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INTRODUCTION: Real-time cardiovascular imaging during hypergravity exposure has been historically limited by technological and physical challenges. Previous efforts at sonographic hypergravity imaging have used fixed ultrasound probes; the use of hand-held ultrasound, particularly performed by minimally trained laypersons, has been less explored. Here we will discuss handheld sonography to self-visualize carotid vascular and cardiac changes during hypergravity. METHODS: Three subjects with variable ultrasound experience ranging from no familiarity to extensive clinical experience used handheld ultrasound at rest and under stepwise +G z hypergravity exposures (maximum +3.5 G z ) to visualize carotid vascular changes. Subxiphoid cardiac ultrasound was obtained by the most experienced subject. Subjects had variable prior hypergravity experience; all were trained in anti-G straining techniques. Sonographically inexperienced subjects underwent a brief (< 5 min) familiarization with the ultrasound probe, user interface, and desirable viewing window immediately prior to centrifugation; real-time coaching was provided. Ultrasound images were correlated to self-reported symptoms and hemodynamic data. RESULTS: Handheld ultrasound performed as desired; all subjects were successful at obtaining ultrasound images with adequate capture of windows of interest. Subxiphoid imaging efforts were limited by probe overheating and associated with variable quality of imaging due to probe displacement from straining techniques; the subject noted transient, mild discomfort and ecchymosis after imaging in the subxiphoid region. DISCUSSION: Even individuals with minimal or no ultrasound experience successfully obtained usable images under centrifuge conditions. While there were some limitations, this technical demonstration provides initial validation of handheld sonography as an available tool for real-time cardiovascular imaging in a hypergravity environment. Blue RS, Ong KM. Handheld sonographic cardiovascular imaging under hypergravity conditions . Aerosp Med Hum Perform. 2024; 95(3):158-164.

INTRODUCTION: Human access to space is expanding rapidly in the commercial environment, with various private companies offering commercial flights to spaceflight participants (SFPs). SFPs are more likely than career astronauts to have medical conditions novel to spaceflight and may not have undergone as rigorous a medical screening process as that used for career astronauts, representing new and unstudied risks in the spaceflight environment. We report participation of a subject with recent median sternotomy for aortic valve replacement and atrial septal defect closure in centrifuge-simulated dynamic phases of orbital and suborbital spaceflight. CASE REPORT: A 40-yr-old man with a history of congenital bicuspid aortic valve and atrial septal defect with successful repair 8 mo prior participated in an ongoing human centrifuge research study. The subject had the opportunity to participate in up to five centrifuge runs in an 8-h period, with profiles simulating commercial spaceflight. Maximum exposures included +4.0 G z , +4.5 G x , 6.1 G resultant, and maximum onset rate < 0.5 G z · s -1 and +1 G x · s -1 . Physiological data acquisition included hemodynamics, electrocardiogram, neurovestibular exams, and postrun questionnaires covering motion sickness, disorientation, and similar. The subject tolerated the physiological aspects of hypergravity well, noting progressive sternal pain with increasing +G x , ultimately leading him to opt out of the final profile. DISCUSSION: Postcardiothoracic surgery risks to SFPs are largely unknown, especially within 12 mo of a significant surgical procedure. This case provides an approach for risk stratification, preparticipation evaluation, and medical management of a postsurgical patient with significant cardiac history in spaceflight and analog environments. Fernandez WL, Blue RS, Harrison MF, Powers W, Shah R, Auñón-Chancellor S. Centrifuge-simulated spaceflight after aortic valve replacement and atrial septal defect repair . Aerosp Med Hum Perform. 2024; 95(2):123-131.

Human spaceflight is entering a time of markedly increased activity fueled by collaboration between governmental and private industry entities. This has resulted in successful mission planning for destinations in low Earth orbit, lunar destinations (Artemis program, Gateway station) as well as exploration to Mars. The planned construction of additional commercial space stations will ensure continued low Earth orbit presence and destinations for science but also commercial spaceflight participants. The human in the journey to space is exposed to numerous environmental challenges including increased gravitational forces, microgravity, altered human physiology during adaptation to weightlessness in space, altered ambient pressure, as well as other important stressors contingent on the type of mission and destination. This chapter will cover clinically important aspects relevant to lung function in a normally proceeding mission; emergency scenarios such as decompression, fire, etc., will not be covered as these are beyond the scope of this review. To date, participation in commercial spaceflight by those with pre-existing chronic medical conditions is very limited, and hence, close collaboration between practicing pulmonary specialists and aerospace medicine specialists is of critical importance to guarantee safety, proper clinical management, and hence success in these important endeavors., Competing Interests: None declared., (Thieme. All rights reserved.)

BACKGROUND: While catastrophic spaceflight events resulting in crew loss have occurred, human spaceflight has never suffered an on-orbit fatality with survival of other crewmembers on board. Historical plans for management of an on-orbit fatality have included some consideration for forensic documentation and sample collection, human remains containment, and disposition of remains; however, such plans have not included granular detailing of crew or ground controller actions. The NASA Johnson Space Center Contingency Medical Operations Group, under authority from the Space and Occupational Medicine Branch, the Space Medicine Operations Division, and the Human Health and Performance Directorate, undertook the development of a comprehensive plan, including an integrated Mission Control Center response for flight control teams and Flight Surgeons for a single on-orbit crew fatality on the International Space Station (ISS) and subsequent events. Here we detail the operational considerations for a crew fatality should it occur during spaceflight onboard the ISS, including forensic and timeline constraints, behavioral health factors, and considerations for final disposition of decedent remains. Future considerations for differential survival and crewmember fatality outside of low-Earth orbit operations will additionally be discussed, including consideration of factors unique to planetary and surface operations and disposition limitations in exploration spaceflight. While the efforts detailed herein were developed within the constraints of the ISS concept of operations, future platforms may benefit from the procedural validation and product verifications steps described. Ultimately, any response to spaceflight fatality must preserve the goal of handling decedent remains and disposition with dignity, honor, and respect. Stepaniak PC, Blue RS, Gilmore S, Beven GE, Chough NG, Tsung A, McMonigal KA, Mazuchowski EL II, Bytheway JA, Lindgren KN, Barratt MR. Operational considerations for crew fatality on the International Space Station . Aerosp Med Hum Perform. 2023; 94(9):705-714.

INTRODUCTION: Prior study has indicated that individuals of varied age, medical history, and limited-to-no experience tolerate spaceflight conditions. We sought to expand upon the understanding of layperson response to hypergravity conditions expected in commercial spaceflight by exposing subjects, following minimal training, to centrifuge-simulated, high-fidelity commercial spaceflight profiles. We further explored how these individuals perform in simulated operational activities during and following hypergravity. METHODS: Volunteer subjects participated in up to five centrifuge runs (maximum +4.0 G z , +4.5 G x , 6.1 G resultant; onset rate <0.5 G z · s -1 , ≤1 G x · s -1 ). Profiles included two winged spacecraft simulations with sequential and combined +G x /+G z and two capsule simulations representing nominal +G x launch and reentry. The final profile simulated a capsule launch abort, with a more dynamic cycling of +G x exposures and oscillatory multi-axis exposures simulating parachutes and water motion. Touchscreen tablets were used to administer pattern-replication tasks during and after profiles. RESULTS: A total of 46 subjects participated, including 4 diabetics and 9 with cardiac disease. There was increased frequency of motion sickness, subjectively associated with capsule-type profiles, and increased termination of participation compared to prior studies. There was no association between medical history, age, sex, or motion sickness history and tolerance or noncompletion. Tablet test errors were common; accuracy and time to completion were associated with age. There was no association between any time metric or accuracy and sex. DISCUSSION: This study improves understanding of layperson tolerance in commercial spaceflight analog conditions, and the capsular profiles broaden the applicability of the findings. The frequency of task errors highlights the potential for mistakes in operational activities when performed by laypersons. Blue RS, Ong KM, Ray K, Menon A, Mateus J, Auñón-Chancellor S, Shah R, Powers W. Layperson physiological tolerance and operational performance in centrifuge-simulated spaceflight . Aerosp Med Hum Perform. 2023; 94(8):584-595.

