Hyper-Ballistic Superdiffusion of Competing Microswimmers.

Hyper-ballistic diffusion is shown to arise from a simple model of microswimmers moving through a porous media while competing for resources. By using a mean-field model where swimmers interact through the local concentration, we show that a non-linear Fokker-Planck equation arises. The solution exhibits hyper-ballistic superdiffusive motion, with a diffusion exponent of four. A microscopic simulation strategy is proposed, which shows excellent agreement with theoretical analysis.

Darcy's law of yield stress fluids on a treelike network.

Understanding the flow of yield stress fluids in porous media is a major challenge. In particular, experiments and extensive numerical simulations report a nonlinear Darcy law as a function of the pressure gradient. In this letter we consider a treelike porous structure for which the problem of the flow can be resolved exactly due to a mapping with the directed polymer (DP) with disordered bond energies on the Cayley tree. Our results confirm the nonlinear behavior of the flow and expresses its full pressure dependence via the density of low-energy paths of DP restricted to vanishing overlap. These universal predictions are confirmed by extensive numerical simulations.

Common carotid artery responses to the cold-pressor test are impaired in individuals with cervical spinal cord injury.

Cervical spinal cord injury (SCI) leads to autonomic cardiovascular dysfunction that underlies the three- to fourfold elevated risk of cardiovascular disease in this population. Reduced common carotid artery (CCA) dilatory responsiveness during the cold-pressor test (CPT) is associated with greater cardiovascular disease risk and progression. The cardiovascular and CCA responses to the CPT may provide insight into cardiovascular autonomic dysfunction and cardiovascular disease risk in individuals with cervical SCI. Here, we used CPT to perturb the autonomic nervous system in 14 individuals with cervical SCI and 12 uninjured controls, while measuring cardiovascular responses and CCA diameter. The CCA diameter responses were 55% impaired in those with SCI compared with uninjured controls (P = 0.019). The CCA flow, velocity, and shear response to CPT were reduced in SCI by 100% (P < 0.001), 113% (P = 0.001), and 125% (P = 0.002), respectively. The association between mean arterial pressure and CCA dilation observed in uninjured individuals (r = 0.54, P = 0.004) was absent in the SCI group (r = 0.22, P = 0.217). Steady-state systolic blood pressure (P = 0.020), heart rate (P = 0.003), and cardiac contractility (P < 0.001) were reduced in those with cervical SCI, whereas total peripheral resistance was increased compared with uninjured controls (P = 0.042). Relative cerebral blood velocity responses to CPT were increased in the SCI group and reduced in controls (middle cerebral artery, P = 0.010; posterior cerebral artery, P = 0.026). The CCA and cardiovascular responsiveness to CPT are impaired in those with cervical SCI.NEW & NOTEWORTHY This is the first study demonstrating that CCA responses during CPT are suppressed in SCI. Specifically, CCA diameter, flow, velocity, and shear rate were reduced. The relationship between changes in MAP and CCA dilatation in response to CPT was absent in individuals with SCI, despite similar cardiovascular activation between SCI and uninjured controls. These findings support the notion of elevated cardiovascular disease risk in SCI and that the cardiovascular responses to environmental stimuli are impaired.

Evaluating Autonomous Urban Perception and Planning in a 1/10th Scale MiniCity.

We present the MiniCity, a multi-vehicle evaluation platform for testing perception hardware and software for autonomous vehicles. The MiniCity is a 1/10th scale city consisting of realistic urban scenery, intersections, and multiple fully autonomous 1/10th scale vehicles with state-of-the-art sensors and algorithms. The MiniCity is used to evaluate and test perception algorithms both upstream and downstream in the autonomy stack, in urban driving scenarios such as occluded intersections and avoiding multiple vehicles. We demonstrate the MiniCity's ability to evaluate different sensor and algorithm configurations for perception tasks such as object detection and localization. For both tasks, the MiniCity platform is used to evaluate the task itself (accuracy in estimating obstacle pose and ego pose in the map) as well as the downstream performance in collision avoidance and lane following, respectively.

Aging and Failure of a Polymer Chain under Tension.

