| 1. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 2. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 3. |
- Tran, Dien M., et al.
(författare)
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High prevalence of colonisation with carbapenem-resistant Enterobacteriaceae among patients admitted to Vietnamese hospitals : Risk factors and burden of disease
- 2019
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Ingår i: Journal of Infection. - : Saunders Elsevier. - 0163-4453 .- 1532-2742. ; 79:2, s. 115-122
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCarbapenem-resistant Enterobacteriaceae (CRE) is an increasing problem worldwide, but particularly problematic in low- and middle-income countries (LMIC) due to limitations of resources for surveillance of CRE and infection prevention and control (IPC).MethodsA point prevalence survey (PPS) with screening for colonisation with CRE was conducted on 2233 patients admitted to neonatal, paediatric and adult care at 12 Vietnamese hospitals located in northern, central and southern Vietnam during 2017 and 2018. CRE colonisation was determined by culturing of faecal specimens on selective agar for CRE. Risk factors for CRE colonisation were evaluated. A CRE admission and discharge screening sub-study was conducted among one of the most vulnerable patient groups; infants treated at an 80-bed Neonatal ICU from March throughout June 2017 to assess CRE acquisition, hospital-acquired infection (HAI) and treatment outcome.ResultsA total of 1165 (52%) patients were colonised with CRE, most commonly Klebsiella pneumoniae (n=805), Escherichia coli (n=682) and Enterobacter spp. (n=61). Duration of hospital stay, HAI and treatment with a carbapenem were independent risk factors for CRE colonisation. The PPS showed that the prevalence of CRE colonisation increased on average 4.2 % per day and mean CRE colonisation rates increased from 13% on the day of admission to 89% at day 15 of hospital stay. At the NICU CRE colonisation increased from 32% at admission to 87% at discharge, mortality was significantly associated (OR 5•5, P < 0•01) with CRE colonisation and HAI on admission.ConclusionThese data indicate that there is an epidemic spread of CRE in Vietnamese hospitals with rapid transmission to hospitalised patients.
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| 4. |
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| 5. |
- 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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| 6. |
- Osorio, Ana, et al.
(författare)
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DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
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| 7. |
- Zeng, Chenjie, et al.
(författare)
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Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
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| 8. |
- Bolton, Kelly L., et al.
(författare)
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Association Between BRCA1 and BRCA2 Mutations and Survival in Women With Invasive Epithelial Ovarian Cancer
- 2012
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Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598. ; 307:4, s. 382-390
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Tidskriftsartikel (refereegranskat)abstract
- Context Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear. Objective To characterize the survival of BRCA carriers with EOC compared with noncarriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns. Design, Setting, and Participants A pooled analysis of 26 observational studies on the survival of women with ovarian cancer, which included data from 1213 EOC cases with pathogenic germline mutations in BRCA1 (n=909) or BRCA2 (n=304) and from 2666 noncarriers recruited and followed up at variable times between 1987 and 2010 (the median year of diagnosis was 1998). Main Outcome Measure Five-year overall mortality. Results The 5-year overall survival was 36% (95% CI, 34%-38%) for noncarriers, 44% (95% CI, 40%-48%) for BRCA1 carriers, and 52% (95% CI, 46%-58%) for BRCA2 carriers. After adjusting for study and year of diagnosis, BRCA1 and BRCA2 mutation carriers showed a more favorable survival than noncarriers (for BRCA1: hazard ratio [HR], 0.78; 95% CI, 0.68-0.89; P<.001; and for BRCA2: HR, 0.61; 95% CI, 0.50-0.76; P<.001). These survival differences remained after additional adjustment for stage, grade, histology, and age at diagnosis (for BRCA1: HR, 0.73; 95% CI, 0.64-0.84; P<.001; and for BRCA2: HR, 0.49; 95% CI, 0.39-0.61; P<.001). The BRCA1 HR estimate was significantly different from the HR estimated in the adjusted model (P for heterogeneity=.003). Conclusion Among patients with invasive EOC, having a germline mutation in BRCA1 or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis. JAMA. 2012;307(4):382-390
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| 9. |
- Bosma, R. H., et al.
