| 1. |
- Murari, A., et al.
(författare)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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| 2. |
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Barucca, G., et al.
(författare)
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The potential of Λ and Ξ- studies with PANDA at FAIR
- 2021
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Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Tidskriftsartikel (refereegranskat)abstract
- The antiproton experiment PANDA at FAIR is designed to bring hadron physics to a new level in terms of scope, precision and accuracy. In this work, its unique capability for studies of hyperons is outlined. We discuss ground-state hyperons as diagnostic tools to study non-perturbative aspects of the strong interaction, and fundamental symmetries. New simulation studies have been carried out for two benchmark hyperon-antihyperon production channels: p¯ p→ Λ¯ Λ and p¯ p→ Ξ¯ +Ξ-. The results, presented in detail in this paper, show that hyperon-antihyperon pairs from these reactions can be exclusively reconstructed with high efficiency and very low background contamination. In addition, the polarisation and spin correlations have been studied, exploiting the weak, self-analysing decay of hyperons and antihyperons. Two independent approaches to the finite efficiency have been applied and evaluated: one standard multidimensional efficiency correction approach, and one efficiency independent approach. The applicability of the latter was thoroughly evaluated for all channels, beam momenta and observables. The standard method yields good results in all cases, and shows that spin observables can be studied with high precision and accuracy already in the first phase of data taking with PANDA.
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| 7. |
- Barucca, G., et al.
(författare)
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Study of excited Ξ baryons with the P¯ ANDA detector
- 2021
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Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Tidskriftsartikel (refereegranskat)abstract
- The study of baryon excitation spectra provides insight into the inner structure of baryons. So far, most of the world-wide efforts have been directed towards N∗ and Δ spectroscopy. Nevertheless, the study of the double and triple strange baryon spectrum provides independent information to the N∗ and Δ spectra. The future antiproton experiment P¯ANDA will provide direct access to final states containing a Ξ¯ Ξ pair, for which production cross sections up to μb are expected in p¯p reactions. With a luminosity of L= 10 31 cm- 2 s- 1 in the first phase of the experiment, the expected cross sections correspond to a production rate of ∼106events/day. With a nearly 4 π detector acceptance, P¯ANDA will thus be a hyperon factory. In this study, reactions of the type p¯p → Ξ¯ +Ξ∗ - as well as p¯p → Ξ¯ ∗ +Ξ- with various decay modes are investigated. For the exclusive reconstruction of the signal events a full decay tree fit is used, resulting in reconstruction efficiencies between 3 and 5%. This allows high statistics data to be collected within a few weeks of data taking.
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| 8. |
- Blach, S., et al.
(författare)
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Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study
- 2022
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Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:5, s. 396-415
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Tidskriftsartikel (refereegranskat)abstract
- Background Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. Methods This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age =0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. Findings Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0.7% (95% UI 0.7-0.9), corresponding to 56.8 million (95% UI 55.2-67.8) infections, on Jan 1, 2020. This number represents a decrease of 6.8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63.6 million (61.8-75.8) infections (0.9% [0.8-1.0] prevalence). By the end of 2020, an estimated 12.9 million (12.5-15.4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641 000 (623 000-765 000) patients initiated treatment. Interpretation At the beginning of 2020, there were an estimated 56.8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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| 9. |
- Lumbers, R. T., et al.
(författare)
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The genomics of heart failure: design and rationale of the HERMES consortium
- 2021
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Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541
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Tidskriftsartikel (refereegranskat)abstract
- Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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| 10. |
- Hageman, S., et al.
(författare)
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SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 42:25, s. 2439-2454
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Tidskriftsartikel (refereegranskat)abstract
- Aims The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40-69 years in Europe. Methods and results We derived risk prediction models using individual-participant data from 45 cohorts in 13 countries (677 684 individuals, 30 121 CVD events). We used sex-specific and competing risk-adjusted models, including age, smoking status, systolic blood pressure, and total- and HDL-cholesterol. We defined four risk regions in Europe according to country-specific CVD mortality, recalibrating models to each region using expected incidences and risk factor distributions. Region-specific incidence was estimated using CVD mortality and incidence data on 10 776 466 individuals. For external validation, we analysed data from 25 additional cohorts in 15 European countries (1 133 181 individuals, 43 492 CVD events). After applying the derived risk prediction models to external validation cohorts, C-indices ranged from 0.67 (0.65-0.68) to 0.81 (0.76-0.86). Predicted CVD risk varied several-fold across European regions. For example, the estimated 10-year CVD risk for a 50-year-old smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and HDL-cholesterol of 1.3 mmol/L, ranged from 5.9% for men in low- risk countries to 14.0% for men in very high-risk countries, and from 4.2% for women in low-risk countries to 13.7% for women in very high-risk countries. Conclusion SCORE2-a new algorithm derived, calibrated, and validated to predict 10-year risk of first-onset CVD in European populations-enhances the identification of individuals at higher risk of developing CVD across Europe.
