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F EBRUARY 2014, N O 4

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About ISOPTWPO International Space Flight & Operations - Personnel Recruitment, Training, Welfare, Protocol Programs Office (International Space Academy). It is a division of the ISA organization. Mr. Martin Cabaniss is director and Mr. Abhishek Kumar Sinha is Assistant Director of ISOPTWPO. — International Space Agency(ISA)

“Ad Astra! To The Stars! In Peace For all Mankind!

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Differential Effects on Homozygous Twin Astronauts Associated with Differences in Exposure to Spaceflight Factors There is a singular opportunity to propose limited, short-term investigations examining the differences in genetic, proteomic, metabolomics, and related functions in twin male monozygous astronauts associated with differential exposure to spaceflight conditions. This opportunity has emerged from NASA’s decision to fly veteran NASA astronaut Scott Kelly aboard the International Space Station (ISS) for a period of one year commencing in March 2015, while his identical twin brother, retired NASA astronaut Mark Kelly, remains on Earth. Scott Kelly, a veteran of two Space Shuttle flights as well as a six-month ISS mission, will have a cumulative duration of 540 days in low Earth orbit at the conclusion of the one-year flight, while Mark Kelly, a veteran of four Space Shuttle flights, has a cumulative duration of 54 days in low Earth orbit. This opportunity originated at the initiative of the twin astronauts themselves. This project will center on established plans for blood sampling on the flying twin at regular intervals before, during and after the one-year ISS mission, and will obtain corresponding samples from the non-flying twin, who will otherwise maintain his normal lifestyle. Limited additional sampling (blood, saliva, buccal cheek swabs, and stool) or tests of psychological or physical performance will also be considered if: 1) they do not interfere with the previously scheduled HRP ISS flight experiments and 2) they require monozygous twins to illuminate one or more aspects of transient or long-term effects of spaceflight on humans.

NASA Astronauts and Navy Capts. Scott Kelly, left, and twin brother Mark Kelly. Image Credit:NASA Research Emphases 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. 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.

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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 observations should be synchronized with relevant bio-specimen sampling, to enable analyzed - omics data to 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. Whereever possible, psychosocial and neurobehavioral experiments and observations should be synchronized with relevant bio-specimen sampling, to enable analyzed - omics data to be directly compared to psychosocial and neurobehavioral measurements. Investigators should also carefully specify which physiological and psychological meta-data (e.g. blood pressure, pulse rate, body temperature, alertness levels as measured by Psychomotor Vigilance Test or PVT, mood, the occurrence of any illnesses or injuries, etc.), should be concomitantly collected along with the - omics data, so that genotype can be precisely mapped to phenotype. In addition, it is important that over the time course of experiments, the space radiation field(s) on board and external to the International Space Station - as well as in Mark Kelly’s home in Tucson, AZ - be as completely characterized as possible, particularly in regards to lineal energy, particle fluence, particle species, particle energy and other microdosimetry parameters. Reference:Human Exploration Research Opportunities (HERO),NNJ13ZSA002N-TWINS

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NASA FLIGHT ANALOGS PROJECT BED REST EXPERIMENT The standard platform for bed rest studies is 60 days of six degrees head down tilt (HDT) bed rest. Durations of 14-days, 30-days and 90-days can also be accommodated if warranted by study requirements. NASA bed rest studies are performed at the Flight Analogs Research Unit (FARU) as part of the Institute for Translational Sciences-Clinical Research Center (ITS - CRC) located at the University of Texas Medical Branch in Galveston, TX. BED REST STANDARDIZED CONDITIONS • Duration: 60 days • Bed Position: 6 degrees head down tilt, continuous for the duration of the study • Room Temperature: 72 F (+/- 2 degrees) • Humidity: 70% (+/- 5%) • Light/Dark Cycle: Lights on 0600, lights out 2200, 7 days per week, no napping is permitted • Daily Measurements: – Blood Pressure, Heart Rate, Respiratory Rate, Body Temperature – Body Weight – Fluid Intake and Output • Monitoring: By Subject Monitors in person or via in-room camera 24 hours a day • Stretching Regimen: Twice daily • Physiotherapy: Every other day during bed rest and every day for the first seven days post bed rest • Psychological support is provided once weekly during the study and available as needed at all times BED REST STANDARDIZED DIET • Metabolically controlled diet based on the NASA space flight nutritional requirements • Carbohydrate:Fat:Protein ratio - 55:30:15 • Minimal fluid intake of 28.5 ml/kg body wt (2000 ml/70 kg subject); additional water may be consumed • No caffeine, cocoa, chocolate, tea or herbal beverages • All food must be consumed • Caloric intake adjusted to maintain weight within 3% of day 3 of head down tilt • Iron supplementation is provided for all female subjects • Iron supplementation is provided for male subjects with a low ferritin (less than 35 ng/ml) at study entry • Vitamin D supplementation (800 IU/day) is provided throughout bedrest • Subjects with low vitamin D levels (less than 50 nmoles/L) at study entry will be supplemented during the pre-bed rest phase

