the second part, four methods for compression ratio estimation based on cylinder pressure traces are developed and evaluated for both simulated and experimental cycles. Three methods rely upon a model of polytropic compression for the cylinder pressure. It is shown that they give a good estimate of the compression ratio at low compression ratios, although the estimates are biased. A method based on a variable projection algorithm with a logarithmic norm of the cylinder pressure yields the smallest confidence intervals and shortest computational time for these three methods. This method is recommended when computational time is an important issue. The polytropic pressure model lacks information about heat transfer and therefore the estimation bias increases with the compression ratio.The fourth method includes heat transfer, crevice effects, and a commonly used heat release model for firing cycles. This method estimates the compression ratio more accurately in terms of bias and variance. The method is more computationally demanding and thus recommended when estimation accuracy is the most important property. In order to estimate the compression ratio as accurately as possible, motored cycles with as high initial pressure as possible should be used.The objective in part 3 is to develop an estimation tool for heat release analysis that is accurate, systematic and efficient. Two methods that incorporate prior knowledge of the parameter nominal value and uncertainty in a systematic manner are presented and evaluated. Method 1 is based on using a singular value decomposition of the estimated hessian, to reduce the number of estimated parameters one-by-one. Then the suggested number of parameters to use is found as the one minimizing the Akaike final prediction error. Method 2 uses a regularization technique to include the prior knowledge in the criterion function.Method 2 gives more accurate estimates than method 1. For method 2, prior knowledge with individually set parameter uncertainties yields more accurate and robust estimates. Once a choice of parameter uncertainty has been done, no user interaction is needed. Method 2 is then formulated for three different versions, which differ in how they determine how strong the regularization should be. The quickest version is based on ad-hoc tuning and should be used when computational time is important. Another version is more accurate and flexible to changing operating conditions, but is more computationally demanding.
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| 44. |
- Lemming, Dag, 1962-, et al.
(författare)
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Cuff Pressure Pain Detection Is Associated with Both Sex and Physical Activity Level in Nonathletic Healthy Subjects
- 2017
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Ingår i: Pain medicine (Malden, Mass.). - Oxford : Oxford University Press. - 1526-2375 .- 1526-4637. ; 18:8, s. 1573-1581
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. The aim of this study was to evaluate pressure pain sensitivity on leg and arm in 98 healthy persons (50 women) using cuff algometry. Furthermore, associations with sex and physical activity level were investigated.Method. Normal physical activity level was defined as Godin Leisure-Time Exercise Questionnaire (GLTEQ) score ≤ 45 and high activity level as GLTEQ > 45. A pneumatic double-chamber cuff was placed around the arm or leg where a single chamber was inflated. The cuff inflation rate (1 kPa/s) was constant, and pain intensity was registered continuously on a 10 cm electronic visual analogue scale (VAS). The pain detection threshold (PDT) was defined as when the pressure was perceived as painful, and pain tolerance (PTT) was when the subject terminated the cuff inflation. For PTT, the corresponding VAS score was recorded (VAS-PTT). The protocol was repeated with two chambers inflated.Result. Only single cuff results are given. For women compared with men, the PDT was lower when assessed in the arm (P = 0.002), PTTs were lower in the arm and leg (P < 0.001), and the VAS-PTT was higher in the arm and leg (P < 0.033). Highly active participants compared with less active had higher PDT (P = 0.027) in the leg. Women showed facilitated spatial summation (P < 0.014) in the arm and leg and a steeper VAS slope (i.e., the slope of the VAS pressure curve between PDT and PPT) in the arm and leg (P < 0.003).Conclusion. This study indicates that reduced pressure pain sensitivity is associated both with male sex and physical activity level.
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| 45. |
- Lemming, Dag, et al.
