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- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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- Vihma, T., et al.
(författare)
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Advances in understanding and parameterization of small-scale physical processes in the marine Arctic climate system : a review
- 2014
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 14:17, s. 9403-9450
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Forskningsöversikt (refereegranskat)abstract
- The Arctic climate system includes numerous highly interactive small-scale physical processes in the atmosphere, sea ice, and ocean. During and since the International Polar Year 2007-2009, significant advances have been made in understanding these processes. Here, these recent advances are reviewed, synthesized, and discussed. In atmospheric physics, the primary advances have been in cloud physics, radiative transfer, mesoscale cyclones, coastal, and fjordic processes as well as in boundary layer processes and surface fluxes. In sea ice and its snow cover, advances have been made in understanding of the surface albedo and its relationships with snow properties, the internal structure of sea ice, the heat and salt transfer in ice, the formation of superimposed ice and snow ice, and the small-scale dynamics of sea ice. For the ocean, significant advances have been related to exchange processes at the ice-ocean interface, diapycnal mixing, double-diffusive convection, tidal currents and diurnal resonance. Despite this recent progress, some of these small-scale physical processes are still not sufficiently understood: these include wave-turbulence interactions in the atmosphere and ocean, the exchange of heat and salt at the ice-ocean interface, and the mechanical weakening of sea ice. Many other processes are reasonably well understood as stand-alone processes but the challenge is to understand their interactions with and impacts and feedbacks on other processes. Uncertainty in the parameterization of small-scale processes continues to be among the greatest challenges facing climate modelling, particularly in high latitudes. Further improvements in parameterization require new year-round field campaigns on the Arctic sea ice, closely combined with satellite remote sensing studies and numerical model experiments.
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- Bertucci, F., et al.
(författare)
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The genomic grade index predicts postoperative clinical outcome in patients with soft-tissue sarcoma
- 2018
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 29:2, s. 459-465
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Tidskriftsartikel (refereegranskat)abstract
- Background: Soft-tissue sarcomas (STSs) are a group of rare, heterogeneous, and aggressive tumors, with high metastatic risk and relatively few efficient systemic therapies. We hypothesized that the Genomic Grade Index (GGI), a 108-gene signature previously developed in early-stage breast cancer, might improve the prognostic assessment of patients with early-stage STS. Patients and methods: We collected gene expression and clinicopathological data of 678 operated STS, and searched for correlations between the GGI-based classification and clinicopathological variables, including the metastasis-free survival (MFS). Results: Based on GGI, 275 samples (41%) were classified as 'GGI-low' and 403 (59%) as 'GGI-high'. The 'GGI-high' class was more associated with poor-prognosis features than the 'GGI-low' class: pathological grade 3 (P=9.50E-11), undifferentiated sarcomas and leiomyosarcomas (P<1.00E-06), location in extremities (P<1.00E-06), and complex genetic profile (P=2.1E-20). The 5-year MFS was 53% (95%CI 47-59) in the 'GGI-high' class versus 78% (95%CI 72-85) in the 'GGI-low' class (P=3.02E-11), with a corresponding hazard ratio for metastatic relapse equal to 2.92 (95%CI 2.10-4.07; P=2.23E-10). In multivariate analysis, the GGI-based classification remained significant, whereas the pathological grade did not. In fact, the GGI-based classification stratified the patients with pathological grades 1 and 2 and those with pathological grade 3 in two classes with different 5-year MFS. Comparison of the GGI and CINSARC multigene signatures revealed similar correlations with clinicopathological variables, which were, however, stronger with GGI than with CINSARC, a strong concordance (71%) in terms of low-risk or high-risk classifications, and independent prognostic value for MFS in multivariate analysis, suggesting complementary prognostic information. Conclusion: GGI refines the prediction of MFS in operated STS and might improve the tailoring of adjuvant chemotherapy. Further clinical validation is warranted in larger retrospective, then prospective series, as well as the functional validation of relevant genes that could provide new therapeutic targets.
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- Van, den Berg M, et al.
(författare)
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Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife
- 1998
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Ingår i: ENVIRONMENTAL HEALTH PERSPECTIVES. - : US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE. ; 106:12, s. 775-792
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Recension (övrigt vetenskapligt/konstnärligt)abstract
- An expert meeting was organized by the World Health Organization (WHO) and held in Stockholm on 15-18 June 1997. The objective of this meeting was to derive consensus toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs) and diben
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- Allen, Joseph G., et al.
