| 1. |
- Patel, Riyaz S., et al.
(författare)
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Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
- 2019
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Ingår i: Circulation. - 2574-8300. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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| 2. |
- Patel, Riyaz S., et al.
(författare)
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Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
- 2019
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Ingår i: Circulation. - 2574-8300. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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| 3. |
- MacMinn, Christopher W., et al.
(författare)
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Fluid-Driven Deformation of a Soft Granular Material
- 2015
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Ingår i: Physical Review X. - 2160-3308. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Compressing a porous, fluid-filled material drives the interstitial fluid out of the pore space, as when squeezing water out of a kitchen sponge. Inversely, injecting fluid into a porous material can deform the solid structure, as when fracturing a shale for natural gas recovery. These poromechanical interactions play an important role in geological and biological systems across a wide range of scales, from the propagation of magma through Earth's mantle to the transport of fluid through living cells and tissues. The theory of poroelasticity has been largely successful in modeling poromechanical behavior in relatively simple systems, but this continuum theory is fundamentally limited by our understanding of the pore-scale interactions between the fluid and the solid, and these problems are notoriously difficult to study in a laboratory setting. Here, we present a high-resolution measurement of injection-driven poromechanical deformation in a system with granular microsctructure: We inject fluid into a dense, confined monolayer of soft particles and use particle tracking to reveal the dynamics of the multiscale deformation field. We find that a continuum model based on poroelasticity theory captures certain macroscopic features of the deformation, but the particle-scale deformation field exhibits dramatic departures from smooth, continuum behavior. We observe particle-scale rearrangement and hysteresis, as well as petal-like mesoscale structures that are connected to material failure through spiral shear banding.
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| 4. |
- MacMinn, Christopher W., et al.
(författare)
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Large Deformations of a Soft Porous Material
- 2016
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Ingår i: Physical Review Applied. - : American Physical Society. - 2331-7019. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- Compressing a porous material will decrease the volume of the pore space, driving fluid out. Similarly, injecting fluid into a porous material can expand the pore space, distorting the solid skeleton. This poromechanical coupling has applications ranging from cell and tissue mechanics to geomechanics and hydrogeology. The classical theory of linear poroelasticity captures this coupling by combining Darcy's law with Terzaghi's effective stress and linear elasticity in a linearized kinematic framework. Linear poroelasticity is a good model for very small deformations, but it becomes increasingly inappropriate for moderate to large deformations, which are common in the context of phenomena such as swelling and damage, and for soft materials such as gels and tissues. The well-known theory of large-deformation poroelasticity combines Darcy's law with Terzaghi's effective stress and nonlinear elasticity in a rigorous kinematic framework. This theory has been used extensively in biomechanics to model large elastic deformations in soft tissues and in geomechanics to model large elastoplastic deformations in soils. Here, we first provide an overview and discussion of this theory with an emphasis on the physics of poromechanical coupling. We present the large-deformation theory in an Eulerian framework to minimize the mathematical complexity, and we show how this nonlinear theory simplifies to linear poroelasticity under the assumption of small strain. We then compare the predictions of linear poroelasticity with those of large-deformation poroelasticity in the context of two uniaxial model problems: fluid outflow driven by an applied mechanical load (the consolidation problem) and compression driven by a steady fluid throughflow. We explore the steady and dynamical errors associated with the linear model in both situations, as well as the impact of introducing a deformation-dependent permeability. We show that the error in linear poroelasticity is due primarily to kinematic nonlinearity and that this error (i) plays a surprisingly important role in the dynamics of the deformation and (ii) is amplified by nonlinear constitutive behavior, such as deformation-dependent permeability.
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| 5. |
- Schollick, Julia M. H., et al.
(författare)
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Segregated Ice Growth in a Suspension of Colloidal Particles
- 2016
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 120:16, s. 3941-3949
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Tidskriftsartikel (refereegranskat)abstract
- We study the freezing of a dispersion of colloidal silica particles in water, focusing on the formation of segregated ice in the form of ice lenses. Local temperature measurements in combination with video microscopy give insight into the rich variety of factors that control ice lens formation. We observe the initiation of the lenses, their growth morphology, and their final thickness and spacing over a range of conditions, in particular the effect of the particle packing and the cooling rate. We find that increasing the particle density drastically reduces the thickness of lenses but has little effect on the lens spacing. Therefore, the fraction of segregated ice formed reduces. The effect of the cooling rate, which is the product of the temperature gradient and the pulling speed across the temperature gradient, depends on which parameter is varied. A larger temperature gradient causes ice lenses to be initiated more frequently, while a lower pulling speed allows for more time for ice lenses to grow: both increase the fraction of segregated ice. Surprisingly, we find that the growth rate of a lens does not depend on its undercooling. Finally, we have indications of pore ice in front of the warmest ice lens, which has important consequences for the interpretation of the measured trends. Our findings are relevant for ice segregation occurring in a wide range of situations, ranging from model lab experiments and theories to geological and industrial processes, like frost heave and frozen food production.