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BED REST STANDARD MEASURES Standard measures provide a characterization of the physiologic responses to bed rest in humans across disciplines. These protocols are performed at the Institute for Translational Sciences - Clinical Research Center (ITS - CRC) and are integrated with science investigation requirements on a non-interfering basis. The standard measures can be utilized to describe gender differences in the physiological responses to bed rest, provide a basis for comparisons of bed rest results with results from spaceflight investigations, and provide ancillary data to individual investigators. BONE MINERAL DENSITY (DXA) Dual Energy X-Ray Absorptiometry (DXA) will be used to obtain measures of bone mineral density. BONE MASS AND GEOMETRY (QCT) Quantitative Computerized Tomography (QCT) will be used to evaluate bone mass and geometry. Lumbar and hip scans will measure bone density and analyze regional changes in bone. QCT scans will be analyzed to determine volumetric bone mineral density (vBMD), bone mineral content, and bone size. CLINICAL NUTRITIONAL ASSESSMENT General blood and urine chemistry, electrolytes, selected markers of hematological, protein, vitamin and mineral status, markers of oxidative damage, and markers of bone metabolism will be assessed. In addition, cellular mineral content (sodium, potassium, chloride, calcium, phosphorous, magnesium) will be will be analyzed from sublingual epithelial cells collected with a wooden spatula by scraping the floor of the mouth. Serum Measurements for Nutrition Standard Measure Chemistry Sodium, Potassium, Chloride, Creatinine, Aspartate Transaminase (AST), Alanine Transaminase (ALT), Cholesterol, LDL Cholesterol, HDL Cholesterol, Triglyceride, hs-CRP, IL-1 beta, Total Lipids, TNF-alpha Portable Clinical Blood Analyzer Hemoglobin, Hematocrit, Ph, Ionized Calcium, Potassium, Sodium, Glucose Mineral Status Zinc, Selenium, Iodine, Copper, Ceruloplasmin, Phosphorus, Magnesium Calcium and Bone Metabolism Markers 25-Hydroxyvitamin D, 1, 25 - Dihydroxyvitamin D, Intact Parathyroid Hormone (PTH), Osteocalcin, Alkaline Phosphatase, Bone Specific Alkaline Phosphatase (BSAP), Serum Calcium, Osteoprotegerin (OPG), Osteoprotegerin ligand (receptor activator of nuclear factor - kB ligand or RANKL), Insulin-like Growth Factor, Leptin Hematologic and Iron Status Indicators Hemoglobin, Hematocrit, Mean Corpuscular Volume (MCV), Transferrin Receptors, Transferrin, Ferritin, Ferritin Iron, Ferritin Iron % Saturation, Iron, Fibrinogen Protein Status Retinol Binding Protein, Transthyretin, Total Protein, Albumin, Alpha 1 globulin, Alpha 2 globulin, Beta globulin, Gamma globulin Hormones Testosterone, Free Testosterone, Estradiol, Dehydroepiandrosterone (DHEA), Dehydroepiandrosterone Sulfate (DHEAS), Cortisol Water Soluble Vitamin Status Erythrocyte Transketolase Stimulation, Erythrocyte Glutathione Reductase Activity, Erythrocyte nicotinamide adenosine dinucleotide and nicotinamide adenosine dinucleotide phosphate (NAD/NADP), Erythrocyte Transaminase Activity, Folate, RBC and Serum, Homocysteine, Vitamin C, Pyridoxal 5-phosphate (PLP) Fat Soluble Vitamin Status Retinol, Retinyl palmitate, β - carotene, Serum Phylloquinone, α - tocopherol, γ - tocopherol, Tocopherol : lipid ratio,

