Showing papers by "Mathias Basner published in 2019"

The NASA Twins Study: A multidimensional analysis of a year-long human spaceflight.

Abstract: INTRODUCTION To date, 559 humans have been flown into space, but long-duration (>300 days) missions are rare (n = 8 total). Long-duration missions that will take humans to Mars and beyond are planned by public and private entities for the 2020s and 2030s; therefore, comprehensive studies are needed now to assess the impact of long-duration spaceflight on the human body, brain, and overall physiology. The space environment is made harsh and challenging by multiple factors, including confinement, isolation, and exposure to environmental stressors such as microgravity, radiation, and noise. The selection of one of a pair of monozygotic (identical) twin astronauts for NASA’s first 1-year mission enabled us to compare the impact of the spaceflight environment on one twin to the simultaneous impact of the Earth environment on a genetically matched subject. RATIONALE The known impacts of the spaceflight environment on human health and performance, physiology, and cellular and molecular processes are numerous and include bone density loss, effects on cognitive performance, microbial shifts, and alterations in gene regulation. However, previous studies collected very limited data, did not integrate simultaneous effects on multiple systems and data types in the same subject, or were restricted to 6-month missions. Measurement of the same variables in an astronaut on a year-long mission and in his Earth-bound twin indicated the biological measures that might be used to determine the effects of spaceflight. Presented here is an integrated longitudinal, multidimensional description of the effects of a 340-day mission onboard the International Space Station. RESULTS Physiological, telomeric, transcriptomic, epigenetic, proteomic, metabolomic, immune, microbiomic, cardiovascular, vision-related, and cognitive data were collected over 25 months. Some biological functions were not significantly affected by spaceflight, including the immune response (T cell receptor repertoire) to the first test of a vaccination in flight. However, significant changes in multiple data types were observed in association with the spaceflight period; the majority of these eventually returned to a preflight state within the time period of the study. These included changes in telomere length, gene regulation measured in both epigenetic and transcriptional data, gut microbiome composition, body weight, carotid artery dimensions, subfoveal choroidal thickness and peripapillary total retinal thickness, and serum metabolites. In addition, some factors were significantly affected by the stress of returning to Earth, including inflammation cytokines and immune response gene networks, as well as cognitive performance. For a few measures, persistent changes were observed even after 6 months on Earth, including some genes’ expression levels, increased DNA damage from chromosomal inversions, increased numbers of short telomeres, and attenuated cognitive function. CONCLUSION Given that the majority of the biological and human health variables remained stable, or returned to baseline, after a 340-day space mission, these data suggest that human health can be mostly sustained over this duration of spaceflight. The persistence of the molecular changes (e.g., gene expression) and the extrapolation of the identified risk factors for longer missions (>1 year) remain estimates and should be demonstrated with these measures in future astronauts. Finally, changes described in this study highlight pathways and mechanisms that may be vulnerable to spaceflight and may require safeguards for longer space missions; thus, they serve as a guide for targeted countermeasures or monitoring during future missions.

Patient Safety Outcomes under Flexible and Standard Resident Duty-Hour Rules

Abstract: Background Concern persists that extended shifts in medical residency programs may adversely affect patient safety. Methods We conducted a cluster-randomized noninferiority trial in 63 int...

Effects of acute exposures to carbon dioxide on decision making and cognition in astronaut-like subjects

Abstract: Acute exposure to carbon dioxide (CO2) concentrations below those found on the International Space Station are reported to deteriorate complex decision-making. Effective decision-making is critical to human spaceflight, especially during an emergency response. Therefore, effects of acutely elevated CO2 on decision-making competency and various cognitive domains were assessed in astronaut-like subjects by the Strategic Management Simulation (SMS) and Cognition test batteries. The double-blind cross-over study included 22 participants at the Johnson Space Center randomly assigned to one of four groups. Each group was exposed to a different sequence of four concentrations of CO2 (600, 1200, 2500, 5000 ppm). Subjects performed Cognition before entering the chamber, 15 min and 2.5 h after entering the chamber, and 15 min after exiting the chamber. The SMS was administered 30 min after subjects entered the chamber. There were no clear dose–response patterns for performance on either SMS or Cognition. Performance on most SMS measures and aggregate speed, accuracy, and efficiency scores across Cognition tests were lower at 1200 ppm than at baseline (600 ppm); however, at higher CO2 concentrations performance was similar to or exceeded baseline for most measures. These outcomes, which conflict with those of other studies, likely indicate differing characteristics of the various subject populations and differences in the aggregation of unrecognized stressors, in addition to CO2, are responsible for disparate outcomes among studies. Studies with longer exposure durations are needed to verify that cognitive impairment does not develop over time in crew-like subjects.

