| 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. |
- Buchanan, E. M., et al.
(författare)
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The Psychological Science Accelerator's COVID-19 rapid-response dataset
- 2023
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data.
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| 6. |
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| 7. |
- Thomas, H. J. D., et al.
(författare)
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Global plant trait relationships extend to the climatic extremes of the tundra biome
- 2020
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The majority of variation in six traits critical to the growth, survival and reproduction of plant species is thought to be organised along just two dimensions, corresponding to strategies of plant size and resource acquisition. However, it is unknown whether global plant trait relationships extend to climatic extremes, and if these interspecific relationships are confounded by trait variation within species. We test whether trait relationships extend to the cold extremes of life on Earth using the largest database of tundra plant traits yet compiled. We show that tundra plants demonstrate remarkably similar resource economic traits, but not size traits, compared to global distributions, and exhibit the same two dimensions of trait variation. Three quarters of trait variation occurs among species, mirroring global estimates of interspecific trait variation. Plant trait relationships are thus generalizable to the edge of global trait-space, informing prediction of plant community change in a warming world.
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| 8. |
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| 11. |
- 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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| 12. |
- Criado, M. G., et al.
(författare)
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Plant traits poorly predict winner and loser shrub species in a warming tundra biome
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Climate change is leading to species redistributions. In the tundra biome, shrubs are generally expanding, but not all tundra shrub species will benefit from warming. Winner and loser species, and the characteristics that may determine success or failure, have not yet been fully identified. Here, we investigate whether past abundance changes, current range sizes and projected range shifts derived from species distribution models are related to plant trait values and intraspecific trait variation. We combined 17,921 trait records with observed past and modelled future distributions from 62 tundra shrub species across three continents. We found that species with greater variation in seed mass and specific leaf area had larger projected range shifts, and projected winner species had greater seed mass values. However, trait values and variation were not consistently related to current and projected ranges, nor to past abundance change. Overall, our findings indicate that abundance change and range shifts will not lead to directional modifications in shrub trait composition, since winner and loser species share relatively similar trait spaces. Functional trait data could guide predictions of species responses to environmental change. Here, the authors show that winner and loser shrub species in the warming tundra biome overlap in trait space and may therefore be difficult to predict based on commonly measured traits.
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| 13. |
- Oskarsdottir, Solveig, 1953, et al.
(författare)
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Updated clinical practice recommendations for managing children with 22q11.2 deletion syndrome
- 2023
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Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600 .- 1530-0366. ; 25:3
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Tidskriftsartikel (refereegranskat)abstract
- This review aimed to update the clinical practice guidelines for managing children and adolescents with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society, the international scientific organization studying chromosome 22q11.2 differences and related conditions, recruited expert clinicians worldwide to revise the original 2011 pediatric clinical practice guidelines in a stepwise process: (1) a systematic literature search (1992-2021), (2) study selection and data extraction by clinical experts from 9 different countries, covering 24 subspecialties, and (3) creation of a draft consensus document based on the literature and expert opinion, which was further shaped by survey results from family support organizations regarding perceived needs. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text reviews, including 1545 meeting criteria for potential relevance to clinical care of children and adolescents. Informed by the available literature, recommendations were formulated. Given evidence base limitations, multidisciplinary recommendations represent consensus statements of good practice for this evolving field. These recommendations provide contemporary guidance for evaluation, surveillance, and management of the many 22q11.2DSassociated physical, cognitive, behavioral, and psychiatric morbidities while addressing important genetic counseling and psychosocial issues.& COPY; 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.
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| 14. |
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| 15. |
- Champenois, Elio G., et al.
(författare)
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Femtosecond Electronic and Hydrogen Structural Dynamics in Ammonia Imaged with Ultrafast Electron Diffraction
- 2023
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Ingår i: Physical Review Letters. - : American Physical Society (APS). - 0031-9007 .- 1079-7114. ; 131:14
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Tidskriftsartikel (refereegranskat)abstract
- Directly imaging structural dynamics involving hydrogen atoms by ultrafast diffraction methods is complicated by their low scattering cross sections. Here we demonstrate that megaelectronvolt ultrafast electron diffraction is sufficiently sensitive to follow hydrogen dynamics in isolated molecules. In a study of the photodissociation of gas phase ammonia, we simultaneously observe signatures of the nuclear and corresponding electronic structure changes resulting from the dissociation dynamics in the time-dependent diffraction. Both assignments are confirmed by ab initio simulations of the photochemical dynamics and the resulting diffraction observable. While the temporal resolution of the experiment is insufficient to resolve the dissociation in time, our results represent an important step towards the observation of proton dynamics in real space and time.
