Serum levels of soluble receptor for advanced glycation end products and of S100 proteins are associated with inflammatory, autoantibody, and classical risk markers of joint and vascular damage in rheumatoid arthritis

Introduction: The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptor molecules. High concentrations of three of its putative proinflammatory ligands, S100A8/A9 complex (calprotectin), S100A8, and S100A12, are found in rheumatoid arthritis (RA) serum and synovial fluid. In contrast, soluble RAGE (sRAGE) may prevent proinflammatory effects by acting as a decoy. This study evaluated the serum levels of S100A9, S100A8, S100A12 and sRAGE in RA patients, to determine their relationship to inflammation and joint and vascular damage. Methods: Serum sRAGE, S100A9, S100A8 and S100A12 levels from 138 patients with established RA and 44 healthy controls were measured by ELISA and compared by unpaired t test. In RA patients, associations with disease activity and severity variables were analyzed by simple and multiple linear regressions. Results: Serum S100A9, S100A8 and S100A12 levels were correlated in RA patients. S100A9 levels were associated with body mass index (BMI), and with serum levels of S100A8 and S100A12. S100A8 levels were associated with serum levels of S100A9, presence of anti-citrullinated peptide antibodies (ACPA), and rheumatoid factor (RF). S100A12 levels were associated with presence of ACPA, history of diabetes, and serum S100A9 levels. sRAGE levels were negatively associated with serum levels of C-reactive protein (CRP) and high-density lipoprotein (HDL), history of vasculitis, and the presence of the RAGE 82Ser polymorphism. Conclusions: sRAGE and S100 proteins were associated not just with RA inflammation and autoantibody production, but also with classical vascular risk factors for end-organ damage. Consistent with its role as a RAGE decoy molecule, sRAGE had the opposite effects to S100 proteins in that S100 proteins were associated with autoantibodies and vascular risk, whereas sRAGE was associated with protection against joint and vascular damage. These data suggest that RAGE activity influences co-development of joint and vascular disease in rheumatoid arthritis patients.

Impacts of wind power integration on small signal stability and low frequency oscillation characteristics of interconnected power systems

为研究风电并网对互联系统低频振荡的影响,基于完整的双馈风电机组模型,定性分析了两区域互联系统在风电机组并网前后阻尼特性的变化情况.从双馈风电机组并网输送距离、并网容量、互联系统联络线传送功率、是否加装电力系统稳定器等多个方面,多角度分析了风电场并网对互联系统小干扰稳定及低频振荡特性的影响.之后,以两个包括两个区域的电力系统为例,进行了系统的计算分析和比较.结果表明,有双馈风电机组接入的互联电力系统,在不同运行模式下,双馈风电机组的并网输送距离、出力水平、联络线传送功率对低频振荡模式的影响在趋势和程度上均有显著差异,这样在对风电场进行入网规划、设计和运行时就需要综合考虑这些因素的影响.

The root locus method: application to linear stability analysis and design of cooperative car-following models

A global framework for linear stability analyses of traffic models, based on the dispersion relation root locus method, is presented and is applied taking the example of a broad class of car-following (CF) models. This approach is able to analyse all aspects of the dynamics: long waves and short wave behaviours, phase velocities and stability features. The methodology is applied to investigate the potential benefits of connected vehicles, i.e. V2V communication enabling a vehicle to send and receive information to and from surrounding vehicles. We choose to focus on the design of the coefficients of cooperation which weights the information from downstream vehicles. The coefficients tuning is performed and different ways of implementing an efficient cooperative strategy are discussed. Hence, this paper brings design methods in order to obtain robust stability of traffic models, with application on cooperative CF models

Human body stability in floodwaters: The 2011 flood in Brisbane CBD

The flooding of urbanised areas constitutes a hazard to the population and infrastructure. Floods through inundated urban environments have been studied recently and the potential impact of flowing waters on pedestrians is not well known. Herein the stability of individuals in floodwaters is reviewed based upon the re-analysis of detailed field measurements in an inundated section of the central business district of the City of Brisbane (Australia) during the 2011 flood. Detailed water elevation and velocity data were recorded. On-site observations showed some hydrodynamic instability linked to local topographic effects, in the form of a combination of fast turbulent fluctuations and (very) slow fluctuations of water level and velocity associated with surges. The flow conditions in Gardens Point Road was unsafe for individuals and a review of past guidelines suggests that many previous recommendations are over-optimistic and unsafe in real floodwaters.

