| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 3. |
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| 4. |
- 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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| 5. |
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| 6. |
- Elsik, Christine G., et al.
(författare)
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The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
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Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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| 7. |
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| 8. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 9. |
- Aprile, E., et al.
(författare)
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An approximate likelihood for nuclear recoil searches with XENON1T data
- 2022
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 82:11
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Tidskriftsartikel (refereegranskat)abstract
- The XENON collaboration has published stringent limits on specific dark matter – nucleon recoil spectra from dark matter recoiling on the liquid xenon detector target. In this paper, we present an approximate likelihood for the XENON1T 1 t-year nuclear recoil search applicable to any nuclear recoil spectrum. Alongside this paper, we publish data and code to compute upper limits using the method we present. The approximate likelihood is constructed in bins of reconstructed energy, profiled along the signal expectation in each bin. This approach can be used to compute an approximate likelihood and therefore most statistical results for any nuclear recoil spectrum. Computing approximate results with this method is approximately three orders of magnitude faster than the likelihood used in the original publications of XENON1T, where limits were set for specific families of recoil spectra. Using this same method, we include toy Monte Carlo simulation-derived binwise likelihoods for the upcoming XENONnT experiment that can similarly be used to assess the sensitivity to arbitrary nuclear recoil signatures in its eventual 20 t-year exposure.
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| 10. |
- Aprile, E., et al.
(författare)
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Application and modeling of an online distillation method to reduce krypton and argon in XENON1T
- 2022
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Ingår i: Progress of Theoretical and Experimental Physics. - : Oxford University Press (OUP). - 2050-3911. ; 2022:5
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Tidskriftsartikel (refereegranskat)abstract
- A novel online distillation technique was developed for the XENON1T dark matter experiment to reduce intrinsic background components more volatile than xenon, such as krypton or argon, while the detector was operating. The method is based on a continuous purification of the gaseous volume of the detector system using the XENON1T cryogenic distillation column. A krypton-in-xenon concentration of (360 +/- 60) ppq was achieved. It is the lowest concentration measured in the fiducial volume of an operating dark matter detector to date. A model was developed and fitted to the data to describe the krypton evolution in the liquid and gas volumes of the detector system for several operation modes over the time span of 550 days, including the commissioning and science runs of XENON1T. The online distillation was also successfully applied to remove Ar-37 after its injection for a low-energy calibration in XENON1T. This makes the usage of Ar-37 as a regular calibration source possible in the future. The online distillation can be applied to next-generation liquid xenon time projection chamber experiments to remove krypton prior to, or during, any science run. The model developed here allows further optimization of the distillation strategy for future large-scale detectors.
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| 11. |
- Aprile, E., et al.
(författare)
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Double-weak decays of 124Xe and 136Xe in the XENON1T and XENONnT experiments
- 2022
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Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 106:2
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Tidskriftsartikel (refereegranskat)abstract
- We present results on the search for two-neutrino double-electron capture (2νECEC) of 124Xe and neutrinoless double-β decay (0νββ) of 136Xe in XENON1T. We consider captures from the K shell up to the N shell in the 2νECEC signal model and measure a total half-life of T2νECEC1/2=(1.1±0.2stat±0.1sys)×1022yr with a 0.87 kg yr isotope exposure. The statistical significance of the signal is 7.0σ. We use XENON1T data with 36.16 kg yr of 136Xe exposure to search for 0νββ. We find no evidence of a signal and set a lower limit on the half-life of T0νββ1/2>1.2×1024 yr at 90%CL. This is the best result from a dark matter detector without an enriched target to date. We also report projections on the sensitivity of XENONnT to 0νββ. Assuming a 275 kg yr 136Xe exposure, the expected sensitivity is T0νββ1/2>2.1×1025 yr at 90%CL, corresponding to an effective Majorana mass range of ⟨mββ⟩<(0.19–0.59)eV/c2.
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| 12. |
- Aprile, E., et al.
(författare)
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Effective Field Theory and Inelastic Dark Matter Results from XENON1T
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In this work we expand on the XENON1T nuclear recoil searches and study the individual signals of Dark Matter interactions from operators up to dimension-eight in a Chiral Effective Field Theory (ChEFT) as well as a model of inelastic Dark Matter using data from the two science runs of the detector totalling 1 tonne*year exposure. For these analyses we extended the region of interest from [4.9, 40.9]keVnr to [4.9, 54.4]keVnr to enhance our sensitivity for signals that peak at nonzero energies. We show that the data is consistent with a background only hypothesis, with small excesses in the models which peak between 20 and 50keVnr, obtaining a maximum local discovery significance of 1.7 for the VVs ChEFT model for a WIMP mass of 70GeV/c2, and 1.8 for an iDM particle of 50GeV/c2 with a mass splitting of 100keV/c2. For each model we report 90% confidence level upper limits. We also report limits on three benchmark models of WIMP interaction using ChEFT for which we investigate the effect of isospin breaking interactions, reporting up to 6 orders of magnitude weaker limits with respect to the isospin conserving case driven by cancellations in the expected rate.
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| 13. |
- Aprile, E., et al.
(författare)
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Emission of single and few electrons in XENON1T and limits on light dark matter
- 2022
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 106:2
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Tidskriftsartikel (refereegranskat)abstract
- Delayed single- and few-electron emissions plague dual-phase time projection chambers, limiting their potential to search for light-mass dark matter. This paper examines the origins of these events in the XENON1T experiment. Characterization of the intensity of delayed electron backgrounds shows that the resulting emissions are correlated, in time and position, with high-energy events and can effectively be vetoed. In this work we extend previous S2-only analyses down to a single electron. From this analysis, after removing the correlated backgrounds, we observe rates <30 events/(electron×kg×day) in the region of interest spanning 1 to 5 electrons. We derive 90% confidence upper limits for dark matter-electron scattering, first direct limits on the electric dipole, magnetic dipole, and anapole interactions, and bosonic dark matter models, where we exclude new parameter space for dark photons and solar dark photons.
