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- Kero, Tanja, et al.
(författare)
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Evaluation of quantitative CMR perfusion imaging by comparison with simultaneous 15O-water-PET
- 2021
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Ingår i: Journal of Nuclear Cardiology. - : Springer Science and Business Media LLC. - 1071-3581 .- 1532-6551. ; 28, s. 1252-1266
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundWe assessed the quantitative accuracy of cardiac perfusion measurements using dynamic contrast-enhanced MRI with simultaneous 15O-water PET as reference with a fully integrated PET-MR scanner.Methods15 patients underwent simultaneous DCE MRI and 15O-water PET scans at rest and adenosine-stress on an integrated PET-MR scanner. Correlation and agreement between MRI- and PET-based global and regional MBF values were assessed using correlation and Bland–Altman analysis.ResultsThree subjects were excluded due to technical problems. Global mean (± SD) MBF values at rest and stress were 0.97 ± 0.27 and 3.19 ± 0.70 mL/g/min for MRI and 1.02 ± 0.28 and 3.13 ± 1.16 mL/g/min for PET (P = 0.66 and P = 0.81). The correlations between global and regional MRI- and PET-based MBF values were strong (r = 0.86 and r = 0.75). The biases were negligible for both global and regional MBF comparisons (0.01 and 0.00 mL/min/g for both), but the limits of agreement were wide for both global and regional MBF, with larger variability for high MBF-values.ConclusionThe correlation between simultaneous MBF measurements with DCE MRI and 15O-water PET measured in an integrated PET-MRI was strong but the agreement was only moderate indicating that MRI-based quantitative MBF measurements is not ready for clinical introduction.
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- Parker, Victoria E. R., et al.
(författare)
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Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes
- 2023
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Ingår i: Nature Metabolism. - : NATURE PORTFOLIO. - 2522-5812. ; 5, s. 2086-2093
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Tidskriftsartikel (refereegranskat)abstract
- Cotadutide is a dual glucagon-like peptide 1 and glucagon receptor agonist under development for the treatment of non-alcoholic steatohepatitis and type 2 diabetes mellitus (T2DM) and chronic kidney disease. Non-alcoholic steatohepatitis is a complex disease with no approved pharmacotherapies, arising from an underlying state of systemic metabolic dysfunction in association with T2DM and obesity. Cotadutide has been shown to improve glycaemic control, body weight, lipids, liver fat, inflammation and fibrosis. We conducted a two-part, randomized phase 2a trial in men and women with overweight or obesity diagnosed with T2DM to evaluate the efficacy and safety of cotadutide compared with placebo and liraglutide. The primary endpoints were change from baseline to day 28 of treatment in postprandial hepatic glycogen (part A) and to day 35 of treatment in fasting hepatic glycogen (part B) with cotadutide versus placebo. Secondary endpoints in part B were changes in fasting hepatic glycogen with cotadutide versus the mono glucagon-like peptide 1 receptor agonist, liraglutide, and change in hepatic fat fraction. The trial met its primary endpoint. We showed that cotadutide promotes greater reductions in liver glycogen and fat compared with placebo and liraglutide. Safety and tolerability findings with cotadutide were comparable to those of previous reports. Thus, this work provides evidence of additional benefits of cotadutide that could be attributed to glucagon receptor engagement. Our results suggest that cotadutide acts on the glucagon receptor in the human liver to promote glycogenolysis and improve the metabolic health of the liver. ClinicalTrials.gov registration: NCT03555994. In a two-part randomized phase 2a trial in men and women with overweight or obesity and type 2 diabetes mellitus, cotadutide promoted greater reductions in liver glycogen and fat than placebo and liraglutide.
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- Heurling, Kerstin, et al.