Effectiveness of incentives and follow-up on increasing survey response rates and participation in field studies.

Abstract: Questionnaires are valuable data collection instruments in public health research, and can serve to pre-screen respondents for suitability in future studies. Survey non-response leads to reduced effective sample sizes and can decrease representativeness of the study population, so high response rates are needed to minimize the risk of bias. Here we present results on the success of different postal questionnaire strategies at effecting response, and the effectiveness of these strategies at recruiting participants for a field study on the effects of aircraft noise on sleep. In total, we mailed 17 rounds of 240 questionnaires (total n = 4080) to randomly selected households around Atlanta International Airport. Different mailing rounds were varied in the length of the questionnaire (11, 26 or 55 questions), survey incentive (gift card or $2 cash), number of follow-up waves (0, 2 or 3), incentive for participating in a 5-night in-home sleep study ($100, $150 or $200), and address personalization. We received completed questionnaires from 407 respondents (response rate 11.4%). Personalizing the address, enclosing a $2 cash incentive with the initial questionnaire mailing and repeated follow-up mailings were effective at increasing response rate. Despite the increased expense of these approaches in terms of each household mailed, the higher response rates meant that they were more cost-effective overall for obtaining an equivalent number of responses. Interest in participating in the field study decreased with age, but was unaffected by the mailing strategies or cash incentives for field study participation. The likelihood that a respondent would participate in the field study was unaffected by survey incentive, survey length, number of follow-up waves, field study incentive, age or sex. Pre-issued cash incentives and sending follow-up waves could maximize the representativeness and numbers of people from which to recruit, and may be an effective strategy for improving recruitment into field studies.

Comparing the Effects of Road, Railway, and Aircraft Noise on Sleep: Exposure–Response Relationships from Pooled Data of Three Laboratory Studies

Abstract: Objectives: Air, road, and railway traffic, the three major sources of traffic noise, have been reported to differently impact on annoyance. However, these findings may not be transferable to physiological reactions during sleep which are considered to decrease nighttime recovery and might mediate long-term negative health effects. Studies on awakenings from sleep indicate that railway noise, while having the least impact on annoyance, may have the most disturbing properties on sleep compared to aircraft noise. This study presents a comparison between the three major traffic modes and their probability to cause awakenings. In combining acoustical and polysomnographical data from three laboratory studies sample size and generalizability of the findings were increased. Methods: Data from three laboratory studies were pooled, conducted at two sites in Germany (German Aerospace Center, Cologne, and Leibniz Research Centre for Working Environment and Human Factors, Dortmund). In total, the impact of 109,836 noise events on polysomnographically assessed awakenings was analyzed in 237 subjects using a random intercept logistic regression model. Results: The best model fit according to the Akaike Information Criterion (AIC) included different acoustical and sleep parameters. After adjusting for these moderators results showed that the probability to wake up from equal maximum A-weighted sound pressure levels (SPL) increased in the order aircraft < road < railway noise, the awakening probability from road and railway noise being not significantly different (p = 0.988). At 70 dB SPL, it was more than 7% less probable to wake up due to aircraft noise than due to railway noise. Conclusions: The three major traffic noise sources differ in their impact on sleep. The order with which their impact increased was inversed compared to the order that was found in annoyance surveys. It is thus important to choose the correct concept for noise legislation, i.e., physiological sleep metrics in addition to noise annoyance for nighttime noise protection.

