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Editorial Dear Reader It is my pleasure to introduce the ISOPTWPO. ISOPTWPO(International Space Flight & Operations - Personnel Recruitment, Training, Welfare, Protocol Programs Office) is part of ISA, which support research on Human Space Flight and its complications. The International Space Agency (ISA) was founded by Mr. Rick Dobson, Jr., a U.S. Navy Veteran, and established as a non-profit corporation for the purpose of advancing Man’s visionary quest to journey to other planets and the stars. ISOPTWPO will research on NASA’S Human Research Roadmap. It will also research on long duration spaceflight and publish special issues on one year mission at ISS and twin study. Mr. Martin Cabaniss

Director: Mr. Martin Cabaniss ISOPTWPO – International Space Agency(ISA) http: // www. international-space-agency. us/ Email:martin.cabaniss@international-space-agency.us


IN THIS EDITION Page No. 5-12

Article Name Twins Study

14-17

One Year Mission at ISS

19-22

Genetic markers of dierential vulnerability to sleep loss

22-29

Human performance during long-term spaceflight

33-39

Sleep deprivation and fatigue in Astronauts

40-43

Geometric illusions in astronauts during longduration spaceight

43-49

Distance and Size Perception in Astronauts during Long-Duration Spaceight


Special Issue ’Long-duration Spaceflight’

Twins Study

NASA Selects 10 Proposals to Explore Genetic Aspects of Space ight Scientific and technical experts from academia and government reviewed 40 proposals submitted in response to the research announcement "Human Exploration Research Opportunities - Differential Effects on Homozygous Twin Astronauts Associated with Differences in Exposure to Spaceflight Factors." Differential Effects on Homozygous Twin Astronauts Associated with Differences in Exposure to Spaceflight Factors(NNJ13ZSA002N-TWINS) Research Emphases This Human Exploration Research Opportunities (HERO) program element welcomes submission of research proposals that will implement integrated -omics studies, employing a plurality of the following methodologies: 1. Genomic studies to investigate the effects of the space environment (in particular space radiation) on the DNA (i.e., the exome, genome or specific targeted genes or loci) of Scott Kelly (compared to Mark Kelly) over the period of the one-year mission. In particular there is strong interest in investigating the possible occurrence of genetic mosaicism due to possible radiation induced spontaneous somatic mutations.

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Special Issue ’Long-duration Spaceflight’

2. Transcriptomic studies to investigate the effects of "G transitions"(i.e., weightlessness and return to terrestrial gravity), immediately before and after the launch and landing phases of the spaceflight - on RNA constructs (i.e., both messenger RNA and non-coding RNA) of Scott Kelly (compared to Mark Kelly) during the period of the one-year ISS mission. 3. Epigenomic alterations (viz. longtitudinal temporal monitoring of methylated cytosine bases, CpG islands, or histone modifications) to probe the transient effects of the space environment (in particular radiation, weightlessness, stress, and a confined environment, etc.) on the dynamic epigenomes of Scott Kelly (compared to Mark Kelly) during the period of the one-year ISS mission. 4. Plasma, saliva or urine based proteomic profiling using either mass spectrometric based proteomics or multiplexed immunoassays to investigate the effects of "G-transitions", space radiation, stress and confinement on Scott Kelly (relative to Mark Kelly) immediately before and after launch and landing, as well as periodically during the period of the one-year ISS mission. These proteomic studies should perform surveillance on both protein expression levels, as well as the occurrence of informative post-translational modifications (e.g., phosphorylation, ubiquitination, glycosylation, etc.). 5. Metabolomic sampling to investigate changes in the concentrations of metabolites and other small molecules within the blood, saliva, urine or stool samples of Scott Kelly (compared to Mark Kelly) that may be perturbed a result of the astronaut diet, stress, weightlessness and unique responses to the spaceflight environment. 6. Metagenomic sequencing to investigate changes in the microbiome or bacteriome residing within the gastrointestinal tract of Scott Kelly (relative to Mark Kelly) as a result of dietary differences and responses to the spaceflight environment such as elevated levels of radiation and stress. 7. Physiologically based experiments to study and catalog the effects of the space environment over an extended one-year period of time on key organs and systems such the heart, blood vessels, lungs, muscles, bones, senses, brain, balance organs, eyes etc. Where-ever possible, physiological experiments and obser˝ omics data to vations should be synchronized with relevant bio-specimen sampling, to enable analyzed U be directly compared to physiological measurements. 8. Psychosocial and neurobehavioral experiments to investigative and characterize any differences between Scott and Mark Kelly in cognition, decision making ability, alertness levels, stress, and overall emotional well-being, as a result of the spaceflight environment, i.e. confinement, weightlessness, stress, and space radiation. Where-ever possible, psychosocial and neurobehavioral experiments and observations should ˝ omics data to be directly be synchronized with relevant bio-specimen sampling, to enable analyzed U compared to psychosocial and neurobehavioral measurements.

The following 10 selected proposals, which are from 10 institutions in seven states, will receive a combined $1.5 million during a three-year period: 1. Emmanuel Mignot, Stanford University School of Medicine, HERO Twin Astronaut Study Consortium (TASC): Immunome Changes in Space. 2. Michael Snyder, Stanford University, HERO Twin Astronaut Study Consortium (TASC) Project: Longitudinal integrated multi-omics analysis of the biomolecular effects of space travel. 3. Brinda Rana, University of California, Proteomic Assessment of Fluid Shifts and Association with Visual Impairment and Intracranial Pressure in Twin Astronauts. 4. Susan Bailey, Colorado State University, Differential effects on telomeres and telomerase in twin astronauts associated with spaceflight. 5. Fred Turek, Northwestern University, HERO Twin Astronaut Study Consortium (TASC) Project: Metagenomic Sequencing of the Bacteriome in GI Tract of Twin Astronauts.

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Special Issue ’Long-duration Spaceflight’

6. Andrew Feinberg, Johns Hopkins University School of Medicine, Comprehensive whole genome analysis of differential epigenetic effects of space travel on monozygotic twins. 7. Christopher Mason, Weill Medical College of Cornell University, The Landscape of DNA and RNA Methylation Before, During, and After Human Space Travel. 8. Mathias Basner, University of Pennsylvania School of Medicine, HERO Twin Astronaut Study Consortium (TASC) Project: Cognition on Monozygotic Twin on Earth. 9. Stuart Lee, Wyle Laboratories, Metabolomic And Genomic Markers Of Atherosclerosis As Related To Oxidative Stress, Inflammation, And Vascular Function In Twin Astronauts. 10. Scott Smith, NASA Johnson Space Center, Biochemical Profile: Homozygous Twin control for a 12 month Space Flight Exposure.

Twins Study

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Special Issue ’Long-duration Spaceflight’

Twins Study

Twins Study

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Special Issue ’Long-duration Spaceflight’

Twins Study

Twins Study

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Special Issue ’Long-duration Spaceflight’

Twins Study

Twins Study

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Special Issue ’Long-duration Spaceflight’

Twins Study

Twins Study

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Special Issue ’Long-duration Spaceflight’

Twins Study

Twins Study

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D ID YOU KNOW ? P SYCHOLOGICAL D ANGERS OF L ONG -D URATION S PACE FLIGHT

Psychological Dangers of Long-Duration Space ight Some Russian space flight missions in the 1970s and 1980s were terminated early due to psychological factors (Cooper, 1976). In 1976, during the Soyuz- 21 mission to the Salyut-5 space station, the crew was brought home early after the cosmonauts complained of a pungent odor. No source for this odor was ever found, nor did other crews smell it. Since the crew had not been getting along, the odor may have been a hallucination. In 1985, the crew of the Soyuz T-14 mission to Salyut-7 was brought home after 65 days because cosmonaut Vladimir Vasyutin complained that he had a prostate infection (Clark, 2007). Doctors later believed that the problem was partly psychological. The Soyuz TM-2 mission in 1987 was similarly cut short because of some apparent psychosocial factors (Clark, 2007). The early termination of these missions may have prevented escalation of behavioral and psychiatric occurrences.

Con ict between the Skylab 4 crew and Mission Control On 27 December 1973, the Skylab 4 astronauts conducted a daylong "sit-down strike." Cooper described the crew pejoratively as hostile, irritable, and downright grumpy, while other writers have described the "strike" as a legitimate reaction to overwork (Connors et al. 1985).

Reference: [1].Burrough, Bryan (1998), Dragonfly: NASA and the Crisis Aboard Mir, HarperCollins, p. 185, ISBN 0-88730783-3. [2].David Michael Harland, John Catchpole (March 2002). Creating the International Space Station. Springer. p. 416. [3].Connors, M.M., Harrison, A.A., Akins, F.R.: Living Aloft: Human Requirements for Extended Spaceflight. NASA SP-483, Washington, DC (1985).


Special Issue ’Long-duration Spaceflight’

One-Year Mission

Selected crew members for the one-year mission aboard the International Space Station, U.S. Astronaut Scott Kelly (pictured left) and Russian Cosmonaut Mikhail Kornienko. The one year mission to ISS will not be the longest single spaceflight to be performed - four Cosmonauts have performed missions of one year and beyond, all to the Mir space station. At the top stands Valeri Polyakov with a mission of 438 days performed in 1994/95 followed by Sergei Avdeyev who spent 380 days in space in the closing years of Mir, from August 1998 to August 1999. Vladimir Titov and Musa Manarov performed a mission of exactly 365 days in 1987/88 aboard Mir. The longest mission to ISS was performed by the crew of Soyuz TMA9, Mikhail Tyurin & Michael Lopez-Alegria in 2006/07 with a total duration of 215 days. Mikhail Kornienko has made one prior mission to ISS as part of Expedition 23/24, logging 176 days in space. He comes from an engineering background working on rocket engines, also specializing in EVA equipment and launch operations. He was selected as a Cosmonaut in 1998 , but had to wait nearly 12 years to finally fly into space. During his mission to ISS, Kornienko performed one spacewalk of six hours and 42 minutes. Scott Kelly is a former Captain in the U.S. Navy and also has an engineering background in aviation systems. As part of his career in the military, Kelly worked as a test pilot and logged over 8,000 flying hours. After his selection by NASA, Kelly served as a Pilot on Space Shuttle Discovery on mission STS103 to the Hubble Space Telescope in 1999. His second flight was as a commander aboard Shuttle Endeavour for mission STS118 that delivered the S5 truss to ISS. Launching on Soyuz, Kelly made his first long duration mission to ISS as part of Expedition 25/26 in 2010/11. Overall, he logged 180 days in space as part of his three missions.

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Special Issue ’Long-duration Spaceflight’

Functional Research These investigations will examine the changes in crew member performance of functional tasks after 12 months in a low-gravity environment: Field Test and Functional Task Test. Recovery of Functional Sensorimotor Performance Following Long Duration Space Flight (Field Test) Millard F. Reschke, Ph.D. Inessa B. Kozlovskaya, M.D. Physiological Factors Contributing to Post-flight Changes in Functional Performance (FTT/Functional Task Test) Jacob Bloomberg, Ph.D.