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| 16. |
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| 17. |
- Myers-Smith, Isla H., et al.
(författare)
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Complexity revealed in the greening of the Arctic
- 2020
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Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 10:2, s. 106-117
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Tidskriftsartikel (refereegranskat)abstract
- As the Arctic warms, vegetation is responding, and satellite measures indicate widespread greening at high latitudes. This ‘greening of the Arctic’ is among the world’s most important large-scale ecological responses to global climate change. However, a consensus is emerging that the underlying causes and future dynamics of so-called Arctic greening and browning trends are more complex, variable and inherently scale-dependent than previously thought. Here we summarize the complexities of observing and interpreting high-latitude greening to identify priorities for future research. Incorporating satellite and proximal remote sensing with in-situ data, while accounting for uncertainties and scale issues, will advance the study of past, present and future Arctic vegetation change.
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| 18. |
- Thompson, EJ, et al.
(författare)
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Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 3528-
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Tidskriftsartikel (refereegranskat)abstract
- The frequency of, and risk factors for, long COVID are unclear among community-based individuals with a history of COVID-19. To elucidate the burden and possible causes of long COVID in the community, we coordinated analyses of survey data from 6907 individuals with self-reported COVID-19 from 10 UK longitudinal study (LS) samples and 1.1 million individuals with COVID-19 diagnostic codes in electronic healthcare records (EHR) collected by spring 2021. Proportions of presumed COVID-19 cases in LS reporting any symptoms for 12+ weeks ranged from 7.8% and 17% (with 1.2 to 4.8% reporting debilitating symptoms). Increasing age, female sex, white ethnicity, poor pre-pandemic general and mental health, overweight/obesity, and asthma were associated with prolonged symptoms in both LS and EHR data, but findings for other factors, such as cardio-metabolic parameters, were inconclusive.
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| 19. |
- Walmsley, T., et al.
(författare)
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Characterizing the multi-dimensional reaction dynamics of dihalomethanes using XUV-induced Coulomb explosion imaging
- 2023
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Ingår i: Journal of Chemical Physics. - 0021-9606. ; 159:14
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Tidskriftsartikel (refereegranskat)abstract
- Site-selective probing of iodine 4d orbitals at 13.1 nm was used to characterize the photolysis of CH2I2 and CH2BrI initiated at 202.5 nm. Time-dependent fragment ion momenta were recorded using Coulomb explosion imaging mass spectrometry and used to determine the structural dynamics of the dissociating molecules. Correlations between these fragment momenta, as well as the onset times of electron transfer reactions between them, indicate that each molecule can undergo neutral three-body photolysis. For CH2I2, the structural evolution of the neutral molecule was simultaneously characterized along the C-I and I-C-I coordinates, demonstrating the sensitivity of these measurements to nuclear motion along multiple degrees of freedom.
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| 20. |
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| 21. |
- Maccari, Maria Elena, et al.
(författare)
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Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity.
- 2023
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Ingår i: The Journal of allergy and clinical immunology. - 1097-6825. ; 152:4
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Tidskriftsartikel (refereegranskat)abstract
- Activated phosphoinositide-3-kinase δ syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking.This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease; and identify predictors of severity in APDS.Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs.The analysis of 170 patients with APDS outlines high penetrance and early onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common, particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS.APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEIs is substantial. Some specific features distinguish APDS1 from APDS2. Early onset is a risk factor for severe disease course calling for specific treatment studies in younger patients.
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| 22. |
- Reintam Blaser, A., et al.