INTRODUCTION: Inhalation of hydrazine or hydrazine-derivative (for example, monomethylhydrazine) vapors during spaceflight operations remains a risk to crew and ground support personnel. Here we sought to provide an evidence-based approach to inform acute clinical treatment guidelines for inhalational exposures during a noncatastrophic contingency spaceflight recovery scenario. METHODS: A review of published literature was conducted concerning hydrazine/hydrazine-derivative exposure and clinical sequelae. Priority was given to studies that described inhalation though studies of alternative routes of exposure were additionally reviewed. Where possible, human clinical presentations were prioritized over animal studies. RESULTS: Rare human case reports of inhalational exposure and multiple animal studies provide evidence of varied clinical sequelae, including mucosal irritation, respiratory concerns, neurotoxicity, hepatotoxicity, hemotoxicity (including Heinz body development and methemoglobinemia), and longitudinal risks. In an acute timeframe (minutes to hours), clinical sequelae are likely to be limited to mucosal and respiratory risk; neurological, hepatotoxic, and hemotoxic sequelae are unlikely without recurrent, longitudinal, or noninhalational exposure. CONCLUSIONS: Acute clinical management should focus on likely clinical concerns as supported by existing data; recovery medical personnel should be prepared to manage mucosal irritation and respiratory concerns, including the potential need for advanced airway management. There is little evidence supporting the need for acute interventions for neurotoxicity and there is no evidence that acute hemotoxic sequelae would drive the need for on-scene management of methemoglobinemia, Heinz body development, or hemolytic anemia. Training that overemphasizes neurotoxic or hemotoxic sequelae or specific treatments for such conditions potentially raises the risk for inappropriate treatment or operational fixation. Hanshaw BC, Ryder VE, Johansen BD, Pattarini JM, Nguyen HN, Nowadly CD, Blue RS. Spaceflight recovery considerations for acute inhalational exposure to hydrazines . Aerosp Med Hum Perform. 2023; 94(7):532-543.

INTRODUCTION: With increasing engagement of commercial spaceflight participants in spaceflight activities, the evaluation of individuals with medical conditions not previously characterized in the spaceflight environment is of particular interest. Factors such as acceleration forces experienced during launch, reentry, and landing of spacecraft could pose an altered risk profile in some individuals due to known disease. Bleeding diatheses present a unique concern in the spaceflight environment given hypergravity exposure and, particularly, the potential for injury resulting from transient or impact acceleration. CASE REPORT: A 26-yr-old Caucasian man with severe hemophilia A and no detectable endogenous Factor VIII (FVIII) volunteered for participation in hypergravity exposures simulating spaceflight. His treatment regimen included 50 IU · kg -1 FVIII-Fc fusion protein intravenous administration every 96 h, with supplemental FVIII administration as needed for injury or bleeding. The subject experienced two profiles at the National Aerospace Training and Research Center (NASTAR), with maximum exposure +4.0 G z , +4.5 G x , 6.1 G resultant, and maximum onset rate <0.5 G z · s -1 and +1 G x · s -1 . The subject reported no abnormal events during the profiles other than brief mild vertigo. No petechial hemorrhage, ecchymosis, or other bleeding was noted during or after profiles. Supplemental FVIII was not required before, during, or after exposure. DISCUSSION: Inherited bleeding disorders present several potential concerns that must be evaluated prior to spaceflight participation. Cautious review and management of medical history, adherence and barriers to treatment, duration of spaceflight and longitudinal management concerns, and a thorough and detailed risk/benefit assessment may provide a future pathway for inclusion of individuals with hematological disorders in commercial spaceflight. Reeves IA, Blue RS, Auñon-Chancellor S, Harrison MF, Shah R, Powers WE. Tolerance of centrifuge-simulated commercial spaceflight in a subject with hemophilia A . Aerosp Med Hum Perform. 2023; 94(6):470-474.

BACKGROUND: Maintenance and disposition of decedent remains during spaceflight require the isolation of biohazardous products of decomposition in microgravity and in the absence of refrigeration. Containment and isolation options would preferably offer sufficient time to enable crew and ground support teams to determine appropriate disposition of remains and even potentially return remains to the Earth. The pilot study described herein undertook an effort to develop a postmortem containment unit for the isolation and maintenance of decedent remains in a microgravity environment. METHODS: Commercial off-the-shelf containment units were modified to meet the needs of a microgravity spaceflight environment and to offer the best likelihood of successful containment and management of remains. A subsequent evaluation of modified containment unit performance was undertaken utilizing human cadavers, with measurement and analysis of volatile off-gassing over time followed by impact testing of the units containing cadaverous remains in a simulated spaceflight vehicle seat. RESULTS: Modifications were implemented without significant negative design impact. Failure was observed in one modified unit after 9 d and attributed to improper filter application. The remaining unit successfully contained remains beyond the intended endpoint of the study. DISCUSSION: These pilot efforts offer important insight into the development of effective postmortem containment options for future spaceflight. Further study is needed to ensure repeatability of the findings and to further characterize the failure modes of the modified units evaluated, the impact of microgravity conditions, and the identification of additional modifications that would improve remains disposition. Houser T, Lindgren KN, Mazuchowski EL II, Barratt MR, Haines DC, Jayakody M, Blue RS, Bytheway JA, Stepaniak PC. Remains containment considerations for death in low-Earth orbit . Aerosp Med Hum Perform. 2023; 94(5):368-376.

INTRODUCTION: Sympathetic stimulation is known to be associated with transient alterations of blood glucose (BG) concentration; spaceflight acceleration may be similarly associated with alterations of BG, potentially posing a risk to diabetic individuals engaging in future spaceflight activities. Despite prior studies demonstrating diabetic subjects' tolerance to centrifuge-simulated spaceflight, data are lacking regarding blood glucose response to hypergravity. It remains unclear whether hypergravity or associated physiological response may pose a risk to diabetics. Continuous glucose monitors (CGM) offer a means of noninvasive glucose monitoring and may be useful in spaceflight and analog environments. Here, we describe the results of continuous glucose monitoring during centrifuge-simulated spaceflight. METHODS: Subjects participated in 1-5 centrifuge-simulated spaceflight profiles (maximum +4.0 G z , +6.0 G x , 6.1 G resultant). Data collection included heart rate, blood pressure, electrocardiogram, continuous glucose via CGM, intermittent fingerstick BG, and postrun questionnaires regarding symptoms related to hypergravity exposure. RESULTS: CGM data were collected from 26 subjects, including 4 diabetics. While diabetic subjects had significantly higher BG compared to nondiabetics, this was not associated with any difference in symptoms or tolerance. Transient hypergravity-associated CGM glucose alterations did not affect tolerance of the centrifuge experience. CGM data were found to be reliable with occasional exceptions, including four instances of false critical low glucose alarms. DISCUSSION: While further study is necessary to better characterize CGM fidelity during hypergravity and other spaceflight-related stressors, CGM may be a feasible option for spaceflight and analog settings. As in prior studies, individuals with well-controlled diabetes appear able to tolerate the accelerations anticipated for commercial spaceflight. Ong KM, Rossitto JJ, Ray K, Dufurrena QA, Blue RS. Blood glucose alterations and continuous glucose monitoring in centrifuge-simulated spaceflight . Aerosp Med Hum Perform. 2022; 93(9):688-695.

Abstract INTRODUCTION: For over 50 yr, investigators have studied the physiological adaptations of the human system during short- and long-duration spaceflight exposures. Much of the knowledge gained in developing health countermeasures for astronauts onboard the International Space Station demonstrate terrestrial applications. To date, a systematic process for translating these space applications to terrestrial human health has yet to be defined. METHODS: In the summer of 2017, a team of 38 international scientists launched the Bellagio ll Summit Initiative. The goals of the Summit were: 1) To identify space medicine findings and countermeasures with highest probability for future terrestrial applications; and 2) To develop a roadmap for translation of these countermeasures to future terrestrial application. The team reviewed public domain literature, NASA databases, and evidence books within the framework of the five-stage National Institutes of Health (NIH) translation science model, and the NASA two-stage translation model. Teams then analyzed and discussed interdisciplinary findings to determine the most significant evidence-based countermeasures sufficiently developed for terrestrial application. RESULTS: Teams identified published human spaceflight research and applied translational science models to define mature products for terrestrial clinical practice. CONCLUSIONS: The Bellagio ll Summit identified a snapshot of space medicine research and mature science with the highest probability of translation and developed a Roadmap of terrestrial application from space medicine-derived countermeasures. These evidence-based findings can provide guidance regarding the terrestrial applications of best practices, countermeasures, and clinical protocols currently used in spaceflight. Sides MB, Johnston SL III, Sirek A, Lee PH, Blue RS, Antonsen EL, Basner M, Douglas GL, Epstein A, Flynn-Evans EE, Gallagher MB, Hayes J, Lee SMC, Lockley SW, Monseur B, Nelson NG, Sargsyan A, Smith SM, Stenger MB, Stepanek J, Zwart SR; Bellagio II Team. Bellagio II report: terrestrial applications of space medicine research . Aerosp Med Hum Perform. 2021; 92(8):650669.

