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- Albani, S, et al.
(författare)
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Twelve thousand years of dust : the Holocene global dust cycle constrained by natural archives
- 2015
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 11:6, s. 869-903
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Tidskriftsartikel (refereegranskat)abstract
- Mineral dust plays an important role in the climate system by interacting with radiation, clouds, and biogeochemical cycles. In addition, natural archives show that the dust cycle experienced variability in the past in response to global and local climate change. The compilation of the DIRTMAP paleodust datasets in the last two decades provided a target for paleoclimate models that include the dust cycle, following a time slice approach. We propose an innovative framework to organize a paleodust dataset that moves on from the positive experience of DIRTMAP and takes into account new scientific challenges, by providing a concise and accessible dataset of temporally resolved records of dust mass accumulation rates and particle grain-size distributions. We consider data from ice cores, marine sediments, loess/paleosol sequences, lake sediments, and peat bogs for this compilation, with a temporal focus on the Holocene period. This global compilation allows investigation of the potential, uncertainties and confidence level of dust mass accumulation rates reconstructions, and highlights the importance of dust particle size information for accurate and quantitative reconstructions of the dust cycle. After applying criteria that help to establish that the data considered represent changes in dust deposition, 43 paleodust records have been identified, with the highest density of dust deposition data occurring in the North Atlantic region. Although the temporal evolution of dust in the North Atlantic appears consistent across several cores and suggest that minimum dust fluxes are likely observed during the Early to mid-Holocene period (6000–8000 years ago), the magnitude of dust fluxes in these observations is not fully consistent, suggesting that more work needs to be done to synthesize datasets for the Holocene. Based on the data compilation, we used the Community Earth System Model to estimate the mass balance and variability of the global dust cycle during the Holocene, with dust load ranging from 17.1 to 20.5 Tg between 2000 and 10 000 years ago, and a minimum in the Early to Mid-Holocene (6000–8000 years ago).
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- Gafar, Fajri, et al.
(författare)
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Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents : a systematic review and individual patient data meta-analysis
- 2023
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 61:3
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Forskningsöversikt (refereegranskat)abstract
- Background Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level.Methods We systematically searched MEDLINE, Embase and Web of Science (1990–2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration–time curve from 0 to 24 h post-dose (AUC0–24) and peak plasma concentration (Cmax) were assessed with random-effects models, normalised with current World Health Organization-recommended paediatric doses. Determinants of AUC0–24 and Cmax were assessed with linear mixed-effects models.Results Of 55 eligible studies, individual patient data were available for 39 (71%), including 1628 participants from 12 countries. Geometric means of steady-state AUC0–24 were summarised for isoniazid (18.7 (95% CI 15.5–22.6) h·mg·L−1), rifampicin (34.4 (95% CI 29.4–40.3) h·mg·L−1), pyrazinamide (375.0 (95% CI 339.9–413.7) h·mg·L−1) and ethambutol (8.0 (95% CI 6.4–10.0) h·mg·L−1). Our multivariate models indicated that younger age (especially <2 years) and HIV-positive status were associated with lower AUC0–24 for all first-line anti-TB drugs, while severe malnutrition was associated with lower AUC0–24 for isoniazid and pyrazinamide. N-acetyltransferase 2 rapid acetylators had lower isoniazid AUC0–24 and slow acetylators had higher isoniazid AUC0–24 than intermediate acetylators. Determinants of Cmax were generally similar to those for AUC0–24.Conclusions This study provides the most comprehensive estimates of plasma exposures to first-line anti-TB drugs in children and adolescents. Key determinants of drug exposures were identified. These may be relevant for population-specific dose adjustment or individualised therapeutic drug monitoring.
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- Grieser, M., et al.
(författare)
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Storage ring at HIE-ISOLDE
- 2012
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Ingår i: European Physical Journal: Special Topics. - : Springer Science and Business Media LLC. - 1951-6401 .- 1951-6355. ; 207:1, s. 1-117
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Tidskriftsartikel (refereegranskat)abstract
- We propose to install a storage ring at an ISOL-type radioactive beam facility for the first time. Specifically, we intend to setup the heavy-ion, low-energy ring TSR at the HIE-ISOLDE facility in CERN, Geneva. Such a facility will provide a capability for experiments with stored secondary beams that is unique in the world. The envisaged physics programme is rich and varied, spanning from investigations of nuclear ground-state properties and reaction studies of astrophysical relevance, to investigations with highly-charged ions and pure isomeric beams. The TSR might also be employed for removal of isobaric contaminants from stored ion beams and for systematic studies within the neutrino beam programme. In addition to experiments performed using beams recirculating within the ring, cooled beams can also be extracted and exploited by external spectrometers for high-precision measurements. The existing TSR, which is presently in operation at the Max-Planck Institute for Nuclear Physics in Heidelberg, is well-suited and can be employed for this purpose. The physics cases as well as technical details of the existing ring facility and of the beam and infrastructure requirements at HIE-ISOLDE are discussed in the present technical design report.
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| 6. |
- Grieser, M., et al.
