Physiology-Enhanced Data Analytics to Evaluate the Effect of Altitude on Intraocular Pressure and Ocular Hemodynamics.

Altitude affects intraocular pressure (IOP); however, the underlying mechanisms involved and its relationship with ocular hemodynamics remain unknown. Herein, a validated mathematical modeling approach was used for a physiology-enhanced (pe-) analysis of the Mont Blanc study (MBS), estimating the effects of altitude on IOP, blood pressure (BP), and retinal hemodynamics. In the MBS, IOP and BP were measured in 33 healthy volunteers at 77 and 3466 m above sea level. Pe-retinal hemodynamics analysis predicted a statistically significant increase (p < 0.001) in the model predicted blood flow and pressure within the retinal vasculature following increases in systemic BP with altitude measured in the MBS. Decreased IOP with altitude led to a non-monotonic behavior of the model predicted retinal vascular resistances, with significant decreases in the resistance of the central retinal artery (p < 0.001) and retinal venules (p = 0.003) and a non-significant increase in the resistance in the central retinal vein (p = 0.253). Pe-aqueous humor analysis showed that a decrease in osmotic pressure difference (OPD) may underlie the difference in IOP measured at different altitudes in the MBS. Our analysis suggests that venules bear the significant portion of the IOP pressure load within the ocular vasculature, and that OPD plays an important role in regulating IOP with changes in altitude.

Evaluating the sensitivity of SARS-CoV-2 infection rates on college campuses to wastewater surveillance.

As college campuses reopened in fall 2020, we saw a large-scale experiment unfold on the efficacy of various strategies to contain the SARS-CoV-2 virus. Traditional individual surveillance testing via nasal swabs and/or saliva is among the measures that colleges are pursuing to reduce the spread of the virus on campus. Additionally, some colleges are testing wastewater on their campuses for signs of infection, which can provide an early warning signal for campuses to locate COVID-positive individuals. However, a representation of wastewater surveillance has not yet been incorporated into epidemiological models for college campuses, nor has the efficacy of wastewater screening been evaluated relative to traditional individual surveillance testing, within the structure of these models. Here, we implement a new model component for wastewater surveillance within an established epidemiological model for college campuses. We use a hypothetical residential university to evaluate the efficacy of wastewater surveillance for maintaining low infection rates. We find that wastewater sampling with a 1-day lag to initiate individual screening tests, plus completing the subsequent tests within a 4-day period can keep overall infections within 5% of the infection rates seen with traditional individual surveillance testing. Our results also indicate that wastewater surveillance can effectively reduce the number of false positive cases by identifying subpopulations for surveillance testing where infectious individuals are more likely to be found. Through a Monte Carlo risk analysis, we find that surveillance testing that relies solely on wastewater sampling can be fragile against scenarios with high viral reproductive numbers and high rates of infection of campus community members by outside sources. These results point to the practical importance of additional surveillance measures to limit the spread of the virus on campus and the necessity of a proactive response to the initial signs of outbreak.

Waveform parameters of retrobulbar vessels in glaucoma patients with different demographics and disease severity.

INTRODUCTION: To identify novel velocity waveform parameters of the ophthalmic artery and central retinal artery by computer-aided image processing of Doppler ultrasonography measurements, and to evaluate correlations between the waveform parameters and different demographics and disease severity of open-angle glaucoma patients. METHODS: Thirty-six images of 36 open-angle glaucoma patients were considered. A semiautomated image processing code was used to detect the digitalized ophthalmic artery and central retinal artery velocity waveforms and to extract the waveform parameters. Concordance correlation coefficient, two-sample t-test, and Pearson's correlation coefficient were used to test for similarities, differences, and associations among variables. RESULTS: Female glaucoma patients showed a statistically higher ophthalmic artery normalized distance between ascending and descending limb (p = 0.004), hypertensive glaucoma patients a statistically higher ophthalmic artery peak systolic velocity time (p = 0.025), glaucoma patients with hyperlipidemia a statistically higher ophthalmic artery resistivity index (p = 0.023) and a statistically higher ophthalmic artery peak systolic velocity acceleration (p = 0.025), glaucoma patients with cardiovascular diseases a statistically lower central retinal artery normalized distance between ascending and descending limb of the wave (p = 0.033) and a statistically higher central retinal artery period (p = 0.028), and patients with different body mass index a statistically different central retinal artery normalized distance between ascending and descending limb of the wave (p = 0.016). Groups with different disease severity, classified following the Brusini glaucoma staging system 2, showed statistically different central retinal artery normalized distance between ascending and descending limb of the wave (p < 0.001) and central retinal artery period (p = 0.016). No statistical differences were found in regard to race, diabetes status, glaucoma family history, and smoking. DISCUSSION: Ophthalmic artery and central retinal artery computer-aided analysis of velocity waveforms could identify novel waveform parameters capable of differentiating among different demographics and disease severity of open-angle glaucoma patients.

