| 1. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Bravo, L, 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. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 5. |
- Delios, A., et al.
(författare)
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Examining the generalizability of research findings from archival data
- 2022
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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. - 0027-8424 .- 1091-6490. ; 119:30
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Tidskriftsartikel (refereegranskat)abstract
- This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability-for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples.
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| 6. |
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| 7. |
- Stacchiotti, S., et al.
(författare)
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Epithelioid hemangioendothelioma, an ultra-rare cancer : a consensus paper from the community of experts
- 2021
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 6:3
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Forskningsöversikt (refereegranskat)abstract
- Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.
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| 8. |
- Ortega, FB, et al.
(författare)
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European fitness landscape for children and adolescents: updated reference values, fitness maps and country rankings based on nearly 8 million test results from 34 countries gathered by the FitBack network
- 2023
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Ingår i: British journal of sports medicine. - : BMJ. - 1473-0480 .- 0306-3674. ; 57:5, s. 299-
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Tidskriftsartikel (refereegranskat)abstract
- (1) To develop reference values for health-related fitness in European children and adolescents aged 6–18 years that are the foundation for the web-based, open-access and multilanguage fitness platform (FitBack); (2) to provide comparisons across European countries.MethodsThis study builds on a previous large fitness reference study in European youth by (1) widening the age demographic, (2) identifying the most recent and representative country-level data and (3) including national data from existing fitness surveillance and monitoring systems. We used the Assessing Levels of PHysical Activity and fitness at population level (ALPHA) test battery as it comprises tests with the highest test–retest reliability, criterion/construct validity and health-related predictive validity: the 20 m shuttle run (cardiorespiratory fitness); handgrip strength and standing long jump (muscular strength); and body height, body mass, body mass index and waist circumference (anthropometry). Percentile values were obtained using the generalised additive models for location, scale and shape method.ResultsA total of 7 966 693 test results from 34 countries (106 datasets) were used to develop sex-specific and age-specific percentile values. In addition, country-level rankings based on mean percentiles are provided for each fitness test, as well as an overall fitness ranking. Finally, an interactive fitness platform, including individual and group reporting and European fitness maps, is provided and freely available online (www.fitbackeurope.eu).ConclusionThis study discusses the major implications of fitness assessment in youth from health, educational and sport perspectives, and how the FitBack reference values and interactive web-based platform contribute to it. Fitness testing can be conducted in school and/or sport settings, and the interpreted results be integrated in the healthcare systems across Europe.
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| 9. |
- Rheinbay, E, et al.
(författare)
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Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 102-
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of drivers of cancer has traditionally focused on protein-coding genes1–4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53, in the 3′ untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
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| 10. |
- Carlevaro-Fita, J, et al.
(författare)
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Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis
- 2020
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 56-
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Tidskriftsartikel (refereegranskat)abstract
- Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis.
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| 11. |
- Goetz, Charlotte, et al.
(författare)
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The plasma environment of comet 67P/Churyumov-Gerasimenko
- 2022
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Ingår i: Space Science Reviews. - : Springer. - 0038-6308 .- 1572-9672. ; 218:8
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Forskningsöversikt (refereegranskat)abstract
- The environment of a comet is a fascinating and unique laboratory to study plasma processes and the formation of structures such as shocks and discontinuities from electron scales to ion scales and above. The European Space Agency's Rosetta mission collected data for more than two years, from the rendezvous with comet 67P/Churyumov-Gerasimenko in August 2014 until the final touch-down of the spacecraft end of September 2016. This escort phase spanned a large arc of the comet's orbit around the Sun, including its perihelion and corresponding to heliocentric distances between 3.8 AU and 1.24 AU. The length of the active mission together with this span in heliocentric and cometocentric distances make the Rosetta data set unique and much richer than sets obtained with previous cometary probes. Here, we review the results from the Rosetta mission that pertain to the plasma environment. We detail all known sources and losses of the plasma and typical processes within it. The findings from in-situ plasma measurements are complemented by remote observations of emissions from the plasma. Overviews of the methods and instruments used in the study are given as well as a short review of the Rosetta mission. The long duration of the Rosetta mission provides the opportunity to better understand how the importance of these processes changes depending on parameters like the outgassing rate and the solar wind conditions. We discuss how the shape and existence of large scale structures depend on these parameters and how the plasma within different regions of the plasma environment can be characterised. We end with a non-exhaustive list of still open questions, as well as suggestions on how to answer them in the future.