Behavioral Health Research These investigations will examine psychological effects of long-duration spaceflight on crew members by conducting cognition tests, neuromapping studies, sleep monitoring, journaling analyses and a reaction self-test. Individualized Real-Time Neurocognitive Assessment Toolkit for Space Flight Fatigue (Cognition) Mathias Basner, M.D., Ph.D Spaceflight Effects on Neurocognitive Performance: Extent, Longevity, and Neural Bases (Neuromapping) Rachael Seidler, Ph.D. Sleep-Wake Actigraphy and Light Exposure on ISS-12 (Sleep ISS-12) Laura K. Barger, Ph.D. Behavioral Issues Associated with Isolation and Confinement: Review and Analysis of Astronaut Journals (Journals) Jack Stuster, Ph.D. Psychomotor Vigilance Self Test on ISS (PVT) (Reaction Self Test) David F. Dinges, Ph.D. The Effect of Long-term Microgravity Exposure on Cardiac Autonomic Function by Analyzing 48-hour Electrocardiogram (Biological Rhythms - 48 hours) - JAXA Chiaki Mukai, M.D., Ph.D.

Visual Impairment Research

These investigations will examine ocular health and the body’s response to fluid shifts in a weightless environment. This includes examining techniques to measure intracranial pressure. Integrated Fluid Volume (Integrated Fluid Volume/Fluid Shifts) Alan R. Hargens, Ph.D. Michael B. Stenger, Ph.D. Scott A. Dulchavsky, M.D., Ph.D. Prospective Observational Study of Ocular Health in ISS Crews (Ocular Health) Christian Otto, M.D. Non-invasive Assessment of Intracranial Pressure for Space Flight and Related Visual Impairment (IPVI) - JAXA Chiaki Mukai, M.D., Ph.D.

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Special Issue ’Long-duration Spaceflight’

Metabolic Research These investigations will examine integrated immune, salivary markers, biochemical profiles and the relationship between biological markers of oxidative and inflammatory stress and the risk for atherosclerosis in a long-duration, weightless environment. An integrated immune monitoring strategy also will be validated. NASA Biochemical Profile Project (Biochemical Profile) Scott M. Smith, Ph.D. Defining the Relationship Between Biomarkers of Oxidative and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts During and After Long-Duration Spaceflight (Cardio Ox) Steven H. Platts, Ph.D. Validation of Procedures for Monitoring Crewmember Immune Function (Integrated Immune) Clarence Sams, Ph.D. Neuroendocrine and Immune Response in Humans During and after Long Term Stay at ISS (Immuno-2) - ESA Alexander Chouker, M.D. Astronaut’s Energy Requirements for Long-term Space Flight (Energy) - ESA Stephane Blanc, Ph.D.

Physical Performance Research

These investigations will examine exercise capability with a focus on physical performance of bone, muscle and the cardiovascular system over time in a weightless environment: Sprint Study and Hip QCT Study. Integrated Resistance and Aerobic Training Study (Sprint) Lori Ploutz-Snyder, Ph.D. Occupational Risk Surveillance for Bone: Pilot Study-Effects of In-flight Countermeasures on Sub-regions of the Hip Bone (HIP QCT) Jean Sibonga, Ph.D. Early Detection of Osteoporosis in Space (EDOS) - ESA Laurence Vico, Ph.D. Joern Rittweger, Dr. med.

Microbial Research These investigations will examine changes in the microbiome of crewmembers. Study of the Impact of Long-term Space Travel on the Astronaut’s Microbiome (Microbiome) Hernan Lorenzi Mycological Evaluation of Crew Exposure to ISS Ambient Air (Myco) - JAXA Chiaki Mukai, M.D., Ph.D.

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Special Issue ’Long-duration Spaceflight’

Human Factors Research These investigations will examine how astronauts interact with their environment aboard the International Space Station focusing on fine motor performance, habitability, and training retention. Effects of Long-duration Microgravity on Fine Motor Skills (Fine Motor Skills/Fine Motor Control) Kritina L. Holden, Ph.D. Assessment of International Space Station Vehicle Habitability Sherry Thaxton, Ph.D.

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D ID YOU KNOW ? Windows Space ight Cognitive Assessment Tool(Win-SCAT)

The Spacefight Cognitive Assessment Tool for Windows (Win-SCAT) was used to evaluate the neurocognitive performance of the crew. The WinSCAT was developed by an integrated product team as a tool to support medical operations at the National Aeronautics and Space Administration’s (NASA) Johnson Space Center and was used to monitor the neurocognitive status of crews in space. The test uses cognitive subtests that measure sustained concentration, working memory, attention, short-term memory, spatial processing, mathematic skills, and processing effciency. Types of functions evaluated by WinSCAT include: 1.Mathematical processing (MTH) Subjects attempt to solve addition and subtraction problems and press the left or right buttons of the laptop’s keypad to indicate if the correct response is < or >5. Individual problems appear on-screen and each problem requires either addition or subtraction. The MTH portion measures basic computational skills, concentration, and working memory. 2.Running memory continuous performance test (CPT) During this test, a series of 160 numbers are displayed about one per second on-screen. Subjects determine if the number shown is the same as the one presented immediately before it. Except for the first number, a press of a mouse button is required each time a number appears on-screen. Either a left- or right-click is used to indicate whether the current number is identical to the previous number. The CPT measures attention/concentration, working memory, and lapses in attention. 3.Delayed matching-to-sample (MTS) In this test, first, a sample stimulus in the form of a large box with colored squares is shown on-screen. After 3 seconds, the sample box disappears for 5 s to defeat the retinal afterimage and 2 comparison boxes appear side-by-side. Subjects are asked to determine, which of these 2 comparison boxes matches the sample box and to indicate their choice via either a left- or right-click of the mouse. The MTS measures spatial processing and visuo-spatial working memory. 4.Code substitution (CDS) In the CDS test, a row of symbols and a row of numbers are shown on-screen. Each number has a corresponding symbol that appears in the box above the number. During the test, a sample box with a symbol and a number is displayed below the rows. For each trial, subjects are asked to determine whether the sample box was shown with the correct corresponding symbol and to indicate their choice with a left- or right-click of the mouse. The CDS measures sustained attention and concentration, visual search, verbal learning, and recall. Data from the first 8 months of the Mars500 experiment (a 520-day simulation of a spaceflight mission to Mars, conducted in a chamber with 6 crewmembers) was collected using the WinSCAT computerized neurocognitive battery. Table 1 shows WinSCAT results for reaction and accuracy indices. Apparent variations were identified both between subjects and within subjects. Using the cutoff rules originally developed for astronauts and automatically generated by the WinSCAT software, a number of off-nominal scores were observed.


Special Issue ’Long-duration Spaceflight’

These off-nominal scores are designated "red flags" by NASA, indicating a 25% increase in reaction time or a 75% below-expected score in accuracy for highly motivated and skilled individuals (astronauts). Several red flags were observed in the preprocessing analysis of off-nominal scores, especially for reaction times, during the 8 months corresponding to the duration of the present study. However, it is difficult to attribute these red flags to a specific source, as fatigue, monotony, and sleep issues are all possible candidates.Bivariate correlations were performed to evaluate for correlations between age and performance (reaction time and accuracy) on the different tasks. We looked into reaction time and accuracy indices for the monthly trials. Correlations were identified between age and reaction time in the CPT (r = 0.303; p ≤ 0.001), MTH (r = 0.377; p≤0.001), MTS (r = 0.189; p = 0.020), and in the number of lapses, or time misses for CPT (r = 0.214; p = 0.008; Table 1). On the CDS subtest, no correlations were identified between age and reaction time, but a significant correlation was found between age and accuracy (r = 0.165; p = 0.043). In addition, reaction times and accuracy for the different WinSCAT indices were compared with respect to native language of each subject. Native Russian-speaking subjects had greater reaction times on most of the subtests, but also had better accuracy scores, than other language speakers (Table 2). Native Russian-speaking subjects as a group had a higher mean age (37.66 yr), compared to the other group (mean age: 30.33 yr).

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Special Issue ’Long-duration Spaceflight’

Further analyses were performed investigating the effects of language and age on WinSCAT performance (Table 3). Multiples ANOVAS were performed with posthoc t-tests. Significant differences were identified for reaction time on the MTH (F = 19.30,p ≤ 0.01) and MTS subtests (F = 18.10, p ≤ 0.01) and accuracy on the CPT (F = 3.62, p = 0.05) and CDS subtests (F = 3.99, p = 0.04).

However, non-significant differences were obtained for several indices: accuracy in the MTH subtest (F = 0.00, p = 0.96), MTS accuracy (F = 0.27, p = 0.60), and CDS reaction time (F = 0.83, p = 0.63). WinSCAT showed sensitivity and detected lower performance than expected when it occurred based on cutoff scores inherent to the computerized battery for low cognitive performance. In summary, while one group of subjects, the younger subjects as a group that spoke languages other than Russian, demonstrated lower reaction times, the other group of subjects, the older subjects that spoke Russian, obtained better accuracy scores. However this language factor may also be considered secondary to much broader factors, such as culture difference or type of training received. The results obtained in this study clearly suggest differences in performance based on age and language, and demonstrate a high sensitivity of reaction time measures for neurocognitive performance during the Mars500 simulation. Using the cutoff rules automatically generated by the WinSCAT software, a number of off-nominal scores were observed. Time-dependent selective attention and psychomotor tasks represent a key issue in neurocognitive profiling and training of future astronauts. Some of the currently available tests such as WinSCAT are sensitive to these time effects, could serve as indicators of neurocognitive compromise, and could aid in detection of performance decrements and serve as early indicators of brain injury in space. Radiation, hypokinesis, and long-term exposure to microgravity are expected to impact brain function. New tools are being developed that will offer better efficacy in the management of these important tasks by eliminating task-related problems, such as the learning effect. References: Neurocognitive performance using the Windows spaceflight cognitive assessment tool (WinSCAT) in human spaceflight simulations

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Special Issue ’Long-duration Spaceflight’

