Ocular perfusion pressure is not reduced in response to lower body negative pressure.

Lower body negative pressure (LBNP) has been proposed as a countermeasure to mitigate the cephalad fluid shift occurring during spaceflight, which may be associated with the development of Spaceflight Associated Neuro-ocular Syndrome (SANS). This study quantifies the effect of LBNP on intraocular pressure (IOP), mean arterial pressure at eye level (MAPeye), and ocular perfusion pressure (OPP). Twenty-four subjects (12 male, 12 female) were subjected to graded LBNP in 0° supine and 15° head-down tilt (HDT) postures from 0 mmHg to -50 mmHg in 10 mmHg increments. IOP decreased significantly with LBNP pressure in 0° supine (by 0.7 ± 0.09 mmHg per 10 mmHg LBNP pressure, p < 0.001) and in 15° HDT (by 1.0 ± 0.095 mmHg per 10 mmHg of LBNP pressure, p < 0.001). MAPeye significantly decreased by 0.9 ± 0.4 mmHg per 10 mmHg of LBNP pressure in 0° supine (p = 0.016) but did not significantly change with LBNP in 15° HDT (p = 0.895). OPP did not significantly change with LBNP in 0° supine (p = 0.539) but it significantly increased in 15° HDT at 1.0 ± 0.3 mmHg per 10 mmHg of LBNP pressure (p = 0.010). Sex did not have a significant effect on OPP, MAPeye, or IOP in any condition. In 15° HDT, the reduction in IOP during increasing negative pressure, combined with the relatively constant MAPeye, led to the increase in OPP. Furthermore, results suggest that LBNP, while effective in reducing IOP, is not effective in reducing OPP across all postures investigated.

Gravitational effects on carotid and jugular characteristics in graded head-up and head-down tilt.

Altered gravity affects hemodynamics and blood flow in the neck. At least one incidence of jugular venous thrombosis has been reported in an astronaut on the International Space Station. This investigation explores the impact of changes in the direction of the gravitational vector on the characteristics of the neck arteries and veins. Twelve subjects underwent graded tilt from 45° head-up to 45° head-down in 15° increments in both supine and prone positions. At each angle, the cross-sectional area of the left and right common carotid arteries (ACCA) and internal jugular veins (AIJV) were measured by ultrasound. Internal jugular venous pressure (IJVP) was also measured by compression sonography. Gravitational dose-response curves were generated from experimental data. ACCA did not show any gravitational dependence. Conversely, both AIJV and IJVP increased in a nonlinear fashion with head-down tilt. AIJV was significantly larger on the right side than the left side at all tilt angles. In addition, IJVP was significantly elevated in the prone position compared with the supine position, most likely because of raised intrathoracic pressure while prone. Dose-response curves were compared with existing experimental data from parabolic flight and spaceflight studies, showing good agreement on an acute timescale. The quantification of jugular hemodynamics as a function of changes in the gravitational vector presented here provides a terrestrial model to reference spaceflight-induced changes, contributes to the assessment of the pathogenesis of spaceflight venous thromboembolism events, and informs the development of countermeasures.NEW & NOTEWORTHY Flow stasis and thrombosis have been identified in the jugular vein during spaceflight. We measured the area and pressure of the internal jugular vein and the area of the common carotid artery in graded head-up and head-down tilt. Experimental data are used to generate gravitational dose-response curves for the measured variables, demonstrating that jugular vein area and pressure exhibit a nonlinear response to altered gravity. Gravitational dose-response curves show good agreement with spaceflight and parabolic flight studies.

Virtual Reality "exergames": A promising countermeasure to improve motivation and restorative effects during long duration spaceflight missions.