INTRODUCTION: As NASA and its international partners, as well as the commercial spaceflight industry, prepare for missions of increasing duration and venturing outside of low-Earth orbit, mitigation of medical risk is of high priority. Gynecologic considerations constitute one facet of medical risk for female astronauts. This manuscript will review the preflight, in-flight, and postflight clinical evaluation, management, and prevention considerations for reducing gynecologic and reproductive risks in female astronauts. METHODS: Relevant gynecological articles from databases including Ovid, Medline, Web of Science, various medical libraries, and NASA archives were evaluated for this review. In particular, articles addressing preventive measures or management of conditions in resource-limited environments were evaluated for applicability to future long-duration exploration spaceflight. RESULTS: Topics including abnormal uterine bleeding, anemia, bone mineral density, ovarian cysts, venous thromboembolism, contraception, fertility, and health maintenance were reviewed. Prevention and treatment strategies are discussed with a focus on management options that consider limitations of onboard medical capabilities. DISCUSSION: Long-duration exploration spaceflight will introduce new challenges for maintenance of gynecological and reproductive health. The impact of the space environment outside of low-Earth orbit on gynecological concerns remains unknown, with factors such as increased particle radiation exposure adding complexity and potential risk. While the most effective means of minimizing the impact of gynecologic or reproductive pathology for female astronauts is screening and prevention, gynecological concerns can arise unpredictably as they do on Earth. Careful consideration of gynecological risks and potential adverse events during spaceflight is a critical component to risk analysis and preventive medicine for future exploration missions. Steller JG, Blue RS, Burns R, Bayuse TM, Antonsen EL, Jain V, Blackwell MM, Jennings RT. Gynecologic risk mitigation considerations for long-duration spaceflight . Aerosp Med Hum Perform. 2020; 91(7):543-564.

Introduction: Flight surgeons play a vital role in U.S. Air Force aviation operations by ensuring that pilots are medically prepared to meet the demands of military aviation. However, there is natural tension between pilots and flight surgeons. A pilot may be reluctant to share medical information with a flight surgeon who could negatively impact the pilot's career or flight status. In this preliminary study, we sought to identify pilot-perceived strengths and weaknesses in the relationship between U.S. Air Force aviators and their flight surgeons., Materials and Methods: An online survey regarding pilot-flight surgeon confidence and perceived values was distributed electronically to a convenience sample of U.S. Air Force aviators. Participants included U.S. Air Force active duty and Air Reserve Component (Air Force Reserve and Air National Guard) military aviators in addition to U.S. Air Force Academy aviation cadets., Results: One hundred and seventy-three aviators participated in the survey. Respondents reported variable comfort in approaching flight surgeons with medical concerns and suggested that they believed other pilots might be withholding medical information from flight surgeons or seeking care from civilian physicians for career protection., Conclusions: We sought to examine the pilot-flight surgeon relationship and its impact on daily flying operations. While limited, results suggest that there may be gaps in trust between pilots and their flight surgeons. These findings could present an opportunity to improve the pilot-flight surgeon relationship by identifying factors that contribute to closer pilot-flight surgeon relationships., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

INTRODUCTION: Analysis of historical solar particle events (SPEs) provides context for some understanding of acute radiation exposure risk to astronauts who will travel outside of low-Earth orbit. Predicted levels of radiation exposures to exploration crewmembers could produce some health impacts, including nausea, emesis, and fatigue, though more severe clinical manifestations are unlikely. Using current models of anticipated physiological sequelae, we evaluated the clinical challenges of managing radiation-related clinical concerns during exploration spaceflight. METHODS: A literature review was conducted to identify terrestrial management standards for radiation-induced illnesses, focusing on prodromal symptom treatment. Terrestrial management was compared to current spaceflight medical capabilities to identify gaps and highlight challenges involved in expanding capabilities for future exploration spaceflight. RESULTS: Current spaceflight medical resources, such as those found on the International Space Station, may be sufficient to manage some aspects of radiation-induced illness, although effective treatment of all potential manifestations would require substantial expansion of capabilities. Terrestrial adjunctive therapies or more experimental treatments are unavailable in current spaceflight medical capabilities but may have a role in future management of acute radiation exposure. DISCUSSION: Expanded medical capabilities for managing radiation-induced illnesses could be included onboard future exploration vehicles. However, this would require substantial research, time, and funding to reach flight readiness, and vehicle limitations may restrict such capabilities for exploration missions. The benefits of including expanded capabilities should be weighed against the likelihood of significant radiation exposure and extensive mission design constraints. Blue RS, Chancellor JC, Suresh R, Carnell LS, Reyes DP, Nowadly CD, Antonsen EL. Challenges in clinical management of radiation-induced illnesses during exploration spaceflight . Aerosp Med Hum Perform. 2019; 90(11):966-977.

In order to maintain crew health and performance during long-duration spaceflight outside of low-Earth orbit, NASA and its international partners must be capable of providing a safe and effective pharmacy. Given few directed studies of pharmaceuticals in the space environment, it is difficult to characterize pharmaceutical effectiveness or stability during spaceflight; this in turn makes it challenging to select an appropriate formulary for exploration. Here, we present the current state of literature regarding pharmaceutical stability, metabolism, and effectiveness during spaceflight. In particular, we have attempted to highlight the gaps in current knowledge and the difficulties in translating terrestrial-based drug studies to a meaningful interpretation of drug stability, safety, and effectiveness in space. We hope to identify high-yield opportunities for future research that might better define and mitigate pharmaceutical risk for exploration missions., Competing Interests: Competing interestsThe authors declare no competing interests.

As human spaceflight seeks to expand beyond low-Earth orbit, NASA and its international partners face numerous challenges related to ensuring the safety of their astronauts, including the need to provide a safe and effective pharmacy for long-duration spaceflight. Historical missions have relied upon frequent resupply of onboard pharmaceuticals; as a result, there has been little study into the effects of long-term exposure of pharmaceuticals to the space environment. Of particular concern are the long-term effects of space radiation on drug stability, especially as missions venture away from the protective proximity of the Earth. Here we highlight the risk of space radiation to pharmaceuticals during exploration spaceflight, identifying the limitations of current understanding. We further seek to identify ways in which these limitations could be addressed through dedicated research efforts aimed toward the rapid development of an effective pharmacy for future spaceflight endeavors., Competing Interests: Competing interestsThe authors declare no competing interests.

Introduction: While NASA requires that commercial spaceflight vehicles provide onboard emergency oxygen supplies for crew, there are currently no requirements in place regarding thermal constraints of delivered gas. The question has been raised whether or not onboard emergency oxygen supplies must be warmed prior to administration to the crew, as inclusion of warming capabilities will increase the complexity and mass of life support systems in the vehicle. We sought to identify the risk of various inhaled oxygen temperatures and resultant pulmonary inflammatory response in potentially injured crewmembers., Methods: A systematic review of published literature was conducted concerning thermal regulation of inhaled gases, reactive airway response, and inflammatory reactions. In particular, we sought literature that correlated inhaled gas temperature to airway response to identify a temperature threshold that would avoid deleterious sequelae., Results: Cold air inhalation can induce acute bronchoconstriction, increased respiratory rate, and associated dyspnea and hypoxia. Physiological response to cold air varies between healthy lungs and injured tissues, and increased inflammation is associated with increasing airway reactivity. Most studies suggest that inhaled gas temperatures below 10°C may induce deleterious physiological sequelae., Discussion: Best practices would include maintenance of inhaled gas temperatures to >10°C to avoid poor physiological response, preferably as close to physiological norms as possible. Given that inhaled gas temperature may be altered by transit through an oxygen delivery system, measurement of actual delivered gas temperature should occur at the point of crewmember inhalation.Pattarini JM, Blue RS, Alexander DJ. Thermal regulation of emergency oxygen supplies in commercial space vehicles. Aerosp Med Hum Perform. 2018; 89(10):918-922.