(författare)
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Incidence, diagnosis, management and outcome of acute mesenteric ischaemia: a prospective, multicentre observational study (AMESI Study)
- 2024
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Ingår i: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 28:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this multicentre prospective observational study was to identify the incidence, patient characteristics, diagnostic pathway, management and outcome of acute mesenteric ischaemia (AMI). Methods: All adult patients with clinical suspicion of AMI admitted or transferred to 32 participating hospitals from 06.06.2022 to 05.04.2023 were included. Participants who were subsequently shown not to have AMI or had localized intestinal gangrene due to strangulating bowel obstruction had only baseline and outcome data collected. Results: AMI occurred in 0.038% of adult admissions in participating acute care hospitals worldwide. From a total of 705 included patients, 418 patients had confirmed AMI. In 69% AMI was the primary reason for admission, while in 31% AMI occurred after having been admitted with another diagnosis. Median time from onset of symptoms to hospital admission in patients admitted due to AMI was 24 h (interquartile range 9-48h) and time from admission to diagnosis was 6h (1–12 h). Occlusive arterial AMI was diagnosed in 231 (55.3%), venous in 73 (17.5%), non-occlusive (NOMI) in 55 (13.2%), other type in 11 (2.6%) and the subtype could not be classified in 48 (11.5%) patients. Surgery was the initial management in 242 (58%) patients, of which 59 (24.4%) underwent revascularization. Endovascular revascularization alone was carried out in 54 (13%), conservative treatment in 76 (18%) and palliative care in 46 (11%) patients. From patients with occlusive arterial AMI, revascularization was undertaken in 104 (45%), with 40 (38%) of them in one site admitting selected patients. Overall in-hospital and 90-day mortality of AMI was 49% and 53.3%, respectively, and among subtypes was lowest for venous AMI (13.7% and 16.4%) and highest for NOMI (72.7% and 74.5%). There was a high variability between participating sites for most variables studied. Conclusions: The overall incidence of AMI and AMI subtypes varies worldwide, and case ascertainment is challenging. Pre-hospital delay in presentation was greater than delays after arriving at hospital. Surgery without revascularization was the most common management approach. Nearly half of the patients with AMI died during their index hospitalization. Together, these findings suggest a need for greater awareness of AMI, and better guidance in diagnosis and management. Trial registration: NCT05218863 (registered 19.01.2022).
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| 23. |
- Berner, Logan T., et al.
(författare)
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The Arctic plant aboveground biomass synthesis dataset
- 2024
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Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Plant biomass is a fundamental ecosystem attribute that is sensitive to rapid climatic changes occurring in the Arctic. Nevertheless, measuring plant biomass in the Arctic is logistically challenging and resource intensive. Lack of accessible field data hinders efforts to understand the amount, composition, distribution, and changes in plant biomass in these northern ecosystems. Here, we present The Arctic plant aboveground biomass synthesis dataset, which includes field measurements of lichen, bryophyte, herb, shrub, and/or tree aboveground biomass (g m−2) on 2,327 sample plots from 636 field sites in seven countries. We created the synthesis dataset by assembling and harmonizing 32 individual datasets. Aboveground biomass was primarily quantified by harvesting sample plots during mid- to late-summer, though tree and often tall shrub biomass were quantified using surveys and allometric models. Each biomass measurement is associated with metadata including sample date, location, method, data source, and other information. This unique dataset can be leveraged to monitor, map, and model plant biomass across the rapidly warming Arctic.
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| 24. |
- Borne, Kurtis D., et al.
(författare)
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Ultrafast electronic relaxation pathways of the molecular photoswitch quadricyclane
- 2024
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Ingår i: NATURE CHEMISTRY. - 1755-4330 .- 1755-4349. ; 16, s. 499-505
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Tidskriftsartikel (refereegranskat)abstract
- The light-induced ultrafast switching between molecular isomers norbornadiene and quadricyclane can reversibly store and release a substantial amount of chemical energy. Prior work observed signatures of ultrafast molecular dynamics in both isomers upon ultraviolet excitation but could not follow the electronic relaxation all the way back to the ground state experimentally. Here we study the electronic relaxation of quadricyclane after exciting in the ultraviolet (201 nanometres) using time-resolved gas-phase extreme ultraviolet photoelectron spectroscopy combined with non-adiabatic molecular dynamics simulations. We identify two competing pathways by which electronically excited quadricyclane molecules relax to the electronic ground state. The fast pathway (<100 femtoseconds) is distinguished by effective coupling to valence electronic states, while the slow pathway involves initial motions across Rydberg states and takes several hundred femtoseconds. Both pathways facilitate interconversion between the two isomers, albeit on different timescales, and we predict that the branching ratio of norbornadiene/quadricyclane products immediately after returning to the electronic ground state is approximately 3:2.
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| 25. |
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| 26. |
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| 27. |
- Pathak, S., et al.