(författare)
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Changing opinion, knowledge, skill and behaviour of Vietnamese shrimp farmers by using serious board games
- 2020
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Ingår i: The Journal of Agricultural Education and Extension. - : Routledge. - 1389-224X .- 1750-8622. ; 26:2, s. 203-221
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Mekong Delta's shrimp farming contributes to socio-economic development but tends to reduce the mangrove area. On the one hand, NGOs advocate balancing ecology and economy, while on the other hand, the Vietnamese government supports intensifying shrimp production. The latter strategy increases shrimp diseases and marginalises smallholders. To influence the opinions, knowledge and behaviour of shrimp farmers, we developed and tested a serious board game. Approach: Through several iterations, we designed a realistic board game mimicking local shrimp farming. Then, after conducting three sessions of gameplay with farmers in three sites, we assessed how this gameplay influenced players. We used a semi-experimental set-up by collecting data on the day of the gameplay, and on two further time-points. Findings: After the gameplays, farmers reported to have learned about the risks of monoculture-intensive-shrimp system and the advantages of hybrid systems. Likert ratings showed that players adopted innovations faster and, in case of shrimp diseases, consulted commercial service-providers less, but with other farmers more. They confirmed to have learned that the best strategy for them would be to adopt hybrid systems, i.e. intensify part of the area of mixed-mangrove or improved-extensive shrimp farms. Theoretical implications: Realistic board games can create opportunities for social learning and training of groups which are not always easy to reach. Practical implications: Board games can support transfer of knowledge and skills to farmers, and can develop their critical thinking. Creation: The findings that board games are effective in the context of a top-down extension systems offer value opportunities.
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| 10. |
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| 11. |
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| 12. |
- Laruelle, G. G., et al.
(författare)
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Anthropogenic perturbations of the silicon cycle at the global scale: Key role of the land-ocean transition
- 2009
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Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 23
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Forskningsöversikt (refereegranskat)abstract
- Silicon (Si), in the form of dissolved silicate (DSi), is a key nutrient in marine and continental ecosystems. DSi is taken up by organisms to produce structural elements (e.g., shells and phytoliths) composed of amorphous biogenic silica (bSiO(2)). A global mass balance model of the biologically active part of the modern Si cycle is derived on the basis of a systematic review of existing data regarding terrestrial and oceanic production fluxes, reservoir sizes, and residence times for DSi and bSiO(2). The model demonstrates the high sensitivity of biogeochemical Si cycling in the coastal zone to anthropogenic pressures, such as river damming and global temperature rise. As a result, further significant changes in the production and recycling of bSiO(2) in the coastal zone are to be expected over the course of this century.
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| 13. |
- Leebens-Mack, James H., et al.
(författare)
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One thousand plant transcriptomes and the phylogenomics of green plants
- 2019
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
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Tidskriftsartikel (refereegranskat)abstract
- Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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| 14. |
- Srivastava, Ankur, 1989, et al.
(författare)
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A DSO Support Framework for Assessment of Future-Readiness of Distribution Systems: Technical, Market, and Policy Perspectives
- 2019
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Ingår i: CIRED Conference Proceedings. - 2032-9644. - 9782960241501
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Konferensbidrag (refereegranskat)abstract
- This paper presents the initial ideas for a framework to support the distribution system operators for assessing current status of network infrastructures, market/business models, and policies applicable to distribution systems, and thus identify future-readiness of their network. The assessment framework consists of two steps as the identification of the key indicators associated with this transition and assessing the current status by evaluation of these indicators based on inputs from distribution system operators. Case studies have been carried out for distribution system operators in three European countries, i.e., Göteborg Energi (Sweden), SOREA (France), and ENEXIS (The Netherlands). The key results have shown that presently the three distribution system operators have a small proportion of renewable power generation in their grids, but it is going to increase in the future. Hence, they need investments in flexibilities, generation and load forecasting, advanced network control, and protection strategies, etc. The results also suggest needs for development of novel business models for customers and changes in the policy and regulations. Finally, a comparative assessment of three distribution system operators is presented in the paper.