(författare)
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PBDE flame retardants, thyroid disease, and menopausal status in U.S. women
- 2016
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Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Women have elevated rates of thyroid disease compared to men. Environmental toxicants have been implicated as contributors to this dimorphism, including polybrominated diphenyl ethers (PBDEs), flame retardant chemicals that disrupt thyroid hormone action. PBDEs have also been implicated in the disruption of estrogenic activity, and estrogen levels regulate thyroid hormones. Post-menopausal women may therefore be particularly vulnerable to PBDE induced thyroid effects, given low estrogen reserves. The objective of this study was to test for an association between serum PBDE concentrations and thyroid disease in women from the United States (U.S.), stratified by menopause status.METHODS: Serum PBDE concentrations (BDEs 47, 99, 100 and 153) from the National Health and Examination Survey (NHANES) and reports on thyroid problems were available in the NHANES 2003-2004 cycle. Odds ratios (ORs) were calculated using multivariate logistic regression models accounting for population-weighted survey techniques and controlling for age, body mass index (BMI), education, smoking, alcohol consumption and thyroid medication. Menopause status was obtained by self-reported absence of menstruation in the previous 12 months and declared menopause.RESULTS: Women in the highest quartile of serum concentrations for BDEs 47, 99, and 100 had increased odds of currently having thyroid disease (ORs: 1.5, 1.8, 1.5, respectively) compared to the reference group (1st and 2nd quartiles combined); stronger associations were observed when the analysis was restricted to postmenopausal women (ORs: 2.2, 3.6, 2.0, respectively).CONCLUSION: Exposure to BDEs 47, 99, and 100 is associated with thyroid disease in a national sample of U.S. women, with greater effects observed post-menopause, suggesting that the disruption of thyroid signaling by PBDEs may be enhanced by the altered estrogen levels during menopause.
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- Birnbaum, D., et al.
(författare)
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Spatial thought
- 2018
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Ingår i: Superhumanity. - Minneapolis, MN : University of Minnesota Press. - 9781452957876 - 9781517905217 ; , s. 169-176
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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- Jha, Suryatapa Ghosh, et al.
(författare)
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Vision, challenges and opportunities for a Plant Cell Atlas
- 2021
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Ingår i: eLIFE. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- With growing populations and pressing environmental problems, future economies will be increasingly plant-based. Now is the time to reimagine plant science as a critical component of fundamental science, agriculture, environmental stewardship, energy, technology and healthcare. This effort requires a conceptual and technological framework to identify and map all cell types, and to comprehensively annotate the localization and organization of molecules at cellular and tissue levels. This framework, called the Plant Cell Atlas (PCA), will be critical for understanding and engineering plant development, physiology and environmental responses. A workshop was convened to discuss the purpose and utility of such an initiative, resulting in a roadmap that acknowledges the current knowledge gaps and technical challenges, and underscores how the PCA initiative can help to overcome them.
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- vom Saal, Frederick S., et al.
(författare)
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The Conflict between Regulatory Agencies over the 20,000-Fold Lowering of the Tolerable Daily Intake (TDI) for Bisphenol A (BPA) by the European Food Safety Authority (EFSA)
- 2024
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Ingår i: Journal of Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 132:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: The European Food Safety Authority (EFSA) recommended lowering their estimated tolerable daily intake (TDI) for bisphenol A (BPA) 20,000-fold to 0.2 ng/kg body weight (BW)/day. BPA is an extensively studied high production volume endocrine disrupting chemical (EDC) associated with a vast array of diseases. Prior risk assessments of BPA by EFSA as well as the US Food and Drug Administration (FDA) have relied on industry-funded studies conducted under good laboratory practice protocols (GLP) requiring guideline end points and detailed record keeping, while also claiming to examine (but rejecting) thousands of published findings by academic scientists. Guideline protocols initially formalized in the mid-twentieth century are still used by many regulatory agencies. EFSA used a 21st century approach in its reassessment of BPA and conducted a transparent, but time-limited, systematic review that included both guideline and academic research. The German Federal Institute for Risk Assessment (BfR) opposed EFSA’s revision of the TDI for BPA.Objectives: We identify the flaws in the assumptions that the German BfR, as well as the FDA, have used to justify maintaining the TDI for BPA at levels above what a vast amount of academic research shows to cause harm. We argue that regulatory agencies need to incorporate 21st century science into chemical hazard identifications using the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) nonguideline academic studies in a collaborative government–academic program model.Discussion: We strongly endorse EFSA’s revised TDI for BPA and support the European Commission’s (EC) apparent acceptance of this updated BPA risk assessment. We discuss challenges to current chemical risk assessment assumptions about EDCs that need to be addressed by regulatory agencies to, in our opinion, become truly protective of public health. Addressing these challenges will hopefully result in BPA, and eventually other structurally similar bisphenols (called regrettable substitutions) for which there are known adverse effects, being eliminated from all food-related and many other uses in the EU and elsewhere.
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