| 1. |
- Kanai, M, et al.
(författare)
-
- 2023
-
swepub:Mat__t
|
|
| 2. |
- Campbell, PJ, et al.
(författare)
-
Pan-cancer analysis of whole genomes
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
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.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Mikkelsen, T N, et al.
(författare)
-
Experimental design of multifactor climate change experiments with elevated CO2, warming and drought: the CLIMAITE project
- 2008
-
Ingår i: Functional Ecology. - : Wiley. - 1365-2435 .- 0269-8463. ; 22:1, s. 185-195
-
Tidskriftsartikel (refereegranskat)abstract
- Recent findings indicate that the interactions among CO2, temperature and water can be substantial, and that the combined effects on the biological systems of several factors may not be predicted from experiments with one or a few factors. Therefore realistic multifactorial experiments involving a larger set of main factors are needed. We describe a new Danish climate change-related field scale experiment, CLIMAITE, in a heath/grassland ecosystem. CLIMAITE is a full factorial combination of elevated CO2, elevated temperature and prolonged summer drought. The manipulations are intended to mimic anticipated major environmental changes at the site by year 2075 as closely as possible. The impacts on ecosystem processes and functioning (at ecophysiological levels, through responses by individuals and communities to ecosystem-level responses) are investigated simultaneously. The increase of [CO2] closely corresponds with the scenarios for year 2075, while the warming treatment is at the lower end of the predictions and seems to be the most difficult treatment to increase without unwanted side effects on the other variables. The drought treatment follows predictions of increased frequency of drought periods in summer. The combination of the treatments does not create new unwanted side effects on the treatments relative to the treatments alone.
|
|
| 7. |
- Timotijevic, L., et al.
(författare)
-
Designing a research infrastructure (RI) on food behaviour and health : Balancing user needs, business model, governance mechanisms and technology
- 2021
-
Ingår i: Trends in Food Science & Technology. - : Elsevier Ltd. - 0924-2244 .- 1879-3053. ; 116, s. 405-414
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A better understanding of food-related behaviour and its determinants can be achieved through harmonisation and linking of the various data-sources and knowledge platforms. Scope: We describe the key decision-making in the development of a prototype of the Determinants and Intake Platform (DI Platform), a data platform that aims to harmonise and link data on consumer food behaviour. It will be part of the Food Nutrition Health Research Infrastructure (FNH-RI) that will facilitate health, social and food sciences. Approach: The decision-making was based on the evidence of user needs and data characteristics that guided the specification of the key building blocks of the DI Platform. Eight studies were carried out, including consumer online survey; interview studies of key DI Platform stakeholders; desk research and workshops. Key findings: Consumers were most willing to share data with universities, then industry and government. Trust, risk perception and altruism predicted willingness to share. For most other stakeholders non-proprietary data was most likely to be shared. Lack of data standards, and incentives for sharing were the main barriers for sharing data among the key stakeholders. The value of various data types would hugely increase if linked with other sources. Finding the right balance between optimizing data sharing and minimizing ethical and legal risks was considered a key challenge. Conclusions: The development of DI Platform is based on careful balancing of the user, technical, business, legal and ethical requirements, following the FAIR principles and the need for financial sustainability, technical flexibility, transparency and multi-layered organisational governance.
|
|
| 8. |
- Fowler, D., et al.
(författare)
-
Atmospheric composition change : Ecosystems-Atmosphere interactions
- 2009
-
Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 43:33, s. 5193-5267
-
Forskningsöversikt (refereegranskat)abstract
- Ecosystems and the atmosphere: This review describes the state of understanding the processes involved in the exchange of trace gases and aerosols between the earth's surface and the atmosphere. The gases covered include NO, NO2, HONO, HNO3, NH3, SO2, DMS, Biogenic VOC, O-3, CH4, N2O and particles in the size range 1 nm-10 mu m including organic and inorganic chemical species. The main focus of the review is on the exchange between terrestrial ecosystems, both managed and natural and the atmosphere, although some new developments in ocean-atmosphere exchange are included. The material presented is biased towards the last decade, but includes earlier work, where more recent developments are limited or absent. New methodologies and instrumentation have enabled, if not driven technical advances in measurement. These developments have advanced the process understanding and upscaling of fluxes, especially for particles, VOC and NH3. Examples of these applications include mass spectrometric methods, such as Aerosol Mass Spectrometry (AMS) adapted for field measurement of atmosphere-surface fluxes using micrometeorological methods for chemically resolved aerosols. Also briefly described are some advances in theory and techniques in micrometeorology. For some of the compounds there have been paradigm shifts in approach and application of both techniques and assessment. These include flux measurements over marine surfaces and urban areas using micrometeorological methods and the up-scaling of flux measurements using aircraft and satellite remote sensing. The application of a flux-based approach in assessment of O-3 effects on vegetation at regional scales is an important policy linked development secured through improved quantification of fluxes. The coupling of monitoring, modelling and intensive flux measurement at a continental scale within the NitroEurope network represents a quantum development in the application of research teams to address the underpinning science of reactive nitrogen in the cycling between ecosystems and the atmosphere in Europe. Some important developments of the science have been applied to assist in addressing policy questions, which have been the main driver of the research agenda, while other developments in understanding have not been applied to their wider field especially in chemistry-transport models through deficiencies in obtaining appropriate data to enable application or inertia within the modelling community. The paper identifies applications, gaps and research questions that have remained intractable at least since 2000 within the specialized sections of the paper, and where possible these have been focussed on research questions for the coming decade.
|
|
| 9. |
- Hartoog, O. E., et al.