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| 15. |
- Antoniou, Antonis C., et al.
(författare)
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A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:10, s. 885-892
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Tidskriftsartikel (refereegranskat)abstract
- Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P-trend = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P-trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P-trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P-trend = 1.1 x 10(-7)).
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| 16. |
- Antoniou, Antonis C., et al.
(författare)
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Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2011
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
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Tidskriftsartikel (refereegranskat)abstract
- Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
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| 17. |
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| 18. |
- Candido-dos-Reis, Francisco J, et al.
(författare)
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Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer
- 2015
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 21:3, s. 7-652
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis.EXPERIMENTAL DESIGN: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using Fine and Gray model.RESULTS: The combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become greater than 1 at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors and to ovarian cancer-specific mortality.CONCLUSIONS: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.
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| 19. |
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| 20. |
- Ding, Yuan C, et al.
(författare)
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A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
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| 21. |
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| 22. |
- Guzzi, Nicola, et al.
(författare)
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Pseudouridylation of tRNA-Derived Fragments Steers Translational Control in Stem Cells
- 2018
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 173:5, s. 26-1216
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Tidskriftsartikel (refereegranskat)abstract
- Pseudouridylation (Ψ) is the most abundant and widespread type of RNA epigenetic modification in living organisms; however, the biological role of Ψ remains poorly understood. Here, we show that a Ψ-driven posttranscriptional program steers translation control to impact stem cell commitment during early embryogenesis. Mechanistically, the Ψ “writer” PUS7 modifies and activates a novel network of tRNA-derived small fragments (tRFs) targeting the translation initiation complex. PUS7 inactivation in embryonic stem cells impairs tRF-mediated translation regulation, leading to increased protein biosynthesis and defective germ layer specification. Remarkably, dysregulation of this posttranscriptional regulatory circuitry impairs hematopoietic stem cell commitment and is common to aggressive subtypes of human myelodysplastic syndromes. Our findings unveil a critical function of Ψ in directing translation control in stem cells with important implications for development and disease. Translational control in stem cells is orchestrated by pseudouridylation of specific tRNA-derived fragments, impacting stem cell commitment during key developmental processes.
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| 23. |
- Kumar, Pardeep, et al.
(författare)
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Access Control Protocol With Node Privacy in Wireless Sensor Networks
- 2016
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Ingår i: IEEE Sensors Journal. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 1530-437X .- 1558-1748. ; 16:22, s. 8142-8150
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Tidskriftsartikel (refereegranskat)abstract
- For preventing malicious nodes joining wireless sensor networks (WSNs), an access control mechanism is necessary for the trustworthy cooperation between the nodes. In addition to access control, recently, privacy has been an important topic regarding how to achieve privacy without disclosing the real identity of communicating entities in the WSNs. Based on elliptic curve cryptography, in this paper, we present an access control protocol with node privacy (called ACP) for the WSN. The proposed scheme not only accomplishes the node authentication but also provides the identity privacy (i.e., source to destination and vice-versa) for the communicating entities. Compared with the current state of the art, the proposed solution can defend actively against attacks. The efficacy and the efficiency of the proposed ACP are confirmed through the test bed analysis and performance evaluations.
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| 24. |
- Kumar, Pardeep, et al.