(författare)
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Tracking the ultraviolet-induced photochemistry of thiophenone during and after ultrafast ring opening
- 2020
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Ingår i: Nature Chemistry. - : Springer Science and Business Media LLC. - 1755-4330 .- 1755-4349. ; 12:9, s. 795-800
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Tidskriftsartikel (refereegranskat)abstract
- Photoinduced isomerization reactions lie at the heart of many chemical processes in nature. The mechanisms of such reactions are determined by a delicate interplay of coupled electronic and nuclear dynamics occurring on the femtosecond scale, followed by the slower redistribution of energy into different vibrational degrees of freedom. Here we apply time-resolved photoelectron spectroscopy with a seeded extreme ultraviolet free-electron laser to trace the ultrafast ring opening of gas-phase thiophenone molecules following ultraviolet photoexcitation. When combined with ab initio electronic structure and molecular dynamics calculations of the excited- and ground-state molecules, the results provide insights into both the electronic and nuclear dynamics of this fundamental class of reactions. The initial ring opening and non-adiabatic coupling to the electronic ground state are shown to be driven by ballistic S-C bond extension and to be complete within 350 fs. Theory and experiment also enable visualization of the rich ground-state dynamics that involve the formation of, and interconversion between, ring-opened isomers and the cyclic structure, as well as fragmentation over much longer timescales.
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| 28. |
- da Bandeira, Diana Sa, et al.
(författare)
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PDGFR beta(+) cells play a dual role as hematopoietic precursors and niche cells during mouse ontogeny
- 2022
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Ingår i: Cell Reports. - : CELL PRESS. - 2211-1247. ; 40:3
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cell (HSC) generation in the aorta-gonad-mesonephros region requires HSC specification signals from the surrounding microenvironment. In zebrafish, PDGF-B/PDGFR beta signaling controls hematopoietic stem/progenitor cell (HSPC) generation and is required in the HSC specification niche. Little is known about murine HSPC specification in vivo and whether PDGF-B/PDGFR beta is involved. Here, we show that PDGFR beta is expressed in distinct perivascular stromal cell layers surrounding the mid-gestation dorsal aorta, and its deletion impairs hematopoiesis. We demonstrate that PDGFR beta(+) cells play a dual role in murine hematopoiesis. They act in the aortic niche to support HSPCs, and in addition, PDGFR beta(+) embryonic precursors give rise to a subset of HSPCs that persist into adulthood. These findings provide crucial information for the controlled production of HSPCs in vitro.
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| 29. |
- Dennis, Martin, et al.
(författare)
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Fluoxetine to improve functional outcomes in patients after acute stroke : the FOCUS RCT
- 2020
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Ingår i: Health technology assessment (Winchester, England). - : National Institute for Health Research. - 2046-4924 .- 1366-5278. ; 24:22, s. 1-
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Rapport (refereegranskat)abstract
- BackgroundOur Cochrane review of selective serotonin inhibitors for stroke recovery indicated that fluoxetine may improve functional recovery, but the trials were small and most were at high risk of bias.ObjectivesThe Fluoxetine Or Control Under Supervision (FOCUS) trial tested the hypothesis that fluoxetine improves recovery after stroke.DesignThe FOCUS trial was a pragmatic, multicentre, parallel-group, individually randomised, placebo-controlled trial.SettingThis trial took place in 103 UK hospitals.ParticipantsPatients were eligible if they were aged ≥ 18 years, had a clinical stroke diagnosis, with focal neurological deficits, between 2 and 15 days after onset.InterventionsPatients were randomly allocated 20 mg of fluoxetine once per day or the matching placebo for 6 months via a web-based system using a minimisation algorithm.Main outcome measuresThe primary outcome was the modified Rankin Scale at 6 months. Patients, carers, health-care staff and the trial team were masked to treatment allocation. Outcome was assessed at 6 and 12 months after randomisation. Patients were analysed by their treatment allocation as specified in a published statistical analysis plan.ResultsBetween 10 September 2012 and 31 March 2017, we recruited 3127 patients, 1564 of whom were allocated fluoxetine and 1563 of whom were allocated placebo. The modified Rankin Scale score at 6 months was available for 1553 out of 1564 (99.3%) of those allocated fluoxetine and 1553 out of 1563 (99.4%) of those allocated placebo. The distribution across modified Rankin Scale categories at 6 months was similar in the two groups (common odds ratio adjusted for minimisation variables 0.951, 95% confidence interval 0.839 to 1.079; p = 0.439). Compared with placebo, patients who were allocated fluoxetine were less likely to develop a new episode of depression by 6 months [210 (13.0%) vs. 269 (16.9%), difference –3.78%, 95% confidence interval –1.26% to –6.30%; p = 0.003], but had more bone fractures [45 (2.9%) vs. 23 (1.5%), difference 1.41%, 95% confidence interval 0.38% to 2.43%; p = 0.007]. There were no statistically significant differences in any other recorded events at 6 or 12 months. Health economic analyses showed no differences between groups in health-related quality of life, hospital bed usage or health-care costs.LimitationsSome non-adherence to trial medication, lack of face-to-face assessment of neurological status at follow-up and lack of formal psychiatric diagnosis during follow-up.Conclusions20 mg of fluoxetine daily for 6 months after acute stroke did not improve patients’ functional outcome but decreased the occurrence of depression and increased the risk of fractures. These data inform decisions about using fluoxetine after stroke to improve functional outcome or to prevent or treat mood disorders. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) (Australasia/Vietnam) and Efficacy oF Fluoxetine – a randomisEd Controlled Trial in Stroke (EFFECTS) (Sweden) trials recruited an additional 2780 patients and will report their results in 2020. These three trials have an almost identical protocol, which was collaboratively developed. Our planned individual patient data meta-analysis will provide more precise estimates of the effects of fluoxetine after stroke and indicate whether or not effects vary depending on patients’ characteristics and health-care setting.
