The ESA Life Science Programme on the International Space Station

1. The ESA Life Science Programmeon the International Space Station TsNIIMASH, Nov 25th, 2010 Moscow ESA UNCLASSIFIED – For Official Use

2. Ongoing ISS experiments - Physiology • IMMUNO – Immune function (Russian joint experiment • NeuroSpat - NeuroCognitive • CARD – Cardiovascular • SOLO – Nutrition/Bone Loss • 3D SPACE – Neurovestibular/Cognitive • PASSAGES - Neurovestibular/Cognitive • EKE – Exercise Capacity (joint protocol with NASA VO2MAX expt) • Thermolab – Thermoregulation (joint protocol with NASA VO2MAX expt) • Vessel Imaging – Vascular function • ZAG – Neurovestibular • OTOLITH – Neurovestibular • EDOS – Bone loss (trabecular structure) (Russian joint experiment) • SPIN–GAZE – Neurovestibular/Cardiovascular (Russian joint experiment) ESA UNCLASSIFIED – For Official Use

3. Upcoming Experiments – rather near-term ENERGY (potentially Russian cooperation) • To measure changes in energy balance during long term Spaceflight • To measure adaptations in the components of the total energy expenditure • To derive an equation for the energy requirements of astronauts SARCOLAB Contractile characteristics of the plantarflexors during static (isometric contractions at different joint angles) and dynamic (isokinetic contractions at different angular velocities) contractions performed on the MARES dynamometer, ESA UNCLASSIFIED – For Official Use

4. DEX on Columbus GRIP (Dexterous Manipulation in Microgravity) - ILSRA-2004-133 PI: Dr Thonnard (BE) • To study the long-term adaptation of grip-force/load-force coordination to conditions of microgravity environment. • Effects of weight versus mass. • Point-to-point movement kinematics and dynamics • Grip force during controlled collisions • To study the interaction between cognitive and proprioceptive cues with respect to control of grip force and movement kinematics for ‘upward’ versus ‘downward’ movements. ESA UNCLASSIFIED – For Official Use

5. Space Headaches: Incidence and characteristicsILSRA 2009-0950 • PI: Alla Vein (NL) • The main scientific objective of the experiment is to assess headache occurrence and to analyze headache characteristics in astronaut/cosmonauts during space missions. • Specifically designed questionnaires based on the criteria of the International Classification of Headache Disorders (ICHD) will be filled out by the crew daily for the first week on-orbit and weekly thereafter. • Retrospective questionnaires to astronauts that flown previously ESA UNCLASSIFIED – For Official Use

6. Perspective-Reversible Figures in Microgravity ILSRA 2009-1047 • PI: Gilles Clement (FR) • Percept reversals during the visualization of perspective-reversible figures will be compared before, during and after long-term duration exposure to microgravity. The hypothesis is that the percept reversals of perspective-based reversible figures will be altered in microgravity compared to normal gravity, but that the percept reversal of 2D figures will not be changed. - Six free-floating subjects will be tested in six sessions while viewing ambiguous, perspective-reversible figures through a lightweight headset and a finger trackball connected to a laptop. ESA UNCLASSIFIED – For Official Use

7. Patterns of Acceleration and Navigation on board the ISS - ILSRA 2009-1048 • PI: Gilles Clement (FR) - This research is intended (1) to quantify the normal patterns of head-and-body acceleration experienced by astronauts during adaptation to microgravity, and (2) to examine the navigation strategies employed by the astronauts inside the ISS. - Linear and angular accelerations of the head and body will be continuously monitored using digital sensors and processors in compact, self-contained packages mounted on a headband and belt. Navigation strategies will be assessed using RFID technology. ESA UNCLASSIFIED – For Official Use

8. Straight Ahead in Microgravity - ILSRA 2009-1093 • PI: Gilles Clement (FR) - This project looks into the adaptive processes within the central nervous system to take into account the new environment and compute new spatial egocentric and world-centered representations or frames of reference. This project will measure and monitor how these frames change over time by investigating eye movements and perceptual reports. • Subjects will be tested during free-floating while looking at the apparent straight-ahead direction in darkness, fixating on imaginary targets at different distances along the apparent straight-ahead direction. Eye-tracking will be done during these protocol. A row of tactors embedded in a vest worn by the subject will also be used to assess the effects of vibrotactile feedback on spatial orientation and apparent straight-ahead. ESA UNCLASSIFIED – For Official Use