(författare)
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Storage ring at HIE-ISOLDE Technical design report
- 2012
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Ingår i: The European Physical Journal Special Topics. - : Springer Science and Business Media LLC. - 1951-6355 .- 1951-6401. ; 207:1, s. 1-117
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Forskningsöversikt (refereegranskat)abstract
- We propose to install a storage ring at an ISOL-type radioactive beam facility for the first time. Specifically, we intend to setup the heavy-ion, low-energy ring TSR at the HIE-ISOLDE facility in CERN, Geneva. Such a facility will provide a capability for experiments with stored secondary beams that is unique in the world. The envisaged physics programme is rich and varied, spanning from investigations of nuclear ground-state properties and reaction studies of astrophysical relevance, to investigations with highly-charged ions and pure isomeric beams. The TSR might also be employed for removal of isobaric contaminants from stored ion beams and for systematic studies within the neutrino beam programme. In addition to experiments performed using beams recirculating within the ring, cooled beams can also be extracted and exploited by external spectrometers for high-precision measurements. The existing TSR, which is presently in operation at the Max-Planck Institute for Nuclear Physics in Heidelberg, is well-suited and can be employed for this purpose. The physics cases as well as technical details of the existing ring facility and of the beam and infrastructure requirements at HIE-ISOLDE are discussed in the present technical design report.
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| 8. |
- Gobel, K., et al.
(författare)
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Measurement of the Mo-92,Mo-93,Mo-94,Mo-100(gamma,n) reactions by Coulomb Dissociation
- 2016
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 665:1, s. art. no. 012034-
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Konferensbidrag (refereegranskat)abstract
- The Coulomb Dissociation (CD) cross sections of the stable isotopes Mo-92,Mo-94,Mo-100 and of the unstable isotope Mo-93 were measured at the LAND/(RB)-B-3 setup at GSI Helmholtzzentrum fur Schwerionenforschung in Darmstadt, Germany. Experimental data on these isotopes may help to explain the problem of the underproduction of Mo-92,Mo-94 and Ru-96,Ru-98 in the models of p-process nucleosynthesis. The CD cross sections obtained for the stable Mo isotopes are in good agreement with experiments performed with real photons, thus validating the method of Coulomb Dissociation. The result for the reaction Mo-93(gamma,n) is especially important since the corresponding cross section has not been measured before. A preliminary integral Coulomb Dissociation cross section of the Mo-94(gamma,n) reaction is presented. Further analysis will complete the experimental database for the (gamma,n) production chain of the p-isotopes of molybdenum.
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- Lazar, J., et al.
(författare)
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Human-computer interaction and international public policymaking : A framework for understanding and taking future actions
- 2015
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Ingår i: Foundations and Trends in Human-Computer Interaction. - : Now Publishers Inc.. - 1551-3955 .- 1551-3963. ; 9:2, s. 69-149
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Tidskriftsartikel (refereegranskat)abstract
- This monograph lays out a discussion framework for understanding the role of human-computer interaction (HCI) in public policymaking. We take an international view, discussing potential areas for research and application, and their potential for impact. Little has been written about the intersection of HCI and public policy; existing reports typically focus on one specific policy issue or incident. To date, there has been no overarching view of the areas of existing impact and potential impact. We have begun that analysis and argue here that such a global view is needed. Our aims are to provide a solid foundation for discussion, cooperation and collaborative interaction, and to outline future programs of activity. The five sections of this report provide relevant background along with a preliminary version of what we expect to be an evolving framework. Sections 1 and 2 provides an introduction to HCI and public policy. Section 3 discusses how HCI already informs public policy, with representative examples. Section 4 discusses how public policy influences HCI and provides representative public policy areas relevant to HCI, where HCI could have even more impact in the future: (i) laws, regulations, and guidelines for HCI research, (ii) HCI research assessments, (iii) research funding, (iv) laws for interface design - accessibility and language, (v) data privacy laws and regulations, (vi) intellectual property, and (vii) laws and regulations in specific sectors. There is a striking difference between where the HCI community has had impact (Section 3) and the many areas of potential involvement (Section 4). Section 5 a framework for action by the HCI community in public policy internationally. This monograph summarizes the observations and recommendations from a daylong workshop at the CHI 2013 conference in Paris, France. The workshop invited the community's perspectives regarding the intersection of governmental policies, international and domestic standards, recent HCI research discoveries, and emergent considerations and challenges. It also incorporates contributions made after the workshop by workshop participants and by individuals who were unable to participate in the workshop but whose work and interests were highly related and relevant.
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| 10. |
- Barretina, Jordi, et al.
(författare)
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Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy.
- 2010
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:8, s. 715-21
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Tidskriftsartikel (refereegranskat)abstract
- Soft-tissue sarcomas, which result in approximately 10,700 diagnoses and 3,800 deaths per year in the United States, show remarkable histologic diversity, with more than 50 recognized subtypes. However, knowledge of their genomic alterations is limited. We describe an integrative analysis of DNA sequence, copy number and mRNA expression in 207 samples encompassing seven major subtypes. Frequently mutated genes included TP53 (17% of pleomorphic liposarcomas), NF1 (10.5% of myxofibrosarcomas and 8% of pleomorphic liposarcomas) and PIK3CA (18% of myxoid/round-cell liposarcomas, or MRCs). PIK3CA mutations in MRCs were associated with Akt activation and poor clinical outcomes. In myxofibrosarcomas and pleomorphic liposarcomas, we found both point mutations and genomic deletions affecting the tumor suppressor NF1. Finally, we found that short hairpin RNA (shRNA)-based knockdown of several genes amplified in dedifferentiated liposarcoma, including CDK4 and YEATS4, decreased cell proliferation. Our study yields a detailed map of molecular alterations across diverse sarcoma subtypes and suggests potential subtype-specific targets for therapy.
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