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| 30. |
- Forbes, Ruaridh, et al.
(författare)
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Time-resolved site-selective imaging of predissociation and charge transfer dynamics : The CH3I B-band
- 2020
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Ingår i: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 53:22
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Tidskriftsartikel (refereegranskat)abstract
- The predissociation dynamics of the 6s (B2E) Rydberg state of gas-phase CH3I were investigated by time-resolved Coulomb-explosion imaging using extreme ultraviolet (XUV) free-electron laser pulses. Inner-shell ionization at the iodine 4d edge was utilized to provide a site-specific probe of the ensuing dynamics. The combination of a velocity-map imaging (VMI) spectrometer coupled with the pixel imaging mass spectrometry (PImMS) camera permitted three-dimensional ionic fragment momenta to be recorded simultaneously for a wide range of iodine charge states. In accord with previous studies, initial excitation at 201.2 nm results in internal conversion and subsequent dissociation on the lower-lying A-state surface on a picosecond time scale. Examination of the time-dependent yield of low kinetic energy iodine fragments yields mechanistic insights into the predissociation and subsequent charge transfer following multiple ionization of the iodine products. The effect of charge transfer was observed through differing delay-dependencies of the various iodine charge states, from which critical internuclear distances for charge transfer could be inferred and compared to a classical over-the-barrier model. Time-dependent photofragment angular anisotropy parameters were extracted from the central slice of the Newton sphere, without Abel inversion, and highlight the effect of rotation of the parent molecule before dissociation, as observed in previous
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| 31. |
- Iscaro, Alessandra, et al.
(författare)
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Targeting circulating monocytes with CCL2-loaded liposomes armed with an oncolytic adenovirus
- 2022
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Ingår i: Nanomedicine. - : Elsevier. - 1549-9634 .- 1549-9642. ; 40
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Tidskriftsartikel (refereegranskat)abstract
- Oncolytic viruses (OVs) selectively replicate in and destroy cancer cells resulting in anti-tumor immunity. However, clinical use remains a challenge because of virus clearance upon intravenous delivery. OV packaging using a nanomedicine approach could overcome this. Here we encapsulate an oncolytic adenovirus (Ad[I/PPT-E1A]) into CCL2-coated liposomes in order to exploit recruitment of CCR2-expressing circulating monocytes into tumors. We demonstrate successful encapsulation of Ad[I/PPT-E1A] into CCL2-coated liposomes that were preferentially taken up by CCR2-expressing monocytes. No complex-related toxicities were observed following incubation with prostate tumor cells and the encapsulation did not affect virus oncolytic activity in vitro. Furthermore, intravenous administration of our nanomedicine resulted in a significant reduction in tumor size and pulmonary metastasis in prostate cancer-bearing mice whereby a 1000-fold less virus was needed compared to Ad[I/PPT-E1A] alone. Taken together our data provide an opportunity to target OVs via circulation to inaccessible tumors using liposome-assisted drug delivery. (c) 2021 Elsevier Inc. All rights reserved.
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| 35. |
- Mashindi, Victor, et al.