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| 14. |
- Aprile, E., et al.
(författare)
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Search for New Physics in Electronic Recoil Data from XENONnT
- 2022
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 129:16
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Tidskriftsartikel (refereegranskat)abstract
- We report on a blinded analysis of low-energy electronic recoil data from the first science run of the XENONnT dark matter experiment. Novel subsystems and the increased 5.9 ton liquid xenon target reduced the background in the (1, 30) keV search region to (15.8±1.3) events/(ton×year×keV), the lowest ever achieved in a dark matter detector and ∼5 times lower than in XENON1T. With an exposure of 1.16 ton-years, we observe no excess above background and set stringent new limits on solar axions, an enhanced neutrino magnetic moment, and bosonic dark matter.
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| 15. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 16. |
- Micah, Angela E., et al.
(författare)
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Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
- 2021
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
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Forskningsöversikt (refereegranskat)abstract
- Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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| 17. |
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| 18. |
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| 19. |
- Aalbers, J., et al.
(författare)
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A next-generation liquid xenon observatory for dark matter and neutrino physics
- 2023
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 50:1
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Forskningsöversikt (refereegranskat)abstract
- The nature of dark matter and properties of neutrinos are among the most pressing issues in contemporary particle physics. The dual-phase xenon time-projection chamber is the leading technology to cover the available parameter space for weakly interacting massive particles, while featuring extensive sensitivity to many alternative dark matter candidates. These detectors can also study neutrinos through neutrinoless double-beta decay and through a variety of astrophysical sources. A next-generation xenon-based detector will therefore be a true multi-purpose observatory to significantly advance particle physics, nuclear physics, astrophysics, solar physics, and cosmology. This review article presents the science cases for such a detector.
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| 20. |
- Gemmell, Neil J., et al.
(författare)
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The tuatara genome reveals ancient features of amniote evolution
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 584:7821, s. 403-409
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Tidskriftsartikel (refereegranskat)abstract
- The tuatara (Sphenodon punctatus)—the only living member of the reptilian order Rhynchocephalia (Sphenodontia), once widespread across Gondwana1,2—is an iconic species that is endemic to New Zealand2,3. A key link to the now-extinct stem reptiles (from which dinosaurs, modern reptiles, birds and mammals evolved), the tuatara provides key insights into the ancestral amniotes2,4. Here we analyse the genome of the tuatara, which—at approximately 5 Gb—is among the largest of the vertebrate genomes yet assembled. Our analyses of this genome, along with comparisons with other vertebrate genomes, reinforce the uniqueness of the tuatara. Phylogenetic analyses indicate that the tuatara lineage diverged from that of snakes and lizards around 250 million years ago. This lineage also shows moderate rates of molecular evolution, with instances of punctuated evolution. Our genome sequence analysis identifies expansions of proteins, non-protein-coding RNA families and repeat elements, the latter of which show an amalgam of reptilian and mammalian features. The sequencing of the tuatara genome provides a valuable resource for deep comparative analyses of tetrapods, as well as for tuatara biology and conservation. Our study also provides important insights into both the technical challenges and the cultural obligations that are associated with genome sequencing.
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| 21. |
- Ebersole, Charles R., et al.
(författare)
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Many Labs 5: Testing Pre-Data-Collection Peer Review as an Intervention to Increase Replicability
- 2020
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Ingår i: Advances in Methods and Practices in Psychological Science. - : Sage. - 2515-2467 .- 2515-2459. ; 3:3, s. 309-331
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Tidskriftsartikel (refereegranskat)abstract
- Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3-9; median total sample = 1,279.5, range = 276-3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Delta r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00-.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19-.50).
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| 22. |
- Field, Christopher B., et al.
(författare)
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Summary for Policymakers
- 2014
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Ingår i: Climate Change 2014: Impacts, Adaptation, and Vulnerability. Part A: Global and SectoralAspects.. - 9781107415379 ; , s. 1-32
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Bokkapitel (refereegranskat)
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| 23. |
- Groenewold, Nynke A., et al.
(författare)
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Volume of subcortical brain regions in social anxiety disorder : mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group
- 2023
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 28:3, s. 1079-1089
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Tidskriftsartikel (refereegranskat)abstract
- There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = −0.077, pFWE = 0.037; right: d = −0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = −0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = −0.141, pFWE < 0.001; right: d = −0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.
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| 24. |
- Holmqvist, Kenneth, et al.
(författare)
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Eye tracking : empirical foundations for a minimal reporting guideline
- 2023
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Ingår i: Behavior Research Methods. - : Springer Science and Business Media LLC. - 1554-3528. ; 55:1, s. 364-416
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we present a review of how the various aspects of any study using an eye tracker (such as the instrument, methodology, environment, participant, etc.) affect the quality of the recorded eye-tracking data and the obtained eye-movement and gaze measures. We take this review to represent the empirical foundation for reporting guidelines of any study involving an eye tracker. We compare this empirical foundation to five existing reporting guidelines and to a database of 207 published eye-tracking studies. We find that reporting guidelines vary substantially and do not match with actual reporting practices. We end by deriving a minimal, flexible reporting guideline based on empirical research (Section "An empirically based minimal reporting guideline").
