| 1. |
- Ahearn, Thomas U., et al.
(författare)
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Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
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Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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| 2. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 3. |
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| 4. |
- Dixon-Suen, Suzanne C, et al.
(författare)
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Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
- 2022
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Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.METHODS: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.RESULTS: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).CONCLUSION: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
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| 5. |
- Kapoor, Pooja Middha, et al.
(författare)
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Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
- 2021
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
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| 6. |
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| 7. |
- Kurian, Thomas, 1981-
(författare)
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An experimental investigation of disturbance growth in boundary layer flows
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis deals with the early stages of transition to turbulence in two different baseflows, namely the Falkner-Skan-Cooke boundary layer (FSC) and the asymptotic suction boundary layer (ASBL). Grid-generated turbulence is studied in order to characterise the isotropy levels, free-stream turbulence levels and characteristic length scales that will be present in the receptivity study. By varying the grids and their location it is possible to control the turbulence intensity level, Tu, and the integral length scale independently. Comparisons with other studies show that for increasing Re_M the isotropy levels and the rate of kinetic energy decay asymptotically approach the theoretical values. The FSC describes a a 3D boundary layer subjected to a pressure gradient. The FSC is stable to TS-waves, but becomes susceptible to both travelling and stationary crossflow disturbances. In the experiments the travelling modes were triggered using free-stream turbulence (FST) and the stationary modes were triggered using an array of cylindrical roughness elements. The receptivity phase to FST was linear as well as the initial growth. For high enough $Tu$ inside the boundary layer, nonlinear behaviour was observed further downstream. The stationary mode could only be triggered using tall roughness elements, with low heights resulting in no noticeable disturbances. The receptivity is found to be nonlinear for the roughness heights tested and the growth of the disturbances is exponential. For low levels of FST, Tu < 0.25%, the travelling mode as well as the stationary mode grew. The ASBL is formed when uniform suction is applied to the surface of a porous plate with a flow over it. This baseflow is very stable to TS-waves, and was used to study the transient growth. For the ASBL, stationary disturbances were triggered using a spanwise array or cylindrical roughness elements. The velocity signals were decomposed using a spatial Fourier transform to study the growth of individual modes. The fundamental mode as well as some harmonics were seen to undergo transient growth, before finally decaying exponentially. Comparisons were made to the experimental data using optimal perturbation theory. The global optimals did not describe the transient growth effects well. The calculations were redone for suboptimal times and showed agreement with the experimental data, showing that optimal perturbation theory can describe transient growth if the initial disturbance state is known.
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| 8. |
- Kurian, Thomas, et al.
(författare)
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Boundary layer receptivity to free-stream turbulence and surface roughness over a swept flat plate
- 2011
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Ingår i: Physics of fluids. - : AIP Publishing. - 1070-6631 .- 1089-7666. ; 23:3, s. 034107-
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Tidskriftsartikel (refereegranskat)abstract
- An experimental study of the receptivity of disturbances and their subsequent development into a three-dimensional boundary layer has been carried out. The three-dimensional boundary layer was set up using a flat plate with a swept leading edge and a pressure gradient using a displacement body at the ceiling of the test section. Low level free-stream turbulence was generated with five different screens and was shown to generate traveling crossflow modes for all but the lowest turbulence level, i.e., for Tu > 0.2%, where instead a stationary crossflow disturbance dominated. Stationary crossflow disturbances were triggered by small cylindrical roughness elements arranged in an array. For high enough roughness Reynolds number (Re-k) stationary disturbances growing exponentially were seen and their amplitude seems to scale with Re-k(2.3).
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| 9. |
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| 10. |
- Kurian, Thomas, et al.
(författare)
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Evolution of traveling crossflow modes over a swept flat plate
- 2009
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Konferensbidrag (refereegranskat)abstract
- An experimental investigation has been carried out to examine the growth of traveling crossflow instabilities over a swept flat plate mimicking the Falkner-Skan-Cooke boundary layer. Different turbulence generating grids were placed upstream of the leading edge to vary incoming parameters. Hot-wire measurements were taken for one component of velocity and compared with linear PSE analysis. These showed a decrease in the growth rate for increasing turbulence intensity, which was most likely cause by nonlinear effects. Streamwise correlation measurements were also taken. All the cases except one triggered the same spanwise integral length scale inside the boundary layer. Receptivity coefficients are needed to do the PSE calculations and to see the need for nonlinear PSE.
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