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- 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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- Tsao, K., et al.
(författare)
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Effects of regional differences and demography in modelling foot-and-mouth disease in cattle at the national scale
- 2020
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Ingår i: Interface Focus. - : Royal Society Publishing. - 2042-8898 .- 2042-8901. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Foot-and-mouth disease (FMD) is a fast-spreading viral infection that can produce large and costly outbreaks in livestock populations. Transmission occurs at multiple spatial scales, as can the actions used to control outbreaks. The US cattle industry is spatially expansive, with heterogeneous distributions of animals and infrastructure. We have developed a model that incorporates the effects of scale for both disease transmission and control actions, applied here in simulating FMD outbreaks in US cattle. We simulated infection initiating in each of the 3049 counties in the contiguous US, 100 times per county. When initial infection was located in specific regions, large outbreaks were more likely to occur, driven by infrastructure and other demographic attributes such as premises clustering and number of cattle on premises. Sensitivity analyses suggest these attributes had more impact on outbreak metrics than the ranges of estimated disease parameter values. Additionally, although shipping accounted for a small percentage of overall transmission, areas receiving the most animal shipments tended to have other attributes that increase the probability of large outbreaks. The importance of including spatial and demographic heterogeneity in modelling outbreak trajectories and control actions is illustrated by specific regions consistently producing larger outbreaks than others. © 2019 The Author(s) Published by the Royal Society. All rights reserved.
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- Gilbertson, Kendra, et al.
(författare)
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The Importance of Livestock Demography and Infrastructure in Driving Foot and Mouth Disease Dynamics
- 2022
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Ingår i: Life. - : MDPI. - 2075-1729. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- Transboundary animal diseases, such as foot and mouth disease (FMD) pose a significant and ongoing threat to global food security. Such diseases can produce large, spatially complex outbreaks. Mathematical models are often used to understand the spatio-temporal dynamics and create response plans for possible disease introductions. Model assumptions regarding transmission behavior of premises and movement patterns of livestock directly impact our understanding of the ecological drivers of outbreaks and how to best control them. Here, we investigate the impact that these assumptions have on model predictions of FMD outbreaks in the U.S. using models of livestock shipment networks and disease spread. We explore the impact of changing assumptions about premises transmission behavior, both by including within-herd dynamics, and by accounting for premises type and increasing the accuracy of shipment predictions. We find that the impact these assumptions have on outbreak predictions is less than the impact of the underlying livestock demography, but that they are important for investigating some response objectives, such as the impact on trade. These results suggest that demography is a key ecological driver of outbreaks and is critical for making robust predictions but that understanding management objectives is also important when making choices about model assumptions.
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- Sellman, Stefan, et al.
(författare)
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Modeling nation-wide US swine movement networks at the resolution of the individual premises
- 2022
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Ingår i: Epidemics. - : Elsevier. - 1755-4365 .- 1878-0067. ; 41
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Tidskriftsartikel (refereegranskat)abstract
- The spread of infectious livestock diseases is a major cause for concern in modern agricultural systems. In the dynamics of the transmission of such diseases, movements of livestock between herds play an important role. When constructing mathematical models used for activities such as forecasting epidemic development, evaluating mitigation strategies, or determining important targets for disease surveillance, including between -premises shipments is often a necessity. In the United States (U.S.), livestock shipment data is not routinely collected, and when it is, it is not readily available and mostly concerned with between-state shipments. To bridge this gap in knowledge and provide insight into the complete livestock shipment network structure, we have developed the U.S. Animal Movement Model (USAMM). Previously, USAMM has only existed for cattle shipments, but here we present a version for domestic swine. This new version of USAMM consists of a Bayesian model fit to premises demography, county-level livestock industry variables, and two limited data sets of between-state swine movements. The model scales up the data to simulate nation-wide networks of both within-and between-state shipments at the level of individual premises. Here we describe this shipment model in detail and subsequently explore its usefulness with a rudimentary predictive model of the prevalence of porcine epidemic diarrhea virus (PEDv) across the U.S. Additionally, in order to promote further research on livestock disease and other topics involving the movements of swine in the U.S., we also make 250 synthetic premises-level swine shipment networks with complete coverage of the entire conterminous U.S. freely available to the research community as a useful surrogate for the absent shipment data.
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- Sellman, Stefan, et al.
(författare)
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Modeling US cattle movements until the cows come home: Who ships to whom and how many?
- 2022
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Ingår i: Computers and Electronics in Agriculture. - : ELSEVIER SCI LTD. - 0168-1699 .- 1872-7107. ; 203
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Tidskriftsartikel (refereegranskat)abstract
- Livestock movements between agricultural premises is an important pathway for the spread of infectious disease. Data providing details about the origin and destination of shipments, as well as information about the shipment size is an important component of computer models used to formulate mitigation strategies and design surveillance programs. The United States (U.S.) currently lacks a comprehensive database of farm animal shipments, which hinders such efforts. With the U.S. Animal Movement Model (USAMM), earlier work has successfully scaled up from limited data based on interstate certificates of veterinary inspection (CVI) to comprehensive county-level shipment networks at the national scale. In this work, we present three major improvements to earlier versions of USAMM: (1) increased resolution of the model and simulated networks to the level of individual premises; (2) predictions of shipment sizes; (3) taking into account the types and herd sizes of the premises. We fitted parameters in a Bayesian framework to two sets of CVI data consisting of sub-samples of one years between-state beef and dairy shipments. Through posterior predictive simulation, we then created 1,000 synthetic beef and dairy networks, which we make publicly available to support livestock disease modeling. The simulated networks were validated against summary statistics of the training data as well as out-of-sample CVI data from subsequent years. This new development opens up the possibility of using USAMM in a broader spectrum of applications where information about shipment size and premises identity is necessary and gives novel insights into the U.S. cattle shipment network.
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