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| 11. |
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| 12. |
- Boen, Rune, et al.
(författare)
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Beyond the global brain differences : intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers
- 2024
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Ingår i: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 95:2, s. 147-160
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Tidskriftsartikel (refereegranskat)abstract
- Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference.Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness.Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
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| 13. |
- Sønderby, Ida E., et al.
(författare)
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1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
- 2021
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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| 14. |
- van der Meer, Dennis, et al.
(författare)
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Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
- 2020
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
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| 15. |
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| 16. |
- Charette, M. A., et al.
(författare)
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The Transpolar Drift as a Source of Riverine and Shelf-Derived Trace Elements to the Central Arctic Ocean
- 2020
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Ingår i: Journal of Geophysical Research-Oceans. - : American Geophysical Union (AGU). - 2169-9275 .- 2169-9291. ; 125:5
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Tidskriftsartikel (refereegranskat)abstract
- A major surface circulation feature of the Arctic Ocean is the Transpolar Drift (TPD), a current that transports river-influenced shelf water from the Laptev and East Siberian Seas toward the center of the basin and Fram Strait. In 2015, the international GEOTRACES program included a high-resolution pan-Arctic survey of carbon, nutrients, and a suite of trace elements and isotopes (TEIs). The cruises bisected the TPD at two locations in the central basin, which were defined by maxima in meteoric water and dissolved organic carbon concentrations that spanned 600 km horizontally and similar to 25-50 m vertically. Dissolved TEIs such as Fe, Co, Ni, Cu, Hg, Nd, and Th, which are generally particle-reactive but can be complexed by organic matter, were observed at concentrations much higher than expected for the open ocean setting. Other trace element concentrations such as Al, V, Ga, and Pb were lower than expected due to scavenging over the productive East Siberian and Laptev shelf seas. Using a combination of radionuclide tracers and ice drift modeling, the transport rate for the core of the TPD was estimated at 0.9 +/- 0.4 Sv (10(6) m(3)s(-1)). This rate was used to derive the mass flux for TEIs that were enriched in the TPD, revealing the importance of lateral transport in supplying materials beneath the ice to the central Arctic Ocean and potentially to the North Atlantic Ocean via Fram Strait. Continued intensification of the Arctic hydrologic cycle and permafrost degradation will likely lead to an increase in the flux of TEIs into the Arctic Ocean. Plain Language Summary A major feature of the Arctic Ocean circulation is the Transpolar Drift (TPD), a surface current that carries ice and continental shelf-derived materials from Siberia across the North Pole to the North Atlantic Ocean. In 2015, an international team of oceanographers conducted a survey of trace elements in the Arctic Ocean, traversing the TPD. Near the North Pole, they observed much higher concentrations of trace elements in surface waters than in regions on either side of the current. These trace elements originated from land, and their journey across the Arctic Ocean is made possible by chemical reactions with dissolved organic matter that originates mainly in Arctic rivers. This study reveals the importance of rivers and shelf processes combined with strong ocean currents in supplying trace elements to the central Arctic Ocean and onward to the Atlantic. These trace element inputs are expected to increase as a result of permafrost thawing and increased river runoff in the Arctic, which is warming at a rate much faster than anywhere else on Earth. Since many of the trace elements are essential building blocks for ocean life, these processes could lead to significant changes in the marine ecosystems and fisheries of the Arctic Ocean.
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| 17. |
- Forstner, A. J., et al.
(författare)
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Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 4179-4190
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Tidskriftsartikel (refereegranskat)abstract
- Panic disorder (PD) has a lifetime prevalence of 2–4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0–34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10−4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10−7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.
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| 18. |
- Lønborg, C., et al.
