| 1. |
- 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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| 2. |
- Couch, Fergus J., et al.
(författare)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 3. |
- Wilking, N., et al.
(författare)
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Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
- 2007
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:4, s. 694-700
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below theage of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. © 2007 Oxford University Press.
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| 4. |
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| 5. |
- Blomqvist, Anders, et al.
(författare)
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OBITUARY: A. D. (Bud) Craig, Jr. (1951-2023)
- 2023
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Ingår i: Nature Neuroscience. - : NATURE PORTFOLIO. - 1097-6256 .- 1546-1726. ; 26, s. 1835-1836
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Bud Craig, an outstanding neuroscientist, died on 15 July 2023 at age 71. Bud made unique contributions to the fields of pain and interoception, challenging major dogmas and offering powerful explanations for various phenomena including central pain and the subjective awareness of feelings, with great implications for our understanding of consciousness.
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| 6. |
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| 7. |
- Dórea, Fernanda C., et al.
(författare)
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Drivers for the development of an Animal Health Surveillance Ontology (AHSO)
- 2019
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Ingår i: Preventive Veterinary Medicine. - : Elsevier. - 0167-5877 .- 1873-1716. ; 166:1, s. 39-48
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Tidskriftsartikel (refereegranskat)abstract
- Comprehensive reviews of syndromic surveillance in animal health have highlighted the hindrances to integration and interoperability among systems when data emerge from different sources. Discussions with syndromic surveillance experts in the fields of animal and public health, as well as computer scientists from the field of information management, have led to the conclusion that a major component of any solution will involve the adoption of ontologies. Here we describe the advantages of such an approach, and the steps taken to set up the Animal Health Surveillance Ontological (AHSO) framework. The AHSO framework is modelled in OWL, the W3C standard Semantic Web language for representing rich and complex knowledge. We illustrate how the framework can incorporate knowledge directly from domain experts or from data-driven sources, as well as by integrating existing mature ontological components from related disciplines. The development and extent of AHSO will be community driven and the final products in the framework will be open-access.
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| 8. |
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| 9. |
- Hernandez, Jorge, et al.
(författare)
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Human-Associated Extended-Spectrum beta-Lactamase in the Antarctic
- 2012
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Ingår i: Applied and Environmental Microbiology. - Washington, DC, United States : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 78:6, s. 2056-2058
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Tidskriftsartikel (refereegranskat)abstract
- Escherichia coli bacteria with extended-spectrum beta-lactamase (ESBL) type CTX-M resistance were isolated from water samples collected close to research stations in Antarctica. The isolates had bla(CTX-M-1) and bla(CTX-M-15) genotypes and sequence types (ST) indicative of a human-associated origin. This is the first record of ESBL-producing enterobacteria from Antarctica.
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| 10. |
- Lundberg, C., et al.
(författare)
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Driving tests with older patients : Effect of unfamiliar versus familiar vehicle
- 2003
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Ingår i: Transportation Research Part F. - 1369-8478 .- 1873-5517. ; 6:3, s. 163-173
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to study the effect, for older license holders, of taking a driving test with an unfamiliar vehicle, as compared to their own cars. The study population consisted of licensed patients 65-85 years referred to the Traffic Medicine Centre (TrMC), Huddinge University Hospital, for an evaluation of their medical and cognitive fitness to drive. In the clinical practice of TrMC, driving tests have been used since 1997, with inspectors from the Swedish National Road Administration (SNRA) acting as evaluators. Initially, patients were allowed to use their own cars. From the beginning of the year 2000, however, dual brakes were made mandatory and most evaluations were then made with SNRA cars. When comparing the outcomes of driving tests from the period prior to 2000 (n=96) and after 2000 (n=69), it was found that the number of drivers who failed the test increased by 16%. Also, those who passed the test after more than one trial decreased by 20%. The potential of the neuropsychological assessment to correctly classify drivers in outcome groups was considerably reduced in the period after 2000. These results support the view that, for older drivers with cognitive deterioration, the need to adapt to an unfamiliar vehicle represents a supplementary cognitive load that may compromise their driving ability and the validity of the assessment. A measure aimed only at increasing the safety of examiners and examinees thus had an unintended side-effect that is detrimental to older clinical populations. © 2003 Elsevier Ltd. All rights reserved.
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