(författare)
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Lightweight Authentication and Key Agreement for Smart Metering in Smart Energy Networks
- 2019
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Ingår i: IEEE Transactions on Smart Grid. - : Institute of Electrical and Electronics Engineers (IEEE). - 1949-3053 .- 1949-3061. ; 10:4, s. 4349-4359
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Tidskriftsartikel (refereegranskat)abstract
- Smart meters are considered as foundational part of the smart metering infrastructure (SMI) in smart energy networks. Smart meter is a digital device that makes use of twoway communication between consumer and utility to exchange, manage and control energy consumptions within a home. However, despite all the features, a smart meter raises several securityrelated concerns. For instance, how to exchange data between the legal entities (e.g., smart meter and utility server) while maintaining privacy of the consumer. To address these concerns, authentication and key agreement in SMI can provide important security properties that not only to maintain a trust between the legitimate entities but also to satisfy other security services. This work presents a lightweight authentication and key agreement (LAKA) that enables trust, anonymity, integrity and adequate security in the domain of smart energy network. The proposed scheme employs hybrid cryptography to facilitate mutual trust (authentication), dynamic session key, integrity, and anonymity. We justify the feasibility of the proposed scheme with a testbed using 802.15.4 based device (i.e., smart meter). Moreover, through the security and performance analysis, we show that the proposed scheme is more effective and energy efficient compared to the previous schemes.
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| 25. |
- Laato, Samuli, et al.
(författare)
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Evaluation of the Pedagogical Quality of Mobile Math Games in App Marketplaces
- 2020
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Ingår i: Proceedings. - : IEEE.
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Konferensbidrag (refereegranskat)abstract
- The number of available educational games has enormously grown and it is difficult for users to identify which games are pedagogically effective among the multitude of options in app marketplaces. Recent studies on math games have highlighted the importance of (1) linking learning attributes and gameplay and (2) game design that supports students' deliberate practise. Using these as a measure for pedagogical quality, we investigated 109 math games found on Google Play Store (n=61) and iOS App Store (n=48). Furthermore, monetization solutions, data use permissions, target age group and type of mathematical content were retrieved from the apps. The analysis showed that only 11,0% of the games integrated learning attributes with gameplay and 12,0% of the games contained tasks which support learners' deliberate practice. The most commonly featured math subject was arithmetic and the games were targeted mostly to early childhood (6–12 years). Finally, games following curricula content and recommended design principles were difficult to locate using the search tools of the app marketplaces.
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| 26. |
- Larsson, Andreas, et al.
(författare)
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Multiword atomic read/write registers on multiprocessor systems
- 2009
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Ingår i: ACM Journal of Experimental Algorithmics. - : Association for Computing Machinery, Inc.. - 1084-6654. ; 13:1, s. 1.7-1.30
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Tidskriftsartikel (refereegranskat)abstract
- Modern multiprocessor systems offer advanced synchronization primitives, built in hardware, to support the development of efficient parallel algorithms. In this article, we develop a simple and efficient algorithm, the READERSFIELD algorithm, for atomic registers (variables) of arbitrary length. The simplicity and better complexity of the algorithm is achieved via the utilization of two such common synchronization primitives. In this article, we also experimentally evaluate the performance of our algorithm, together with lock-based approaches and a practical, previously previously known algorithm that is based that is based only on read and write primitives. The experimental evaluation is performed on three well-known parallel architectures. This evaluation clearly shows that both algorithms are practical and that as the size of the register increases the READERSFIELD algorithm performs better, following its analytical evaluation.
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| 27. |
- Mai, Tam T., et al.
(författare)
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An overview of grid-edge control with the digital transformation
- 2021
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Ingår i: Electrical Engineering. - : Springer Science and Business Media LLC. - 1432-0487 .- 0948-7921. ; 103:4, s. 1989-2007
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Tidskriftsartikel (refereegranskat)abstract
- Distribution networks are evolving to become more responsive with increasing integration of distributed energy resources (DERs) and digital transformation at the grid edges. This evolution imposes many challenges to the operation of the network, which then calls for new control and operation paradigms. Among others, a so-called grid-edge control is emerging to harmonise the coexistence of the grid control system and DER’s autonomous control. This paper provides a comprehensive overview of the grid-edge control with various control architectures, layers, and strategies. The challenges and opportunities for such an approach at the grid edge with the integration of DERs and digital transformation are summarised. The potential solutions to support the network operation by using the inherent controllability of DER and the availability of the digital transformation at the grid edges are discussed.