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| 25. |
- Smith, A., et al.
(författare)
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LunarEX-a proposal to cosmic vision
- 2009
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Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 23:3, s. 711-740
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Tidskriftsartikel (refereegranskat)
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| 26. |
- Solmi, Marco, et al.
(författare)
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Physical and mental health impact of COVID-19 on children, adolescents, and their families :
- 2022
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Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 299, s. 367-376
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Tidskriftsartikel (refereegranskat)abstract
- Background: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. Methods: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www. coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6-18 months plus 24-36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14-17 years), and children (age 6-13 years), recruited via nonprobability/snowball and representative sampling and assessed via self-rating and parental rating. Nonmodifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life. Results: Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COHFIT project, with representative samples from eleven countries. Limitations: Cross-sectional and anonymous design. Conclusions: Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on childrens, adolescents and families, mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth.
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| 27. |
- Solmi, Marco, et al.
(författare)
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The collaborative outcomes study on health and functioning during infection times in adults (COH-FIT-Adults) : Design and methods of an international online survey targeting physical and mental health effects of the COVID-19 pandemic
- 2022
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Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 299, s. 393-407
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Tidskriftsartikel (refereegranskat)abstract
- Background: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. Methods: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative sampling. COH-FIT aims to identify non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to improve social/health outcomes in the general population/vulnerable subgrous during/after COVID-19. In adults, co-primary outcomes are change from pre-COVID-19 to intra-COVID-19 in well-being (WHO-5) and a composite psychopathology P-Score. Key secondary outcomes are a P-extended score, global mental and physical health. Secondary outcomes include health-service utilization/ functioning, treatment adherence, functioning, symptoms/behaviors/emotions, substance use, violence, among others. Results: . Starting 04/26/2020, up to 14/07/2021 >151,000 people from 155 countries/territories/regions and six continents have participated. Representative samples of >= 1,000 adults have been collected in 15 countries. Overall, 43.0% had prior physical disorders, 16.3% had prior mental disorders, 26.5% were health care workers, 8.2% were aged >= 65 years, 19.3% were exposed to someone infected with COVID-19, 76.1% had been in quarantine, and 2.1% had been COVID 19-positive. Limitations: . Cross-sectional survey, preponderance of non-representative participants. Conclusions: . Results from COH-FIT will comprehensively quantify the impact of COVID-19, seeking to identify high-risk groups in need for acute and long-term intervention, and inform evidence-based health policies/strategies during this/future pandemics.
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| 28. |
- Solmi, Marco, et al.
(författare)
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Validation of the Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) questionnaire for adults
- 2023
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Ingår i: Journal of Affective Disorders. - : ELSEVIER. - 0165-0327 .- 1573-2517. ; 326, s. 249-261
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the in-ternal validity of the co-primary outcome, a composite psychopathology "P-score". Methods: The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r >= 0.5 with validated companion question-naires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed. Results: From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (omega = 0.95). Factor structure was consistent across age and sex. Conclusions: COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health.
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| 29. |
- A. da Cruz, Márcia G., et al.
(författare)
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Solvent-free synthesis of photoluminescent carbon nanoparticles from lignin-derived monomers as feedstock
- 2023
-
Ingår i: Green Chemistry Letters and Reviews. - 1751-8253 .- 1751-7192. ; 16:1
-
Tidskriftsartikel (refereegranskat)abstract
- Photoluminescent carbon nanoparticles (CNPs), such as carbon dots (CDs), have attracted much attention owing to a unique set of properties, like high and tunable fluorescence. In this way, the use of carbon-rich lignin has been demonstrated to be a sustainable approach to producing a broad range of photoluminescent CNPs. However, the valorization of this complex polyphenol is limited when it comes to green and efficient ways of conversion. In addition, the existing solvothermal approaches using lignin often result in CDs with low photoluminescence, while flammable and/or toxic solvents are employed. Here, we depolymerized technical lignins, i.e. kraft and soda, through electroreductive cleavage in two different sustainable media: deep eutectic solvent and levulinic acid. After depolymerization, lignin-derived monomers were generated, with a predominance of aryl ether and phenolic groups, which were further combined with 1,2-Phenylenediamine to produce N-doped CNPs in a solvent-free approach. Photoluminescent CNPs with varied sizes were generated (5–50 nm), which presented a wide photoluminescence emission, from blue to red, depending on solvent polarity. These results demonstrate a feasible and sustainable route for the solvent-free synthesis of photoluminescent CNPs using lignin-derived monomers as carbon source, which may find applications in a wide range of fields.
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| 30. |
- Abbot, Stewart, et al.
(författare)
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Report of the international conference on manufacturing and testing of pluripotent stem cells
- 2018
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Ingår i: Biologicals. - : Elsevier BV. - 1045-1056. ; 56, s. 67-83
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Sessions included an overview of past cell therapy (CT) conferences sponsored by the International Alliance for Biological Standardization (IABS). The sessions highlighted challenges in the field of human pluripotent stem cells (hPSCs) and also addressed specific points on manufacturing, bioanalytics and comparability, tumorigenicity testing, storage, and shipping. Panel discussions complemented the presentations. The conference concluded that a range of new standardization groups is emerging that could help the field, but ways must be found to ensure that these efforts are coordinated. In addition, there are opportunities for regulatory convergence starting with a gap analysis of existing guidelines to determine what might be missing and what issues might be creating divergence. More specific global regulatory guidance, preferably from WHO, would be welcome. IABS and the California Institute for Regenerative Medicine (CIRM) will explore with stakeholders the development of a practical and innovative road map to support early CT product (CTP) developers.
