| 1. |
- Abdo, A. A., et al.
(författare)
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Gamma-ray emission concurrent with the nova in the symbiotic binary V407 cygni
- 2010
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 329:5993, s. 817-821
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Tidskriftsartikel (refereegranskat)abstract
- Novae are thermonuclear explosions on a white dwarf surface fueled by mass accreted from a companion star. Current physical models posit that shocked expanding gas from the nova shell can produce x-ray emission, but emission at higher energies has not been widely expected. Here, we report the Fermi Large Area Telescope detection of variable γ-ray emission (0.1 to 10 billion electron volts) from the recently detected optical nova of the symbiotic star V407 Cygni. We propose that the material of the nova shell interacts with the dense ambient medium of the red giant primary and that particles can be accelerated effectively to produce π0 decay γ-rays from proton-proton interactions. Emission involving inverse Compton scattering of the red giant radiation is also considered and is not ruled out.
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| 2. |
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| 3. |
- Sharma, T., et al.
(författare)
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Biomarkers associated with vulnerable plaques
- 2022
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 43:Suppl. 2, s. 1292-1292
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Cardiovascular heart disease is the leading cause of mortality worldwide, with the rupture or thrombosis of an atherosclerotic plaque being the main reason behind an acute coronary syndrome. It has already been established that the morphology of atherosclerotic plaques determine their stability. A lipid rich lesion with a thin fibrous cap is more prone to rupture compared to solid fibrous lesions. In the PROSPECTII study we used Near infrared spectroscopy (NIRS) and Intravascular ultrasound (IVUS) to identify atherosclerotic plaques in the coronary arteries; NIRS-derived lipid core burden index (LCBI) and IVUS-derived plaque burden (PB) identified plaques that caused adverse cardiovascular events.Purpose: Our aim is to find biomarkers associated with LCBI or PB, to understand the development of vulnerable plaques.Methods: 902 patients were enrolled in this study after successful percutaneous coronary intervention (PCI). A combined NIRS-IVUS catheter was then used to analyze approximately 200m of coronary arteries. Blood samples for biomarker analysis were taken before the PCI procedure and plasma levels of 182 proteins associated with cardiovascular disease were assessed using a novel method for measuring proximity extension assay. Adjusted linear regression models were calculated between the biomarkers and the outcomes of interest, followed by a false discovery rate (FDR) correction.Results: We found 24 proteins associated with plaque burden and 28 proteins associated with LCBI after using a cut off of two tailed P value <0.05. An overlap of 8 biomarkers could be seen between the two groups. After adjusting the P values with FDR, Angiopoeitin like 3 (ANGPTL3) retain edits association to LCBI, and Interleukin 18 receptor 1 (IL18R1) and colony stimulating factor 1 (CSF-1) to plaque burden.Conclusion: We were able to identify different biomarker patterns associated with plaque burden compared to lipid rich vulnerable plaques. ANGPTL3 was shown to only have an association with lipid rich plaques and not with solid fibrous lesions which further supports its role in vulnerable plaques.
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| 4. |
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| 5. |
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| 6. |
- Ali, Ziad A., et al.
(författare)
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Optical Coherence Tomography Characterization of Coronary Lithoplasty for Treatment of Calcified Lesions : First Description
- 2017
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Ingår i: JACC: Cardiovascular Imaging. - : Elsevier BV. - 1936-878X. ; 10:8, s. 897-906
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This study sought to determine the mechanistic effects of a novel balloon-based lithoplasty system on heavily calcified coronary lesions and subsequent stent placement using optical coherence tomography (OCT). Background The Shockwave Coronary Rx Lithoplasty System (Shockwave Medical, Fremont, California) delivers localized, lithotripsy-enhanced disruption of calcium within the target lesion (i.e., lithoplasty) for vessel preparation before stent implantation. Methods We analyzed OCT findings in 31 patients in whom lithoplasty was used to treat severely calcified stenotic coronary lesions. Results After lithoplasty, intraplaque calcium fracture was identified in 43% of lesions, with circumferential multiple fractures noted in >25%. The frequency of calcium fractures per lesion increased in the most severely calcified plaques (highest tertile vs. lowest tertile; p = 0.009), with a trend toward greater incidence of calcium fracture (77.8% vs. 22.2%; p = 0.057). Post-lithoplasty, mean acute area gain was 2.1 mm2, which further increased with stent implantation, achieving a minimal stent area of 5.94 ± 1.98 mm2 and mean stent expansion of 112.0 ± 37.2%. Deep dissections, as part of the angioplasty effect, occurred in 13% of cases and were successfully treated with stent implantation without incidence of acute closure, slow flow/no reflow, or perforation. Conclusions High-resolution imaging by OCT delineated calcium modification with fracture as a major mechanism of action of lithoplasty in vivo and demonstrated efficacy in the achievement of significant acute area gain and favorable stent expansion.