(författare)
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Disturbances in brain energy metabolism in insulin resistance and diabetes and Alzheimer's disease — Learnings from brain imaging biomarkers
- 2020
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Ingår i: International Review of Neurobiology. - : Elsevier. - 0074-7742. ; 154, s. 111-130
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Forskningsöversikt (refereegranskat)abstract
- Medical imaging techniques, such as structural and functional magnetic resonance imaging and positron emission tomography, have been used to gain a better understanding of the alterations of the metabolic processes in the brain relating to type 2 diabetes melltius, insulin resistance and Alzheimer's disease. These studies have shown that there are several similarities in the effects that these seemingly disparate diseases have on the brain, and that some of the abnormalities are reversed by metabolic interventions. This review provides an overview of the overlap between these diseases using medical imaging, focusing on glucose metabolism, mitochondrial function and lipid metabolism.
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| 7. |
- Johansson, Edvin, et al.
(författare)
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Scenario-based trajectory generation and density estimation towards risk analysis of autonomous vehicles
- 2023
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Ingår i: IEEE Conference on Intelligent Transportation Systems, Proceedings, ITSC. ; , s. 1375-1380
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Konferensbidrag (refereegranskat)abstract
- A large amount of testing is needed to determine when autonomous vehicles are sufficiently safe. To achieve this goal, test cases should be representative of real-world driving but also designed to provide sufficient coverage of both frequent and rare events. This is a crucial step in finding potential high consequence events, failure borders of the Autonomous Driving (AD) function and accurate estimation of the corresponding residual risks. In this paper, we propose a new method to adapt generative models to generate vehicle trajectories that are representative of the ones collected from the real world. The method uses Non-Uniform Rational B-Splines (NURBS) combined with normalizing flows to build a statistical scenario model. The method allows us to estimate a joint probability density that can be used to evaluate the likelihood of different trajectory occurrences. We demonstrate the method for statistical modeling on the (smooth and abrupt) cut-in traffic scenario and we give an example of how the estimated joint probability distribution can be used to assess the risk (trajectory occurrence probability and criticality) for different test cases. The results can be used for accelerated testing purposes, where the aim is to sample the rare tests more frequently, but can also be used to calculate the failure probability of AD functions.
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| 8. |
- Karlsson, Edvin, et al.
(författare)
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Airborne microbial biodiversity and seasonality in Northern and Southern Sweden
- 2020
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Ingår i: PeerJ. - : PeerJ. - 2167-8359. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Microorganisms are essential constituents of ecosystems. To improve our understanding of how various factors shape microbial diversity and composition in nature it is important to study how microorganisms vary in space and time. Factors shaping microbial communities in ground level air have been surveyed in a limited number of studies, indicating that geographic location, season and local climate influence the microbial communities. However, few have surveyed more than one location, at high latitude or continuously over more than a year. We surveyed the airborne microbial communities over two full consecutive years in Kiruna, in the Arctic boreal zone, and Ljungbyhed, in the Southern nemoral zone of Sweden, by using a unique collection of archived air filters. We mapped both geographic and seasonal differences in bacterial and fungal communities and evaluated environmental factors that may contribute to these differences and found that location, season and weather influence the airborne communities. Location had stronger influence on the bacterial community composition compared to season, while location and season had equal influence on the fungal community composition. However, the airborne bacterial and fungal diversity showed overall the same trend over the seasons, regardless of location, with a peak during the warmer parts of the year, except for the fungal seasonal trend in Ljungbyhed, which fluctuated more within season. Interestingly, the diversity and evenness of the airborne communities were generally lower in Ljungbyhed. In addition, both bacterial and fungal communities varied significantly within and between locations, where orders like Rhizobiales, Rhodospirillales and Agaricales dominated in Kiruna, whereas Bacillales, Clostridiales and Sordariales dominated in Ljungbyhed. These differences are a likely reflection of the landscape surrounding the sampling sites where the landscape in Ljungbyhed is more homogenous and predominantly characterized by artificial and agricultural surroundings. Our results further indicate that local landscape, as well as seasonal variation, shapes microbial communities in air.
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- Oldgren, Jonas, 1964-, et al.