Long duration spaceflight missions will require novel exercise systems to protect astronaut crew from the detrimental effects of microgravity exposure. The SPRINT protocol is a novel and promising exercise prescription that combines aerobic and resistive training using a flywheel device, and it was successfully employed in a 70-day bed-rest study as well as onboard the International Space Station. Our team created a VR simulation to further augment the SPRINT protocol when using a flywheel ergometer training device (the Multi-Mode Exercise Device or M-MED). The simulation aspired to maximal realism in a virtual river setting while providing real-time biometric feedback on heart rate performance to subjects. In this pilot study, five healthy, male, physically-active subjects aged 35 ± 9.0 years old underwent 2 weeks of SPRINT protocol, either with or without the VR simulation. After a 1-month washout period, subjects returned for a subsequent 2 weeks in the opposite VR condition. We measured physiological and cognitive variables of stress, performance, and well-being. While physiological effects did not suggest much difference with the VR condition over 2 weeks, metrics of motivation, affect, and mood restoration showed detectable differences, or trended toward more positive outcomes than exercise without VR. These results provide evidence that a well-designed VR "exergaming" simulation with biometric feedback could be a beneficial addition to exercise prescriptions, especially if users are exposed to isolation and confinement.

Gravitational Dose-Response Curves for Acute Cardiovascular Hemodynamics and Autonomic Responses in a Tilt Paradigm.

Background The cardiovascular system is strongly dependent on the gravitational environment. Gravitational changes cause mechanical fluid shifts and, in turn, autonomic effectors influence systemic circulation and cardiac control. We implemented a tilt paradigm to (1) investigate the acute hemodynamic response across a range of directions of the gravitational vector, and (2) to generate specific dose-response relationships of this gravitational dependency. Methods and Results Twelve male subjects were tilted from 45° head-up tilt to 45° head-down tilt in 15° increments, in both supine and prone postures. We measured the steady-state hemodynamic response in a range of variables including heart rate, stroke volume, cardiac output, oxygen consumption, total peripheral resistance, blood pressure, and autonomic indices derived from heart rate variability analysis. There is a strong gravitational dependence in almost all variables considered, with the exception of oxygen consumption, whereas systolic blood pressure remained controlled to within ≈3% across the tilt range. Hemodynamic responses are primarily driven by differential loading on the baroreflex receptors, combined with differences in venous return to the heart. Thorax compression in the prone position leads to reduced venous return and increased sympathetic nervous activity, raising heart rate, and systemic vascular resistance while lowering cardiac output and stroke volume. Conclusions Gravitational dose-response curves generated from these data provide a comprehensive baseline from which to assess the efficacy of potential spaceflight countermeasures. Results also assist clinical management of terrestrial surgery in prone posture or head-down tilt positions.

Distance travelled by military recruits during basic training is a significant risk factor for lower limb overuse injury.

INTRODUCTION: Military initial training results in a high incidence of lower limb overuse injuries (stress fractures and medial tibial stress syndrome). This study aimed to determine whether the distance travelled by recruits, both on and off duty, was a risk factor for overuse injury. METHODS: 14 male airborne infantry recruits from three training platoons carried global positioning system receivers throughout the first 19 weeks of basic military training. Total distance travelled each day was recorded. This was compared with time of clinical manifestation of 52 lower limb overuse injuries (stress fractures and medial tibial stress syndrome) collected from the 276 airborne infantry recruits in the period immediately preceding the study. RESULTS: Recruits travelled significantly farther than the UK average male population in 17 of 18 measured weeks. Pearson correlation between distance travelled per week and injuries was not significant (p=0.4448); however, correlation between distance travelled per week and injuries two weeks later was significant (p=0.0263). A generalised linear model found distance travelled as a significant covariate (p=0.0144) to the expected number of injuries two weeks later. CONCLUSION: Recruits travel long distances during basic training, particularly in the first few weeks when they are not yet conditioned. This distance travelled is likely a contributing risk factor to the high incidence of overuse injuries seen during training, and strategies to reduce this distance should be explored.

Gravitational effects on intraocular pressure and ocular perfusion pressure.