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| 31. |
- Alonso-Blanco, Carlos, et al.
(författare)
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1,135 Genomes Reveal the Global Pattern of Polymorphism in Arabidopsis thaliana
- 2016
-
Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 166:2, s. 481-491
-
Tidskriftsartikel (refereegranskat)abstract
- Arabidopsis thaliana serves as a model organism for the study of fundamental physiological, cellular, and molecular processes. It has also greatly advanced our understanding of intraspecific genome variation. We present a detailed map of variation in 1,135 high-quality re-sequenced natural inbred lines representing the native Eurasian and North African range and recently colonized North America. We identify relict populations that continue to inhabit ancestral habitats, primarily in the Iberian Peninsula. They have mixed with a lineage that has spread to northern latitudes from an unknown glacial refugium and is now found in a much broader spectrum of habitats. Insights into the history of the species and the fine-scale distribution of genetic diversity provide the basis for full exploitation of A. thaliana natural variation through integration of genomes and epigenomes with molecular and non-molecular phenotypes.
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| 32. |
- Andersson, Anna, et al.
(författare)
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The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias.
- 2015
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:4, s. 192-330
-
Tidskriftsartikel (refereegranskat)abstract
- Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older children (MLL-R cases) with leukemia. Our data show that infant MLL-R ALL has one of the lowest frequencies of somatic mutations of any sequenced cancer, with the predominant leukemic clone carrying a mean of 1.3 non-silent mutations. Despite this paucity of mutations, we detected activating mutations in kinase-PI3K-RAS signaling pathway components in 47% of cases. Surprisingly, these mutations were often subclonal and were frequently lost at relapse. In contrast to infant cases, MLL-R leukemia in older children had more somatic mutations (mean of 6.5 mutations/case versus 1.3 mutations/case, P = 7.15 × 10(-5)) and had frequent mutations (45%) in epigenetic regulators, a category of genes that, with the exception of MLL, was rarely mutated in infant MLL-R ALL.
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| 33. |
- Baschieri, Angela, et al.
(författare)
-
"Every Newborn-INDEPTH" (EN-INDEPTH) study protocol for a randomised comparison of household survey modules for measuring stillbirths and neonatal deaths in five Health and Demographic Surveillance sites
- 2019
-
Ingår i: Journal of Global Health. - : International Global Health Society. - 2047-2978 .- 2047-2986. ; 9:1, s. 1-15
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Under-five and maternal mortality were halved in the Millennium Development Goals (MDG) era, with slower reductions for 2.6 million neonatal deaths and 2.6 million stillbirths. The Every Newborn Action Plan aims to accelerate progress towards national targets, and includes an ambitious Measurement Improvement Roadmap. Population-based household surveys, notably Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys, are major sources of population-level data on child mortality in countries with weaker civil registration and vital statistics systems, where over two-thirds of global child deaths occur. To estimate neonatal/child mortality and pregnancy outcomes (stillbirths, miscarriages, birthweight, gestational age) the most common direct methods are: (1) the standard DHS-7 with Full Birth History with additional questions on pregnancy losses in the past 5 years (FBH+) or (2) a Full Pregnancy History (FPH). No direct comparison of these two methods has been undertaken, although descriptive analyses suggest that the FBH+ may underestimate mortality rates particularly for stillbirths.Methods: This is the protocol paper for the Every Newborn-INDEPTH study (INDEPTH Network, International Network for the Demographic Evaluation of Populations and their Health Every Newborn, Every Newborn Action Plan), aiming to undertake a randomised comparison of FBH+ and FPH to measure pregnancy outcomes in a household survey in five selected INDEPTH Network sites in Africa and South Asia (Bandim in urban and rural Guinea-Bissau; Dabat in Ethiopia; IgangaMayuge in Uganda; Kintampo in Ghana; Matlab in Bangladesh). The survey will reach >68 000 pregnancies to assess if there is ≥15% difference in stillbirth rates. Additional questions will capture birthweight, gestational age, birth/death certification, termination of pregnancy and fertility intentions. The World Bank's Survey Solutions platform will be tailored for data collection, including recording paradata to evaluate timing. A mixed methods assessment of barriers and enablers to reporting of pregnancy and adverse pregnancy outcomes will be undertaken.Conclusions: This large-scale study is the first randomised comparison of these two methods to capture pregnancy outcomes. Results are expected to inform the evidence base for survey methodology, especially in DHS, regarding capture of stillbirths and other outcomes, notably neonatal deaths, abortions (spontaneous and induced), birthweight and gestational age. In addition, this study will inform strategies to improve health and demographic surveillance capture of neonatal/child mortality and pregnancy outcomes.
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| 34. |
- Beukes, Eldre W., et al.