Despite years of research, understanding of the space radiation environment and the risk it poses to long-duration astronauts remains limited. There is a disparity between research results and observed empirical effects seen in human astronaut crews, likely due to the numerous factors that limit terrestrial simulation of the complex space environment and extrapolation of human clinical consequences from varied animal models. Given the intended future of human spaceflight, with efforts now to rapidly expand capabilities for human missions to the moon and Mars, there is a pressing need to improve upon the understanding of the space radiation risk, predict likely clinical outcomes of interplanetary radiation exposure, and develop appropriate and effective mitigation strategies for future missions. To achieve this goal, the space radiation and aerospace community must recognize the historical limitations of radiation research and how such limitations could be addressed in future research endeavors. We have sought to highlight the numerous factors that limit understanding of the risk of space radiation for human crews and to identify ways in which these limitations could be addressed for improved understanding and appropriate risk posture regarding future human spaceflight., Competing Interests: The authors declare no competing interests.

Objective: Individuals with diabetes are increasingly seeking pretravel advice, but updated professional recommendations remain scant. We performed a systematic review on diabetes management during air travel to summarize current recommendations, assess supporting evidence, and identify areas of future research., Methods: A systematic review of the English literature on diabetes management during air travel was undertaken utilizing PubMed and MEDLINE. Publications regarding general travel advice; adjustment of insulin and noninsulin therapies; and the use of insulin pumps, glucometers and subcutaneous glucose sensors at altitude were included. Gathered information was used to create an updated summary of glucose-lowering medication adjustment during air travel., Results: Sixty-one publications were identified, most providing expert opinion and few offering primary data (47 expert opinion, 2 observational studies, 2 case reports, 10 device studies). General travel advice was uniform, with increasing attention to preflight security. Indications for oral antihyperglycemic therapy adjustments varied. There were few recommendations on contemporary agents and on nonhypoglycemic adverse events. There was little consensus on insulin adjustment protocols, many antedating current insulin formulations. Most publications advocated adjusting insulin pump time settings after arrival; however, there was disagreement on timing and rate adjustments. Glucometers and subcutaneous glucose sensors were reported to be less accurate at altitude, but not to an extent that would preclude their clinical use., Conclusion: Recommendations for diabetes management during air travel vary significantly and are mostly based on expert opinion. Data from systematic investigation on glucose-lowering medication adjustment protocols may support the development of a future consensus statement., Abbreviations: CSII = continuous subcutaneous insulin infusion (device) DPP-4 = dipeptidyl peptidase 4 EGA = error grid analysis GDH = glucose dehydrogenase GOX = glucose oxidase GLP1 = glucagon-like peptide-1 NPH = neutral protamine Hagedorn SGLT2 = sodium-glucose cotransporter-2.

Introduction: The provision of medical care in exploration-class spaceflight is limited by mass, volume, and power constraints, as well as limitations of available skillsets of crewmembers. A quantitative means of exploring the risks and benefits of inclusion or exclusion of onboard medical capabilities may help to inform the development of an appropriate medical system. A pilot project was designed to demonstrate the utility of an early tradespace analysis tool for identifying high-priority resources geared toward properly equipping an exploration mission medical system., Methods: Physician subject matter experts identified resources, tools, and skillsets required, as well as associated criticality scores of the same, to meet terrestrial, U.S.-specific ideal medical solutions for conditions concerning for exploration-class spaceflight. A database of diagnostic and treatment actions and resources was created based on this input and weighed against the probabilities of mission-specific medical events to help identify common and critical elements needed in a future exploration medical capability., Results: Analysis of repository data demonstrates the utility of a quantitative method of comparing various medical resources and skillsets for future missions. Directed database queries can provide detailed comparative estimates concerning likelihood of resource utilization within a given mission and the weighted utility of tangible and intangible resources., Discussion: This prototype tool demonstrates one quantitative approach to the complex needs and limitations of an exploration medical system. While this early version identified areas for refinement in future version development, more robust analysis tools may help to inform the development of a comprehensive medical system for future exploration missions.Antonsen EL, Mulcahy RA, Rubin D, Blue RS, Canga MA, Shah R. Prototype development of a tradespace analysis tool for spaceflight medical resources. Aerosp Med Hum Perform. 2018; 89(2):108-114.

Introduction: With the development of the commercial space industry, growing numbers of spaceflight participants will engage in activities with a risk for pulmonary injuries, including pneumothorax, ebullism, and decompression sickness, as well as other concomitant trauma. Medical triage capabilities for mishaps involving pulmonary conditions have not been systematically reviewed. Recent studies have advocated the use of point-of-care ultrasound to screen for lung injury or illness. The operational utility of portable ultrasound systems in disaster relief and other austere settings may be relevant to commercial spaceflight., Methods: A systematic review of published literature was conducted concerning the use of point-of-care pulmonary ultrasound techniques in austere environments, including suggested examination protocols for triage and diagnosis., Results: Recent studies support the utility of pulmonary ultrasound examinations when performed by skilled operators, and comparability of the results to computed tomography and chest radiography for certain conditions, with important implications for trauma management in austere environments., Discussion: Pulmonary injury and illness are among the potential health risks facing spaceflight participants. Implementation of point-of-care ultrasound protocols could aid in the rapid diagnosis, triage, and treatment of such conditions. Though operator-dependent, ultrasound, with proper training, experience, and equipment, could be a valuable tool in the hands of a first responder supporting remote spaceflight operations.Johansen BD, Blue RS, Castleberry TL, Antonsen EL, Vanderploeg JM. Point-of-care ultrasound for pulmonary concerns in remote spaceflight triage environments. Aerosp Med Hum Perform. 2018; 89(2):122-129.

Introduction: There are limited data on cardiac dysrhythmias in laypersons during hypergravity exposure. We report layperson electrocardiograph (ECG) findings and tolerance of dysrhythmias during centrifuge-simulated suborbital spaceflight., Methods: Volunteers participated in varied-length centrifuge training programs of 2-7 centrifuge runs over 0.5-2 d, culminating in two simulated suborbital spaceflights of combined +Gz and +Gx (peak +4.0 Gz, +6.0 Gx, duration 5 s). Monitors recorded pre- and post-run mean arterial blood pressure (MAP), 6-s average heart rate (HR) collected at prespecified points during exposures, documented dysrhythmias observed on continuous 3-lead ECG, self-reported symptoms, and objective signs of intolerance on real-time video monitoring., Results: Participating in the study were 148 subjects (43 women). Documented dysrhythmias included sinus pause (N = 5), couplet premature ventricular contractions (N = 4), bigeminy (N = 3), accelerated idioventricular rhythm (N = 1), and relative bradycardia (RB, defined as a transient HR drop of >20 bpm; N = 63). None were associated with subjective symptoms or objective signs of acceleration intolerance. Episodes of RB occurred only during +Gx exposures. Subjects had a higher post-run vs. pre-run MAP after all exposures, but demonstrated no difference in pre- and post-run HR. RB was more common in men, younger individuals, and subjects experiencing more centrifuge runs., Discussion: Dysrhythmias in laypersons undergoing simulated suborbital spaceflight were well tolerated, though RB was frequently noted during short-duration +Gx exposure. No subjects demonstrated associated symptoms or objective hemodynamic sequelae from these events. Even so, heightened caution remains warranted when monitoring dysrhythmias in laypersons with significant cardiopulmonary disease or taking medications that modulate cardiac conduction.Suresh R, Blue RS, Mathers CH, Castleberry TL, Vanderploeg JM. Dysrhythmias in laypersons during centrifuge-stimulated suborbital spaceflight. Aerosp Med Hum Perform. 2017; 88(11):1008-1015.

