A PIV comparison of the flow field and wall shear stress in rigid and compliant models of healthy carotid arteries

Certain systems relevant to circulatory disease have walls which are neither rigid nor static, for example, the coronary arteries, the carotid artery and the heart chambers. In vitro modeling allows the fluid mechanics of the circulatory system to be studied without the ethical and safety issues associated with animal and human experiments. Computational methods in which the equations are coupled governing the flow and the elastic walls are maturing. Currently there is a lack of experimental data in compliant arterial systems to validate the numerical predictions. Previous experimental work has commonly used rigid wall boundaries, ignoring the effect of wall compliance. Particle Image Velocimetry is used to provide a direct comparison of both the flow field and wall shear stress (WSS) observed in experimental phantoms of rigid and compliant geometries representing an idealized common carotid artery. The input flow waveform and the mechanical response of the phantom are physiologically realistic. The results show that compliance affects the velocity profile within the artery. A rigid boundary causes severe overestimation of the peak WSS with a maximum relative difference of 61% occurring; showing compliance protects the artery from exposure to high magnitude WSS. This is important when trying to understand the development of diseases like atherosclerosis. The maximum, minimum and time averaged WSS in the rigid geometry was 2.3, 0.51 and 1.03Pa and in the compliant geometry 1.4, 0.58 and 0.84Pa, respectively

Modelling nasal high flow therapy effects on upper airway resistance and resistive work of breathing

Aim The goal of this paper is to quantify upper airway resistance with and without nasal high flow (NHF) therapy. For adults, NHF therapy feeds 30–60 L/min of warm humidified air into the nose through short cannulas which do not seal the nostril. NHF therapy has been reported to increase airway pressure, increase tidal volume (Vt) and decrease respiratory rate (RR), but it is unclear how these findings affect the work done to overcome airway resistance to air flow during expiration. Also, there is little information on how the choice of nasal cannula size may affect work of breathing. In this paper, estimates of airway resistance without and with different NHF flow (applied via different cannula sizes) were made. The breathing efforts required to overcome airway resistance under these conditions were quantified. Method NHF was applied via three different cannula sizes to a 3-D printed human upper airway. Pressure drop and flow rate were measured and used to estimate inspiratory and expiratory upper airway resistances. The resistance information was used to compute the muscular work required to overcome the resistance of the upper airway to flow. Results NHF raises expiratory resistance relative to spontaneous breathing if the breathing pattern does not change but reduces work of breathing if peak expiratory flow falls. Of the cannula sizes used, the large cannula produced the greatest resistance and the small cannula produced the least. The work required to cause tracheal flow through the upper airway was reduced if the RR and minute volume are reduced by NHF. NHF has been observed to do so in COPD patients (Bräunlich et al., 2013). A reduction in I:E ratio due to therapy was found to reduce work of breathing if the peak inspiratory flow is less than the flow below which no inspiratory effort is required to overcome upper airway resistance. Conclusion NHF raises expiratory resistance but it can reduce the work required to overcome upper airway resistance via a fall in inspiratory work of breathing, RR and minute volume

Fabrication of a compliant phantom of the human aortic arch for use in Particle Image Velocimetry (PIV) experimentation

Compliant phantoms of the human aortic arch can mimic patient specific cardiovascular dysfunctions in vitro. Hence, phantoms may enable elucidation of haemodynamic disturbances caused by aortic dysfunction. This paper describes the fabrication of a thin-walled silicone phantom of the human ascending aorta and brachiocephalic artery. The model geometry was determined via a meta-analysis and modelled in SolidWorks before 3D printing. The solid model surface was smoothed and scanned with a 3D scanner. An offset outer mould was milled from Ebalta S-Model board. The final phantom indicated that ABS was a suitable material for the internal model, the Ebalta S-Model board yielded a rough external surface. Co-location of the moulds during silicone pour was insufficient to enable consistent wall thickness. The resulting phantom was free of air bubbles but did not have the desired wall thickness consistency