Genetic markers of di erential vulnerability to sleep loss In addition to its prevalence in the general adult population, disturbed sleep quality and reduced sleep duration are common in space operations. Such loss in astronauts has been attributed to operational factors that include the following: high workload; shift work; altered light-dark cycles; performance of critical operational tasks; space adaptation syndrome; motion sickness; noise and vibration; movement of other astronauts; excitement; stress; and ambient temperature NASA has determined that a number of factors in spaceflight-especially work-rest schedules-disrupt and shorten sleep, producing acute sleep loss (e.g., for slam shifts) and chronic partial sleep loss. NASA evidencebased reviews have concluded that such decrements pose a clear risk to operational performance during long-duration space flight, and to behavioral health and psychosocial functions. An Institute of Medicine panel assessed NASA HRP’s evidenced-based reviews and concurred with the importance of mitigating the risks posed by fatigue, and noted that individual differences in the effects of sleep loss and fatigue on human perfor-mance are important considerations . Thus, biomarkers are needed to predict large individual differences in fatigue and neurobehavioral decrements in response to fatiguing conditions in spaceflight. Stable phenotypic individual differences in response to sleep loss The laboratory was the first to experimentally demonstrate that subjects undergoing acute total sleep deprivation (TSD)-in which no sleep is obtained-show differential vulnerability to sleep loss, demonstrating robust inter-individual (trait-like, phenotypic) differences in response to the same laboratory conditions, as measured by various physiological and subjective sleep measures and neurobehavioral tasks sensitive to sleep loss. The intraclass correlation coefficients (ICCs)- which express the proportion of variance in the data explained by systematic interindividual variability- revealed that stable responses accounted for 58% and 68% of the overall variance in Psychomotor Vigilance Test (PVT) lapses (greater than 500 ms reaction times) between multiple sleep-deprivation exposures in the same subjects. Thus, individuals who showed high PVT lapse rates during TSD after one exposure also showed high PVT lapse rates during a second exposure; similarly, those with low PVT lapse rates during one exposure showed low PVT lapse rates during a second exposure. Most importantly, because these high ICCs were found when the subjects were exposed to TSD 2-3 times under markedly different conditions (e.g., high versus low sti-mulation; 6 h versus 12 h sleep time per night), the vast differences in cognitive vulnerability to sleep deprivation are considered trait-like. While some indivi-duals are highly vulnerable to cognitive performance deficits when sleep deprived (Type 3 responses), others show remarkable levels of cognitive resistance to sleep loss (Type 1 responses), and others show intermediate (Type 2) responses. The stable, trait-like inter-individual differences observed in response to acute TSD-with intraclass correlation coefficients accounting for 58-92% of the variance in neurobehavioral measures -point to an underlying genetic component. Until recently, however, the genetic basis of such differential vulnerability to sleep loss in normal healthy subjects has received little attention. Available recent data suggest that common genetic variations (polymorphisms) involved in sleep-wake, circadian, and cognitive regulation may underlie symptomatic aspects of these large inter-individual differences in neurobehavioral vulnerability to sleep deprivation in healthy adults . Specifically, we used laboratory studies to investigate the role of several common candidate gene variants [PERIOD3 (PER3), DQB1*0602, and catechol-O-methyltransferase (COMT)-each independentlyin relation to cumulative neurobehavioral and sleep homeostatic responses to sleep restriction. These and other relevant genetic biomarker findings are reviewed below. PERIOD3 VNTR polymorphism: Role of a circadian gene in differential vulnerability to acute TSD and chronic PSD Three related studies investigated the role of the variable number tandem repeat (VNTR) polymorphism of the circadian gene PERIOD3 (PER3)-which shows similar allelic frequencies in African Americans and Caucasians and is characterized by a 54-nucleo-tide coding region motif repeating in four or five units-in response to TSD using a small group of the same subjects specifically recruited for the homozygotic versions of this polymorphism. Compared with the 4-repeat allele (PER34/4 ; 14 subjects), the longer, 5-repeat allele (PER35/5 ; 10 subjects) was associated with higher sleep propensity including SWA in the sleep EEG both before and after TSD and worse cognitive performance, as assessed by a composite score of 12 tests, following TSD. A subsequent report-using the same 24 subjects-clarified that the PER35/5 overall performance deficits were selective: they only occurred on certain executive function tests, and only at 2-4 h following the melatonin rhythm peak, from approximately 6-8 am. Such performance differences were hypothesized to be mediated

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Special Issue ’Long-duration Spaceflight’

by sleep homeostasis. Another publication using the same subjects showed that PER35/5 subjects had more slow-wave sleep and elevated sympathetic predominance and a reduction of parasympathetic activity during baseline sleep. These studies found no significant differences in the melatonin and cortisol circadian rhythms, PER3 mRNA levels, or in a self-report morningness- eveningness measure, although another study using these same subjects found PER3 expression and sleep timing were more strongly correlated in PER35/5 subjects. A subsequent neuroimaging study found that 27 healthy subjects categorized according to homozygosity for the PER3 VNTR genotype (15 PER34/4 subjects, 12 PER35/5 subjects) showed markedly different cerebral blood flow profiles using blood oxygenation level depen-dent functional magnetic resonance imaging (BOLD fMRI) and corresponding differences in vulnerability of executive function performance in response to TSD. More studies examining the relationship of the neural mechanisms mediating trait-like differential vulnerability to sleep deprivation with selective candidate genes (beyond the PER3 VNTR polymorphism) are warranted. The PER3 findings in TSD may not generalize to responses to chronic PSD. We recently evaluated whether the PER3 VNTR polymorphism contributed to sleep homeostatic responses and cumulative neurobehavioral deficits during chronic PSD in PER34/4 (40% of our population), PER34/5 (49% of our population) and PER35/5 (11% of our population) healthy adults. During chronic PSD, PER35/5 subjects had slightly but reliably elevated sleep homeostatic pressure as measured by NREM SWE compared with PER34/4 subjects. The PER34/4 , PER34/5 and PER35/5 genotypes also demonstrated large, but equivalent cumulative increases in sleepiness and cumulative decreases in cognitive performance and physiological alertness, with increasing daily inter-subject variability in all genotypes. In contrast to the aforementioned data in TSD, the PER3 VNTR variants did not differ on baseline sleep measures or in their physiological sleepiness, cognitive, executive functioning or subjective responses to chronic PSD. Thus, the PER3 VNTR polymorphism does not appear to be a genetic marker of differential vulnerability to the cumulative neurobehavioral effects of chronic PSD. It remains possible, however, that the PER35/5 genotype may contribute to differential neurobehavioral vulnerability to acute TSD because it involves wakefulness at a specific circadian time in the early morning hours (6-8 am), when subjects in the PSD study were asleep. DQB1*0602 allele predicts interindividual differences in physiological sleep structure, sleepiness and fatigue in PSD The human leukocyte antigen DQB1*0602 allele, found in 12-38% of healthy adult sleepers in the general population, is closely associated with narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, fragmented sleep, and shortened REM latency, although it is neither necessary nor sufficient for its development. In one large study, DQB1*0602 positive healthy sleepers showed shorter night time REM sleep latency, greater sleep continuity, and more REM sleep, but no differences in daytime sleepiness. Positivity for DQB1*0602 also was related to more sleep-onset REM sleep periods and greater REM sleep duration during naps. Thus, DQB1*0602 positive subjects displayed subclinical presentations of some sleep features that were reminiscent of narcolepsy. We evaluated whether DQB1*0602 was a novel marker of differential vulnerability to homeostatic, sleepiness and neurobehavioral deficits during chronic PSD in healthy sleepers positive and negative for DQB1*0602. DQB1*0602 positive subjects showed decreased sleep homeostatic pressure with differentially steeper declines, and greater sleepiness and fatigue during baseline. During chronic PSD, positive subjects displayed SWE elevation comparable to negative subjects, despite higher sleepiness and fatigue. DQB1*0602 positive subjects also had more fragmented sleep during baseline and PSD and showed differentially greater REM sleep latency reductions and smaller stage 2 reductions, along with differentially greater increases in fatigue. Both groups demonstrated com-parable cumulative decreases in cognitive performance and increases in physiological sleepiness to chronic PSD, and did not differ on executive function tasks. Thus, DQB1*0602 associated with inter-individual differences in sleep homeostasis, physiological sleep, sleepiness and fatigue, but not cognitive responses, during baseline and PSD. DQB1*0602 may be a genetic marker for predicting such individual differences in both basal (fully-rested) and sleep loss conditions; moreover, its positivity in healthy subjects may represent a continuum of some sleep-wake features of narcolepsy, though more research is needed. The influence of the DQB1*0602 allele on sleep homeostatic and

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neurobehavioral responses has not yet been examined in healthy subjects undergoing acute TSD or replicated in an independent sample of individuals undergoing chronic PSD. Catechol-O-methyltransferase (COMT) Val158Met polymorphism: Role of a cognitive gene in differential vulnerability to TSD and chronic PSD The valine158methionine (Val158Met) polymorphism of the catechol-O-methyltransferase (COMT) gene replaces valine (Val) with methionine (Met) at codon 158 of the COMT protein. As a result of this common substitution, activity of the COMT enzyme, which modulates dopaminergic catabolism in the prefrontal cortex, is reduced 3-to-4-fold in COMT Met carriers compared with Val carriers, translating into more dopamine availability at the receptors and higher cortical dopamine concentrations . This COMT poly-morphism functionally predicts less efficient prefrontal cortex functioning and poor working memory performance in healthy subjects who have the high-activity Val allele. In sleep and neurodegenerative disorders, the COMT Val158Met polymorphism has been linked to daytime sleepiness. Val/Val female narcoleptic patients fell asleep two times faster than the Val/Met or Met/Met genotypes during the multiple sleep latency test (MSLT) while the opposite was true for males . Met/Met narcoleptic patients also showed more sleep onset REM periods during the MSLT while Val/Val subjects showed less sleep paralysis and were more responsive to modafinil’s stimulating effects. Met/Met and Val/Met Parkinson’s disease subjects demonstrated higher subjective daytime sleepiness than Val/Val subjects. In healthy men, the COMT Val158Met polymorphism also was associated with sleep physiology. In acute TSD, this polymorphism predicted inter individual differences in brain alpha oscillations in wakefulness and 11-13 Hz EEG activity in wakefulness, rapid-eye movement (REM) and non-REM sleep. It also modulated the effects of the wake-promoting drug modafinil on subjective well-being, sustained vigilant attention and executive functioning, and on 3.0-6.75 Hz and >16.75 Hz activity in non-REM sleep, but was not associated with subjective sleepiness, slow-wave activity or slow-wave sleep changes in recovery sleep following TSD or at baseline. Authors recently evaluated whether COMT Val158Met polymorphism contributed to cumulative neurobehavioral deficits and sleep homeostatic responses during chronic PSD in Met/Met (15% of our population), Val/Met (50% of our population) and Val/Val (35% of our population) healthy adults. Met/Met subjects had differentially larger declines in NREM SWE-the putative homeostatic marker of sleep drive-compared with Val/Met and Val/Val subjects. The genotypes did not differ significantly at baseline in demographic characteristics, habitual sleep, circadian phase, cognitive performance, or physiological or subjective sleepiness. All genotypes demonstrated comparable cumulative decreases in cognitive performance, and increases in subjective and physiological sleepiness to chronic PSD, with increasing daily inter-subject variability. The genotypes also did not differ on executive function tasks. The COMT Val158Met polymorphism related to individual differences in sleep homeostatic, but not neurobehavioral, responses to chronic PSD. Thus, the COMT Val158Met polymorphism may be a novel genetic marker for predicting such differ-ential sleep responses resulting from sleep deprivation, though replication studies are needed. Adenosine genes: Role for predicting individual differences and response to total sleep deprivation Several studies have investigated the role of select adenosine-related candidate genes in individual differences and in response to acute TSD. Re´tey et al. found that the 22 G → A polymorphism of the adenosine deaminase gene (ADA) was associated with enhanced slow-wave sleep and NREM SWA, contributing to inter-individual variability in baseline sleep. Specifically, indi-viduals with the G/A genotype (7 subjects) showed 30 min more slow-wave sleep than subjects with the G/G geno-type (7 subjects) and consistent with this finding, SWA was higher in G/A than G/G subjects. This polymorphism also related to differential responses to TSD: individuals with the G/A genotype (about 13% of the population) showed poorer performance on the PVT, higher sleep pressure, increased sleepiness and reduced vigor. This laboratory also found that the c.1083T>C polymorphism of the adenosine A2A receptor gene (ADORA2A) related to objective and subjective differences in the effects of caffeine on NREM sleep after TSD, with the C/C genotype (32% of the population) showing particular sensitivity to disturbed sleep after caffeine. The polymorphism also associated with individual differences in various measures of baseline EEG during sleep and

