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| 2. |
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| 3. |
- Fenstermacher, M.E., et al.
(författare)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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| 4. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 5. |
- de Graauw, Th., et al.
(författare)
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The Herschel-Heterodyne Instrument for the Far-Infrared (HIFI)
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L6-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This paper describes the Heterodyne Instrument for the Far-Infrared (HIFI) that was launched onboard ESA's Herschel Space Observatory in May 2009. Methods: The instrument is a set of 7 heterodyne receivers that are electronically tuneable, covering 480-1250 GHz with SIS mixers and the 1410-1910 GHz range with hot electron bolometer (HEB) mixers. The local oscillator (LO) subsystem comprises a Ka-band synthesizer followed by 14 chains of frequency multipliers and 2 chains for each frequency band. A pair of auto-correlators and a pair of acousto-optical spectrometers process the two IF signals from the dual-polarization, single-pixel front-ends to provide instantaneous frequency coverage of 2 × 4 GHz, with a set of resolutions (125 kHz to 1 MHz) that are better than 0.1 km s-1. Results: After a successful qualification and a pre-launch TB/TV test program, the flight instrument is now in-orbit and completed successfully the commissioning and performance verification phase. The in-orbit performance of the receivers matches the pre-launch sensitivities. We also report on the in-orbit performance of the receivers and some first results of HIFI's operations. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.
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| 7. |
- Kim, Jae-Young, et al.
(författare)
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Event Horizon Telescope imaging of the archetypal blazar 3C 279 at an extreme 20 microarcsecond resolution
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 640
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Tidskriftsartikel (refereegranskat)abstract
- 3C 279 is an archetypal blazar with a prominent radio jet that show broadband flux density variability across the entire electromagnetic spectrum. We use an ultra-high angular resolution technique - global Very Long Baseline Interferometry (VLBI) at 1.3mm (230 GHz) - to resolve the innermost jet of 3C 279 in order to study its fine-scale morphology close to the jet base where highly variable-ray emission is thought to originate, according to various models. The source was observed during four days in April 2017 with the Event Horizon Telescope at 230 GHz, including the phased Atacama Large Millimeter/submillimeter Array, at an angular resolution of ∼20 μas (at a redshift of z = 0:536 this corresponds to ∼0:13 pc ∼ 1700 Schwarzschild radii with a black hole mass MBH = 8 × 108 M⊙). Imaging and model-fitting techniques were applied to the data to parameterize the fine-scale source structure and its variation.We find a multicomponent inner jet morphology with the northernmost component elongated perpendicular to the direction of the jet, as imaged at longer wavelengths. The elongated nuclear structure is consistent on all four observing days and across diffierent imaging methods and model-fitting techniques, and therefore appears robust. Owing to its compactness and brightness, we associate the northern nuclear structure as the VLBI "core". This morphology can be interpreted as either a broad resolved jet base or a spatially bent jet.We also find significant day-to-day variations in the closure phases, which appear most pronounced on the triangles with the longest baselines. Our analysis shows that this variation is related to a systematic change of the source structure. Two inner jet components move non-radially at apparent speeds of ∼15 c and ∼20 c (∼1:3 and ∼1:7 μas day-1, respectively), which more strongly supports the scenario of traveling shocks or instabilities in a bent, possibly rotating jet. The observed apparent speeds are also coincident with the 3C 279 large-scale jet kinematics observed at longer (cm) wavelengths, suggesting no significant jet acceleration between the 1.3mm core and the outer jet. The intrinsic brightness temperature of the jet components are ≤1010 K, a magnitude or more lower than typical values seen at ≥7mm wavelengths. The low brightness temperature and morphological complexity suggest that the core region of 3C 279 becomes optically thin at short (mm) wavelengths.
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| 8. |
- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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| 9. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 10. |
- Bruder, Carl E G, et al.
(författare)
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Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles
- 2008
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 82:3, s. 763-71
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Tidskriftsartikel (refereegranskat)abstract
- The exploration of copy-number variation (CNV), notably of somatic cells, is an understudied aspect of genome biology. Any differences in the genetic makeup between twins derived from the same zygote represent an irrefutable example of somatic mosaicism. We studied 19 pairs of monozygotic twins with either concordant or discordant phenotype by using two platforms for genome-wide CNV analyses and showed that CNVs exist within pairs in both groups. These findings have an impact on our views of genotypic and phenotypic diversity in monozygotic twins and suggest that CNV analysis in phenotypically discordant monozygotic twins may provide a powerful tool for identifying disease-predisposition loci. Our results also imply that caution should be exercised when interpreting disease causality of de novo CNVs found in patients based on analysis of a single tissue in routine disease-related DNA diagnostics.