9. BICE (Biomechanical Quantification of Bone and Muscle Loading to Improve the Quality of 0g Countermeasure Prescriptions for Resistive Exercise) - ILSRA-2009-1080 • PI: Dr Ferrigno (IT) • The objective is to evaluate movement kinematics in weightlessness, comparing with the situation on ground in 1-g. Load paths will be evaluated as well as joint torques. Modelling of bone strain and muscle force is also intended. • Four different exercises (deadlift and different versions of Squats) using the advanced Resistance Exercise Device (aRED) will be examined, using the ELITE-S2 system. H/W is available on orbit. ESA UNCLASSIFIED – For Official Use

10. EKET (Metabolic and cardiovascular demands and effects of in-flight exercise countermeasures) - ILSRA-2009-873 • PI: Dr Hoffmann (DE) • The objective is to evaluate the kinetics of oxygen uptake during exercise on ISS. The hypothesis is that the changes in kinetics will follow changes in work capacity, and furthermore that modelling will allow to understanding of changes in metabolism in the working muscles and cardiovascular regulation. • Breath-by breath VO2-uptake will be measured during treadmill running or cycling (during regular training sessions) using a new portable (wearable) oxygen uptake system, and during fitness tests using the Portable PFS. ESA UNCLASSIFIED – For Official Use

11. Effect of microgravity on cartilage morphology and biology - ILSRA-2009-0994 PI: Prof. Brueggemann (DE) Objective: Investigate the effects of microgravity on articular cartilage health & cartilage metabolism to assess the risk of cartilage degeneration during space mission Magnetic Resonance Imaging of the knee cartilage, pre-flight and two times post-flight, to measeure thickness and volume Desired to also get blood and urine samples on orbit (x2): in order to measure biomarkers of cartilage metabolism ESA UNCLASSIFIED – For Official Use

12. Spaceflight induced neuroplasticity studied with advanced magnetic resonance imaging methods - ILSRA-2009-1062 • PI. Dr Wuyts (BE) • Advanced MRI methods (Diffusion tensor magnetic resonance imaging (DTI), Voxel Based Analysis (VBA) and Resting state Functional MRI (rfMRI)) will unravel spaceflight induced neuroplasticity (human central nervous system adaptation). The study will focus on specific regions of interest and fiber tracts that are expected to be involved in mainly neuro-vestibular and vestibuloautonomic processes. Cognition, mood and motor control will also be investigated. Resting state fMRI will be used to verify that the default state of the brain is undergoing neuroplastic changes • 3 Tesla MRI machine is needed, measurements before and three times after flight (R+5, -10, and -45) ESA UNCLASSIFIED – For Official Use

13. Consequences of Stress Challenges on Stress Response Systems and Immunity in Space: a multidisciplinary approach - ILSRA-2009-1121 • PI: Dr Chouker • This project aims at investigating the complex interaction of stress and the different biological stress-response systems on the “upstream” (brain) and “downstream” (immunity) functions in an integrative manner. • To this end, the different facets of the topic will be studied with a variety of methods, that include standard questionnaires and tests, as well as newly evolved methodological and technical means helping to monitor (patho-) physiological stress-responses and stress-dependent immune changes • Saliva, hair, exhaled air, blood samples; Tests/questionnaires; ECG and actigraph;pulse oxymetry; DTI (pre/post only) • Three in-flight sessions + pre- and post-flight measurements • This experiment has a heritage in the current “IMMUNO” experiment ESA UNCLASSIFIED – For Official Use

14. Monitoring the Cellular Immunity by in vitro Delayed Type Hypersensitivity assay on the ISS - ILSRA-2009-1149 • PI: Dr Chouker • The immune system consists of complex cellular mechanisms that are controlled by stress-dependent, neuroendocrine, inflammatory and metabolic pathways to protect the organism from disease. To maintain adequate immune responses, a wide variety of immune cells from the innate (e.g. granulocytes) and the adaptive immune system (e.g. T-lymphocytes) are orchestrated to fight against invading organisms and to control dormant virus load (e.g. Herpes). • In light of the dysfunction of the immune system in space flight, this project aims at to test global functional cellular immunity in a standardized way, using an in vitro assay to mirror “delayed type hypersensitivity (DTH)” immune reactions. • Saliva, blood samples (smear, and to be incubated with different antigens or standard / reference stimuli for the in-vitro DTH-like tests) ESA UNCLASSIFIED – For Official Use

15. Airway NO in space - ILSRA-2009-801 • PI: Dr Linnarsson (SE) • The experiments investigates the methodological and physiological mechanisms underlying the lowered base-line exhaled nitric oxide (NO) experienced in microgravity and at reduced ambient pressure, both conditions relevant for space missions. • Measurements of exhaled NO will be made at multiple flow rates in normal and in reduced ambient pressure (in an air lock). These data will be compared to ground controls. • PFS or PPFS. Niox MINO handheld analyzer (previously used on ISS) will be used. Three sessions on orbit with measurements at both normal (1000 hPa) and reduced (600-700 hPa) pressure. Blood samples pre- and post-flight (Endogenous NO synthase inhibitors and catecholamines including dopamine) ESA UNCLASSIFIED – For Official Use

