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At least 73 records · Page 4

Salivary Pharmacodynamics and Bioavailability of Promethazine in Human Subjects

The acute effects of exposure to microgravity include the development of space motion sickness which usually requires therapeutic intervention. The current drug of choice, promethazine (PMZ), has side effects which include nausea, drowsiness, dizziness, sedation and impaired psychomotor performance. In a ground-based study with commercial airline pilots and shuttle simulator trainers, we measured sleep and psychomotor performance variables, and physiological variables such as blood pressure and heart rate, as a function of circulating drug concentrations in the body. We evaluated a non-invasive sampling method (saliva) as a means of assessing pharmacodynamics following a single intramuscular (IM) dose of PMZ.

Putcha, Lakshmi↗

Neurochemical background and approaches in the understanding of motion sickness

The problems and nature of space motion sickness were defined. The neurochemical and neurophysiological bases of vestibular system function and of the expression of motion sickness wre reviewed. Emphasis was given to the elucidation of the neuropharmacological mechanisms underlying the effects of scopolamine and amphetamine on motion sickness. Characterization of the ascending reticular activating system and the limbic system provided clues to the etiology of the side effects of scopolamine. The interrelationship between central cholinergic pathways and the peripheral (autonomic) expression of motion sickness was described. A correlation between the stress of excessive motion and a variety of hormonal responses to that stress was also detailed. The cholinergic system is involved in the efferent modulation of the vestibular hair cells, as an afferent modulator of the vestibular nuclei, in the activation of cortical and limbic structures, in the expression of motion sickness symptoms and most likely underscores a number of the hormonal changes that occur in stressful motion environments. The role of lecithin in the regulation of the levels of neurotransmitters was characterized as a possible means by which cholinergic neurochemistry can be modulated.

Kohl, R. L.↗

Benefits, Consequences, and Uncertainties of Conventional (Exercise) Countermeasure Approaches

This presentation will review the pros, cons, and uncertainties of using exercise countermeasures in hypothetical long duration exploration missions. The use of artificial gravity and exercise will be briefly discussed. One benefit to continued use of exercise is related to our extensive experience with spaceflight exercise hardware and programming. Exercise has been a part of each space mission dating back to the 1960's when simple isometric and bungee exercises were performed in the Gemini capsule. Over the next 50 years, exercise hardware improved cumulating in today's ISS suite of exercise equipment: Cycle Ergometer with Vibration Isolation and Stabilization System (CEVIS), Treadmill (T2) and Advanced Resistive Exercise Device (ARED). Today's exercise equipment is the most robust ever to be flown in space and allows the variety and intensity of exercise that might reasonably be expected to maintain muscle mass and function, bone density and cardiovascular fitness. A second benefit is related to the large body of research literature on exercise training. There is a considerable body of supporting research literature including >40,000 peer reviewed research articles on exercise training in humans. A third benefit of exercise is its effectiveness. With the addition of T2 and ARED to our ISS exercise suite, crew member outcomes on standard medical tests have improved. Additionally exercise has other positive side effects such as stress relief, possible improvement of immune function, improved sleep, etc. Exercise is not without its consequences. The major cons to performance of in‐flight exercise are the time and equipment required. Currently crew are scheduled 2.5 hrs/day for exercise and there is considerable cost to develop, fly and maintain exercise hardware. While no major injuries have been reported on ISS, there is always some risk of injury with any form of exercise There are several uncertainties going forward; these relate mostly to the development of small compact robust effective exercise devices for the next generation of space vehicles. It is becoming increasingly apparent that high intensity exercise is required for maintenance of fitness and functional capability and so future hardware will need to be developed, tested and implemented that allow for a wide variety of exercise, at high intensity while likely involving low mass, volume and power. There are many unanswered issues related to the minimum number and type of exercise devices required for exploration, optimizing exercise prescriptions for these devices, whether a treadmill is absolutely required, and even whether any single countermeasure can adequately protect muscle, bone, cardiovascular and sensorimotor function.

