BACKGROUND: The impact of the spaceflight environment on endogenous estrogen production in female crewmembers and the resulting impact on other adaptations, like bone loss, is an under-investigated topic. Hence, we investigated the interaction of exogenous 17- estradiol (E2) treatment and disuse to test the hypothesis that E2 treatment would mitigate disuse-induced bone loss.METHODS: There were 40 virgin female Sprague-Dawley rats (5 mo old) randomized to placebo (PL; 0 ppm E2) or estrogen (E2; 10 ppm E2) treatments, delivered via custom-made rodent diets; half of each group was randomized to either weightbearing (WB) or hindlimb unloading (HU) for 39 d.RESULTS: We observed expected lower values after HU (615%) in volumetric BMD and cross-sectional areas at the proximal tibia metaphysis (PTM, by pQCT), 20% lower %BV/TV (nonsignificant) at the PTM, and 11% lower femoral neck maximal load; none of these HU-induced impacts were modified by E2. Impaired PTM periosteal expansion was observed in all E2-treated rats, with smaller (13 to 18%) cross-sectional areas. Midshaft tibial geometry was unaffected by E2 treatment, but large reductions (73 to 81%) in periosteal bone formation indices were observed in E2-treated rats.DISCUSSION: In summary, modest supplementation of exogenous E2 did not mitigate decrements in volumetric BMD, PTM cross-sectional geometry, or femoral neck strength observed with HU. However, numerous independent impacts of E2 treatment were observed, with significant suppression of periosteal bone formation indices. If maintained over time, this might impact negatively on cortical bone integrity during prolonged nonweightbearing.Mantri AV, Allaway HCM, Brezicha JE, Hogan HA, Bloomfield SA. Oral estradiol impact on mitigating unloading-induced bone loss in ovary-intact rats. Aerosp Med Hum Perform. 2021; 92(2):6574.

BACKGROUND: Ischemic hypoxia induced by suprathreshold G-force loading can adversely affect vision, cognition, and lead to loss of consciousness (LOC). The purpose of this study was to determine whether reductions in cerebral oxygenation, caused by subthreshold G-forces (up to 4 G_z and of limited durations that do not lead to LOC), would affect visual perception and working memory performance.METHODS: Sixteen subjects performed visual perception and working memory tasks both before and during G_z exposures (1, 2.2, 3, 4 with leg pressurization, 4 with leg and abdomen pressurization) within a human-use centrifuge.RESULTS: As measured using near-infrared spectroscopy, blood oxygenation over medial prefrontal cortex was similar in the 1 and 2.2 G_z conditions, but was reduced to a similar extent in the 3 and 4 G_z conditions. In parallel, visual perception accuracy was reduced in the 3 and 4 G_z conditions, with no difference between the 3 and 4 G_z conditions. No change in reaction time was seen. Conversely, neither accuracy nor reaction time changes were observed for the visual working memory task.DISCUSSION: These results indicate that although visual working memory is not affected, the ability to visually discriminate between stimuli is reduced at G-forces as low as 3 and 4 G_z. This may have important ramifications for pilots who are routinely subjected to such forces.Croft RJ, Klegrd R, Tribukait A, Taylor NAS, Eiken O. Effects of acceleration-induced reductions in retinal and cerebral oxygenation on human performance. Aerosp Med Hum Perform. 2021; 92(2):7582.

BACKGROUND: In-flight breaks are used during augmented long-haul flight operations, allowing pilots a sleep opportunity. The U.S. Federal Aviation Administration duty and rest regulations restrict the pilot flying the landing to using the third rest break. It is unclear how effective these restrictions are on pilots ability to obtain sleep. We hypothesized there would be no difference in self-reported sleep, alertness, and fatigue between pilots taking the second vs. third rest breaks.METHODS: Pilots flying augmented operations in two U.S.-based commercial airlines were eligible for the study. Volunteers completed a survey at top-of-descent (TOD), including self-reported in-flight sleep duration, and Samn-Perelli fatigue and Karolinska Sleepiness Scale ratings. We compared the second to third rest break using noninferiority analysis. The influence of time of day (home-base time; HBT) was evaluated in 4-h blocks using repeated measures ANOVA.RESULTS: From 787 flights 500 pilots provided complete data. The second rest break was noninferior to the third break for self-reported sleep duration (1.5 0.7 h vs. 1.4 0.7 h), fatigue (2.0 1.0 vs. 2.9 1.3), and sleepiness (2.6 1.4 vs. 3.8 1.8) at TOD for landing pilots. Measures of sleep duration, fatigue, and sleepiness were influenced by HBT circadian time of day.DISCUSSION: We conclude that self-reported in-flight sleep, fatigue, and sleepiness from landing pilots taking the second in-flight rest break are equivalent to or better than pilots taking the third break. Our findings support providing pilots with choice in taking the second or third in-flight rest break during augmented operations.Gregory KB, Soriano-Smith RN, Lamp ACM, Hilditch CJ, Rempe MJ, Flynn-Evans EE, Belenky GL. Flight crew alertness and sleep relative to timing of in-flight rest periods in long-haul flights. Aerosp Med Hum Perform. 2021; 92(2):8391.