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Vitamin D Binding Protein, Plasma Heme, Undercarbolxylated Osteocalcin Antioxidants and Markers of Oxidative Damage Total Antioxidant Capacity (TAC), Superoxide Dismutase (SOD), Glutathione Peroxidase (GPX), Malondialdehyde (MDA), Total Lipid Peroxides Glutathione Protein Carbonyls, Reduced and Oxidized Glutathione Urinary Measurements for Nutrition Standard Measure General Total volume, pH, Creatinine, Chloride, Cortisol Bone Metabolism Markers N - telopeptide (NTX), Pyridinoline (PYD), Deoxypyridinoline (DPD), γ - carboxy glutamic acid, C-telopeptide (CTX), Helical Peptide (HP) Minerals Calcium, Phosphorus, Magnesium, Copper, Selenium, Zinc, Iodine Water Sol. Vitamins N - methyl nicotinamide, 2 - pyridone, 4 - pyroidoxic acid Protein Status 3 - methyl histidine, Nitrogen Antioxidants 8 - OH deoxyguanosine, Prostaglandin F2 α (PG F2 α) Renal Stone Risk Sodium, Potassium, Uric Acid, Citrate, Oxalate, Sulfate, Supersaturation of Calcium Oxalate, Brushite, Struvite, Urate CLINICAL LABORATORY ASSESSMENT Additional blood and urine studies will be performed to monitor subject health status and provide additional data. Serum Measurements for Clinical Laboratory Standard Measure Chemistry Profile Carbon Dioxide, Chloride, Creatinine, Glucose, Potassium, Sodium, Blood Urea Nitrogen, Glomerular Filtration Rate, Phosphorous, Magnesium, Bilirubin, Glutamyltransferase, Alkaline Phosphatase, Lactate Dehydrogenase, Creatine Kinase, Uric Acid, C Reactive Protein (hs CRP) Aspartate Transaminase, Alanine Transaminase, albumin, total protein, calcium. CBC/differential/platelets White Blood Count and differential, Red Blood Count, Hemoglobin, Hematocrit, Mean Corpuscular Volume, Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Hemoglobin Concentration (MCHC), Relative (Red Cell) Distributive Width (RDW), Platelet Count, Reticulocyte Count Iron Profile Iron, Total Iron Binding Capacity (TIBC), Transferrin, Transferrin Saturation, Ferritin Ionized Calcium Profile Serum Ionized Calcium, pH - Serum, Ionized Calcium at pH 7.40 Hormones Thyroxine (Free T4), Thyroid Stimulating Hormone (hTSH III)

Urinary Measurements for Clinical Laboratory Standard Measure

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Urinanalysis Specific Gravity, pH, Color, Appearance, Protein, Glucose, Bilirubin, Urobilinogen, Ketone, Nitrite, Blood, Leukocyte Esterase Other Creatinine Reference:Human Research Program Flight Analogs Project Information Package for Bed Rest Studies,NASA