The rupture of a polymer chain maintained at temperature T under fixed tension is prototypical to a wide array of systems failing under constant external stress and random perturbations. Past research focused on analytic and numerical studies of the mean rate of collapse of such a chain. Surprisingly, an analytic calculation of the probability distribution function (PDF) of collapse rates appears to be lacking. Since rare events of rapid collapse can be important and even catastrophic, we present here a theory of this distribution, with a stress on its tail of fast rates. We show that the tail of the PDF is a power law with a universal exponent that is theoretically determined. Extensive numerics validate the offered theory. Lessons pertaining to other problems of the same type are drawn.

RTVue XR AngioVue Optical Coherence Tomography Angiography Software Upgrade Impacts on Retinal Thickness and Vessel Density Measurements.

Purpose: To determine the impact of an AngioVue software upgrade on total retinal thickness (RT) and inner retinal vessel density (VD) measurements derived from optical coherence tomography angiography (OCTA). Methods: Optovue OCTA images (3 × 3 mm) from 126 individuals (105 healthy eyes and 72 eyes with retinal disease) were acquired before an upgrade of the AngioVue software, which resulted in an inward shift of the outer boundary of the inner retinal vessels and improved Bruch's membrane segmentation. Total RT and inner retinal VD values were extracted before and after the software upgrade for comparison. Bias and limits of agreement (LA) were calculated. Results: The mean (SD) age of participants was 46 (17) years. Mean (LA) foveal RT increased by 3.0 (-11 to +17) and 3.7 (-11 to +18) µm (P < 0.001) and parafoveal RT increased by 9.7 (-3.8 to +23) and 6.4 (-2.5 to +15) µm (P < 0.001) in healthy and diseased retina, respectively. Mean (LA) foveal inner retinal VD decreased by 6.6 (2.5-11) and 7.7 (0.4-15) percentage units (P < 0.001) and parafoveal inner retinal VD decreased by 4.1 (1.2-7.0) and 4.7 (0.5-8.9) percentage units (P < 0.001) in healthy and diseased retina, respectively. Conclusions: The AngioVue software upgrade resulted in an unexpected increase in total RT and an expected reduction in inner retinal VD measurements in all regions due to altered segmentation. Translational Relevance: RT and VD measures derived from the newer AngioVue software version are not directly comparable to the reported normative data derived from the older software.

Clinical validation of the RTVue optical coherence tomography angiography image quality indicators.

IMPORTANCE: All automated image quality indicators for en face optical coherence tomography angiography (OCTA) images require gold standard validation for determining optimum thresholds. BACKGROUND: A manual grading system (gold standard) for OCTA images was validated and compared to two automated image quality indicators: signal strength index (SSI) and scan quality index (SQI) generated by different software versions of the Optovue OCTA device. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: A total of 52 eyes of 52 healthy individual and 77 eyes of 51 patients with retinal vascular diseases. METHODS: A total of 129 OCTA images of the superficial vascular plexus were graded manually by three independent examiners. Each image was assigned grades 1 to 4 (1-2, unacceptable; 3-4, acceptable) masked to the software-generated quality indicators. MAIN OUTCOME MEASURES: Inter-grader agreement and comparison of the utility of SSI and SQI in discriminating between acceptable and unacceptable OCTA images. RESULTS: There was a substantial agreement between the three graders (κ = 0.63). Mean SSI and SQI was significantly different between acceptable and unacceptable images (P < .001). SQI outperformed SSI in separating acceptable from unacceptable images (areas under the receiver operating characteristic curve: 0.87 vs 0.80) and the optimum cut-off was ≥7 for SQI and ≥70 for SSI for acceptable images. Up to 30% of images with quality indicators reaching the optimum SQI and SSI cut-off thresholds still had unacceptable quality on manual grading. Unacceptable images were found in 33% and 66% of healthy and diseased eyes, respectively. CONCLUSIONS AND RELEVANCE: SQI is closely related to manual grading but we caution reliance on the optimized threshold to determine image quality. SQI is superior to SSI in discriminating between acceptable and unacceptable images.

Comprehensive comparison of pore-scale models for multiphase flow in porous media.

