Jerry G. Myers

Intimal Thickness Is not Associated With Wall Shear Stress Patterns in the Human Right Coronary Artery

Objective—Low wall shear stress has been implicated in atherogenesis throughout the arterial tree, including the right coronary artery (RCA). The objective of this study was to determine the level of covariation of intimal thickness and wall shear stress in the human RCA. Methods and Results—Postmortem histological measurements of intimal thickness were compared with wall shear stresses calculated from computational flow modeling in 4 human right coronary arteries. A statistically significant correlation between intimal thickness and wall shear stress was found in only 1 of the 4 arteries studied. Conclusion—Wall shear stress does not appear to be related to intimal thickness in the 4 RCAs studied.

Microgravity-Induced Fluid Shift and Ophthalmic Changes

Although changes to visual acuity in spaceflight have been observed in some astronauts since the early days of the space program, the impact to the crew was considered minor. Since that time, missions to the International Space Station have extended the typical duration of time spent in microgravity from a few days or weeks to many months. This has been accompanied by the emergence of a variety of ophthalmic pathologies in a significant proportion of long-duration crewmembers, including globe flattening, choroidal folding, optic disc edema, and optic nerve kinking, among others. The clinical findings of affected astronauts are reminiscent of terrestrial pathologies such as idiopathic intracranial hypertension that are characterized by high intracranial pressure. As a result, NASA has placed an emphasis on determining the relevant factors and their interactions that are responsible for detrimental ophthalmic response to space. This article will describe the Visual Impairment and Intracranial Pressure syndrome, link it to key factors in physiological adaptation to the microgravity environment, particularly a cephalad shifting of bodily fluids, and discuss the implications for ocular biomechanics and physiological function in long-duration spaceflight.

Theoretical analysis of the mechanisms of a gender differentiation in the propensity for orthostatic intolerance after spaceflight

BackgroundA tendency to develop reentry orthostasis after a prolonged exposure to microgravity is a common problem among astronauts. The problem is 5 times more prevalent in female astronauts as compared to their male counterparts. The mechanisms responsible for this gender differentiation are poorly understood despite many detailed and complex investigations directed toward an analysis of the physiologic control systems involved.MethodsIn this study, a series of computer simulation studies using a mathematical model of cardiovascular functioning were performed to examine the proposed hypothesis that this phenomenon could be explained by basic physical forces acting through the simple common anatomic differences between men and women. In the computer simulations, the circulatory components and hydrostatic gradients of the model were allowed to adapt to the physical constraints of microgravity. After a simulated period of one month, the model was returned to the conditions of earths gravity and the standard postflight tilt test protocol was performed while the model output depicting the typical vital signs was monitored.ConclusionsThe analysis demonstrated that a 15% lowering of the longitudinal center of gravity in the anatomic structure of the model was all that was necessary to prevent the physiologic compensatory mechanisms from overcoming the propensity for reentry orthostasis leading to syncope.

Credibility, Replicability, and Reproducibility in Simulation for Biomedicine and Clinical Applications in Neuroscience

Modeling and simulation in computational neuroscience is currently a research enterprise to better understand neural systems. It is not yet directly applicable to the problems of patients with brain disease. To be used for clinical applications, there must not only be considerable progress in the field but also a concerted effort to use best practices in order to demonstrate model credibility to regulatory bodies, to clinics and hospitals, to doctors, and to patients. In doing this for neuroscience, we can learn lessons from long-standing practices in other areas of simulation (aircraft, computer chips), from software engineering, and from other biomedical disciplines. In this manuscript, we introduce some basic concepts that will be important in the development of credible clinical neuroscience models: reproducibility and replicability; verification and validation; model configuration; and procedures and processes for credible mechanistic multiscale modeling. We also discuss how garnering strong community involvement can promote model credibility. Finally, in addition to direct usage with patients, we note the potential for simulation usage in the area of Simulation-Based Medical Education, an area which to date has been primarily reliant on physical models (mannequins) and scenario-based simulations rather than on numerical simulations.

