IntroductionCOVID-19 may lead to persistent and potentially incapacitating clinical manifestations (post-acute sequelae of SARS-CoV-2 infection (PASC)). Using easy-to-apply questionnaires and scales (often by telephone interviewing), several studies evaluated samples of COVID-19 inpatients from 4 weeks to several months after discharge. However, studies conducting systematic multidisciplinary assessments of PASC manifestations are scarce, with thorough in-person objective evaluations restricted to modestly sized subsamples presenting greatest disease severity.Methods and analysesWe will conduct a prospective observational study of surviving individuals (above 18 years of age) from a cohort of over 3000 subjects with laboratory-confirmed COVID-19 who were treated as inpatients at the largest academic health centre in Sao Paulo, Brazil (Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo). All eligible subjects will be consecutively invited to undergo a 1–2-day series of multidisciplinary assessments at 2 time-points, respectively, at 6–9 months and 12–15 months after discharge. Assessment schedules will include detailed multidomain questionnaires applied by medical research staff, self-report scales, objective evaluations of cardiopulmonary functioning, physical functionality and olfactory status, standardised neurological, psychiatric and cognitive examinations, as well as diagnostic laboratory, muscle ultrasound and chest imaging exams. Remaining material from blood tests will be incorporated by a local biobank for use in future investigations on inflammatory markers, genomics, transcriptomics, peptidomics and metabolomics.Ethics and disseminationAll components of this programme have been approved by local research ethics committees. We aim to provide insights into the frequency and severity of chronic/post-COVID multiorgan symptoms, as well as their interrelationships and associations with acute disease features, sociodemographic variables and environmental exposures. Findings will be disseminated in peer-reviewed journals and at scientific meetings. Additionally, we aim to provide a data repository to allow future pathophysiological investigations relating clinical PASC features to biomarker data extracted from blood samples.Trial registration numberRBR-8z7v5wc; Pre-results.
The prediction of the transition dynamics of high-enthalpy boundary-layer flows requires appropriate thermodynamic and transport models. This work quantifies the influence of transport, diffusion, collision, equilibrium, and chemical-kinetics modeling on the stability characteristics and the estimated transition-onset location of canonical boundary layers. The computed behavior of second-mode instabilities is consistently highly dependent on the base-flow’s boundary-layer height. The Blottner-Eucken-Wilke transport model is seen to underpredict the boundary-layer height, hence overpredicting the growth-rate distribution and forecasting the transition onset to occur ∼38% sooner. The other low-order transport models (Brokaw and Yos) returned very close results to the most-accurate Chapman-Enskog model. The use of Gupta et al.’s collisional data instead of Wright et al.’s more accurate data is also seen to predict the transition onset to occur ∼8% closer to the leading edge. The modeling of mass diffusion and the chemical-equilibrium constant is observed to have a negligible influence on the boundary-layer height and transition-onset-location estimations (less than 5% and 2%, respectively). For the analyzed conditions, all chemical models predict the same transition-onset location (±1%); since at the streamwise positions where perturbations have reached sufficiently large amplitudes, the flow is close to equilibrium and thus independent of the reaction rates. The use of different transport models for the perturbation terms, while maintaining the same model for the basic state, leads to negligible differences in the predictions. This further reinforces the thesis that the boundary-layer height calculation is paramount to the simulation of the development of second-mode instabilities.
A combined experimental and numerical approach to the analysis of the secondary stability of realistic swept-wing boundary layers is presented. Global linear stability theory is applied to experimentally measured base flows. These base flows are three-dimensional laminar boundary layers subject to spanwise distortion due to the presence of primary stationary crossflow vortices. A full three-dimensional description of these flows is accessed through the use of tomographic particle image velocimetry (PIV). The stability analysis solves for the secondary high-frequency modes of type I and type II, ultimately responsible for turbulent breakdown. Several pertinent parameters arising from the application of the proposed methodology are investigated, including the mean flow ensemble size and the measurement domain extent. Extensive use is made of the decomposition of the eigensolutions into the terms of the Reynolds–Orr equation, allowing insight into the production and/or destruction of perturbations from various base flow features. Stability results demonstrate satisfactory convergence with respect to the mean flow ensemble size and are independent of the handling of the exterior of the measurement domain. The Reynolds–Orr analysis reveals a close relationship between the type I and type II instability modes with spanwise and wall-normal gradients of the base flow, respectively. The structural role of the in-plane velocity components in the perturbation growth, topology and sensitivity is identified. Using the developed framework, further insight is gained into the linear growth mechanisms and later stages of transition via the primary and secondary crossflow instabilities. Furthermore, the proposed methodology enables the extension and enhancement of the experimental measurement data to the pertinent instability eigenmodes. The present work is the first demonstration of the use of a measured base flow for stability analysis applied to the swept-wing boundary layer, directly avoiding the modelling of the primary vortices receptivity processes.
Background Past studies reported a low correlation between rhinomanometry and computational fluid dynamics (CFD), but the source of the discrepancy was unclear. Low correlation or lack of correlation has also been reported between subjective and objective measures of nasal patency. Objective: This study investigates (1) the correlation and agreement between nasal resistance derived from CFD (RCFD) and rhinomanometry (RRMN), and (2) the correlation between objective and subjective measures of nasal patency. Methods Twenty-five patients with nasal obstruction underwent anterior rhinomanometry before and after mucosal decongestion with oxymetazoline. Subjective nasal patency was assessed with a 0-10 visual analog scale (VAS). CFD simulations were performed based on computed tomography scans obtained after mucosal decongestion. To validate the CFD methods, nasal resistance was measured in vitro (REXPERIMENT) by performing pressure-flow experiments in anatomically accurate plastic nasal replicas from 6 individuals. Results Mucosal decongestion was associated with a reduction in bilateral nasal resistance (0.34 ± 0.23 Pa.s/ml to 0.19 ± 0.24 Pa.s/ml, p = 0.003) and improved sensation of nasal airflow (bilateral VAS decreased from 5.2 ± 1.9 to 2.6 ± 1.9, p < 0.001). A statistically significant correlation was found between VAS in the most obstructed cavity and unilateral airflow before and after mucosal decongestion (r = −0.42, p = 0.003). Excellent correlation was found between RCFD and REXPERIMENT (r = 0.96, p < 0.001) with good agreement between the numerical and in vitro values (RCFD/REXPERIMENT = 0.93 ± 0.08). A weak correlation was found between RCFD and RRMN (r = 0.41, p = 0.003) with CFD underpredicting nasal resistance derived from rhinomanometry (RCFD/RRMN = 0.65 ± 0.63). A stronger correlation was found when unilateral airflow at a pressure drop of 75 Pa was used to compare CFD with rhinomanometry (r = 0.76, p < 0.001). Conclusion CFD and rhinomanometry are moderately correlated, but CFD underpredicts nasal resistance measured in vivo due in part to the assumption of rigid nasal walls. Our results confirm previous reports that subjective nasal patency correlates better with unilateral than with bilateral measurements and in the context of an intervention.
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