Risk of Behavioral and Psychiatric Conditions Space flight, whether of long or short duration, occurs in an extreme environment that has unique stressors. Even with excellent selection methods, behavioral problems among space flight crews remain a threat to mission success. Assessment of factors that are related to behavioral health can help minimize the chances of distress and, thus, reduce the likelihood of behavioral conditions and psychiatric disorders arising within a crew. Similarly, countermeasures that focus on prevention and treatment can mitigate the behavioral conditions and psychiatric disorders that, should they arise, would impact mission success. Based on space flight and analog evidence, the average incidence rate of an adverse behavioral health event occurring during a space mission is relatively low. While mood and anxiety disturbances have occurred, no behavioral emergencies have been reported to date in space flight. Anecdotal and empirical evidence indicates that the likelihood of a behavioral condition or psychiatric disorder occurring increases with the length of a mission. Further, while behavioral conditions or psychiatric disorders might not immediately and directly threaten mission success, such conditions can, and do, adversely impact individual and crew health, welfare, and performance, thus indirectly affecting mission success. Many factors predict or otherwise play a role in the occurrence of a behavioral condition or psychiatric disorder. These include: sleep and circadian disruption, personality, negative emotions, physiological changes that occur when adapting to microgravity, lack of autonomy, daily personal irritants, physical conditions of life in space, workload, fatigue, monotony, cultural and organizational factors, family and interpersonal issues, and environmental factors. Positive or salutary aspects of space flight also contribute to behavioral health outcomes. Some factors have both detrimental and salutary aspects; teamwork, giving and receiving social support, and leadership responsibilities are a few examples of these.

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Disorders such as anxiety, post-traumatic stress, sleep loss/insomnia, adjustment, and depression can also develop unexpectedly in otherwise healthy individuals. A recent study indicates that the average age of onset of depression for persons who have no family history of depression is 41 years (standard deviation (SD)=13.67); therefore, even astronauts who have never experienced depression are not immune from its development. The age of astronaut candidates when selected for the Astronaut Corps has ranged between 26 and 46 years (NASA, 2008b). Between 1989 and 2003, the average age of the astronauts who were selected was 36.5 years. It is important to note that depression could occur at any phase of an astronautŠs career. Furthermore, behavioral problems that occur during space flight often do not terminate when the mission ends, but can linger with notable aftereffects (Category IV). According to the "NASA Categories of Evidence" • Category I data are based on at least one randomized controlled trial. • Category II data are based on at least one controlled study without randomization, including cohort, casecontrolled or subject operating as own control. • Category III data are non-experimental observations or comparative, correlation and case, or case-series studies. • Category IV data are expert committee reports or opinions of respected authorities that are based on clinical experiences, bench research, or "first principles." The NASA Human Research Program (HRP) is organized into topical areas called Elements; the Behavioral Health and Performance (BHP) Element is tasked with the responsibility of managing three risks: (1) risk of performance errors due to sleep loss, circadian desynchronization, fatigue, and work overload; (2) risk of performance errors due to poor team cohesion and performance, inadequate selection/team composition, inadequate training, and poor ISOPTWPO Today Human Space Flight c International Space Agency(ISA)

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psychosocial adaptation; and (3) risk of behavioral and psychiatric conditions. Behavioral and psychiatric emergencies NASA considers any behavioral condition or psychiatric disorder that causes serious behavioral or cognitive symptoms leading to incapacitation and severe mission impact as a behavioral emergency. Examples include the development of delirium due to a head injury, or a brief psychotic disorder following a tragic event such as the death of a family member or an international catastrophe.To date, no behavioral emergencies have occurred before or during any U.S. space flight. Some Russian space flight missions in the 1970s and 1980s were terminated early due to psychological factors. 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. 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 . Mood and mood disorders Mood disorders, which are categorized in the NASA integrated medical model (IMM) as depression and anxiety, have occurred during space flight. Data that were collected for 28.84 person-years of NASA space flight reveal that 24 cases of anxiety occurred in space flight for an incidence rate of .832 cases per personyear (NASA, 2007a). Over the same 28.84 person-years, four astronauts experienced signs and symptoms of depression during space flight for an incidence rate of .139 per person-year (NASA, 2007a). In other words, signs and symptoms of anxiety during space flight occurred once every 1.2 years, and signs and symptoms of depression occurred once every 7.2 years. Asthenia Asthenia or neurasthenia is one of the psychological conditions that has been observed, but it has been seen only by Russian medical and psychological personnel in cosmonauts after they have spent 4 months living in space. In the mid - 1970s, Russian psychiatrists and psychologists considered asthenia a syndrome that should be viewed as an adaptive reaction due to exhaustion of the nervous system as a result of overexertion, lack of proper nutrition, disruptions in intracellular metabolism, and intoxication. However, during this same timeframe, one Russian psychologist defined asthenia as a state characterized by heightened susceptibility to fatigue, fast onset of exhaustion, and partial or total loss of capacity for prolonged physical activity or mental exertion. Aleksandrovskiy (1976) stated that asthenia in space develops in three phases: Stage one (hyperesthesia): There is a general increase in sensitivity to external stimuli, resulting in hyper-arousal and increased (sometimes pointless) activity, emotional instability and irritability, impatience, decreased memory, poor attention and concentration, fatigue, headaches, perspiration, instability of pulse and blood pressure, and sleep disturbances. Stage two: Irritable weakness, irritability, and emotional instability progress into more severe fatigue, negative emotional reactions, and somnolence. Stage three: There is indifference and inertness, apathy, constant fatigue, passiveness, and lack of work capability. On the other hand, some researchers from the United States. have specifically looked at asthenia in space using the Profile of Mood States (POMS). Kanas and colleagues could not demonstrate the presence of asthenia in space as operationally defined using the POMS, as the POMS addresses only emotional and not physiological aspects of the syndrome. Psychosomatic reactions Psychosomatic reactions occasionally have been reported during space flight. Psychosomatic is defined as "pertaining

