| 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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| 4. |
- Frago, Enric, et al.
(författare)
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Common pheromone use among host-associated populations of the browntail moth, euproctis chrysorrhoea, displaying different adult phenologies
- 2019
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Ingår i: Entomologia Generalis. - : Schweizerbart. - 0171-8177. ; 39:3-4, s. 295-306
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Tidskriftsartikel (refereegranskat)abstract
- The diversity of herbivorous insects may arise from colonization and subsequent specialization on different host plants. Such specialization requires changes in several insect traits, which may lead to host race formation if they reduce gene flow among populations that feed on different plants. Behavioural changes may play a relevant role in host race formation, for example if different races evolve distinct sexual communication signals or adult phenology. Previous research has revealed differences in larval phenology in different host-associated populations of the browntail moth, Euproctis chrysorrhoea (Lepidoptera: Erebidae). Here, sex pheromones among populations of this species are compared, and pheromone trapping data obtained is used in the field to build a phenological model that tests whether populations that feed on different plants differ in their adult flight period. The chemical and electrophysiological analyses revealed that two E. chrysorrhoea populations (on Prunus and on Arbutus unedo) use the same sex pheromone component for mate finding. Our trapping data, however, showed that males fly on average 25 days earlier in populations whose larvae feed on A. unedo compared to those whose larvae feed on Quercus species. Although the shifted phenology described here may underlie host-plant specialization in E. chrysorrhoea, and adults of this species are short-lived, the use of a common sexual pheromone and a large overlap in flight periods suggest that host race formation via allochronic isolation is unlikely in this moth.
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| 5. |
- Ahola, T, et al.
(författare)
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Therapeutics and vaccines against chikungunya virus
- 2015
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Ingår i: Vector borne and zoonotic diseases (Larchmont, N.Y.). - : Mary Ann Liebert Inc. - 1557-7759 .- 1530-3667. ; 15:4, s. 250-257
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Green, L, et al.
(författare)
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Data supporting: Invader at the edge - genomic origins and physiological differences of round gobies across a steep urban salinity gradient
- 2022
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Annan publikationabstract
- Species invasions are a global problem of increasing concern, especially in highly connected aquatic environments. Despite this, salinity conditions can pose physiological barriers to their spread and understanding them is important for management. In Scandinavia’s largest cargo port, the invasive round goby (Neogobius melanostomus), is established across a steep salinity gradient. We used 12 937 SNPs to identify the genetic origin and diversity of three sites along the salinity gradient and round goby from western, central and northern Baltic Sea, as well as north European rivers. Fish from two sites from the extreme ends of the gradient were also acclimated to freshwater and seawater, and tested for respiratory and osmoregulatory physiology. Fish from the high salinity environment in the outer port showed higher genetic diversity, and closer relatedness to the other regions, compared to fish from lower salinity upstream the river. Fish from the high salinity site also had higher maximum metabolic rate, fewer blood cells and lower blood Ca2+. Despite these genotypic and phenotypic differences, salinity acclimation affected fish from both sites in the same way: seawater increased the blood osmolality and Na+ levels, and freshwater increased the levels of the stress hormone cortisol. Our results show genotypic and phenotypic differences over short spatial scales across this steep salinity gradient. These patterns of the physiologically robust round goby are likely driven by multiple introductions into the high salinity site, and a process of sorting, likely based on behaviour or selection, along the gradient. Since this euryhaline fish risks spreading from this area, seascape genomics and phenotypic characterisation can inform management strategies even within an area as small as a coastal harbour inlet.
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| 10. |
- Zdziarski, Andrzej A., et al.
(författare)
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Hybrid Comptonization and Electron-Positron Pair Production in the Black-hole X-Ray Binary MAXI J1820+070
- 2021
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 914:1
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Tidskriftsartikel (refereegranskat)abstract
- We study X-ray and soft gamma-ray spectra from the hard state of the accreting black-hole binary MAXI J1820+070. We perform an analysis of two joint spectra from NuSTAR and INTEGRAL, covering the range of 3-650 keV, and of an average joint spectrum over the rise of the hard state, covering the 3-2200 keV range. The spectra are well modeled by Comptonization of soft seed photons. However, the distributions of the scattering electrons are not purely thermal; we find they have substantial high-energy tails, well modeled as power laws. The photon tail in the average spectrum is detected well beyond the threshold for electron-positron pair production, 511 keV. This allows us to calculate the rate of the electron-positron pair production and put a lower limit on the size of the source from pair equilibrium. At the fitted Thomson optical depth of the Comptonizing plasma, the limit is about 4 gravitational radii. If we adopt the sizes estimated by us from the reflection spectroscopy of >20 gravitational radii, the fractional pair abundance becomes much less than unity. The low pair abundance is confirmed by the lack of both an annihilation feature and of a pair absorption cutoff above 511 keV in the average spectrum.