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| 28. |
- Shubin, Nicholas J., et al.
(författare)
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Proteome analysis of mast cell releasates reveals a role for chymase in the regulation of coagulation factor XIIIA levels via proteolytic degradation
- 2017
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Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 139:1, s. 323-334
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mast cells are significantly involved in IgE-mediated allergic reactions; however, their roles in health and disease are incompletely understood. Objective: We aimed to define the proteome contained in mast cell releasates on activation to better understand the factors secreted by mast cells that are relevant to the contribution of mast cells in diseases. Methods: Bone marrow-derived cultured mast cells (BMCMCs) and peritoneal cell-derived mast cells were used as "surrogates'' for mucosal and connective tissue mast cells, respectively, and their releasate proteomes were analyzed by mass spectrometry. Results: Our studies showed that BMCMCs and peritoneal cell-derived mast cells produced substantially different releasates following IgE-mediated activation. Moreover, we observed that the transglutaminase coagulation factor XIIIA (FXIIIA) was one of the most abundant proteins contained in the BMCMC releasates. Mast cell-deficient mice exhibited increased FXIIIA plasma and activity levels as well as reduced bleeding times, indicating that mast cells are more efficient in their ability to downregulate FXIIIA than in contributing to its amounts and functions in homeostatic conditions. We found that human chymase and mouse mast cell protease-4 (the mouse homologue of human chymase) had the ability to reduce FXIIIA levels and function via proteolytic degradation. Moreover, we found that chymase deficiency led to increased FXIIIA amounts and activity, as well as reduced bleeding times in homeostatic conditions and during sepsis. Conclusions: Our study indicates that the mast cell protease content can shape its releasate proteome. Moreover, we found that chymase plays an important role in the regulation of FXIIIA via proteolytic degradation.
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| 29. |
- Tran, Minh Quan, et al.
(författare)
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Coordination of Load Tap Changer and Distributed Energy Resources to Improve Long-term Voltage Stability
- 2022
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Ingår i: ENERGYCON 2022 - 2022 IEEE 7th International Energy Conference, Proceedings.
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Konferensbidrag (refereegranskat)abstract
- Along With the increased installation of the distributed energy resources (DER) in distribution system, long-term voltage stability at the transmission level can be improved if proper coordination is developed between DERs and the existing grid controllers, e.g., load tap changer (LTC). This paper analyzes the problem of long-term voltage instability and presenting possible countermeasures. The study summarizes essential aspects for modelling, including LTC, DERs, and especially voltage dependent load. A coordination between DERs and LTC is proposed to allocate better power supply, especially at the coupling points between transmission and distribution networks, i.e. primary substation. A case study is performed using a modified CIGRE medium-voltage benchmark network. The simulation results have shown that the coordination has substantially improved the long-term voltage stability in the way of using the reactive power support from DERs and increasing the LTC position instated of decreasing as the traditional method.
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| 30. |
- Tran, Minh Quan, et al.
(författare)
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MPC-Based Coordinated Voltage Control in LV Distribution Systems: A Case Study in Chalmers Campus Network
- 2023
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Ingår i: Conference Proceedings - 2023 IEEE Asia Meeting on Environment and Electrical Engineering, EEE-AM 2023.
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Konferensbidrag (refereegranskat)abstract
- This paper presents detailed analysis results of a model predictive control (MPC)-based coordinated voltage control demonstrated in a real low voltage network, the Chalmers campus in Sweden. First, the modeling of the MPC is presented, and the state space mode is obtained by linearization of the power flow equation around the operation point. Thus, an updated voltage vector in the grid is calculated through the sensitivity gain corresponding to reactive power deviation in the grid. Second, the developed MPC model is integrated into an Internet of Things (IoT) platform developed under the European FlexiGrid project. The state measurements in the Chalmers campus network are collected through the IoT platform as the input for the MPC model. Then, the optimal setpoints for distributed energy resources (DERs) are calculated and sent to DERs via the IoT platform. Lastly, onsite demonstration results are analyzed, showing the performance of the MPC-based voltage control in low-voltage distribution systems.