Introduction: Antarctica is a useful analog for spaceflight, as both environments are remote, isolated, and with limited resources. While previous studies have demonstrated increased asymptomatic viral shedding in both the Antarctic and spaceflight environments, clinical manifestations of reactivated viral disease have been less frequently identified. We sought to identify the incidence of clinical herpes zoster from viral reactivation in the Antarctic winter-over population., Methods: Medical records from the 2014 winter season were reviewed for the incidence of zoster in U.S. Antarctic personnel and then compared to the age-matched U.S., Results: Five cases of clinical herpes zoster occurred in the Antarctic Station population of 204 persons, for an incidence of 33.3 per 1000 person-years vs. 3.2 per 1000 person-years in the general population. Four cases were in persons under age 40, yielding an incidence of 106.7 per 1000 person-years in persons ages 30-39 compared to an incidence of 2.0 per 1000 person-years in the same U.S. age group., Discussion: Immune suppression due to the stressful Antarctic environment may have contributed to the increased incidence of herpes zoster in U.S. Antarctic personnel during the winter of 2014. Working and living in isolated, confined, and extreme environments can cause immune suppression, reactivating latent viruses and increasing viral shedding and symptomatic disease. Such changes have been observed in other austere environments, including spaceflight, suggesting that clinical manifestations of viral reactivation may be seen in future spaceflight.Reyes DP, Brinley AA, Blue RS, Gruschkus SK, Allen AT, Parazynski SE. Clinical herpes zoster in Antarctica as a model for spaceflight. Aerosp Med Hum Perform. 2017; 88(8):784-788.

Introduction: Hypergravitational exposures during human centrifugation are known to provoke dysrhythmias, including sinus dysrhythmias/tachycardias, premature atrial/ventricular contractions, and even atrial fibrillations or flutter patterns. However, events are generally short-lived and resolve rapidly after cessation of acceleration. This case report describes a prolonged ectopic ventricular rhythm in response to high G exposure., Case Report: A previously healthy 30-yr-old man voluntarily participated in centrifuge trials as a part of a larger study, experiencing a total of 7 centrifuge runs over 48 h. Day 1 consisted of two +Gz runs (peak +3.5 Gz, run 2) and two +Gx runs (peak +6.0 Gx, run 4). Day 2 consisted of three runs approximating suborbital spaceflight profiles (combined +Gx and +Gz). Hemodynamic data collected included blood pressure, heart rate, and continuous three-lead electrocardiogram. Following the final acceleration exposure of the last Day 2 run (peak +4.5 Gx and +4.0 Gz combined, resultant +6.0 G), during a period of idle resting centrifuge activity (resultant vector +1.4 G), the subject demonstrated a marked change in his three-lead electrocardiogram from normal sinus rhythm to a wide-complex ectopic ventricular rhythm at a rate of 91-95 bpm, consistent with an accelerated idioventricular rhythm (AIVR). This rhythm was sustained for 2 m, 24 s before reversion to normal sinus. The subject reported no adverse symptoms during this time., Discussion: While prolonged, the dysrhythmia was asymptomatic and self-limited. AIVR is likely a physiological response to acceleration and can be managed conservatively. Vigilance is needed to ensure that AIVR is correctly distinguished from other, malignant rhythms to avoid inappropriate treatment and negative operational impacts.Suresh R, Blue RS, Mathers C, Castleberry TL, Vanderploeg JM. Sustained accelerated idioventricular rhythm in a centrifuge-simulated suborbital spaceflight. Aerosp Med Hum Perform. 2017; 88(8):789-793.

Introduction: In commercial spaceflight, anxiety could become mission-impacting, causing negative experiences or endangering the flight itself. We studied layperson response to four varied-length training programs (ranging from 1 h-2 d of preparation) prior to centrifuge simulation of launch and re-entry acceleration profiles expected during suborbital spaceflight. We examined subject task execution, evaluating performance in high-stress conditions. We sought to identify any trends in demographics, hemodynamics, or similar factors in subjects with the highest anxiety or poorest tolerance of the experience., Methods: Volunteers participated in one of four centrifuge training programs of varied complexity and duration, culminating in two simulated suborbital spaceflights. At most, subjects underwent seven centrifuge runs over 2 d, including two +Gz runs (peak +3.5 Gz, Run 2) and two +Gx runs (peak +6.0 Gx, Run 4) followed by three runs approximating suborbital spaceflight profiles (combined +Gx and +Gz, peak +6.0 Gx and +4.0 Gz). Two cohorts also received dedicated anxiety-mitigation training. Subjects were evaluated on their performance on various tasks, including a simulated emergency., Results: Participating in 2-7 centrifuge exposures were 148 subjects (105 men, 43 women, age range 19-72 yr, mean 39.4 ± 13.2 yr, body mass index range 17.3-38.1, mean 25.1 ± 3.7). There were 10 subjects who withdrew or limited their G exposure; history of motion sickness was associated with opting out. Shorter length training programs were associated with elevated hemodynamic responses. Single-directional G training did not significantly improve tolerance., Discussion: Training programs appear best when high fidelity and sequential exposures may improve tolerance of physical/psychological flight stressors. The studied variables did not predict anxiety-related responses to these centrifuge profiles.Blue RS, Bonato F, Seaton K, Bubka A, Vardiman JL, Mathers C, Castleberry TL, Vanderploeg JM. The effects of training on anxiety and task performance in simulated suborbital spaceflight. Aerosp Med Hum Perform. 2017; 88(7):641-650.

Introduction: Anxiety may present challenges for commercial spaceflight operations, as little is known regarding the psychological effects of spaceflight on laypersons. A recent investigation evaluated measures of anxiety during centrifuge-simulated suborbital commercial spaceflight, highlighting the potential for severe anxiousness to interrupt spaceflight operations., Methods: To pave the way for future research, an extensive literature review identified existing knowledge that may contribute to formation of interventions for anxiety in commercial spaceflight. Useful literature was identified regarding anxiety from a variety of fields, including centrifugation, fear of flying, motion sickness, and military operations., Results: Fear of flying is the most extensively studied area, with some supportive evidence from centrifugation studies. Virtual reality exposure (VRE) is as effective as actual training flight exposure (or analog exposure) in mitigation of flight-related anxiety. The addition of other modalities, such as cognitive behavioral therapy or biofeedback, to VRE improves desensitization compared to VRE alone. Motion sickness-susceptible individuals demonstrate higher trait anxiety than nonsusceptible individuals; for this reason, motion sickness susceptibility questionnaires may be useful measures to identify at-risk individuals. Some military studies indicate that psychiatric history and personality classification may have predictive value in future research. Medication countermeasures consisting of benzodiazepines may quell in-flight anxiety, but do not likely improve anxiety on repeat exposure., Discussion: The scarce available literature addressing anxiety in unique environments indicates that training/repeated exposure may mitigate anxiety. Anxiety and personality indices may be helpful screening tools, while pharmaceuticals may be useful countermeasures when needed. Mulcahy RA, Blue RS, Vardiman JL, Castleberry TL, Vanderploeg JM. Screening and mitigation of layperson anxiety in aerospace environments. Aerosp Med Hum Perform. 2016; 87(10):882-889.

Introduction: Commercial spaceflight participants (SFPs) will introduce new medical challenges to the aerospace community, with unique medical conditions never before exposed to the space environment. This is a case report regarding the response of a subject with multiple cardiac malformations, including aortic insufficiency, pulmonary atresia, pulmonary valve replacement, ventricular septal defect (post-repair), and pulmonary artery stenosis (post-dilation), to centrifuge acceleration simulating suborbital flight., Case Report: A 23-yr-old man with a history of multiple congenital cardiac malformations underwent seven centrifuge runs over 2 d. Day 1 consisted of two +G(z) runs (peak = +3.5 G(z), run 2) and two +G(x) runs (peak = +6.0 G(x), run 4). Day 2 consisted of three runs approximating suborbital spaceflight profiles (combined +G(x) and +G(z)). Data collected included blood pressure, electrocardiogram, pulse oximetry, neurovestibular exams, and post-run questionnaires regarding motion sickness, disorientation, greyout, and other symptoms. Despite the subject's significant medical history, he tolerated the acceleration profiles well and demonstrated no significant abnormal physiological responses., Discussion: Potential risks to SFPs with aortic insufficiency, artificial heart valves, or valvular insufficiency include lower +G(z) tolerance, earlier symptom onset, and ineffective mitigation strategies such as anti-G straining maneuvers. There are no prior studies of prolonged accelerations approximating spaceflight in such individuals. This case demonstrates tolerance of acceleration profiles in an otherwise young and healthy individual with significant cardiac malformations, suggesting that such conditions may not necessarily preclude participation in commercial spaceflight.