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| 11. |
- Cadenas-Sanchez, Cristina, et al.
(författare)
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Differences in Brain Volume between Metabolically Healthy and Unhealthy Overweight and Obese Children : The Role of Fitness
- 2020
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine whether metabolically healthy overweight/obese children have greater global and regional gray matter volumes than their metabolically unhealthy peers. We further examined the association between gray matter volume and academic achievement, along with the role of cardiorespiratory fitness in these associations. A total of 97 overweight/obese children (10.0 +/- 1.2 years) participated. We classified children as metabolically healthy/unhealthy based on metabolic syndrome cut-offs. Global and regional brain volumes were assessed by magnetic resonance imaging. Academic achievement was assessed using the Woodcock-Munoz standardized test. Cardiorespiratory fitness was assessed by the 20 m shuttle run test. Metabolically healthy overweight/obese (MHO) children had greater regional gray matter volume compared to those who were metabolically unhealthy (MUO) (all p <= 0.001). A similar trend was observed for global gray matter volume (p = 0.06). Global gray matter volume was positively related to academic achievement (beta = 0.237, p = 0.036). However, all the associations were attenuated or disappeared after adjusting for cardiorespiratory fitness (p > 0.05). The findings of the present study support that metabolically healthy overweight/obese children have greater gray matter volume compared to those that are metabolically unhealthy, which is in turn related to better academic achievement. However, cardiorespiratory fitness seems to explain, at least partially, these findings.
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| 12. |
- Cadenas-Sanchez, C, et al.
(författare)
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Do fitter kids have bigger brains?
- 2020
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Ingår i: Scandinavian journal of medicine & science in sports. - : Wiley. - 1600-0838 .- 0905-7188. ; 30:12, s. 2498-2502
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 13. |
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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. |
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| 19. |
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| 20. |
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| 21. |
- Esteban-Cornejo, Irene, et al.
(författare)
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Fitness, cortical thickness and surface area in overweight/obese children: The mediating role of body composition and relationship with intelligence
- 2019
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Ingår i: NeuroImage. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1053-8119 .- 1095-9572. ; 186, s. 771-781
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Tidskriftsartikel (refereegranskat)abstract
- Cortical thickness and surface area are thought to be genetically unrelated and shaped by independent neurobiological events suggesting that they should be considered separately in morphometric analyses. Although the developmental trajectories of cortical thickness and surface area may differ across brain regions and ages, there is no consensus regarding the relationships of physical fitness with cortical thickness and surface area as well as for its subsequent influence on intelligence. Thus, this study examines: (i) the associations of physical fitness components (i.e., cardiorespiratory fitness, speed-agility and muscular fitness) with overall and regional cortical thickness and surface area; (ii) whether body composition indicators (i.e., body mass index, fat-free mass index and fat mass index) mediate these associations; and (iii) the association of physical fitness and cortical thickness with intelligence in overweight/obese children. A total of 101 overweight/obese children aged 8-11 years were recruited in Granada, Spain. The physical fitness components were assessed following the ALPHA health-related fitness test battery. T1-weighted images were acquired with a 3.0 Tesla Siemens Magnetom Tim Trio system. We used FreeSurfer software version 5.3.0 to assess cortical thickness (mm) and surface area (mm(2)). The main results showed that cardiorespiratory fitness and speed-agility were related to overall cortical thickness (beta = 0.321 and beta = 0.302, respectively; both P amp;lt; 0.05), and in turn, cortical thickness was associated with higher intelligence (beta = 0.198, P amp;lt; 0.05). Muscular fitness was not related to overall cortical thickness. None of the three physical fitness components were related to surface area (p amp;gt; 0.05). The associations of cardiorespiratory fitness and speed-agility with overall cortical thickness were mediated by fat mass index (56.86% amp; 62.28%, respectively). In conclusion, cardiorespiratory fitness and speed-agility, but not muscular fitness, are associated with overall cortical thickness, and in turn, thicker brain cortex is associated with higher intelligence in overweight/obese children. Yet, none of the three physical fitness components were related to surface area. Importantly, adiposity may hinder the benefits of cardiorespiratory fitness and speed-agility on cortical thickness. Understanding individual differences in brain morphology may have important implications for educators and policy makers who aim to determine policies and interventions to maximize academic learning and occupational success later in life.