BACKGROUND: The effects of seasickness on working performance during motion exposure have been reported, while the aftereffects on working ability and life quality decline (WLD) still remain unclarified.METHODS: Two cohorts of healthy male Chinese subjects received either a single (SSV) or repeated (RSV) sea voyage training program on different vessels. A seasickness incidence (SSI) questionnaire was administered to assess the prevalence of seasickness symptoms (vomiting, nausea, other, or no symptoms). A WLD questionnaire was used to survey the general feeling of WLD (severe, moderate, slight, and none) by a 4-point score as well as the incidence rate (IR) of specific WLD items within 24 h after landing.RESULTS: The RSV cohort had lower overall IR of WLD than the SSV cohort (54.64% vs. 63.78%, N 657 for both cohorts). The landing ship trainees in both cohorts showed higher general WLD score and higher IRs of physical fatigue, sleep disorder, and spontaneous locomotion decrement than those trained on the small vessels. Subjects with vomiting or nausea had higher general WLD score and higher IRs of concentration distraction, physical fatigue, anorexia, and spontaneous locomotion decrement than those with no symptoms. Higher IRs of firing accuracy decline (SSV: 21.35% vs. 7.13%, 9.14%; RSV: 22.11% vs. 9.28%, 5.27%), equipment operation disturbance (SSV: 16.85% vs. 3.57%, 6.85%; RSV: 20.47% vs. 7.85%, 7.03%) were also observed in the vomiting subjects than those with other symptoms and no symptoms.DISCUSSION: Significant WLD after landing was associated with transportation types, seasickness severity, and habituation during sea voyage training.Qi R-R, Xiao S-F, Su Y, Mao Y-Q, Pan L-L, Li C-H, Lu Y-L, Wang J-Q, Cai Y-L. Sea voyage training and motion sickness effects on working ability and life quality after landing. Aerosp Med Hum Perform. 2021; 92(2):9298.

INTRODUCTION: In-flight medical emergencies (IFMEs) average 1 of every 604 flights and are expected to increase as the population ages and air travel increases. Flight diversions, or the rerouting of a flight to an alternate destination, occur in 2 to 13% of IFME cases, but may or may not be necessary as determined after the fact. Estimating the effect of IFME diversions compared to nonmedical diversions can be expected to improve our understanding of their impact and allow for more appropriate decision making during IFMEs.METHODS: The current study matched multiple disparate datasets, including medical data, flight plan and track data, passenger statistics, and financial data. Chi-squared analysis and independent samples t-tests compared diversion delays and costs metrics between flights diverted for medical vs. nonmedical reasons. Data were restricted to domestic flights between 1/1/2018 and 6/30/2019.RESULTS: Over 70% of diverted flights recover (continue on to their intended destination after diverting); however, flights diverted due to IFMEs recover more often and more quickly than do flights diverted for nonmedical reasons. IFME diversions introduce less delay overall and cost less in terms of direct operating costs and passenger value of time (averaging around 38,000) than do flights diverted for nonmedical reasons.DISCUSSION: Flights diverted due to IFMEs appear to have less impact overall than do flights diverted for nonmedical reasons. However, the lack of information related to costs for nonrecovered flights and the decision factors involved during nonmedical diversions hinders our ability to offer further insights.Lewis BA, Gawron VJ, Esmaeilzadeh E, Mayer RH, Moreno-Hines F, Nerwich N, Alves PM. Data-driven estimation of the impact of diversions due to in-flight medical emergencies on flight delay and aircraft operating costs. Aerosp Med Hum Perform. 2021; 92(2):99105.

