| 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. |
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| 4. |
- Namkoong, H, et al.
(författare)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 5. |
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| 6. |
- Wang, QBS, et al.
(författare)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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| 7. |
- Acharya, B. S., et al.
(författare)
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Introducing the CTA concept
- 2013
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. (C) 2013 Elsevier B.V. All rights reserved.
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| 8. |
- Actis, M., et al.
(författare)
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Design concepts for the Cherenkov Telescope Array CTA : an advanced facility for ground-based high-energy gamma-ray astronomy
- 2011
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Ingår i: Experimental astronomy. - : Springer. - 0922-6435 .- 1572-9508. ; 32:3, s. 193-316
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Tidskriftsartikel (refereegranskat)abstract
- Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 14. |
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| 15. |
- Yamaga, Takumi, et al.
(författare)
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Study of the elementary (K -, n) reactions to search for the K NN bound state via the 3He (K -, n) reaction at J-PARC
- 2016
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Ingår i: XVIth International Conference on Hadron Spectroscopy, Hadron 2015. - : Author(s). - 9780735413894 ; 1735
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Konferensbidrag (refereegranskat)abstract
- We have searched for the simplest kaonic nuclear state, K̄NN, using the in-flight 3He (K-, n) reaction at the J-PARC hadron experimental facility. In the semi-inclusive neutron missing-mass spectrum at θnlab=0°, an excess of yield was observed just below the K- pp mass-threshold, which cannot be explained by any elementary reactions [PTEP 2015, 061D01]. To understand the missing-mass spectrum of 3He (K-, n) X, we investigated the elementary (K-, n) reactions using hydrogen and deuterium targets. The p (K-, n) X missing-mass spectrum was well described by the charge-exchange reaction. However, in the d (K-, n) X spectrum, we observed an excess of yield just below the K- p mass-threshold, which was similar to that in the 3He (K-, n) X spectrum.
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| 16. |
- Asano, H., et al.
(författare)
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Spectroscopic study of the Λ(1405) resonance via the d (K-, n) reaction at J-PARC
- 2019
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Ingår i: 13th International Conference on Hypernuclear and Strange Particle Physics, HYP 2018. - : AIP Publishing. - 9780735418721 ; 2130
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Konferensbidrag (refereegranskat)abstract
- The structure of the Λ(1405) hyperon is an important and long-standing issue related to the K̄-nucleus interaction. The J-PARC E31 experiment has been performed to investigate the Λ(1405) spectrum shape. Because it is hard to form the Λ(1405) directly by a K̄N scattering in free space, E31 uses the d(K-, n) reaction with an incident kaon momentum of 1 GeV/c. We will identify three final states - ς-π+, ς+π-, ς0π0-so that the isospin structure of hyperon resonance states produced can be decomposed. The first physics run of the E31 experiment was performed in 2016. To enhance the statistics of the data set, we have performed the second physics run in the beginning of 2018. During the second run of E31, around 3.9×1010 kaons impacted on the deuteron target.
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| 17. |
- Forrest, ARR, et al.
(författare)
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A promoter-level mammalian expression atlas
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 507:7493, s. 462-
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Tidskriftsartikel (refereegranskat)
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| 18. |
- Sada, Y., et al.
(författare)
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Structure near the K- + p + p threshold in the in-flight 3He(K-, Λp)n reaction
- 2016
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Ingår i: Progress of Theoretical and Experimental Physics. - : Oxford University Press (OUP). - 2050-3911. ; 2016:5
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Tidskriftsartikel (refereegranskat)abstract
- To search for an S = -1 di-baryonic state which decays toΛp, the 3He(K-,Λp)nmissing reaction was studied at 1.0 GeV/c. Unobserved neutrons were kinematically identified from the missing mass MX of the 3He (K-,Λp) X reaction in order to have a large acceptance for the Λpn final state. The observed Λpn events, distributed widely over the kinematically allowed region of the Dalitz plot, establish that the major component comes from a three-nucleon absorption process. A concentration of events at a specific neutron kinetic energy was observed in a region of low momentum transfer to the Λp. To account for the observed peak structure, the simplest S-wave polewas assumed to exist in the reaction channel, having a Breit-Wigner formin energy and with a Gaussian form factor. A minimum X2 method was applied to deduce its mass, MX = 2355+6 -8 (stat.) ±12 (syst.)MeV/c2, and decay width, γX = 110+19 -17 (stat.) ±27 (syst.)MeV/c2, respectively. The form factor parameter QX ∼ 400MeV/c implies that the range of the interaction is about 0.5 fm.
