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| 2. |
- Bergström, Göran, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 3. |
- Brautigam, Lars, et al.
(författare)
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Glutaredoxin regulates vascular development by reversible glutathionylation of sirtuin 1
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:50, s. 20057-20062
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Tidskriftsartikel (refereegranskat)abstract
- Embryonic development depends on complex and precisely orchestrated signaling pathways including specific reduction/oxidation cascades. Oxidoreductases of the thioredoxin family are key players conveying redox signals through reversible posttranslational modifications of protein thiols. The importance of this protein family during embryogenesis has recently been exemplified for glutaredoxin 2, a vertebrate-specific glutathione-disulfide oxidoreductase with a critical role for embryonic brain development. Here, we discovered an essential function of glutaredoxin 2 during vascular development. Confocal microscopy and time-lapse studies based on two-photon microscopy revealed that morpholino-based knockdown of glutaredoxin 2 in zebrafish, a model organism to study vertebrate embryogenesis, resulted in a delayed and disordered blood vessel network. We were able to show that formation of a functional vascular system requires glutaredoxin 2-dependent reversible S-glutathionylation of the NAD(+)-dependent protein deacetylase sirtuin 1. Using mass spectrometry, we identified a cysteine residue in the conserved catalytic region of sirtuin 1 as target for glutaredoxin 2-specific deglutathionylation. Thereby, glutaredoxin 2-mediated redox regulation controls enzymatic activity of sirtuin 1, a mechanism we found to be conserved between zebrafish and humans. These results link S-glutathionylation to vertebrate development and successful embryonic angiogenesis.
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| 4. |
- Carlbring, Per, et al.
(författare)
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Behavioral Activation vs. Physical Exercise in the Treatment of Mild to Moderate Depression
- 2015
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Despite their potential as low-threshold, low-cost and high-flexibility treatments of depression, behavioral activation and physical exercise have not yet been directly compared. This study has examined the effects of these interventions, administered via the Internet. In this randomized controlled trial a total of 312 participants meeting the diagnostic criteria for mild to moderate major depression, recruited in multiple cycles and randomized to either a waiting list control group with delayed treatment, or one of the four active treatment groups: (1) physical exercise without a clear psychological treatment rationale; (2) physical exercise with a psychological treatment rationale; (3) behavioral activation a la Lewinsohn; or (4) behavioral activation a la Martel. A total of 72% were women and the average age of the participants were M=42.3 years (SD=13,5). More than half (53,9%) had a history of previous psychological treatment. Primary outcome measure was the 9-item Patient Health Questionnaire. Assessments were made on a weekly basis for the full duration of the acute treatment which was 12 weeks. The preliminary results are in line with previous online studies showing that all active treatment groups were superior to the waitlist (large effect sizes) and that only minor differences could be identified between the four active groups (large within effect sizes). At the time of the conference 6-month follow-up data will be available in addition to the already collected post-assessment data (analyzed according to the intention-to-treat principle).
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| 5. |
- Carlbring, Per, et al.
(författare)
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The effects on depression of Internet-administered behavioral activation vs. physical exercise
- 2015
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Despite their potential as low-threshold, low-cost and high-flexibility treatments of depression, behavioral activation and physical exercise have not yet been directly compared. This study has examined the effects of these interventions, administered via the Internet. In this randomized controlled trial a total of 312 participants meeting the diagnostic criteria for mild to moderate major depression, recruited in multiple cycles and randomized to either a waiting list control group with delayed treatment, or one of the four active treatment groups: (1) physical exercise without a clear psychological treatment rationale; (2) physical exercise with a psychological treatment rationale; (3)behavioral activation a la Lewinsohn; or (4) behavioral activation a la Martel. A total of 72% were women and the average age of the participants were M=42.3 years (SD=13,5). More than half (53,9%) had a history of previous psychological treatment. Primary outcome measure was the 9-item Patient Health Questionnaire. Assessments were made on a weekly basis for the full duration of the acute treatment which was 12 weeks. The preliminary results are in line with previous online studies showing that all active treatment groups were superior to the waitlist (large effect sizes) and that only minor differences could be identified between the four active groups (large within effect sizes). At the time of the conference 6-month follow-up data will be available in addition to the already collected post-assessment data (analyzed according to the intention-to-treat principle).
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| 6. |
- Dédinaité, Andra, et al.