Ploutz-Snyder, Lori↗

Stabilized NADH as a Countermeasure for Jet Lag

Current remedies for jet lag (phototherapy, melatonin, stimulant, and sedative medications) are limited in efficacy and practicality. The efficacy of a stabilized, sublingual form of reduced nicotin amide adenine dinucleotide (NADH, ENADAlert, Menuco Corp.) as a countermeasure for jet lag was examined. Because NADH increases cellular production of ATP and facilitates dopamine synthesis, it may counteract the effects of jet lag on cognitive functioning and sleepiness. Thirty-five healthy, employed subjects participated in this double-blind, placebo-controlled study. Training and baseline testing were conducted on the West Coast before subjects flew overnight to the East Coast, where they would experience a 3-hour time difference. Upon arrival, individuals were randomly assigned to receive either 20 mg of sublingual stabilized ADH (n=18) or identical placebo tablets (n=17). All participants completed computer-administered tests (including CogScreen7) to assess changes in cognitive functioning, mood, and sleepiness in the morning and afternoon. Jet lag resulted in increased sleepiness for over half the participants and deterioration of cognitive functioning for approximately one third. The morning following the flight, subjects experienced lapses of attention in addition to disruptions in working memory, divided attention, and visual perceptual speed. Individuals who received NADH performed significantly better on 5 of 8 cognitive and psychomotor test measures (P less than or equal to 0.5) and showed a trend for better performance on the other three measures (P less than or equal to .l0). Subjects also reported less sleepiness compared with those who received placebo. No adverse effects were observed with NADH treatment. Stabilized NADH significantly reduced jet lag-induced disruptions of cognitive functioning, was easily administered, and was found to have no adverse side effects.

Kay, Gary G.↗

Artificial Gravity as a Multi-System Countermeasure: Effects on Cognitive Function

The Space Flight Cognitive Assessment Tool for Windows (WinSCAT) is a medical requirement on the International Space Station, and its purpose is to evaluate cognitive functioning after physical insult (e.g., head trauma, decompression sickness, exposure to toxic gases, medication side effects). The current objective is to assess cognitive functioning in a long duration space mission analog environment where Artificial Gravity is being applied as a countermeasure in a Bed Rest study. Methods: Fifteen male subjects (8 treatment and 7 control) who participated in 21 days of -6 degree head-down bed rest were assessed. Three practice and three baseline WinSCAT test sessions were administered during the pre-bed rest phase of study participation. During the bed rest phase, the WinSCAT test was scheduled every other day, following the centrifuge, for a total of 10 test sessions. (The treatment group received 60 minutes of centrifugation each day during the 21 days of bed rest. The control subjects were strapped to the centrifuge for the same length of time as the treatment group but were not spun.) During the post-bed rest (reconditioning) phase, the test was administered 4 times. Results: Individual differences were found both within and between the treatment and control groups. After controlling for the number of subjects in each group, the treatment group accounted for more off-nominal WinSCAT scores than the control group. Conclusions:There is some preliminary evidence that centrifuge spinning might negatively impact cognitive functioning. However, due to sample size limitations, it cannot be ascertained whether there were significant differences in cognitive performance between the treatment and control groups. If centrifugation had a negative effect on cognitive functioning, consistent decrements would be expected to be found with all treatment subjects across time. Individual differences in underlying cognitive ability and motivation level are other possible explanations for the results found in this study.

Sipes, Walter E.↗

Therapeutic effects of antimotion sickness medications on the secondary symptoms of motion sickness

In addition to nausea and vomiting, motion sickness involves slowing of brain waves, loss of performance, inhibition of gastric motility and the Sopite Syndrome. The therapeutic effects of antimotion sickness drugs on these reactions were evaluated. The subjects were rotated to the M-III end-point of motion sickness. Intramuscular (IM) medications were then administered. Side effects before and after rotation were reported on the Cornell Medical Index. Brain waves were recorded on a Grass Model 6 Electroencephalograph (EEG), and gastric emptying was studied after an oral dose of 1 mCi Technetium 99m DTPA in 10 oz. isotonic saline. An increase in dizziness and drowsiness was reported with placebo after rotation. This was not prevented by IM scopolamine 0.1 mg or ephedrine 25 mg. EEG recordings indicated a slowing of alpha waves with some thea and delta waves from the frontal areas after rotation. IM ephedine and dimenhydrinate counteracted the slowing while 0.3 mg scopolamine had an additive effect. Alterations of performance on the pursuit meter correlated with the brain wave changes. Gastric emptying was restored by IM metoclopramide. Ephedrine IM but not scopolamine is effective for some of the secondary effects of motion sickness after it is established.

