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Meyers, V.

Publications and source records attributed to Meyers, V..

Exploration Analysis of Carbon Dioxide Levels and Ultrasound Measures of the Eye During ISS Missions

Enhanced screening for the Visual Impairment/Intracranial Pressure (VIIP) Syndrome, including in-flight ultrasound, was implemented in 2010 to better characterize the changes in vision observed in some long-duration crewmembers. Suggested possible risk factors for VIIP include cardiovascular changes, diet, anatomical and genetic factors, and environmental conditions. As a potent vasodilator, carbon dioxide (CO (sub 2)), which is chronically elevated on the International Space Station (ISS) relative to typical indoor and outdoor ambient levels on Earth, seems a plausible contributor to VIIP. In an effort to understand the possible associations between CO (sub 2) and VIIP, this study analyzes the relationship between ambient CO (sub 2) levels on ISS and ultrasound measures of the eye obtained from ISS fliers. CO (sub 2) measurements will be pulled directly from Operational Data Reduction Complex for the Lab and Node 3 major constituent analyzers (MCAs) on ISS or from sensors located in the European Columbus module, as available. CO (sub 2) measures between ultrasound sessions will be summarized using standard time series class metrics in MATLAB including time-weighted means and variances. Cumulative CO (sub 2) exposure metrics will also be developed. Regression analyses will be used to quantify the relationships between the CO (sub 2) metrics and specific ultrasound measures. Generalized estimating equations will adjust for the repeated measures within individuals. Multiple imputation techniques will be used to adjust for any possible biases in missing data for either CO (sub 2) or ultrasound measures. These analyses will elucidate the possible relationship between CO (sub 2) and changes in vision and also inform future analysis of inflight VIIP data.

Young, M.

Toxicity of Mineral Dusts and a Proposed Mechanism for the Pathogenesis of Particle-Induced Lung Diseases

Humans will set foot on the moon again. The lunar surface has been bombarded for 4 billion years by micrometeoroids and cosmic radiation, creating a layer of fine dust having a potentially reactive particle surface. To investigate the impact of surface reactivity (SR) on the toxicity of particles, and in particular, lunar dust (LD), we ground 2 Apollo 14 LD samples to increase their SR and compare their toxicity with those of unground LD, TiO2 and quartz. Intratracheally instilled at 0, 1, 2.5, or 7.5 mg/rat, all dusts caused dose-dependent increases in pulmonary lesions, and enhancement of biomarkers of toxicity assessed in bronchoalveolar lavage fluids (BALF). The toxicity of LD was greater than that of TiO2 but less than that of quartz. Three LDs differed 14-fold in SR but were equally toxic; quartz had the lowest SR but was most toxic. These results show no correlation between particle SR and toxicity. Often pulmonary toxicity of a dust can be attributed to oxidative stress (OS). We further observed dose-dependent and dustcytotoxicity- dependent increases in neutrophils. The oxidative content per BALF cell was also directly proportional to both the dose and cytotoxicity of the dusts. Because neutrophils are short-lived and release of oxidative contents after they die could initiate and promote a spectrum of lesions, we postulate a general mechanism for the pathogenesis of particle-induced diseases in the lung that involves chiefly neutrophils, the source of persistent endogenous OS. This mechanism explains why one dust (e.g., quartz or nanoparticles) is more toxic than another (e.g., micrometer-sized TiO2), why dust-induced lesions progress with time, and why lung cancer occurs in rats but not in mice and hamsters exposed to the same duration and concentration of dust.

Lam, C.‐W.