Aircraft Noise Effects on Sleep—Results of a Pilot Study Near Philadelphia International Airport

Abstract: Current objective data on aircraft noise effects on sleep are needed in the US to inform policy. In this pilot field study, heart rate and body movements were continuously measured during sleep of residents living in the vicinity of Philadelphia International Airport (PHL) and in a control region without aircraft noise with sociodemographic characteristics similar to the exposed region (N = 40 subjects each). The primary objective was to establish the feasibility of unattended field measurements. A secondary objective was to compare objective and subjective measures of sleep and health between control and aircraft noise exposed groups. For all measurements, there was less than 10% of data loss, demonstrating the feasibility of unattended home measurements. Based on 2375 recorded aircraft noise events, we found a significant (unadjusted p = 0.0136) exposure-response function between the maximum sound pressure level of aircraft noise events and awakening probability inferred from heart rate increases and body movements, which was similar to previous studies. Those living near the airport reported poorer sleep quality and poorer health than the control group in general, but when asked in the morning about their last night’s sleep, no significant difference was found between groups. Neither systolic nor diastolic morning blood pressures differed between study regions. While this study demonstrates the feasibility of unattended field study measurements, for a national study around multiple US airports refinements of the study design are necessary to further lower methodological expense and increase participation rates.

Survey Results of a Pilot Sleep Study Near Atlanta International Airport

Abstract: Aircraft noise can disturb the sleep of residents living near airports. To investigate potential effects of aircraft noise on sleep, recruitment surveys for a pilot field study were mailed to households around Atlanta International Airport. Survey items included questions about sleep quality, sleep disturbance by noise, noise annoyance, coping behaviors, and health. Of 3159 deliverable surveys, 319 were returned (10.1%). Calculated outdoor nighttime aircraft noise (Lnight) was significantly associated with lower sleep quality (poor or fair; odds ratio (OR) = 1.04/decibel (dB); p < 0.05), trouble falling asleep within 30 min ≥1/week (OR = 1.06/dB; p < 0.01), and trouble sleeping due to awakenings ≥1/week (OR = 1.04/dB; p < 0.05). Lnight was also associated with increased prevalence of being highly sleep disturbed (OR = 1.15/dB; p < 0.0001) and highly annoyed (OR = 1.17/dB; p < 0.0001) by aircraft noise. Furthermore Lnight was associated with several coping behaviors. Residents were more likely to report often or always closing their windows (OR = 1.05/dB; p < 0.01), consuming alcohol (OR = 1.10/dB; p < 0.05), using television (OR = 1.05/dB; p < 0.05) and using music (OR = 1.07/dB; p < 0.05) as sleep aids. There was no significant relationship between Lnight and self-reported general health or likelihood of self-reported diagnosis of sleep disorders, heart disease, hypertension or diabetes. Evidence of self-reported adverse effects of aircraft noise on sleep found in this pilot study warrant further investigation in larger, more representative subject cohorts.

Effects of zolpidem and zaleplon on cognitive performance after emergent morning awakenings at Tmax: a randomized placebo-controlled trial.

Abstract: STUDY OBJECTIVES Prescription sleep aids are frequently used in the general population and even more frequently in spaceflight. To evaluate the risk to operational safety, a ground-based, double-blind, placebo-controlled study on the emergent awakening effects of zolpidem and zaleplon was conducted. METHODS N = 34 participants (age M = 42.1 ± 9.7; 25 males; 9 Astronauts, 7 Astronaut candidates, and 18 Flight Controllers) were investigated for three nights separated by M = 10 days. They were randomized to ingestion of one of the following at lights out: placebo, 10 mg zaleplon, and either 5 mg (N = 20) or 10 mg (N = 14) zolpidem. They were awakened abruptly by alarm at the expected PK,max (1 hr after lights out for zaleplon; 1.5 hr for placebo/zolpidem). Participants were required to turn off the alarm and perform a cognitive test battery twice, separated by a 20-30 min reading break. They then returned to sleep and were awakened to perform the same cognitive tasks at an average of 6.7 hr after drug ingestion. RESULTS Relative to placebo, the effects of 10 mg zaleplon and 5 mg zolpidem on cognitive performance were minor. In contrast, 10 mg zolpidem adversely affected cognitive throughput (p < 0.001), psychomotor vigilance (p < 0.001), working memory (p < 0.01), delayed word recall (p < 0.05), and subjective sleepiness (p < 0.01) at the first emergent awakening. At terminal awakening, neither cognitive performance nor subjective sleepiness was impaired after ingestion of zaleplon or zolpidem (5 mg and 10 mg) compared with placebo. CONCLUSIONS Presleep ingestion of sleep medications, especially 10 mg zolpidem, poses a risk for performance errors after emergent awakenings near the expected PK,max. REGISTRATION Optimize Astronaut Sleep Medication Efficacy and Individual Effects (clinicaltrials.gov ID NCT03526575).