Development, Validation, and Implementation of a Medical Judgment Metric:

Background: Medical decision making is a critical, yet understudied, aspect of medical education. Aims: To develop the Medical Judgment Metric (MJM), a numerical rubric to quantify good decisions in practice in simulated environments; and to obtain initial preliminary evidence of reliability and validity of the tool. Methods: The individual MJM items, domains, and sections of the MJM were built based on existing standardized frameworks. Content validity was determined by a convenient sample of eight experts. The MJM instrument was pilot tested in four medical simulations with a team of three medical raters assessing 40 participants with four levels of medical experience and skill. Results: Raters were highly consistent in their MJM scores in each scenario (intraclass correlation coefficient 0.965 to 0.987) as well as their evaluation of the expected patient outcome (Fleiss’s Kappa 0.791 to 0.906). For each simulation scenario, average rater cut-scores significantly predicted expected loss of life or stabilization (Cohen’s Kappa 0.851 to 0.880). Discussion: The MJM demonstrated preliminary evidence of reliability and validity.

Predicting head injury risk during International Space Station increments.

INTRODUCTION NASAs Human Research Program is using a probabilistic risk assessment approach to identify acute and chronic medical risks to manned spaceflight. The objective of this project was to estimate the likelihood of a neurological head injury to a crewmember severe enough to require medical assessment, treatment, or evacuation during a typical International Space Station (ISS) increment. METHODS A 2 degree-of-freedom analytical model of the human head was created to allow for analysis of the impact response. The output of the model is acceleration of the head, which was used to determine the probability that the simulated impact resulted in a head injury with an Abbreviated Injury Scale (AIS) score of 3 or greater. These data were then integrated into a probabilistic risk assessment, which outputs a likelihood of injury with a representative measure of the uncertainty. RESULTS A Monte Carlo simulation was performed to vary input parameters over their defined distributions. The mean probability of a moderate neurological injury (AIS 3 or greater) occurring due to a head impact by a crewmember translating through the ISS is 1.16 x 10(-4) per 6-mo mission increment (2.32 x 10(-4) per year). DISCUSSION Our head injury prediction model has shown that there is a low, yet not insignificant, probability of neurological head injury of AIS score 3 or greater. The results from this simulation will be input into the parent Integrated Medical Model, which incorporates the risks of over 80 different medical events in order to inform mission planning scenarios.

An extravehicular suit impact load attenuation study to improve astronaut bone fracture prediction.

INTRODUCTION Understanding the contributions to the risk of bone fracture during spaceflight is essential for mission success. METHODS A pressurized extravehicular activity (EVA) suit analogue test bed was developed, impact load attenuation data were obtained, and the load at the hip of an astronaut who falls to the side during an EVA was characterized. Offset (representing the gap between the EVA suit and the astronauts body), impact load magnitude, and EVA suit operating pressure were factors varied in the study. The attenuation data were incorporated into a probabilistic model of bone fracture risk during spaceflight, replacing the previous load attenuation value that was based on commercial hip protector data. RESULTS Load attenuation was more dependent on offset than on pressurization or load magnitude, especially at small offset values. Load attenuation factors for offsets between 0.1-1.5 cm were 0.69 +/- 0.15, 0.49 +/- 0.22, and 0.35 +/- 0.18 for mean impact forces of 4827, 6400, and 8467 N, respectively. Load attenuation factors for offsets of 2.8-5.3 cm were 0.93 +/- 0.2, 0.94 +/- 0.1, and 0.84 +/- 0.5 for the same mean impact forces. The mean and 95th percentile bone fracture risk index predictions were each reduced by 65-83%. The mean and 95th percentile bone fracture probability predictions were both reduced approximately 20-50%. DISCUSSION The reduction in uncertainty and improved confidence in bone fracture predictions increased the fidelity and credibility of the fracture risk model and its benefit to mission design and in-flight operational decisions.