Introduction: With commercial spaceflight comes the possibility of spaceflight participants (SFPs) with significant medical conditions. Those with previously untested medical conditions, such as diabetes mellitus (DM) and the use of indwelling medical devices, represent a unique challenge. It is unclear how SFPs with such devices will react to the stresses of spaceflight. This case report describes two subjects with Type I DM using insulin pumps who underwent simulated dynamic phases of spaceflight via centrifuge G force exposure., Case Report: Two Type I diabetic subjects with indwelling Humalog insulin pumps, a 23-yr-old man averaging 50 u of Humalog daily and a 27-yr-old man averaging 60 u of Humalog daily, underwent seven centrifuge runs over 48 h. Day 1 consisted of two +Gz runs (peak = +3.5 Gz, run 2) and two +Gx runs (peak = +6.0 Gx, run 4). Day 2 consisted of three runs approximating suborbital spaceflight profiles (combined +Gx and +Gz). Data collected included blood pressure, electrocardiogram, pulse oximetry, neurovestibular evaluation, and questionnaires regarding motion sickness, disorientation, greyout, and other symptoms. Neither subject experienced adverse clinical responses to the centrifuge exposure. Both maintained blood glucose levels between 110-206 mg · dl(-1)., Discussion: Potential risks to SFPs with insulin pump dependent DM include hypo/hyperglycemia, pump damage, neurovestibular dysfunction, skin breakdown, and abnormal stress responses. A search of prior literature did not reveal any previous studies of individuals with DM on insulin pumps exposed to prolonged accelerations. These cases suggest that individuals with conditions dependent on continuous medication delivery might tolerate the accelerations anticipated for commercial spaceflight.

Introduction: Future commercial spaceflight participants (SFPs) with conditions requiring personal medical devices represent a unique challenge. The behavior under stress of cardiac implanted devices (CIDs) such as pacemakers is of special concern. No known data currently exist on how such devices may react to the stresses of spaceflight. We examined the responses of two volunteer subjects with CIDs to G forces in a centrifuge to evaluate how similar potential commercial SFPs might tolerate the forces of spaceflight., Case Report: Two subjects, 75- and 79-yr-old men with histories of atrial fibrillation and implanted dual-lead, rate-responsive pacemakers, underwent seven centrifuge runs over 2 d. Day 1 consisted of two +Gz runs (peak = +3.5 Gz, run 2) and two +Gx runs (peak = +6.0 Gx, run 4). Day 2 consisted of three runs approximating suborbital spaceflight profiles (combined +Gx/+Gz). Data collected included blood pressures, electrocardiograms, pulse oximetry, neurovestibular exams, and postrun questionnaires regarding motion sickness, disorientation, greyout, and other symptoms. Despite both subjects' significant medical histories, neither had abnormal physiological responses. Post-spin analysis demonstrated no lead displacement, damage, or malfunction of either CID., Discussion: Potential risks to SFPs with CIDs include increased arrhythmogenesis, lead displacement, and device damage. There are no known prior studies of individuals with CIDs exposed to accelerations anticipated during the dynamic phases of suborbital spaceflight. These cases demonstrate that even individuals with significant medical histories and implanted devices can tolerate the acceleration exposures of commercial spaceflight. Further investigation will determine which personal medical devices present significant risks during suborbital flight and beyond.

Introduction: Historically, space has been the venue of the healthy individual. With the advent of commercial spaceflight, we face the novel prospect of routinely exposing spaceflight participants (SPFs) with multiple comorbidities to the space environment. Preflight screening procedures must be developed to identify those individuals at increased risk during flight. We examined the responses of volunteers to centrifuge accelerations mimicking commercial suborbital spaceflight profiles to evaluate how potential SFPs might tolerate such forces. We evaluated our screening process for medical approval of subjects for centrifuge participation for applicability to commercial spaceflight operations., Methods: All registered subjects completed a medical questionnaire, physical examination, and electrocardiogram. Subjects with identified concerns including cardiopulmonary disease, hypertension, and diabetes were required to provide documentation of their conditions., Results: There were 335 subjects who registered for the study, 124 who completed all prescreening, and 86 subjects who participated in centrifuge trials. Due to prior medical history, five subjects were disqualified, most commonly for psychiatric reasons or uncontrolled medical conditions. Of the subjects approved, four individuals experienced abnormal physiological responses to centrifuge profiles, including one back strain and three with anxiety reactions., Discussion: The screening methods used were judged to be sufficient to identify individuals physically capable of tolerating simulated suborbital flight. Improved methods will be needed to identify susceptibility to anxiety reactions. While severe or uncontrolled disease was excluded, many subjects successfully participated in centrifuge trials despite medical histories of disease that are disqualifying under historical spaceflight screening regimes. Such screening techniques are applicable for use in future commercial spaceflight operations.

Introduction: Some commercial spaceflight participants (SFPs) may have medical conditions that require implanted medical devices (IMDs), such as cardiac pacemakers, defibrillators, insulin pumps, or similar electronic devices. The effect of space radiation on the function of IMDs is unknown. This review will identify known effects of terrestrial and aviation electromagnetic interference (EMI) and radiation on IMDs in order to provide insight into the potential effects of radiation exposures in the space environment., Methods: A systematic literature review was conducted on available literature on human studies involving the effects of EMI as well as diagnostic and therapeutic radiation on IMDs., Results: The literature review identified potential transient effects from EMI and diagnostic radiation levels as low as 10 mGy on IMDs. High-energy, therapeutic, ionizing radiation can cause more permanent device malfunctions at doses as low as 40 mGy. Radiation doses from suborbital flight altitudes and durations are anticipated to be less than those experienced during an average round-trip, cross-country airline flight and are unlikely to result in significant detriment, though longer, orbital flights may expose SFPs to doses potentially harmful to IMD function., Discussion: Individuals with IMDs should experience few, if any, radiation-related device malfunctions during suborbital flight, but could have problems with radiation exposures associated with longer, orbital flights.

Introduction: Red Bull Stratos was a commercial program that brought a test parachutist, protected by a full-pressure suit, in a stratospheric balloon with pressurized capsule to over 127,582 ft (38,969 m), from which he free fell and subsequently parachuted to the ground. Given that the major risks to the parachutist included ebullism, negative Gz (toe-to-head) acceleration exposure from an uncontrolled flat spin, and trauma, a comprehensive plan was developed to recover the parachutist under nominal conditions and to respond to any medical contingencies that might have arisen. In this report, the project medical team describes the experience of providing emergency medical support and crew recovery for the manned balloon flights of the program., Methods: The phases of flight, associated risks, and available resources were systematically evaluated., Results: Six distinct phases of flight from an Emergency Medical Services (EMS) standpoint were identified. A Medical Support Plan was developed to address the risks associated with each phase, encompassing personnel, equipment, procedures, and communications., Discussion: Despite geographical, communications, and resource limitations, the medical team was able to implement the Medical Support Plan, enabling multiple successful manned balloon flights to 71,615 ft (21,828 m), 97,221 ft (29,610 m), and 127,582 ft (38,969 m). The experience allowed refinement of the EMS and crew recovery procedures for each successive flight and could be applied to other high altitude or commercial space ventures.

Introduction: U.S. astronauts undergo extensive job-related screening and medical examinations prior to selection in order to identify candidates optimally suited for careers in spaceflight. Screening medical standards evolved over many years and after extensive spaceflight experience. These standards assess health-related risks for each astronaut candidate, minimizing the potential for medical impact on future mission success. This document discusses the evolution of the Shuttle-era medical selection standards and the most common reasons for medical dis-qualification of applicants., Methods: Data for astronaut candidate finalists were compiled from medical records and NASA archives from the period of 1978 to 2004 and were retrospectively reviewed for medically disqualifying conditions., Results: During Shuttle selection cycles, a total of 372 applicants were disqualified due to 425 medical concerns. The most common disqualifying conditions included visual, cardiovascular, psychiatric, and behavioral disorders. During this time period, three major expert panel reviews resulted in refinements and alterations to selection standards for future cycles., Discussion: Shuttle-era screening, testing, and specialist evaluations evolved through periodic expert reviews, evidence-based medicine, and astronaut medical care experience. The Shuttle medical program contributed to the development and implementation of NASA and international standards, longitudinal data collection, improved medical care, and occupational surveillance models. The lessons learned from the Shuttle program serve as the basis for medical selection for the ISS, exploration-class missions, and for those expected to participate in commercial spaceflight.

