Reduction in arterial wall strain with aggressive lipid-lowering therapy in patients with carotid artery disease

Background: Inflammation and biomechanical factors have been associated with the development of vulnerable atherosclerotic plaques. Lipid-lowering therapy has been shown to be effective in stabilizing them by reducing plaque inflammation. Its effect on arterial wall strain, however, remains unknown. The aim of the present study was to investigate the role of high- and low-dose lipid-lowering therapy using an HMG-CoA reductase inhibitor, atorvastatin, on arterial wall strain. Methods and Results: Forty patients with carotid stenosis >40% were successfully followed up during the Atorvastatin Therapy: Effects on Reduction Of Macrophage Activity (ATHEROMA; ISRCTN64894118) Trial. All patients had plaque inflammation as shown by intraplaque accumulation of ultrasmall super paramagnetic particles of iron oxide on magnetic resonance imaging at baseline. Structural analysis was performed and change of strain was compared between high- and low-dose statin at 0 and 12 weeks. There was no significant difference in strain between the 2 groups at baseline (P=0.6). At 12 weeks, the maximum strain was significantly lower in the 80-mg group than in the 10-mg group (0.085±0.033 vs. 0.169±0.084; P=0.001). A significant reduction (26%) of maximum strain was observed in the 80-mg group at 12 weeks (0.018±0.02; P=0.01). Conclusions: Aggressive lipid-lowering therapy is associated with a significant reduction in arterial wall strain. The reduction in biomechanical strain may be associated with reductions in plaque inflammatory burden.

In vivo velocity vector imaging and time-resolved strain rate measurements in the wall of blood vessels using MRI

In this paper, we present a new approach for velocity vector imaging and time-resolved measurements of strain rates in the wall of human arteries using MRI and we prove its feasibility on two examples: in vitro on a phantom and in vivo on the carotid artery of a human subject. Results point out the promising potential of this approach for investigating the mechanics of arterial tissues in vivo.

Normalized wall index specific and MRI-based stress analysis of atherosclerotic carotid plaques: A study comparing acutely symptomatic and asymptomatic patients

Background: Biomechanical stresses play an important role in determining plaque stability. Quantification of these simulated stresses can be potentially used to assess plaque vulnerability and differentiate different patient groups. Methods and Results: 54 asymptomatic and 45 acutely symptomatic patients underwent in vivo multicontrast magnetic resonance imaging (MRI) of the carotid arteries. Plaque geometry used for finite element analysis was derived from in vivo MRI at the sites of maximum and minimum plaque burden. In total, 198 slices were used for the computational simulations. A pre-shrink technique was used to refine the simulation. Maximum principle stress at the vulnerable plaque sites (ie, critical stress) was extracted for the selected slices and a comparison was performed between the 2 groups. Critical stress in the slice with maximum plaque burden is significantly higher in acutely symptomatic patients as compared to asymptomatic patients (median, inter quartile range: 198.0 kPa (119.8-359.0 kPa) vs 138.4 kPa (83.8-242.6 kPa), P=0.04). No significant difference was found in the slice with minimum plaque burden between the 2 groups (196.7 kPa (133.3-282.7 kPa) vs 182.4 kPa (117.2-310.6 kPa), P=0.82). Conclusions: Acutely symptomatic carotid plaques have significantly high biomechanical stresses than asymptomatic plaques. This might be potentially useful for establishing a biomechanical risk stratification criteria based on plaque burden in future studies.

Computed wall stress may predict the growth of abdominal aortic aneurysm

Growth rate of abdominal aortic aneurysm (AAA) is thought to be an important indicator of the potential risk of rupture. Wall stress is also thought to be a trigger for its rupture. However, stress change during the expansion of an AAA is unclear. Forty-four patients with AAAs were included in this longitudinal follow-up study. They were assessed by serial abdominal ultrasonography and computerized tomography (CT) scans if a critical size was reached or a rapid expansion occurred. Patient-specific 3-dimensional AAA geometries were reconstructed from the follow-up CT images. Structural analysis was performed to calculate the wall stresses of the AAA models at both baseline and final visit. A non-linear large-strain finite element method was used to compute the wall stress distribution. The average growth rate was 0.66cm/year (range 0-1.32 cm/year). A significantly positive correlation between shoulder tress at baseline and growth rate was found (r=0.342; p=0.02). A higher shoulder stress is associated with a rapidly expanding AAA. Therefore, it may be useful for estimating the growth expansion of AAAs and further risk stratification of patients with AAAs.