Multiphase flows in porous media are important in many natural and industrial processes. Pore-scale models for multiphase flows have seen rapid development in recent years and are becoming increasingly useful as predictive tools in both academic and industrial applications. However, quantitative comparisons between different pore-scale models, and between these models and experimental data, are lacking. Here, we perform an objective comparison of a variety of state-of-the-art pore-scale models, including lattice Boltzmann, stochastic rotation dynamics, volume-of-fluid, level-set, phase-field, and pore-network models. As the basis for this comparison, we use a dataset from recent microfluidic experiments with precisely controlled pore geometry and wettability conditions, which offers an unprecedented benchmarking opportunity. We compare the results of the 14 participating teams both qualitatively and quantitatively using several standard metrics, such as fractal dimension, finger width, and displacement efficiency. We find that no single method excels across all conditions and that thin films and corner flow present substantial modeling and computational challenges.

Cerebrovascular Function in the Large Arteries Is Maintained Following Moderate Intensity Exercise.

Exercise has been shown to induce cerebrovascular adaptations. However, the underlying temporal dynamics are poorly understood, and regional variation in the vascular response to exercise has been observed in the large cerebral arteries. Here, we sought to measure the cerebrovascular effects of a single 20-min session of moderate-intensity exercise in the one hour period immediately following exercise cessation. We employed transcranial Doppler (TCD) ultrasonography to measure cerebral blood flow velocity (CBFV) in the middle cerebral artery (MCAv) and posterior cerebral artery (PCAv) before, during, and following exercise. Additionally, we simultaneously measured cerebral blood flow (CBF) in the internal carotid artery (ICA) and vertebral artery (VA) before and up to one hour following exercise cessation using Duplex ultrasound. A hypercapnia challenge was used before and after exercise to examine exercise-induced changes in cerebrovascular reactivity (CVR). We found that MCAv and PCAv were significantly elevated during exercise (p = 4.81 × 10-5 and 2.40 × 10-4, respectively). A general linear model revealed that these changes were largely explained by the partial pressure of end-tidal CO2 and not a direct vascular effect of exercise. After exercise cessation, there was no effect of exercise on CBFV or CVR in the intracranial or extracranial arteries (all p > 0.05). Taken together, these data confirm that CBF is rapidly and uniformly regulated following exercise cessation in healthy young males.

Intrasession Repeatability and Interocular Symmetry of Foveal Avascular Zone and Retinal Vessel Density in OCT Angiography.

PURPOSE: To measure intrasession repeatability and interocular symmetry of the foveal avascular zone area (FAZA) and superficial retinal vessel density (SRVD) using AngioVue Analytics optical coherence tomography angiography (OCTA). METHODS: Fifty healthy individuals were prospectively enrolled. OCTA scans (3 × 3 and 6 × 6 mm) were acquired twice in right and once in left eyes. FAZA (with and without rescaling) and SRVD for 18 regions (whole, fovea, parafovea, six parafoveal subregions, and nine square zones) were compared between two scans in right eyes (repeatability) and between both eyes (symmetry). Coefficients of repeatability (CRs) and limits of agreement (LAs) were calculated. RESULTS: Axial length-based image size rescaling had negligible impact on the intrasession CR of FAZA in both 3 × 3- and 6 × 6-mm images. The intrasession CRs for the foveal SRVD were 3.3% and 6.1% in the 3 × 3- and 6 × 6-mm OCTA images, respectively. Age and axial length did not influence test-retest variability of FAZA or SRVD. The interocular LAs in FAZA (0.039-0.059 mm2) was comparable to its CR. However, the interocular LAs in foveal SRVD were -4.5% to +3.8%, with 13% of the cohort showing an interocular difference greater than the CR. CONCLUSIONS: FAZA repeatability is not influenced by image size correction, and foveal SRVD is more variable in 6 × 6- than 3 × 3-mm OCTA images. Low image quality may contribute to interocular SRVD asymmetry. TRANSLATIONAL RELEVANCE: CRs and LAs can be used to set a threshold for true changes in FAZA and SRVD in longitudinal studies of healthy individuals.

