Plantar pressure in diabetic peripheral neuropathy patients with active foot ulceration, previous ulceration and no history of ulceration: A meta-analysis of observational studies

Aims Elevated dynamic plantar pressures are a consistent finding in diabetes patients with peripheral neuropathy with implications for plantar foot ulceration. This meta-analysis aimed to compare the plantar pressures of diabetes patients that had peripheral neuropathy and those with neuropathy with active or previous foot ulcers. Methods Published articles were identified from Medline via OVID, CINAHL, SCOPUS, INFORMIT, Cochrane Central EMBASE via OVID and Web of Science via ISI Web of Knowledge bibliographic databases. Observational studies reporting barefoot dynamic plantar pressure in adults with diabetic peripheral neuropathy, where at least one group had a history of plantar foot ulcers were included. Interventional studies, shod plantar pressure studies and studies not published in English were excluded. Overall mean peak plantar pressure (MPP) and pressure time integral (PTI) were primary outcomes. The six secondary outcomes were MPP and PTI at the rear foot, mid foot and fore foot. The protocol of the meta-analysis was published with PROPSERO, (registration number CRD42013004310). Results Eight observational studies were included. Overall MPP and PTI were greater in diabetic peripheral neuropathy patients with foot ulceration compared to those without ulceration (standardised mean difference 0.551, 95% CI 0.290–0.811, p<0.001; and 0.762, 95% CI 0.303–1.221, p = 0.001, respectively). Sub-group analyses demonstrated no significant difference in MPP for those with neuropathy with active ulceration compared to those without ulcers. A significant difference in MPP was found for those with neuropathy with a past history of ulceration compared to those without ulcers; (0.467, 95% CI 0.181– 0.753, p = 0.001). Statistical heterogeneity between studies was moderate. Conclusions Plantar pressures appear to be significantly higher in patients with diabetic peripheral neuropathy with a history of foot ulceration compared to those with diabetic neuropathy without a history of ulceration. More homogenous data is needed to confirm these findings.

Genome-wide association study of intraocular pressure identifies the GLCCI1/ICA1 region as a glaucoma susceptibility locus

To discover quantitative trait loci for intraocular pressure, amajor risk factor for glaucoma and the only modifiable one,weperformed agenome-wide association studyonadiscoverycohort of2175individualsfromSydney, Australia. We found a novel association between intraocular pressure and a common variant at 7p21 near to GLCCI1 and ICA1. The findings in this region were confirmed through two UK replication cohorts totalling 4866 individuals (rs59072263, Pcombined = 1.10 × 10-8). A copy of the G allele at this SNP is associated with an increase in mean IOP of 0.45 mmHg (95%CI = 0.30-0.61 mmHg). These results lend support to the implication of vesicle trafficking and glucocorticoid inducibility pathways in the determination of intraocular pressure and in the pathogenesis of primary open-angle glaucoma.

Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls

Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with diseaseIRGM for Crohns disease, HLA for Crohns disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetesalthough in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases. © 2010 Macmillan Publishers Limited. All rights reserved.

Genome-wide association study identifies eight loci associated with blood pressure

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N 71,225 European ancestry, N 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10 24), CYP1A2 (P = 1 × 10 23), FGF5 (P = 1 × 10 21), SH2B3 (P = 3 × 10 18), MTHFR (P = 2 × 10 13), c10orf107 (P = 1 × 10 9), ZNF652 (P = 5 × 10 9) and PLCD3 (P = 1 × 10 8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

The measurement of intraocular pressure over positive soft contact lenses by rebound tonometry [Medición de la presión intraocular sobre lentes de contacto blandas positivas, mediante tonometría de rebote]

Purpose To investigate if the accuracy of intraocular pressure (IOP) measurements using rebound tonometry over disposable hydrogel (etafilcon A) contact lenses (CL) is affected by the positive power of the CLs. Methods The experimental group comprised 26 subjects, (8 male, 18 female). IOP measurements were undertaken on the subjects’ right eyes in random order using a Rebound Tonometer (ICare). The CLs had powers of +2.00D and +6.00D. Measurements were taken over each contact lens and also before and after the CLs had been worn. Results The IOP measure obtained with both CLs was significantly lower compared to the value without CLs (t test; p<0.001) but no significant difference was found between the two powers of CLs. Conclusions Rebound tonometry over positive hydrogel CLs leads to a certain degree of IOP underestimation. This result didn’t change for the two positive lenses used in the experiment, despite their large difference in power and therefore in lens thickness. Optometrists should bear this in mind when measuring IOP with the rebound tonometer over plus power contact lenses.