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wakefulness. While promising, replication of these data in independent samples is needed; in addition, the role of these two genetic variants in response to chronic PSD has not yet been investigated. Other candidate genes relating to response to sleep loss The orexin-hypocretin system is involved in normal regulation of sleep and wakefulness and is disturbed in narcolepsy. The -909 C/T polymorphism of the pre-pro-hypocretin/prepro-orexin (HCRT) gene is associated with an increased risk of sudden onset of sleep/sleep attacks in Parkinson’s patients, although it is not associated with susceptibility to narcolepsy. Authors are currently investigating whether the HCRT-909 C/T polymorphism contributes to cumulative neurobehavioral deficits and sleep homeostatic responses during chronic sleep restriction. The T3111C polymorphism of CLOCK, a core circadian gene, has been associated with aspects of sleep, sleepiness, and morningness-eveningness in healthy adults and with insomnia in bipolar disorder and major depressive disorder. Authors are currently investigating whether the CLOCK T3111C polymorphism contributes to cumulative neurobehavioral deficits and sleep homeo-static responses during chronic PSD. In summary, a number of common genetic polymorphisms involved in circadian, sleep-wake, and cognitive regulation appear to underlie inter-individual differences in basal (fully-rested) sleep parameters and homeostatic regulation of sleep in response to sleep loss (both chronic restriction and acute total sleep deprivation) in healthy adults.

Human performance during long-term space ight 438-days space mission of one Russian cosmonaut Valeri Vladimirovich Polyakov, which set a new world record for humans in space, provided a unique opportunity to monitor the efficency of cognitive, visuo - motor and higher attentional processes during an extraordinary long-term space mission. Performance assessment was done by the same set of laboratory tasks of the AGARD STRES battery that had been used previously, and included pre-flight, in-flight, and post-flight assessments as well as a follow-up assessment 6 months after the mission. Performance tasks Performance tasks were selected from the AGARD battery of Standardized Tests for Research with Environmental Stressors (STRES).Four tasks were used: Grammatical Reasoning Task (GRT) This task required complex logical reasoning operations based on grammatical transformations. Each trial consisted of two statements describing a sequence of three symbols (e.g. & BEFORE *,* AFTER#) which were presented together with a certain set of three symbols (e.g. & * #). The subject had to evaluate whether the two statements were true for the given set of symbols. If the truth values of both statements were the same, the subject had to press a key for ’same’ . If the truth values differed (one statement true, the other false) he had to press a key for ’different’ . Response times and errors were scored for each single item. Memory Search Task (MS2; MS4) The subject had to memorize a set of letters (the memory-set) and was then presented with a series of single probe letters. By pressing a key for either ’yes’ or ’no’ , he had to indicate whether or not the letter belonged to the memory set. Fixed memory sets of two (MS2) and four (MS4) letters were used in separate 3- min blocks of trials. Response times and errors were scored as the performance measures for each single probe.

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Unstable Tracking Task (UTT) In this task a horizontally-moving cursor had to be centred by means of a joystick within a marked target located in the middle of the screen. The inherent dynamics of the tracking loop included a positive feedback of the tracking error resulting in system instability which was further increased by a divergent element (λ = 2 ). Performance was quantified by calculating the root-mean square tracking error (RMSE) integrated over blocks of 1 s and averaged across each 3-min run. Dual-Task (DT2; DT4) This task required simultaneous performance of UTT with MS2 (DT2) or MS4 (DT4), respectively, resulting in two versions of dual-task with different memory-load. The subject was instructed to divide his attention equally between both tasks. Performance scores were the same as for the single tasks. Result Cognitive task performance Grammatical reasoning Grammatical reasoning performance showed a considerable slowing at the two near-launch pre-flight sessions compared to baseline performance 3 months and 4 weeks before launch. During the first 5 days in space, however, a rapid recovery of GRT performance was observed and response rates then remained relatively stable on pre-flight baseline level until post-flight and follow-up sessions. This pattern of effects was confirmed by the ANOVA results which revealed a significant effect of Session (F(39, 289) = 8.61, p< 0.01). Pairwise comparisons of baseline performance (mean of performance at days - 87 and - 34) with all other sessions showed significant decrements in response rates only at days - 3, - 2 (both p < 0.01), and in-flight day 4 (p < 0.03), and even a significant improvement of performance 6 months after the mission (first assessment at day + 168, p < 0.05). Memory search Speed of memory search performance was analysed separately for both levels of memory load by 2-way ANOVAs of response rates with factors defined as Task-Mode (single-task versus dual-task performance) and Session (40 levels). These analyses revealed significant main effects of task-mode for both MS2 (F(1,1316) = 370.40, p<0.01) and MS4 (F(1,1316) = 159.53, p< 0.01). For both loading conditions, single-task performance was better than dual-task performance. In addition, the main effects of session became significant (MS2: F(39,1316)= 70.88, p< 0.01; MS4: F(39,1316) = 68.44, p< 0.01). Tracking performance This analysis showed that tracking error varied significantly across experimental sessions (main effect of session (F(39, 1027) = 9.05, p < 0.01). Most strikingly, tracking error increased during both the first sessions in space as well as the first sessions after return to Earth. Subjective mood ratings Nine of the 15 mood scales showed extreme low (< 1.0) or high (> 4.0) means or only small variations (s< 1.0) across the 41 experimental sessions: ’aggressive’ (mean = 0.05/s = 0.32), ’bored’ (0.03/0.16), ’carefree’ (0.59/1.02), ’concentrated’ (4.51/0.81), ’distracted’ (0.78/1.24), ’happy’ (0.80/0.75), ’interested’ (5.0/0.0), ’nervous’ (0.34/0.69) and ’relaxed’ (2.24/0.80). Strength was perceived to be high at all pre-flight sessions, most of the in-flight sessions during the 2nd to 14th month in space, and at follow-up assessments. In contrast to this generally high level of strength, however, considerable changes were observed during the first 3 weeks in space and the first 2 weeks after return to Earth. During these phases perceived strength decreased considerably (most pronounced at in-flight days 4, 5, 11, 12, 19 and post-flight days + 4 [second assessment], + 6, + 11, + 12). ’Sadness’ showed a striking increase immediately before launch, compared to pre-flight baseline values at days - 87, - 34 and both follow-up assessments, but was back to baseline level already at the first assessment in space. During the following months in space, rated sadness increased slightly above baseline values at most of the in-flight days, with obvious deviations from this general level at days 20, 96, 348(lowest scores) and days 27, 199, 398, 413 (highest scores). After return to Earth sadness

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ratings remained on the general in-flight level at the first three assessments, and were clearly elevated at post-flight days + 6 and + 12.

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D ID YOU KNOW ? CogGauge CogGauge is a game based cognitive assessment tool inspired by "The Automated Neuro-physiological Assessment Metrics (ANAM r)" battery and intended to engage the user in an entertaining experience while performing cognitive assessment tasks to measure short term memory, attention, spatial processing and other perceptual abilities. CogGauge is intended to be beneficial to multiple domains and is currently being evaluated for use by airport baggage screening personnel. In particular, CogGauge is intended to be sensitive to cognitive decrements that may manifest from emotional stress or physical and mental fatigue during or following a shift. The original intended domain for CogGauge was the astronaut population, particularly for tracking cognitive function over time during extended stay on the ISS or during long flight missions in the future such as to NEOs. Development of a tool to meet two vastly different domains, and maintain usefulness presents multiple challenges to the developmental team. Reference: Reeves, D.L., Winter, K.P., Bleiberg, J., and Kane, R.L. (2007). ANAM r Genogram: Historical perspectives, description, and current endeavors. Archives of Clinical Neuropsychology, 22, Supplement 1, Pages 15-37.

NINscan TD: Toward Imaging Brain Function in Space ight Spaceflight poses numerous risks to the brain and central nervous system, including high-energy radiation, toxic gasses, chronic stress, sleep deprivation, fluid shifts, hormone imbalances, and injury . Unfortunately, the standard technologies for brain assessment-MRI, PET, or CT are not suitable to the flight environment, as they require excessive mass, power, and volume. Near-infrared neuroimaging (NIN) can be used to measure the key cerebral variables of blood volume and oxygenation and can also be miniaturized for flight. NINscan TD is powered by two embeded rechargeable Li-ion batteries, provides 8 optical channels, and weighs less than 500 grams. The system includes 16-bit A/D conversion and programmable light power and detector gain for optimized data acquistion on different subjects. Most important, the TDM microcontroller design can be scaled to develop whole-head imaging devices with similar size and power requirements. Reference: [1] Strangman G, Culver JP, Thompson JH, Boas DA. A quantitative comparison of simultaneous BOLD fMRI and NIRS recordings during functional brain activation. NeuroImage. Oct 2002;17(2):719-731. [2] Zhang Q, Yan X, Strangman GE. Development of motion resistant instrumentation for ambulatory near-infrared spectroscopy. J Biomed Opt. Aug 2011;16(8):087008.


Special Issue ’Long-duration Spaceflight’

NEUROCATS The aim of this NSBRI-funded project (10/2011-09/2015) is to develop an individualized real-time neurocognitive assessment toolkit for space flight fatigue (NeuroCATS). The project addresses the NSBRI Human Factors and Performance Team goal to develop tools to assess crew performance in real-time and evaluate countermeasures to mitigate the effects of fatigue, circadian misalignment and work-overload. It is responsive to the critical need to identify how a range of cognitive functions of astronauts can be affected in space flight by fatigue alone, its interaction with other risk factors and conditions (e.g., elevated CO2, intracranial pressure, space fog), and countermeasures. The project will deliver a comprehensive, software-based, neurocognitive toolkit. By building on state-of-the-art neuropsychological test development, the toolkit will permit evaluation of a full range of cognitive functions using brief (1-5 min), validated procedures, some of them using adaptive testing based on item response theory.

Reference: National Space Biomedical Research Institute (NSBRI).

Facial Expression Coding System (FACES) During space flight astronauts must maintain high-level performance while experiencing potentially lethal environmental risks and psychosocial stressors (e.g., isolation, confinement, high workload). Negative emotions can jeopardize individual and team performance in space. There is a need for an objective means to unobtrusively detect changes in astronaut emotions in space. This study is developing and validating an optical computer recognition (OCR) algorithm based on a single-camera input as an objective, unobtrusive, computational model-based tracker that reliably detects facial expressions of positive and negative emotions. The Facial Expression Coding System (FACES) was used by trained personnel to score (blinded to emotioninduction condition) videotaped recordings of emotional facial expressions in N=31 subjects (16 females). Facial videos were also scored by the OCR model-based tracker algorithm . These frame-by-frame scores were then used to calculate the duration of emotional expression and which emotion was predominantly expressed. Videos were compared between human scorers and the OCR model-based tracker algorithm using epochs, which were defined as the emotion predominantly expressed in the face for a period of time ranging from a few seconds to a number of minutes.