Introduction: Anxiety and psychological concerns may pose a challenge to future commercial spaceflight. To help identify potential measures of anxiousness and indicators of flight-related stress, the psychiatric histories and anxiousness responses of volunteers exposed to G forces in centrifuge-simulated spaceflight acceleration profiles were examined., Methods: Over 2 d, 86 individuals (63 men, 23 women), 20-78 yr old, underwent up to 7 centrifuge runs. Day 1 consisted of two +G(z) runs (peak = +3.5 G(z)) and two +Gx runs (peak = +6.0 G(x)). Day 2 consisted of three runs approximating suborbital spaceflight profiles (combined +G(x) and +G(z)). Hemodynamic data were collected during the profiles. Subjects completed a retrospective self-report anxiety questionnaire. Medical monitors identified individuals exhibiting varying degrees of anxiousness during centrifuge exposure, medical histories of psychiatric disease, and other potential indicators of psychological intolerance of spaceflight., Results: The retrospective survey identified 18 individuals self-reporting anxiousness, commonly related to unfamiliarity with centrifuge acceleration and concerns regarding medical history. There were 12 individuals (5 men, 7 women, average age 46.2 yr) who were observed to have anxiety that interfered with their ability to complete training; of these, 4 reported anxiousness on their questionnaire and 9 ultimately completed the centrifuge profiles. Psychiatric history was not significantly associated with anxious symptoms., Discussion: Anxiety is likely to be a relevant and potentially disabling problem for commercial spaceflight participants; however, positive psychiatric history and self-reported symptoms did not predict anxiety during centrifuge performance. Symptoms of anxiousness can often be ameliorated through training and coaching. Even highly anxious individuals are likely capable of tolerating commercial spaceflight.

Introduction: We examined responses of volunteers with known medical disease to G forces in a centrifuge to evaluate how potential commercial spaceflight participants (SFPs) might tolerate the forces of spaceflight despite significant medical history., Methods: Volunteers were recruited based upon suitability for each of five disease categories (hypertension, cardiovascular disease, diabetes, lung disease, back or neck problems) or a control group. Subjects underwent seven centrifuge runs over 2 d. Day 1 consisted of two +G(z) runs (peak = +3.5 G(z), Run 2) and two +G(x), runs (peak = +6.0 G(x), Run 4). Day 2 consisted of three runs approximating suborbital spaceflight profiles (combined +G(x) and +G(z), peak = +6.0 G(x)/+4.0 G(z)). Data collected included blood pressure, electrocardiogram, pulse oximetry, neurovestibular exams, and post-run questionnaires regarding motion sickness, disorientation, grayout, and other symptoms., Results: A total of 335 subjects registered for participation, of which 86 (63 men, 23 women, age 20-78 yr) participated in centrifuge trials. The most common causes for disqualification were weight and severe and uncontrolled medical or psychiatric disease. Five subjects voluntarily withdrew from the second day of testing: three for anxiety reasons, one for back strain, and one for time constraints. Maximum hemodynamic values recorded included HR of 192 bpm, systolic BP of 217 mmHg, and diastolic BP of 144 mmHg. Common subjective complaints included grayout (69%), nausea (20%), and chest discomfort (6%). Despite their medical history, no subject experienced significant adverse physiological responses to centrifuge profiles., Discussion: These results suggest that most individuals with well-controlled medical conditions can withstand acceleration forces of launch and re-entry profiles of current commercial spaceflight vehicles.

Introduction: The Red Bull Stratos Project consisted of incremental high altitude parachute jumps [maximum altitude 127,852 ft (38,969 m)] from a pressurized capsule suspended from a stratospheric helium-filled balloon. A physiological monitoring system was worn by the parachutist to provide operational medical and acceleration data and to record a unique set of data in a supersonic environment., Methods: Various physiological parameters, including heart rate (HR), respiratory rate (RR), skin temperature, and triaxial acceleration, were collected during the ascent, high altitude float, free fall, and parachute opening and descent stages of multiple low- and high altitude jumps. Physiologic data were synchronized with global positioning system (GPS) and audiovisual data for a comprehensive understanding of the environmental stressors experienced., Results: HR reached maximum during capsule egress and remained elevated throughout free fall and landing. RR reached its maximum during free fall. Temperature data were unreliable and did not provide useful results. The highest accelerations parameters were recorded during parachute opening and during landing. During each high altitude jump, immediately after capsule egress, the parachutist experienced a few seconds of microgravity during which some instability occurred. Control was regained as the parachutist entered denser atmosphere., Discussion: The high altitude environment resulted in extremely high vertical speeds due to little air resistance in comparison to lower altitude jumps with similar equipment. The risk for tumbling was highest at initial step-off. Physiological responses included elevated HR and RR throughout critical phases of free fall. The monitoring unit performed well despite the austere environment and extreme human performance activities.

Introduction: To reduce excessive iodine consumption by astronauts, the National Aeronautics and Space Administration (NASA) has developed various methods of removing residual iodine after iodine-based water purification aboard spacecraft. The Low Iodine Residual System (LIRS) was developed as an iodine removal system for use aboard the space shuttle. This is a case report of an accidental, potentially toxic ingestion by astronauts aboard a space shuttle mission following exposure to contaminated water from LIRS filtration and the medical response operations that followed., Case Report: Astronauts ingested significant levels of trialkylamines from water that had passed through gamma-irradiated, de-iodination resin in the LIRS hardware. Medical response operations included crew evaluations, consultations with toxicologists and systems experts, hardware testing, contaminant evaluation, and close crewmember follow-up., Discussion: Despite the significant ingestion there were no adverse clinical symptoms in any of the exposed astronauts; however, the case highlights a simple pitfall in the classification of hardware that ultimately lead to a potentially harmful toxic ingestion among the crewmembers, and the real-time response of medical personnel to ensure crew safety.

Introduction: Red Bull Stratos was a commercial program that brought a test parachutist protected by a full pressure suit to 127,852 ft (38,964 m), via a stratospheric balloon with a pressurized capsule, from which he free fell and subsequently parachuted to the ground. In light of the uniqueness of the operation and the medical threats faced, medical protocols specific to distinctive injury patterns were developed. One unique threat was that of a flat spin during free fall with resultant exposure to -Gz (toe-to-head) acceleration. In preparation for stratospheric free fall, the medical team conducted a review of the literature on the spectrum of human and animal injury patterns attributable to -Gz exposures. Based on the findings, an emergency medical field response protocol was developed for the rapid assessment, diagnosis, and treatment of individuals suspected of -Gz injury., Methods: A systematic review was conducted on available literature on human and animal studies involving significant -Gz exposure, with subsequent development of an applicable field treatment protocol., Results: The literature review identified pathophysiologic processes and mitigation strategies that were used to develop a prevention and treatment protocol, outlining appropriate interventions using current best medical practices. A medical field treatment protocol was successfully established for the high-altitude balloon program., Discussion: Available literature provided insight into best medical practices for the prevention and treatment of significant -Gz exposures during high-altitude parachute activity. Using the protocol developed for the field medical response, injuries from sustained -Gz exposure can be effectively managed in similar high-altitude and space operations.

Introduction: Red Bull Stratos was a commercial program designed to bring a test parachutist protected by a full-pressure suit via a stratospheric balloon with a pressurized capsule to 120,000 ft (36,576 m), from which he would freefall and subsequently parachute to the ground. On March 15, 2012, the Red Bull Stratos program successfully conducted a preliminary manned balloon test flight and parachute jump, reaching a final altitude of 71,581 ft (21,818 m). In light of the uniqueness of the operation and medical threats faced, a comprehensive medical plan was needed to ensure prompt and efficient response to any medical contingencies. This report will serve to discuss the medical plans put into place before the first manned balloon flight and the actions of the medical team during that flight., Methods: The medical operations developed for this program will be systematically evaluated, particularly, specific recommendations for improvement in future high-altitude and commercial space activities., Results: A multipronged approach to medical support was developed, consisting of event planning, medical personnel, equipment, contingency-specific considerations, and communications., Discussion: Medical operations were found to be highly successful when field-tested during this stratospheric flight, and the experience allowed for refinement of medical operations for future flights. The lessons learned and practices established for this program can easily be used to tailor a plan specific to other aviation or spaceflight events.