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| 12. |
- Léget, P-F, et al.
(författare)
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SUGAR : An improved empirical model of Type Ia supernovae based on spectral features
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 636
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Tidskriftsartikel (refereegranskat)abstract
- Context. Type Ia supernovae (SNe Ia) are widely used to measure the expansion of the Universe. Improving distance measurements of SNe Ia is one technique to better constrain the acceleration of expansion and determine its physical nature.Aims. This document develops a new SNe Ia spectral energy distribution (SED) model, called the SUpernova Generator And Reconstructor (SUGAR), which improves the spectral description of SNe Ia, and consequently could improve the distance measurements.Methods. This model was constructed from SNe Ia spectral properties and spectrophotometric data from the Nearby Supernova Factory collaboration. In a first step, a principal component analysis-like method was used on spectral features measured at maximum light, which allowed us to extract the intrinsic properties of SNe Ia. Next, the intrinsic properties were used to extract the average extinction curve. Third, an interpolation using Gaussian processes facilitated using data taken at different epochs during the lifetime of an SN Ia and then projecting the data on a fixed time grid. Finally, the three steps were combined to build the SED model as a function of time and wavelength. This is the SUGAR model.Results. The main advancement in SUGAR is the addition of two additional parameters to characterize SNe Ia variability. The first is tied to the properties of SNe Ia ejecta velocity and the second correlates with their calcium lines. The addition of these parameters, as well as the high quality of the Nearby Supernova Factory data, makes SUGAR an accurate and efficient model for describing the spectra of normal SNe Ia as they brighten and fade.Conclusions. The performance of this model makes it an excellent SED model for experiments like the Zwicky Transient Facility, the Large Synoptic Survey Telescope, or the Wide Field Infrared Survey Telescope.
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| 13. |
- Maggiolo, R., et al.
(författare)
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The Effect of Cosmic Rays on Cometary Nuclei. II. Impact on Ice Composition and Structure
- 2020
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Ingår i: Astrophysical Journal. - : IOP PUBLISHING LTD. - 0004-637X .- 1538-4357. ; 901:2
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Tidskriftsartikel (refereegranskat)abstract
- Since their formation in the protosolar nebula some similar to 4.5 billion years ago, comets are in storage in cold distant regions of the solar system, the Kuiper Belt/scattered disk or Oort Cloud. Therefore, they have been considered as mostly unaltered samples of the protosolar nebula. However, a significant dose of energy is deposited by galactic cosmic rays (GCRs) into the outermost tens of meters of cometary nuclei during their stay in the Oort Cloud or Kuiper Belt. We investigate the impact of energy deposition by GCRs on cometary nuclei. We use experimental results from laboratory experiments and the energy deposition by GCRs estimated by Gronoff et al. (2020), to discuss the depth down to which the cometary nucleus is altered by GCRs. We show that GCRs do not significantly change the isotopic composition of cometary material but modify the chemical composition and the ice structure in the outer layers of the nucleus, which cannot be considered as pristine solar nebula material. We discuss the effect of the collisional history of comets on the distribution of processed material inside the nucleus and its implication on the observation of comets.
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| 14. |
- Rigault, M., et al.