Wood, C. D.↗

Lack of effects of astemizole on vestibular ocular reflex, motion sickness, and cognitive performance in man

Astemizole was orally administered to 20 subjects in a randomized, double-blind design to assess the efficacy of this peripherally active antihistamine as an antimotion sickness drug possessing no central side-effects. Measures of vestibular ocular reflex (VOR) were made to evaluate the agent as a selective vestibular depressant. Following one week of orally administered astemizole (30 mg daily), a Staircase Profile Test, a VOR test, and a variety of tests of cognitive performance were administered. These tests revealed no statistically significant effects of astemizole. This leads to the conclusion that, although the drug probably reaches the peripheral vestibular apparatus in man by crossing the blood-vestibular barrier, a selective peripheral antihistamine (H1) action is inadequate to control motion sickness induced through cross-coupled accelerative semicircular canal stimulation in a rotating chair.

Kohl, Randall L.↗

Pharmaceutical Product Development: Intranasal Scopolamine (INSCOP) Metered Dose Spray

Motion sickness (MS) has been a problem associated with space flight, the modern military and commercial air and water transportation for many years. Clinical studies have shown that scopolamine is the most effective medication for the prevention of motion sickness (Dornhoffer et al, 2004); however, the two most common methods of administration (transdermal and oral) have performance limitations that compromise its utility. Intranasal administration offers a noninvasive treatment modality, and has been shown to counter many of the problems associated with oral and transdermal administration. With the elimination of the first pass effect by the liver, intranasal delivery achieves higher and more reliable bioavailability than an equivalent oral dose. This allows for the potential of enhanced efficacy at a reduced dose, thus minimizing the occurrence of untoward side effects. An Intranasal scopolamine (INSCOP) gel formulation was prepared and tested in four ground-based clinical trials under an active Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Although there were early indicators that the intranasal gel formulation was effective, there were aspects of formulation viscosity and the delivery system that were less desirable. The INSCOP gel formulation has since been reformulated into an aqueous spray dosage form packaged in a precise, metered dose delivery system; thereby enhancing dose uniformity, increased user satisfaction and palatability, and a potentially more rapid onset of action. Recent reports of new therapeutic indications for scopolamine has prompted a wide spread interest in new scopolamine dosage forms. The novel dosage form and delivery system of INSCOP spray shows promise as an effective treatment for motion sickness targeted at the armed forces, spaceflight, and commercial sea, air, and space travel markets, as well as prospective psychotherapy for mental and emotional disorders.

Putcha, Lakshmi↗

Bioavailability and Pharmacodynamics of Promethazine in Human Subjects

The acute effects of exposure to microgravity include the development of space motion sickness, which usually requires therapeutic intervention. The current drug of choice, promethazine (PMZ), is available to astronauts in three different dosage forms during space flight; its side effects include nausea, dizziness, sedation and impaired psychomotor performance. This ground-based study is designed to validate flight-suitable methods for pharmacodynamic evaluation of PMZ and to estimate bioavailability and pharmacodynamics of PMZ. Experimental design consists of intramuscular administration of three doses of PMZ (12.5,25 and 50 mg) and placebo in a randomized double blind fashion to human subjects and collecting blood, urine and saliva samples for 72 h. Subjects also complete cognitive performance test batteries, WinSCAT (Windows based Space Cognitive Assessment Test) and ARES (ANAM Readiness Evaluation System). Preliminary results indicate a significant relationship (p=9.88e-05) between circulating PMZ levels and cognitive performance parameters. Time to accurately complete memory tasks increases significantly with concentrations; higher concentrations also increase response time and decrease accuracy of substitution and matching tasks. AUC and half-life estimates for PMZ ranged between 0.12 and 1.7 mg.h/L and 15 and 50 h, respectively. These preliminary results indicate that PMZ may exhibit dose-dependent pharmacokinetics in humans; also, WinSCAT and ARES are sensitive for pharmacodynamic assessment of PMZ, and may be applicable for assessing the pharmacodynamics of other neurocognitive drugs.

