Structure, diffusion and rheology of Brownian suspensions by Stokesian Dynamics simulation

The non-equilibrium behaviour of concentrated colloidal dispersions is studied using Stokesian Dynamics, a molecular-dynamics-like simulation technique for analysing suspensions of particles immersed in a Newtonian fluid. The simulations are of a monodisperse suspension of Brownian hard spheres in simple shear flow as a function of the Péclet number, Pe, which measures the relative importance of hydrodynamic and Brownian forces, over a range of volume fraction 0.316 [less-than-or-eq, slant] [phi] [less-than-or-eq, slant] 0.49. For Pe < 10, Brownian motion dominates the behaviour, the suspension remains well-dispersed, and the viscosity shear thins. The first normal stress difference is positive and the second negative. At higher Pe, hydrodynamics dominate resulting in an increase in the long-time self-diffusivity and the viscosity. The first normal stress difference changes sign when hydrodynamics dominate. Simulation results are shown to agree well with both theory and experiment

Self-diffusion in sheared suspensions by dynamic simulation

The behaviour of the long-time self-diffusion tensor in concentrated colloidal dispersions is studied using dynamic simulation. The simulations are of a suspension of monodisperse Brownian hard spheres in simple shear flow as a function of the Péclet number, Pe, which measures the relative importance of shear and Brownian forces, and the volume fraction, [phi]. Here, Pe = &[gamma]dot;a^2/D0, where &[gamma]dot; is the shear rate, a the particle size and D0 = kT/6[pi][eta]a is the Stokes–Einstein diffusivity of an isolated particle of size a with thermal energy kT in a solvent of viscosity [eta]. Two simulations algorithms are used: Stokesian Dynamics for inclusion of the many-body hydrodynamic interactions, and Brownian Dynamics for suspensions without hydrodynamic interactions. A new procedure for obtaining high-quality diffusion data based on averaging the results of many short simulations is presented and utilized. At low shear rates, low Pe, Brownian diffusion due to a random walk process dominates and the characteristic scale for diffusion is the Stokes–Einstein diffusivity, D0. At zero Pe the diffusivity is found to be a decreasing function of [phi]. As Pe is slowly increased, O(Pe) and O(Pe^3/2) corrections to the diffusivity due to the flow are clearly seen in the Brownian Dynamics system in agreement with the theoretical results of Morris & Brady (1996). At large shear rates, large Pe, both systems exhibit diffusivities that grow linearly with the shear rate by the non-Brownian mechanism of shear-induced diffusion. In contrast to the behaviour at low Pe, this shear-induced diffusion mode is an increasing function of [phi]. Long-time rotational self-diffusivities are of interest in the Stokesian Dynamics system and show similar behaviour to their translational analogues. An off-diagonal long-time self-diffusivity, Dxy, is reported for both systems. Results for both the translational and rotational Dxy show a sign change from low Pe to high Pe due to different mechanisms in the two regimes. A physical explanation for the off-diagonal diffusivities is proposed

Unsteady shear flows of colloidal hard-sphere suspensions by dynamic simulation

The rheology during the start-up and cessation of simple shear flow has been investigated for near hard-sphere colloidal suspensions. Simulations augmented by theoretical analysis are used to determine how the non-Newtonian stress development and relaxation depend on the microstructure. Accelerated Stokesian dynamics (ASD) and Brownian dynamics (BD) simulations are used for 0.05 ≤ Pe ≤ 500 in concentrated freely flowing suspensions; the Péclet number defining the ratio of shear to thermal motion is Pe=3πηγ ̇a^3/kT with η the suspending fluid viscosity, γ ̇ the shear rate, and kT the thermal energy. Theoretical predictions based on the Smoluchowski equation for dilute suspensions are made, and these are primarily used for comparison with results from BD simulations in which hydrodynamic interactions are neglected. For suspensions with hydrodynamics, simulations by ASD are used to probe start-up and flow cessation over a large range of Pe; these studies focus on solid volume fraction ϕ=0.4, with more limited examinations at other ϕ. The use of both BD and ASD simulations allows us to discriminate hydrodynamic interaction effects on the suspension rheology. The Brownian stresses computed by either method exhibit overshoots of their steady state value during the start-up of shear flow. The overshoots occur at strain amplitudes which depend on Pe, and the overshoot is described by a model based on extension of the concept of cage-breaking from glass dynamics. Results from the relaxation of a sheared suspension show that the distortion of the pair distribution function from its equilibrium form has a fast radial relaxation and a slow angular relaxation. The various rheometric functions (relative viscosity; first and second normal stress differences) are found to respond on different timescales, reflecting their different dependences on the flow-induced structure. A re-examination of steady shear flow allows us to find normal stress differences which tend properly toward zero at small Pe, unlike prior work; the discrepancy is found to be due to finite size scaling, as small simulations used in prior work resulted in excessively large normal stress responses at small Pe

Lower Extremity Biomechanics Are Altered Across Maturation in Sport-Specialized Female Adolescent Athletes