(författare)
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Changes in Tinnitus Experiences During the COVID-19 Pandemic
- 2020
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Ingår i: Frontiers In Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 8, s. 1-13
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The COVID-19 pandemic has disrupted delivery of healthcare, economic activity, and affected social interactions. Identifying and supporting those most affected by the pandemic is required. The purpose of this study was to determine the impact of the pandemic on individuals with tinnitus and to identify mediating factors. Methods: This is a mixed-methods exploratory cross-sectional study, using data collected via an online survey from 3,103 individuals with tinnitus from 48 countries. The greatest representation was from North America (49%) and Europe (47%) and other countries were only marginally represented. Results: Although the study was aimed at those with pre-existing tinnitus, 7 individuals reported having COVID-19 initiated tinnitus. Having COVID-19 symptoms exacerbated tinnitus in 40% of respondents, made no change in 54%, and improved tinnitus in 6%. Other mediating factors such as the social and emotional consequences of the pandemic made pre-existing tinnitus more bothersome for 32% of the respondents, particularly for females and younger adults, better for 1%, and caused no change to tinnitus for 67%. Pre-existing tinnitus was significantly exacerbated for those self-isolating, experiencing loneliness, sleeping poorly, and with reduced levels of exercise. Increased depression, anxiety, irritability, and financial worries further significantly contributed to tinnitus being more bothersome during the pandemic period. Conclusions: These findings have implications for tinnitus management, because they highlight the diverse response both internal and external factors have on tinnitus levels. Clinical services should be mindful that tinnitus may be caused by contracting COVID-19 and pre-existing tinnitus may be exacerbated, although in the majority of respondents there was no change. Additional support should be offered where tinnitus severity has increased due to the health, social, and/or emotional effects of the COVID-19 pandemic. Tinnitus may be more bothersome for those experiencing loneliness, having fewer social interactions, and who are more anxious or worried.
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| 35. |
- Beukes, Eldre W., et al.
(författare)
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Investigating tinnitus subgroups based on hearing-related difficulties
- 2021
-
Ingår i: International journal of clinical practice (Esher). - : John Wiley & Sons. - 1368-5031 .- 1742-1241. ; 75:10
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose Meaningfully grouping individuals with tinnitus who share a common characteristics (ie, subgrouping, phenotyping) may help tailor interventions to certain tinnitus subgroups and hence reduce outcome variability. The purpose of this study was to test if the presence of tinnitus subgroups are discernible based on hearing-related comorbidities, and to identify predictors of tinnitus severity for each subgroup identified. Methods An exploratory cross-sectional study was used. The study was nested within an online survey distributed worldwide to investigate tinnitus experiences during the COVID-19 pandemic. The main outcome measure was the tinnitus Handicap Inventory- Screening Version. Results From the 3400 respondents, 2980 were eligible adults with tinnitus with an average age of 58 years (SD = 14.7) and 49% (n = 1457) being female. A three-cluster solution identified distinct subgroups, namely, those with tinnitus-only (n = 1306; 44%), those presenting with tinnitus, hyperacusis, hearing loss and/or misophonia (n = 795; 27%), and those with tinnitus and hearing loss (n = 879; 29%). Those with tinnitus and hyperacusis reported the highest tinnitus severity (M = 20.3; SD = 10.5) and those with tinnitus and no hearing loss had the lowest tinnitus severity (M = 15.7; SD = 10.4). Younger age and the presence of mental health problems predicted greater tinnitus severity for all groups (beta <= -0.1, P <= .016). Conclusion Further exploration of these potential subtypes are needed in both further research and clinical practice by initially triaging tinnitus patients prior to their clinical appointments based on the presence of hearing-related comorbidities. Unique management pathways and interventions could be tailored for each tinnitus subgroup.
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| 36. |
- Bock, Wolfgang, et al.
(författare)
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Testing, social distancing and age specific quarantine for COVID-19 : Case studies in Iligan City and Cagayan de Oro City, Philippines
- 2020
-
Ingår i: 9th Jagna International Workshop Stochastic Analysis – Mathematical Methods and Real-World Models, 8–18 January 2020, Bohol, Philippines. - : American Institute of Physics (AIP). - 9780735440166
-
Konferensbidrag (refereegranskat)abstract
- The world today grapples with the health crisis caused by the novel COVID-19. Unfortunately, the Philippines, which was spared from the previous epidemics like Ebola and SARS, is now facing this major obstacle. The local government units of the country responded by issuing guidelines to mitigate the spread of infection. Two neighboring cities in the Philippines, namely, Iligan and Cagayan de Oro have been the focus of this study. Simulations have been undertaken to investigate the prevalence of the disease and the health care systems capacity to accommodate critically ill patients over time. The effects of mitigating strategies like social distancing, age specific quarantine and testing were considered. The model used for the spread of COVID-19 is an individual-based SIR model. The results indicated that social distancing and age specific quarantine can effectively slow down the progression of the disease. Moreover, social distancing combined with an effective testing strategy can keep the epidemic subcritical.
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| 37. |
- Day, Louise T., et al.
(författare)
-
"Every Newborn-BIRTH" protocol : observational study validating indicators for coverage and quality of maternal and newborn health care in Bangladesh, Nepal and Tanzania
- 2019
-
Ingår i: Journal of Global Health. - : International Global Health Society. - 2047-2978 .- 2047-2986. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: To achieve Sustainable Development Goals and Universal Health Coverage, programmatic data are essential. The Every Newborn Action Plan, agreed by all United Nations member states and >80 development partners, includes an ambitious Measurement Improvement Roadmap. Quality of care at birth is prioritised by both Every Newborn and Ending Preventable Maternal Mortality strategies, hence metrics need to advance from health service contact alone, to content of care. As facility births increase, monitoring using routine facility data in DHIS2 has potential, yet validation research has mainly focussed on maternal recall surveys. The Every Newborn - Birth Indicators Research Tracking in Hospitals (EN-BIRTH) study aims to validate selected newborn and maternal indicators for routine tracking of coverage and quality of facility-based care for use at district, national and global levels.Methods: EN-BIRTH is an observational study including >20000 facility births in three countries (Tanzania, Bangladesh and Nepal) to validate selected indicators. Direct clinical observation will be compared with facility register data and a pre-discharge maternal recall survey for indicators including: uterotonic administration, immediate newborn care, neonatal resuscitation and Kangaroo mother care. Indicators including neonatal infection management and antenatal corticosteroid administration, which cannot be easily observed, will be validated using inpatient records. Trained clinical observers in Labour/Delivery ward, Operation theatre, and Kangaroo mother care ward/areas will collect data using a tablet-based customised data capturing application. Sensitivity will be calculated for numerators of all indicators and specificity for those numerators with adequate information. Other objectives include comparison of denominator options (ie, true target population or surrogates) and quality of care analyses, especially regarding intervention timing. Barriers and enablers to routine recording and data usage will be assessed by data flow assessments, quantitative and qualitative analyses.Conclusions: To our knowledge, this is the first large, multi-country study validating facility-based routine data compared to direct observation for maternal and newborn care, designed to provide evidence to inform selection of a core list of indicators recommended for inclusion in national DHIS2. Availability and use of such data are fundamental to drive progress towards ending the annual 5.5 million preventable stillbirths, maternal and newborn deaths.