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The results suggest that a computational model-based tracker of the human face that can detect facial expressions of positive and negative emotions is feasible when people are interacting in situations involving other people and events, and it has the potential to perform at the level of human observers of facial expressions if head tracking and feature contrasts are optimized for a single-camera system. Continued correction of the OCR algorithm programming for facial expressions to enhance its facial tracking capability (e.g., of the face partially out of view), its contrast detection capability (e.g., using infrared), and its quality-control features (e.g., avoidance of false positives and false negatives) will be necessary to make it optimally useful in spaceflight, and for a wide range of Earth-based operations. Reference: [1] Michael N. et al. (2011) 18th IAA Humans in Space Symposium, 2306. [2] Ito T.A. et al. (1998) Personality and Social Psychology Bulletin 24, 855- 881. [3] Gross J.J. and Levenson R.W. (1995) Cognition & Emotion 9(1), 87-108. [4] Kring A.M. and Sloan D.M. (2007) Psychological Assessment 19, 210-224.

Beck Depression Inventory (BDI) The Beck Depression Inventory (BDI) is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression (Beck, et al., 1961). The BDI has been developed in different forms, including several computerized forms, a card form (May, Urquhart, Tarran, 1969, cited in Groth-Marnat, 1990), the 13-item short form and the more recent BDI-11 by Beck, Steer & Brown, 1996. (See Steer, Rissmiller & Beck , 2000 for information on the clinical utility of the BDI-11.) The BDI takes approximately 10 minutes to complete, although clients require a fifth - sixth grade reading level to adequately understand the questions (Groth-Marnat, 1990).Internal consistency for the BDI ranges from .73 to .92 with a mean of .86. (Beck, Steer, & Garbin, 1988). Similar reliabilities have been found for the 13-item short form (Groth-Marnat, 1990). The BDI demonstrates high internal consistency, with alpha coefficients of .86 and .81 for psychiatric and non-psychiatric populations respectively (Beck et al., 1988). Reference: American Psychological Association

Pro le of Mood States Short Form (POMS-SF) The Profile of Mood States (POMS; P. M. McNair et al, 1981) is a commonly used measure of psychological distress. The length of this scale (65 items) may limit its use with physically ill or otherwise impaired populations or prevent its inclusion in multiinstrument assessment protocols. This study evaluated the psychometric properties of a shorter, 37-item version of the POMS developed by S. Shacham (1983; POMS-SF). Data were provided by 600 respondents representing five different clinical samples and one sample of healthy adults. For all samples, internal consistency estimates for the POMS-SF subscales were very comparable to those for the original POMS. Furthermore, correlations between total mood disturbance and subscale scores on the POMS-SF and those from the original POMS all exceeded .95. The POMS-SF is considered an excellent alternative to the original POMS when a brief measure of psychological distress is desired. Reference: Curran, Shelly L.; Andrykowski, Michael A.; Studts, Jamie L. Psychological Assessment, Vol 7(1), Mar 1995, 80-83.

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E ects of Promethazine and Midodrine on Orthostatic Tolerance Astronauts experience many clinical symptoms after spaceflight, across multiple physiological systems. Two of the most common of these are severe orthostatic hypotension and severe nausea and vomiting resulting from return to gravity. As these occur concurrently, crew physicians are faced with choices for treatment strategies that can be conflicted. There is no standard pharmaceutical treatment for postflight orthostatic hypotension, but the Îą 1-adrenergic agonist midodrine, developed for treatment of orthostatic hypotension in patients with autonomic dysfunction, has successfully prevented orthostatic hypotension postflight. There is a standard pharmaceutical treatment for postflight emesis. The most common antiemetic used by flight surgeons is promethazine. Reference: SHI S-J,PLATTS SH,ZIEGLER MG,MECK JV. Effects of promethazine and midodrine on orthostatic tolerance. Aviat Space Environ Med 2011; 82:9 - 12.

Heart Rate and Daily Physical Activity with Long-Duration Habitation of the ISS Authors investigated the pattern of activity and heart rate (HR) during daily living on the International Space Station (ISS) compared to on Earth in 7 long-duration astronauts to test the hypotheses that the HR responses on the ISS would be similar to preflight values, although the pattern of activity would shift to a dominance of arm activity, and postflight HR would be elevated compared to preflight during similar levels of activity. HR and ankle and wrist activity collected for 24-h periods before, during, and after spaceflight were divided into night, morning, afternoon, and evening segments. Exercise was excluded and analyzed separately. Results: Consistent with the hypotheses, HR during daily activities on the ISS was unchanged compared to preflight; activity patterns shifted to predominantly arm in space. Contrary to the hypothesis, only night time HR was elevated postflight, although this was very small ( + 4 Âą 3 bpm compared to preflight). A trend was found for higher postflight HR in the afternoon (+ 10 Âą 10 bpm) while ankle activity level was not changed (99 Âą 48, 106 Âą 52 counts pre- to postflight, respectively). Astronauts engaged in aerobic exercise 4-8 times/week, 30-50 min/session, on a cycle ergometer and treadmill.Resistance exercise sessions were completed 4-6 times/week for 58 Âą 14 min/session. Astronauts on ISS maintained their HR during daily activities; on return to Earth there were only very small increases in HR, suggesting that cardiovascular fitness was maintained to meet the demands of normal daily activities. Reference: FRASER KS, GREAVES DK, SHOEMAKER JK, BLABER AP, HUGHSON RL.Heart rate and daily physical activity with long-duration habitation of the International Space Station. Aviat Space Environ Med 2012;83:577-84.

Temazepam, but Not Zolpidem, Causes Orthostatic Hypotension in Astronauts After Space ight Insomnia is a common symptom, not only in the adult population but also in many astronauts. Hypnotics, such as temazepam (a benzodiazepine) and zolpidem (an imidazopyridine), are often taken to relieve insomnia.Temazepam has been shown clinically to have hemodynamic side effects, particularly in the elderly; however, the mechanism is not clear. Zolpidem does not cause hemodynamic side effects. The purpose of this

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study was to determine whether the use of different hypnotics during spaceflight might contribute significantly to the high incidence of postflight orthostatic hypotension, and to compare the findings in astronauts with clinical research. Astronauts were separated into three groups: control (n=40), temazepam (15 or 30 mg; n=9), and zolpidem (5 or 10 mg; n=8). In this study, temazepam and zolpidem were only taken the night before landing. The systolic and diastolic blood pressures and heart rates of the astronauts were measured during stand tests before spaceflight and on landing day. On landing day, systolic pressure decreased significantly and heart rate increased significantly in the temazepam group, but not in the control group or in the zolpidem group. Temazepam may aggravate orthostatic hypotension after spaceflight when astronauts are hemodynamically compromised. Temazepam should not be the initial choice as a sleeping aid for astronauts. These results in astronauts may help to explain the hemodynamic side effects in the elderly who are also compromised. Zolpidem may be a better choice as a sleeping aid in these populations. Reference: Temazepam, but not zolpidem, causes orthostatic hypotension in astronauts after spaceflight.Shi SJ, Garcia KM, Meck JV. J Cardiovasc Pharmacol. 2003 Jan;41(1):31-9.

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Sleep deprivation and fatigue in Astronauts After landing on the moon in 1969, astronaut Neil Armstrong was reportedly unable to sleep all night and astronaut Buzz Aldrin managed only "a couple of hours of mentally fitful drowsing" during their 21.6 h on the moon, reportedly because they could not escape from light and noise in the small cabin of their spacecraft and because the cooling system of the spacesuit made it too cold for sleeping. Because sleep deficiency-an inadequate quantity or quality of sleep-increases the risk of errors and accidents, and human error contributes to between 60% and 80% of aviation accidents, the National Aeronautics and Space Administration (NASA) has improved sleeping conditions for astronauts during spaceflight, and even provides light-attenuated and soundattenuated(<50 dB) sleep stations for astronauts aboard the International Space Station (ISS). However, sleep deprivation and fatigue remain common complaints among astronauts, leading some investigators to postulate that microgravity interferes with the ability to sleep. Previous studies of sleep and hypnotic drug use in space have been limited to post-flight subjective survey data or in-flight objective data collection from a small number of crew members as part of specifi c science payloads. To characterise more representative sleep patterns of astronauts during spaceflight, authors did a large-scale study before, during, and after Space Transportation System space shuttle and ISS missions to measure both objective and subjective measures of sleep that have been validated against polysomnographically-recorded sleep in space. Authors collected data from 64 astronauts on 80 space shuttle missions (26 flights, 1063 in-flight days) and 21 astronauts on 13 ISS missions (3248 in-flight days), with ground-based data from all astronauts (4014 days). All non-Russian crew members assigned to shuttle flights with in-flight experiments from July 12, 2001, until July 21, 2011, or ISS expeditions from Sept 18, 2006,to March 16, 2011, were eligible to participate. NASA excluded the Russian cosmonauts because of conflicting policies regarding participation in research, and commanders sometimes restricted the number of crew members on a mission who could participate in any given experiment because of operational time constraints. Of 193 eligible crew members, 114 (59%) consented to participate. 101 crew members (80 shuttle crew members and 21 ISS crew members; 94% of the 107 who consented and returned to Earth safely) completed the study (54% of the 186 who were eligible and returned to Earth safely). 64 astronauts (n=10 women) participated as 80 crew members on 26 shuttle flights. 14 of these astronauts completed the study twice and one astronaut completed the study three times. Mean age of shuttle crew members was 46.4 years (SD 4.5; range 37.7-57.9). Investigation of sleep among shuttle crew members consisted of 4173 nights of data collection, including 1063 nights during spaceflight. 21 astronauts (n=6 women) participated as 21 crew members on 13 ISS expeditions (expedition 14 until expedition 26) as none participated in two ISS missions. Mean age of ISS crew members was 46.7 years (SD 3.9; range 40.1-55.8). Investigation of sleep among ISS crew members consisted of 4152 nights of data collection, including 3248 nights during spaceflight. Because seven astronauts participated in both a shuttle and an ISS mission, these data were obtained from 78 individual astronauts. Crew members who completed the study were similar in age and sex to those who did not enroll or complete the study (mean age 46.4 [SD 4.4] vs 45.9 years [4.6] and 19 [19%] of 101 vs 15 [16%] of 92 women). During spaceflight, crew members removed the actigraphy device for all extravehicular activity and sometimes for other operational duties or for exercise; crew members neglecting to put the device back on before they went to sleep resulted in the loss of actigraphy recordings on 40 (3.8%) of 1063 nights on shuttle missions and on 297 (9.1%) of 3248 nights on ISS missions. The duration of time astronauts attempted to sleep per night (time in bed assessed by diary) was signif-

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icantly less on shuttle missions, during the 11 days before spaceflight, and during the 2 week interval scheduled about 3 months before spacefl ight than it was on their return to Earth (p<0.0001; table 1). Crew members on shuttle missions took longer to fall asleep (sleep latency assessed by diary) and they slept signifi cantly less (total sleep time assessed by actigraphy) during their shuttle missions, in the 11 days before spaceflight, and in the 2 week interval scheduled about 3 months before spaceflight than during the first 7 days after landing (p<0.0001 for both measures; figure 1, table 1). Age and sex were not significant in the model (data not shown). The mean duration of sleep during spaceflight was 5.96 h (SD 0.56; table 1). Crew members slept on average 20 min longer each night during the 2 week interval scheduled about 3 months before spaceflight, and 47 minutes longer each night in the first 7 days after landing, than they did during spaceflight (table 1).