UBC-Nepal Expedition: acute alterations in sympathetic nervous activity do not influence brachial artery endothelial function at sea level and high altitude.

Evidence indicates that increases in sympathetic nervous activity (SNA), and acclimatization to high altitude (HA), may reduce endothelial function as assessed by brachial artery flow-mediated dilatation (FMD); however, it is unclear whether such changes in FMD are due to direct vascular constraint, or consequential altered hemodynamics (e.g., shear stress) associated with increased SNA as a consequence of exposure to HA. We hypothesized that 1) at rest, SNA would be elevated and FMD would be reduced at HA compared with sea-level (SL); and 2) at SL and HA, FMD would be reduced when SNA was acutely increased, and elevated when SNA was acutely decreased. Using a novel, randomized experimental design, brachial artery FMD was assessed at SL (344 m) and HA (5,050 m) in 14 participants during mild lower-body negative pressure (LBNP; -10 mmHg) and lower-body positive pressure (LBPP; +10 mmHg). Blood pressure (finger photoplethysmography), heart rate (electrocardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (Duplex ultrasound) were recorded during LBNP, control, and LBPP trials. Muscle SNA was recorded (via microneurography) in a subset of participants (n = 5). Our findings were 1) at rest, SNA was elevated (P < 0.01), and absolute FMD was reduced (P = 0.024), but relative FMD remained unaltered (P = 0.061), at HA compared with SL; and 2) despite significantly altering SNA with LBNP (+60.3 ± 25.5%) and LBPP (-37.2 ± 12.7%) (P < 0.01), FMD was unaltered at SL (P = 0.448) and HA (P = 0.537). These data indicate that acute and mild changes in SNA do not directly influence brachial artery FMD at SL or HA.NEW & NOTEWORTHY The role of the sympathetic nervous system on endothelial function remains unclear. We used lower-body negative and positive pressure to manipulate sympathetic nervous activity at sea level and high altitude and measured brachial endothelial function via flow-mediated dilation. We found that acutely altering sympathetic nervous activity had no effect on endothelial function.

Effective Rheology of Two-Phase Flow in Three-Dimensional Porous Media: Experiment and Simulation.

We present an experimental and numerical study of immiscible two-phase flow of Newtonian fluids in three-dimensional (3D) porous media to find the relationship between the volumetric flow rate (Q) and the total pressure difference ([Formula: see text]) in the steady state. We show that in the regime where capillary forces compete with the viscous forces, the distribution of capillary barriers at the interfaces effectively creates a yield threshold ([Formula: see text]), making the fluids reminiscent of a Bingham viscoplastic fluid in the porous medium. In this regime, Q depends quadratically on an excess pressure drop ([Formula: see text]). While increasing the flow rate, there is a transition, beyond which the overall flow is Newtonian and the relationship is linear. In our experiments, we build a model porous medium using a column of glass beads transporting two fluids, deionized water and air. For the numerical study, reconstructed 3D pore networks from real core samples are considered and the transport of wetting and non-wetting fluids through the network is modeled by tracking the fluid interfaces with time. We find agreement between our numerical and experimental results. Our results match with the mean-field results reported earlier.

Axial Length Variation Impacts on Superficial Retinal Vessel Density and Foveal Avascular Zone Area Measurements Using Optical Coherence Tomography Angiography.

Purpose: To evaluate the impact of image magnification correction on superficial retinal vessel density (SRVD) and foveal avascular zone area (FAZA) measurements using optical coherence tomography angiography (OCTA). Methods: Participants with healthy retinas were recruited for ocular biometry, refraction, and RTVue XR Avanti OCTA imaging with the 3 × 3-mm protocol. The foveal and parafoveal SRVD and FAZA were quantified with custom software before and after correction for magnification error using the Littman and the modified Bennett formulae. Relative changes between corrected and uncorrected SRVD and FAZA were calculated. Results: Forty subjects were enrolled and the median (range) age of the participants was 30 (18-74) years. The mean (range) spherical equivalent refractive error was -1.65 (-8.00 to +4.88) diopters and mean (range) axial length was 24.42 mm (21.27-28.85). Images from 13 eyes were excluded due to poor image quality leaving 67 for analysis. Relative changes in foveal and parafoveal SRVD and FAZA after correction ranged from -20% to +10%, -3% to +2%, and -20% to +51%, respectively. Image size correction in measurements of foveal SRVD and FAZA was greater than 5% in 51% and 74% of eyes, respectively. In contrast, 100% of eyes had less than 5% correction in measurements of parafoveal SRVD. Conclusions: Ocular biometry should be performed with OCTA to correct image magnification error induced by axial length variation. We advise caution when interpreting interocular and interindividual comparisons of SRVD and FAZA derived from OCTA without image size correction.

