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| 2. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 3. |
- Hoshino, Ayuko, et al.
(författare)
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Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers
- 2020
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Ingår i: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 182:4, s. 1044-
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Tidskriftsartikel (refereegranskat)abstract
- There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n =151) and plasma-derived (n =120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.
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| 4. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Drielsma, Johannes A., et al.
(författare)
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Mineral resources in life cycle impact assessment—defining the path forward
- 2016
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Ingår i: The International Journal of Life Cycle Assessment. - : Springer Science and Business Media LLC. - 0948-3349 .- 1614-7502. ; 21:1, s. 85-105
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Despite 20 years of research, there remains no robust, globally agreed upon method—or even problem statement—for assessing mineral resource inputs in life cycle impact assessment (LCIA). As a result, inclusion of commonly used methods such as abiotic depletion potential (ADP) in life cycle assessment (LCA)-related evaluation schemes could lead to incorrect decisions being made in many applications. In this paper, we explore in detail how to improve the way that life cycle thinking is applied to the acquisition of mineral resources and their metal counterparts. Methods: This paper evaluates the current body of work in LCIA with regard to “depletion potential” of mineral resources. Viewpoints from which models are developed are described and analyzed. The assumptions, data sources, and calculations that underlie currently used methods are examined. A generic metal-containing product is analyzed to demonstrate the vulnerability of results to the denominator utilized in calculating ADP. The adherence to the concept of the area of protection (AOP) is evaluated for current models. The use of ore grades, prices, and economic availability in LCIA is reviewed. Results and discussion: Results demonstrate that any work on resource depletion in a life cycle context needs to have a very clear objective or LCIA will not accurately characterize mineral resource use from any perspective and decision-making will continue to suffer. New, harmonized terminology is proposed so that LCA practitioners can build better mutual understanding with the mineral industry and recommendations regarding more promising tools for use in life cycle sustainability assessment (LCSA) are given. Conclusions: The economic issue of resource availability should be evaluated in parallel with traditional LCA, not within. LCIA developers should look to economists, the market, and society in general, for broader assessments that consider shorter-time horizons than the traditional LCIA methods. To do so, the concept of the AOP in LCA needs to be redefined for LCSA to ensure that models estimate what is intended. Finally, recommendations regarding mineral resource assessment are provided to ensure that future research has a sound basis and practitioners can incorporate the appropriate tools in their work.
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| 6. |
- Gowin, Krisstina, et al.
(författare)
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Survival following allogeneic transplant in patients with myelofibrosis
- 2020
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Ingår i: Blood Advances. - : AMER SOC HEMATOLOGY. - 2473-9529 .- 2473-9537. ; 4:9, s. 1965-1973
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). In this large multicenter retrospective study, overall survival (OS) in MF patients treated with allogeneic HCT (551 patients) and without HCT (non-HCT) (1377 patients) was analyzed with Cox proportional hazards model. Survival analysis stratified by the Dynamic International Prognostic Scoring System (DIPSS) revealed that the first year of treatment arm assignment, due to upfront risk of transplant-related mortality (TRM), HCT was associated with inferior OS compared with non-HCT (non-HCT vs HCT: DIPSS intermediate 1 [Int-1]: hazard ratio [HR] = 0.26, P < .0001; DIPSS-Int-2 and higher: HR, 0.39, P < .0001). Similarly, in the DIPSS low-risk MF group, due to upfront TRM risk, OS was superior with non-HCT therapies compared with HCT in the first-year post treatment arm assignment (HR, 0.16, P = .006). However, after 1 year, OS was not significantly different (HR, 1.38, P = .451). Beyond 1 year of treatment arm assignment, an OS advantage with HCT therapy in Int-1 and higher DIPSS score patients was observed (non-HCT vs HCT: DIPSS-Int-1: HR, 2.64, P < .0001; DIPSS-Int-2 and higher: HR, 2.55, P < .0001). In conclusion, long-term OS advantage with HCT was observed for patients with Int-1 or higher risk MF, but at the cost of early TRM. The magnitude of OS benefit with HCT increased as DIPSS risk score increased and became apparent with longer follow-up.
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| 7. |
- Jones, Felicity C., et al.
(författare)
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The genomic basis of adaptive evolution in threespine sticklebacks
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 484:7392, s. 55-61
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Tidskriftsartikel (refereegranskat)abstract
- Marine stickleback fish have colonized and adapted to thousands of streams and lakes formed since the last ice age, providing an exceptional opportunity to characterize genomic mechanisms underlying repeated ecological adaptation in nature. Here we develop a high-quality reference genome assembly for threespine sticklebacks. By sequencing the genomes of twenty additional individuals from a global set of marine and freshwater populations, we identify a genome-wide set of loci that are consistently associated with marine-freshwater divergence. Our results indicate that reuse of globally shared standing genetic variation, including chromosomal inversions, has an important role in repeated evolution of distinct marine and freshwater sticklebacks, and in the maintenance of divergent ecotypes during early stages of reproductive isolation. Both coding and regulatory changes occur in the set of loci underlying marine-freshwater evolution, but regulatory changes appear to predominate in this well known example of repeated adaptive evolution in nature.
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| 8. |
- Reed, Mark S., et al.
(författare)
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Land Use Partnerships using a Natural Capital Approach : Lessons for Scotland
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Regional Land Use Partnerships (RLUPs) are being set up in Scotland to help achieve Scotland’s climate change targets through land use change and a natural capital approach. These partnerships facilitate engagement between local and national government, communities, landowners, land managers, and a range of other relevant stakeholders. Five RLUP pilots will produce a Regional Land Use Framework (RLUF) by 2023 using a natural capital approach which considers key natural assets and the benefits these provide to communities and the regional economy.This project examines evidence from the UK and Europe for the use of the natural capital approach in successful partnerships, working across multiple sectors and landownership boundaries. It focuses on outcomes for climate change, biodiversity and benefits to local communities. It includes six case studies of partnerships which have incorporated elements of a natural capital approach.Based on our analysis, a natural capital approach can help:- build a balanced overview of the range of ecosystem services and benefits to communities and stakeholders that land and natural assets can provide;- understanding of how different services may interact in response to projects and interventions, leading to multiple benefits or negative unintended consequences;- contextualise and respond to the different priorities and interests of specific partners and stakeholders, helping pre-empt and manage conflicts of interest;- act as a stimulus for local investment; and- bring stakeholders together to co-produce plans that can meet multiple objectives.
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