| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Kousathanas, A, et al.
(författare)
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Whole-genome sequencing reveals host factors underlying critical COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 607:7917, s. 97-
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Tidskriftsartikel (refereegranskat)abstract
- Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.
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| 4. |
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| 5. |
- Naidoo-Bagwell, Aaron A., et al.
(författare)
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A diatom extension to the cGEnIE Earth system model - EcoGEnIE 1.1
- 2024
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Ingår i: Geoscientific Model Development. - 1991-959X. ; 17:4, s. 1729-1748
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Tidskriftsartikel (refereegranskat)abstract
- We extend the ecological component (ECOGEM) of the carbon-centric Grid-Enabled Integrated Earth system model (cGEnIE) to include a diatom functional group. ECOGEM represents plankton community dynamics via a spectrum of ecophysiological traits originally based on size and plankton food web (phyto- and zooplankton; EcoGEnIE 1.0), which we developed here to account for a diatom functional group (EcoGEnIE 1.1). We tuned EcoGEnIE 1.1, exploring a range of ecophysiological parameter values specific to phytoplankton, including diatom growth and survival (18 parameters over 550 runs) to achieve best fits to observations of diatom biogeography and size class distribution as well as to global ocean nutrient and dissolved oxygen distributions. This, in conjunction with a previously developed representation of opal dissolution and an updated representation of the ocean iron cycle in the water column, resulted in an improved distribution of dissolved oxygen in the water column relative to the previous EcoGEnIE 1.0, with global export production (7.4GtCyr-1) now closer to previous estimates. Simulated diatom biogeography is characterised by larger size classes dominating at high latitudes, notably in the Southern Ocean, and smaller size classes dominating at lower latitudes. Overall, diatom biological productivity accounts for ∼20% of global carbon biomass in the model, with diatoms outcompeting other phytoplankton functional groups when dissolved silica is available due to their faster maximum photosynthetic rates and reduced palatability to grazers. Adding a diatom functional group provides the cGEnIE Earth system model with an extended capability to explore ecological dynamics and their influence on ocean biogeochemistry.
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| 6. |
- Hendry, Alexandra, et al.
(författare)
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Inhibitory control and problem solving in early childhood : Exploring the burdens and benefits of high self-control
- 2022
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Ingår i: Infant and Child Development. - : John Wiley & Sons. - 1522-7227 .- 1522-7219. ; 31:3
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Tidskriftsartikel (refereegranskat)abstract
- Low inhibitory control (IC) is sometimes associated with enhanced problem-solving amongst adults, yet for young children high IC is primarily framed as inherently better than low IC. Here, we explore associations between IC and performance on a novel problem-solving task, amongst 102 English 2- and 3-year-olds (Study 1) and 84 Swedish children, seen at 18-months and 4-years (Study 2). Generativity during problem-solving was negatively associated with IC, as measured by prohibition-compliance (Study 1, both ages, Study 2 longitudinally from 18-months). High parent-reported IC was associated with poorer overall problem-solving success, and greater perseveration (Study 1, 3-year-olds only). Benefits of high parent-reported IC on persistence could be accounted for by developmental level. No concurrent association was observed between problem-solving performance and IC as measured with a Delay-of-Gratification task (Study 2, concurrent associations at 4-years). We suggest that, for young children, high IC may confer burden on insight- and analytic-aspects of problem-solving.
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| 7. |
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| 8. |
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| 9. |
- Schell, Carl Otto, et al.
(författare)
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Essential Emergency and Critical Care : a consensus among global clinical experts.
- 2021
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 6:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Globally, critical illness results in millions of deaths every year. Although many of these deaths are potentially preventable, the basic, life-saving care of critically ill patients are often overlooked in health systems. Essential Emergency and Critical Care (EECC) has been devised as the care that should be provided to all critically ill patients in all hospitals in the world. EECC includes the effective care of low cost and low complexity for the identification and treatment of critically ill patients across all medical specialties. This study aimed to specify the content of EECC and additionally, given the surge of critical illness in the ongoing pandemic, the essential diagnosis-specific care for critically ill patients with COVID-19.METHODS: In a Delphi process, consensus (>90% agreement) was sought from a diverse panel of global clinical experts. The panel iteratively rated proposed treatments and actions based on previous guidelines and the WHO/ICRC's Basic Emergency Care. The output from the Delphi was adapted iteratively with specialist reviewers into a coherent and feasible package of clinical processes plus a list of hospital readiness requirements.RESULTS: The 269 experts in the Delphi panel had clinical experience in different acute medical specialties from 59 countries and from all resource settings. The agreed EECC package contains 40 clinical processes and 67 requirements, plus additions specific for COVID-19.CONCLUSION: The study has specified the content of care that should be provided to all critically ill patients. Implementing EECC could be an effective strategy for policy makers to reduce preventable deaths worldwide.
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| 10. |
- Ward, James P.J., et al.
(författare)
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Stable silicon isotopes uncover a mineralogical control on the benthic silicon cycle in the Arctic Barents Sea
- 2022
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Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier BV. - 0016-7037. ; 329, s. 206-230
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Tidskriftsartikel (refereegranskat)abstract
- Biogeochemical cycling of silicon (Si) in the Barents Sea is under considerable pressure from physical and chemical changes, including dramatic warming and sea ice retreat, together with a decline in dissolved silicic acid (DSi) concentrations of Atlantic inflow waters since 1990. Associated changes in the community composition of phytoplankton blooms will alter the material comprising the depositional flux, which will subsequently influence recycling processes at and within the seafloor. In this study we assess the predominant controls on the early diagenetic cycling of Si, a key nutrient in marine ecosystems, by combining stable isotopic analysis (δ30Si) of pore water DSi and of operationally defined reactive pools of the solid phase. We show that low biogenic silica (BSi) contents (0.26–0.52 wt% or 92–185 μmol g dry wt−1) drive correspondingly low asymptotic concentrations of pore water DSi of ∼100 μM, relative to biosiliceous sediments (>20 wt% BSi) wherein DSi can reach ∼900 μM. While Barents Sea surface sediments appear almost devoid of BSi, we present evidence for the rapid recycling of bloom derived BSi that generates striking transient peaks in sediment pore water [DSi] of up to 300 μM, which is a feature that is subject to future shifts in phytoplankton community compositions. Using a simple isotopic mass balance calculation we show that at two of three stations the pore water DSi pool at 0.5 cm below the seafloor (+0.96 to +1.36 ‰) is sourced from the mixing of core top waters (+1.46 to +1.69 ‰) with the dissolution of BSi (+0.82 to +1.50 ‰), supplemented with a lithogenic Si source (LSi) (−0.89 ±0.16‰). Further, our sediment pore water δ30Si profiles uncover a coupling of the Si cycle with the redox cycling of metal oxides associated with isotopically light Si (−2.88 ±0.17‰). We suggest that a high LSi:BSi ratio and apparent metal oxide influence could lead to a degree of stability in the annual background benthic flux of DSi, despite current pressures on pelagic phytoplankton communities. Coupled with supporting isotopic evidence for the precipitation of authigenic clays in Barents Sea sediment cores, our observations have implications for the regional Si budget.
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