| 1. |
- Couch, Fergus J., et al.
(author)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Journal article (peer-reviewed)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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| 2. |
- Hallberg, Daniel, 1968-
(author)
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Essays on Household Behavior and Time-Use
- 2002
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Doctoral thesis (other academic/artistic)abstract
- Essay 1 studies the household's decision to supply labor and tests if the so-called unitary model holds. What is subject to a test is the resulting symmetry of the Slutsky matrix, i.e., that the compensated cross-wage effects are equal. The test uses Swedish time budget data from 1984 and 1993. Contrary to most other studies from other countries, the conclusion is that symmetry cannot be rejected.Essay 2 (with Anders Klevmarken) analyzes the trade-off between parents' time with their own kids and market work, and its dependence on out-of-home day care. Process benefit scores indicate that time with one's own children is prefered above all other activites, closely followed by market work. Our empirical results suggest that, using a simultaneous equation framework, parents' decisions about market work and time with their children are strongly interdependent. Economic incentives primarily work through decisions about market work, while the direct effects on time with their children are weak. The results suggest that a change in the mother's working hours has less influence on the parents' time with their children than a change in the father's working hours. This would imply that a policy working to increase the time with people's own children should primarily influence the father's work hours. We also find that parents prefer joint activities with their children, and that out-of-home child care is not chosen as a substitute for own time with children.Essay 3 examines the temporal choices of time-use, synchronous leisure of spouses and the extent to which spouses spend time together. I test if spouses coordinate their working schedule so that they obtain more synchronous leisure and estimate the size of the effect of coordination in terms of additional synchronous leisure by using a control group of matched singles. The time budget data set used in this paper allows for a distinction between simultaneous time-use of spouses and the actual time that spouses meet. The empirical results suggest that the effect of spouses' coordination of work and leisure schedules is 45 minutes of additional synchronous leisure. Spouses' decisions about market work and leisure timing are very interdependent during most hours of the day. The results also suggest that, conditional on synchronous leisure, parents with small children spend less time together than others, while couples below 40 spend more time together than older ones. There is also some support for more educated people allocating less time to their spouses.Essay 4 (with Per Johansson) gives general conditions for the data generating process to facilitate the testing of structural dependence of turnover on the average (or median) price in the homogenous housing market. Furthermore, the implications of aggregation over sub-markets is studied. A plausible explanation of the disparate empirical findings in this literature may be aggregation over heterogenous sub-markets. This conclusion is supported by empirical findings using longitudinal quarterly data for 289 Swedish municipalities during 1981:1-2000:2.
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| 3. |
- Lawrenson, Kate, et al.
(author)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)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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| 4. |
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| 5. |
- Shu, Xiang, et al.
(author)
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Associations of obesity and circulating insulin and glucose with breast cancer risk : a Mendelian randomization analysis
- 2019
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In: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 48:3, s. 795-806
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Journal article (peer-reviewed)abstract
- Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
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| 6. |
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| 7. |
- Zeng, Chenjie, et al.
(author)
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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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In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
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Journal article (peer-reviewed)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. |
- Akander, Jan, et al.
(author)
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Simulated Long-term Thermal Performance of a Building That Utilizes a Heat Pump System and Borehole
- 2008
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In: Durability of Building Materials & Components 11. - Istanbul, Turkey : Istanbul Technical University. - 9789755613253 - 9789755613291
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Conference paper (peer-reviewed)abstract
- Over the last decades, installation and use of heat pumps has grown rapidly in Sweden, to the extent that these mainly or partly heat roughly 25 % of the heated floor space in single-family houses. A majority are ground coupled where the heat exchanger is a borehole of 60-220 m depth. As the heat pump system operates, heat extraction will in time reduce borehole temperatures, rendering lowered efficiency of the heat pump system thus directly affecting its economical and environmental aspects. Within the building sector, durability and life performance dynamics of energy systems is often not reflected upon. System performance and efficiency is assumed to be static over time, changing only due to different operation scenarios. This paper serves to quantify the long-term thermal performance degradation of a component, in this case the borehole, and how the degradation of this component affects performance-over-time of an entire system, in this case the heating system of the building. A dynamic thermal simulation model is used to assess the long-term thermal performance of the borehole. The building, which the heat pump serves, is assumed to be a typical Swedish house with normal energy consumption. Simulation results show that the depth of the borehole is of great importance to limit over-time temperature drops. The efficiency of the heat pump system is directly dependent of temperatures in the borehole. How the overall system performance is affected by component performance degradation, is highlighted.
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| 9. |
- Baumgarten, Matthias, et al.
(author)
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Embedding Self-Awareness into Objects of Daily Life - The Smart Kettle
- 2010
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In: 6th International Conference on Intelligent Environments. - Los Alamitos, Calif. - 9781424478361 ; , s. 34-39
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Conference paper (peer-reviewed)abstract
- Intelligent Environments on varying scales and for different purposes are slowly becoming a reality. In the near future, global smart world infrastructures will become a commodity that will support various activities of daily life at different degrees of realism. Such infrastructures have the potential to offer dedicated, context- and situation-aware information and services by simultaneously providing the next-generation of data collection, execution and service provisioning layers. One key aspect of this vision is the correct monitoring and understanding of how people interact with their environment; how they can actually benefit from the added intelligence; and finally how future services can be improved or better personalized to enhance human environment interaction as a whole. This level of intelligence is of particular relevance in the health and social care domain where person-centric services can be deployed to assist or even enable a person in performing activities of daily living. This paper discusses the concept of embedded self-aware profiles for smart devices that can be used to gain a deeper contextual understanding of their use and also discusses the emergence of a general model of Ambient Intelligence that is based on the collective existence and behavior of such smart devices. Although generic in principle, the proposed concepts have been exemplified by a distinct use case, namely a smart kettle.
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| 10. |
- Bellander, Rickard, et al.
(author)
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Durability of outdoor exposed wood : a comparative study on a noise barrier
- 2003
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Other publication (pop. science, debate, etc.)abstract
- In March 1996 nine test sections of a noise barrier were built along the Arlandaline in co-operation with Banverket, Royal Institute of Technology (KTH), Swedish National Testing Research Institute (SP), Beijer Bygg AB and different wood preservative manufactures. Each sections has an approximately length of 4 meters per section and a height of 3,1 meter. Three sections are made of non-treated pine, spruce and larch respectively. The rest of the sections are made of pine, treated with different wood preservations. The aim of this study is to find the most appropriate wood material for a specific construction, in this case a noise barrier, regard to durability and decomposition, and in the extension to find the most ecological and economic wood material. By comparing different wood species and preservations of wood regard to durability of outdoor exposed wood gives an indication of the most appropriate wood material to be chosen for this type of construction. The untreated spruce, pine and larch boards in contact with ground is in a bad condition, an assessed service life of about 5-15 years according to the results in this study, while the untreated wood above ground is hardly affected at all by biological attacks. No degradation is detected on the different preserved pine sections. More data is needed to assess the residual service life of the wood preserved sections.
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