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| 11. |
- Baudry, T., et al.
(författare)
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Invasion and distribution of the redclaw crayfish, Cherax quadricarinatus, in Martinique
- 2020
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Ingår i: Knowledge and Management of Aquatic Ecosystems. - : EDP Sciences. - 1961-9502. ; :421
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Tidskriftsartikel (refereegranskat)abstract
- The redclaw crayfish, Cherax quadricarinatus, was introduced to Martinique Island for aquaculture purposes in 2004, in an attempt to revitalize the freshwater crustacean aquaculture sector. In 2015, three wild populations were discovered during an electrofishing survey on fish diversity. In 2018, a specific crayfish survey was performed at night using spotlighting and baited traps at 34 sites throughout the island. The species was mostly found in the center and northern part of the island, specifically, a total of 105 specimens were captured in eight streams and five closed water bodies. We sequenced a 491 base-pair fragment of the COI gene to understand the invasion history and pathway from the presumed source population at the Mangatal hatchery. Among the eight haplotypes found, three were dominant, of which, two occurred in the Mangatal hatchery. As crayfish are sold alive, there is a high risk of further human-mediated introductions across the island hydrographic basins. Thus, the distribution of this species could rapidly expand throughout Martinique freshwater ecosystems, with ecological impacts on native communities yet to be determined and requiring urgent investigation.
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| 12. |
- Jones, Robert P., et al.
(författare)
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Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma : A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
- 2019
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Ingår i: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 154:11, s. 1038-1048
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Tidskriftsartikel (refereegranskat)abstract
- Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P=.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P=.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P=.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P=.85 and P=.35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P=.03).Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.Trial Registration: ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434. This secondary analysis of a randomized clinical trial investigates patterns of recurrence after adjuvant chemotherapy in pancreatic cancer and the association with survival.
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| 13. |
- Nashef, Samer A. M., et al.
(författare)
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EuroSCORE II dagger
- 2012
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Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 41:4, s. 734-745
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Tidskriftsartikel (refereegranskat)abstract
- To update the European System for Cardiac Operative Risk Evaluation (EuroSCORE) risk model. A dedicated website collected prospective risk and outcome data on 22 381 consecutive patients undergoing major cardiac surgery in 154 hospitals in 43 countries over a 12-week period (May-July 2010). Completeness and accuracy were validated during data collection using mandatory field entry, error and range checks and after data collection using summary feedback confirmation by responsible officers and multiple logic checks. Information was obtained on existing EuroSCORE risk factors and additional factors proven to influence risk from research conducted since the original model. The primary outcome was mortality at the base hospital. Secondary outcomes were mortality at 30 and 90 days. The data set was divided into a developmental subset for logistic regression modelling and a validation subset for model testing. A logistic risk model (EuroSCORE II) was then constructed and tested. Compared with the original 1995 EuroSCORE database (in brackets), the mean age was up at 64.7 (62.5) with 31% females (28%). More patients had New York Heart Association class IV, extracardiac arteriopathy, renal and pulmonary dysfunction. Overall mortality was 3.9% (4.6%). When applied to the current data, the old risk models overpredicted mortality (actual: 3.9%; additive predicted: 5.8%; logistic predicted: 7.57%). EuroSCORE II was well calibrated on testing in the validation data subset of 5553 patients (actual mortality: 4.18%; predicted: 3.95%). Very good discrimination was maintained with an area under the receiver operating characteristic curve of 0.8095. Cardiac surgical mortality has significantly reduced in the last 15 years despite older and sicker patients. EuroSCORE II is better calibrated than the original model yet preserves powerful discrimination. It is proposed for the future assessment of cardiac surgical risk.
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