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| 19. |
- Lu, C. W., et al.
(författare)
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Heart Failure and Patient-Reported Outcomes in Adults With Congenital Heart Disease from 15 Countries
- 2022
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Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Heart failure (HF) is the leading cause of mortality and associated with significant morbidity in adults with congenital heart disease. We sought to assess the association between HF and patient-report outcomes in adults with congenital heart disease. METHODS AND RESULTS: As part of the APPROACH-IS (Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease-International Study), we collected data on HF status and patient-reported outcomes in 3959 patients from 15 countries across 5 continents. Patient-report outcomes were: perceived health status (12-item Short Form Health Survey), quality of life (Linear Analogue Scale and Satisfaction with Life Scale), sense of coherence-13, psychological distress (Hospital Anxiety and Depression Scale), and illness perception (Brief Illness Perception Questionnaire). In this sample, 137 (3.5%) had HF at the time of investigation, 298 (7.5%) had a history of HF, and 3524 (89.0%) had no current or past episode of HF. Patients with current or past HF were older and had a higher prevalence of complex congenital heart disease, arrhythmias, implantable cardioverter-defibrillators, other clinical comorbidities, and mood disorders than those who never had HF. Patients with HF had worse physical functioning, mental functioning, quality of life, satisfaction with life, sense of coherence, depressive symptoms, and illness perception scores. Magnitudes of differences were large for physical functioning and illness perception and moderate for mental functioning, quality of life, and depressive symptoms. CONCLUSIONS: HF in adults with congenital heart disease is associated with poorer patient-reported outcomes, with large effect sizes for physical functioning and illness perception.
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| 20. |
- Noguchi, S, et al.
(författare)
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FANTOM5 CAGE profiles of human and mouse samples
- 2017
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Ingår i: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4, s. 170112-
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Tidskriftsartikel (refereegranskat)abstract
- In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
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| 21. |
- Fujita, S., et al.
(författare)
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Spatial and temporal variability of snow accumulation rate on the East Antarctic ice divide between Dome Fuji and EPICA DML
- 2011
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Ingår i: The Cryosphere. - : Copernicus GmbH. - 1994-0416 .- 1994-0424. ; 5:4, s. 1057-1081
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Tidskriftsartikel (refereegranskat)abstract
- To better understand the spatio-temporal variability of the glaciological environment in Dronning Maud Land (DML), East Antarctica, a 2800-km-long Japanese-Swedish traverse was carried out. The route includes ice divides between two ice-coring sites at Dome Fuji and EPICA DML. We determined the surface mass balance (SMB) averaged over various time scales in the late Holocene based on studies of snow pits and firn cores, in addition to radar data. We find that the large-scale distribution of the SMB depends on the surface elevation and continentality, and that the SMB differs between the windward and leeward sides of ice divides for strong-wind events. We suggest that the SMB is highly influenced by interactions between the large-scale surface topography of ice divides and the wind field of strong-wind events that are often associated with high-precipitation events. Local variations in the SMB are governed by the local surface topography, which is influenced by the bedrock topography. In the eastern part of DML, the accumulation rate in the second half of the 20th century is found to be higher by similar to 15% than averages over longer periods of 722 a or 7.9 ka before AD 2008. A similar increasing trend has been reported for many inland plateau sites in Antarctica with the exception of several sites on the leeward side of the ice divides.
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| 22. |
- Fujita, S., et al.