Ensemble distribution for immiscible two-phase flow in porous media.

We construct an ensemble distribution to describe steady immiscible two-phase flow of two incompressible fluids in a porous medium. The system is found to be ergodic. The distribution is used to compute macroscopic flow parameters. In particular, we find an expression for the overall mobility of the system from the ensemble distribution. The entropy production at the scale of the porous medium is shown to give the expected product of the average flow and its driving force, obtained from a black-box description. We test numerically some of the central theoretical results.

Adenosine receptor-dependent signaling is not obligatory for normobaric and hypobaric hypoxia-induced cerebral vasodilation in humans.

Hypoxia increases cerebral blood flow (CBF) with the underlying signaling processes potentially including adenosine. A randomized, double-blinded, and placebo-controlled design, was implemented to determine if adenosine receptor antagonism (theophylline, 3.75 mg/Kg) would reduce the CBF response to normobaric and hypobaric hypoxia. In 12 participants the partial pressures of end-tidal oxygen ([Formula: see text]) and carbon dioxide ([Formula: see text]), ventilation (pneumotachography), blood pressure (finger photoplethysmography), heart rate (electrocardiogram), CBF (duplex ultrasound), and intracranial blood velocities (transcranial Doppler ultrasound) were measured during 5-min stages of isocapnic hypoxia at sea level (98, 90, 80, and 70% [Formula: see text]). Ventilation, [Formula: see text] and [Formula: see text], blood pressure, heart rate, and CBF were also measured upon exposure (128 ± 31 min following arrival) to high altitude (3,800 m) and 6 h following theophylline administration. At sea level, although the CBF response to hypoxia was unaltered pre- and postplacebo, it was reduced following theophylline (P < 0.01), a finding explained by a lower [Formula: see text] (P < 0.01). Upon mathematical correction for [Formula: see text], the CBF response to hypoxia was unaltered following theophylline. Cerebrovascular reactivity to hypoxia (i.e., response slope) was not different between trials, irrespective of [Formula: see text] At high altitude, theophylline (n = 6) had no effect on CBF compared with placebo (n = 6) when end-tidal gases were comparable (P > 0.05). We conclude that adenosine receptor-dependent signaling is not obligatory for cerebral hypoxic vasodilation in humans.NEW & NOTEWORTHY The signaling pathways that regulate human cerebral blood flow in hypoxia remain poorly understood. Using a randomized, double-blinded, and placebo-controlled study design, we determined that adenosine receptor-dependent signaling is not obligatory for the regulation of human cerebral blood flow at sea level; these findings also extend to high altitude.

The effect of α1 -adrenergic blockade on post-exercise brachial artery flow-mediated dilatation at sea level and high altitude.