Changes in the gravitational vector by postural changes or weightlessness induce fluid shifts, impacting ocular hemodynamics and regional pressures. This investigation explores the impact of changes in the direction of the gravitational vector on intraocular pressure (IOP), mean arterial pressure at eye level (MAPeye), and ocular perfusion pressure (OPP), which is critical for ocular health. Thirteen subjects underwent 360° of tilt (including both prone and supine positions) at 15° increments. At each angle, steady-state IOP and MAPeye were measured, and OPP calculated as MAPeye - IOP. Experimental data were also compared to a six-compartment lumped-parameter model of the eye. Mean IOP, MAPeye, and OPP significantly increased from 0° supine to 90° head-down tilt (HDT) by 20.7 ± 1.7 mmHg (P < 0.001), 38.5 ± 4.1 mmHg (P < 0.001), and 17.4 ± 3.2 mmHg (P < 0.001), respectively. Head-up tilt (HUT) significantly decreased OPP by 16.5 ± 2.5 mmHg (P < 0.001). IOP was significantly higher in prone versus supine position for much of the tilt range. Our study indicates that OPP is highly gravitationally dependent. Specifically, data show that MAPeye is more gravitationally dependent than IOP, thus causing OPP to increase during HDT and to decrease during HUT. In addition, IOP was elevated in prone position compared with supine position due to the additional hydrostatic column between the base of the rostral globe to the mid-coronal plane, supporting the notion that hydrostatic forces play an important role in ocular hemodynamics. Changes in OPP as a function of changes in gravitational stress and/or weightlessness may play a role in the pathogenesis of spaceflight-associated neuro-ocular syndrome.NEW & NOTEWORTHY Maintaining appropriate ocular perfusion pressure (OPP) is critical for ocular health. We measured the relative changes in intraocular and mean arterial pressures during 360° tilt and calculated OPP, which was elevated during head-down tilt and decreased during head-up tilt. Experimental data are also explained by our computational model. We demonstrate that OPP is more gravitationally dependent than previously recognized and may be a factor in the overall patho-etiology behind the weightlessness-induced spaceflight-associated neuro-ocular syndrome.

Indirect measurement of absolute cardiac output during exercise in simulated altered gravity is highly dependent on the method.

PURPOSE: Altered gravity environments introduce cardiovascular changes that may require continuous hemodynamic monitoring in both spaceflight and terrestrial analogs. Conditions in such environments are often prohibitive to direct/invasive methods and therefore, indirect measurement techniques must be used. This study compares two common cardiac measurement techniques used in the human spaceflight domain, pulse contour analysis (PCA-Nexfin) and inert gas rebreathing (IGR-Innocor), in subjects completing ergometer exercise under altered gravity conditions simulated using a tilt paradigm. METHODS: Seven subjects were tilted to three different angles representing Martian, Lunar, and microgravity conditions in the rostrocaudal direction. They completed a 36-min submaximal cardiovascular exercise protocol in each condition. Hemodynamics were continuously monitored using Nexfin and Innocor. RESULTS: Linear mixed-effects models revealed a significant bias of [Formula: see text] ml ([Formula: see text]) in stroke volume and [Formula: see text] l/min ([Formula: see text]) in cardiac output, with Nexfin measuring greater than Innocor in both variables. These values are in agreement with a Bland-Altman analysis. The correlation of stroke volume and cardiac output measurements between Nexfin and Innocor were [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]) respectively. CONCLUSION: There is a poor agreement in absolute stroke volume and cardiac output values between measurement via PCA (Nexfin) and IGR (Innocor) in subjects who are exercising in simulated altered gravity environments. These results suggest that the chosen measurement method and device greatly impacts absolute measurements of cardiac output. However, there is a good level of agreement between the two devices when measuring relative changes. Either of these devices seem adequate to capture cardiac changes, but should not be solely relied upon for accurate measurement of absolute cardiac output.

Modeling individual differences in cardiovascular response to gravitational stress using a sensitivity analysis.