Introduction: Ebullism is the spontaneous evolution of liquid water in tissues to water vapor at body temperature when the ambient pressure is 47 mmHg or less. While injuries secondary to ebullism are generally considered fatal, some reports have described recovery after exposure to near vacuum for several minutes. The objectives of this article are to review the current literature on ebullism and to present prevention and treatment recommendations that can be used to enhance the safety of high altitude activities and space operations., Methods: A systematic review was conducted on currently available information and published literature of human and animal studies involving rapid decompression to vacuum and ebullism, with subsequent development of an applicable treatment protocol., Results: Available research on ebullism in human and animal subjects is extremely limited. Literature available identified key pathophysiologic processes and mitigation strategies that were used for treatment protocol design and outlining appropriate interventions using current best medical practices and technologies., Discussion: Available literature suggests that the pathophysiology of ebullism leads to predictable and often treatable injuries, and that many exposures may be survivable. With the growing number of high altitude and space-related activities, more individuals will be at risk for ebullism. An integrated medical protocol can provide guidance for the prevention and treatment of ebullism and help to mitigate this risk in the future.

Introduction: Medical knowledge of the human body in microgravity and hypergravity is based upon studies of healthy individuals well-conditioned for such environments. Little data exist regarding the effects of spaceflight on untrained commercial passengers. We examined the responses of potential spaceflight participants (SFP) to centrifuge G-force exposure., Methods: There were 77 individuals (65 men, 12 women), 22-88 yr old, who underwent 6 centrifuge runs over 48 h. Day 1 consisted of two +Gz runs (peak = 3.5+Gz, run 2) and two +Gx runs (peak = 6.0+Gx, run 4). Day 2 consisted of two runs approximating a suborbital spaceflight profile. Data included blood pressure, electrocardiogram, and postrun questionnaires regarding motion sickness, disorientation, greyout, and other symptoms., Results: Of the 77 participants, average age was 50.4 +/- 12.7 yr. Average heart rate (HR) varied by sex and direction of G-exposure (+Gz: F 150 +/- 19, M 123 +/- 27; +Gx: F 135 +/- 30, M 110 +/- 27). Age and peak HR were inversely related (HR < 120 bpm: 60.2 +/- 12.2 yr, HR > 120: 47.1 +/- 10.9 yr). HR during peak G-exposure for the final run was associated with post-run imbalance (no imbalance: HR 126 +/- 26, imbalance: HR 145 +/- 21); no other significant hemodynamic change, sex, or age variation was associated with imbalance. Age and greyout were inversely associated; there was no association between greyout and vital sign change, sex, or G-force magnitude. Baseline/pretrial mean arterial pressure (MAP) was not associated with any symptoms., Discussion: The results suggest that most individuals with well-controlled medical conditions can withstand acceleration forces involved in launch/landing profiles of commercial spaceflight vehicles. Further investigation will help refine which conditions present significant risk during suborbital flight and beyond.

Introduction: Human performance is affected by sleep disruption and sleep deprivation can critically affect mission outcome in both spaceflight and other extreme environments. In this study, the seven-person crew (four men, three women) lived a Martian sol (24.65 h) for 37 d during a long-term stay at the Flashline Mars Arctic Research Station (FMARS) on Devon Island, Canada. Crewmembers underwent cardiopulmonary monitoring for signs of circadian disruption and completed a modified Pittsburgh Sleep Diary to monitor subjective fatigue. Crewmembers underwent cognitive testing to identify the effects, if any, of sleep disruption upon cognitive skill., Methods: A Martian sol was implemented for 37 d during the Arctic mission. Each crewmember completed an adapted version of the Pittsburgh Sleep Diary in tandem with electrocardiograph (ECG) cardiopulmonary monitoring of sleep by the Cardiac Adapted Sleep Parameters Electrocardiogram Recorder (CASPER). Crewmembers also underwent cognitive testing during this time period., Results: Sleep diary data indicate improvement in alertness with the onset of the sol (fatigue decreasing from 5.1 to 4.0, alertness increasing from 6.1 to 7.0). Cardiopulmonary data suggest sleep instability, though trends were not statistically significant. Crewmember decision speed time scores improved from pre-Mars to Mars (average improving from 66.5 to 84.0%), though the remainder of cognitive testing results were not significant., Discussion: While subjective data demonstrate improved sleep and alertness during the sol, objective data demonstrate no significant alteration of sleep patterns. There was no apparent cognitive decline over the course of the mission.

Non-contact, non-invasive monitoring of hemodynamic parameters would be ideal for medical monitoring in a variety of environments. Radio Frequency Impedance Interrogation (RFII) measures hemodynamic function via resonance frequency coupling to a hydrophilic protein molecule. While the application of this technology to hemodynamic monitoring has demonstrated initial success, this preliminary study examined the use of RFII for subject identification by waveform signal analysis, which would allow confirmation of the identity of a subject in an operational setting prior to rescue efforts. Preliminary results demonstrate an excellent recognition rate using the RFII signature and pattern classification. Each individual has a consistent pattern during the initial waveform identification period that is visually distinct from the other individuals in the data set. These results suggest that RFII may be of great utility in the pre-hospital triage setting for patient monitoring and for the rapid identification of subjects in the operational setting.

Electrical impedance images were made using the ACT 3 instrument, which applies currents simultaneously to 32 electrodes and measures the resulting voltages on those same electrodes. A reconstruction algorithm was written for a three-dimensional cylinder having electrodes in two or four layers, using current patterns that pass current among different planes of electrodes, as well as within each plane. We have previously reported useful vertical resolution by the use of added layers of electrodes. The aim of the present study was to demonstrate that physiologically useful information can be obtained by examining cephalo-caudal differences in three-dimensional images. Phasic changes throughout the cardiac cycle are seen to be markedly different at the heart compared to lung region, both above and beside it. We formed hydrogel electrodes each 3 cm tall and 7 cm wide and applied them to the thorax of an upright human subject in four horizontal rows; each row contained eight electrodes. During breath-holding, cardiac activity was seen in all layers. With systole, conductivity in the anterior of the lowest layers decreased, but not in the upper layer. In the upper layers, conductivity increased with systole in many regions. These observations are consistent with the opposite changes in blood volume of the heart and lungs and the locations of these organs. This paper demonstrates the feasibility of producing and displaying physiologically interpretable three-dimensional images of the chest in real time.

Electrical impedance tomography is a technology for producing images of internal body structures based upon electrical measurements made from electrodes on the body surface. Typically a single plane of electrodes is used, seeking to reconstruct a cross section of the body. Yet the majority of image reconstruction algorithms ignore the three-dimensional (3D) characteristics of the current flow in the body. Actually, a substantial amount of current flows out of the electrode plane, creating distortions in the resulting images. This paper describes a reconstruction algorithm, ToDLeR, for solving a linearized 3D inverse problem in impedance imaging. The algorithm models the body as a homogeneous cylinder and accounts for the 3D current flow in the body by analytically solving for the current flow from one or more layers of electrodes on the surface of the cylinder. The algorithm was implemented on the ACT3 real-time imaging system and data were collected from a 3D test phantom using one, two and four layers of electrodes. By using multiple planes of electrodes, improved accuracy in any particular electrode plane was obtained, with decreased sensitivity to out-of-plane objects. A cylindrical target located vertically more than 8 cm below a single layer of 16 electrodes, and positioned radially midway between the centre and the boundary, produced an image that had 35% of the value obtained when the target was in the electrode plane. By adding an additional layer of 16 electrodes below the first electrode plane, and using 3D current patterns, this artefact was reduced to less than 10% of the peak value. We conclude that the 3D algorithm, used with multiple planes of electrodes, reduces the distortions from out-of-plane structures in the body.

The sensitivity of an impedance imaging system to small cylindrical inhomogeneities in two-dimensional (2-D) and three-dimensional (3-D) saline tanks was studied for different height electrodes and different height targets. Experimental results were compared with analytical models. Inhomogeneities in the 3-D tank having limited vertical extent were detected by electrodes of vertical size comparable to that of the inhomogeneity. Taller electrodes had increased sensitivity to short targets to only a limited extent. When the electrode height was more than twice that of the target, sensitivity decreased or remained the same with further increases in electrode height. The system was less sensitive to inhomogeneities in the 3-D tank than to those in the 2-D tank. The distinguishability of conductors was greater than that of insulators in the 3-D tank, and the opposite was true in the 2-D tank, consistent with an analytical result.