(författare)
-
VLT/X-Shooter spectroscopy of the afterglow of the Swift GRB 130606A Chemical abundances and reionisation at z similar to 6
- 2015
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 580
-
Tidskriftsartikel (refereegranskat)abstract
- Context: The reionisation of the Universe is a process that is thought to have ended around z similar to 6, as inferred from spectroscopy of distant bright background sources, such as quasars (QSO) and gamma-ray burst (GRB) afterglows. Furthermore, spectroscopy of a GRB afterglow provides insight in its host galaxy, which is often too dim and distant to study otherwise.Aims: For the Swift GRB 130606A at z = 5.913 we have obtained a high S/N spectrum covering the full optical and near-IR wavelength region at intermediate spectral resolution with VLT/X-Shooter. We aim to measure the degree of ionisation of the intergalactic medium (IGM) between z = 5.02-5.84 and to study the chemical abundance pattern and dust content of its host galaxy.Methods: We estimated the UV continuum of the GRB afterglow using a power-law extrapolation, then measured the flux decrement due to absorption at Ly alpha,beta, and gamma wavelength regions. Furthermore, we fitted the shape of the red damping wing of Lya. The hydrogen and metal absorption lines formed in the host galaxy were fitted with Voigt profiles to obtain column densities. We investigated whether ionisation corrections needed to be applied.Results: Our measurements of the Ly alpha-forest optical depth are consistent with previous measurements of QSOs, but have a much smaller uncertainty. The analysis of the red damping wing yields a neutral fraction x(HI) < 0.05 (3 sigma). We obtain column density measurements of H, Al, Si, and Fe; for C, O, S and Ni we obtain limits. The ionisation due to the GRB is estimated to be negligible (corrections < 0.03 dex), but larger corrections may apply due to the pre-existing radiation field (up to 0.4 dex based on sub-DLA studies). Assuming that [Si/Fe] = +0.79 +/- 0.13 is due to dust depletion, the dust-to-metal ratio is similar to the Galactic value.Conclusions: Our measurements confirm that the Universe is already predominantly ionised over the redshift range probed in this work, but was slightly more neutral at z > 5.6. GRBs are useful probes of the ionisation state of the IGM in the early Universe, but because of internal scatter we need a larger statistical sample to draw robust conclusions. The high [Si/Fe] in the host can be due to dust depletion, a-element enhancement, or a combination of both. The very high value of [Al/Fe] = 2.40 +/- 0.78 might be due to a proton capture process and is probably connected to the stellar population history. We estimate the host metallicity to be -1.7 < [M/H] < -0.9 (2%-13% of solar).
|
|
| 10. |
- Leiva, R. A., et al.
(författare)
-
High real-world effectiveness of 12-week elbasvir/grazoprevir without resistance testing in the treatment of patients with HCV genotype 1a infection in Norway
- 2023
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 58:3, s. 264-268
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The recommended treatment duration of hepatitis C virus (HCV) genotype 1a (GT1a) infection with elbasvir/grazoprevir (EBR/GZR) in the presence of a high baseline viral load and resistance associated substitutions (RAS) is 16 weeks with ribavirin added. The objective of this study was to evaluate the real-world effectiveness of 12 weeks of EBR/GZR without ribavirin and regardless of baseline viral load and RAS testing. Method: This retrospective, observational cohort study was performed at five Norwegian hospitals that did not systematically utilize RAS testing. All adult patients with chronic HCV GT1a and compensated liver disease who had received 12 weeks of EBR/GZR without ribavirin and baseline RAS testing, were included. The primary endpoint was sustained virologic response at week 12 (SVR12), or if not available, at week 4 (SVR4). Results: We included 433 patients and attained SVR data on 388. The mean age was 45.7 years (22–73 years). 67.2% were male. HIV co-infection was present in 3.8% (16/424) and cirrhosis in 4% (17/424). The viral load was >800 000 IU/mL in 55.0% (235/427) of patients. Overall SVR was achieved in 97.2% (377/388). SVR was achieved in 98.3% (169/172) of those with viral load ≤800 000 IU/mL and in 96.2% (202/210) of those with viral load >800 000 IU/mL. Conclusion: We observed high SVR rates among patients with HCV GT1a infection treated with EBR/GZR for 12 weeks without ribavirin, with no regard to baseline viral load and no RAS testing. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
|
|