The human cardiovascular (CV) system elicits a physiological response to gravitational environments, with significant variation between different individuals. Computational modeling can predict CV response, however model complexity and variation of physiological parameters in a normal population makes it challenging to capture individual responses. We conducted a sensitivity analysis on an existing 21-compartment lumped-parameter hemodynamic model in a range of gravitational conditions to 1) investigate the influence of model parameters on a tilt test CV response and 2) to determine the subset of those parameters with the most influence on systemic physiological outcomes. A supine virtual subject was tilted to upright under the influence of a constant gravitational field ranging from 0 g to 1 g. The sensitivity analysis was conducted using a Latin hypercube sampling/partial rank correlation coefficient methodology with subsets of model parameters varied across a normal physiological range. Sensitivity was determined by variation in outcome measures including heart rate, stroke volume, central venous pressure, systemic blood pressures, and cardiac output. Results showed that model parameters related to the length, resistance, and compliance of the large veins and parameters related to right ventricular function have the most influence on model outcomes. For most outcome measures considered, parameters related to the heart are dominant. Results highlight which model parameters to accurately value in simulations of individual subjects' CV response to gravitational stress, improving the accuracy of predictions. Influential parameters remain largely similar across gravity levels, highlighting that accurate model fitting in 1 g can increase the accuracy of predictive responses in reduced gravity.NEW & NOTEWORTHY Computational modeling is used to predict cardiovascular responses to altered gravitational environments. However, considerable variation between subjects and model complexity makes accurate parameter assignment for individuals challenging. This computational effort studies sensitivity in cardiovascular model outcomes due to varying parameters across a normal physiological range. This allows determination of which parameters have the largest influence on outcomes, i.e., which parameters must be most carefully selected to give accurate predictions of individual responses.

An ecological study of socioeconomic predictors in detection of COVID-19 cases across neighborhoods in New York City.

BACKGROUND: New York City was the first major urban center of the COVID-19 pandemic in the USA. Cases are clustered in the city, with certain neighborhoods experiencing more cases than others. We investigate whether potential socioeconomic factors can explain between-neighborhood variation in the COVID-19 test positivity rate. METHODS: Data were collected from 177 Zip Code Tabulation Areas (ZCTA) in New York City (99.9% of the population). We fit multiple Bayesian Besag-York-Mollié (BYM) mixed models using positive COVID-19 tests as the outcome, a set of 11 representative demographic, economic, and health-care associated ZCTA-level parameters as potential predictors, and the total number of COVID-19 tests as the exposure. The BYM model includes both spatial and nonspatial random effects to account for clustering and overdispersion. RESULTS: Multiple regression approaches indicated a consistent, statistically significant association between detected COVID-19 cases and dependent children (under 18 years old), population density, median household income, and race. In the final model, we found that an increase of only 5% in young population is associated with a 2.3% increase in COVID-19 positivity rate (95% confidence interval (CI) 0.4 to 4.2%, p=0.021). An increase of 10,000 people per km2 is associated with a 2.4% (95% CI 0.6 to 4.2%, p=0.011) increase in positivity rate. A decrease of $10,000 median household income is associated with a 1.6% (95% CI 0.7 to 2.4%, p<0.001) increase in COVID-19 positivity rate. With respect to race, a decrease of 10% in White population is associated with a 1.8% (95% CI 0.8 to 2.8%, p<0.001) increase in positivity rate, while an increase of 10% in Black population is associated with a 1.1% (95% CI 0.3 to 1.8%, p<0.001) increase in positivity rate. The percentage of Hispanic (p=0.718), Asian (p=0.966), or Other (p=0.588) populations were not statistically significant factors. CONCLUSIONS: Our findings indicate associations between neighborhoods with a large dependent youth population, densely populated, low-income, and predominantly black neighborhoods and COVID-19 test positivity rate. The study highlights the importance of public health management during and after the current COVID-19 pandemic. Further work is warranted to fully understand the mechanisms by which these factors may have affected the positivity rate, either in terms of the true number of cases or access to testing.