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| 6. |
- Style, Robert W., et al.
(författare)
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Patterning droplets with durotaxis
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:31, s. 12541-12544
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Tidskriftsartikel (refereegranskat)abstract
- Numerous cell types have shown a remarkable ability to detect and move along gradients in stiffness of an underlying substrate-a process known as durotaxis. The mechanisms underlying durotaxis are still unresolved, but generally believed to involve active sensing and locomotion. Here, we show that simple liquid droplets also undergo durotaxis. By modulating substrate stiffness, we obtain fine control of droplet position on soft, flat substrates. Unlike other control mechanisms, droplet durotaxis works without imposing chemical, thermal, electrical, or topographical gradients. We show that droplet durotaxis can be used to create large-scale droplet patterns and is potentially useful for many applications, such as microfluidics, thermal control, and microfabrication.
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| 7. |
- Style, Robert W., et al.
(författare)
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Stiffening solids with liquid inclusions
- 2015
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Ingår i: Nature Physics. - 1745-2473 .- 1745-2481. ; 11:1, s. 82-87
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Tidskriftsartikel (refereegranskat)abstract
- From bone and wood to concrete and carbon fibre, composites are ubiquitous natural and synthetic materials. Eshelby's inclusion theory describes how macroscopic stress fields couple to isolated microscopic inclusions, allowing prediction of a composite's bulk mechanical properties from a knowledge of its microstructure. It has been extended to describe a wide variety of phenomena from solid fracture to cell adhesion. Here, we show experimentally and theoretically that Eshelby's theory breaks down for small liquid inclusions in a soft solid. In this limit, an isolated droplet's deformation is strongly size-dependent, with the smallest droplets mimicking the behaviour of solid inclusions. Furthermore, in opposition to the predictions of conventional composite theory, we find that finite concentrations of small liquid inclusions enhance the stiffness of soft solids. A straightforward extension of Eshelby's theory, accounting for the surface tension of the solid-liquid interface, explains our experimental observations. The counterintuitive stiffening of solids by fluid inclusions is expected whenever inclusion radii are smaller than an elastocapillary length, given by the ratio of the surface tension to Young's modulus of the solid matrix. These results suggest that surface tension can be a simple and effective mechanism to cloak the far-field elastic signature of inclusions.
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| 8. |
- Style, Robert W., et al.
(författare)
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Surface tension and the mechanics of liquid inclusions in compliant solids
- 2015
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Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 11:4, s. 672-679
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Tidskriftsartikel (refereegranskat)abstract
- Eshelby's theory of inclusions has wide-reaching implications across the mechanics of materials and structures including the theories of composites, fracture, and plasticity. However, it does not include the effects of surface stress, which has recently been shown to control many processes in soft materials such as gels, elastomers and biological tissue. To extend Eshelby's theory of inclusions to soft materials, we consider liquid inclusions within an isotropic, compressible, linear-elastic solid. We solve for the displacement and stress fields around individual stretched inclusions, accounting for the bulk elasticity of the solid and the surface tension (i.e. isotropic strain-independent surface stress) of the solid-liquid interface. Surface tension significantly alters the inclusion's shape and stiffness as well as its near-and far-field stress fields. These phenomena depend strongly on the ratio of the inclusion radius, R, to an elastocapillary length, L. Surface tension is significant whenever inclusions are smaller than 100L. While Eshelby theory predicts that liquid inclusions generically reduce the stiffness of an elastic solid, our results show that liquid inclusions can actually stiffen a solid when R < 3L/2. Intriguingly, surface tension cloaks the far-field signature of liquid inclusions when R = 3L/2. These results are have far-reaching applications from measuring local stresses in biological tissue, to determining the failure strength of soft composites.
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| 9. |
- Style, Robert W., et al.
(författare)
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Universal Deformation of Soft Substrates Near a Contact Line and the Direct Measurement of Solid Surface Stresses
- 2013
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 110:6, s. 066103-
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Tidskriftsartikel (refereegranskat)abstract
- Droplets deform soft substrates near their contact lines. Using confocal microscopy, we measure the deformation of silicone gel substrates due to glycerol and fluorinated-oil droplets for a range of droplet radii and substrate thicknesses. For all droplets, the substrate deformation takes a universal shape close to the contact line that depends on liquid composition, but is independent of droplet size and substrate thickness. This shape is determined by a balance of interfacial tensions at the contact line and provides a novel method for direct determination of the surface stresses of soft substrates. Moreover, we measure the change in contact angle with droplet radius and show that Young's law fails for small droplets when their radii approach an elastocapillary length scale. For larger droplets the macroscopic contact angle is constant, consistent with Young's law. DOI: 10.1103/PhysRevLett.110.066103
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