(författare)
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Platinum Nanocatalysts Supported on Defective Hollow Carbon Spheres : Oxygen Reduction Reaction Durability Studies
- 2022
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Ingår i: Frontiers in Chemistry. - : Frontiers Media SA. - 2296-2646. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The durability and long-term applicability of catalysts are critical parameters for the commercialization and adoption of fuel cells. Even though a few studies have been conducted on hollow carbon spheres (HCSs) as supports for Pt in oxygen reduction reactions (ORR) catalysis, in-depth durability studies have not been conducted thus far. In this study, Pt/HCSs and Pt/nitrogen-doped HCSs (Pt/NHCSs) were prepared using a reflux deposition technique. Small Pt particles were formed with deposition on the outside of the shell and inside the pores of the shell. The new catalysts demonstrated high activity (>380 μA cm−2 and 240 mA g−1) surpassing the commercial Pt/C by more than 10%. The catalysts demonstrated excellent durability compared to a commercial Pt/C in load cycling, experiencing less than 50% changes in the mass-specific activity (MA) and surface area-specific activity (SA). In stop-start durability cycling, the new materials demonstrated high stability with more than 50% retention of electrochemical active surface areas (ECSAs). The results can be rationalised by the high BET surface areas coupled with an array of meso and micropores that led to Pt confinement. Further, pair distribution function (PDF) analysis of the catalysts confirmed that the nitrogen and oxygen functional groups, as well as the shell curvature/roughness provided defects and nucleation sites for the deposition of the small Pt nanoparticles. The balance between graphitic and diamond-like carbon was critical for the electronic conductivity and to provide strong Pt-support anchoring.
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| 36. |
- McCusker, Gillian Young, et al.
(författare)
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Evaluating Arctic clouds modelled with the Unified Model and Integrated Forecasting System
- 2023
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Ingår i: Atmospheric Chemistry And Physics. - 1680-7316 .- 1680-7324. ; 23:8, s. 4819-4847
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Tidskriftsartikel (refereegranskat)abstract
- By synthesising remote-sensing measurements made in the central Arctic into a model-gridded Cloudnet cloud product, we evaluate how well the Met Office Unified Model (UM) and the European Centre for Medium-Range Weather Forecasting (ECMWF) Integrated Forecasting System (IFS) capture Arctic clouds and their associated interactions with the surface energy balance and the thermodynamic structure of the lower troposphere. This evaluation was conducted using a 4-week observation period from the Arctic Ocean 2018 expedition, where the transition from sea ice melting to freezing conditions was measured. Three different cloud schemes were tested within a nested limited-area model (LAM) configuration of the UM – two regionally operational single-moment schemes (UM_RA2M and UM_RA2T) and one novel double-moment scheme (UM_CASIM-100) – while one global simulation was conducted with the IFS, utilising its default cloud scheme (ECMWF_IFS).Consistent weaknesses were identified across both models, with both the UM and IFS overestimating cloud occurrence below 3 km. This overestimation was also consistent across the three cloud configurations used within the UM framework, with >90 % mean cloud occurrence simulated between 0.15 and 1 km in all the model simulations. However, the cloud microphysical structure, on average, was modelled reasonably well in each simulation, with the cloud liquid water content (LWC) and ice water content (IWC) comparing well with observations over much of the vertical profile. The key microphysical discrepancy between the models and observations was in the LWC between 1 and 3 km, where most simulations (all except UM_RA2T) overestimated the observed LWC.Despite this reasonable performance in cloud physical structure, both models failed to adequately capture cloud-free episodes: this consistency in cloud cover likely contributes to the ever-present near-surface temperature bias in every simulation. Both models also consistently exhibited temperature and moisture biases below 3 km, with particularly strong cold biases coinciding with the overabundant modelled cloud layers. These biases are likely due to too much cloud-top radiative cooling from these persistent modelled cloud layers and were consistent across the three UM configurations tested, despite differences in their parameterisations of cloud on a sub-grid scale. Alarmingly, our findings suggest that these biases in the regional model were inherited from the global model, driving a cause–effect relationship between the excessive low-altitude cloudiness and the coincident cold bias. Using representative cloud condensation nuclei concentrations in our double-moment UM configuration while improving cloud microphysical structure does little to alleviate these biases; therefore, no matter how comprehensive we make the cloud physics in the nested LAM configuration used here, its cloud and thermodynamic structure will continue to be overwhelmingly biased by the meteorological conditions of its driving model.
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| 37. |
- Mead, Gillian Elizabeth, et al.