16. BISE: Bone recovery and Impact exercise after Space Exposure – ILSRA-2009-976 and Assessment of bone turn-over and bone morphology during the early phase after microgravity exposure - is there a 're-entry bone loss‘ – ILSRA-2009-922 • PIs: Dr Rittweger (DE) and Dr Vico (FR) • Study bones changes due to microgravity and recovery process. Measurements will look at bone structures using 2 complementary devices (extreme pQCT and QCT), as well as bone markers in blood and urine with registered diet and activity. • Actimetry in-flight and during several occasions post-flight • Bone markers obtained from blood and urine • The itention is merge these experiments into one protocol, and subsequently aim to incorporate this into the current EDOS protocol which is a joint ESA/IBMP experiment. ESA UNCLASSIFIED – For Official Use

17. Validation of skin physiological changes in space and skin as a model for other body systems – ILSRA-2009-1142 • PIs: Dr Heinrich and Dr Rodic • Study skin aging in microgravity and consequently develop a mathematical model of aging skin. • In-flight measurements with corneometer, tewameter, visioscan, high resolution ultrasound 20Mhz, laser doppler for microcirculation; and additional measurements with cutometer, reviscometer, skin temperature probes pre- and post-flight • A pilot-study was conducted in the Astrolab mission (one subject). Among the most prominent results were an accelareted aging of the skin visible as increased coarsening of the skin fields as well as a dramatic degradation of the dermal connective tissue. ESA UNCLASSIFIED – For Official Use

18. 3-D Ballistocardiography in microgravity – ILSRA-2009-729 • The objective is to correlate cardiovascular parameters with ballisto-cardiography (BCG, a non-invasive technique) parameters obtained through a novel analysis of 3 dimensions (3D) movements of the human body that are due to the mechanical action of the beating heart and the ejection of blood in the arteries. • 3D-BCG assessment should provide new information on mechanical aspects of the cardiovascular system and information on autonomic adaptation in individual astronauts during long term space flights. • 3D-BCG will be recorded on free floating astronauts at rest, during asymmetric motor tasks and during imposed and controlled breathing protocols. Echocardiography, impedance cardiography and respiration will be recorded simultaneously or consecutively to help understanding the physiological determinants of the 3D-BCG curve and interpret its possible changes during the flight. The analysis of heart rate variability will help assessing the possible contribution of autonomic adaptation. ESA UNCLASSIFIED – For Official Use

19. DEX on Columbus Gravitational reference frames for Sensorimotor Performance: Reaching and Grasping – ILSRA-2009-989 • The human nervous system uses sensory information from a variety of sources to coordinate reaching movements of the hand with visual information about an object to be grasped. It is hypothesized that sensory and motor information is encoded in parallel in different reference frames within the neural networks of the brain. The weightless environment of Earth orbit, coupled with techniques borrowed from the field of virtual reality and the use of multisensory conflict, will be used to tease out the contribution of gravitationally-encoded internal representations to the overall behavior of aligning the hand to the target. • Head-Mounted Display to provide a virtual environment, tracking system, pointing device and trigger. To a large extent it is foreseen to use the GRIP (Dexterous Manipulation) H/W. • The subjects will aim and orient the pointing device in an environment indicating different degrees of roll. The experiment will be done in different sensory feedback conditions and with and without sensory conflict. ESA UNCLASSIFIED – For Official Use

20. Changes of circadian rhythm in humans during spaceflight – ILSRA-2009-395 • Maintaining synchronized circadian rhythms is important to health and well-being. It is hypothesized that long-term spaceflights significantly affect the synchronization of the circadian rhythm in humans due to changes of a non-24-hour light-dark cycle, reduced physical activity, body composition, and/or changes of heat transfer and thermoregulation in space. • Data on circadian rhythm obtained with a ”double sensor” (core temperature measurement) pre- in-, and post-flight shall be correlated with melatonin, a hormone that follows the circadian pattern. • The outcomes might be useful: (i) to understand the time course and basic principles of the adaptations of the human autonomic nervous system in space, (ii) to be able to adjust more adequately physical exercise as well as rest- and work shifts, and (iii) to foster adequate workplace illumination in the sense of occupational healthcare to humans in space. ESA UNCLASSIFIED – For Official Use