(författare)
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Strong dependence of Type Ia supernova standardization on the local specific star formation rate
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 644
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Tidskriftsartikel (refereegranskat)abstract
- As part of an on-going effort to identify, understand and correct for astrophysics biases in the standardization of Type Ia supernovae (SN Ia) for cosmology, we have statistically classified a large sample of nearby SNe Ia into those that are located in predominantly younger or older environments. This classification is based on the specific star formation rate measured within a projected distance of 1 kpc from each SN location (LsSFR). This is an important refinement compared to using the local star formation rate directly, as it provides a normalization for relative numbers of available SN progenitors and is more robust against extinction by dust. We find that the SNe Ia in predominantly younger environments are ΔY = 0.163 ± 0.029 mag (5.7σ) fainter than those in predominantly older environments after conventional light-curve standardization. This is the strongest standardized SN Ia brightness systematic connected to the host-galaxy environment measured to date. The well-established step in standardized brightnesses between SNe Ia in hosts with lower or higher total stellar masses is smaller, at ΔM = 0.119 ± 0.032 mag (4.5σ), for the same set of SNe Ia. When fit simultaneously, the environment-age offset remains very significant, with ΔY = 0.129 ± 0.032 mag (4.0σ), while the global stellar mass step is reduced to ΔM = 0.064 ± 0.029 mag (2.2σ). Thus, approximately 70% of the variance from the stellar mass step is due to an underlying dependence on environment-based progenitor age. Also, we verify that using the local star formation rate alone is not as powerful as LsSFR at sorting SNe Ia into brighter and fainter subsets. Standardization that only uses the SNe Ia in younger environments reduces the total dispersion from 0.142 ± 0.008 mag to 0.120 ± 0.010 mag. We show that as environment-ages evolve with redshift, a strong bias, especially on the measurement of the derivative of the dark energy equation of state, can develop. Fortunately, data that measure and correct for this effect using our local specific star formation rate indicator, are likely to be available for many next-generation SN Ia cosmology experiments.
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| 15. |
- Tartaglia, Leonardo, et al.
(författare)
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The long-lived Type IIn SN 2015da : Infrared echoes and strong interaction within an extended massive shell star star star
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 635
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we report the results of the first similar to four years of spectroscopic and photometric monitoring of the Type IIn supernova SN 2015da (also known as PSN J13522411+3941286, or iPTF16tu). The supernova exploded in the nearby spiral galaxy NGC 5337 in a relatively highly extinguished environment. The transient showed prominent narrow Balmer lines in emission at all times and a slow rise to maximum in all bands. In addition, early observations performed by amateur astronomers give a very well-constrained explosion epoch. The observables are consistent with continuous interaction between the supernova ejecta and a dense and extended H-rich circumstellar medium. The presence of such an extended and dense medium is difficult to reconcile with standard stellar evolution models, since the metallicity at the position of SN 2015da seems to be slightly subsolar. Interaction is likely the mechanism powering the light curve, as confirmed by the analysis of the pseudo bolometric light curve, which gives a total radiated energy greater than or similar to 10(51) erg. Modeling the light curve in the context of a supernova shock breakout through a dense circumstellar medium allowed us to infer the mass of the prexisting gas to be similar or equal to 8 M-circle dot, with an extreme mass-loss rate for the progenitor star similar or equal to 0.6 M-circle dot yr(-1), suggesting that most of the circumstellar gas was produced during multiple eruptive events. Near- and mid-infrared observations reveal a fluxexcess in these domains, similar to those observed in SN 2010jl and other interacting transients, likely due to preexisting radiatively heated dust surrounding the supernova. By modeling the infrared excess, we infer a mass greater than or similar to 0.4 x 10(-3) M-circle dot for the dust.
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| 16. |
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The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
- 2022
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Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
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Tidskriftsartikel (refereegranskat)abstract
- This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
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| 17. |
- Thrane, Kim, et al.