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| 22. |
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| 23. |
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| 24. |
- Hawthorn, F., et al.
(författare)
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TOI-836: A super-Earth and mini-Neptune transiting a nearby K-dwarf
- 2023
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 520:3, s. 3649-3668
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Tidskriftsartikel (refereegranskat)abstract
- We present the discovery of two exoplanets transiting TOI-836 (TIC 440887364) using data from TESS Sector 11 and Sector 38. TOI-836 is a bright (T = 8.5 mag), high proper motion (∼200 mas yr−1), low metallicity ([Fe/H]≈−0.28) K-dwarf with a mass of 0.68 ± 0.05 M and a radius of 0.67 ± 0.01 R. We obtain photometric follow-up observations with a variety of facilities, and we use these data sets to determine that the inner planet, TOI-836 b, is a 1.70 ± 0.07 R super-Earth in a 3.82-d orbit, placing it directly within the so-called ‘radius valley’. The outer planet, TOI-836 c, is a 2.59 ± 0.09 R mini-Neptune in an 8.60-d orbit. Radial velocity measurements reveal that TOI-836 b has a mass of 4.5 ± 0.9 M, while TOI-836 c has a mass of 9.6 ± 2.6 M. Photometric observations show Transit Timing Variations (TTVs) on the order of 20 min for TOI-836 c, although there are no detectable TTVs for TOI-836 b. The TTVs of planet TOI-836 c may be caused by an undetected exterior planet.
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| 25. |
- Hou, Meijun, et al.
(författare)
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Human dopaminergic system in the exercise-cognition link
- 2024
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Ingår i: Trends in Molecular Medicine. - : Elsevier. - 1471-4914 .- 1471-499X.
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Tidskriftsartikel (refereegranskat)abstract
- While the dopaminergic system is important for cognitive processes, it is also sensitive to the influence of physical activity (PA). We summarize current evidence on whether PA-related changes in the human dopaminergic system are associated with alterations in cognitive performance, discuss recent advances, and highlight challenges and opportunities for future research.
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| 26. |
- Jimenez, MT, et al.
(författare)
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The miR-181 family regulates colonic inflammation through its activity in the intestinal epithelium
- 2022
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 219:12
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Tidskriftsartikel (refereegranskat)abstract
- The intestinal epithelium is a key physical interface that integrates dietary and microbial signals to regulate nutrient uptake and mucosal immune cell function. The transcriptional programs that regulate intestinal epithelial cell (IEC) quiescence, proliferation, and differentiation have been well characterized. However, how gene expression networks critical for IECs are posttranscriptionally regulated during homeostasis or inflammatory disease remains poorly understood. Herein, we show that a conserved family of microRNAs, miR-181, is significantly downregulated in IECs from patients with inflammatory bowel disease and mice with chemical-induced colitis. Strikingly, we showed that miR-181 expression within IECs, but not the hematopoietic system, is required for protection against severe colonic inflammation in response to epithelial injury in mice. Mechanistically, we showed that miR-181 expression increases the proliferative capacity of IECs, likely through the regulation of Wnt signaling, independently of the gut microbiota composition. As epithelial reconstitution is crucial to restore intestinal homeostasis after injury, the miR-181 family represents a potential therapeutic target against severe intestinal inflammation.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Lassinantti, Lena, et al.