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On 480 (47.1%) of 1020 nights aboard shuttle missions,astronauts slept for fewer than 6 h (figure 2). This finding might partly be due to a reduction in the duration of time spent attempting to sleep before and during the flight (table 1). Objective actigraphy recordings showed that only 32 (3%) sleep episodes (i.e, the duration of time in bed attempting to sleep) on shuttle flights, 139 (16.1%) episodes 11 days before spaceflight, and 246 (23.5%) episodes in the 2 week interval scheduled about 3 months before spaceflight were 8 h or more long, compared with 236 (46.2%) post-flight episodes (table 2). The appendix provides details of causes of sleep disturbances reported by crew members.

33 crew members were required to undertake 83 extravehicular activities. Actigraphy data were available for 80 of the nights before extravehicular activities. Crew members slept fewer than 6 h on 41 (51.3%) of the nights before accomplishment of extravehicular activities. Crew members obtained 8 h of sleep on 1 (1.3%) night before these crucial tasks (figure 2, table 2). Crew members reported significantly less total sleep time on shuttle missions, during the 11 days before spaceflight, and in the 2 week interval scheduled about 3 months before spaceflight than in the first 7 days after landing (p<0.0001; figure 1, table 1). Subjective ratings of sleep quality and alertness were significantly higher in the first 7 days after landing than during the shuttle missions (adjusted p<0.0001 for sleep quality, adjusted p=0.0011 for alertness), in the 2 week interval scheduled about 3 months before spaceflight (adjusted p=0.024 for sleep quality, adjusted p=0.19 for alertness), and 11 days before spaceflight (adjusted p=0.0033 for sleep quality, adjusted p=0.033 for alertness; table 1). Sleep deficiency during ISS missions was similar to that during shuttle missions. Crew members slept significantly less (total sleep time as recorded by actigraphy) on ISS missions than during the 2 week interval scheduled about 3 months before spaceflight (adjusted p=0.0019) and the first 7 days after landing (adjusted p<0.0001), but for a similar duration to the 11 days before spaceflight (adjusted p=1.0; table 1). Astronauts obtained fewer than 6 h of sleep on 1294 (43.8%) of 2951 nights aboard ISS missions (table 2, figure 2). We noted no significant trends in sleep variables over the duration of the mission (appendix). Crew members reported sleeping on average more than 40 min more per night 7 days after landing than 11 days before spaceflight and in-flight (table 1).

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Roughly three-quarters of shuttle crew members reported taking sleep-promoting drugs in-flight (table 1). Use of sleep drugs was reported on 500 (52%) of the 963 in-flight nights, with two doses of sleep drugs on 87 (17%) of 500 nights on which such drugs were taken (appendix). Use of sleep drugs was reported on 60% of nights before extravehicular activities (table 1). On the four shuttle missions on which all crew members participated, all crew members reported taking sleep drugs on the same night 6% of the time (18 of 308 crewmember nights); this happened on 5% (3/56) of the nights on those four missions. Sleep drugs were taken less frequently in the 11 days before spaceflight, and during the 2 week interval scheduled about 3 months before spaceflight, and 7 days after landing, than in-flight (p<0.0001; table 1). Zolpidem and zolpidem controlled release were the most frequently used drugs on shuttle mis-

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sions, accounting for 301 (73%) and 49 (12%) of the 413 nights, respectively, when one dose of drug was reported. Zaleplon use was reported on 45 (11%) of 413 nights. Other sleep-promoting drugs reported by shuttle crew members during the 413 nights included temazepam on 8 (2%) nights, eszopiclone on 2 (<1%) nights, melatonin on 7 (2%) nights, and quetiapine fumarate on 1 (<1%) night. The most common drugs used during the 87 nights when two doses were reported were zolpidem (22 [25%] nights) or zolpidem controlled release (15 [17%] nights). Various combinations were used when two different drugs were reported in the same night; the most common were zolpidem and zaleplon (14 [16%] nights), zolpidem and melatonin (10 [11%] nights),zolpidem controlled release and melatonin (8 [9%] nights), and zolpidem controlled release and zaleplon (7 [8%] nights). Within-participant analysis (n=607) showed that total sleep time estimated by actigraphy, and self-reported alertness during the in-flight nights when sleep drug use was reported, did not differ significantly from the results from in-flight nights for which no sleep drug use was reported (table 3). However, sleep efficiency was lower,self-reported sleep latency was greater, and subjective sleep quality was slightly lower on nights with no reported drug use. Of the 21 ISS crew members, more than a third (n=8) declined to answer the question about drug use on the sleep log at some point during the mission, which prevented the question being asked in future logs. Three of those eight participants indicated sleeppromoting drug use in the mission before declining to answer the question. Thus, including these three crew members, 12 (75%) of 16 crew members reported use of sleep-promoting drugs. Sleep drugs were reported as being used on 96 (11%) of 852 sleep logs. On 18 (19%) of 96 days when sleep-promoting drugs were used, two doses were reported.

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Geometric illusions in astronauts during long-duration space ight Eight astronauts (one woman and seven men, aged 45-56 years) were tested before, during, and after a long duration mission on board the ISS. Mission durations ranged from 57 to 195 days (mean 154.4). All the participants were tested at least three times before the flight (at BL - 90, L - 60, and L- 30 days), four times in-flight [flight day (FD)], and three times after the flight (at R+0 or R+1, R+4, and R+8 days). In addition, a control population of 91 participants (34 women and 57 men, aged 34-57 years) was tested in normal gravity (1g) on the ground. Informed consent was obtained from all participants. Study approvals were obtained from the investigators’ institutional review boards, as well as from ESA, NASA, and JAXA medical boards. All participants had normal or corrected-to-normal vision with no known visual or vestibular deficits. Geometric illusions Participants were presented with the inverted-T, Ponzo, and Muller-Lyer figures (Fig.1a-c) in a head-mounted visual display (Z800 3DVisor; eMagin Corporation, Bellevue, Washington, USA). All external visual references were blocked by a fabric cover placed over the head-mounted display. The figures were made of white lines on a black background. The figures subtended a viewing angle of 30◦ at a perceived distance of ≈50 cm. The three figures are known to generate systematic distortions in the apparent size of some of the pattern elements . The participants were asked to adjust one segment of the figures using a finger trackball mouse (3G GreenGlobe Co., Ltd, Taipei City, Taiwan) so that it had the same apparent size as a reference segment. When presented with the inverted-T figure, the participants could decrease or increase the size of the vertical line segment to match that of the horizontal line segment, or vice versa. Six trials were performed, half of them with the horizontal segment, the other half with the vertical segment. In each trial, one segment started off with a very large size differential. The same method was used for the other two figures, with the participant adjusting the size of one of the vertical lines in the Muller-Lyer figure or the size of one of the horizontal segments in the Ponzo figure. During each session, the figures were presented in a random order. Line drawings In the second test, a 5-s video clip showing someone drawing a square or a cross was shown in the headmounted display. The test participants then drew the specified shape using an electronic pen on a digital writing tablet (Intuos A4; Wacom Co., Ltd, Vancouver, Washington) without visual feedback. The participants were instructed to match their drawing to their internal representation of a perfect square or cross. The size of the tablet’s active area was 305 X 231mm and the spatial resolution was 5080 lpi. The tablet was attached to the participants’ thighs by knee straps. Each shape was drawn six times. There was no time limit set for the duration of the drawings. Data analysis For the geometric illusions, authors calculated the size differential between the adjusted and the reference segments. For each of the hand drawings, authors calculated the ratio between the vertical and the horizontal length of the figure drawn. The responses for the six trials were averaged individually and the mean and SD were calculated for each flight period. Because the in-flight sessions were not performed at the exact same days for each participant (depending on the mission duration and other on-board operations), the responses were binned by flight periods, that is, FD6-30, FD38-60, FD65-120, and FD133-192. The number of data points per flight period was not the same. However, all the data were included in the analysis because of their rarity. Statistical analysis consisted of one-way analysis of variance (ANOVA) with post-hoc Dunnet’s adjustment across eight levels (the combined 1g data of the control group and the astronauts L- 30 days session; the four in-flight sessions, and the three postflight sessions). Result of Geometric illusions Figure 1 shows the results with the geometric illusions for the eight astronauts before the flight, in-flight, and after the flight. The shaded area on each graph also represents the range of responses seen in the ground-based, healthy participants (n=91). Their mean size differential was 9.6±3.7% (SD) for the inverted-T, 5.2±2.5% for the Ponzo, and 4.3±3.5% for the Muller-Lyer figures. There was no significant difference between the three preflight responses across all astronauts and illusions (F<1), which confirmed that the magnitude of the illusions did not change with the repetition of the tests. The preflight responses of the astro-

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nauts were generally smaller than the ground-based controls, but this difference was not found to be significant.

Therefore, the ground-based data and the last trial of the astronaut preflight data (L - 30 days) were combined (n=99) for analysis. When taken all together, during ground-based testing, the overall size differential was significantly larger [F(2,294)=76.78, P<0.001] for the inverted-T figure (mean 9.4%) than for the Ponzo (mean 5.1%) and Muller-Lyer (mean 4.1%) figures. A one-way ANOVA [F(7,157)=2.09, P=0.048] showed that the inverted-T figure is the only illusion that showed a significant change in-flight compared with before the flight (Fig. 1a). The size differential of the inverted-T illusion decreased to 6.6% after 3 months in orbit. This decrease carried over (7%) to the early postflight period (R+0 to R+1 day). Later postflight (R+4 and R+8 days) responses had returned to preflight values (8.3% on L - 30). The decrease in the inverted-T illusion seen in the astronauts is consistent with that previously reported by otolithic patients on Earth. Result of Line drawings One-way ANOVAs showed that the ratios of vertical versus horizontal length for the hand drawings of squares and crosses were significantly reduced during spaceflight [F(7,157)=4.49, P<0.001 and F(7,156)=3.813, P=0.001, respectively]. When comparing the results for the eight astronauts, there was no difference between the three preflight responses across participants, which also confirmed that repeating the tests at regular

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intervals did not alter the individual responses. In-flight, the astronauts drew squares with a shorter height (mean 5.4-12.1%) than width (Fig. 2a) and a cross with a vertical bar shorter (mean 9.2-12.6%) than the horizontal bar(Fig. 2b). This decrease was significant for FD38-60 (P=0.009), FD65-120 (P=0.034), and FD133-192 (P=0.004) for the square, and for FD65-120 (P= 0.029) and FD133-192 (P=0.028) for the cross. The responses for both drawings returned to normal within 1 day after the flight. This result indicates that simple geometrical shapes with a shorter vertical size presumably appeared normal to astronauts after long-term exposure to 0g.

