Understanding the fluid mechanics behind transverse wall shear stress

The patchy distribution of atherosclerosis within arteries is widely attributed to local variation in haemodynamic wall shear stress (WSS). A recently-introduced metric, the transverse wall shear stress (transWSS), which is the average over the cardiac cycle of WSS components perpendicular to the temporal mean WSS vector, correlates particularly well with the pattern of lesions around aortic branch ostia. Here we use numerical methods to investigate the nature of the arterial flows captured by transWSS and the sensitivity of transWSS to inflow waveform and aortic geometry. TransWSS developed chiefly in the acceleration, peak systolic and deceleration phases of the cardiac cycle; the reverse flow phase was too short, and WSS in diastole was too low, for these periods to have a significant influence. Most of the spatial variation in transWSS arose from variation in the angle by which instantaneous WSS vectors deviated from the mean WSS vector rather than from variation in the magnitude of the vectors. The pattern of transWSS was insensitive to inflow waveform; only unphysiologically high Womersley numbers produced substantial changes. However, transWSS was sensitive to changes in geometry. The curvature of the arch and proximal descending aorta were responsible for the principal features, the non-planar nature of the aorta produced asymmetries in the location and position of streaks of high transWSS, and taper determined the persistence of the streaks down the aorta. These results reflect the importance of the fluctuating strength of Dean vortices in generating transWSS

Multidirectional near-wall flow in arteries and its spatial correlation with atherosclerosis

Atherosclerotic lesions develop non-uniformly throughout the arterial system and their distribution around branches changes with age. This thesis investigates whether multidirectional blood flow, characterised by the transverse wall shear stress metric (transWSS), is related to the initiation of atherosclerosis. The spectral/hp element method was used to simulate pulsatile blood flow in immature and mature rabbit aortic geometries obtained by microCT of vascular corrosion casts. Bootstrapping was used to quantitatively correlate spatial maps around intercostal branch ostia, and found that the low/oscillatory shear theory did not correlate with disease, and could not account for age-related changes in macromolecule uptake. However, evidence for the multidirectional theory was found: transWSS related strongly and positively with disease at both ages and with wall permeability in young rabbits. The pulsatility of the blood is necessary for the existence of multidirectionality, yet the precise nature of the cardiac waveform did not dominantly influence both the large- and small-scale pattern of transWSS. Simulations in partially-idealised vessels revealed that geometry instead was crucial. Vessel curvature was responsible for a Dean vortex pair, whose changing strength over the cardiac cycle created changes in the shear direction at the wall, resulting in two large-scale axial streaks of high transWSS. Vessel torsion determined the asymmetry in their strengths and spatial locations over the descending aorta. Two distributions of transWSS resembling the age-dependent lesion patterns were identified at the individual-branch level, but which arose equally in both age groups. The small-scale patterns were found to depend on the branch's location with respect to the large-scale streaks, and therefore primarily on torsion, for which no statistically significant difference between age groups was found. Multidirectional flow relates well to disease at the aggregate-level and may explain age-dependent lesion patterns. The importance of geometry was highlighted, and calls into question how accurately it is captured.Open Acces

Postpartum psychosis and management: a case study

Postpartum (or puerperal) psychosis is an acute mood disorder requiring close specialist care. It is a disorder that is rare and poorly understood, but has devastating consequences. This work retrospectively describes the case study of a young woman who suffered postpartum psychosis following the birth of her first child. A critical appraisal of the care received follows this, focusing specifically on the postnatal period when she was most affected. It was found that critical information was not unearthed at the initial booking appointment, nor were her presenting symptoms recognised in a timely manner; detailing a need for greater training among midwives and care givers regarding early recognition and referral for postpartum psychosis

Exploration of A Self-Supervised Speech Model: A Study on Emotional Corpora

Self-supervised speech models have grown fast during the past few years and have proven feasible for use in various downstream tasks. Some recent work has started to look at the characteristics of these models, yet many concerns have not been fully addressed. In this work, we conduct a study on emotional corpora to explore a popular self-supervised model -- wav2vec 2.0. Via a set of quantitative analysis, we mainly demonstrate that: 1) wav2vec 2.0 appears to discard paralinguistic information that is less useful for word recognition purposes; 2) for emotion recognition, representations from the middle layer alone perform as well as those derived from layer averaging, while the final layer results in the worst performance in some cases; 3) current self-supervised models may not be the optimal solution for downstream tasks that make use of non-lexical features. Our work provides novel findings that will aid future research in this area and theoretical basis for the use of existing models.Comment: Accepted to SLT 202

Change of direction in the biomechanics of atherosclerosis

The non-uniform distribution of atherosclerosis within the arterial system has been attributed to pro-atherogenic influences of low, oscillatory haemodynamic wall shear stress (WSS) on endothelial cells (EC). This theory is challenged by the changes in lesion location that occur with age in human and rabbit aortas. Furthermore, a number of point-wise comparisons of lesion prevalence and WSS have failed to support it. Here we investigate the hypothesis that multidirectional flow-characterized as the average magnitude of WSS components acting transversely to the mean vector (transWSS)-plays a key role. Maps of lesion prevalence around aortic branch ostia in immature and mature rabbits were compared with equivalent maps of time average WSS, the OSI (an index characterizing oscillatory flow) and transWSS, obtained from computational simulations; Spearman's rank correlation coefficients were calculated for aggregated data and 95% confidence intervals were obtained by bootstrapping methods. Lesion prevalence correlated positively, strongly and significantly with transWSS at both ages. Correlations of lesion prevalence with the other shear metrics were not significant or were significantly lower than those obtained for transWSS. No correlation supported the low, oscillatory WSS theory. The data are consistent with the view that multidirectional near-wall flow is highly pro-atherogenic. Effects of multidirectional flow on EC, and methods for investigating them, are reviewed. The finding that oscillatory flow has pro-inflammatory effects when acting perpendicularly to the long axis of EC but anti-inflammatory effects when acting parallel to it may explain the stronger correlation of lesion prevalence with transWSS than with the OSI