(författare)
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A global database of dissolved organic matter (DOM) concentration measurements in coastal waters (CoastDOM v1)
- 2024
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Ingår i: Earth System Science Data. - : Copernicus Publications. - 1866-3508 .- 1866-3516. ; 16:2, s. 1107-1119
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of dissolved organic carbon (DOC), nitrogen (DON), and phosphorus (DOP) concentrations are used to characterize the dissolved organic matter (DOM) pool and are important components ofbiogeochemical cycling in the coastal ocean. Here, we present the first edition of a global database (CoastDOMv1; available at https://doi.org/10.1594/PANGAEA.964012, Lønborg et al., 2023) compiling previously published and unpublished measurements of DOC, DON, and DOP in coastal waters. These data are complementedby hydrographic data such as temperature and salinity and, to the extent possible, other biogeochemical variables(e.g. chlorophyll a, inorganic nutrients) and the inorganic carbon system (e.g. dissolved inorganic carbon andtotal alkalinity). Overall, CoastDOM v1 includes observations of concentrations from all continents. However,most data were collected in the Northern Hemisphere, with a clear gap in DOM measurements from the SouthernHemisphere. The data included were collected from 1978 to 2022 and consist of 62 338 data points for DOC,20 356 for DON, and 13 533 for DOP. The number of measurements decreases progressively in the sequenceDOC > DON > DOP, reflecting both differences in the maturity of the analytical methods and the greater focuson carbon cycling by the aquatic science community. The global database shows that the average DOC concentration in coastal waters (average ± standard deviation (SD): 182±314 µmolC L−1; median: 103 µmolC L−1) is13-fold higher than the average coastal DON concentration (13.6 ± 30.4 µmol N L−1; median: 8.0 µmol N L−1),which is itself 39-fold higher than the average coastal DOP concentration (0.34 ± 1.11 µmol P L−1; median:0.18 µmol P L−1). This dataset will be useful for identifying global spatial and temporal patterns in DOM and willhelp facilitate the reuse of DOC, DON, and DOP data in studies aimed at better characterizing local biogeochemical processes; closing nutrient budgets; estimating carbon, nitrogen, and phosphorous pools; and establishing abaseline for modelling future changes in coastal waters.
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| 19. |
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| 20. |
- Charette, M, et al.
(författare)
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The Transpolar Drift as a Source of Riverine and Shelf‐Derived Trace Elements to the Central Arctic Ocean
- 2020
-
Ingår i: Journal of Geophysical Research - Oceans. - 2169-9275 .- 2169-9291. ; 125, s. 1-34
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Tidskriftsartikel (refereegranskat)abstract
- A major surface circulation feature of the Arctic Ocean is the Transpolar Drift (TPD), a current that transports river‐influenced shelf water from the Laptev and East Siberian Seas toward the center of the basin and Fram Strait. In 2015, the international GEOTRACES program included a high‐resolution pan‐Arctic survey of carbon, nutrients, and a suite of trace elements and isotopes (TEIs). The cruises bisected the TPD at two locations in the central basin, which were defined by maxima in meteoric water and dissolved organic carbon concentrations that spanned 600 km horizontally and ~25–50 m vertically. Dissolved TEIs such as Fe, Co, Ni, Cu, Hg, Nd, and Th, which are generally particle‐reactive but can be complexed by organic matter, were observed at concentrations much higher than expected for the openocean setting. Other trace element concentrations such as Al, V, Ga, and Pb were lower than expected due to scavenging over the productive East Siberian and Laptev shelf seas. Using a combination of radionuclide tracers and ice drift modeling, the transport rate for the core of the TPD was estimated at 0.9 ± 0.4 Sv(106m3 s−1). This rate was used to derive the mass flux for TEIs that were enriched in the TPD, revealing the importance of lateral transport in supplying materials beneath the ice to the central Arctic Ocean and potentially to the North Atlantic Ocean via Fram Strait. Continued intensification of the Arctic hydrologicc ycle and permafrost degradation will likely lead to an increase in the flux of TEIs into the Arctic Ocean.
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| 21. |
- Shah, S, et al.
(författare)
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Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
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| 22. |
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| 23. |
- Arheimer, Berit, et al.
(författare)
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The IAHS Science for Solutions decade, with Hydrology Engaging Local People IN a Global world (HELPING)
- 2024
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Ingår i: Hydrological Sciences Journal. - 0262-6667 .- 2150-3435.
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Tidskriftsartikel (refereegranskat)abstract
- The new scientific decade (2023-2032) of the International Association of Hydrological Sciences (IAHS) aims at searching for sustainable solutions to undesired water conditions - may it be too little, too much or too polluted. Many of the current issues originate from global change, while solutions to problems must embrace local understanding and context. The decade will explore the current water crises by searching for actionable knowledge within three themes: global and local interactions, sustainable solutions and innovative cross-cutting methods. We capitalise on previous IAHS Scientific Decades shaping a trilogy; from Hydrological Predictions (PUB) to Change and Interdisciplinarity (Panta Rhei) to Solutions (HELPING). The vision is to solve fundamental water-related environmental and societal problems by engaging with other disciplines and local stakeholders. The decade endorses mutual learning and co-creation to progress towards UN sustainable development goals. Hence, HELPING is a vehicle for putting science in action, driven by scientists working on local hydrology in coordination with local, regional, and global processes.
