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- 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. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 5. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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- Aguirre-Gutierrez, Jesus, et al.
(författare)
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Long-term droughts may drive drier tropical forests towards increased functional, taxonomic and phylogenetic homogeneity
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Tropical ecosystems adapted to high water availability may be highly impacted by climatic changes that increase soil and atmospheric moisture deficits. Many tropical regions are experiencing significant changes in climatic conditions, which may induce strong shifts in taxonomic, functional and phylogenetic diversity of forest communities. However, it remains unclear if and to what extent tropical forests are shifting in these facets of diversity along climatic gradients in response to climate change. Here, we show that changes in climate affected all three facets of diversity in West Africa in recent decades. Taxonomic and functional diversity increased in wetter forests but tended to decrease in forests with drier climate. Phylogenetic diversity showed a large decrease along a wet-dry climatic gradient. Notably, we find that all three facets of diversity tended to be higher in wetter forests. Drier forests showed functional, taxonomic and phylogenetic homogenization. Understanding how different facets of diversity respond to a changing environment across climatic gradients is essential for effective long-term conservation of tropical forest ecosystems. Different aspects of biodiversity may not necessarily converge in their response to climate change. Here, the authors investigate 25-year shifts in taxonomic, functional and phylogenetic diversity of tropical forests along a spatial climate gradient in West Africa, showing that drier forests are less stable than wetter forests.
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| 7. |
- Bacquart, Thomas, et al.
(författare)
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Hydrogen fuel quality from two main production processes : Steam methane reforming and proton exchange membrane water electrolysis
- 2019
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Ingår i: Journal of Power Sources. - : Elsevier B.V.. - 0378-7753 .- 1873-2755. ; 444
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Tidskriftsartikel (refereegranskat)abstract
- The absence of contaminants in the hydrogen delivered at the hydrogen refuelling station is critical to ensure the length life of FCEV. Hydrogen quality has to be ensured according to the two international standards ISO 14687–2:2012 and ISO/DIS 19880-8. Amount fraction of contaminants from the two hydrogen production processes steam methane reforming and PEM water electrolyser is not clearly documented. Twenty five different hydrogen samples were taken and analysed for all contaminants listed in ISO 14687-2. The first results of hydrogen quality from production processes: PEM water electrolysis with TSA and SMR with PSA are presented. The results on more than 16 different plants or occasions demonstrated that in all cases the 13 compounds listed in ISO 14687 were below the threshold of the international standards. Several contaminated hydrogen samples demonstrated the needs for validated and standardised sampling system and procedure. The results validated the probability of contaminants presence proposed in ISO/DIS 19880-8. It will support the implementation of ISO/DIS 19880-8 and the development of hydrogen quality control monitoring plan. It is recommended to extend the study to other production method (i.e. alkaline electrolysis), the HRS supply chain (i.e. compressor) to support the technology growth.
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| 8. |
- Barker, Roger A., et al.
(författare)
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Designing stem-cell-based dopamine cell replacement trials for Parkinson’s disease
- 2019
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25, s. 1045-1053
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Tidskriftsartikel (refereegranskat)abstract
- Clinical studies of Parkinson’s disease (PD) using a dopamine cell replacment strategy have been tried for more than 30 years. The outcomes following transplantation of human fetal ventral mesencephalic tissue (hfVM) have been variable, with some patients coming off their anti-PD treatment for many years and others not responding and/or developing significant side effects, including graft-induced dyskinesia. This led to a re-appraisal of the best way to do such trials, which resulted in a new European-Union-funded allograft trial with fetal dopamine cells across several centers in Europe. This new trial, TRANSEURO (NCT01898390), is an open-label study in which some individuals in a large observational cohort of patients with mild PD who were undergoing identical assessments were randomly selected to receive transplants of hfVM. The TRANSEURO trial is currently ongoing as researchers have completed both recruitment into a large multicenter observational study of younger onset early-stage PD and transplantation of hfVM in 11 patients. While completion of TRANSEURO is not expected until 2021, we feel that sharing the rationale for the design of TRANSEURO, along with the lessons we have learned along the way, can help inform researchers and facilitate planning of transplants of dopamine-producing cells derived from human pluripotent stem cells for future clinical trials.
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| 9. |
- Huaraca Huasco, Walter, et al.
(författare)
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Fine root dynamics across pantropical rainforest ecosystems
- 2021
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Ingår i: Global Change Biology. - : John Wiley & Sons. - 1354-1013 .- 1365-2486. ; 27:15, s. 3657-3680
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Tidskriftsartikel (refereegranskat)abstract
- Fine roots constitute a significant component of the net primary productivity (NPP) of forest ecosystems but are much less studied than aboveground NPP. Comparisons across sites and regions are also hampered by inconsistent methodologies, especially in tropical areas. Here, we present a novel dataset of fine root biomass, productivity, residence time, and allocation in tropical old-growth rainforest sites worldwide, measured using consistent methods, and examine how these variables are related to consistently determined soil and climatic characteristics. Our pantropical dataset spans intensive monitoring plots in lowland (wet, semi-deciduous, and deciduous) and montane tropical forests in South America, Africa, and Southeast Asia (n = 47). Large spatial variation in fine root dynamics was observed across montane and lowland forest types. In lowland forests, we found a strong positive linear relationship between fine root productivity and sand content, this relationship was even stronger when we considered the fractional allocation of total NPP to fine roots, demonstrating that understanding allocation adds explanatory power to understanding fine root productivity and total NPP. Fine root residence time was a function of multiple factors: soil sand content, soil pH, and maximum water deficit, with longest residence times in acidic, sandy, and water-stressed soils. In tropical montane forests, on the other hand, a different set of relationships prevailed, highlighting the very different nature of montane and lowland forest biomes. Root productivity was a strong positive linear function of mean annual temperature, root residence time was a strong positive function of soil nitrogen content in montane forests, and lastly decreasing soil P content increased allocation of productivity to fine roots. In contrast to the lowlands, environmental conditions were a better predictor for fine root productivity than for fractional allocation of total NPP to fine roots, suggesting that root productivity is a particularly strong driver of NPP allocation in tropical mountain regions.
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| 10. |
- Malhi, Yadvinder, et al.
(författare)
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The Global Ecosystems Monitoring network : Monitoring ecosystem productivity and carbon cycling across the tropics
- 2021
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Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207. ; 253
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Tidskriftsartikel (refereegranskat)abstract
- A rich understanding of the productivity, carbon and nutrient cycling of terrestrial ecosystems is essential in the context of understanding, modelling and managing the future response of the biosphere to global change. This need is particularly acute in tropical ecosystems, home to over 60% of global terrestrial productivity, over half of planetary biodiversity, and hotspots of anthropogenic pressure. In recent years there has been a surge of activity in collecting data on the carbon cycle, productivity, and plant functional traits of tropical ecosystems, most intensively through the Global Ecosystems Monitoring network (GEM). The GEM approach provides valuable insights by linking field-based ecosystem ecology with the needs of Earth system science. In this paper, we review and synthesize the context, history and recent scientific output from the GEM network. Key insights have emerged on the spatial and temporal variability of ecosystem productivity and on the role of temperature and drought stress on ecosystem function and resilience. New work across the network is now linking carbon cycling to nutrient cycling and plant functional traits, and subsequently to airborne remote sensing. We discuss some of the novel emerging patterns and practical and methodological challenges of this approach, and examine current and possible future directions, both within this network and as lessons for a more general terrestrial ecosystem observation scheme.
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