Using and Distributing Spaceflight Data: The Johnson Space Center Life Sciences Data Archive

Life sciences data collected before, during and after spaceflight are valuable and often irreplaceable. The Johnson Space Center Life is hard to find, and much of the data (e.g. Sciences Data Archive has been designed to provide researchers, engineers, managers and educators interactive access to information about and data from human spaceflight experiments. The archive system consists of a Data Acquisition System, Database Management System, CD-ROM Mastering System and Catalog Information System (CIS). The catalog information system is the heart of the archive. The CIS provides detailed experiment descriptions (both written and as QuickTime movies), hardware descriptions, hardware images, documents, and data. An initial evaluation of the archive at a scientific meeting showed that 88% of those who evaluated the catalog want to use the system when completed. The majority of the evaluators found the archive flexible, satisfying and easy to use. We conclude that the data archive effectively provides key life sciences data to interested users

Pharmacotherapeutics of Intranasal Scopolamine: FDA Regulations and Procedures for Clinical Applications

Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during the early flight days of a space mission. Bioavailability of oral (PO) SMS medications is often low and highly variable; additionally, physiological changes in a microgravity environment exacerbate variability and decrease bioavailability. These factors prompted NASA to develop an intranasal dosage form of scopolamine (INSCOP) suitable for the treatment of SMS. However, to assure safety and efficacy of treatment in space, NASA physicians prescribe commercially available pharmaceutical products only. Development of a pharmaceutical preparation for clinical use must follow distinct clinical phases of testing, phase I through IV to be exact, before it can be approved by the FDA for approval for clinical use. After a physician sponsored Investigative New Drug (IND) application was approved by the FDA, a phase I clinical trial of INSCOP formulation was completed in normal human subjects and results published. The current project includes three phase II clinical protocols for the assessment of pharmacokinetics and pharmacodynamics (PK/PD), efficacy, and safety of INSCOP. Three clinical protocols that were submitted to FDA to accomplish the project objectives: 1) 002-A, a FDA Phase II dose ranging study with four dose levels between 0.1 and 0.4 mg in 12 subjects to assess PK/PD, 2) 002-B, a phase II clinical efficacy study in eighteen healthy subjects to compare efficacy of 0.2 (low dose) and 0.4 mg (high dose) INSCOP for prophylactic treatment of motion-induces (off-axis vertical rotation) symptoms, and (3) 002-C, a phase II clinical study with twelve subjects to determine bioavailability and pharmacodynamics of two doses (0.2 and 0.4 mg) of INSCOP in simulated microgravity, antiorthostatic bedrest. All regulatory procedures were competed that include certification for Good laboratory Procedures by Theradex , clinical documentation, personnel training, selection of clinical research operations contractor, data capturing and management, and annual reporting of results to FDA were successfully completed. Protocol 002-A was completed and sample and data analysis is currently in progress. Protocol 002-B is currently in progress at Dartmouth Hitchcock Medical Center and Protocol 002-C has been submitted to the FDA and will be implemented at the same contractor site as 002-A. An annual report was filed as required by FDA on the results of Protocol 002-A. Once all the three Phase II protocols are completed, a New Drug Administration application will be filed with FDA for Phase III clinical assessment and approval for marketing of the formulation. A commercial vendor will be identified for this phase. This is critical for making this available for treatment of SMS in astronauts and military personnel on duty. Once approved by FDA, INSCOP can be also used by civilian population for motion sickness associated with recreational travel and other ailments that require treatment with anticholinergic drugs

The Relationship Between Central Auditory Tests and Neurocognitive Domains in Adults Living With HIV

Objective: Tests requiring central auditory processing, such as speech perception-in-noise, are simple, time efficient, and correlate with cognitive processing. These tests may be useful for tracking brain function. Doing this effectively requires information on which tests correlate with overall cognitive function and specific cognitive domains. This study evaluated the relationship between selected central auditory focused tests and cognitive domains in a cohort of normal hearing adults living with HIV and HIV– controls. The long-term aim is determining the relationships between auditory processing and neurocognitive domains and applying this to analyzing cognitive function in HIV and other neurocognitive disorders longitudinally. Method: Subjects were recruited from an ongoing study in Dar es Salaam, Tanzania. Central auditory measures included the Gap Detection Test (Gap), Hearing in Noise Test (HINT), and Triple Digit Test (TDT). Cognitive measures included variables from the Test of Variables of Attention (TOVA), Cogstate neurocognitive battery, and Kiswahili Montreal Cognitive Assessment (MoCA). The measures represented three cognitive domains: processing speed, learning, and working memory. Bootstrap resampling was used to calculate the mean and standard deviation of the proportion of variance explained by the individual central auditory tests for each cognitive measure. The association of cognitive measures with central auditory variables taking HIV status and age into account was determined using regression models. Results: Hearing in Noise Tests and TDT were significantly associated with Cogstate learning and working memory tests. Gap was not significantly associated with any cognitive measure with age in the model. TDT explained the largest mean proportion of variance and had the strongest relationship to the MoCA and Cogstate tasks. With age in the model, HIV status did not affect the relationship between central auditory tests and cognitive measures. Age was strongly associated with multiple cognitive tests. Conclusion: Central auditory tests were associated with measures of learning and working memory. Compared to the other central auditory tests, TDT was most strongly related to cognitive function. These findings expand on the association between auditory processing and cognitive domains seen in other studies and support evaluating these tests for tracking brain health in HIV and other neurocognitive disorders

Proposed mechanism for reduced jugular vein flow in microgravity

Internal jugular flow is reduced in space compared with supine values, which can be associated with internal jugular vein (IJV) thrombosis. The mechanism is unknown but important to understand to prevent potentially serious vein thromboses on long duration flights. We used a novel, microgravity-focused numerical model of the cranial vascular circulation to develop hypotheses for the reduced flow. This model includes the effects of removing hydrostatic gradients and tissue compressive forces - unique effects of weightlessness. The IJV in the model incorporates sensitivity to transmural pressure across the vein, which can dramatically affect resistance and flow in the vein. The model predicts reduced IJV flow in space. Although tissue weight in the neck is reduced in weightlessness, increasing transmural pressure, this is more than offset by the reduction in venous pressure produced by the loss of hydrostatic gradients and tissue pressures throughout the body. This results in a negative transmural pressure and increased IJV resistance. Unlike the IJV, the walls of the vertebral plexus are rigid; transmural pressure does not affect its resistance and so its flow increases in microgravity. This overall result is supported by spaceflight measurements, showing reduced IJV area inflight compared with supine values preflight. Significantly, this hypothesis suggests that interventions that further decrease internal IJV pressure (such as lower body negative pressure), which are not assisted by other drainage mechanisms (e.g. gravity), might lead to stagnant flow or IJV collapse with reduced flow, which could increase rather than decrease the risk of venous thrombosis. &nbsp;</p