Linear and weakly nonlinear stability analyses of cooperative car-following models

Stability analyses have been widely used to better understand the mechanism of traffic jam formation. In this paper, we consider the impact of cooperative systems (a.k.a. connected vehicles) on traffic dynamics and, more precisely, on flow stability. Cooperative systems are emerging technologies enabling communication between vehicles and/or with the infrastructure. In a distributed communication framework, equipped vehicles are able to send and receive information to/from other equipped vehicles. Here, the effects of cooperative traffic are modeled through a general bilateral multianticipative car-following law that improves cooperative drivers' perception of their surrounding traffic conditions within a given communication range. Linear stability analyses are performed for a broad class of car-following models. They point out different stability conditions in both multianticipative and nonmultianticipative situations. To better understand what happens in unstable conditions, information on the shock wave structure is studied in the weakly nonlinear regime by the mean of the reductive perturbation method. The shock wave equation is obtained for generic car-following models by deriving the Korteweg de Vries equations. We then derive traffic-state-dependent conditions for the sign of the solitary wave (soliton) amplitude. This analytical result is verified through simulations. Simulation results confirm the validity of the speed estimate. The variation of the soliton amplitude as a function of the communication range is provided. The performed linear and weakly nonlinear analyses help justify the potential benefits of vehicle-integrated communication systems and provide new insights supporting the future implementation of cooperative systems.

Errors in the knee joint forces and moments during gait depending on the foot and knee prosthetic components

Background Previously studies showed that inverse dynamics based on motion analysis and force-plate is inaccurate compared to direct measurements for individuals with transfemoral amputation (TFA). Indeed, direct measurements can appropriately take into account the absorption at the prosthetic foot and the resistance at the prosthetic knee. [1-3] However, these studies involved only a passive prosthetic knee. Aim The objective of the present study was to investigate if different types of prosthetic feet and knees can exhibit different levels of error in the knee joint forces and moments. Method Three trials of walking at self-selected speed were analysed for 9 TFAs (7 males and 2 females, 47±9 years old, 1.76±0.1 m 79±17 kg) with a motion analysis system (Qualisys, Goteborg, Sweden), force plates (Kitsler, Winterthur, Switzerland) and a multi-axial transducer (JR3, Woodland, USA) mounted above the prosthetic knee [1-17]. TFAs were all fitted with an osseointegrated implant system. The prostheses included different type of foot (N=5) and knee (N=3) components. The root mean square errors (RMSE) between direct measurements and the knee joint forces and moments estimated by inverse dynamics were computed for stance and swing phases of gait and expressed as a percentage of the measured amplitudes. A one-way Kruskal-Wallis ANOVA was performed (Statgraphics, Levallois-Perret, France) to analyse the effects of the prosthetic components on the RMSEs. Cross-effects and post-hoc tests were not analysed in this study. Results A significant effect (*) was found for the type of prosthetic foot on anterior-posterior force during swing (p=0.016), lateral-medial force during stance (p=0.009), adduction-abduction moment during stance (p=0.038), internal-external rotation moment during stance (p=0.014) and during swing (p=0.006), and flexion-extension moment during stance (p = 0.035). A significant effect (#) was found for the type of prosthetic knee on anterior-posterior force during swing (p=0.018) and adduction-abduction moment during stance (p=0.035). Discussion & Conclusion The RMSEs were larger during swing than during stance. It is because the errors on accelerations (as derived from motion analysis) become substantial with respect to the external loads. Thus, inverse dynamics during swing should be analysed with caution because the mean RMSEs are close to 50%. Conversely, there were fewer effects of the prosthetic components on RMSE during swing than during stance and, accordingly, fewer effects due to knees than feet. Thus, inverse dynamics during stance should be used with caution for comparison of different prosthetic components.

The role of IL-17-secreting mast cells in inflammatory joint disease

The proinflammatory cytokine IL-17 has an important role in pathogenesis of several inflammatory diseases. In immune-mediated joint diseases, IL-17 can induce secretion of other proinflammatory cytokines such as IL-1, IL-6 and TNF, as well as matrix metalloproteinase enzymes, leading to inflammation, cartilage breakdown, osteoclastogenesis and bone erosion. In animal models of inflammatory arthritis, mice deficient in IL-17 are less susceptible to development of disease. The list of IL-17-secreting cells is rapidly growing, and mast cells have been suggested to be a dominant source of IL-17 in inflammatory joint disease. However, many other innate sources of IL-17 have been described in both inflammatory and autoinflammatory conditions, raising questions as to the role of mast cells in orchestrating joint inflammation. This article will critically assess the contribution of mast cells and other cell types to IL-17 production in the inflammatory milieu associated with inflammatory arthritis, understanding of which could facilitate targeted therapeutic approaches. © 2013 Macmillan Publishers Limited. All rights reserved.

A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. We mapped FOP to chromosome 2q23-24 by linkage analysis and identified an identical heterozygous mutation (617G→A; R206H) in the glycine-serine (GS) activation domain of ACVR1, a BMP type I receptor, in all affected individuals examined. Protein modeling predicts destabilization of the GS domain, consistent with constitutive activation of ACVR1 as the underlying cause of the ectopic chondrogenesis, osteogenesis and joint fusions seen in FOP.