Methylome-wide association study of early life stressors and adult mental health

The environment and events that we are exposed to in utero, during birth and in early childhood influence our future physical and mental health. The underlying mechanisms that lead to these outcomes are unclear, but long-term changes in epigenetic marks, such as DNA methylation, could act as a mediating factor or biomarker. DNA methylation data were assayed at 713 522 CpG sites from 9537 participants of the Generation Scotland: Scottish Family Health Study, a family-based cohort with extensive genetic, medical, family history and lifestyle information. Methylome-wide association studies of eight early life environment phenotypes and two adult mental health phenotypes (major depressive disorder and brief resilience scale) were conducted using DNA methylation data collected from adult whole blood samples. Two genes involved with different developmental pathways (PRICKLE2, Prickle Planar Cell Polarity Protein 2 and ABI1, Abl-Interactor-1) were annotated to CpG sites associated with preterm birth (P < 1.27 × 10(−9)). A further two genes important to the development of sensory pathways (SOBP, Sine Oculis Binding Protein Homolog and RPGRIP1, Retinitis Pigmentosa GTPase Regulator Interacting Protein) were annotated to sites associated with low birth weight (P < 4.35 × 10(−8)). The examination of methylation profile scores and genes and gene-sets annotated from associated CpGs sites found no evidence of overlap between the early life environment and mental health conditions. Birth date was associated with a significant difference in estimated lymphocyte and neutrophil counts. Previous studies have shown that early life environments influence the risk of developing mental health disorders later in life; however, this study found no evidence that this is mediated by stable changes to the methylome detectable in peripheral blood

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

New model for light propagation in highly inhomogeneous polydisperse turbid media with applications in spray diagnostics

Modern optical diagnostics for quantitative characterization of polydisperse sprays and other aerosols which contain a wide range of droplet size encounter difficulties in the dense regions due to the multiple scattering of laser radiation with the surrounding droplets. The accuracy and efficiency of optical measurements can only be improved if the radiative transfer within such polydisperse turbid media is understood. A novel Monte Carlo code has been developed for modeling of optical radiation propagation in inhomogeneous polydisperse scattering media with typical drop size ranging from 2 µm to 200 µm in diameter. We show how strong variations of both particle size distribution and particle concentration within a 3D scattering medium can be taken into account via the Monte Carlo approach. A new approximation which reduces ~20 times the computational memory space required to determine the phase function is described. The approximation is verified by considering four log-normal drop size distributions. It is found valid for particle sizes in the range of 10-200 µm with increasing errors, due to additional photons scattered at large angles, as the number of particles below than 10 µm increases. The technique is applied to the simulation of typical planar Mie imaging of a hollow cone spray. Simulated and experimental images are compared and shown to agree well. The code has application in developing and testing new optical diagnostics for complex scattering media such as dense sp

Crossed source-detector geometry for a novel spray diagnostic: Monte Carlo simulation and analytical results

Sprays and other industrially relevant turbid media can be quantitatively characterized by light scattering. However, current optical diagnostic techniques generate errors in the intermediate scattering regime where the average number of light scattering is too great for the single scattering to be assumed, but too few for the diffusion approximation to be applied. Within this transitional single-to-multiple scattering regime, we consider a novel crossed source-detector geometry that allows the intensity of single scattering to be measured separately from the higher scattering orders. We verify Monte Carlo calculations that include the imperfections of the experiment against analytical results. We show quantitatively the influence of the detector numerical aperture and the angle between the source and the detector on the relative intensity of the scattering orders in the intermediate single-to-multiple scattering regime. Monte Carlo and analytical calculations of double light-scattering intensity are made with small particles that exhibit isotropic scattering. The agreement between Monte Carlo and analytical techniques validates use of the Monte Carlo approach in the intermediate scattering regime. Monte Carlo calculations are then performed for typical parameters of sprays and aerosols with anisotropic (Mie) scattering in the intermediate single-to-multiple scattering regime