(författare)
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Single-Cell and Spatial Transcriptomic Analysis of Human Skin Delineates Intercellular Communication and Pathogenic Cells
- 2023
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 143:11, s. 13-2177
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Tidskriftsartikel (refereegranskat)abstract
- Epidermal homeostasis is governed by a balance between keratinocyte proliferation and differentiation with contributions from cell–cell interactions, but conserved or divergent mechanisms governing this equilibrium across species and how an imbalance contributes to skin disease are largely undefined. To address these questions, human skin single-cell RNA sequencing and spatial transcriptomics data were integrated and compared with mouse skin data. Human skin cell–type annotation was improved using matched spatial transcriptomics data, highlighting the importance of spatial context in cell-type identity, and spatial transcriptomics refined cellular communication inference. In cross-species analyses, we identified a human spinous keratinocyte subpopulation that exhibited proliferative capacity and a heavy metal processing signature, which was absent in mouse and may account for species differences in epidermal thickness. This human subpopulation was expanded in psoriasis and zinc-deficiency dermatitis, attesting to disease relevance and suggesting a paradigm of subpopulation dysfunction as a hallmark of the disease. To assess additional potential subpopulation drivers of skin diseases, we performed cell-of-origin enrichment analysis within genodermatoses, nominating pathogenic cell subpopulations and their communication pathways, which highlighted multiple potential therapeutic targets. This integrated dataset is encompassed in a publicly available web resource to aid mechanistic and translational studies of normal and diseased skin.
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| 18. |
- Caron, Bénédicte, et al.
(författare)
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IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis : the PROCTRIAL Consensus
- 2022
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 20:11, s. 2169-2627.e1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the PROCTRIAL (Definition and endpoints for ulcerative PROCtitis in clinical TRIALs) initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults.METHODS: Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters.RESULTS: The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity is proposed. Secondary endpoints which should be evaluated include endoscopic remission, histological remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life.CONCLUSION: In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the PROCTRIAL consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials.
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| 19. |
- Enbody, Erik D., et al.
(författare)
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A multispecies BCO2 beak color polymorphism in the Darwin's finch radiation
- 2021
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Ingår i: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 31:24, s. 5597-5604.e7
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Tidskriftsartikel (refereegranskat)abstract
- Carotenoid-based polymorphisms are widespread in populations of birds, fish, and reptiles,(1) but generally little is known about the factors affecting their maintenance in populations.(2) We report a combined field and molecular-genetic investigation of a nestling beak color polymorphism in Darwin's finches. Beaks are pink or yellow, and yellow is recessive.(3) Here we show that the polymorphism arose in the Galapagos half a million years ago through a mutation associated with regulatory change in the BCO2 gene and is shared by 14 descendant species. The polymorphism is probably a balanced polymorphism, maintained by ecolog- ical selection associated with survival and diet. In cactus finches, the frequency of the yellow genotype is correlated with cactus fruit abundance and greater hatching success and may be altered by introgressive hybridization. Polymorphisms that are hidden as adults, as here, may be far more common than is currently recognized, and contribute to diversification in ways that are yet to be discovered.
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| 20. |
- Galand, M., et al.
(författare)
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Far-ultraviolet aurora identified at comet 67P/Churyumov-Gerasimenko
- 2020
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Ingår i: Nature Astronomy. - : NATURE RESEARCH. - 2397-3366. ; 4:11, s. 1084-1091
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Tidskriftsartikel (refereegranskat)abstract
- In situ measurements from the Rosetta spacecraft reveal the presence of atomic emissions close to comet 67P's nucleus. Such emissions are due to dissociative excitation of molecules by the interaction with the solar wind, identifying them as a form of aurora. Having a nucleus darker than charcoal, comets are usually detected from Earth through the emissions from their coma. The coma is an envelope of gas that forms through the sublimation of ices from the nucleus as the comet gets closer to the Sun. In the far-ultraviolet portion of the spectrum, observations of comae have revealed the presence of atomic hydrogen and oxygen emissions. When observed over large spatial scales as seen from Earth, such emissions are dominated by resonance fluorescence pumped by solar radiation. Here, we analyse atomic emissions acquired close to the cometary nucleus by the Rosetta spacecraft and reveal their auroral nature. To identify their origin, we undertake a quantitative multi-instrument analysis of these emissions by combining coincident neutral gas, electron and far-ultraviolet observations. We establish that the atomic emissions detected from Rosetta around comet 67P/Churyumov-Gerasimenko at large heliocentric distances result from the dissociative excitation of cometary molecules by accelerated solar-wind electrons (and not by electrons produced from photo-ionization of cometary molecules). Like the discrete aurorae at Earth and Mars, this cometary aurora is driven by the interaction of the solar wind with the local environment. We also highlight how the oxygen line Oiat wavelength 1,356 A could be used as a tracer of solar-wind electron variability.