(författare)
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Enterococcal PrgU Provides Additional Regulation of Pheromone-Inducible Conjugative Plasmids
- 2021
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Ingår i: mSphere. - : American Society for Microbiology (ASM). - 2379-5042. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- Efficient horizontal gene transfer of the conjugative plasmid pCF10 from Enterococcus faecalis depends on the expression of its type 4 secretion system (T4SS) genes, controlled by the PQ promoter. Transcription from the PQ promoter is tightly regulated, partially to limit cell toxicity caused by overproduction of PrgB, a T4SS adhesin. PrgU plays an important role in regulating this toxicity by decreasing PrgB levels. PrgU has an RNA-binding fold, prompting us to test whether PrgU exerts its regulatory control through binding of prgQ transcripts. We used a combination of in vivo methods to quantify PrgU effects on prgQ transcripts at both single-cell and population levels. PrgU function requires a specific RNA sequence within an intergenic region (IGR) about 400 bp downstream of PQ. PrgU interaction with the IGR reduces levels of downstream transcripts. Single-cell expression analysis showed that cells expressing prgU decreased transcript levels more rapidly than isogenic prgU-minus cells. PrgU bound RNA in vitro without sequence specificity, suggesting that PrgU requires a specific RNA structure or one or more host factors for selective binding in vivo. PrgU binding to its IGR target might recruit RNase(s) for targeted degradation of downstream transcripts or reduce elongation of nascent transcripts beyond the IGR.IMPORTANCE: Bacteria utilize type 4 secretion systems (T4SS) to efficiently transfer DNA between donor and recipient cells, thereby spreading genes encoding antibiotic resistance as well as various virulence factors. Regulation of expression of the T4SS proteins and surface adhesins in Gram-positive bacteria is crucial, as some of these are highly toxic to the cell. The significance of our research lies in identifying the novel mechanism by which PrgU performs its delicate fine-tuning of the expression levels. As prgU orthologs are present in various conjugative plasmids and transposons, our results are likely relevant to understanding of diverse clinically important transfer systems.
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| 31. |
- Matsui, H., et al.
(författare)
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Dipolarization in the inner magnetosphere during a geomagnetic storm on 7 October 2015
- 2016
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 43:18, s. 9397-9405
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Tidskriftsartikel (refereegranskat)abstract
- A dipolarization event was observed by the Magnetospheric Multiscale (MMS) spacecraft at L = 3.8 and 19.8 magnetic local time starting at similar to 23:42:36 UT on 7 October 2015. The magnetic and electric fields showed initially coherent variations between the spacecraft. The sunward convection turned tailward after the dipolarization. The observation is interpreted in terms of the pressure balance or the momentum equation. This was followed by a region traversed where the fields were irregular. The scale length was of the order of the ion gyroradius, suggesting the kinetic nature of the fluctuations. Combination of the multi-instrument, multispacecraft data reveals a more detailed picture of the dipolarization event in the inner magnetosphere. Conjunction ionosphere-plasmasphere observations from DMSP, two-dimensional GPS total electron content, the Millstone Hill midlatitude incoherent scatter radar, and AMPERE measurements imply that MMS observations are located on the poleward edge of the ionospheric trough where Region 2 field-aligned currents flow.
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| 32. |
- Migueles, JH, et al.
(författare)
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Associations of Objectively-Assessed Physical Activity and Sedentary Time with Hippocampal Gray Matter Volume in Children with Overweight/Obesity
- 2020
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated physical activity (PA) and sedentary time (SED) in relation to hippocampal gray matter volume (GMV) in pediatric overweight/obesity. Ninety-three children (10 ± 1 year) were classified as overweight, obesity type I, or type II–III. PA was assessed with non-dominant wrist accelerometers. GMV was acquired by magnetic resonance imaging (MRI). Neither PA nor SED associated with GMV in the hippocampus in the whole sample (p > 0.05). However, we found some evidence of moderation by weight status (p < 0.150). Moderate-to-vigorous PA (MVPA) positively associated with GMV in the right hippocampus in obesity type I (B = 5.62, p = 0.017), which remained when considering SED, light PA, and sleep using compositional data (γ = 375.3, p = 0.04). Compositional models also depicted a negative association of SED relative to the remaining behaviors with GMV in the right hippocampus in overweight (γ = −1838.4, p = 0.038). Reallocating 20 min/day of SED to MVPA was associated with 100 mm3 GMV in the right hippocampus in obesity type I. Multivariate pattern analysis showed a negative-to-positive association pattern between PA of increasing intensity and GMV in the right hippocampus in obesity type II–III. Our findings support that reducing SED and increasing MVPA are associated with greater GMV in the right hippocampus in pediatric overweight/obesity. Further studies should corroborate our findings.
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| 33. |
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| 34. |
- Ortega, Francisco B., et al.