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| 7. |
- Candelaresi, Simon, et al.
(författare)
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SUPERFLARE OCCURRENCE AND ENERGIES ON G-, K-, AND M-TYPE DWARFS
- 2014
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 792:1, s. 67-
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Tidskriftsartikel (refereegranskat)abstract
- Kepler data from G-, K-, and M-type stars are used to study conditions that lead to superflares with energies above 10(34) erg. From the 117,661 stars included, 380 show superflares with a total of 1690 such events. We study whether parameters, like effective temperature or rotation rate, have any effect on the superflare occurrence rate or energy. With increasing effective temperature we observe a decrease in the superflare rate, which is analogous to the previous findings of a decrease in dynamo activity with increasing effective temperature. For slowly rotating stars, we find a quadratic increase of the mean occurrence rate with the rotation rate up to a critical point, after which the rate decreases linearly. Motivated by standard dynamo theory, we study the behavior of the relative starspot coverage, approximated as the relative brightness variation. For faster rotating stars, an increased fraction of stars shows higher spot coverage, which leads to higher superflare rates. A turbulent dynamo is used to study the dependence of the Ohmic dissipation as a proxy of the flare energy on the differential rotation or shear rate. The resulting statistics of the dissipation energy as a function of dynamo number is similar to the observed flare statistics as a function of the inverse Rossby number and shows similarly strong fluctuations. This supports the idea that superflares might well be possible for solar-type G stars.
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| 8. |
- Dweck, MR, et al.
(författare)
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Contemporary rationale for non-invasive imaging of adverse coronary plaque features to identify the vulnerable patient: a Position Paper from the European Society of Cardiology Working Group on Atherosclerosis and Vascular Biology and the European Association of Cardiovascular Imaging
- 2020
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Ingår i: European heart journal. Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2412 .- 2047-2404. ; 21:11, s. 1177-1183
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Tidskriftsartikel (refereegranskat)abstract
- Atherosclerotic plaques prone to rupture may cause acute myocardial infarction (MI) but can also heal without causing an event. Certain common histopathological features, including inflammation, a thin fibrous cap, positive remodelling, a large necrotic core, microcalcification, and plaque haemorrhage are commonly found in plaques causing an acute event. Recent advances in imaging techniques have made it possible to detect not only luminal stenosis and overall coronary atherosclerosis burden but also to identify such adverse plaque characteristics. However, the predictive value of identifying individual adverse atherosclerotic plaques for future events has remained poor. In this Position Paper, the relationship between vulnerable plaque imaging and MI is addressed, mainly for non-invasive assessments but also for invasive imaging of adverse plaques in patients undergoing invasive coronary angiography. Dynamic changes in atherosclerotic plaque development and composition may indicate that an adverse plaque phenotype should be considered at the patient level rather than for individual plaques. Imaging of adverse plaque burden throughout the coronary vascular tree, in combination with biomarkers and biomechanical parameters, therefore holds promise for identifying subjects at increased risk of MI and for guiding medical and invasive treatment.
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| 9. |
- Erlinge, David, et al.
(författare)
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Identification of vulnerable plaques and patients by intracoronary near-infrared spectroscopy and ultrasound (PROSPECT II) : a prospective natural history study
- 2021
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 397:10278, s. 985-995
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Tidskriftsartikel (refereegranskat)abstract
- Background: Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs).Methods: PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065.Findings: Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55-70] years). Median follow-up was 3.7 (IQR 3.0-4.4) years. Adverse events within 4 years occurred in 112 (13.2%, 95% CI 11.0-15.6) of 898 patients, with 66 (8.0%, 95% CI 6.2-10.0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46.9% [SD 15.9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2.27, 95% CI 1.25-4.13) and nonculprit lesion-specific MACEs (7.83, 4.12-14.89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7.0% (95% CI 4.0-10.0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13.2% (95% CI 9.4-17.6).Interpretation: Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes.
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| 10. |
- Figtree, Gemma A, et al.