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| 21. |
- Geneid, A., et al.
(författare)
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Union of the European Phoniatricians position statement on the exit strategy of phoniatric and laryngological services: staying safe and getting back to normal after the peak of coronavirus disease 2019 (issued on 25th May 2020)
- 2020
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Ingår i: Journal of Laryngology and Otology. - : CAMBRIDGE UNIV PRESS. - 0022-2151 .- 1748-5460. ; 134:8, s. 661-664
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Tidskriftsartikel (refereegranskat)abstract
- Background The following position statement from the Union of the European Phoniatricians, updated on 25th May 2020 (superseding the previous statement issued on 21st April 2020), contains a series of recommendations for phoniatricians and ENT surgeons who provide and/or run voice, swallowing, speech and language, or paediatric audiology services. Objectives This material specifically aims to inform clinical practices in countries where clinics and operating theatres are reopening for elective work. It endeavours to present a current European view in relation to common procedures, many of which fall under the aegis of aerosol generating procedures. Conclusion As evidence continues to build, some of the recommended practices will undoubtedly evolve, but it is hoped that the updated position statement will offer clinicians precepts on safe clinical practice.
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| 22. |
- Gilet, N., et al.
(författare)
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Observations of a mix of cold and warm electrons by RPC-MIP at 67P/Churyumov-Gerasimenko
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 640
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Tidskriftsartikel (refereegranskat)abstract
- Context. The Mutual Impedance Probe (MIP) of the Rosetta Plasma Consortium (RPC) onboard the Rosetta orbiter which was in operation for more than two years, between August 2014 and September 2016 to monitor the electron density in the cometary ionosphere of 67P/Churyumov-Gerasimenko. Based on the resonance principle of the plasma eigenmodes, recent models of the mutual impedance experiment have shown that in a two-electron temperature plasma, such an instrument is able to separate the two isotropic electron populations and retrieve their properties.Aims. The goal of this paper is to identify and characterize regions of the cometary ionized environment filled with a mix of cold and warm electron populations, which was observed by Rosetta during the cometary operation phase.Methods. To reach this goal, this study identifies and investigates the in situ mutual impedance spectra dataset of the RPC-MIP instrument that contains the characteristics of a mix of cold and warm electrons, with a special focus on instrumental signatures typical of large cold-to-total electron density ratio (from 60 to 90%), that is, regions strongly dominated by the cold electron component.Results. We show from the observational signatures that the mix of cold and warm cometary electrons strongly depends on the cometary latitude. Indeed, in the southern hemisphere of 67P, where the neutral outgassing activity was higher than in northern hemisphere during post-perihelion, the cold electrons were more abundant, confirming the role of electron-neutral collisions in the cooling of cometary electrons. We also show that the cold electrons are mainly observed outside the nominal electron-neutral collision-dominated region (exobase), where electrons are expected to have cooled down. This which indicates that the cold electrons have been transported outward. Finally, RPC-MIP detected cold electrons far from the perihelion, where the neutral outgassing activity is lower, in regions where no electron exobase was expected to have formed. This suggests that the cometary neutrals provide a more frequent or efficient cooling of the electrons than expected for a radially expanding ionosphere.
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| 23. |
- Hochman, Assaf, et al.