Time and Space Resolved Wall Temperature Measurements During Nucleate Boiling With Constant Heat Flux Boundary Conditions

The lack of temporally and spatially resolved measurements under nucleate bubbles has complicated efforts to fully explain pool-boiling phenomena. The objective of this current work is to acquire time and space resolved temperature distributions under nucleate bubbles on a constant heat flux surface. This was performed using a microheater array with 100 μm resolution that allowed effectively simultaneous measurements of surface temperature while supplying a constant dissipative heat flux. This data is then correlated with high speed (> 1000Hz) visual recordings of the bubble growth and departure from the heater surface acquired from below and from the side of the heater. The data indicate that a significant source of energy during bubble nucleation and initial growth is the superheated layer around the bubble. Bubble coalescence was not observed to decrease surface temperature as significantly as bubble departure from the surface. Since bubble departure is typically followed by a sharp increase in the heater surface temperature, it is surmised that the departing bubble effectively removes the superheated layer, allowing a higher local heat transfer rate with the bulk fluid through transient conduction/micro-convection during rewetting.Copyright

Forecasting Postflight Hip Fracture Probability Using Probabilistic Modeling

A probabilistic model predicts hip fracture probability for post-flight male astronauts during lateral fall scenarios from various heights. A biomechanical representation of the hip provides impact load. Correlations relate spaceflight bone mineral density (BMD) loss and post-flight BMD recovery to bone strength. Translations convert fracture risk index, the ratio of applied load to bone strength, to fracture probability. Parameter distributions capture uncertainty and Monte Carlo simulations provide probability outcomes. The fracture probability for a 1 m fall 0 days post-flight is 15% greater than preflight and remains 6% greater than pre-flight at 365 days post-flight. Probability quantification provides insight into how spaceflight induced BMD loss affects fracture probability. A bone loss rate reflecting improved exercise countermeasures and dietary intake further reduces the post-flight fracture probability to 6% greater than preflight at 0 days post-flight and 2% greater at 365 days post-flight. Quantification informs assessments of countermeasure effectiveness. When preflight BMD is one standard deviation below mean astronaut preflight BMD, fracture probability at 0 days post-flight is 34% greater than the preflight fracture probability calculated with mean BMD and 28% greater at 365 days post-flight. Quantification aids review of astronaut BMD fitness for duty standards. Increases in post-flight fracture probability are associated with an estimated 18% reduction in post-flight bone strength. Therefore, a 0.82 deconditioning coefficient modifies force application limits for crew vehicles.

The impact of ocular hemodynamics and intracranial pressure on intraocular pressure during acute gravitational changes

Exposure to microgravity causes a bulk fluid shift toward the head, with concomitant changes in blood volume/pressure, and intraocular pressure (IOP). These and other factors, such as intracranial pressure (ICP) changes, are suspected to be involved in the degradation of visual function and ocular anatomical changes exhibited by some astronauts. This is a significant health concern. Here, we describe a lumped-parameter numerical model to simulate volume/pressure alterations in the eye during gravitational changes. The model includes the effects of blood and aqueous humor dynamics, ICP, and IOP-dependent ocular compliance. It is formulated as a series of coupled differential equations and was validated against four existing data sets on parabolic flight, body inversion, and head-down tilt (HDT). The model accurately predicted acute IOP changes in parabolic flight and HDT, and was satisfactory for the more extreme case of inversion. The short-term response to the changing gravitational field was dominated by ocular blood pressures and compliance, while longer-term responses were more dependent on aqueous humor dynamics. ICP had a negligible effect on acute IOP changes. This relatively simple numerical model shows promising predictive capability. To extend the model to more chronic conditions, additional data on longer-term autoregulation of blood and aqueous humor dynamics are needed.NEW & NOTEWORTHY A significant percentage of astronauts present anatomical changes in the posterior eye tissues after spaceflight. Hypothesized increases in ocular blood volume and intracranial pressure (ICP) in space have been considered to be likely factors. In this work, we provide a novel numerical model of the eye that incorporates ocular hemodynamics, gravitational forces, and ICP changes. We find that changes in ocular hemodynamics govern the response of intraocular pressure during acute gravitational change.