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| 31. |
- Tran, Minh Quan, et al.
(författare)
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Self-adaptive Controllers for Renewable Energy Communities Based on Transformer Loading Estimation
- 2022
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Ingår i: 2022 IEEE International Conference on Environment and Electrical Engineering and 2022 IEEE Industrial and Commercial Power Systems Europe, EEEIC / I and CPS Europe 2022.
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Konferensbidrag (refereegranskat)abstract
- In this paper, self-adaptive controllers for renewable energy communities based on data-driven approach are proposed to mitigate the voltage rise and transformer congestion at the community level. In the proposed approach, the transformer loading percentage is estimated by the trained data-driven model, which uses the extreme gradient boosting regression algorithm based on a measurement set acquired from critical coupling points of the communities. To avoid voltage rise issues, the droop control parameters (i.e., voltage threshold for P - V, Q - V curves) are adaptively tuned based on the solar irradiance availability and estimated transformer loading. The proposed approach has been tested in the IEEE European LV distribution network. Results showed that the control approach could effectively reduce 22.2 % of the total overloaded instances, while still keeping voltage magnitude in the operation range. This method can help DSOs manage voltage violation and congestion without further communication.
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| 32. |
- Tran, Trung Thai, et al.
(författare)
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Virtual Oscillator based Hierarchical Control Strategy for Multi-mode Operation of Microgrids
- 2022
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Ingår i: IEEE PES Innovative Smart Grid Technologies Conference Europe. ; 2022-October
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Konferensbidrag (refereegranskat)abstract
- One of the most important challenges in controlling a Microgrid is to enable a multi-mode operation with a smooth change from different modes. Recently, hierarchical control is considered as an effective approach to control and manage a Microgrid. This paper proposes a compatible hierarchical control strategy, leveraging the superior characteristics of Andronov-Hopf Oscillator, that enables both grid-connected and islanded operation, as well as seamless, reliable transition between operation modes. The proposed control strategy includes a PI-based Power Tracking Control loop, a Power Sharing Control loop using average consensus approach, a PR-based Synchronization Control, and a Fault Initiated Islanding Detection based on wideband, online impedance estimation. The results in MATLAB/Simulink are provided to validate the effectiveness of the proposed strategy.
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| 33. |
- Vigorito, Elena, et al.
(författare)
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Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95% CI: 0.68 to 0.79, p-value 2x 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95% CI: 0.59 to 0.80, p-value 1.0 x 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
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| 34. |
- Zalakeviciute, Rasa, et al.
(författare)
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The effect of national protest in Ecuador on PM pollution.
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Particulate matter (PM) accounts for millions of premature deaths in the human population every year. Due to social and economic inequality, growing human dissatisfaction manifests in waves of strikes and protests all over the world, causing paralysis of institutions, services and circulation of transport. In this study, we aim to investigate air quality in Ecuador during the national protest of 2019, by studying the evolution of PM2.5 (PM ≤ 2.5 µm) concentrations in Ecuador and its capital city Quito using ground based and satellite data. Apart from analyzing the PM2.5 evolution over time to trace the pollution changes, we employ machine learning techniques to estimate these changes relative to the business-as-usual pollution scenario. In addition, we present a chemical analysis of plant samples from an urban park housing the strike. Positive impact on regional air quality was detected for Ecuador, and an overall - 10.75 ± 17.74% reduction of particulate pollution in the capital during the protest. However, barricade burning PM peaks may contribute to a release of harmful heavy metals (tire manufacture components such as Co, Cr, Zn, Al, Fe, Pb, Mg, Ba and Cu), which might be of short- and long-term health concerns.
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