(författare)
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Extreme weather and societal impacts in the eastern Mediterranean
- 2022
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Ingår i: Earth System Dynamics. - : Copernicus GmbH. - 2190-4979 .- 2190-4987. ; 13:2, s. 749-777
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Forskningsöversikt (refereegranskat)abstract
- Gaining a holistic understanding of extreme weather, from its physical drivers to its impacts on society and ecosystems, is key to supporting future risk reduction and preparedness measures. Here, we provide an overview of the state of the art, knowledge gaps and key open questions in the study of extreme weather events over the vulnerable eastern Mediterranean. This region is situated in a transition zone between subtropical and mid-latitude climates. The large-scale atmospheric circulation and its interaction with regional synoptic systems (i.e., Cyprus Lows, Red Sea Troughs, Persian Troughs, “Sharav” Lows) and high-pressure systems mainly govern extreme weather. Complex orographic features further play an important role in the generation of extreme weather. Most extreme weather events, including heavy precipitation, cold spells, floods and windstorms, are associated with Cyprus Lows or active Red Sea Troughs, whereas heat waves are related with either Persian Troughs and sub-tropical high-pressure systems in summer or the Sharav Low during springtime. In future decades, heat waves and droughts are projected to significantly increase in both frequency and intensity. Changes in heavy precipitation may vary in sign and magnitude depending on the scale, severity and region of interest. There are still relatively large uncertainties concerning the physical understanding and the projected changes of cold spells, windstorms and compound extremes, as these types of events received comparatively little attention in the literature. We further identify knowledge gaps that relate to the societal impacts of extreme weather. These gaps mainly relate to the effects extreme weather may have on mortality, morbidity and infrastructure in the eastern Mediterranean. Research is currently limited in this context, and we recommend strengthening the database of analyzed case studies. We trust that this can only be suitably accomplished by inter-disciplinary and international regional collaboration (in spite of political unrest).
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| 24. |
- Hommerding, O, et al.
(författare)
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[Molecular pathology of urogenital tumors : Recommendations from the 2019 International Society of Urological Pathology (ISUP) Consensus Conference]
- 2021
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Ingår i: Der Pathologe. - : Springer Science and Business Media LLC. - 1432-1963 .- 0172-8113. ; 42:3, s. 310-318
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Tidskriftsartikel (refereegranskat)abstract
- Das zunehmende Verständnis molekularer Grundlagen von Tumoren sowie der Fortschritt in der Diversifizierung der onkologischen Therapien versprechen individualisierte Therapieoptionen, welche bislang jedoch nur ansatzweise in die Therapieplanung von urologischen Tumoren eingegangen sind. Daher hat die Internationale Gesellschaft für Urologische Pathologie (ISUP) im März 2019 eine Konsenskonferenz zur Erarbeitung evidenzbasierter Handlungsempfehlungen zur molekularpathologischen Diagnostik beim Urothelkarzinom, Nierenzellkarzinom, Prostatakarzinom, Peniskarzinom und testikulären Keimzelltumoren durchgeführt. Die auf dieser Konsenskonferenz erarbeiteten Empfehlungen sind kürzlich in 5 separaten Manuskripten veröffentlich worden und werden in der vorliegenden Arbeit zusammengefasst.Im Rahmen der Konferenzvorbereitung wurde eine umfassende Umfrage zur derzeitigen Praxis molekularer Testungen bei urogenitalen Tumoren unter den Mitgliedern der ISUP durchgeführt. Auf der Konferenz wurden die Ergebnisse und die entsprechenden Hintergrundinformationen durch 5 Arbeitsgruppen präsentiert und Handlungsempfehlungen für die Diagnostik erarbeitet. Eine Übereinstimmung von 66 % der Konferenzteilnehmer wurde als Konsens definiert.
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| 25. |
- Ji, Andrew L., et al.
(författare)
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Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma
- 2020
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Ingår i: Cell. - : Cell Press. - 0092-8674 .- 1097-4172. ; 182:2, s. 497-
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Tidskriftsartikel (refereegranskat)abstract
- To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), we combined single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging from a series of human cSCCs and matched normal skin. cSCC exhibited four tumor subpopulations, three recapitulating normal epidermal states, and a tumor-specific keratinocyte (TSK) population unique to cancer, which localized to a fibrovascular niche. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing TSK cells as a hub for intercellular communication. Multiple features of potential immunosuppression were observed, including T regulatory cell (Treg) co-localization with CD8 T cells in compartmentalized tumor stroma. Finally, single-cell characterization of human tumor xenografts and in vivo CRISPR screens identified essential roles for specific tumor subpopulation-enriched gene networks in tumorigenesis. These data define cSCC tumor and stromal cell subpopulations, the spatial niches where they interact, and the communicating gene networks that they engage in cancer.