(författare)
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Clinical Outcomes in Patients With ST-Segment Elevation MI and No Standard Modifiable Cardiovascular Risk Factors.
- 2022
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Ingår i: JACC. Cardiovascular interventions. - 1876-7605. ; 15:11, s. 1167-1175
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Tidskriftsartikel (refereegranskat)abstract
- The author recently reported ∼50% excess early mortality in patients with first-presentation ST-segment elevation myocardial infarction (STEMI) without standard modifiable cardiovascular risk factors (SMuRFs); the cause of this is not clear.The aim of this study was to examine differences in infarct characteristics and clinical outcomes in patients with versus without SMuRFs (dyslipidemia, hypertension, diabetes mellitus, and smoking).Individual-level data were pooled from 10 randomized percutaneous intervention (PCI) trials in which infarct size was measured within 1 month by either cardiac magnetic resonance or technetium-99m sestamibi single-photon emission computed tomography imaging. First-presentation STEMI was classified into 2 groups according to the presence or absence of at least 1 SMuRF.Among 2,862 patients, 524 (18.3%) were SMuRF-less. After adjusting for study effect, SMuRF-less patients had more frequent poor pre-PCI flow Thrombolysis In Myocardial Infarction 0/1 compared with patients with at least 1 SMuRF (72.0% vs 64.1%; OR: 1.35; 95% CI: 1.08-1.70). There were no independent associations between the presence or absence of SMuRFs at baseline and infarct size (estimate = -0.35; 95% CI: -1.93 to 1.23), left ventricular ejection fraction (estimate = -0.06; 95% CI: -1.33 to 1.20), or mortality at 30 days (HR: 0.46; 95% CI: 0.19-1.07) and 1 year (HR: 0.74; 95% CI: 0.43-1.29).First-presentation STEMI patients with no identifiable baseline SMuRFs had a higher risk of Thrombolysis In Myocardial Infarction flow grade 0/1 pre-PCI. However, after adjustment, there were no significant associations between SMuRF-less status and infarct size, left ventricle ejection fraction, or mortality.
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| 11. |
- Généreux, Philippe, et al.
(författare)
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Randomized evaluation of vessel preparation with orbital atherectomy prior to drug-eluting stent implantation in severely calcified coronary artery lesions: Design and rationale of the ECLIPSE trial.
- 2022
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Ingår i: American heart journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 249, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Severe coronary artery calcification has been associated with stent underexpansion, procedural complications, and increased rates of early and late adverse clinical events in patients undergoing percutaneous coronary intervention. To date, no lesion preparation strategy has been shown to definitively improve outcomes of percutaneous coronary intervention for calcified coronary artery lesions.ECLIPSE (NCT03108456) is a prospective, randomized, multicenter trial designed to evaluate two different vessel preparation strategies in severely calcified coronary artery lesions. The routine use of the Diamondback 360 Coronary Orbital Atherectomy System is compared with conventional balloon angioplasty prior to drug-eluting stent implantation. The trial aims to enroll approximately 2000 subjects with a primary clinical endpoint of target vessel failure, defined as the composite of cardiac death, target vessel-related myocardial infarction, or ischemia-driven target vessel revascularization assessed at 1 year. The co-primary endpoint is the acute post-procedural in-stent minimal cross-sectional area as assessed by optical coherence tomography in a 500-subject cohort. Enrollment is anticipated to complete in 2022 with total clinical follow-up planned for 2 years.ECLIPSE is a large-scale, prospective randomized trial powered to demonstrate whether a vessel preparation strategy of routine orbital atherectomy system is superior to conventional balloon angioplasty prior to implantation of drug-eluting stents in severely calcified coronary artery lesions.
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| 12. |
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| 13. |
- Gyldenkerne, Christine, et al.