Sleep and Work in ICU Physicians During a Randomized Trial of Nighttime Intensivist Staffing.

Abstract: OBJECTIVES To compare sleep, work hours, and behavioral alertness in faculty and fellows during a randomized trial of nighttime in-hospital intensivist staffing compared with a standard daytime intensivist model. DESIGN Prospective observational study. SETTING Medical ICU of a tertiary care academic medical center during a randomized controlled trial of in-hospital nighttime intensivist staffing. PATIENTS Twenty faculty and 13 fellows assigned to rotations in the medical ICU during 2012. INTERVENTIONS As part of the parent study, there was weekly randomization of staffing model, stratified by 2-week faculty rotation. During the standard staffing model, there were in-hospital residents, with a fellow and faculty member available at nighttime by phone. In the intervention, there were in-hospital residents with an in-hospital nighttime intensivist. Fellows and faculty completed diaries detailing their sleep, work, and well-being; wore actigraphs; and performed psychomotor vigilance testing daily. MEASUREMENTS AND MAIN RESULTS Daily sleep time (mean hours [SD]) was increased for fellows and faculty in the intervention versus control (6.7 [0.3] vs 6.0 [0.2]; p < 0.001 and 6.7 [0.1] vs 6.4 [0.2]; p < 0.001, respectively). In-hospital work duration did not differ between the models for fellows or faculty. Total hours of work done at home was different for both fellows and faculty (0.1 [< 0.1] intervention vs 1.0 [0.1] control; p < 0.001 and 0.2 [< 0.1] intervention vs 0.6 [0.1] control; p < 0.001, respectively). Psychomotor vigilance testing did not demonstrate any differences. Measures of well-being including physical exhaustion and alertness were improved in faculty and fellows in the intervention staffing model. CONCLUSIONS Although no differences were measured in patient outcomes between the two staffing models, in-hospital nighttime intensivist staffing was associated with small increases in total sleep duration for faculty and fellows, reductions in total work hours for fellows only, and improvements in subjective well-being for both groups. Staffing models should consider how work duration, sleep, and well-being may impact burnout and sustainability.

Traffic noise and its impact on sleep depth measured by the odds ratio product

Abstract: Traffic noise can lead to cortical and autonomic activation, disrupt sleep and impair physical and mental restoration. We used the odds ratio product (ORP), a validated continuous measure of sleep depth based on automatic analysis of physiologic sleep data in 3-second epochs, to investigate temporal changes of sleep in response to nocturnal noise events. Seventy-two healthy participants slept for 10 nights in a laboratory, during which we measured sleep with polysomnography. In 8 nights, participants were exposed to 40, 80 or 120 road, rail and/or aircraft noise events at 45-65 dB LAS,max. Event-related change of ORP relative to pre-event baseline was analysed with linear mixed models. ORP increased during aircraft, road and rail noise, reflecting reduced sleep depth and quality, and there was a greater response to road and rail noise than to aircraft noise. The clinical relevance of event-related elevations of ORP is currently unknown, and warrants further investigation.

Sleep loss and impaired vigilant attention

Abstract: Sleep is a biologic imperative and necessary to sustain cognitive performance throughout the wake period. Vigilant attention is affected early and profoundly by acute and chronic sleep loss as well as by circadian misalignment. The psychomotor vigilance test (PVT) has become the de-facto gold standard for measuring sleep-related impairments of vigilant attention, likely also due to its favorable properties relative to other more complex cognitive tests, i.e., no aptitude or learning effects. This chapter discusses in detail requirements for accurately measuring response times with the PVT, time-on-task effects related to PVT duration, and the importance of choosing a sensitive PVT outcome variable.