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| 26. |
- Lang, Justin J., et al.
(författare)
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Top 10 International Priorities for Physical Fitness Research and Surveillance Among Children and Adolescents : A Twin-Panel Delphi Study
- 2023
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Ingår i: Sports Medicine. - New Zealand : Adis International Ltd.. - 0112-1642 .- 1179-2035. ; 53:2, s. 549-564
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Tidskriftsartikel (refereegranskat)abstract
- Background The measurement of physical fitness has a history that dates back nearly 200 years. Recently, there has been an increase in international research and surveillance on physical fitness creating a need for setting international priorities that could help guide future efforts. Objective This study aimed to produce a list of the top 10 international priorities for research and surveillance on physical fitness among children and adolescents. Methods Using a twin-panel Delphi method, two independent panels consisting of 46 international experts were identified (panel 1 = 28, panel 2 = 18). The panel participants were asked to list up to five priorities for research or surveillance (round 1), and then rated the items from their own panel on a 5-point Likert scale of importance (round 2). In round 3, experts were asked to rate the priorities identified by the other panel. Results There was strong between-panel agreement (panel 1: r(s) = 0.76, p < 0.01; panel 2: r(s) = 0.77, p < 0.01) in the priorities identified. The list of the final top 10 priorities included (i) "conduct longitudinal studies to assess changes in fitness and associations with health". This was followed by (ii) "use fitness surveillance to inform decision making", and (iii) "implement regular and consistent international/national fitness surveys using common measures". Conclusions The priorities identified in this study provide guidance for future international collaborations and research efforts on the physical fitness of children and adolescents over the next decade and beyond.
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| 27. |
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| 28. |
- Rafati, Nima, et al.
(författare)
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Reconstruction of the birth of a male sex chromosome present in Atlantic herring
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy Of Sciences. - 0027-8424 .- 1091-6490. ; 117:39, s. 24359-24368
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms underlying sex determination are astonishingly plastic. Particularly the triggers for the molecular machinery, which recalls either the male or female developmental program, are highly variable and have evolved independently and repeatedly. Fish show a huge variety of sex determination systems, including both genetic and environmental triggers. The advent of sex chromosomes is assumed to stabilize genetic sex determination. However, because sex chromosomes are notoriously cluttered with repetitive DNA and pseudogenes, the study of their evolution is hampered. Here we reconstruct the birth of a Y chromosome present in the Atlantic herring. The region is tiny (230 kb) and contains only three intact genes. The candidate male-determining gene BMPR1BBY encodes a truncated form of a BMP1B receptor, which originated by gene duplication and translocation and underwent rapid protein evolution. BMPR1BBY phosphorylates SMADs in the absence of ligand and thus has the potential to induce testis formation. The Y region also contains two genes encoding subunits of the sperm-specific Ca2+ channel CatSper required for male fertility. The herring Y chromosome conforms with a characteristic feature of many sex chromosomes, namely, suppressed recombination between a sex-determining factor and genes that are beneficial for the given sex. However, the herring Y differs from other sex chromosomes in that suppression of recombination is restricted to an ∼500-kb region harboring the male-specific and sex-associated regions. As a consequence, any degeneration on the herring Y chromosome is restricted to those genes located in the small region affected by suppressed recombination.
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| 29. |
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| 30. |
- Reyna, Matthew A, et al.
(författare)
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Pathway and network analysis of more than 2500 whole cancer genomes
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
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| 31. |
- Rubin, O, et al.
(författare)
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The COVID-19 quandemic
- 2024
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Ingår i: Globalization and health. - 1744-8603. ; 20:1, s. 19-
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Tidskriftsartikel (refereegranskat)
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| 32. |
- Rubin, T., et al.