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| 38. |
- Day, Louise T, et al.
(författare)
-
"Every Newborn-BIRTH" protocol: observational study validating indicators for coverage and quality of maternal and newborn health care in Bangladesh, Nepal and Tanzania.
- 2019
-
Ingår i: Journal of global health. - : International Global Health Society. - 2047-2986 .- 2047-2978. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- To achieve Sustainable Development Goals and Universal Health Coverage, programmatic data are essential. The Every Newborn Action Plan, agreed by all United Nations member states and >80 development partners, includes an ambitious Measurement Improvement Roadmap. Quality of care at birth is prioritised by both Every Newborn and Ending Preventable Maternal Mortality strategies, hence metrics need to advance from health service contact alone, to content of care. As facility births increase, monitoring using routine facility data in DHIS2 has potential, yet validation research has mainly focussed on maternal recall surveys. The Every Newborn - Birth Indicators Research Tracking in Hospitals (EN-BIRTH) study aims to validate selected newborn and maternal indicators for routine tracking of coverage and quality of facility-based care for use at district, national and global levels.EN-BIRTH is an observational study including >20 000 facility births in three countries (Tanzania, Bangladesh and Nepal) to validate selected indicators. Direct clinical observation will be compared with facility register data and a pre-discharge maternal recall survey for indicators including: uterotonic administration, immediate newborn care, neonatal resuscitation and Kangaroo mother care. Indicators including neonatal infection management and antenatal corticosteroid administration, which cannot be easily observed, will be validated using inpatient records. Trained clinical observers in Labour/Delivery ward, Operation theatre, and Kangaroo mother care ward/areas will collect data using a tablet-based customised data capturing application. Sensitivity will be calculated for numerators of all indicators and specificity for those numerators with adequate information. Other objectives include comparison of denominator options (ie, true target population or surrogates) and quality of care analyses, especially regarding intervention timing. Barriers and enablers to routine recording and data usage will be assessed by data flow assessments, quantitative and qualitative analyses.To our knowledge, this is the first large, multi-country study validating facility-based routine data compared to direct observation for maternal and newborn care, designed to provide evidence to inform selection of a core list of indicators recommended for inclusion in national DHIS2. Availability and use of such data are fundamental to drive progress towards ending the annual 5.5 million preventable stillbirths, maternal and newborn deaths.
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| 39. |
- Desmarais, John J., et al.
(författare)
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DABs are inorganic carbon pumps found throughout prokaryotic phyla
- 2019
-
Ingår i: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 4:12, s. 2204-2215
-
Tidskriftsartikel (refereegranskat)abstract
- Bacterial autotrophs often rely on CO2 concentrating mechanisms (CCMs) to assimilate carbon. Although many CCM proteins have been identified, a systematic screen of the components of CCMs is lacking. Here, we performed a genome-wide barcoded transposon screen to identify essential and CCM-related genes in the γ-proteobacterium Halothiobacillus neapolitanus. Screening revealed that the CCM comprises at least 17 and probably no more than 25 genes, most of which are encoded in 3 operons. Two of these operons (DAB1 and DAB2) contain a two-gene locus that encodes a domain of unknown function (Pfam: PF10070) and a putative cation transporter (Pfam: PF00361). Physiological and biochemical assays demonstrated that these proteins—which we name DabA and DabB, for DABs accumulate bicarbonate—assemble into a heterodimeric complex, which contains a putative β-carbonic anhydrase-like active site and functions as an energy-coupled inorganic carbon (Ci) pump. Interestingly, DAB operons are found in a diverse range of bacteria and archaea. We demonstrate that functional DABs are present in the human pathogens Bacillus anthracis and Vibrio cholerae. On the basis of these results, we propose that DABs constitute a class of energized Ci pumps and play a critical role in the metabolism of Ci throughout prokaryotic phyla.
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| 40. |
- Faber, Zachary J, et al.
(författare)
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The genomic landscape of core-binding factor acute myeloid leukemias
- 2016
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 48, s. 1551-1556
-
Tidskriftsartikel (refereegranskat)abstract
- Acute myeloid leukemia (AML) comprises a heterogeneous group of leukemias frequently defined by recurrent cytogenetic abnormalities, including rearrangements involving the core-binding factor (CBF) transcriptional complex. To better understand the genomic landscape of CBF-AMLs, we analyzed both pediatric (n = 87) and adult (n = 78) samples, including cases with RUNX1-RUNX1T1 (n = 85) or CBFB-MYH11 (n = 80) rearrangements, by whole-genome or whole-exome sequencing. In addition to known mutations in the Ras pathway, we identified recurrent stabilizing mutations in CCND2, suggesting a previously unappreciated cooperating pathway in CBF-AML. Outside of signaling alterations, RUNX1-RUNX1T1 and CBFB-MYH11 AMLs demonstrated remarkably different spectra of cooperating mutations, as RUNX1-RUNX1T1 cases harbored recurrent mutations in DHX15 and ZBTB7A, as well as an enrichment of mutations in epigenetic regulators, including ASXL2 and the cohesin complex. This detailed analysis provides insights into the pathogenesis and development of CBF-AML, while highlighting dramatic differences in the landscapes of cooperating mutations for these related AML subtypes.