(författare)
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Managing chronic whiplash associated pain with a combination of low-dose opioid (remifentanil) and NMDA-antagonist (ketamine)
- 2007
-
Ingår i: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 11:7, s. 719-732
-
Tidskriftsartikel (refereegranskat)abstract
- The aim was to investigate the efficacy of a combination of low-dose remifentanil (REMI) and ketamine (KET) compared to the single drugs and placebo (P) on whiplash associated pain (WAD) in a double-blind, randomized, placebo-controlled, cross-over study. Twenty patients with chronic (>1 year) WAD were included. Four different drug combinations were tested in four sessions: placebo/placebo (P/P), placebo/remifentanil (P/REMI), ketamine/placebo (KET/P) and ketamine/remifentanil (KET/REMI). Target concentrations were 1 and 2 ng/ml (stepwise) for remifentanil and 100 ng/ml for ketamine. Habitual pain intensity was assessed on a visual analogue scale (VAS). Experimental pain was assessed with electrical stimulation (single and repeated) of tibialis anterior (TA) muscle, pressure pain algometry applied over infraspinatus (IS) and TA muscles and VAS scores after intramuscular hypertonic saline infusion in TA. KET/REMI significantly reduced habitual pain. KET/REMI infused at low REMI target concentration (1 ng/ml) significantly elevated electrical intramuscular pain thresholds (single and repeated). Pain thresholds to electrical stimulation were similarly increased by both P/REMI and KET/REMI at 2 ng/ml target concentration. Pressure pain thresholds were increased by both KET/REMI and P/REMI. VAS-scores after intramuscular saline were also similarly decreased by both REMI combinations. Seven out of 20 subjects were non-responders (<50% pain relief). No correlation was found between effects on spontaneous pain and experimental pain. KET/REMI showed an analgesic effect on habitual pain. Experimental pain was attenuated by both combinations containing the opioid, however, KET seemed to enhance the effect of REMI on electrical pain thresholds when a low REMI target concentration was used.
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| 46. |
- Lemming, Dag, et al.
(författare)
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Single-point but not tonic cuff pressure pain sensitivity is associated with level of physical fitness : a study of non-athletic healthy subjects
- 2015
-
Ingår i: PLOS ONE. - Linköping : Public Library of Science. - 1932-6203. ; 10:5
-
Tidskriftsartikel (refereegranskat)abstract
- Exercise is often used for pain rehabilitation but the link between physical activity level and pain sensitivity is still not fully understood. Pressure pain sensitivity to cuff algometry and conditioned pain modulation (CPM) were evaluated in highly active men (n=22), normally active men (n=26), highly active women (n=27) and normally active women (n=23) based on the Godin Leisure-Time Exercise Questionnaire. Cuff pressure pain sensitivity was assessed at the arm and lower leg. The subjects scored the pain intensity on an electronic Visual Analogue Scale (VAS) during ten minutes with 25 kPa constant cuff pressure and two minutes with zero pressure. The maximal VAS score and area under the VAS-curve were extracted. Pressure pain thresholds (PPT) were recorded by manual pressure algometry on the ipsilateral tibialis anterior muscle before, during and after the tonic arm stimulation.Tonic cuff stimulation of the arm and leg resulted in higher VAS peak scores in women compared with men (p<0.04). In all groups the PPTs were reduced during and after the cuff stimulation compared with baseline (p=0.001). PPT were higher in men compared with women (p=0.03) and higher in highly physical active compared with normal active (p=0.048). Besides the well-known gender difference in pressure pain sensitivity this study demonstrates that a high physical fitness degree in non-athletic subjects is associated with increased pressure pain thresholds but does not affect cuff pressure pain sensitivity in healthy people.
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| 47. |
- Lemming, Dag, et al.
(författare)
-
The responses to pharmacological challenges and experimental pain in patients with chronic whiplash-associated pain
- 2005
-
Ingår i: The Clinical Journal of Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0749-8047 .- 1536-5409. ; 21:5, s. 412-421
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study evaluates the analgesic responses to intravenous administration of morphine, lidocaine, and ketamine and their relations to duration of chronic pain after whiplash trauma. In addition, experimental muscle pain sensitivity and its correlation to pain duration and pharmacological responses were assessed. Methods: Thirty-three patients with diagnosed whiplash-associated disorder grade II in the chronic stage, according to the Quebec classification, were included. The pharmacological evaluation was performed in a randomized, double-blind, cross-over design and consisted of a 30-minute period of intravenous administration of morphine (0.3 mg/kg), lidocaine (5 mg/kg), ketamine (0.3 mg/kg), or placebo (isotonic saline). Intensity ratings of habitual pain on a visual analogue scale were taken before, during, and after the infusion. The patients were classified as nonresponders, placebo-responders, or responders (minimum 50% decrease of pain intensity) of the drugs. Pressure pain thresholds and intramuscular and cutaneous electrical stimulation pain thresholds were measured. The pain intensity during experimental muscle pain by intramuscular hypertonic saline was also recorded. Experimental pain assessments were performed on the lower legs outside the habitual painful area. Results: Thirty patients completed the study; 2 were placebo responders and 10 were nonresponders. Of 18 responders, there were 15 morphine responders, 11 lidocaine responders, and 14 ketamine responders. In the patients with whiplash-associated disorder duration less than 2 years, 7 responded to morphine, 5 to lidocaine, and 8 to ketamine. In the patients with pain duration longer than 2 years, 8 responded to morphine, 6 to lidocaine, and 6 to ketamine. Thus, no pattern with respect to pain duration was found. Seventeen patients participated in the experimental pain assessment, and no significant differences in the variables of the intramuscular and cutaneous stimulation and intramuscular-induced pain with respect to response to the pharmacological challenges or whiplash-associated disorder duration existed. Discussion: The pharmacological challenges identified subgroups of patients with chronic whiplash-associated disorder that might be considered before instituting therapeutic interventions or research. However, the pattern of responses to the pharmacological challenges did not show any clear relationships with pain duration or the experimental pain tests.