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| 24. |
- Sonderby, Ida E., et al.
(författare)
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
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Tidskriftsartikel (refereegranskat)abstract
- Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
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| 25. |
- Mlecnik, B, et al.
(författare)
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Clinical Performance of the Consensus Immunoscore in Colon Cancer in the Asian Population from the Multicenter International SITC Study
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:18
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In this study, we evaluated the prognostic value of Immunoscore in patients with stage I–III colon cancer (CC) in the Asian population. These patients were originally included in an international study led by the Society for Immunotherapy of Cancer (SITC) on 2681 patients with AJCC/UICC-TNM stages I–III CC. METHODS: CD3+ and cytotoxic CD8+ T-lymphocyte densities were quantified in the tumor and invasive margin by digital pathology. The association of Immunoscore with prognosis was evaluated for time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS). RESULTS: Immunoscore stratified Asian patients (n = 423) into different risk categories and was not impacted by age. Recurrence-free rates at 3 years were 78.5%, 85.2%, and 98.3% for a Low, Intermediate, and High Immunoscore, respectively (HR[Low-vs-High] = 7.26 (95% CI 1.75−30.19); p = 0.0064). A High Immunoscore showed a significant association with prolonged TTR, OS, and DFS (p < 0.05). In Cox multivariable analysis stratified by center, Immunoscore association with TTR was independent (HR[Low-vs-Int+High] = 2.22 (95% CI 1.10–4.55) p = 0.0269) of the patient’s gender, T-stage, N-stage, sidedness, and MSI status. A significant association of a High Immunoscore with prolonged TTR was also found among MSS (HR[Low-vs-Int+High] = 4.58 (95% CI 2.27−9.23); p ≤ 0.0001), stage II (HR[Low-vs-Int+High] = 2.72 (95% CI 1.35−5.51); p = 0.0052), low-risk stage-II (HR[Low-vs-Int+High] = 2.62 (95% CI 1.21−5.68); p = 0.0146), and high-risk stage II patients (HR[Low-vs-Int+High] = 3.11 (95% CI 1.39−6.91); p = 0.0055). CONCLUSION: A High Immunoscore is significantly associated with the prolonged survival of CC patients within the Asian population.
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| 26. |
- Mlecnik, B, et al.
(författare)
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Multicenter International Study of the Consensus Immunoscore for the Prediction of Relapse and Survival in Early-Stage Colon Cancer
- 2023
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prognostic value of Immunoscore was evaluated in Stage II/III colon cancer (CC) patients, but it remains unclear in Stage I/II, and in early-stage subgroups at risk. An international Society for Immunotherapy of Cancer (SITC) study evaluated the pre-defined consensus Immunoscore in tumors from 1885 AJCC/UICC-TNM Stage I/II CC patients from Canada/USA (Cohort 1) and Europe/Asia (Cohort 2). METHODS: Digital-pathology is used to quantify the densities of CD3+ and CD8+ T-lymphocyte in the center of tumor (CT) and the invasive margin (IM). The time to recurrence (TTR) was the primary endpoint. Secondary endpoints were disease-free survival (DFS), overall survival (OS), prognosis in Stage I, Stage II, Stage II-high-risk, and microsatellite-stable (MSS) patients. RESULTS: High-Immunoscore presented with the lowest risk of recurrence in both cohorts. In Stage I/II, recurrence-free rates at 5 years were 78.4% (95%-CI, 74.4–82.6), 88.1% (95%-CI, 85.7–90.4), 93.4% (95%-CI, 91.1–95.8) in low, intermediate and high Immunoscore, respectively (HR (Hi vs. Lo) = 0.27 (95%-CI, 0.18–0.41); p < 0.0001). In Cox multivariable analysis, the association of Immunoscore to outcome was independent (TTR: HR (Hi vs. Lo) = 0.29, (95%-CI, 0.17–0.50); p < 0.0001) of the patient’s gender, T-stage, sidedness, and microsatellite instability-status (MSI). A significant association of Immunoscore with survival was found for Stage II, high-risk Stage II, T4N0 and MSS patients. The Immunoscore also showed significant association with TTR in Stage-I (HR (Hi vs. Lo) = 0.07 (95%-CI, 0.01–0.61); P = 0.016). The Immunoscore had the strongest (69.5%) contribution χ2 for influencing survival. Patients with a high Immunoscore had prolonged TTR in T4N0 tumors even for patients not receiving chemotherapy, and the Immunoscore remained the only significant parameter in multivariable analysis. CONCLUSION: In early CC, low Immunoscore reliably identifies patients at risk of relapse for whom a more intensive surveillance program or adjuvant treatment should be considered.
