Elastic wave measurement in rock engineering

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The use of Fluid Haemodynamics in the Diagnosis of Cardiovascular Disease

Currently the diagnostic methods used to detect cardiovascular disease largely rely on the inference of the presence of arterial stenosis. There is a clinical interest in the development of a diagnostic screening technique which can indicate the risk of developing cardiovascular disease at an early stage so that non-surgical treatments can be applied. The goal of this work was to develop and validate a diagnostic screening technique for cardiovascular disease using the mechanical biomarker wall shear stress. Improvements in wall shear stress measurements were made by using a 2D Fourier transform to extract additional spectral information from the ultrasound pulse and decrease the spectral variance by integrating across the bandwidth of transmitted frequencies. This technique was validated for a series of anatomically realistic flow phantoms which precisely mimicked the progression of wall stiffening that characterises cardiovascular disease. The newly developed spectral analysis technique demonstrated a higher diagnostic performance than the other techniques tested, both in terms of a greater degree of significance in detecting differences in vessel wall stiffness and in terms of the sensitivity and specificity of the technique. The technique could not be tested in pulsatile flow due to hardware limitations, but preliminary testing indicated that the increased performance of the technique would likely transfer to a physiological flow regime. The results of this work indicated that the algorithm had the potential to rival the diagnostic power of the current gold standard while being applicable at an earlier stage of cardiovascular disease

Polyvinyl Alcohol Cryogel Based Vessel Mimicking Material for Modelling the Progression of Atherosclerosis

Purpose The stiffness of Polyvinyl-alcohol cryogel can be adjusted through application of consecutive freeze-thaw cycles. This material has potential applications in the production of tissue mimicking phantoms in diagnostic ultrasound. The aim of this study was to use PVA-c to produce a range of geometrically and acoustically identical vessel phantoms modelling stages of atherosclerosis which could be verified through mechanical testing, thus allowing for more precision in quantitative in-vitro flow analysis of atherosclerosis. Methods A series of anatomically realistic walled renal artery flow phantoms were constructed using PVA-c. In order to ensure precise modelling of atherosclerosis, a modified procedure of ISO27:2017 was used to compare the mechanical properties of PVA-c. Results were compared for the standard “dumbbell” test object and a modified vessel test object. The geometric accuracy and reproducibility of the vessel models were tested before and after implantation in flow phantoms. Results No significant difference was found between the mechanical properties of the dumbbell test samples and the vessels for any number of freeze thaw cycles, with a correlation coefficient of R2 = 0.9767 across the dataset, indicating that a direct comparison between the mechanical properties of the dumbbell test samples and the phantom vessels was established. The geometric reproducibility showed that before and after implantation there was no significant difference between individual vessel geometries (p = 0.337 & p = 0.176 respectively). Conclusions Polyvinyl-alcohol cryogel is a useful material for the production of arterial flow phantoms. Care should be taken when using this material to ensure its mechanical properties have been correctly characterised. The guidelines of ISO37:2017 potentially provide the best procedure to ensure this

Steroid-sensitive nephrotic syndrome candidate gene CLVS1 regulates podocyte oxidative stress and endocytosis

We performed next-generation sequencing in patients with familial steroid-sensitive nephrotic syndrome (SSNS) and identified a homozygous segregating variant (p.H310Y) in the gene encoding clavesin-1 (CLVS1) in a consanguineous family with 3 affected individuals. Knockdown of the clavesin gene in zebrafish (clvs2) produced edema phenotypes due to disruption of podocyte structure and loss of glomerular filtration barrier integrity that could be rescued by WT CLVS1 but not the p.H310Y variant. Analysis of cultured human podocytes with CRISPR/Cas9-mediated CLVS1 knockout or homozygous H310Y knockin revealed deficits in clathrin-mediated endocytosis and increased susceptibility to apoptosis that could be rescued with corticosteroid treatment, mimicking the steroid responsiveness observed in patients with SSNS. The p.H310Y variant also disrupted binding of clavesin-1 to α-tocopherol transfer protein, resulting in increased reactive oxygen species (ROS) accumulation in CLVS1-deficient podocytes. Treatment of CLVS1-knockout or homozygous H310Y-knockin podocytes with pharmacological ROS inhibitors restored viability to control levels. Taken together, these data identify CLVS1 as a candidate gene for SSNS, provide insight into therapeutic effects of corticosteroids on podocyte cellular dynamics, and add to the growing evidence of the importance of endocytosis and oxidative stress regulation to podocyte function

Investigation of the assessment of low degree (\u3c50%) renal artery stenosis based on velocity flow profile analysis using Doppler ultrasound: An in-vitro study

Purpose: Renal arterial stenosis can lead to disrupted renal function due to reduced blood flow to the kidneys and is largely thought to be caused by atherosclerosis. Current diagnostic strategies for renal arterial stenosis rely on detecting large degree stenoses (\u3e50%). This study aimed to test the viability of using Doppler ultrasound to assess velocity profiles to detect the presence of low degree (\u3c50%) stenoses. Methods: A series of anatomically realistic renal artery flow phantoms were constructed exhibiting a range of low degree stenoses (symmetric and asymmetric). The behaviour of fluid flow in the phantoms was examined using Doppler ultrasound and analysed to calculate the clinical biomarker, wall shear stress. Results: A number of fluid behaviours were observed in relation to stenosis degree: asymmetric stenoses tended to result in a skewing of peak velocities away from the centre of the vessel towards the outer wall, the magnitude of increase in velocity was observed to correlate with stenosis degree, and the wall shear stress curves observed large peaks in the presence of even the lowest degree stenosis (20%). Conclusions: Doppler ultrasound could potentially be utilised to diagnose low degree stenoses in a clinical setting. Doppler ultrasound in conjunction with wall shear stress analysis in particular has significant potential in the diagnosis of renal artery stenosis

Emergency Caesarean Section: Influences on the Decision-to-Delivery Interval

RCOG/NICE guidelines recommend that, for fetal compromise in labour, delivery should be accomplished ideally within 30 minutes. In this study, we investigated the factors which affect the decision-to-delivery (DD) intervals for emergency caesareans. To achieve this, prospective data were collected for all grade 1 and 2 caesareans performed on a busy labour ward over 12 months. We found that the ratio of labouring women to midwives had a significant effect on the DD intervals, which were significantly prolonged when 1 : 1 care was not provided (P < 0.001). The observed effect resulted exclusively from a prolonged transfer time to theatre. General anesthesia use shortened the DD interval for grade 1 caesareans (P < 0.001) and was more likely to be used during the day shift (P < 0.009). We conclude that midwifery staffing levels and the form of anaesthesia employed influence on DD intervals for the most urgent caesarean sections

DISASTER RISK MANAGEMENT FOR CULTURAL RESOURCE PRESERVATION

Advisory Committee: Donald Linebaugh and Dennis Pogue