| 1. |
- 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. |
- Drake, TM, et al.
(författare)
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Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
- 2020
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
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| 6. |
- Barausse, Enrico, et al.
(författare)
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Prospects for fundamental physics with LISA
- 2020
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Ingår i: General Relativity and Gravitation. - : SPRINGER/PLENUM PUBLISHERS. - 0001-7701 .- 1572-9532. ; 52:8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, which is of programmatic rather than quantitative nature, we aim to further delineate and sharpen the future potential of the LISA mission in the area of fundamental physics. Given the very broad range of topics that might be relevant to LISA,we present here a sample of what we view as particularly promising fundamental physics directions. We organize these directions through a "science-first" approach that allows us to classify how LISA data can inform theoretical physics in a variety of areas. For each of these theoretical physics classes, we identify the sources that are currently expected to provide the principal contribution to our knowledge, and the areas that need further development. The classification presented here should not be thought of as cast in stone, but rather as a fluid framework that is amenable to change with the flow of new insights in theoretical physics.
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| 7. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Aghanim, N., et al.
(författare)
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Planck 2018 results I. Overview and the cosmological legacy of Planck
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 641
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Tidskriftsartikel (refereegranskat)abstract
- The European Space Agency's Planck satellite, which was dedicated to studying the early Universe and its subsequent evolution, was launched on 14 May 2009. It scanned the microwave and submillimetre sky continuously between 12 August 2009 and 23 October 2013, producing deep, high-resolution, all-sky maps in nine frequency bands from 30 to 857 GHz. This paper presents the cosmological legacy of Planck, which currently provides our strongest constraints on the parameters of the standard cosmological model and some of the tightest limits available on deviations from that model. The 6-parameter Lambda CDM model continues to provide an excellent fit to the cosmic microwave background data at high and low redshift, describing the cosmological information in over a billion map pixels with just six parameters. With 18 peaks in the temperature and polarization angular power spectra constrained well, Planck measures five of the six parameters to better than 1% (simultaneously), with the best-determined parameter (theta (*)) now known to 0.03%. We describe the multi-component sky as seen by Planck, the success of the Lambda CDM model, and the connection to lower-redshift probes of structure formation. We also give a comprehensive summary of the major changes introduced in this 2018 release. The Planck data, alone and in combination with other probes, provide stringent constraints on our models of the early Universe and the large-scale structure within which all astrophysical objects form and evolve. We discuss some lessons learned from the Planck mission, and highlight areas ripe for further experimental advances.
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| 9. |
- Aghanim, N., et al.
(författare)
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Planck 2018 results VI. Cosmological parameters
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 641
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Tidskriftsartikel (refereegranskat)abstract
- We present cosmological parameter results from the final full-mission Planck measurements of the cosmic microwave background (CMB) anisotropies, combining information from the temperature and polarization maps and the lensing reconstruction. Compared to the 2015 results, improved measurements of large-scale polarization allow the reionization optical depth to be measured with higher precision, leading to significant gains in the precision of other correlated parameters. Improved modelling of the small-scale polarization leads to more robust constraints on many parameters, with residual modelling uncertainties estimated to affect them only at the 0.5 sigma level. We find good consistency with the standard spatially-flat 6-parameter Lambda CDM cosmology having a power-law spectrum of adiabatic scalar perturbations (denoted base Lambda CDM in this paper), from polarization, temperature, and lensing, separately and in combination. A combined analysis gives dark matter density Omega (c)h(2)=0.120 +/- 0.001, baryon density Omega (b)h(2)=0.0224 +/- 0.0001, scalar spectral index n(s)=0.965 +/- 0.004, and optical depth tau =0.054 +/- 0.007 (in this abstract we quote 68% confidence regions on measured parameters and 95% on upper limits). The angular acoustic scale is measured to 0.03% precision, with 100 theta (*)=1.0411 +/- 0.0003. These results are only weakly dependent on the cosmological model and remain stable, with somewhat increased errors, in many commonly considered extensions. Assuming the base-Lambda CDM cosmology, the inferred (model-dependent) late-Universe parameters are: Hubble constant H-0=(67.4 +/- 0.5) km s(-1) Mpc(-1); matter density parameter Omega (m)=0.315 +/- 0.007; and matter fluctuation amplitude sigma (8)=0.811 +/- 0.006. We find no compelling evidence for extensions to the base-Lambda CDM model. Combining with baryon acoustic oscillation (BAO) measurements (and considering single-parameter extensions) we constrain the effective extra relativistic degrees of freedom to be N-eff=2.99 +/- 0.17, in agreement with the Standard Model prediction N-eff=3.046, and find that the neutrino mass is tightly constrained to Sigma m(nu)< 0.12 eV. The CMB spectra continue to prefer higher lensing amplitudes than predicted in base CDM at over 2 sigma, which pulls some parameters that affect the lensing amplitude away from the Lambda CDM model; however, this is not supported by the lensing reconstruction or (in models that also change the background geometry) BAO data. The joint constraint with BAO measurements on spatial curvature is consistent with a flat universe, Omega (K)=0.001 +/- 0.002. Also combining with Type Ia supernovae (SNe), the dark-energy equation of state parameter is measured to be w(0)=-1.03 +/- 0.03, consistent with a cosmological constant. We find no evidence for deviations from a purely power-law primordial spectrum, and combining with data from BAO, BICEP2, and Keck Array data, we place a limit on the tensor-to-scalar ratio r(0.002)< 0.06. Standard big-bang nucleosynthesis predictions for the helium and deuterium abundances for the base-CDM cosmology are in excellent agreement with observations. The Planck base-Lambda CDM results are in good agreement with BAO, SNe, and some galaxy lensing observations, but in slight tension with the Dark Energy Survey's combined-probe results including galaxy clustering (which prefers lower fluctuation amplitudes or matter density parameters), and in significant, 3.6 sigma, tension with local measurements of the Hubble constant (which prefer a higher value). Simple model extensions that can partially resolve these tensions are not favoured by the Planck data.
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| 10. |
- Akrami, Y., et al.
(författare)
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Planck 2018 results II. Low Frequency Instrument data processing
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 641
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Tidskriftsartikel (refereegranskat)abstract
- We present a final description of the data-processing pipeline for the Planck Low Frequency Instrument (LFI), implemented for the 2018 data release. Several improvements have been made with respect to the previous release, especially in the calibration process and in the correction of instrumental features such as the effects of nonlinearity in the response of the analogue-to-digital converters. We provide a brief pedagogical introduction to the complete pipeline, as well as a detailed description of the important changes implemented. Self-consistency of the pipeline is demonstrated using dedicated simulations and null tests. We present the final version of the LFI full sky maps at 30, 44, and 70 GHz, both in temperature and polarization, together with a refined estimate of the solar dipole and a final assessment of the main LFI instrumental parameters.
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