Sport specialization is a growing trend in youth athletes and may contribute to increased injury risk. The neuromuscular deficits that often manifest during maturation in young, female athletes may be exacerbated in athletes who specialize in a single sport. The purpose of this study was to investigate if sport specialization is associated with increased lower extremity biomechanical deficits pre- to post-puberty in adolescent female athletes. Seventy-nine sport-specialized female adolescent (Mean ± SD age = 13.4 ± 1.8 years) basketball, soccer, and volleyball athletes were identified and matched with seventy-nine multi-sport (soccer, basketball, and volleyball) female athletes from a database of 1,116 female adolescent basketball, soccer, and volleyball athletes who were enrolled in one of two large prospective, longitudinal studies. The athletes were assessed over two visits (Mean ± SD time = 724.5 ± 388.7 days) in which they were classified as pre-pubertal and post-pubertal, respectively. Separate 2 × 2 analyses of covariance were used to compare sport-specialized and multi-sport groups and dominant/non-dominant limbs with respect to pubertal changes in peak knee sagittal, frontal, and transverse plane joint angular measures and moments of force recorded while performing a drop vertical jump task. The sport-specialized group were found to exhibit significantly larger post-pubertal increases in peak knee abduction angle (p = 0.005) and knee abduction moment (p = 0.006), as well as a smaller increase in peak knee extensor moment (p = 0.032) during landing when compared to the multi-sport group. These biomechanical changes are indicative of potentially compromised neuromuscular control that may increase injury risk pre- to post-puberty in sport-specialized female athletes. Consideration of maturation status may be an important factor in assessing the injury risk profiles of adolescent athletes who specialize in sport

Combined cognitive–behavioural and mindfulness programme for people living with dystonia : a proof-of-concept study

Objectives To design and test the delivery of an intervention targeting the non-motor symptoms of dystonia and pilot key health and well-being questionnaires in this population. Design A proof-of-concept study to test the delivery, acceptability, relevance, structure and content for a 3-day group residential programme for the management of dystonia. Setting Participants were recruited from a single botulinum toxin clinic. The intervention was delivered in the community. Participants 14 participants consented to take part (2 withdrew prior to the starting of intervention). The average age was 60 years (range 44–77), 8 of whom were female. After drop-out, 9 participants completed the 3-day programme. Intervention A 3-day group residential programme. Primary and secondary outcome measures Process evaluation and interviews were carried out before and after the intervention to explore participant's views and expectations, as well as experiences of the intervention. Select questionnaires were completed at baseline, 1-month and 3-month follow-up. Results Although participants were not sure what to expect from the programme, they found it informative and for many this together with being in a group with other people with dystonia legitimised their condition. Mindfulness was accepted and adopted as a coping strategy. This was reflected in the 1-month follow-up. Conclusions We successfully delivered a 3-day residential programme to help those living with dystonia manage their condition. Further improvements are suggested. The quantitative outcome measures were acceptable to this group of patients with dystonia

Intra- and inter-individual genetic differences in gene expression

Genetic variation is known to influence the amount of mRNA produced by a gene. Given that the molecular machines control mRNA levels of multiple genes, we expect genetic variation in the components of these machines would influence multiple genes in a similar fashion. In this study we show that this assumption is correct by using correlation of mRNA levels measured independently in the brain, kidney or liver of multiple, genetically typed, mice strains to detect shared genetic influences. These correlating groups of genes (CGG) have collective properties that account for 40-90% of the variability of their constituent genes and in some cases, but not all, contain genes encoding functionally related proteins. Critically, we show that the genetic influences are essentially tissue specific and consequently the same genetic variations in the one animal may up-regulate a CGG in one tissue but down-regulate the same CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. The implication of this study is that this class of genetic variation can result in complex inter- and intra-individual and tissue differences and that this will create substantial challenges to the investigation of phenotypic outcomes, particularly in humans where multiple tissues are not readily available.&#xd;&#xa;&#xd;&#xa

The theory of the firm and its critics: a stocktaking and assessment

Includes bibliographical references."Prepared for Jean-Michel Glachant and Eric Brousseau, eds. New Institutional Economics: A Textbook, Cambridge, Cambridge University Press.""This version: August 22, 2005."Since its emergence in the 1970s the modern economic or Coasian theory of the firm has been discussed and challenged by sociologists, heterodox economists, management scholars, and other critics. This chapter reviews and assesses these critiques, focusing on behavioral issues (bounded rationality and motivation), process (including path dependence and the selection argument), entrepreneurship, and the challenge from knowledge-based theories of the firm

Personalized versus standardized dosing strategies for the treatment of childhood amblyopia: study protocol for a randomized controlled trial

Background: Amblyopia is the commonest visual disorder of childhood in Western societies, affecting, predominantly, spatial visual function. Treatment typically requires a period of refractive correction (‘optical treatment’) followed by occlusion: covering the nonamblyopic eye with a fabric patch for varying daily durations. Recent studies have provided insight into the optimal amount of patching (‘dose’), leading to the adoption of standardized dosing strategies, which, though an advance on previous ad-hoc regimens, take little account of individual patient characteristics. This trial compares the effectiveness of a standardized dosing strategy (that is, a fixed daily occlusion dose based on disease severity) with a personalized dosing strategy (derived from known treatment dose-response functions), in which an initially prescribed occlusion dose is modulated, in a systematic manner, dependent on treatment compliance. Methods/design: A total of 120 children aged between 3 and 8 years of age diagnosed with amblyopia in association with either anisometropia or strabismus, or both, will be randomized to receive either a standardized or a personalized occlusion dose regimen. To avoid confounding by the known benefits of refractive correction, participants will not be randomized until they have completed an optical treatment phase. The primary study objective is to determine whether, at trial endpoint, participants receiving a personalized dosing strategy require fewer hours of occlusion than those in receipt of a standardized dosing strategy. Secondary objectives are to quantify the relationship between observed changes in visual acuity (logMAR, logarithm of the Minimum Angle of Resolution) with age, amblyopia type, and severity of amblyopic visual acuity deficit. Discussion: This is the first randomized controlled trial of occlusion therapy for amblyopia to compare a treatment arm representative of current best practice with an arm representative of an entirely novel treatment regimen based on statistical modelling of previous trial outcome data. Should the personalized dosing strategy demonstrate superiority over the standardized dosing strategy, then its adoption into routine practice could bring practical benefits in reducing the duration of treatment needed to achieve an optimal outcome

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al