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| 27. |
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| 28. |
- Roswall, N., et al.
(författare)
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Long-Term Exposure to Transportation Noise and Risk of Incident Stroke: A Pooled Study of Nine Scandinavian Cohorts
- 2021
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 129:10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Transportation noise is increasingly acknowledged as a cardiovascular risk factor, but the evidence base for an association with stroke is sparse. OBJECTIVE: We aimed to investigate the association between transportation noise and stroke incidence in a large Scandinavian population. METHODS: We harmonized and pooled data from nine Scandinavian cohorts (seven Swedish, two Danish), totaling 135,951 participants. We identified residential address history and estimated road, railway, and aircraft noise for all addresses. Information on stroke incidence was acquired through linkage to national patient and mortality registries. We analyzed data using Cox proportional hazards models, including socioeconomic and lifestyle confounders, and air pollution. RESULTS: During follow-up (median = 19.5 y), 11,056 stroke cases were identified. Road traffic noise (Lden) was associated with risk of stroke, with a hazard ratio (HR) of 1.06 [95% confidence interval (CI): 1.03, 1.08] per 10-dB higher 5-y mean time-weighted exposure in analyses adjusted for individual- and area-level socioeconomic covariates. The association was approximately linear and persisted after adjustment for air pollution [particulate matter (PM) with an aerodynamic diameter of <= 2.5 mu m (PM2.5) and NO2]. Stroke was associated with moderate levels of 5-y aircraft noise exposure (40-50 vs. <= 40 dB) (HR = 1.12; 95% CI: 0.99, 1.27), but not with higher exposure (>= 50 dB, HR = 0.94; 95% CI: 0.79, 1.11). Railway noise was not associated with stroke. DISCUSSION: In this pooled study, road traffic noise was associated with a higher risk of stroke. This finding supports road traffic noise as an important cardiovascular risk factor that should be included when estimating the burden of disease due to traffic noise.
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| 29. |
- Andersson, Per A., et al.
(författare)
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Anger and disgust shape judgments of social sanctions across cultures, especially in high individual autonomy societies
- 2024
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Ingår i: Scientific Reports. - : Nature Research. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions.
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| 30. |
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| 31. |
- Janssens-Maenhout, G., et al.
(författare)
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Toward an operational anthropogenic CO2 emissions monitoring and verification support capacity
- 2020
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Ingår i: Bulletin of the American Meteorological Society. - 0003-0007. ; 101:8, s. 1439-1451
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Tidskriftsartikel (refereegranskat)abstract
- Under the Paris Agreement (PA), progress of emission reduction efforts is tracked on the basis of regular updates to national greenhouse gas (GHG) inventories, referred to as bottom-up estimates. However, only top-down atmospheric measurements can provide observation-based evidence of emission trends. Today, there is no internationally agreed, operational capacity to monitor anthropogenic GHG emission trends using atmospheric measurements to complement national bottom-up inventories. The European Commission (EC), the European Space Agency, the European Centre for Medium-Range Weather Forecasts, the European Organisation for the Exploitation of Meteorological Satellites, and international experts are joining forces to develop such an operational capacity for monitoring anthropogenic CO2 emissions as a new CO2 service under the EC's Copernicus program. Design studies have been used to translate identified needs into defined requirements and functionalities of this anthropogenic CO2 emissions Monitoring and Verification Support (CO2MVS) capacity. It adopts a holistic view and includes components such as atmospheric spaceborne and in situ measurements, bottom-up CO2 emission maps, improved modeling of the carbon cycle, an operational data-assimilation system integrating top-down and bottom-up information, and a policy-relevant decision support tool. The CO2MVS capacity with operational capabilities by 2026 is expected to visualize regular updates of global CO2 emissions, likely at 0.05° x 0.05°. This will complement the PA's enhanced transparency framework, providing actionable information on anthropogenic CO2 emissions that are the main driver of climate change. This information will be available to all stakeholders, including governments and citizens, allowing them to reflect on trends and effectiveness of reduction measures. The new EC gave the green light to pass the CO2MVS from exploratory to implementing phase.
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| 32. |
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| 33. |
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| 34. |
- Pilheden, M., et al.