(författare)
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Effects of an Exercise Program on Brain Health Outcomes for Children With Overweight or Obesity The ActiveBrains Randomized Clinical Trial
- 2022
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Ingår i: JAMA Network Open. - : American Medical Association. - 2574-3805. ; 5:8
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Pediatric overweight and obesity are highly prevalent across the world, with implications for poorer cognitive and brain health. Exercise might potentially attenuate these adverse consequences. OBJECTIVES To investigate the effects of an exercise program on brain health indicators, including intelligence, executive function, academic performance, and brain outcomes, among children with overweight or obesity and to explore potential mediators and moderators of the main effects of exercise. DESIGN, SETTING, AND PARTICIPANTS All preexercise and postexercise data for this 20-week randomized clinical trial of 109 children aged 8 to 11 years with overweight or obesity were collected from November 21, 2014, to June 30, 2016, with neuroimaging data processing and analyses conducted between June 1, 2017, and December 20, 2021. All 109 children were included in the intention-to-treat analyses; 90 children (82.6%) completed the postexercise evaluation and attended 70% or more of the recommended exercise sessions and were included in per-protocol analyses. INTERVENTIONS All participants received lifestyle recommendations. The control group continued their usual routines, whereas the exercise group attended a minimum of 3 supervised 90-minute sessions per week in an out-of-school setting. MAIN OUTCOMES AND MEASURES Intelligence, executive function (cognitive flexibility, inhibition, and working memory), and academic performance were assessed with standardized tests, and hippocampal volume was measured with magnetic resonance imaging. RESULTS The 109 participants included 45 girls (41.3%); participants had a mean (SD) body mass index of 26.8 (3.6) and a mean (SD) age of 10.0 (1.1) years at baseline. In per-protocol analyses, the exercise intervention improved crystallized intelligence, with the exercise group improving from before exercise to after exercise (mean z score, 0.62 [95% CI, 0.44-0.80]) compared with the control group (mean z score, -0.10 [95% CI, -0.28 to 0.09]; difference between groups, 0.72 SDs [95% CI, 0.46-0.97]; P < .001). Total intelligence also improved significantly more in the exercise group (mean z score, 0.69 [95% CI, 0.48-0.89]) than in the control group (mean z score, 0.07 [95% CI, -0.14 to 0.28]; difference between groups, 0.62 SDs [95% CI, 0.31-0.91]; P < .001). Exercise also positively affected a composite score of cognitive flexibility (mean z score: exercise group, 0.25 [95% CI, 0.05-0.44]; control group, -0.17 [95% CI, -0.39 to 0.04]; difference between groups, 0.42 SDs [95% CI, 0.13-0.71]; P = .005). These main effects were consistent in intention-to-treat analyses and after multiple-testing correction. There was a positive, small-magnitude effect of exercise on total academic performance (mean z score: exercise group, 0.31 [95% CI, 0.18-0.44]; control group, 0.10 [95% CI, -0.04 to 0.24]; difference between groups, 0.21 SDs [95% CI, 0.01-0.40]; P = .03), which was partially mediated by cognitive flexibility. Inhibition, working memory, hippocampal volume, and other brain magnetic resonance imaging outcomes studied were not affected by the exercise program. The intervention increased cardiorespiratory fitness performance as indicated by longer treadmill time to exhaustion (mean z score: exercise group, 0.54 [95% CI, 0.27-0.82]; control group, 0.13 [95% CI, -0.16 to 0.41]; difference between groups, 0.42 SDs [95% CI, 0.01-0.82]; P = .04), and these changes in fitness mediated some of the effects (small percentage of mediation [approximately 10%-20%]). The effects of exercise were overall consistent across the moderators tested, except for larger improvements in intelligence among boys compared with girls. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, exercise positively affected intelligence and cognitive flexibility during development among children with overweight or obesity. However, the structural and functional brain changes responsible for these improvements were not identified.
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| 35. |
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| 36. |
- Rodriguez-Ayllon, Maria, et al.