(författare)
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Coronary Artery Lesion Lipid Content and Plaque Burden in Diabetic and Nondiabetic Patients : PROSPECT II
- 2023
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 147:6, s. 469-481
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with diabetes have increased rates of major adverse cardiac events (MACEs). We hypothesized that this is explained by diabetes-associated differences in coronary plaque morphology and lipid content.METHODS: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), 898 patients with acute myocardial infarction with or without ST-segment elevation underwent 3-vessel quantitative coronary angiography and coregistered near-infrared spectroscopy and intravascular ultrasound imaging after successful percutaneous coronary intervention. Subsequent MACEs were adjudicated to either treated culprit lesions or untreated nonculprit lesions. This substudy stratified patients by diabetes status and assessed baseline culprit and nonculprit prevalence of high-risk plaque characteristics defined as maximum plaque burden ≥70% and maximum lipid core burden index ≥324.7. Separate covariate-adjusted multivariable models were performed to identify whether diabetes was associated with nonculprit lesion-related MACEs and high-risk plaque characteristics.RESULTS: Diabetes was present in 109 of 898 patients (12.1%). During a median 3.7-year follow-up, MACEs occurred more frequently in patients with versus without diabetes (20.1% versus 13.5% [odds ratio (OR), 1.94 (95% CI, 1.14-3.30)]), primarily attributable to increased risk of myocardial infarction related to culprit lesion restenosis (4.3% versus 1.1% [OR, 3.78 (95% CI, 1.12-12.77)]) and nonculprit lesion-related spontaneous myocardial infarction (9.3% versus 3.8% [OR, 2.74 (95% CI, 1.25-6.04)]). However, baseline prevalence of high-risk plaque characteristics was similar for patients with versus without diabetes concerning culprit (maximum plaque burden ≥70%: 90% versus 93%, P=0.34; maximum lipid core burden index ≥324.7: 66% versus 70%, P=0.49) and nonculprit lesions (maximum plaque burden ≥70%: 23% versus 22%, P=0.37; maximum lipid core burden index ≥324.7: 26% versus 24%, P=0.47). In multivariable models, diabetes was associated with MACEs in nonculprit lesions (adjusted OR, 2.47 [95% CI, 1.21-5.04]) but not with prevalence of high-risk plaque characteristics (adjusted OR, 1.21 [95% CI, 0.86-1.69]).CONCLUSIONS: Among patients with recent myocardial infarction, both treated and untreated lesions contributed to the diabetes-associated ≈2-fold increased MACE rate during the 3.7-year follow-up. Diabetes-related plaque characteristics that might underlie this increased risk were not identified by multimodality imaging.
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| 14. |
- Johnson, Thomas W., et al.
(författare)
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Clinical use of intracoronary imaging. Part 2 : acute coronary syndromes, ambiguous coronary angiography findings, and guiding interventional decision-making: an expert consensus document of the European Association of Percutaneous Cardiovascular Interventions
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:31, s. 2566-2584
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Tidskriftsartikel (refereegranskat)abstract
- This consensus document is the second of two reports summarizing the views of an expert panel organized by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on the clinical use of intracoronary imaging including intravascular ultrasound (IVUS), optical coherence tomography (OCT), and near infrared spectroscopy (NIRS)-IVUS. Beyond guidance of stent selection and optimization of deployment, invasive imaging facilitates angiographic interpretation and may guide treatment in acute coronary syndrome. Intravascular imaging can provide additional important diagnostic information when confronted with angiographically ambiguous lesions and allows assessment of plaque morphology enabling identification of vulnerability characteristics. This second document focuses on useful imaging features to identify culprit and vulnerable coronary plaque, which offers the interventional cardiologist guidance on when to adopt an intracoronary imaging-guided approach to the treatment of coronary artery disease and provides an appraisal of intravascular imaging-derived metrics to define the haemodynamic significance of coronary lesions.
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| 15. |
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| 16. |
- Stone, Gregg W., et al.