Boyd, J. L.↗

Remote Sensing of the Urban Heat Island Effect: Assessment of Risks to Human Health and Development of Mitigation Strategies for Sustainable Cities

The growth of cities, both in population and in areal extent, appears as an inexorable process. Urbanization continues at a rapid rate, and it is estimated that by the year 2025, 80% of the world's population will live in cities. One of the more egregious side effects of urbanization is the deterioration in air quality as a result of increased vehicular traffic, industrialization and related activities. In the United States alone, under the more stringent air quality guidelines established by the U.S. Environmental Protection Agency (EPA) in 1997, nearly 300 counties in 34 states will not meet the new air quality standards for ground level ozone. The mitigation of one the physical/environmental characteristics of urbanization known as the urban heat island (UHI) effect, is now being looked at more closely as a possible way to bring down ground level ozone levels in cities and assist states in improving air quality. The UHI results from the replacement of "natural" land covers (e.g., trees, grass) with urban land surface types, such as pavement and buildings. Heat stored in these surfaces is released into the air and results in a "dome" of elevated air temperatures that presides over cities. The effect of this dome of elevated air temperatures is known as the UHI, which is most prevalent about 2-3 hours after sunset on days with intense solar radiation and calm winds. Given the local and regional impacts of the UHI, there are significant potential affects on human health, particularly as related to heat stress and ozone on body temperature regulation and on the cardiovascular and respiratory systems. In this study we are using airborne and satellite remote sensing data to analyze how differences in the urban landscape influence or drive the development of the UHI over four U.S. cities. Additionally, we are assessing what the potential impact is on risks to human health, and developing mitigation strategies to make urban areas more environmentally sustainable.

Quattrochi, Dale A.↗

High Spatial Resolution Thermal Remote Sensing of the Urban Heat Island Effect: Assessment of Risks to Human Health and Development of Mitigation Strategies for Sustainable Cities

The growth of cities, both in population and in areal extent, appears as an inexorable process. Urbanization continues at a rapid rate, and it is estimated that by the year 2025, 80% of the world's population will live in cities. One of the more egregious side effects of urbanization is the deterioration in air quality as a result of increased vehicular traffic, industrialization and related activities. In the United States alone, under the more stringent air quality guidelines established by the U.S. Environmental Protection Agency (EPA) in 1997, nearly 300 counties in 34 states will not meet the new air quality standards for ground level ozone. The mitigation of one the physical/environmental characteristics of urbanization known as the urban heat island (UHI) effect, is now being looked at more closely as a possible way to bring down ground level ozone levels in cities and assist states in improving air quality. The UHI results from the replacement of "natural" land covers (e.g., trees, grass) with urban land surface types, such as pavement and buildings. Heat stored in these surfaces is released into the air and results in a "dome" of elevated air temperatures that presides over cities. The effect of this dome of elevated air temperatures is known as the UHI, which is most prevalent about 2-3 hours after sunset on days with intense solar radiation and calm winds. Given the local and regional impacts of the UHI, there are significant potential affects on human health, particularly as related to heat stress and ozone on body temperature regulation and on the cardiovascular and respiratory systems. In this study we are using airborne and satellite remote sensing data to analyze how differences in the urban landscape influence or drive the development of the UHI over four U.S. cities. Additionally, we are assessing what the potential impact is on risks to human health, and developing mitigation strategies to make urban areas more environmentally sustainable.