The same observation was made previously during a short-duration flight in one astronaut and in otolithic patients on Earth. The data reported in fig. 3 of reference included the overall measurements with shapes such as square, a circle, and a cube. When the height of a square was equal to its width, 80.8% of healthy participants and 67.5% of otolithic patients perceived it as a perfect square. When the height was 5% less than its width, only 48.4% of healthy participants continued to perceive it as perfect, whereas this was still the case for 68.5% of otolithic patients. Thus, clearly, both the otolithic patients on Earth and the astronauts in orbit had the similar perception that a 5-10% vertically compressed square looked perfect. The magnitude of the inverted- T illusion and the perceived vertical height of geometrical figures decreased in astronauts during long-term exposure to 0g, just as they did for otolithic patients. The inverted-T illusion became less pronounced (the vertical bar that appeared equal to the horizontal was shorter than usual - more compression) and perfect squares were drawn with the vertical dimensions compressed (suggesting that the vertical lines needed to match the horizontals were shorter than usual - more compression). The changes in the Ponzo and Muller-Lyer illusions were not significant, which also confirms the observations in the otolithic patients. The magnitude of the inverted-T illusion is considerably larger than the other two illusions on the ground; consequently, the magnitude of the Ponzo and Muller-Lyer illusions might be too small to observe a decrease in magnitude. Also, unlike for the inverted-T figure, the illusion for the Ponzo and Muller-Lyer is not that of a length misestimation between two orthogonal lines.

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Therefore, the difference found across the two types of illusions in-flight suggests that it is the judgment between horizontal and vertical segments that becomes less ambiguous after adaptation to 0g. The similarities between the results found in the otolithic patients and the astronauts in terms of both the magnitude of the inverted-T illusion and the representation of geometrical shapes are a further confirmation of the role of the central otolith system in the mental representation of external space. Both the otolithic patients and the astronauts in 0g showed a decrease in the strength of the representation of objects in the vertical dimension. The vertical dimension is particularly affected presumably because the frames of reference normally used for spatial orientation and motion are either based on the gravitational vertical or the long-body vertical axis. Previous experiments conducted on astronauts in orbit have suggested that the magnitude of the idiotropic vector was reduced during adaptation to 0g, but returned to baseline after a few days back on Earth. With a gravitational vertical almost absent and an idiotropic vector whose amplitude is reduced, there would be less of reliance for spatial orientation toward the vertical dimension. Consequently, the geometrical illusions on the basis of the difference between horizontal and vertical sizes would be reduced.

Distance and Size Perception in Astronauts during Long-Duration Space ight Astronauts on board the International Space Station exhibit biases in the perception of their environment. Objects’ heights and depths were perceived as taller and shallower, respectively, and distances were generally underestimated in orbit compared to Earth. Distance Perception Distance perception is the ability for estimating distances between objects in any and all directions relative to an observer’s eye. Absolute distance is the exact distance (e.g., in feet or meters) between the observer’s eye and an object, or between two observed objects. Previous research has demonstrated that horizontal distances are accurately estimated up to 4 m, and underestimated by approximately 10% as distance increases . By contrast, it has been demonstrated that vertical distances are overestimated, by about 30%, especially when looking down. Depth is the distance straight ahead of the observer’s eye, in the direction of or into an object or surface. By definition, depth is looking directly into a hole or tube and estimating forward distances. In this paper, however, the term "depth" will refer to the backward dimension of an object (i.e., the distance from the closest edge of an observed object to the furthest edge of the object within the plane of an observer’s forward gaze), and the term "distance perception" will refer to the judgment of forward distances (i.e., the distance from the observer’s eye to the closest edge of the object). Size Perception Estimates of the size of an object placed at a particular distance can sometimes serve as indirect measures of the apparent distance to the object. The "size-constancy" hypothesis states that people perceive the size of an object by relating its retinal size to its distance . This hypothesis predicts that inaccuracies in distance perception will result from inaccuracies in size perception. There is some evidence that distance and size perception are related . For example, observers generally overestimate the size of farther objects. This relation is not linear, though: the size estimates increase by a factor of 3 to 4 as the distance to the object increases by a factor of 10.

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Nevertheless, the rule is that when we overestimate the distance of an object, we tend to attribute a larger size to this object (and inversely, when we underestimate the distance of an object, we tend to attribute a smaller size to this object). However, size perception does not always relate to distance estimates. Geometrical inconsistencies have been found in studies examining the size-constancy hypothesis. For example, when seen from the top of a building, people and vehicles at ground level look smaller than expected. According to the size-constancy hypothesis, since vertical distances are overestimated, the people/vehicles on the ground should also look larger than normal. Some authors have proposed that the distance scaling of size is not fully operational when looking up or down because the observer is not viewing the area on the ground around his/her feet and this eye height scaling for distance is missing. Eight astronauts (one woman, seven men) ranging from 45 to 56 years (M = 49.4, SD = 3.9) were tested before, during, and after a long-duration mission on board the ISS. Mission durations ranged from 57 to 195 days (M = 154.4, SD = 43.3). Subjects were all tested three times pre-flight (at approximately L-90, L-60, and L-30 days), four times in-flight (FD) and three times post-flight (at R+0 or R+1, R+4, and R+8 days). Additionally, a control population of 91 participants (34 women, 57 men) was tested in normal gravity (1G) on the ground. The average age of participants was 43.2 years (SD = 10.9). The present experiment was designed to answer the questions of whether distance and size perception of objects were affected in astronauts during long-duration exposure to microgravity. Four tests were performed: cube size perception, cube hand drawing, distance perception with cubes, and distance perception with natural scenes. During all the tests, subjects were wearing a head-mounted display subtending a viewing angle of 30◦ (Z800 3DVisor, eMagin Corporation, Bellevue, WA, USA). All external visual references were blocked by a fabric cover placed over the head-mounted display. The tests were delivered through custom-made software on a laptop computer. The subjects interacted with the computer by the means of a finger trackball (3G GreenGlobe Co., Ltd., Taiwan). Cube Size Perception In the first test, subjects were presented with a stereoscopic view of a cube seen in perspective. The cube was made of white lines on a black background. It subtended a viewing angle of 20 ◦ at a perceived distance of approximately 50 cm. One dimension of the cube (i.e., its width, its height, or its depth) was clearly shorter or longer than the other two dimensions. The subjects were asked to adjust this dimension of the cube so that it had the same apparent size as the other two dimensions. During each session, 12 trials were performed, four trials with the width, four with the height, and four with the depth, in random order. For each trial, the size differential was calculated between the final (adjusted) dimension and the reference (normal) dimension of the cube. The responses for all trials were averaged individually and the mean and standard deviation were calculated for each test session. Because the in-flight sessions were not performed on the exact same days from launch for each subject (depending on mission duration and other on-board operations), the responses were binned by flight day (FD) periods, i.e., FD 6-30, FD 38-60, FD 65-120, and FD 133-192. Cube Hand Drawing In the second test, a 5-second video clip showing a line-by-line sequential drawing of a Necker cube was displayed in the head-mounted display. The test subjects then drew the same cube in a smooth motion using an electronic pen on a digital writing tablet (Intuos A4, Wacom Co., Ltd., Vancouver, WA,USA) without visual feedback (i.e., a blank screen was displayed within the head-mounted display).

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The size of the tablet’s active area was 305 X 231 mm and the spatial resolution was 5080 lines per inch. The tablet was attached to the subjects’ thighs by knee-straps. Each cube was drawn six times. There was no time limit imposed for the duration of the drawings. Before the first data collection, subjects practiced by drawing approximately 30 Necker cubes using the procedure described in. In total, 144 cubes were drawn pre-flight (6 trials X 3 sessions X 8 subjects), 192 in-flight (6 trials X 4 sessions X 8 subjects) and 192 post-flight (6 trials X 4 sessions X 8 subjects). For each pre-flight, in-flight, and post-flight cube, the length of the drawn horizontal, vertical, and diagonal lines was measured. Distance Perception with Cubes In the third test, subjects were presented with a stereoscopic view of three cubes in perspective. Two cubes each subtended a viewing angle of 5 ◦ at a perceived forward distance of approximately 30 cm; the third subtended a viewing angle of 2 ◦ at a perceived distance of approximately 60 cm. The distance (and corresponding size) of the far cube, or the distance between the two near cubes, could be adjusted using the finger trackball. The subjects were asked to adjust the position of one cube along the horizontal frontal or sagittal axis so that the apparent distance between all three cubes was equal. During each session, 12 trials were performed: six along the transversal axis, and six along the depth axis. For each trial the size differential was calculated for the adjusted distance and the true distance between the cubes. Distance Perception with Natural Scenes In the fourth test, subjects were presented with 12 stereoscopic (anaglyphs) photographs of natural scenes. The scenes were outdoor photographs of cities, forests, mountains, bridges, towers, etc. Small yellow targets were superimposed on easily recognizable landmarks within each scene, e.g., a remarkable building, the end of a bridge, the top of a mountain, or the bottom of a tower. The subjects were asked to estimate the absolute distance between themselves and the target (egocentric distance) using a conventional metric of their choice (e.g., feet, yards, or meters). Since the photographs were downloaded from the Internet, it was not possible to exactly know the true distances from the landmarks. Therefore, for each of the 12 photographs we calculated the differences between the estimated distances during the pre-flight sessions and those reported during the in-flight or post-flight sessions. Results of Cube Size Perception When comparing the dimensions of the cube that the subjects had adjusted so that it looked normal to them, we found no significant difference between the data collected with the astronauts at L-90 days and with the 91 control participants (Figure 1). In addition there was no difference between the data collected with the astronauts across pre-flight sessions at L-90, L-60, and L-30 days. There was a clear trend for the height of the cube to be smaller and its depth to be larger in-flight compared to pre-flight. A Wilcoxon signed-ranks test for paired differences indicated that the difference in height between the flight day period FD65-120 and the final pre-flight data collection session (L-30) was significantly different from zero (Z = 4.24, p < 0.001, r = 1.5). A significant difference was also observed between the period FD133-192 and L-30 (Z = 3.12, p < 0.001, r = 1.1). The difference in depth between the period FD133-192 and L-30 was also significantly different from zero (Z = 3.92, p < 0.001, r = 1.39).

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Results of Cube Hand Drawing There was no difference in the length of the horizontal, vertical, or oblique lines of the Necker cube drawings between the pre-flight L-90, L-60 and L-30 sessions. During the flight, the data is consistent with the cube size perception data although the effects are not as large. A Wilcoxon signed-ranks test for paired differences indicated that the length of the vertical lines was significantly smaller during the periods FD65-120 (Z = 1.69, p < 0.04, r = 0.6) relative to L-30 (Figure 2). All other paired differences were not significant.

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Results of Distance Perception with Cubes In this test, subjects were asked to estimate the perceived distance of a cube by replicating the extent they were viewing in another direction through visual matching. The true distances ranged between approximately 30 and 60 cm. The perceived distances were fairly accurate on Earth in both the astronauts and the control participants (Figure 3). In orbit, the astronauts underestimated the distance, as consistently shown when adjusting the distance of the cube either along the horizontal frontal or sagittal direction. However, this underestimation was not found to be significant, presumably due to the larger variance in the data for this test, for both the ground-based controls and the astronaut sample.