(författare)
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Radar diagnosis of the subglacial conditions in Dronning Maud Land, East Antarctica
- 2012
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Ingår i: The Cryosphere. - : Copernicus GmbH. - 1994-0416 .- 1994-0424. ; 6:5, s. 1203-1219
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Tidskriftsartikel (refereegranskat)abstract
- In order to better understand the spatial distribution of subglacial environments, ground-based radar profiling data were analyzed for a total distance of similar to 3300 km across Dronning Maud Land, East Antarctica. The relationship between geometrically corrected bed returned power [Pc bed] dB in decibels and ice thickness H was examined. When H is smaller than a critical value that varies according to location, [P-bed(c)](dB) tends to decrease relatively smoothly with increasing H, which is explicable primarily by the cumulative effect of dielectric attenuation within the ice. However, at locations where H is larger than the critical H values, anomalous increases and fluctuations in [P-bed(c)](dB) were observed, regardless of the choice of radar frequency or radar-pulse width. In addition, the amplitude of the fluctuations often range 10 similar to 20 dB. We argue that the anomalous increases are caused by higher bed reflectivity associated with the existence of subglacial water. We used these features to delineate frozen and temperate beds. Approximately two-thirds of the investigated area was found to have a temperate bed. The beds of the inland part of the ice sheet tend to be temperate, with the exception of subglacial high mountains. In contrast, the beds of coastal areas tend to be frozen, with the exception of fast-flowing ice on the subglacial lowland or troughs. We argue that this new analytical method can be applied to other regions.
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| 23. |
- Shapiro, M, et al.
(författare)
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An Earth-system prediction initiative for the twenty-first century: An international interdisciplinary initiative to accelerate advances in knowledge, prediction, use and value of weather, climate and Earth-system information
- 2010
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Ingår i: BULLETIN OF THE AMERICAN METEOROLOGICAL SOCIETY. - 0003-0007. ; 91:10, s. 1377-1388
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Tidskriftsartikel (refereegranskat)abstract
- The necessity and benefits for establishing the international Earth-system Prediction Initiative (EPI) are discussed by scientists associated with the World Meteorological Organization (WMO) World Weather Research Programme (WWRP), World Climate Research Programme (WCRP), International Geosphere–Biosphere Programme (IGBP), Global Climate Observing System (GCOS), and natural-hazards and socioeconomic communities. The proposed initiative will provide research and services to accelerate advances in weather, climate, and Earth system prediction and the use of this information by global societies. It will build upon the WMO, the Group on Earth Observations (GEO), the Global Earth Observation System of Systems (GEOSS) and the International Council for Science (ICSU) to coordinate the effort across the weather, climate, Earth system, natural-hazards, and socioeconomic disciplines. It will require (i) advanced high-performance computing facilities, supporting a worldwide network of research and operational modeling centers, and early warning systems; (ii) science, technology, and education projects to enhance knowledge, awareness, and utilization of weather, climate, environmental, and socioeconomic information; (iii) investments in maintaining existing and developing new observational capabilities; and (iv) infrastructure to transition achievements into operational products and services.
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| 24. |
- Sluman, Maayke A., et al.
(författare)
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Education as important predictor for successful employment in adults with congenital heart disease worldwide
- 2019
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Ingår i: Congenital Heart Disease. - : Computers, Materials and Continua (Tech Science Press). - 1747-079X .- 1747-0803. ; 14:3, s. 362-371
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundConflicting results have been reported regarding employment status and work ability in adults with congenital heart disease (CHD). Since this is an important determinant for quality of life, we assessed this in a large international adult CHD cohort.MethodsData from 4028 adults with CHD (53% women) from 15 different countries were collected by a uniform survey in the cross-sectional APPROACH International Study. Predictors for employment and work limitations were studied using general linear mixed models.ResultsMedian age was 32 years (IQR 25-42) and 94% of patients had at least a high school degree. Overall employment rate was 69%, but varied substantially among countries. Higher education (OR 1.99-3.69) and having a partner (OR 1.72) were associated with more employment; female sex (OR 0.66, worse NYHA functional class (OR 0.67-0.13), and a history of congestive heart failure (OR 0.74) were associated with less employment. Limitations at work were reported in 34% and were associated with female sex (OR 1.36), increasing age (OR 1.03 per year), more severe CHD (OR 1.31-2.10), and a history of congestive heart failure (OR 1.57) or mental disorders (OR 2.26). Only a university degree was associated with fewer limitations at work (OR 0.62).ConclusionsThere are genuine differences in the impact of CHD on employment status in different countries. Although the majority of adult CHD patients are employed, limitations at work are common. Education appears to be the main predictor for successful employment and should therefore be encouraged in patients with CHD.
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