(författare)
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Percutaneous Coronary Intervention for Vulnerable Coronary Atherosclerotic Plaque
- 2020
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 76:20, s. 2289-2301
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Tidskriftsartikel (refereegranskat)abstract
- Background: Acute coronary syndromes most commonly arise from thrombosis of lipid-rich coronary atheromas that have large plaque burden despite angiographically appearing mild. Objectives: This study sought to examine the outcomes of percutaneous coronary intervention (PCI) of non–flow-limiting vulnerable plaques. Methods: Three-vessel imaging was performed with a combination intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) catheter after successful PCI of all flow-limiting coronary lesions in 898 patients presenting with myocardial infarction (MI). Patients with an angiographically nonobstructive stenosis not intended for PCI but with IVUS plaque burden of ≥65% were randomized to treatment of the lesion with a bioresorbable vascular scaffold (BVS) plus guideline-directed medical therapy (GDMT) versus GDMT alone. The primary powered effectiveness endpoint was the IVUS-derived minimum lumen area (MLA) at protocol-driven 25-month follow-up. The primary (nonpowered) safety endpoint was randomized target lesion failure (cardiac death, target vessel–related MI, or clinically driven target lesion revascularization) at 24 months. The secondary (nonpowered) clinical effectiveness endpoint was randomized lesion–related major adverse cardiac events (cardiac death, MI, unstable angina, or progressive angina) at latest follow-up. Results: A total of 182 patients were randomized (93 BVS, 89 GDMT alone) at 15 centers. The median angiographic diameter stenosis of the randomized lesions was 41.6%; by near-infrared spectroscopy–IVUS, the median plaque burden was 73.7%, the median MLA was 2.9 mm2, and the median maximum lipid plaque content was 33.4%. Angiographic follow-up at 25 months was completed in 167 patients (91.8%), and the median clinical follow-up was 4.1 years. The follow-up MLA in BVS-treated lesions was 6.9 ± 2.6 mm2 compared with 3.0 ± 1.0 mm2 in GDMT alone–treated lesions (least square means difference: 3.9 mm2; 95% confidence interval: 3.3 to 4.5; p < 0.0001). Target lesion failure at 24 months occurred in similar rates of BVS-treated and GDMT alone–treated patients (4.3% vs. 4.5%; p = 0.96). Randomized lesion–related major adverse cardiac events occurred in 4.3% of BVS-treated patients versus 10.7% of GDMT alone–treated patients (odds ratio: 0.38; 95% confidence interval: 0.11 to 1.28; p = 0.12). Conclusions: PCI of angiographically mild lesions with large plaque burden was safe, substantially enlarged the follow-up MLA, and was associated with favorable long-term clinical outcomes, warranting the performance of an adequately powered randomized trial. (PROSPECT ABSORB [Providing Regional Observations to Study Predictors of Events in the Coronary Tree II Combined with a Randomized, Controlled, Intervention Trial]; NCT02171065)
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| 17. |
- Tanaka, Masaomi, et al.
(författare)
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DISCOVERY OF DRAMATIC OPTICAL VARIABILITY IN SDSS J1100+4421 : A PECULIAR RADIO-LOUD NARROW-LINE SEYFERT 1 GALAXY?
- 2014
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 793:2, s. L26-
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Tidskriftsartikel (refereegranskat)abstract
- We present our discovery of dramatic variability in SDSS J1100+4421 by the high-cadence transient survey Kiso Supernova Survey. The source brightened in the optical by at least a factor of three within about half a day. Spectroscopic observations suggest that this object is likely a narrow-line Seyfert 1 galaxy (NLS1) at z = 0.840, however, with unusually strong narrow emission lines. The estimated black hole mass of similar to 10(7) M-circle dot implies bolometric nuclear luminosity close to the Eddington limit. SDSS J1100+4421 is also extremely radio-loud, with a radio loudness parameter of R similar or equal to 4 x 10(2)-3 x 10(3), which implies the presence of relativistic jets. Rapid and large-amplitude optical variability of the target, reminiscent of that found in a few radio- and gamma-ray-loud NLS1s, is therefore produced most likely in a blazar-like core. The 1.4 GHz radio image of the source shows an extended structure with a linear size of about 100 kpc. If SDSS J1100+4421 is a genuine NLS1, as suggested here, this radio structure would then be the largest ever discovered in this type of active galaxies.
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| 18. |
- Usoskin, Ilya, et al.
(författare)
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Extreme Solar Events : Setting up a Paradigm
- 2023
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Ingår i: Space Science Reviews. - 0038-6308. ; 219:8
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Forskningsöversikt (refereegranskat)abstract
- The Sun is magnetically active and often produces eruptive events on different energetic and temporal scales. Until recently, the upper limit of such events was unknown and believed to be roughly represented by direct instrumental observations. However, two types of extreme events were discovered recently: extreme solar energetic particle events on the multi-millennial time scale and super-flares on sun-like stars. Both discoveries imply that the Sun might rarely produce events, called extreme solar events (ESE), whose energy could be orders of magnitude greater than anything we have observed during recent decades. During the years following these discoveries, great progress has been achieved in collecting observational evidence, uncovering new events, making statistical analyses, and developing theoretical modelling. The ESE paradigm lives and is being developed. On the other hand, many outstanding questions still remain open and new ones emerge. Here we present an overview of the current state of the art and the forming paradigm of ESE from different points of view: solar physics, stellar–solar projections, cosmogenic-isotope data, modelling, historical data, as well as terrestrial, technological and societal effects of ESEs. Special focus is paid to open questions and further developments. This review is based on the joint work of the International Space Science Institute (ISSI) team #510 (2020–2022).
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