(författare)
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Duplex Sequencing Uncovers Recurrent Low-frequency Cancer-associated Mutations in Infant and Childhood KMT2A-rearranged Acute Leukemia
- 2022
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Ingår i: Hemasphere. - : Ovid Technologies (Wolters Kluwer Health). - 2572-9241. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- Infant acute lymphoblastic leukemia (ALL) with KMT2A-gene rearrangements (KMT2A-r) have few mutations and a poor prognosis. To uncover mutations that are below the detection of standard next-generation sequencing (NGS), a combination of targeted duplex sequencing and NGS was applied on 20 infants and 7 children with KMT2A-r ALL, 5 longitudinal and 6 paired relapse samples. Of identified nonsynonymous mutations, 87 had been previously implicated in cancer and targeted genes recurrently altered in KMT2A-r leukemia and included mutations in KRAS, NRAS, FLT3, TP53, PIK3CA, PAX5, PIK3R1, and PTPN11, with infants having fewer such mutations. Of identified cancer-associated mutations, 62% were below the resolution of standard NGS. Only 33 of 87 mutations exceeded 2% of cellular prevalence and most-targeted PI3K/RAS genes (31/33) and typically KRAS/NRAS. Five patients only had low-frequency PI3K/RAS mutations without a higher-frequency signaling mutation. Further, drug-resistant clones with FLT3(D835H) or NRAS(G13D/G12S) mutations that comprised only 0.06% to 0.34% of diagnostic cells, expanded at relapse. Finally, in longitudinal samples, the relapse clone persisted as a minor subclone from diagnosis and through treatment before expanding during the last month of disease. Together, we demonstrate that infant and childhood KMT2A-r ALL harbor low-frequency cancer-associated mutations, implying a vast subclonal genetic landscape.
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| 35. |
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| 36. |
- Appelgren, M., et al.
(författare)
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Patient-reported outcomes one year after positive sentinel lymph node biopsy with or without axillary lymph node dissection in the randomized SENOMAC trial
- 2022
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Ingår i: Breast. - : Elsevier BV. - 0960-9776 .- 1532-3080. ; 63, s. 16-23
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: This report evaluates whether health related quality of life (HRQoL) and patient-reported arm morbidity one year after axillary surgery are affected by the omission of axillary lymph node dissection (ALND). Methods: The ongoing international non-inferiority SENOMAC trial randomizes clinically node-negative breast cancer patients (T1-T3) with 1-2 sentinel lymph node (SLN) macrometastases to completion ALND or no further axillary surgery. For this analysis, the first 1181 patients enrolled in Sweden and Denmark between March 2015, and June 2019, were eligible. Data extraction from the trial database was on November 2020. This report covers the secondary outcomes of the SENOMAC trial: HRQoL and patient-reported arm morbidity. The EORTC QLQC30, EORTC QLQ-BR23 and Lymph-ICF questionnaires were completed in the early postoperative phase and at one-year follow-up. Adjusted one-year mean scores and mean differences between the groups are presented corrected for multiple testing.
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| 37. |
- de Boniface, J., et al.
(författare)
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Omitting axillary dissection in breast cancer with sentinel-node metastases
- 2024
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 390:13, s. 1163-1175
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Trials evaluating the omission of completion axillary-lymph-node dissection in patients with clinically node-negative breast cancer and sentinel-lymph-node metastases have been compromised by limited statistical power, uncertain nodal radiotherapy target volumes, and a scarcity of data on relevant clinical subgroups.METHODS We conducted a noninferiority trial in which patients with clinically node-negative primary T1 to T3 breast cancer (tumor size, T1, ≤20 mm; T2, 21 to 50 mm; and T3, >50 mm in the largest dimension) with one or two sentinel-node macrometastases (metastasis size, >2 mm in the largest dimension) were randomly assigned in a 1:1 ratio to completion axillary-lymph-node dissection or its omission (sentinel-node biopsy only). Adjuvant treatment and radiation therapy were used in accordance with national guidelines. The primary end point was overall survival. We report here the per-protocol and modified intention-to-treat analyses of the prespecified secondary end point of recurrence-free survival. To show noninferiority of sentinel-node biopsy only, the upper boundary of the confidence interval for the hazard ratio for recurrence or death had to be below 1.44.RESULTS Between January 2015 and December 2021, a total of 2766 patients were enrolled across five countries. The per-protocol population included 2540 patients, of whom 1335 were assigned to undergo sentinel-node biopsy only and 1205 to undergo completion axillary-lymph-node dissection (dissection group). Radiation therapy including nodal target volumes was administered to 1192 of 1326 patients (89.9%) in the sentinel-node biopsy–only group and to 1058 of 1197 (88.4%) in the dissection group. The median follow-up was 46.8 months (range, 1.5 to 94.5). Overall, 191 patients had recurrence or died. The estimated 5-year recurrence-free survival was 89.7% (95% confidence interval [CI], 87.5 to 91.9) in the sentinel-node biopsy–only group and 88.7% (95% CI, 86.3 to 91.1) in the dissection group, with a country-adjusted hazard ratio for recurrence or death of 0.89 (95% CI, 0.66 to 1.19), which was significantly (P<0.001) below the prespecified noninferiority margin.CONCLUSIONS The omission of completion axillary-lymph-node dissection was noninferior to the more extensive surgery in patients with clinically node-negative breast cancer who had sentinel-node macrometastases, most of whom received nodal radiation therapy. (Funded by the Swedish Research Council and others; SENOMAC ClinicalTrials.gov number, NCT02240472.).