The Relationship Between CO2 Levels and CO2 Related Symptoms Reported on the ISS

Medical Operations, Toxicology, and the Lifetime Surveillance of Astronaut Health collaborated to assess the association of CO2 levels on board the International Space Station and USOS crew reported symptoms inflight, i.e. headache and vision changes. Private Medical Conference (PMC) documents and the weekly Space Medicine Operations Team (SMOT) Notes were used to provide a robust data set of inflight medical events. All events and non‐events were documented independent of CO2 levels and other potential contributors. Average (arithmetic mean) and single point maximum ppCO2 was calculated for the 24 hours and 7 days prior to the PMC or SMOT date and time provided by LSAH. Observations falling within the first 7 days of flight (147) were removed from the datasets analyzed to avoid confounding with Space Adaptation Syndrome. The final analysis was based on 1716 observations. For headache, 46 headaches were observed. CO2 level, age at launch, time inflight, and data source were all significantly associated with headache. In particular, for each 1 mmHg increase in CO2, the odds of a crewmember reporting a headache doubled. For vision changes, 29 reports of vision changes were observed. These observations were not found to be statistically associated with CO2 levels as analyzed. While the incidence of headache has was not high (~3%), headaches may be an indicator of underlying increases in intracranial pressure, which may result likely from the synergy between CO2‐induced cerebral vasodilatation and decreased venous drainage in microgravity. Vision changes were inconsistently reported and as a result did not align appropriately with the CO2 levels. Further analysis is needed. Our results support ongoing efforts to lower the CO2 exposure limits in spacecraft.

VanBaalen, M.

Missing Data and Multiple Imputation: An Unbiased Approach

The default method of dealing with missing data in statistical analyses is to only use the complete observations (complete case analysis), which can lead to unexpected bias when data do not meet the assumption of missing completely at random (MCAR). For the assumption of MCAR to be met, missingness cannot be related to either the observed or unobserved variables. A less stringent assumption, missing at random (MAR), requires that missingness not be associated with the value of the missing variable itself, but can be associated with the other observed variables. When data are truly MAR as opposed to MCAR, the default complete case analysis method can lead to biased results. There are statistical options available to adjust for data that are MAR, including multiple imputation (MI) which is consistent and efficient at estimating effects. Multiple imputation uses informing variables to determine statistical distributions for each piece of missing data. Then multiple datasets are created by randomly drawing on the distributions for each piece of missing data. Since MI is efficient, only a limited number, usually less than 20, of imputed datasets are required to get stable estimates. Each imputed dataset is analyzed using standard statistical techniques, and then results are combined to get overall estimates of effect. A simulation study will be demonstrated to show the results of using the default complete case analysis, and MI in a linear regression of MCAR and MAR simulated data. Further, MI was successfully applied to the association study of CO2 levels and headaches when initial analysis showed there may be an underlying association between missing CO2 levels and reported headaches. Through MI, we were able to show that there is a strong association between average CO2 levels and the risk of headaches. Each unit increase in CO2 (mmHg) resulted in a doubling in the odds of reported headaches.

Foy, M.

Challenges in Evaluating Relationships Between Quantitative Data (Carbon Dioxide) and Qualitative Data (Self-Reported Visual Changes)

Understanding the nuances in clinical data is critical in developing a successful data analysis plan. Carbon dioxide (CO2) data are collected on board the International Space Station (ISS) in a continuous stream. Clinical data on ISS are primarily collected via conversations between individual crewmembers and NASA Flight Surgeons during weekly Private Medical Conferences (PMC). Law, et.al, 20141 demonstrated a statistically significant association between weekly average CO2 levels on ISS and self-reported headaches over the reporting period from March 14, 2001 to May 31, 2012. The purpose of this analysis is to describe the evaluation of a possible association between visual changes and CO2 levels on ISS and to discuss challenges in developing an appropriate analysis plan. METHODS & PRELIMINARY RESULTS: A first analysis was conducted following the same study design as the published work on CO2 and self-reported headaches1; substituting self-reported changes in visual acuity in place of self-reported headaches. The analysis demonstrated no statistically significant association between visual impairment characterized by vision symptoms self-reported during PMCs and ISS average CO2 levels over ISS missions. Closer review of the PMC records showed that vision outcomes are not well-documented in terms of clinical severity, timing of onset, or timing of resolution, perhaps due to the incipient nature of vision changes. Vision has been monitored in ISS crewmembers, pre- and post-flight, using standard optometry evaluations. In-flight visual assessments were limited early in the ISS program, primarily consisting of self-perceived changes reported by crewmembers. Recently, on-orbit capabilities have greatly improved. Vision data ranges from self-reported post-flight changes in visual acuity, pre- to postflight changes identified during fundoscopic examination, and in-flight progression measured by advanced on-orbit clinical imaging capabilities at predetermined testing intervals. In contrast, CO2 data are recorded in a continuous stream over time; however, for the initial analysis this data was categorized into weekly averages.

Mendez, C. M.