LibVM: An architecture for shared library sandboxing

Many software applications extend their functionality by dynamically loading libraries into their allocated address space. However, shared libraries are also often of unknown provenance and quality and may contain accidental bugs or, in some cases, deliberately malicious code. Most sandboxing techniques which address these issues require recompilation of the libraries using custom tool chains, require significant modifications to the libraries, do not retain the benefits of single address-space programming, do not completely isolate guest code, or incur substantial performance overheads. In this paper we present LibVM, a sandboxing architecture for isolating libraries within a host application without requiring any modifications to the shared libraries themselves, while still retaining the benefits of a single address space and also introducing a system call inter-positioning layer that allows complete arbitration over a shared library’s functionality. We show how to utilize contemporary hardware virtualization support towards this end with reasonable performance overheads and, in the absence of such hardware support, our model can also be implemented using a software-based mechanism. We ensure that our implementation conforms as closely as possible to existing shared library manipulation functions, minimizing the amount of effort needed to apply such isolation to existing programs. Our experimental results show that it is easy to gain immediate benefits in scenarios where the goal is to guard the host application against unintentional programming errors when using shared libraries, as well as in more complex scenarios, where a shared library is suspected of being actively hostile. In both cases, no changes are required to the shared libraries themselves.

Fatigue crack growth under pulsatile pressure and plaque rupture

Identification of vulnerable plaque pre-rupture is extremely important for patient risk stratification. The mechanism of plaque rupture is still not entirely clear, but it is thought to be a process involving multiple factors. From a biomechanical viewpoint, plaque rupture is usually seen as a structural failure when the plaque cannot resist the hemodynamic blood pressure and shear stress exerted on it. However, the cardiovascular system is naturally a cyclical hemodynamic environment, and myocardial infarction can be a symptomatically quiescent but potentially progressive process when plaque ruptures at stresses much lower than its strength. Therefore, fatigue accumulation is a possible mechanism for plaque rupture. In this study, a crack growth model was developed, and the previously-mentioned hypothesis was tested by conducting a comparative study between 18 symptomatic and 16 asymptomatic patients with carotid stenosis.

Plantar pressure distribution character in young female with mild hallux valgus wearing high-heeled shoes

Young females with mild hallux valgus (HV) have been identified as having an increased risk of first ray deformation. Little is known, however, about the biomechanical changes that might contribute to this increased risk. The purpose of this study was to compare kinetics changes during walking for mild HV subjects with high-heel-height shoes. Twelve female subjects (six with mild HV and six controls) participated in this study with heel height varying from 0 cm (barefoot) to 4.5 cm. Compared to healthy controls, patients had significantly higher peak pressure on the big toe area during barefoot walking. When the heel height increased, loading was transferred to medial side of the forefoot, and the big toe area suffered more impact compared to barefoot in mild HV. This study also demonstrated that the center of pressure (COP) inclines to medial side alteration after high-heeled shoes wearing. These findings indicate that mild HV people should be discouraged from wearing high-heeled shoes.

Impact of coronary tortuosity on coronary pressure: Numerical simulation study

Background: Coronary tortuosity (CT) is a common coronary angiographic finding. Whether CT leads to an apparent reduction in coronary pressure distal to the tortuous segment of the coronary artery is still unknown. The purpose of this study is to determine the impact of CT on coronary pressure distribution by numerical simulation. Methods: 21 idealized models were created to investigate the influence of coronary tortuosity angle (CTA) and coronary tortuosity number (CTN) on coronary pressure distribution. A 2D incompressible Newtonian flow was assumed and the computational simulation was performed using finite volume method. CTA of 30°, 60°, 90°, 120° and CTN of 0, 1, 2, 3, 4, 5 were discussed under both steady and pulsatile conditions, and the changes of outlet pressure and inlet velocity during the cardiac cycle were considered. Results: Coronary pressure distribution was affected both by CTA and CTN. We found that the pressure drop between the start and the end of the CT segment decreased with CTA, and the length of the CT segment also declined with CTA. An increase in CTN resulted in an increase in the pressure drop. Conclusions: Compared to no-CT, CT can results in more decrease of coronary blood pressure in dependence on the severity of tortuosity and severe CT may cause myocardial ischemia.