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to a physical disorder that is caused by or notably influenced by emotional factors" . These health struggles are not imaginary; in fact, more than half of all individuals who are seeking medical attention are suffering from psychosomatically induced or exacerbated illnesses. For example, an otherwise healthy cosmonaut experienced a cardiac arrhythmia that required medication after being exposed to sustained stressors related to on-board equipment failure.There are direct self-reports of somatizing by cosmonaut Valentin Lebedev during the record-breaking length of his Salyut 7 mission. Other psychosomatic reactions include complaints of toothaches after dreams of tooth infections and fears of impotence due to perceived prostatitis. Salutogenesis Antonovsky, in 1979(Category IV), coined "salutogenesis" as the opposite of pathogenesis. Salutogenic experiences are those that promote a sense of health. The key factor of salutogenesis, according to Antonovsky (1979), is a person’s sense of coherence. He defined this sense of coherence as "a global orientation that expresses the extent to which one has a pervasive, enduring though dynamic feeling of confidence that oneŠs internal and external environments are predictable and that there is a high probability that things will work out as well as can reasonably be expected." Preliminary results suggest that a salutogenic response to space flight is common across astronauts and endures for some time post-flight. Astronauts and cosmonauts have reported experiencing transcendental, religious experiences or a sense of the unity of humankind while in space . Analysis of the memoirs of four astronauts reveals that all four reported post-flight feelings of increased spirituality, defined as "meaning and inner harmony through transcendence". Psychosocial adaptation and disorders Anecdotal evidence from crew members illuminates the distress that some individuals encounter during longduration space flight missions. Psychosocial adjustment is, by definition, the psychological and social process of adapting or conforming to new conditions. Unsuccessful psychosocial adaptation can lead to adjustment disorders that are characterized by decrements in performance. In-flight diaries of cosmonauts and astronauts recount periods of psychological distress experienced during extended periods in space. Even crew members with otherwise cheerful dispositions may demonstrate changes in temperament when meeting the challenges of space flight adaptation. Lebedev wrote in his journal, "[M]y nerves were always on edge, I get jumpy at any minor irritation" (Lebedev, 1988, p. 291). Reference: 1.Human Health and Performance Risks of Space Exploration Missions,NASA SP-2009-3405 2.Lebedev V. (1988). Diary of a cosmonaut: 211 days in space. Phytoresource Research Information Service, College Station, Texas.

Human performance during long-term spaceflight 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:

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• 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. • 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. Results Cognitive task performance 1. 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). 2. 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 eOEects of session became significant (MS2: F(39,1316) = 70.88, p< 0.01; MS4: F(39,1316) = 68.44, p< 0.01).

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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).

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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). â&#x20AC;&#x2122;Sadnessâ&#x20AC;&#x2122; 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 ratings remained on the general in-flight level at the first three assessments, and were clearly elevated at post-flight days + 6 and + 12. Reference:Mental performance in extreme environments: results from a performance monitoring study during a 438day spaceflight

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