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| 41. |
- Huang, Yi Shu, et al.
(författare)
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Pharmacological modulation of T cell immunity results in long-term remission of autoimmune arthritis
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 118:19
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic inflammatory diseases like rheumatoid arthritis are characterized by a deficit in fully functional regulatory T cells. DNA-methylation inhibitors have previously been shown to promote regulatory T cell responses and, in the present study, we evaluated their potential to ameliorate chronic and acute animal models of rheumatoid arthritis. Of the drugs tested, decitabine was the most effective, producing a sustained therapeutic effect that was dependent on indoleamine 2,3-dioxygenase (IDO) and was associated with expansion of induced regulatory T cells, particularly at the site of disease activity. Treatment with decitabine also caused apoptosis of Th1 and Th17 cells in active arthritis in a highly selective manner. The molecular basis for this selectivity was shown to be ENT1, a nucleoside transporter, which facilitates intracellular entry of the drug and is up-regulated on effector T cells during active arthritis. It was further shown that short-term treatment with decitabine resulted in the generation of a population of regulatory T cells that were able to suppress arthritis upon adoptive transfer. In summary, a therapeutic approach using an approved drug is described that treats active inflammatory disease effectively and generates robust regulatory T cells with the IDO-dependent capacity to maintain remission.
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| 42. |
- Kawakatsu, Taiji, et al.
(författare)
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Epigenomic Diversity in a Global Collection of Arabidopsis thaliana Accessions
- 2016
-
Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 166:2, s. 492-505
-
Tidskriftsartikel (refereegranskat)abstract
- The epigenome orchestrates genome accessibility, functionality, and three-dimensional structure. Because epigenetic variation can impact transcription and thus phenotypes, it may contribute to adaptation. Here, we report 1,107 high-quality single-base resolution methylomes and 1,203 transcriptomes from the 1001 Genomes collection of Arabidopsis thaliana. Although the genetic basis of methylation variation is highly complex, geographic origin is a major predictor of genome-wide DNA methylation levels and of altered gene expression caused by epialleles. Comparison to cistrome and epicistrome datasets identifies associations between transcription factor binding sites, methylation, nucleotide variation, and co-expression modules. Physical maps for nine of the most diverse genomes reveal how transposons and other structural variants shape the epigenome, with dramatic effects on immunity genes. The 1001 Epigenomes Project provides a comprehensive resource for understanding how variation in DNA methylation contributes to molecular and non-molecular phenotypes in natural populations of the most studied model plant.
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| 43. |
- Koriche, Sifan A., et al.
(författare)
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Impacts of Variations in Caspian Sea Surface Area on Catchment-Scale and Large-Scale Climate
- 2021
-
Ingår i: Journal of Geophysical Research - Atmospheres. - : American Geophysical Union (AGU). - 2169-897X .- 2169-8996. ; 126:18
-
Tidskriftsartikel (refereegranskat)abstract
- The Caspian Sea (CS) is the largest inland lake in the world. Large variations in sea level and surface area occurred in the past and are projected for the future. The potential impacts on regional and large-scale hydroclimate are not well understood. Here, we examine the impact of CS area on climate within its catchment and across the northern hemisphere, for the first time with a fully coupled climate model. The Community Earth System Model (CESM1.2.2) is used to simulate the climate of four scenarios: (a) larger than present CS area, (b) current area, (c) smaller than present area, and (d) no-CS scenario. The results reveal large changes in the regional atmospheric water budget. Evaporation (e) over the sea increases with increasing area, while precipitation (P) increases over the south-west CS with increasing area. P-E over the CS catchment decreases as CS surface area increases, indicating a dominant negative lake-evaporation feedback. A larger CS reduces summer surface air temperatures and increases winter temperatures. The impacts extend eastwards, where summer precipitation is enhanced over central Asia and the north-western Pacific experiences warming with reduced winter sea ice. Our results also indicate weakening of the 500-hPa troughs over the northern Pacific with larger CS area. We find a thermal response triggers a southward shift of the upper troposphere jet stream during summer. Our findings establish that changing CS area results in climate impacts of such scope that CS area variations should be incorporated into climate model simulations, including palaeo and future scenarios.
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- McGuire, A. David, et al.
(författare)
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Variability in the sensitivity among model simulations of permafrost and carbon dynamics in the permafrost region between 1960 and 2009
- 2016
-
Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 30:7, s. 1015-1037
-
Tidskriftsartikel (refereegranskat)abstract
- A significant portion of the large amount of carbon (C) currently stored in soils of the permafrost region in the Northern Hemisphere has the potential to be emitted as the greenhouse gases CO2 and CH4 under a warmer climate. In this study we evaluated the variability in the sensitivity of permafrost and C in recent decades among land surface model simulations over the permafrost region between 1960 and 2009. The 15 model simulations all predict a loss of near-surface permafrost (within 3m) area over the region, but there are large differences in the magnitude of the simulated rates of loss among the models (0.2 to 58.8x10(3)km(2)yr(-1)). Sensitivity simulations indicated that changes in air temperature largely explained changes in permafrost area, although interactions among changes in other environmental variables also played a role. All of the models indicate that both vegetation and soil C storage together have increased by 156 to 954TgCyr(-1) between 1960 and 2009 over the permafrost region even though model analyses indicate that warming alone would decrease soil C storage. Increases in gross primary production (GPP) largely explain the simulated increases in vegetation and soil C. The sensitivity of GPP to increases in atmospheric CO2 was the dominant cause of increases in GPP across the models, but comparison of simulated GPP trends across the 1982-2009 period with that of a global GPP data set indicates that all of the models overestimate the trend in GPP. Disturbance also appears to be an important factor affecting C storage, as models that consider disturbance had lower increases in C storage than models that did not consider disturbance. To improve the modeling of C in the permafrost region, there is the need for the modeling community to standardize structural representation of permafrost and carbon dynamics among models that are used to evaluate the permafrost C feedback and for the modeling and observational communities to jointly develop data sets and methodologies to more effectively benchmark models.