(författare)
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Update to the FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke : statistical analysis plan for the trials and for the individual patient data meta-analysis
- 2020
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Ingår i: Trials. - : Springer Nature. - 1745-6215. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThree large trials of fluoxetine for stroke recovery (FOCUS (fluoxetine or control under supervision), AFFINITY (the Assessment oF FluoxetINe In sTroke recovery) and EFFECTS (Efficacy oF Fluoxetine-a randomisEd Controlled Trial in Stroke)) have been collaboratively designed with the same basic protocol to facilitate an individual patient data analysis (IPDM). The statistical analysis plan for the three individual trials has already been reported in Trials, including a brief description of the IPDM. In this protocol, we describe in detail how we will perform the IPDM.Methods/designData from EFFECTS and AFFINITY will be transferred securely to the FOCUS statistician, who will perform a one-stage IPDM and a two-stage IPDM. For the one-stage IPDM, data will be combined into a single data set and the same analyses performed as described for the individual trials. For the two-stage IPDM, the results for the three individual trials will be combined using fixed effects meta-analyses.The primary and secondary outcome domains for the IPDM are the same as for individual trials. We will also perform analyses according to several subgroups including country of recruitment, ethnicity and trial. We will also explore the effects of fluoxetine on our primary and secondary outcomes in subgroups defined by combinations of characteristics.We also describe additional research questions that will be addressed using the combined data set, and published subsequently, including predictors of important post-stroke problems such as seizures, low mood and bone fractures.DiscussionAn IPDM of our three large trials of fluoxetine for stroke recovery will allow us to provide the most precise estimates of any risks and benefits of fluoxetine vs placebo, to detect reliably a smaller overall effect size than those detectable by the individual trials, to better determine the effects of fluoxetine vs placebo in subgroups of patients and outcomes and to broaden the generalisability of the results. Also, we may identify differences in treatment effects between studies.Trial registrationFOCUS: ISRCTN ISRCTN83290762. Registered on 23 May 2012. EudraCT 2011-005616-29. Registered on 3 February 2012.AFFINITY: Australian New Zealand Clinical Trials Registry ACTRN12611000774921. Registered on 22 July 2011.EFFECTS: ISRCTN ISRCTN13020412. Registered on 19 December 2014. ClinicalTrials.gov NCT02683213. Registered on 2 February 2016. EudraCT 2011-006130-16. Registered on 8 August 2014.
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| 38. |
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| 39. |
- Pape, S. E., et al.
(författare)
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The reliability and validity of DSM 5 diagnostic criteria for neurocognitive disorder and relationship with plasma neurofilament light in a down syndrome population
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The validity of dementia diagnostic criteria depends on their ability to distinguish dementia symptoms from pre-existing cognitive impairments. The study aimed to assess inter-rater reliability and concurrent validity of DSM-5 criteria for neurocognitive disorder in Down syndrome. The utility of mild neurocognitive disorder as a distinct diagnostic category, and the association between clinical symptoms and neurodegenerative changes represented by the plasma biomarker neurofilament light were also examined. 165 adults with Down syndrome were included. Two clinicians independently applied clinical judgement, DSM-IV, ICD-10 and DSM-5 criteria for dementia (or neurocognitive disorder) to each case. Inter-rater reliability and concurrent validity were analysed using the kappa statistic. Plasma neurofilament light concentrations were measured for 55 participants as a marker of neurodegeneration and between group comparisons calculated. All diagnostic criteria showed good inter-rater reliability apart from mild neurocognitive disorder which was moderate (k=0.494). DSM- 5 criteria had substantial concurrence with clinical judgement (k=0.855). When compared to the no neurocognitive disorder group, average neurofilament light concentrations were higher in both the mild and major neurocognitive disorder groups. DSM-5 neurocognitive disorder criteria can be used reliably in a Down syndrome population and has higher concurrence with clinical judgement than the older DSM-IV and ICD-10 criteria. Whilst the inter-rater reliability of the mild neurocognitive disorder criteria was modest, it does appear to identify people in an early stage of dementia with underlying neurodegenerative changes, represented by higher average NfL levels.
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| 40. |
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| 41. |
- Rasmus, Sirpa, et al.
(författare)
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Policy documents considering biodiversity, land use, and climate in the European Arctic reveal visible, hidden, and imagined nexus approaches
- 2024
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Ingår i: One Earth. - : Cell Press. - 2590-3330 .- 2590-3322.
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Tidskriftsartikel (refereegranskat)abstract
- The Arctic is experiencing rapid and interlinked socio-environmental changes. Therefore, governance approaches that take the complex interactions between climate change, biodiversity loss, increasing land use pressures, and local livelihoods into account are needed: nexus approaches. However, an overview of whether and to what extent Arctic policies address these nexus elements in concert has been missing. Here we analyzed a large sample of publicly available assessment reports and policy documents from the terrestrial European Arctic. Our results show that, although nexus approaches are widely adopted in Arctic policy reporting, the emphasis varies among the governance levels, and documents underestimate certain interactions: local communities and traditional livelihoods are seldom seen as actors with agency and impact. Practical implementations were identified as potential advancements in Arctic governance: ecosystem-specific, technological, and authoritative solutions; co-production of knowledge; and adaptive co-management. Implementation of nexus approaches can promote more holistic environmental governance and guide cross-sectoral policies.