(författare)
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Effects of 6 weeks of treatment with dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, on myocardial function and metabolism in patients with type 2 diabetes : A randomized, placebo-controlled, exploratory study
- 2021
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Ingår i: Diabetes, obesity and metabolism. - : John Wiley & Sons. - 1462-8902 .- 1463-1326. ; 23:7, s. 1505-1517
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Tidskriftsartikel (refereegranskat)abstract
- Aim To explore the early effects of dapagliflozin on myocardial function and metabolism in patients with type 2 diabetes without heart failure. Materials and Methods Patients with type 2 diabetes on metformin treatment were randomized to double-blind, 6-week placebo or dapagliflozin 10 mg daily treatment. Investigations included cardiac function and structure with myocardial resonance imaging; cardiac oxygen consumption, perfusion and efficiency with [C-11]-acetate positron emission tomography (PET); and cardiac and hepatic fatty acid uptake with [F-18]-6-thia-heptadecanoic acid PET, analysed by ANCOVA as least square means with 95% confidence intervals. Results Evaluable patients (placebo: n = 24, dapagliflozin: n = 25; 53% males) had a mean age of 64.4 years, a body mass index of 30.2 kg/m(2) and an HbA1c of 6.7%. Body weight and HbA1c were significantly decreased by dapagliflozin versus placebo. Dapagliflozin had no effect on myocardial efficiency, but external left ventricular (LV) work (-0.095 [-0.145, -0.043] J/g/min) and LV oxygen consumption were significantly reduced (-0.30 [-0.49, -0.12] J/g/min) by dapagliflozin, although the changes were not statistically significant versus changes in the placebo group. Change in left atrial maximal volume with dapagliflozin versus placebo was -3.19 (-6.32, -0.07) mL/m(2) (p = .056). Peak global radial strain decreased with dapagliflozin versus placebo (-3.92% [-7.57%, -0.28%]; p = .035), while peak global longitudinal and circumferential strains were unchanged. Hepatic fatty acid uptake was increased by dapagliflozin versus placebo (0.024 [0.004, 0.044] mu mol/g/min; p = .018), while cardiac uptake was unchanged. Conclusions This exploratory study indicates reduced heart work but limited effects on myocardial function, efficiency and cardiac fatty acid uptake, while hepatic fatty acid uptake increased, after 6 weeks of treatment with dapagliflozin.
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| 10. |
- Polesie, Sam, et al.
(författare)
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Can Dermoscopy Be Used to Predict if a Melanoma Is In Situ or Invasive?
- 2021
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Ingår i: Dermatology Practical & Conceptual. - : Mattioli1885. - 2160-9381. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: The preoperative prediction of whether melanomas are invasive or in situ can influence initial management. Objectives: This study evaluated the accuracy rate, interobserver concordance, sensitivity and specificity in determining if a melanoma is invasive or in situ, as well as the ability to predict invasive melanoma thickness based on clinical and dermoscopic images. Methods: In this retrospective, single-center investigation, 7 dermatologists independently reviewed clinical and dermoscopic images of melanomas to predict if they were invasive or in situ and, if invasive, their Breslow thickness. Fleiss' and Cohen's kappa (kappa) were used for interobserver concordance and agreement with histopathological diagnosis. Results: We included 184 melanomas (110 invasive and 74 in situ). Diagnostic accuracy ranged from 67.4% to 76.1%. Accuracy rates for in situ and invasive melanomas were 57.5% (95% confidence interval [I], 53.1%-61.8%) and 81.7% (95% CI, 78.8%-84.4%), respectively. Interobserver concordance was moderate (kappa = 0.47; 95% CI, 0.44-0.51). Sensitivity for predicting invasiveness ranged from 63.6% to 91.8% for 7 observers, while specificity was 32.4%-82.4%. For all correctly predicted invasive melanomas, agreement between predictions and correct thickness over or under 1.0 mm was moderate (kappa = 0.52; 95% CI, 0.45-0.58). All invasive melanomas incorrectly predicted by any observer as in situ had a thickness <1.0 mm. All 32 melanomas >1.0 mm were correctly predicted to be invasive by all observers. Conclusions: Accuracy rates for predicting thick melanomas were excellent, melanomas inaccurately predicted as in situ were all thin, and interobserver concordance for predicting in situ or invasive melanomas was moderate. Preoperative dermoscopy of suspected melanomas is recommended for choosing appropriate surgical margins.
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