Impact of calcification and intraluminal thrombus on the computed wall stresses of abdominal aortic aneurysm

Background: Increased biomechanical stresses within the abdominal aortic aneurysm (AAA) wall contribute to its rupture. Calcification and intraluminal thrombus can be commonly found in AAAs, but the relationship between calcification/intraluminal thrombus and AAA wall stress is not completely described. Methods: Patient-specific three-dimensional AAA geometries were reconstructed from computed tomographic images of 20 patients. Structural analysis was performed to calculate the wall stresses of the 20 AAA models and their altered models when calcification or intraluminal thrombus was not considered. A nonlinear large-strain finite element method was used to compute the wall stress distribution. The relationships between wall stresses and volumes of calcification and intraluminal thrombus were sought. Results: Maximum stress was not correlated with the percentage of calcification, and was negatively correlated with the percentage of intraluminal thrombus (r = -0.56; P = .011). Exclusion of calcification from analysis led to a significant decrease in maximum stress by a median of 14% (range, 2%-27%; P < .01). When intraluminal thrombus was eliminated, maximum stress increased significantly by a median of 24% (range, 5%-43%; P < .01). Conclusion: The presence of calcification increases AAA peak wall stress, suggesting that calcification decrease the biomechanical stability of AAA. In contrast, intraluminal thrombus reduces the maximum stress in AAA. Calcification and intraluminal thrombus should both be considered in the evaluation of wall stress for risk assessment of AAA rupture.

The impact of wall shear stress and pressure drop on the stability of the atherosclerotic plaque

Rupture of vulnerable atheromatous plaque in the carotid and coronary arteries often leads to stroke and heart attack respectively. The mechanism of blood flow and plaque rupture in stenotic arteries is still not fully understood. A three dimensional rigid wall model was solved under steady state conditions and unsteady conditions by assuming a time-varying inlet velocity profile to investigate the relative importance of axial forces and pressure drops in arteries with asymmetric stenosis. Flow-structure interactions were investigated for the same geometry and the results were compared with those retrieved with the corresponding 2D cross-section structural models. The Navier-Stokes equations were used as the governing equations for the fluid. The tube wall was assumed hyperelastic, homogeneous, isotropic and incompressible. The analysis showed that the three dimensional behavior of velocity, pressure and wall shear stress is in general very different from that predicted by cross-section models. Pressure drop across the stenosis was found to be much higher than shear stress. Therefore, pressure may be the more important mechanical trigger for plaque rupture other than shear stress, although shear stress is closely related to plaque formation and progression.

Fire resistance of light gauge steel frame wall systems lined with gypsum plasterboards

Light gauge steel frame (LSF) wall systems are increasingly used in residential and commercial buildings as load bearing and non-load bearing elements. Conventionally, the fire resistance ratings of such building elements are determined using approximate prescriptive methods based on limited standard fire tests. However, recent studies have shown that in some instances real building fire time-temperature curves could be more severe than the standard fire curve, in terms of maximum temperature and rate of temperature rise. This has caused problems for safe evacuation and rescue activities, and in some instances has also lead to the collapse of buildings earlier than the prescribed fire resistance. Therefore a detailed research study into the performance of LSF wall systems under both standard fire and realistic fire conditions was undertaken using full scale fire tests to understand the fire performance of different LSF wall configurations. Both load bearing and non-load bearing full scale fire tests were performed on LSF walls configurations which included single layer, double layer, externally insulated wall panels made up of different steel sections and thicknesses of gypsum plasterboards. The non-load bearing fire test results were utilized to understand the factors affecting the fire resistance of LSF walls, while loading bearing fire test results led to development of simplified methods to predict the fire resistance ratings of load bearing LSF walls exposed to both standard and realistic design fires. This paper presents the results of full scale experimental study and highlights the effects of standard and realistic fire conditions on fire performance of LSF walls.

A reanalysis of 409 European-Ancestry and African American schizophrenia pedigrees reveals significant linkage to 8p23.3 with evidence of locus heterogeneity

The detection and replication of schizophrenia risk loci can require substantial sample sizes, which has prompted various collaborative efforts for combining multiple samples. However, pooled samples may comprise sub-samples with substantial population genetic differences, including allele frequency differences. We investigated the impact of population differences via linkage reanalysis of Molecular Genetics of Schizophrenia 1 (MGS1) affected sibling-pair data, comprising two samples of distinct ancestral origin: European (EA: 263 pedigrees) and African-American (AA: 146 pedigrees). To exploit the linkage information contained within these distinct continental samples, we performed separate analyses of the individual samples, allowing for within-sample locus heterogeneity, and the pooled sample, allowing for both within-sample and between-sample heterogeneity. Significance levels, corrected for the multiple tests, were determined empirically. For all suggestive peaks, stronger linkage evidence was obtained in either the EA or AA sample than the combined sample, regardless of how heterogeneity was modeled for the latter. Notably, we report genomewide significant linkage of schizophrenia to 8p23.3 and evidence for a second, independent susceptibility locus, reaching suggestive linkage, 29 cM away on 8p21.3. We also detected suggestive linkage on chromosomes 5p13.3 and 7q36.2. Many regions showed pronounced differences in the extent of linkage between the EA and AA samples. This reanalysis highlights the potential impact of population differences upon linkage evidence in pooled data and demonstrates a useful approach for the analysis of samples drawn from distinct continental groups.