(författare)
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'Quantum-based realizations of the pascal' status and progress of the empir-project: quantumpascal
- 2022
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Ingår i: 6th TC16 Conference on Pressure and Vacuum Measurement 2022, Together with the 24th TC3 Conference on the Measurement of Force, Mass and Torque, the 14th TC5 Conference on the Measurement of Hardness, and the 5th TC22 Conference on Vibration Measurement. - : International Measurement Confederation (IMEKO). - 9781713870227
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Konferensbidrag (refereegranskat)abstract
- The QuantumPascal (QP) project combines the capabilities of 12 European institutions to enable traceable pressure measurements utilizing quantum-based methods that evaluate the number density instead of force per area to target the wide pressure range between 1 Pa and 3 MPa. This article summarizes the goals and results since the project start in June 2019.
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| 33. |
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| 34. |
- Vitelli-Storelli, F, et al.
(författare)
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Family History and Gastric Cancer Risk: A Pooled Investigation in the Stomach Cancer Pooling (STOP) Project Consortium
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:15
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Tidskriftsartikel (refereegranskat)abstract
- Although there is a clear relationship between family history (FH) and the risk of gastric cancer (GC), quantification is still needed in relation to different histological types and anatomical sites, and in strata of covariates. The objective was to analyze the risk of GC according to first-degree FH in a uniquely large epidemiological consortium of GC. This investigation includes 5946 cases and 12,776 controls from 17 studies of the Stomach Cancer Pooling (StoP) Project consortium. Summary odds ratios (OR) and the corresponding 95% confidence intervals (CIs) were calculated by pooling study-specific ORs using fixed-effect model meta-analysis techniques. Stratified analyses were carried out by sex, age, tumor location and histological type, smoking habit, socioeconomic status, alcohol intake and fruit consumption. The pooled OR for GC was 1.84 (95% CI: 1.64–2.04; I2 = 6.1%, P heterogeneity = 0.383) in subjects with vs. those without first-degree relatives with GC. No significant differences were observed among subgroups of sex, age, geographic area or study period. Associations tended to be stronger for non-cardia (OR = 1.82; 95% CI: 1.59–2.05 for subjects with FH) than for cardia GC (OR = 1.38; 95% CI: 0.98–1.77), and for the intestinal (OR = 1.92; 95% CI: 1.62–2.23) than for the diffuse histotype (OR = 1.62; 95% CI: 1.28–1.96). This analysis confirms the effect of FH on the risk of GC, reporting an approximately doubled risk, and provides further quantification of the risk of GC according to the subsite and histotype. Considering these findings, accounting for the presence of FH to carry out correct prevention and diagnosis measures is of the utmost importance.
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| 35. |
- Williams, S. C., et al.
(författare)
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See Change : VLT spectroscopy of a sample of high-redshift Type Ia supernova host galaxies
- 2020
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 495:4, s. 3859-3880
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Tidskriftsartikel (refereegranskat)abstract
- The Supernova Cosmology Project has conducted the 'See Change' programme, aimed at discovering and observing high-redshift (1.13 <= z <= 1.75) Type Ia supernovae (SNe Ia). We used multifilter Hubble Space Telescope (HST) observations of massive galaxy clusters with sufficient cadence to make the observed SN Ia light curves suitable for a cosmological probe of dark energy at z > 0.5. This See Change sample of SNe Ia with multi-colour light curves will be the largest to date at these redshifts. As part of the See Change programme, we obtained ground-based spectroscopy of each discovered transient and/or its host galaxy. Here, we present Very Large Telescope (VCT) spectra of See Change transient host galaxies, deriving their redshifts, and host parameters such as stellar mass and star formation rate. Of the 39 See Change transients/hosts that were observed with the VLT, we successfully determined the redshift for 26, including 15 SNe Ia at z > 0.97. We show that even in passive environments, it is possible to recover secure redshifts for the majority of SN hosts out to z = 1.5. We find that with typical exposure times of 3-4h on an 8-m-class telescope we can recover similar to 75 per cent of SN Ia redshifts in the range of 0.97 < z < 1.5. Furthermore, we show that the combination of HST photometry and VLT spectroscopy is able to provide estimates of host galaxy stellar mass that are sufficiently accurate for use in a mass-step correction in the cosmological analysis.
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