Quattrochi, Dale A.↗

Complexity and Pilot Workload Metrics for the Evaluation of Adaptive Flight Controls on a Full Scale Piloted Aircraft

Flight research has shown the effectiveness of adaptive flight controls for improving aircraft safety and performance in the presence of uncertainties. The National Aeronautics and Space Administration's (NASA)'s Integrated Resilient Aircraft Control (IRAC) project designed and conducted a series of flight experiments to study the impact of variations in adaptive controller design complexity on performance and handling qualities. A novel complexity metric was devised to compare the degrees of simplicity achieved in three variations of a model reference adaptive controller (MRAC) for NASA's F-18 (McDonnell Douglas, now The Boeing Company, Chicago, Illinois) Full-Scale Advanced Systems Testbed (Gen-2A) aircraft. The complexity measures of these controllers are also compared to that of an earlier MRAC design for NASA's Intelligent Flight Control System (IFCS) project and flown on a highly modified F-15 aircraft (McDonnell Douglas, now The Boeing Company, Chicago, Illinois). Pilot comments during the IRAC research flights pointed to the importance of workload on handling qualities ratings for failure and damage scenarios. Modifications to existing pilot aggressiveness and duty cycle metrics are presented and applied to the IRAC controllers. Finally, while adaptive controllers may alleviate the effects of failures or damage on an aircraft's handling qualities, they also have the potential to introduce annoying changes to the flight dynamics or to the operation of aircraft systems. A nuisance rating scale is presented for the categorization of nuisance side-effects of adaptive controllers.

pilot workload metrics↗

A Comparison of Cilostazol and Pentoxifylline for Treating Intermittent Claudication

A randomized, double-blind, placebo-controlled, parallel-group, phase III multicenter trial was performed to evaluate the relative efficacy and safety of cilostazol and pentoxifylline. The study included 54 outpatient vascular clinics, including sites at Air Force, Veterans Affairs, tertiary care, and university hospitals in the United States. Of 922 consenting patients, 698 met the inclusion criteria, were randomized, and received treatment with either cilostazol 100 mg P0 twice a day, pentoxifylline 400 mg PO 3 times a day, or placebo. Treatment was double-dummy to ensure study blindness. Efficacy was primarily established by maximal walking distance (MWD), measured with constant-speed, variable-grade treadmill testing, assessed at baseline and at 4, 8, 12, 16, 20, and 24 weeks. Mean MWD of cilostazol-treated patients (n=227) was significantly improved at every visit compared with patients who received pentoxifylline (n=232) or placebo (n=239). After 24 weeks of cilostazol, mean MWD increased 53.9% (107.3 m) from baseline, and the effect had not plateaued. This was better (P < 0.001) than the 30.4% (64.4 m) MWD improvement with pentoxifylline. MWD improvement with pentoxifylline was similar (P = 0.82) to that of placebo (64.7 m). Deaths and serious adverse event rates were similar in each group. Common side effects included headache (27.8% with cilostazol, 11.2% with pentoxifylline, 11.7% with placebo), palpitations (17.2% with cilostazol, 2.2% with pentoxifylllne, 1.3% with placebo), and abnormal stools. Cilostazol was significantly better than pentoxifylline or placebo for increasing walking distances; pentoxifylline was no better than placebo.

Dawson, David L.↗

Heat flux instrumentation for HYFLITE thermal protection system

Tasks performed in this project were defined in a September 9, 1994 meeting of representatives of Vatell, NASA Lewis and Virginia Tech. The overall objective agreed upon in the meeting was 'to demonstrate the viability of thin film techniques for heat flux and temperature sensing in HYSTEP thermal protection systems'. We decided to attempt a combination of NASA's and Vatell's best heat flux sensor technology in a sensor which would be tested in the Vortek facility at Lewis early in 1995. The NASA concept for thermocouple measurement of surface temperature was adopted, and Vatell methods for fabrication of sensors on small diameter substrates of aluminum nitride were used to produce a sensor. This sensor was then encapsulated in a NARloy-Z housing. Various improvements to the Vatell substrate design were explored without success. The basic NASA and Vatell sensor layouts were analyzed by finite element modeling, in an attempt to better understand the effects of material properties, dimensions and thermal differential element location on sensor symmetry, bandwidth and sensitivity. This analysis showed that, as long as the thermal resistivity of the thermal differential element material is much larger (10X) than that of the substrate material, the simplest arrangement of layer is best. During calibration of the sensor produced in this project, undesirable side-effects of combining the heat flux and temperature sensor return leads were observed. The sensor did not cleanly separate the heat flux and temperature signals, as sensors with four leads have consistently done before. Task 7 and 8 discussed in the meeting will be performed with a continuation of funding in 1995. The following is a discussion of each of the tasks performed as outlined in the statement of work dated september 26, 1994. Task 1A was added to cover further investigation into the NASA sensor concept.