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| 48. |
- Moreira, J. M. M., et al.
(författare)
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From DSM to 3D building models : A quantitative evaluation
- 2013
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Ingår i: International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences - ISPRS Archives. - Gottingen : Copernicus gesellschaft MBH. ; , s. 213-219
-
Konferensbidrag (refereegranskat)abstract
- The paper reviews the state-of-the-art in 3D city models and building block generation, with a description of the most common solutions and approaches. Then the digital reconstruction and comparison of LoD1 and LoD2 building models obtained with commercial packages and using different input data are presented. As input data, a DSM at 1m resolution derived from a GeoEye-1 stereo-pair, a DSM from an aerial block at 50 cm GSD and a LiDAR-based DSM at 1m resolution are used. The geometric buildings produced with each dataset are evaluated with respect to some ground-truth measurements but also compared between them. Problems such as the quality of the input DSM, the accuracy of the necessary vector datasets containing the building footprints, the flexibility of the approaches and the potentialities of each dataset will be discussed. As reconstruction of the building models is largely influenced by the quality of the building footprints, which may be out-of-date or slightly shifted with respect to the employed DSMs/DTMs, an in-house method is being developed to derive them starting from the produced DSMs.
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| 49. |
- Ng, Bobby G, et al.
(författare)
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ALG1-CDG: Clinical and Molecular Characterization of 39 Unreported Patients.
- 2016
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794.
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Tidskriftsartikel (refereegranskat)abstract
- Congenital disorders of glycosylation (CDG) arise from pathogenic mutations in over one hundred genes leading to impaired protein or lipid glycosylation. ALG1 encodes a β1,4 mannosyltransferase that catalyzes the addition of the first of nine mannose moieties to form a dolichol-lipid linked oligosaccharide intermediate (DLO) required for proper N-linked glycosylation. ALG1 mutations cause a rare autosomal recessive disorder termed ALG1-CDG. To date thirteen mutations in eighteen patients from fourteen families have been described with varying degrees of clinical severity. We identified and characterized thirty-nine previously unreported cases of ALG1-CDG from thirty-two families and add twenty-six new mutations. Pathogenicity of each mutation was confirmed based on its inability to rescue impaired growth or hypoglycosylation of a standard biomarker in an alg1-deficient yeast strain. Using this approach we could not establish a rank order comparison of biomarker glycosylation and patient phenotype, but we identified mutations with a lethal outcome in the first two years of life. The recently identified protein-linked xeno-tetrasaccharide biomarker, NeuAc-Gal-GlcNAc2 , was seen in all twenty-seven patients tested. Our study triples the number of known patients and expands the molecular and clinical correlates of this disorder. This article is protected by copyright. All rights reserved.
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- Pavlova, Elena V., et al.
(författare)
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Inhibition of UDP-glucosylceramide synthase in mice prevents Gaucher disease-associated B-cell malignancy
- 2015
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417. ; 235:1, s. 113-124
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Tidskriftsartikel (refereegranskat)abstract
- Clonal B-cell proliferation is a frequent manifestation of Gaucher disease-a sphingolipidosis associated with a high risk of multiple myeloma and non-Hodgkin lymphoma. Gaucher disease is caused by genetic deficiency of acid -glucosidase, the natural substrates of which (-d-glucosylceramide and -d-glucosylsphingosine) accumulate, principally in macrophages. Mice with inducible deficiency of -glucosidase [Gba(tm1Karl/tm1Karl)Tg(MX1-cre)1Cgn/0] serve as an authentic model of human Gaucher disease; we have recently reported clonal B-cell proliferation accompanied by monoclonal serum paraproteins and cognate tumours in these animals. To explore the relationship between B-cell malignancy and the biochemical defect, we treated Gaucher mice with eliglustat tartrate (GENZ 112638), a potent and selective inhibitor of the first committed step in glycosphingolipid biosynthesis. Twenty-two Gaucher mice received 300mg/kg of GENZ 112638 daily for 3-10 months from 6 weeks of age. Plasma concentrations of -d-glucosylceramide and the unacylated glycosphingolipid, -d-glucosylsphingosine, declined. After administration of GENZ 112638 to Gaucher mice for 3-10 months, serum paraproteins were not detected and there was a striking reduction in the malignant lymphoproliferation: neither lymphomas nor plasmacytomas were found in animals that had received the investigational agent. In contrast, 14 out of 60 Gaucher mice without GENZ 112638 treatment developed these tumours; monoclonal paraproteins were detected in plasma from 18 of the 44 age-matched mice with Gaucher disease that had not received GENZ 112638. Long-term inhibition of glycosphingolipid biosynthesis suppresses the development of spontaneous B-cell lymphoma and myeloma in Gaucher mice. Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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