Uncertainty quantification of wall shear stress in intracranial aneurysms using a data-driven statistical model of systemic blood flow variability

Adverse wall shear stress (WSS) patterns are known to play a key role in the localisation, formation, and progression of intracranial aneurysms (IAs). Com- plex region-specific and time-varying aneurysmal WSS patterns depend both on vascular morphology as well as on variable systemic ow conditions. Com- putational uid dynamics (CFD) has been proposed for characterising WSS patterns in IAs; however, CFD simulations often rely on deterministic bound- ary conditions that are not representative of the actual variations in blood ow. We develop a data-driven statistical model of internal carotid artery (ICA) ow, which is used to generate a virtual population of waveforms used as inlet bound- ary conditions in CFD simulations. This allows the statistics of the resulting aneurysmal WSS distributions to be computed. It is observed that ICA wave- form variations have limited in uence on the time-averaged WSS (TAWSS) on the IA surface. In contrast, in regions where the ow is locally highly multidi- rectional, WSS directionality and harmonic content are strongly affected by the ICA ow waveform. As a consequence, we argue that the effect of blood ow variability should be explicitly considered in CFD-based IA rupture assessment to prevent confounding the conclusions

Understanding mechanobiology in cultured endothelium: A review of the orbital shaker method

A striking feature of atherosclerosis is its highly non-uniform distribution within the arterial tree. This has been attributed to variation in the haemodynamic wall shear stress (WSS) experienced by endothelial cells, but the WSS characteristics that are important and the mechanisms by which they lead to disease remain subjects of intensive investigation despite decades of research. In vivo evidence suggests that multidirectional WSS is highly atherogenic. This possibility is increasingly being studied by culturing endothelial cells in wells that are swirled on an orbital shaker. The method is simple and cost effective, has high throughput and permits chronic exposure, but interpretation of the results can be difficult because the fluid mechanics are complex; hitherto, their description has largely been restricted to the engineering literature. Here we review the findings of such studies, which indicate that putatively atherogenic flow characteristics occur at the centre of the well whilst atheroprotective ones occur towards the edge, and we describe simple mathematical methods for choosing experimental variables that avoid resonance, wave breaking and uncovering of the cells. We additionally summarise a large number of studies showing that endothelium cultured at the centre of the well expresses more pro-inflammatory and fewer homeostatic genes, has higher permeability, proliferation, apoptosis and senescence, and shows more endothelial-to-mesenchymal transition than endothelium at the edge. This simple method, when correctly interpreted, has the potential to greatly increase our understanding of the homeostatic and pathogenic mechanobiology of endothelial cells and may help identify new therapeutic targets in vascular disease

4D Flow Analysis of BAV-Related Fluid-Dynamic Alterations: Evidences of Wall Shear Stress Alterations in Absence of Clinically-Relevant Aortic Anatomical Remodeling

Bicuspid aortic valve (BAV) is the most common congenital cardiac disease and is a foremost risk factor for aortopathies. Despite the genetic basis of BAV and of the associated aortopathies, BAV-related alterations in aortic fluid-dynamics, and particularly in wall shear stresses (WSSs), likely play a role in the progression of aortopathy, and may contribute to its pathogenesis. To test whether WSS may trigger aortopathy, in this study we used 4D Flow sequences of phase-contrast cardiac magnetic resonance imaging (CMR) to quantitatively compare the in vivo fluid dynamics in the thoracic aorta of two groups of subjects: (i) five prospectively enrolled young patients with normo-functional BAV and with no aortic dilation and (ii) ten age-matched healthy volunteers. Through the semi-automated processing of 4D Flow data, the aortic bulk flow at peak systole was quantified, and WSSs acting on the endothelium of the ascending aorta were characterized throughout the systolic phase in terms of magnitude and time-dependency through a method recently developed by our group. Variables computed for each BAV patient were compared vs. the corresponding distribution of values obtained for healthy controls. In BAV patients, ascending aorta diameter was measured on cine-CMR images at baseline and at 3-year follow-up. As compared to controls, normo-functional BAV patients were characterized by minor bulk flow disturbances at peak systole. However, they were characterized by evident alterations of WSS distribution and peak values in the ascending aorta. In particular, in four BAV patients, who were characterized by right-left leaflet fusion, WSS peak values exceeded by 27–46% the 90th percentile of the distribution obtained for healthy volunteers. Only in the BAV patient with right-non-coronary leaflet fusion the same threshold was exceeded by 132%. Also, evident alterations in the time-dependency of WSS magnitude and direction were observed. Despite, these fluid-dynamic alterations, no clinically relevant anatomical remodeling was observed in the BAV patients at 3-year follow-up. In light of previous evidence from the literature, our results suggest that WSS alterations may precede the onset of aortopathy and may contribute to its triggering, but WSS-driven anatomical remodeling, if any, is a very slow process