21. Assessment of inflight bone density, muscle density and muscle morphology changes in the forearm and lower leg and efficiency of countermeasures using peripheral quantitative computed tomography – ILSRA-2009-922 • Development and implementation of a X-ray peripheral CT (pQCT) device on the ISS. • The pQCT device will be used to monitor bone and muscle changes in long-duration spaceflight, and comparisons of these results to those drawn from muscle function testing, will be used to develop a set of optimum parameters for feedback on the effectiveness of countermeasure exercise. • The quantitative measurements will include (i) bone density, cortical thickness and area, strength-strain index at the radius and tibia and (ii) muscle cross-sectional area and muscle density in combination with muscle function parameters. ESA UNCLASSIFIED – For Official Use

22. MARES (Muscle Atrophy Research and Exercise System) ESA UNCLASSIFIED – For Official Use

23. MARES Measurements are done: • - with pre-programmed motions of the subject’s joint, • - driven by the MARES motor, • - while precisely measuring: Torque/Force, Velocity/Position, EMG activity, etc.; • With / without external electrical stimulation • The definition of these measurements is totally open to the scientist Extreme cases: • Muscle-group characterisation at 100% activation • Neural-drive activation: Motor control ESA UNCLASSIFIED – For Official Use

24. MARES in Columbus ESA UNCLASSIFIED – For Official Use

25. Portable Pulmonary Function System ESA UNCLASSIFIED – For Official Use

26. Portable Pulmonary Function System In 2005 ESA has initiated the development of a Portable Pulmonary Function System (PPFS). The PPFS is an evolution to the existing Pulmonary Function System (PFS*). PPFS is supporting a wide range of respiratory and cardiovascular measurements, complementing well the capabilities of the rack-mounted PFS. PPFS are a versatile instrument that can be used station wide for supporting both scientific research and crew health-monitoring activities. ESA UNCLASSIFIED – For Official Use

27. Portable Pulmonary Function System • Cardiac output, Pulmonary Blood Flow • Functional Residual Capacity • Lung Tissue volume (Volume of pulmonary capillary blood) • Oxygen uptake, VO2 • Total Lung Capacity • Breath-by-breath measurements of VO2, VCO2, VE • Respiratory exchange ratio VO2/VCO2. • Alveolar Ventilation • Vital Capacity • Dead Space Volume • Fractional inspiratory and expiratory volumes, FIO 2 and • FEO 2 , FICO 2 and FECO 2 • High Accuracy VO2, VCO2, VE • High Accuracy Respiratory exchange ratio VO2/VCO2. • Expiratory Reserve Volume • Forced Expired Spirometry • Residual Volume • Tidal Volume • Vital Capacity • Heart Rate • ST measurements • ST slope • Arrhythmia’s • Systolic/Diastolic/Mean Blood Pressure ESA UNCLASSIFIED – For Official Use

28. EPM – European Physiology Module ESA UNCLASSIFIED – For Official Use

29. Cardiolab - EPM ESA UNCLASSIFIED – For Official Use

30. Cardiolab - EPM ESA UNCLASSIFIED – For Official Use

31. Multi Electrode Electro-encephalogram Mapping Module- MEEMM ESA UNCLASSIFIED – For Official Use

32. MEEMM • EEG and Evoked Potentials measurements in stationary (MEEMM) or ambulatory mode (PORTEEM) • EMG measurements • Currently used in the Neurospat experiment (for EEG during different cognitive tasks and inputs. ESA UNCLASSIFIED – For Official Use

33. Mode Channels Bipolar interfaces Maximum bandwidth Maximum Sampling frequency Signal envelope Fast stationary Up to 32 Up to 32 1 Hz – 10 kHz 40 kHz +/- 25 mVpp Slow Stationary Up to 128 At least 32 0,01 Hz – 570 Hz 2.2 kHz 25 mVpp Ambulatory & Sleep Up to 16 Up to 4 0,03 Hz – 150 Hz 1 kHz TBD MEEMM ESA UNCLASSIFIED – For Official Use

34. Selection and implementation process – ESA view Announcement of Opportunity ESA Programme Peer Review and Feasibility assessment Selection (PB-HME) Definition SoW Development Implementation Exp Specific Agreement Joint science protocol ESA/Russia Joint documents Selection Into Russian Space Programme Development Russian Programme Implementation ESA UNCLASSIFIED – For Official Use

35. Contact information Biology: Jason.Hatton@esa.int Human Life Science: Patrik.Sundblad@esa.int ESA contact in Russia: Elena.Feichtinger@esa.int Please also keep Elena Lavrenko in cc: egl@tsniimash.ru ESA UNCLASSIFIED – For Official Use