Diller, T. E.↗

Effects of positive ion implantation into antireflection coating of silicon solar cells

The state of technological development of Si solar cells for highest obtained efficiency and radiation resistance is summarized. The various theoretical analyses of Si solar cells are reviewed. It is shown that factors controlling blue response are carrier diffusion length, surface recombination, impurity concentration profile in surface region, high level of surface impurity concentration (degeneracy), reflection coefficient of oxide, and absorption coefficient of Si. The theory of ion implantation of charge into the oxide antireflection coating is developed and side effects are discussed. The experimental investigations were directed at determining whether the blue response of Si solar cells could be improved by phosphorus ion charges introduced into the oxide antireflection coating.

Middleton, A. E.↗

Development of Acoustic Mufflers for Cabin Noise Reduction in Orion Spacecraft

Controlling cabin acoustic noise levels in the Crew Module (CM) of the Orion spacecraft is critical to ensure adequate speech intelligibility, to avoid fatigue, and prevent any possibility of temporary and permanent hearing loss to the crew. The primary source of cabin noise for the on-orbit phase of the mission is from the Environmental Control and Life Support System (ECLSS) which recycles and conditions breathing air and maintains cabin pressurization through its duct network and components. Unfortunately, as a side effect, noise from the ECLSS fans propagates through theses ducts and emanate into the cabin habitable volume via the ECLSS inlet and outlets. To mitigate excessive duct-borne noise, two ECLSS mufflers have been designed to provide significant acoustic transmission loss (TL) so that the cabin noise requirements can be met. Each muffler is meant to be installed in the ducting of the ECLSS air inlet and outlet sides, respectively. Packaging constraints and tight volume requirements necessitated the mufflers to be of complex geometry and compatible with the bends of the ECLSS duct layout. To design and characterize the acoustic performance of the inlet and outlet mufflers, computational acoustic models were developed using the Finite Element Method (FEM) with 𝑤𝑎𝑣𝑒଺ vibroacoustic software. Characterization of the acoustic material and perforations in the mufflers were addressed with poroelastic theory. Once the mufflers were designed on paper and its TL predicted, prototypes of these mufflers were created using additive manufacturing. The muffler prototypes were subsequently tested for acoustic TL in the laboratory with various con-figurations of acoustic materials. Comparing the analytical predictions to the test performance yielded excellent correlation for acoustic TL and demonstrated significant broadband noise attenuation. The ECLSS mufflers are currently scheduled to be installed on the Artemis II Crew Module (CM) of the Orion spacecraft and will provide significant cabin comfort to crew during the mission.