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| 38. |
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| 39. |
- Hatschek, T., et al.
(författare)
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PREDIX HER2 trial : Event-free survival and pathologic complete response in clinical subgroups and stromal TILs levels
- 2020
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Ingår i: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 31:Suppl. 2, s. S49-S49
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Neoadjuvant treatment with Trastuzumab-emtansine was associated with similar rates of pathological complete remission (pCR) as standard therapy withd ocetaxel, trastuzumab and pertuzumab in the PREDIX HER2 trial. Here, results of event-free survival (EFS), and pCR rates in key clinical-pathological subgroups and biomarkers including the abundance of stromal tumor infiltrating lymphocytes (TILs) are presented.Methods: PREDIX HER2 is a randomized, multicenter, open-label, phase 2 study involving 9 Swedish sites. Patients with HER2 positive breast cancer, verified by ISH, T>20 mm and/or verified lymph node metastases were randomized to six three-weekly courses of either docetaxel, trastuzumab SC and pertuzumab (group A), or trastuzumab emtansine (T-DM1, group B). Switch of treatment to the opposite arm was allowed in case of lack of response or severe toxicity. Radiological evaluation included 18F-FDG PET/CT. Patients in both groups received adjuvant chemotherapy with epirubicin and cyclophosphamide. TILs were evaluated using standard methodology, median 10%.Results: In total 197 pts. were evaluable, 99 in group A, and 98 in group B. pCR (ypT0/is ypN0) was achieved in 90 pts, 45.7%, with no significant difference between the two treatment groups. pCR rates were lower in the group of patients with hormone receptor (HR)epositive compared with HR-negative tumors but similar in both treatment groups. pCR rates did not differ between the two treatments in subgroups defined by age, menopausal status, tumor grade, T size, node status, HR-status, HER2 status and Ki67. Progressive disease was observed in 3 pts. (3%) during treatment with T-DM1, none in group A. After a median follow-up of 2.4 years 13 EFS events occurred, with no significant differences between the treatment groups. The presence of 10% TILs predicted pCR significantly (p¼0.009), similar in both treatment groups. We also found that a decrease of SUVmax by more than 80% was highly predictive of pCR. HRQoL was significantly better in pts. receiving T-DM1.Conclusions: Our data suggest that neoadjuvant T-DM1 may be as effective as standard neoadjuvant treatment in all clinical subgroups evaluated. Both TILs and PET/CT showed potential to predict pCR.Clinical trial identification: NCT02568839.
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| 40. |
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| 41. |
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| 42. |
- Xiong, Y., et al.
(författare)
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Polygenic risk scores of lithium response and treatment resistance in major depressive disorder
- 2023
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Ingår i: Translational Psychiatry. - 2158-3188. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Treatment response and resistance in major depressive disorder (MDD) are suggested to be heritable. Due to significant challenges in defining treatment-related phenotypes, our understanding of their genetic bases is limited. This study aimed to derive a stringent definition of treatment resistance and to investigate the genetic overlap between treatment response and resistance in MDD. Using electronic medical records on the use of antidepressants and electroconvulsive therapy (ECT) from Swedish registers, we derived the phenotype of treatment-resistant depression (TRD) and non-TRD within similar to 4500 individuals with MDD in three Swedish cohorts. Considering antidepressants and lithium are first-line treatment and augmentation used for MDD, respectively, we generated polygenic risk scores (PRS) of antidepressants and lithium response for individuals with MDD and evaluated their associations with treatment resistance by comparing TRD with non-TRD. Among 1778 ECT-treated MDD cases, nearly all (94%) used antidepressants before their first ECT and the vast majority had at least one (84%) or two (61%) antidepressants of adequate duration, suggesting these MDD cases receiving ECT were resistant to antidepressants. We did not observe a significant difference in the mean PRS of antidepressant response between TRD and non-TRD; however, we found that TRD cases had a significantly higher PRS of lithium response compared to non-TRD cases (OR = 1.10-1.12 under various definitions). The results support the evidence of heritable components in treatment-related phenotypes and highlight the overall genetic profile of lithium-sensitivity in TRD. This finding further provides a genetic explanation for lithium efficacy in treating TRD.