(författare)
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Role of Physical Activity and Sedentary Behavior in the Mental Health of Preschoolers, Children and Adolescents: A Systematic Review and Meta-Analysis
- 2019
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Ingår i: Sports Medicine. - : ADIS INT LTD. - 0112-1642 .- 1179-2035. ; 49:9, s. 1383-1410
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Forskningsöversikt (refereegranskat)abstract
- Background Evidence suggests that participation in physical activity may support young peoples current and future mental health. Although previous reviews have examined the relationship between physical activity and a range of mental health outcomes in children and adolescents, due to the large increase in published studies there is a need for an update and quantitative synthesis of effects. Objectives The objectives of this study were to determine the effect of physical activity interventions on mental health outcomes by conducting a systematic review and meta-analysis, and to systematically synthesize the observational evidence (both longitudinal and cross-sectional studies) regarding the associations between physical activity and sedentary behavior and mental health in preschoolers (2-5 years of age), children (6-11 years of age) and adolescents (12-18 years of age). Methods A systematic search of the PubMed and Web of Science electronic databases was performed from January 2013 to April 2018, by two independent researchers. Meta-analyses were performed to examine the effect of physical activity on mental health outcomes in randomized controlled trials (RCTs) and non-RCTs (i.e. quasi-experimental studies). A narrative synthesis of observational studies was conducted. Studies were included if they included physical activity or sedentary behavior data and at least one psychological ill-being (i.e. depression, anxiety, stress or negative affect) or psychological well-being (i.e. self-esteem, self-concept, self-efficacy, self-image, positive affect, optimism, happiness and satisfaction with life) outcome in preschoolers, children or adolescents. Results A total of 114 original articles met all the eligibility criteria and were included in the review (4 RCTs, 14 non-RCTs, 28 prospective longitudinal studies and 68 cross-sectional studies). Of the 18 intervention studies, 12 (3 RCTs and 9 non-RCTs) were included in the meta-analysis. There was a small but significant overall effect of physical activity on mental health in children and adolescents aged 6-18 years (effect size 0.173, 95% confidence interval 0.106-0.239, p amp;lt; 0.001, percentage of total variability attributed to between-study heterogeneity [I-2] = 11.3%). When the analyses were performed separately for children and adolescents, the results were significant for adolescents but not for children. Longitudinal and cross-sectional studies demonstrated significant associations between physical activity and lower levels of psychological ill-being (i.e. depression, stress, negative affect, and total psychological distress) and greater psychological well-being (i.e. self-image, satisfaction with life and happiness, and psychological well-being). Furthermore, significant associations were found between greater amounts of sedentary behavior and both increased psychological ill-being (i.e. depression) and lower psychological well-being (i.e. satisfaction with life and happiness) in children and adolescents. Evidence on preschoolers was nearly non-existent. Conclusions Findings from the meta-analysis suggest that physical activity interventions can improve adolescents mental health, but additional studies are needed to confirm the effects of physical activity on childrens mental health. Findings from observational studies suggest that promoting physical activity and decreasing sedentary behavior might protect mental health in children and adolescents. PROSPERO Registration Number: CRD42017060373.
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| 37. |
- Stiernman Jonasson, Lars, 1983-, et al.
(författare)
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Impact of aerobic exercise on brain structure in models of aging : Hippocampus and beyond
- 2021
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Ingår i: Factors Affecting Neurological Aging. - : Elsevier. - 9780128179901 ; , s. 403-413
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Bokkapitel (refereegranskat)abstract
- Evidence from multiple scientific disciplines indicates that aerobic exercise could be effective in enhancing brain health and function in aging, and reducing the risk for cognitive impairment and dementia. Animal models have provided convincing evidence that exercise increases the expression of growth factors involved in neuroplasticity. By triggering signaling cascades in the brain, these growth factors promote proliferation, neurogenesis, neural differentiation, and cell survival in the hippocampus, and angiogenesis and/or synaptic plasticity and neural growth throughout the brain more generally. These growth factor-induced effects partly explain why exercise improves memory. Furthermore, they engender neuroprotective effects by influencing regeneration, remyelination, cell survival, and waste removal. Whereas human intervention evidence supports hippocampal plasticity, cross-sectional studies highlight effects in the cortex too, indicating that exercise-induced gross morphological changes may be regionally specific. Aerobic exercise is a promising nonpharmacological therapy to maintain brain health, although knowledge about the effects of specific exercise parameters (i.e., intensity) on different populations is still lacking.
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| 38. |
- Wilson, Sara I, et al.