Indranil Dandaroy↗

Personalized Risk Assesment for Adverse Drug Reactions and Treatment Failures

As NASA and other space agencies prepare for future long-term space missions beyond the LEO, the cumulative impact of risk factors encountered in space increases substantially rising concerns about astronauts health. Application of on-board medications to mitigate clinical symptoms associated with certain medical conditions and illnesses is the first line of response to ensure sustainable health and performance of crew. Unfortunately, very limited research has been conducted to determine efficacy of the earth-based pharmaceuticals in a microgravity environment. In some instances, orally administered medications taken during flight were reported to be less effective than expected. Evaluation of series of experiments involving astronauts from shuttle flights shows notable individual variability to several pharmaceuticals during flight. These data provide reasonable assumption of perturbation in CYP450 enzymes during spaceflight, which contribute to the hepatic metabolism of the majority of drugs and therefore may have significant effects on therapeutic efficacy and increase treatment-related toxicity. The genes encoding the CYP450 enzymes are highly variable in humans. Inheritable variations of CYP450 hepatic metabolizer enzymes and transport proteins play a crucial role in the inter-individual variability of drug efficiency and risks of adverse drug reactions. Additionally, there are some reports that document changes in the levels of production of drug-metabolizing enzymes in microgravity. Therefore, in order to provide a safe and effective pharmaceutical treatment in space, medications selection should be based not only on the specific efficacy of medications but also on the individual drug sensitivity and flight-induced changes in metabolism of astronauts chosen for a particular mission. To our knowledge, there was no pre-flight drug sensitivity testing on a genetic level for any of the previous manned NASA space missions. Therefore, technologies capable of predicting and managing medication efficacy, side effects, and toxicity of drugs based on individual genetic variability of crew members are increasingly needed. In this report, we present results of testing the market available Personalized Prescribing System (PPS), a comprehensive, non-invasive solution for safer, targeted medication management for every crew member. Statistical accuracy and simplicity of non-invasive sample analysis demonstrate the feasibility of drug sensitivity assessment and record-keeping tool for flight surgeons and astronauts in applying the recommended medications for situations arising in flight. The information on individual drug sensitivity will translate into personalized risk assessment for adverse drug reactions and treatment failures for each drug from the medication kit as well as predefined outcome. This will address the HHC’s raised “Concern of Clinically Relevant Unpredicted Effects of Medication” as recently updated.

medications↗

Estimation of Optimum Stimulus Amplitude for Balance Training using Electrical Stimulation of the Vestibular System

Sensorimotor changes such as posture and gait instabilities can affect the functional performance of astronauts after gravitational transitions. Sensorimotor Adaptability (SA) training can help alleviate decrements on exposure to novel sensorimotor environments based on the concept of 'learning to learn' by exposure to varying sensory challenges during posture and locomotion tasks (Bloomberg 2015). Supra-threshold Stochastic Vestibular Stimulation (SVS) can be used to provide one of many challenges by disrupting vestibular inputs. In this scenario, the central nervous system can be trained to utilize veridical information from other sensory inputs, such as vision and somatosensory inputs, for posture and locomotion control. The minimum amplitude of SVS to simulate the effect of deterioration in vestibular inputs for preflight training or for evaluating vestibular contribution in functional tests in general, however, has not yet been identified. Few studies (MacDougall 2006; Dilda 2014) have used arbitrary but fixed maximum current amplitudes from 3 to 5 mA in the medio-lateral (ML) direction to disrupt balance function in healthy adults. Giving this high level of current amplitude to all the individuals has a risk of invoking side effects such as nausea and discomfort. The goal of this study was to determine the minimum SVS level that yields an equivalently degraded balance performance. Thirteen subjects stood on a compliant foam surface with their eyes closed and were instructed to maintain a stable upright stance. Measures of stability of the head, trunk, and whole body were quantified in the ML direction. Duration of time they could stand on the foam surface was also measured. The minimum SVS dosage was defined to be that level which significantly degraded balance performance such that any further increase in stimulation level did not lead to further balance degradation. The minimum SVS level was determined by performing linear fits on the performance variable at different stimulation levels. Results from the balance task suggest that there are inter-individual differences and the minimum SVS amplitude was found to be in the range of 1 mA to 2.5 mA across subjects. SVS resulted in an average decrement of balance task performance in the range of 62%-73% across different measured variables at the minimum SVS amplitude in comparison to the control trial (no stimulus). Training using supra-threshold SVS stimulation is one of the sensory challenges used for preflight SA training designed to improve adaptability to novel gravitational environments. Inter-individual differences in response to SVS can help customize the SA training paradigms using minimal dosage required. Another application of using SVS is to simulate acute deterioration of vestibular sensory inputs in the evaluation of tests for assessing vestibular function.

Goel, R.↗