KEY POINTS: Our objective was to quantify endothelial function (via brachial artery flow-mediated dilatation) at sea level (344 m) and high altitude (3800 m) at rest and following both maximal exercise and 30 min of moderate-intensity cycling exercise with and without administration of an α1 -adrenergic blockade. Brachial endothelial function did not differ between sea level and high altitude at rest, nor following maximal exercise. At sea level, endothelial function decreased following 30 min of moderate-intensity exercise, and this decrease was abolished with α1 -adrenergic blockade. At high altitude, endothelial function did not decrease immediately after 30 min of moderate-intensity exercise, and administration of α1 -adrenergic blockade resulted in an increase in flow-mediated dilatation. Our data indicate that post-exercise endothelial function is modified at high altitude (i.e. prolonged hypoxaemia). The current study helps to elucidate the physiological mechanisms associated with high-altitude acclimatization, and provides insight into the relationship between sympathetic nervous activity and vascular endothelial function. ABSTRACT: We examined the hypotheses that (1) at rest, endothelial function would be impaired at high altitude compared to sea level, (2) endothelial function would be reduced to a greater extent at sea level compared to high altitude after maximal exercise, and (3) reductions in endothelial function following moderate-intensity exercise at both sea level and high altitude are mediated via an α1 -adrenergic pathway. In a double-blinded, counterbalanced, randomized and placebo-controlled design, nine healthy participants performed a maximal-exercise test, and two 30 min sessions of semi-recumbent cycling exercise at 50% peak output following either placebo or α1 -adrenergic blockade (prazosin; 0.05 mg kg -1 ). These experiments were completed at both sea-level (344 m) and high altitude (3800 m). Blood pressure (finger photoplethysmography), heart rate (electrocardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (ultrasound) were recorded before, during and following exercise. Endothelial function assessed by brachial artery flow-mediated dilatation (FMD) was measured before, immediately following and 60 min after exercise. Our findings were: (1) at rest, FMD remained unchanged between sea level and high altitude (placebo P = 0.287; prazosin: P = 0.110); (2) FMD remained unchanged after maximal exercise at sea level and high altitude (P = 0.244); and (3) the 2.9 ± 0.8% (P = 0.043) reduction in FMD immediately after moderate-intensity exercise at sea level was abolished via α1 -adrenergic blockade. Conversely, at high altitude, FMD was unaltered following moderate-intensity exercise, and administration of α1 -adrenergic blockade elevated FMD (P = 0.032). Our results suggest endothelial function is differentially affected by exercise when exposed to hypobaric hypoxia. These findings have implications for understanding the chronic impacts of hypoxaemia on exercise, and the interactions between the α1 -adrenergic pathway and endothelial function.

Relationship between blood pressure and cerebral blood flow during supine cycling: influence of aging.

The cerebral pressure-flow relationship can be quantified as a high-pass filter, where slow oscillations are buffered (<0.20 Hz) and faster oscillations are passed through relatively unimpeded. During moderate intensity exercise, previous studies have reported paradoxical transfer function analysis (TFA) findings (altered phase or intact gain). This study aimed to determine whether these previous findings accurately represent this relationship. Both younger (20-30 yr; n = 10) and older (62-72 yr; n = 9) adults were examined. To enhance the signal-to-noise ratio, large oscillations in blood pressure (via oscillatory lower body negative pressure; OLBNP) were induced during steady-state moderate intensity supine exercise (∼45-50% of heart rate reserve). Beat-to-beat blood pressure, cerebral blood velocity, and end-tidal Pco2 were monitored. Very low frequency (0.02-0.07 Hz) and low frequency (0.07-0.20 Hz) range spontaneous data were quantified. Driven OLBNP point estimates were sampled at 0.05 and 0.10 Hz. The OLBNP maneuvers augmented coherence to >0.97 at 0.05 Hz and >0.98 at 0.10 Hz in both age groups. The OLBNP protocol conclusively revealed the cerebrovascular system functions as a high-pass filter during exercise throughout aging. It was also discovered that the older adults had elevations (+71%) in normalized gain (+0.46 ± 0.36%/%: 0.05 Hz) and reductions (-34%) in phase (-0.24 ± 0.22 radian: 0.10 Hz). There were also age-related phase differences between resting and exercise conditions. It is speculated that these age-related changes in the TFA metrics are mediated by alterations in vasoactive factors, sympathetic tone, or the mechanical buffering of the compliance vessels.

Local load-sharing fiber bundle model in higher dimensions.

We consider the local load-sharing fiber bundle model in one to five dimensions. Depending on the breaking threshold distribution of the fibers, there is a transition where the fracture process becomes localized. In the localized phase, the model behaves as the invasion percolation model. The difference between the local load-sharing fiber bundle model and the equal load-sharing fiber bundle model vanishes with increasing dimensionality with the characteristics of a power law.