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| 43. |
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| 44. |
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| 45. |
- Båth, Petra, 1988, et al.
(författare)
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Lipidic cubic phase serial femtosecond crystallography structure of a photosynthetic reaction centre
- 2022
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Ingår i: Acta Crystallographica Section D-Structural Biology. - : International Union of Crystallography (IUCr). - 2059-7983. ; 78, s. 698-708
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Tidskriftsartikel (refereegranskat)abstract
- Serial crystallography is a rapidly growing method that can yield structural insights from microcrystals that were previously considered to be too small to be useful in conventional X-ray crystallography. Here, conditions for growing microcrystals of the photosynthetic reaction centre of Blastochloris viridis within a lipidic cubic phase (LCP) crystallization matrix that employ a seeding protocol utilizing detergent-grown crystals with a different crystal packing are described. LCP microcrystals diffracted to 2.25 angstrom resolution when exposed to XFEL radiation, which is an improvement of 0.15 angstrom over previous microcrystal forms. Ubiquinone was incorporated into the LCP crystallization media and the resulting electron density within the mobile Q(B) pocket is comparable to that of other cofactors within the structure. As such, LCP microcrystallization conditions will facilitate time-resolved diffraction studies of electron-transfer reactions to the mobile quinone, potentially allowing the observation of structural changes associated with the two electron-transfer reactions leading to complete reduction of the ubiquinone ligand.
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| 46. |
- Goetz, C., et al.
(författare)
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Cometary plasma science : Open science questions for future space missions
- 2021
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Ingår i: Experimental astronomy. - : Springer Nature. - 0922-6435 .- 1572-9508.
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Tidskriftsartikel (refereegranskat)abstract
- Comets hold the key to the understanding of our Solar System, its formation and its evolution, and to the fundamental plasma processes at work both in it and beyond it. A comet nucleus emits gas as it is heated by the sunlight. The gas forms the coma, where it is ionised, becomes a plasma, and eventually interacts with the solar wind. Besides these neutral and ionised gases, the coma also contains dust grains, released from the comet nucleus. As a cometary atmosphere develops when the comet travels through the Solar System, large-scale structures, such as the plasma boundaries, develop and disappear, while at planets such large-scale structures are only accessible in their fully grown, quasi-steady state. In situ measurements at comets enable us to learn both how such large-scale structures are formed or reformed and how small-scale processes in the plasma affect the formation and properties of these large scale structures. Furthermore, a comet goes through a wide range of parameter regimes during its life cycle, where either collisional processes, involving neutrals and charged particles, or collisionless processes are at play, and might even compete in complicated transitional regimes. Thus a comet presents a unique opportunity to study this parameter space, from an asteroid-like to a Mars- and Venus-like interaction. The Rosetta mission and previous fast flybys of comets have together made many new discoveries, but the most important breakthroughs in the understanding of cometary plasmas are yet to come. The Comet Interceptor mission will provide a sample of multi-point measurements at a comet, setting the stage for a multi-spacecraft mission to accompany a comet on its journey through the Solar System. This White Paper, submitted in response to the European Space Agency’s Voyage 2050 call, reviews the present-day knowledge of cometary plasmas, discusses the many questions that remain unanswered, and outlines a multi-spacecraft European Space Agency mission to accompany a comet that will answer these questions by combining both multi-spacecraft observations and a rendezvous mission, and at the same time advance our understanding of fundamental plasma physics and its role in planetary systems.
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| 47. |
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| 48. |
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| 49. |
- Mattsson-Carlgren, Niklas, et al.
(författare)
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A beta deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer's disease
- 2020
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:16
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Tidskriftsartikel (refereegranskat)abstract
- The links between beta-amyloid ( A beta ) and tau in Alzheimer's disease are unclear. Cognitively unimpaired persons with signs of A beta pathology had increased cerebrospinal fluid (CSF) phosphorylated tau (P-tau181 and P-tau217) and total-tau (T-tau), which increased over time, despite no detection of insoluble tau aggregates [normal Tau positron emission tomography (PET)]. CSF P-tau and T-tau started to increase before the threshold for Amyloid PET positivity, while Tau PET started to increase after Amyloid PET positivity. Effects of Amyloid PET on Tau PET were mediated by CSF P-tau, and high CSF P-tau predicted increased Tau PET rates. Individuals with MAPT mutations and signs of tau deposition (but without A beta pathology) had normal CSF P-tau levels. In 5xFAD mice, CSF tau increased when A beta aggregation started. These results show that A beta pathology may induce changes in soluble tau release and phosphorylation, which is followed by tau aggregation several years later in humans.
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| 50. |
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