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Results of Distance Perception with Natural Scenes Because of the time constraints, only 12 photographs were used: six for testing horizontal distance and six for testing vertical distances. Prior to the flight, the egocentric distances reported by the astronauts ranged from 2 m to 2000 m, with a uniform distribution. All pre-flight measures were not significantly different from each other or from post-flight measures. In addition, these distance estimates were not significantly different from those reported by the 91 participants in the control group. On average, the astronauts reported distances above 50 m to be about 20%-25% smaller in-flight than pre-flight (Figure 4). Wilcoxon tests indicated that this underestimation was significant for distances that were reported to be at 180 m (Z = 1.74, p < 0.04, r = 0.62) and 1500 m (Z = 1.82,p < 0.03, r = 0.64).

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During an elegant experiment performed during the Neurolab space mission, crewmembers were required to catch a ball that fell with a constant velocity in 0G (compared to a constant acceleration on Earth). Results showed that they missed the ball by moving their arms too early. The authors surmised that the subjects were using an internal model of gravity and reacted as if the ball was still accelerating downwards. However, the astronauts’ responses could also be due to an underestimation of the ball distance. Similarly, Paloski et al. reported that during landings of the Space Shuttle, especially after missions lasting more than 10 days, the vehicle’s vertical speed during the final approach was much faster than during shorter missions and during training simulations. This pattern could also be due to an underestimation of distance, in this case vertical distance between the orbiter and the runway, by the pilots after two weeks in orbit. could also be due to an underestimation of distance, in this case vertical distance between the orbiter and the runway, by the pilots after two weeks in orbit. Distortions of the visual space and misperception of object size, distance, and shape during space missions represent potentially serious operational consequences. For example, if a crewmember does not accurately gauge the distance of a target, such as a docking port or an approaching vehicle then the speed of this target may be misevaluated, leading to operational errors. In fact, it is believed that a poor sense of closing speed was a contributing cause to the collision between a Progress supply spacecraft with the Mir space station in 1997.

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R EFERENCES 1.Differential Effects on Homozygous Twin Astronauts Associated with Differences in Exposure to Spaceflight Factors, NNJ13ZSA002N-TWINS,Human Exploration Research Opportunities (HERO),NASA. 2. NASA Selects 10 Proposals to Explore Genetic Aspects of Spaceflight. Available online at http://www.nasa.gov/content/nasa-selects-10-proposals-to-explore-genetic-aspects-of-spaceflight/. 3.NASA Twins Study.Available online at http://www.nasa.gov/content/twins-study/ . 4.Prevalence of sleep deficiency and use of hypnotic drugs in astronauts before, during, and after spaceflight: an observational study Barger, Laura K et al. The Lancet Neurology , Volume 13 , Issue 9 , 904 - 912. 5.Clement G, Skinner A, Richard G, Lathan C. Geometric illusions in astronauts during long-duration spaceflight. Neuroreport. 2012 Oct 24;23(15):894-9.doi: 10.1097/WNR.0b013e3283594705. PubMed PMID: 22955144. 6.Clement, G.; Skinner, A.; Lathan, C.Distance and Size Perception in Astronauts during Long-Duration Spaceflight. Life 2013, 3, 524-537. 7.Namni Goel, David F. Dinges, Predicting risk in space: Genetic markers for differential vulnerability to sleep restriction, Acta Astronautica, Volume 77, August-September 2012, Pages 207-213, ISSN 0094-5765, http://dx.doi.org/10.1016/j.actaastro.2012.04.002. 8.Poljakov, Dietrich Manzey Bernd Lorenz Valeri(1998) ’Mental performance in extreme environments: results from a performance monitoring study during a 438-day spaceflight’, Ergonomics, 41: 4, 537 - 559. 9.Soluble TNF-alpha receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight. Shearer WT, Reuben JM, Mullington JM, Price NJ, Lee BN, Smith EO, Szuba MP, Van Dongen HP, Dinges DF.J Allergy Clin Immunol. 2001 Jan;107(1):165-70.PMID: 11150007 10.Cognitive neuroscience in space.De la Torre GG.Life (Basel). 2014 Jul 3;4(3):281-94. doi: 10.3390/life4030281. Review.PMID: 25370373 11.William T. Shearer, Shaojie Zhang, James M. Reuben, Bang-Ning Lee, Janet S. Butel, Predictors of immune function in space flight, Acta Astronautica, Volume 60, Issues 4-7, February-April 2007, Pages 247-253, ISSN 00945765,http://dx.doi.org/10.1016/j.actaastro.2006.08.005. 12.Automated neuropsychological assessment metrics (ANAM) measures of cognitive effects of Alzheimer’s disease.Levinson D, Reeves D, Watson J, Harrison M.Arch Clin Neuropsychol. 2005 May;20(3):403-8.PMID: 15797175.

13.Zhizhen Liu, Yufeng Wan, Lin Zhang, Yu Tian, Ke Lv, Yinghui Li, Chunhui Wang, Xiaoping Chen, Shanguang Chen, Jinhu Guo, Alterations in the heart rate and activity rhythms of three orbital astronauts on a space mission, Life Sciences in Space Research, Volume 4, January 2015, Pages 62-66, ISSN 2214-5524, http://dx.doi.org/10.1016/j.lssr.2015.01.001. 14.Frank Beckers, Bart Verheyden, Jiexin Liu, André E. Aubert, Cardiovascular autonomic control after shortduration spaceflights, Acta Astronautica, Volume 65, Issues 5-6, September-October 2009, Pages 804-812, ISSN 0094-5765, http://dx.doi.org/10.1016/j.actaastro.2009.03.004. 15.Baevsky RM, Baranov VM, Funtova II, Diedrich A, Pashenko AV, Chernikova AG, Drescher J, Jordan J, Tank J. Autonomic cardiovascular and respiratory control during prolonged spaceflights aboard the International Space Station. J Appl Physiol 103: 156-161, 2007. 16.Recovery of the locomotor function after prolonged microgravity exposure. I. Head-trunk movement and locomotor equilibrium during various tasks. Courtine G, Pozzo T.Exp Brain Res. 2004 Sep;158(1):86-99. Epub 2004 May 26.PMID: 15164151 17.Space motion sickness: incidence, etiology, and countermeasures. Heer M, Paloski WH. Auton Neurosci. 2006 Oct 30;129(1-2):77-9. Epub 2006 Aug 28. Review.PMID: 16935570.

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18.A. R. Kotovskaya and I. F. Vil’-Vil’yams,Characteristics of Physiological Responses to +Gx Loads in Non-Professional Crew Members of Short-Term Missions to the ISS,Human Physiology,December 2011, Volume 37, Issue 7, pp 810815. 19.M. P. Rykova, Yu. G. Gertsik, E. N. Antropova, L. B. Buravkova,Serum levels of immunoglobulins, allergenspecific IgE antibodies, and interleukin-4 in cosmonauts before and after short flights on the International Space Station,Human Physiology, 2006, Volume 32, Number 4, Page 457. 20.A. R. Kotovskaya, I. F. Vil-Viliams, V. Yu. Lukjanjuk,Human Physiological Responses to the G-Load Accompanying the Orbiting and Descent of Soyuz Spacecraft,Human Physiology,November 2003, Volume 29, Issue 6, pp 677-684. 21.Augusto Cogoli,Human lymphocytes in space: 1975-2005, Thirty years of ups and downs,Microgravity - Science and Technology September 2006, Volume 18, Issue 3-4, pp 9-13. 22.Space radiation does not induce a significant increase of intrachromosomal exchanges in astronauts’ lymphocytes.Horstmann M, Durante M, Johannes C, Pieper R, Obe G.Radiat Environ Biophys. 2005 Dec;44(3):219-24. Epub 2005 Oct 11.PMID: 16217644 23.Cardiovascular deconditioning in microgravity: some possible countermeasures.Antonutto G, di Prampero PE.Eur J Appl Physiol. 2003 Oct;90(3-4):283-91. Epub 2003 Jul 8. Review.PMID: 12851824 24.Gilles Clement, Jennifer Thu Ngo-Anh,Space physiology II: adaptation of the central nervous system to space flight-past, current, and future studies,European Journal of Applied Physiology,July 2013, Volume 113, Issue 7, pp 1655-1672. 25.Space physiology VI: exercise, artificial gravity, and countermeasure development for prolonged space flight.Hargens AR, Bhattacharya R, Schneider SM.Eur J Appl Physiol. 2013 Sep;113(9):2183-92. doi: 10.1007/s00421-0122523-5. Epub 2012 Oct 19. Review.PMID: 23079865 26.Orthostatic heart rate responses after prolonged space flights.Tank J, Baevsky RM, Funtova II, Diedrich A, Slepchenkova IN, Jordan J. Clin Auton Res. 2011 Apr;21(2):121-4. doi: 10.1007/s10286-010-0106-2. Epub 2010 Dec 25.PMID: 21188460. 27.Evaluation of mechanisms of postflight orthostatic intolerance with a simple cardiovascular system model.Broskey J, Sharp MK.Ann Biomed Eng. 2007 Oct;35(10):1800-11. Epub 2007 Jun 26.PMID: 17592777. 28.Changes in gastric myoelectric activity during space flight.Harm DL, Sandoz GR, Stern RM.Dig Dis Sci. 2002 Aug;47(8):1737-45. PMID: 12184524. 29.The state of the digestive system organs during long space flight.Afonin BV, Noskov VB, Poliakov VV.Fiziol Cheloveka. 2003 Sep-Oct;29(5):53-7. Russian.PMID: 14611084 30.R. M. Baevsky, V. V. Bogomolov, I. I. Funtova, I. N. Slepchenkova, A. G. Chernikova,Prospects of medical monitoring of long-duration space flights by means of non-contact recording of physiological functions during sleep time,Human Physiology December 2011, Volume 37, Issue 7, pp 816-820.

ISOPTWPO Today Page 51 International Space Agency(ISA)


ISOPTWPO The International Space Agency (ISA) was founded by Mr. Rick Dobson, Jr., a U.S. Navy Veteran, and established as a non-profit corporation for the purpose of advancing Man’s visionary quest to journey to other planets and the stars. ISOPTWPO(International Space Flight & Operations - Personnel Recruitment, Training, Welfare, Protocol Programs Office) is part of ISA, which support research on Human Space Flight and its complications. ISOPTWPO will research on NASA’S Human Research Roadmap. It will also research on long duration spaceflight and publish special issues on one year mission at ISS and twin study. Mr. Martin Cabaniss is director and Mr. Abhishek Kumar Sinha is Assistant Director of ISOPTWPO. Ad Astra ! To The Stars! In Peace For All Mankind ! Mr. Rick R. Dobson, Jr.(Veteran U.S Navy) — International Space Agency (ISA)

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Ad Astra ! To The Stars! In Peace For All Mankind ! Mr. Rick R. Dobson, Jr. (Veteran U.S Navy)

Image Credit: NASA

International Space Agency(ISA) P.O. Box 541053 Omaha, Nebraska 68154 United States

ISA Web Site http://www.international足space足agency.us/


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