(författare)
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Friction in aqueous media tuned by temperature-responsive polymer layers
- 2010
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Ingår i: SOFT MATTER. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 6:11, s. 2489-2498
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Tidskriftsartikel (refereegranskat)abstract
- An atomic force microscope colloidal probe technique has been employed to probe normal and friction forces between silica surfaces coated with adsorbed layers of a diblock copolymer of the composition poly(N-isopropylacrylamide)(48)-block-poly(3-acrylamidopropyl)trimethyla mmonium chloride)(20), abbreviated PNIPAAM(48)-b-PAMPTMA(+)(20). The interactions between the PNIPAAM(48)-b-PAMPTMA(+)(20)-coated surfaces across a 0.1 mM NaCl (pH 6) solution at 25 degrees C are purely repulsive, due to a combination of steric and electrostatic double-layer forces. However, when the temperature is increased to 35 degrees C, and subsequently to 45 degrees C, an attractive force develops at short separations due to the unfavourable PNIPAAM-water interaction at these temperatures. The temperature-dependent polymer-water interaction has implications for the friction force between the layers. At 25 degrees C a frictional force that increases linearly with increasing load is observed once the surfaces are brought into close contact. At higher temperatures significantly higher friction forces appear as a consequence of attractive segment-segment interactions. Further, a clearly expressed hysteresis between friction forces encountered on loading and unloading is detected. Our results demonstrate that both normal and friction forces between surfaces can be controlled by temperature changes when temperature-responsive polymers are employed, and friction forces can be adjusted as required from low to high.
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| 7. |
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| 8. |
- Lu, R.S., et al.
(författare)
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A ring-like accretion structure in M87 connecting its black hole and jet
- 2023
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 616:7958, s. 686-690
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Tidskriftsartikel (refereegranskat)abstract
- The nearby radio galaxy M87 is a prime target for studying black hole accretion and jet formation1,2. Event Horizon Telescope observations of M87 in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was interpreted as gravitationally lensed emission around a central black hole3. Here we report images of M87 obtained in 2018, at a wavelength of 3.5 mm, showing that the compact radio core is spatially resolved. High-resolution imaging shows a ring-like structure of [Formula: see text] Schwarzschild radii in diameter, approximately 50% larger than that seen at 1.3 mm. The outer edge at 3.5 mm is also larger than that at 1.3 mm. This larger and thicker ring indicates a substantial contribution from the accretion flow with absorption effects, in addition to the gravitationally lensed ring-like emission. The images show that the edge-brightened jet connects to the accretion flow of the black hole. Close to the black hole, the emission profile of the jet-launching region is wider than the expected profile of a black-hole-driven jet, suggesting the possible presence of a wind associated with the accretion flow.
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| 9. |
- Lövgren, Tanja, et al.
(författare)
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Complete and long-lasting clinical responses in immune checkpoint inhibitor-resistant, metastasized melanoma treated with adoptive T cell transfer combined with DC vaccination
- 2020
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Ingår i: Oncoimmunology. - : TAYLOR & FRANCIS INC. - 2162-4011 .- 2162-402X. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Development of T cell-directed immune checkpoint inhibitors (ICI) has revolutionized metastatic melanoma (MM) therapy, but <50% of treated patients experience durable responses. This phase I trial (NCT01946373) investigates the safety/feasibility of tumor-infiltrating lymphocyte (TIL) adoptive cell therapy (ACT) combined with dendritic cell (DC) vaccination in MM patients progressing on ICI. An initial cohort (5 patients) received TIL therapy alone to evaluate safety and allow for optimization of TIL expansion protocols. A second cohort (first-in-man, 5 patients) received TIL combined with autologous tumor lysate-loaded DC vaccination. All patients received cyclophosphamide/fludarabine preconditioning prior to, and intravenous (i.v.) IL-2 after, TIL transfer. The DC vaccine was given as five intradermal injections after TIL and IL-2 administration. [F-18]-FDG PET/CT radiology was performed to evaluate clinical response, according to RECIST 1.1 (on the CT part). Immunological monitoring was performed by flow cytometry and T-cell receptor (TCR) sequencing. In the safety/optimization cohort, all patients had a mixed response or stable disease, but none durable. In the combination cohort, two patients experienced complete responses (CR) that are still ongoing (>36 and >18 months, respectively). In addition, two patients had partial responses (PR), one still ongoing (>42 months) with only a small bone-lesion remaining, and one of short duration (<4 months). One patient died early during treatment and did not receive DC. Long-lasting persistency of the injected TILs was demonstrated in blood. In summary, we report clinical responses by TIL therapy combined with DC vaccination in 4 out of 4 treated MM patients who previously failed ICI.
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