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| 48. |
- Lemming, Dag, et al.
(författare)
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Widespread pain hypersensitivity and facilitated temporal summation of deep tissue pain in whiplash associated disorder : an explorative study of women
- 2012
-
Ingår i: Journal of Rehabilitation Medicine. - : Foundation for Rehabilitation Information. - 1650-1977 .- 1651-2081. ; 44:8, s. 648-657
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Widespread deep tissue pain hyperalgesia was evaluated in women with chronic whiplash associated disorder (n=25) and controls (n=10) using computerized cuff pressure algometry and hypertonic saline infusion. Methods: A pneumatic double-chamber cuff was placed around: (i) the arm and (ii) the leg. Cuff inflation rate was constant and the pain intensity was registered continuously on a visual analogue scale (VAS); thresholds of detection and tolerance were extracted. For assessment of spatial summation the protocol was repeated with a single-chamber cuff inflated around the leg. Temporal summation of pain was assessed from the leg with constant cuff pressure stimulation at 2 different pressure intensities for 10 min. Hypertonic saline was infused in the tibialis anterior muscle. Results: Cuff pressure pain thresholds were lower in subjects with whiplash associated disorder compared with controls (pless than0.05). Tonic pressure stimulation evoked higher maximal VAS and larger areas under the VAS curve in subjects with whiplash associated disorder compared with controls (pless than0.05). The pain threshold and tolerance were higher during single cuff than double cuff stimulation. The area under the VAS curve after intramuscular saline infusion was larger in whiplash associated disorder (pless than0.05). Conclusion: The results indicated widespread hyperalgesia in chronic whiplash associated disorder and facilitated temporal summation outside the primary pain area, suggesting involvement of central sensitization.
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| 49. |
- Leufvén, Oskar
(författare)
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Modeling for control of centrifugal compressors
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Downsizing and turbocharging of engines provide a way to meet increasing demands for efficiency and performance in the automotive industry. An engine design is a result of compromises, e.g. the selection of charging system, and the trend is to reduce these compromises by increasing system complexity. Models have come to play a central role to handle this rise in complexity, and are used for simulation, system optimization and control synthesis. The models should describe the entire operating range, be capable of extrapolation, be easily parameterizable, and wide cover a range of applications.A novel compressor model is developed which, in addition to the nominal operation, also covers surge, choke and operation at pressure ratios less than one. The model is based on data from more than 300 compressor maps, measurements from engine test stands, and a surge test stand. The general knowledge gained from the in-depth analysis is condensed in the model equations. The model can be automatically parametrized using a compressor map, is based on static functions for low computational cost, and is shown to extrapolate low speed compressor operation well. Furthermore, it is shown to be applicable to compressors of different size, ranging from small car applications to large heavy duty vehicles. Compressor restriction operation is modeled down to a standstill compressor, and shown to agree well with gas stand measurements. Further, the analysis contributes with new knowledge and models for choking pressure ratio and flow.A method to automatically determine a turbo map, when the turbo is installed on an engine in an engine test stand is developed. The method can be used to validate manufacturer maps or expand the region covered in a map. An analysis of the limits that an engine installation imposes on the reachable points in the compressor map is performed. The addition of a throttle before the compressor is suggested to increase the reachable map region, and an engine and test cell control structure that can be used to automate the measurements is proposed. Two methods that compensate for the deviation between measured and desired speeds, are proposed and investigated. A gas stand map is compared to the map generated in the engine test stand, and a generally good agreement results.An experimental analysis of the applicability of the commonly used correction factors, used for estimating compressor performance when the inlet conditions deviate from nominal, is performed. Correction factors are vital, to e.g. estimate turbocharger performance for driving at high altitude or to characterize second stage compressor performance, where the variations in inlet conditions are large. Measurements from an engine test stand and a gas stand show a small but clearly measurable trend, with decreasing compressor pressure ratio for decreasing compressor inlet pressure, for points with equal corrected shaft speed and corrected mass flow. A method that enables measurements to be analyzed with modified corrections is developed. As a result, an adjusted shaft speed correction quantity is proposed, incorporating also the inlet pressure in the shaft speed correction.
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| 50. |
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