(författare)
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Escape mutants of HIV-1 proteinase : enzymic efficiency and susceptibility to inhibition
- 1997
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Ingår i: Biochimica et Biophysica Acta. - 0006-3002 .- 1878-2434. ; 1339:1, s. 113-125
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Tidskriftsartikel (refereegranskat)abstract
- Genes encoding a number of mutants of HIV-1 proteinase were sub-cloned and expressed in E. coli. The proteinases containing mutations of single residues (e.g., G48V, V82F, I84V and L90M) were purified and their catalytic efficiencies relative to that of wild-type proteinase were examined using a polyprotein (recombinant HIV-1 gag) substrate and several series of synthetic peptides based on the -Hydrophobic * Hydrophobic-, -Aromatic * Pro- and pseudo-symmetrical types of cleavage junction. The L90M proteinase showed only small changes, whereas the activity of the other mutant enzymes was compromised more severely, particularly towards substrates of the -Aromatic * Pro- and pseudo-symmetrical types. The susceptibility of the mutants and the wild-type proteinase to inhibition by eleven different compounds was compared. The L90M proteinase again showed only marginal changes in its susceptibility to all except one of the inhibitors examined. The K(i) values determined for one inhibitor (Ro31-8959) showed that its potency towards the V82F, L90M, I84V and G48V mutant proteinases respectively was 2-, 3-, 17- and 27-fold less than against the wild-type proteinase. Several of the other inhibitors examined form a systematic series with Ro31-8959. The inhibition constants derived with these and a number of other inhibitors, including ABT-538 and L-735,524, are used in conjunction with the data on enzymic efficiency to assess whether each mutation in the proteinase confers an advantage for viral replication in the presence of any given inhibitor.
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| 39. |
- Wulf Hanson, Sarah, et al.
(författare)
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A global systematic analysis of the occurrence, severity, and recovery pattern of long COVID in 2020 and 2021
- 2022
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Importance: While much of the attention on the COVID-19 pandemic was directed at the daily counts of cases and those with serious disease overwhelming health services, increasingly, reports have appeared of people who experience debilitating symptoms after the initial infection. This is popularly known as long COVID.Objective: To estimate by country and territory of the number of patients affected by long COVID in 2020 and 2021, the severity of their symptoms and expected pattern of recovery.Design: We jointly analyzed ten ongoing cohort studies in ten countries for the occurrence of three major symptom clusters of long COVID among representative COVID cases. The defining symptoms of the three clusters (fatigue, cognitive problems, and shortness of breath) are explicitly mentioned in the WHO clinical case definition. For incidence of long COVID, we adopted the minimum duration after infection of three months from the WHO case definition. We pooled data from the contributing studies, two large medical record databases in the United States, and findings from 44 published studies using a Bayesian meta-regression tool. We separately estimated occurrence and pattern of recovery in patients with milder acute infections and those hospitalized. We estimated the incidence and prevalence of long COVID globally and by country in 2020 and 2021 as well as the severity-weighted prevalence using disability weights from the Global Burden of Disease study.Results: Analyses are based on detailed information for 1906 community infections and 10526 hospitalized patients from the ten collaborating cohorts, three of which included children. We added published data on 37262 community infections and 9540 hospitalized patients as well as ICD-coded medical record data concerning 1.3 million infections. Globally, in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8-312.9) people suffered from any of the three symptom clusters of long COVID. This corresponds to 3.69% (1.38-7.96) of all infections. The fatigue, respiratory, and cognitive clusters occurred in 51.0% (16.9-92.4), 60.4% (18.9-89.1), and 35.4% (9.4-75.1) of long COVID cases, respectively. Those with milder acute COVID-19 cases had a quicker estimated recovery (median duration 3.99 months [IQR 3.84-4.20]) than those admitted for the acute infection (median duration 8.84 months [IQR 8.10-9.78]). At twelve months, 15.1% (10.3-21.1) continued to experience long COVID symptoms.Conclusions and relevance: The occurrence of debilitating ongoing symptoms of COVID-19 is common. Knowing how many people are affected, and for how long, is important to plan for rehabilitative services and support to return to social activities, places of learning, and the workplace when symptoms start to wane.Key Points: Question: What are the extent and nature of the most common long COVID symptoms by country in 2020 and 2021?Findings: Globally, 144.7 million people experienced one or more of three symptom clusters (fatigue; cognitive problems; and ongoing respiratory problems) of long COVID three months after infection, in 2020 and 2021. Most cases arose from milder infections. At 12 months after infection, 15.1% of these cases had not yet recovered.Meaning: The substantial number of people with long COVID are in need of rehabilitative care and support to transition back into the workplace or education when symptoms start to wane.
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| 40. |
- Wulf Hanson, Sarah, et al.
(författare)
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Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021
- 2022
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 328:16, s. 1604-1615
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID).OBJECTIVE: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration.DESIGN, SETTING, AND PARTICIPANTS: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022.EXPOSURES: Symptomatic SARS-CoV-2 infection.MAIN OUTCOMES AND MEASURES: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age.RESULTS: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months.CONCLUSIONS AND RELEVANCE: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.
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