Mechanical properties of a hollow-cylindrical-joint honeycomb

In this paper, we constructed a new honeycomb by replacing the three-edge joint of the conventional regular hexagonal honeycomb with a hollow-cylindrical joint, and developed a corresponding theory to study its mechanical properties, i.e., Young's modulus, Poisson's ratio, fracture strength and stress intensity factor. Interestingly, with respect to the conventional regular hexagonal honeycomb, its Young's modulus and fracture strength are improved by 76% and 303%, respectively; whereas, for its stress intensity factor, two possibilities exist for the maximal improvements which are dependent of its relative density, and the two improvements are 366% for low-density case and 195% for high-density case, respectively. Moreover, a minimal Poisson's ratio exists. The present structure and theory could be used to design new honeycomb materials.

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.

Does calcium deposition play a role in the stability of atheroma? Location may be the key

Background: Rupture of vulnerable atheromatous plaque in the carotid and coronary arteries often leads to stroke and heart attack respectively. The role of calcium deposition and its contribution to plaque stability is controversial. This study uses both an idealized and a patient-specific model to evaluate the effect of a calcium deposit on the stress distribution within an atheromatous plaque. Methods: Using a finite-element method, structural analysis was performed on an idealized plaque model and the location of a calcium deposit within it was varied. In addition to the idealized model, in vivo high-resolution MR imaging was performed on 3 patients with carotid atheroma and stress distributions were generated. The individual plaques were chosen as they had calcium at varying locations with respect to the lumen and the fibrous cap. Results: The predicted maximum stress was increased by 47.5% when the calcium deposit was located in the thin fibrous cap in the model when compared with that in a model without a deposit. The result of adding a calcium deposit either to the lipid core or remote from the lumen resulted in almost no increase in maximal stress. Conclusion: Calcification at the thin fibrous cap may result in high stress concentrations, ultimately increasing the risk of plaque rupture. Assessing the location of calcification may, in the future, aid in the risk stratification of patients with carotid stenosis.

How critical is fibrous cap thickness to carotid plaque stability? A flow-plaque interaction model

Background and Purpose Acute cerebral ischemic events are associated with rupture of vulnerable carotid atheroma and subsequent thrombosis. Factors such as luminal stenosis and fibrous cap thickness have been thought to be important risk factors for plaque rupture. We used a flow-structure interaction model to simulate the interaction between blood flow and atheromatous plaque to evaluate the effect of the degree of luminal stenosis and fibrous cap thickness on plaque vulnerability. Methods A coupled nonlinear time-dependent model with a flow-plaque interaction simulation was used to perform flow and stress/strain analysis in a stenotic carotid artery model. The stress distribution within the plaque and the flow conditions within the vessel were calculated for every case when varying the fibrous cap thickness from 0.1 to 2 mm and the degree of luminal stenosis from 10% to 95%. A rupture stress of 300 kPa was chosen to indicate a high risk of plaque rupture. A 1-sample t test was used to compare plaque stresses with the rupture stress. Results High stress concentrations were found in the plaques in arteries with >70% degree of stenosis. Plaque stresses in arteries with 30% to 70% stenosis increased exponentially as fibrous cap thickness decreased. A decrease of fibrous cap thickness from 0.4 to 0.2 mm resulted in an increase of plaque stress from 141 to 409 kPa in a 40% degree stenotic artery. Conclusions There is an increase in plaque stress in arteries with a thin fibrous cap. The presence of a moderate carotid stenosis (30% to 70%) with a thin fibrous cap indicates a high risk for plaque rupture. Patients in the future may be risk stratified by measuring both fibrous cap thickness and luminal stenosis.

Exploring methods of preparing functional cartilage-bone xenografts for joint repair

This thesis explores the feasibility of donor-receiver concept for joint replacement where cartilage-bone tissues can be taken from either human or other mammals and prepared scientifically for repairing focal joint defects in knees, hips and shoulders. The manufactured construct is immunologically inert and is capable of acting as a scaffold for engineering new cartilage-bone laminates when placed in the joint. Innovative manufacturing procedures and assessment techniques were developed for appraising this tissue-based scaffold. This research has demonstrated that tissue replacement technology can be applied in situations where blood vessels are absent such as in articular cartilage.

Morphology-based interslice interpolation on manual segmentations of joint bones and muscles in MRI

This paper presents a validation study on the application of a novel interslice interpolation technique for musculoskeletal structure segmentation of articulated joints and muscles on human magnetic resonance imaging data. The interpolation technique is based on morphological shape-based interpolation combined with intensity based voxel classification. Shape-based interpolation in the absence of the original intensity image has been investigated intensively. However, in some applications of medical image analysis, the intensity image of the slice to be interpolated is available. For example, when manual segmentation is conducted on selected slices, the segmentation on those unselected slices can be obtained by interpolation. We proposed a two- step interpolation method to utilize both the shape information in the manual segmentation and local intensity information in the image. The method was tested on segmentations of knee, hip and shoulder joint bones and hamstring muscles. The results were compared with two existing interpolation methods. Based on the calculated Dice similarity coefficient and normalized error rate, the proposed method outperformed the other two methods.