Image-based midsole insert design and the material effects on heel plantar pressure distribution during simulated walking loads

The primary objective of this paper is to study the use of medical image-based finite element (FE) modelling in subjectspecific midsole design and optimisation for heel pressure reduction using a midsole plug under the calcaneus area (UCA). Plugs with different relative dimensions to the size of the calcaneus of the subject have been incorporated in the heel region of the midsole. The FE foot model was validated by comparing the numerically predicted plantar pressure with biomechanical tests conducted on the same subject. For each UCA midsole plug design, the effect of material properties and plug thicknesses on the plantar pressure distribution and peak pressure level during the heel strike phase of normal walking was systematically studied. The results showed that the UCA midsole insert could effectively modify the pressure distribution, and its effect is directly associated with the ratio of the plug dimension to the size of the calcaneus bone of the subject. A medium hardness plug with a size of 95% of the calcaneus has achieved the best performance for relieving the peak pressure in comparison with the pressure level for a solid midsole without a plug, whereas a smaller plug with a size of 65% of the calcaneus insert with a very soft material showed minimum beneficial effect for the pressure relief.

The mechanical triggers of plaque rupture: Shear stress vs pressure gradient

The aim of this study was to evaluate the mechanical triggers that may cause plaque rupture. Wall shear stress (WSS) and pressure gradient are the direct mechanical forces acting on the plaque in a stenotic artery. Their influence on plaque stability is thought to be controversial. This study used a physiologically realistic, pulsatile flow, two-dimensional, cine phase-contrast MRI sequence in a patient with a 70% carotid stenosis. Instead of considering the full patient-specific carotid bifurcation derived from MRI, only the plaque region has been modelled by means of the idealised flow model. WSS reached a local maximum just distal to the stenosis followed by a negative local minimum. A pressure drop across the stenosis was found which varied significantly during systole and diastole. The ratio of the relative importance of WSS and pressure was assessed and was found to be less than 0.07% for all time phases, even at the throat of the stenosis. In conclusion, although the local high WSS at the stenosis may damage the endothelium and fissure plaque, the magnitude of WSS is small compared with the overall loading on plaque. Therefore, pressure may be the main mechanical trigger for plaque rupture and risk stratification using stress analysis of plaque stability may only need to consider the pressure effect.

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.

Laboratory investigation on the effects of overburden pressure, water, and time on slaking induced material property degradation of coal mine spoil

In open-cut strip mining, waste material is placed in-pit to minimise operational mine costs. Slope failures in these spoil piles pose a significant safety risk to personnel, along with a financial risk from loss of equipment and scheduling delays. It has been observed that most spoil pile failures occur when the pit has been previously filled with water and then subsequently dewatered. The failures are often initiated at the base of spoil piles where the material can undergo significant slaking (disintegration) over time due to overburden pressure and water saturation. It is important to understand how the mechanical properties of base spoil material are affected by slaking when designing safe spoil pile slope angles, heights, and dewatering rates. In this study, fresh spoil material collected from a coal mine in Brown Basin Coalfield of Queensland, Australia was subjected to high overburden pressure (0 – 900 kPa) under saturated condition and maintained over a period of time (0 – 6 months) allowing the material to slake. To create the above conditions, laboratory designed pressure chambers were used. Once a spoil sample was slaked under certain overburden pressure over a period of time, it was tested for classification, permeability, and strength properties. Results of this testing program suggested that the slaking of saturated coal mine spoil increase with overburden pressure and the time duration over which the overburden pressure was maintained. Further, it was observed that shear strength and permeability of spoil decreased with increase in spoil slaking.

The impact of private and shared open space on liveability in subtropical apartment buildings

The study explores the relationship between open space design, factors impacting open space provision, and resident satisfaction with open space in multistorey apartment buildings in the context of the subtropical lifestyle and climate of Brisbane Australia. The purpose of the paper is to identify the specific physical and spatial design characteristics residents perceive to be important in open spaces associated with their private dwellings and with shared open spaces. Firsthand resident evaluations of everyday experiences of residing in inner urban high density environments are explored through a survey of 636 residents and interviews with 24 residents. Private balconies are highly valued, but residents’ satisfaction would be enhanced by spaciousness for diverse activities, privacy and climate responsive design. Communal spaces and facilities are used infrequently by many residents who prefer interactions with community outside of the building. This is related to preferences for a level of anonymity in a setting where privacy is difficult to achieve due to physical proximity of neighbours.