Emergent three-dimensional sperm motility: coupling calcium dynamics and preferred curvature in a Kirchhoff rod model.

Changes in calcium concentration along the sperm flagellum regulate sperm motility and hyperactivation, characterized by an increased flagellar bend amplitude and beat asymmetry, enabling the sperm to reach and penetrate the ovum (egg). The signalling pathways by which calcium increases within the flagellum are well established. However, the exact mechanisms of how calcium regulates flagellar bending are still under investigation. We extend our previous model of planar flagellar bending by developing a fluid-structure interaction model that couples the 3D motion of the flagellum in a viscous Newtonian fluid with the evolving calcium concentration. The flagellum is modelled as a Kirchhoff rod: an elastic rod with preferred curvature and twist. The calcium dynamics are represented as a 1D reaction-diffusion model on a moving domain, the flagellum. The two models are coupled assuming that the preferred curvature and twist of the sperm flagellum depend on the local calcium concentration. To investigate the effect of calcium on sperm motility, we compare model results of flagellar bend amplitude and swimming speed for three cases: planar, helical (spiral with equal amplitude in both directions), and quasi-planar (spiral with small amplitude in one direction). We observe that for the same parameters, the planar swimmer is faster and a turning motion is more clearly observed when calcium coupling is accounted for in the model. In the case of flagellar bending coupled to the calcium concentration, we observe emergent trajectories that can be characterized as a hypotrochoid for both quasi-planar and helical bending.

Effect of intraocular pressure on the hemodynamics of the central retinal artery: a mathematical model.

Retinal hemodynamics plays a crucial role in the pathophysiology of several ocular diseases. There are clear evidences that the hemodynamics of the central retinal artery (CRA) is strongly affected by the level of intraocular pressure (IOP), which is the pressure inside the eye globe. However, the mechanisms through which this occurs are still elusive. The main goal of this paper is to develop a mathematical model that combines the mechanical action of IOP and the blood flow in the CRA to elucidate the mechanisms through which IOP elevation affects the CRA hemodynamics. Our model suggests that the development of radial compressive regions in the lamina cribrosa (a collagen structure in the optic nerve pierced by the CRA approximately in its center) might be responsible for the clinically-observed blood velocity reduction in the CRA following IOP elevation. The predictions of the mathematical model are in very good agreement with experimental and clinical data. Our model also identifies radius and thickness of the lamina cribrosa as major factors affecting the IOP-CRA relationship, suggesting that anatomical differences among individuals might lead to different hemodynamic responses to IOP elevation.

Cerebrospinal fluid pressure and glaucoma: regulation of trans-lamina cribrosa pressure.

Increased trans-lamina cribrosa pressure difference (TLCPD), the difference of intraocular pressure (IOP) and orbital cerebrospinal fluid pressure (CSF-P), has been investigated as a possible risk factor in glaucoma pathogenesis. In fact, lower CSF-P in the setting of normal IOP has been implicated as a potential risk factor for normal tension glaucoma. Increased TLCPD has been associated with decreased neuroretinal rim area and increased visual field defects. Furthermore, dysregulation of systemic blood pressure has been associated with changes in IOP. Recent studies have also suggested that increased body mass index (BMI) is associated with decreased prevalence of glaucoma, which may be due to an increased CSF-P with increased BMI found in many studies. Given the interaction of various pressures, their role in glaucoma pathophysiology has come under investigation and warrants further study in order to better understand the aetiology and progression of glaucoma.

Mathematical modeling approaches in the study of glaucoma disparities among people of African and European descents.

Open angle glaucoma (OAG) is a severe ocular disease characterized by progressive and irreversible vision loss. While elevated intraocular pressure (IOP) is a well-established risk factor for OAG, the progression of OAG in many cases, despite IOP treatment, suggests that other risk factors must play significant roles in the development of the disease. For example, various structural properties of the eye, ocular blood flow properties, and systemic conditions have been identified as risk factors for OAG. Ethnicity has also been indicated as a relevant factor that affects the incidence and prevalence of OAG; in fact, OAG is the leading cause of blindness among people of African descent. Numerous clinical studies have been designed to examine the possible correlation and causation between OAG and these factors; however, these studies are met with the challenge of isolating the individual role of multiple interconnected factors. Over the last decade, various mathematical modeling approaches have been implemented in combination with clinical studies in order to provide a mechanical and hemodynamical description of the eye in relation to the entire human body and to assess the contribution of single risk factors to the development of OAG. This review provides a summary of the clinical evidence of ocular structural differences, ocular vascular differences and systemic vascular differences among people of African and European descent, describes the mathematical approaches that have been proposed to study ocular mechanics and hemodynamics while discussing how they could be used to investigate the relevance to OAG of racial disparities, and outlines possible new directions of research.