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| 42. |
- Selley, Liza, et al.
(författare)
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Brake dust exposure exacerbates inflammation and transiently compromises phagocytosis in macrophages
- 2020
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Ingår i: Metallomics. - : Royal Society of Chemistry. - 1756-5901 .- 1756-591X. ; 12:3, s. 371-386
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Tidskriftsartikel (refereegranskat)abstract
- Studies have emphasised the importance of combustion-derived particles in eliciting adverse health effects, especially those produced by diesel vehicles. In contrast, few investigations have explored the potential toxicity of particles derived from tyre and brake wear, despite their significant contributions to total roadside particulate mass. The objective of this study was to compare the relative toxicity of compositionally distinct brake abrasion dust (BAD) and diesel exhaust particles (DEP) in a cellular model that is relevant to human airways. Although BAD contained considerably more metals/metalloids than DEP (as determined by inductively coupled plasma mass spectrometry) similar toxicological profiles were observed in U937 monocyte-derived macrophages following 24 h exposures to 4–25 μg ml−1 doses of either particle type. Responses to the particles were characterised by dose-dependent decreases in mitochondrial depolarisation (p ≤ 0.001), increased secretion of IL-8, IL-10 and TNF-α (p ≤ 0.05 to p ≤ 0.001) and decreased phagocytosis of S. aureus (p ≤ 0.001). This phagocytic deficit recovered, and the inflammatory response resolved when challenged cells were incubated for a further 24 h in particle-free media. These responses were abrogated by metal chelation using desferroxamine. At minimally cytotoxic doses both DEP and BAD perturbed bacterial clearance and promoted inflammatory responses in U937 cells with similar potency. These data emphasise the requirement to consider contributions of abrasion particles to traffic-related clinical health effects.
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| 43. |
- Yoon, William J., 1984-
(författare)
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Advancing Endovascular Management of Thoracic Aortic Disease
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Despite technological advances and new endograft designs, endovascular treatment of the thoracic aorta still has important limitations. The aims of this thesis were to obtain further understanding on specific limitations in treating complex thoracic aortic pathologies with current technologies, to gain more insights into the hemodynamic consequences of thoracic endografting, and to explores the potential of deep learning algorithm-based automatic assessment of follow-up CTA imaging.Limitations imposed by the aortic arch branches on the proximal landing zone (PLZ) remain the biggest challenge for thoracic endovascular aortic repair (TEVAR). When left subclavian artery (LSA) preservation is required to obtain an adequate PLZ, single-branched endografts, such as the thoracic branch endoprosthesis (TBE), offer a complete endovascular solution, but still are limited by the lack of understanding of the hemodynamic effects and long-term data on clinical performance. Paper I explored the impact of TBE implantation on the LSA hemodynamics using computational fluid dynamic (CFD) analysis. It was shown TBE implantation produces modest hemodynamic disturbances which are unlikely to result in clinically relevant changes.Paper II evaluated the anatomic feasibility of TBE in blunt traumatic aortic injury patients who would require LSA revascularization. Only 32% of these patients had met all the anatomic requirements, justifying the need for additional designs. It was also shown that significant morphologic differences in arch anatomy exist between thoracic aortic pathologies.A major challenge in treating aortic dissection is unsatisfactory compliance of the distal portion of stent-grafts in a dissected aorta. Paper III evaluated the hemodynamic effect of a novel dissection-specific stent-graft (DSSG) with the aim to prevent distal stent graft-induced new entry (dSINE). The CFD analysis showed changes in shear-stress distribution different from that with standard thoracic stent-graft, transitioning high wall shear stress gradient zones into the stent-covered aorta. This transition may help prevent intimal injury and consequent dSINE development.Despite close surveillance imaging, early signs of endograft component separation resulting in type IIIa endoleak and sac repressurization are easily missed. Paper IV developed an AI-assisted fully automated CT image assessment method for early detection of endograft component separation and explored its potential.In depth understanding of the limitations of TEVAR helps continue progress in providing optimal patient- and pathology-specific endovascular solutions. CFD-based hemodynamic analysis and AI-driven automated image assessment have the potential to aid in TEVAR optimization.
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