The importance of modelling heterogeneity in complex disease: application to NIMH Schizophrenia Genetics Initiative data

As for other complex diseases, linkage analyses of schizophrenia (SZ) have produced evidence for numerous chromosomal regions, with inconsistent results reported across studies. The presence of locus heterogeneity appears likely and may reduce the power of linkage analyses if homogeneity is assumed. In addition, when multiple heterogeneous datasets are pooled, inter-sample variation in the proportion of linked families (alpha) may diminish the power of the pooled sample to detect susceptibility loci, in spite of the larger sample size obtained. We compare the significance of linkage findings obtained using allele-sharing LOD scores (LOD(exp))-which assume homogeneity-and heterogeneity LOD scores (HLOD) in European American and African American NIMH SZ families. We also pool these two samples and evaluate the relative power of the LOD(exp) and two different heterogeneity statistics. One of these (HLOD-P) estimates the heterogeneity parameter alpha only in aggregate data, while the second (HLOD-S) determines alpha separately for each sample. In separate and combined data, we show consistently improved performance of HLOD scores over LOD(exp). Notably, genome-wide significant evidence for linkage is obtained at chromosome 10p in the European American sample using a recessive HLOD score. When the two samples are combined, linkage at the 10p locus also achieves genome-wide significance under HLOD-S, but not HLOD-P. Using HLOD-S, improved evidence for linkage was also obtained for a previously reported region on chromosome 15q. In linkage analyses of complex disease, power may be maximised by routinely modelling locus heterogeneity within individual datasets, even when multiple datasets are combined to form larger samples.

Understanding the heterogeneity of entrepreneurship education: going beyond Gartner

This paper seeks to draw attention to the importance of appreciating and using ever-present diversity to achieve increased legitimacy for entrepreneurship education. As such, it aims to draw the reader into a reflective process of discovery as to why entrepreneurship education is important and how such importance can be prolonged. Design/methodology/approach - The paper revisits Gartner's 1985 conceptual framework for understanding the complexity of entrepreneurship. The paper proposes an alternative framework based on the logic of Gartner's framework to advance the understanding of entrepreneurship education. The authors discuss the dimensions of the proposed framework and explain the nature of the dialogic relations contained within. Findings - It is argued that the proposed conceptual framework provides a new way to understand ever-present heterogeneity related to the development and delivery of entrepreneurship education. Practical implications - The paper extends an invitation to the reader to audit their own involvement and proximity to entrepreneurship education. It argues that increased awareness of the value that heterogeneity plays in student learning outcomes and programme branding is directly related to the presence of heterogeneity across the dimensions of the conceptual framework. Originality/value - The paper introduces a simple yet powerlu1 means of understanding what factors contribute to the success or otherwise of developing and delivering entrepreneurship education. The simplicity of the approach suggested provides all entrepreneurship educators with the means to audit all facets of their programme.

Thermal performance of magnesium oxide wall board using numerical modelling

Fire resistance of light-gauge steel frame (LSF) walls can be enhanced by lining them with single or multiple layers of wall boards. This research is focused on the thermal per-formance of Magnesium Oxide (MgO) wall boards in comparison to the conventional gypsum plasterboards exposed to standard fire on one side. Thermal properties of MgO board and gypsum plasterboard were measured first and then used in the finite element heat transfer models of the two types of panels. The measured thermal property results show that MgO board will perform better than the gypsum plasterboards due to its higher specific heat values at elevated temperatures. However, MgO board loses 50% of its ini-tial mass at about 500 °C compared to 16% for gypsum plasterboard. The developed finite element models were validated using the fire test results of gypsum plasterboards and then used to study the thermal performance of MgO board panels. Finite element analysis re-sults show that when MgO board panels are exposed to standard fire on one side the rate of temperature rise on the ambient side is significantly reduced compared to gypsum plas-terboard. This has the potential to improve the overall thermal performance of MgO board lined LSF walls and their fire resistance levels (FRL). However, full scale fire tests are needed to confirm this. This paper presents the details of this investigation and the results.

Reducing luminance contrast on the window wall and users’ interventions in an office room

High luminance contrast between windows and surrounding surfaces could cause discomfort glare, which could reduce office workers’ productivity. It might also increase energy usage of buildings due to occupants’ interventions in lighting conditions to improve indoor visual quality. It is presumed that increasing the luminance of the areas surrounding the windows using a supplementary system, such Light Emitting Diodes (LEDs), could reduce discomfort glare. This paper reports on the results of a pilot study in a conventional office in Brisbane, Australia. The outcomes of this study indicated that a supplementary LED system could reduce the luminance contrast on the window wall from values in the order of 24:1 to 12:1. The results suggest that this reduction could significantly reduce discomfort glare from windows, as well as diminishing the likelihood of users’ intention to turn on the ceiling lights and/ or to move the blind down.