BACKGROUND: Limited research exists into extraterrestrial CPR, despite the drive for interplanetary travel. This study investigated whether the terrestrial CPR method can provide quality external chest compressions (ECCs) in line with the 2015 UK resuscitation guidelines during ground-based hypogravity simulation. It also explored whether gender, weight, and fatigue influence CPR quality.METHODS: There were 21 subjects who performed continuous ECCs for 5 min during ground-based hypogravity simulations of Mars (0.38 G) and the Moon (0.16 G), with Earths gravity (1 G) as the control. Subjects were unloaded using a body suspension device (BSD). ECC depth and rate, heart rate (HR), ventilation (V_E), oxygen uptake (Vo₂), and Borg scores were measured.RESULTS: ECC depth was lower in 0.38 G (42.9 9 mm) and 0.16 G (40.8 9 mm) compared to 1 G and did not meet current resuscitation guidelines. ECC rate was adequate in all gravity conditions. There were no differences in ECC depth and rate when comparing gender or weight. ECC depth trend showed a decrease by min 5 in 0.38 G and by min 2 in 0.16 G. Increases in HR, V_E, and Vo₂ were observed from CPR min 1 to min 5.DISCUSSION: The terrestrial method of CPR provides a consistent ECC rate but does not provide adequate ECC depths in simulated hypogravities. The results suggest that a mixed-gender space crew of varying bodyweights may not influence ECC quality. Extraterrestrial-specific CPR guidelines are warranted. With a move to increasing ECC rate, permitting lower ECC depths and substituting rescuers after 1 min in lunar gravity and 4 min in Martian gravity is recommended.Sriharan S, Kay G, Lee JCY, Pollock RD, Russomano T. Cardiopulmonary resuscitation in hypogravity simulation. Aerosp Med Hum Perform. 2021; 92(2):106112.

INTRODUCTION: The neurological impact (or lack thereof) of certain medical histories and imaging findings is important to understand in the context of air and spaceflight. There are a number of neurological conditions that, if present in pilots and astronauts, carry variable (and sometimes adverse) functional implications for safety and overall mission success. In this systematic overview, the authors will refer to the relevant clinical and radiological features of brain tumors and vascular anomalies, cerebral edema and intracranial hypertension, concussion and the traumatic brain injury (TBI) spectrum, hematomas, cerebrospinal fluid circulation anomalies including hydrocephalus and sequestrations, spinal degenerative changes, and cerebral ischemia and demyelination. It is notable that these last two conditions have recently been reported to be a complication in some people with coronavirus disease 2019 (COVID-19). A paradigm for practical neurological workup of symptomatic pilots and astronauts will be discussed, as will the controversial notion of pre-emptive radiological screening (vs. not screening) in asymptomatic or clinically occult situations. The concepts of medical surveillance in the setting of known or diagnosed pathologies, and expert panel review and simulator and flight checks in complex neurological cases, are also elaborated on in this paper. We believe this overview will contribute toward the enhancement of a broad understanding of neurological conditions, their clinical workup, and their precautionary management in the setting of aviation and aerospace.Khurana VG, Jithoo R, Barnett M. Aerospace implications of key neurological conditions. Aerosp Med Hum Perform. 2021; 92(2):113119.

BACKGROUND: Cavernomas, cavernous angiomas, or cerebral cavernous malformations are clusters of endothelium-lined blood vessels usually found in the brain. With the increasing use of radiological imaging, these are being detected incidentally in asymptomatic aircrew. The UK Civil Aviation Authority (CAA) experience of cavernomas is described and the aeromedical concerns, that is, the risk of epilepsy, hemorrhage, and the development of a neurological deficit, are considered.METHODS: A search of the CAA database between 1990 and 2020 was performed for the term cavernoma. The gender, age at diagnosis, class of certification held, clinical presentation, location, and size of the lesion were noted. A PubMed literature review for papers with complications of cavernoma was performed.RESULTS: Six cases of cavernoma have been declared to the CAA: five professional pilots and one private pilot. Five were men and one was a woman. The age range was between 38 and 60 yr, with a mean of 48 yr. Two cases presented with clinical symptoms and four were asymptomatic. Complication rates for seizure and hemorrhage were extracted from the published literature together with the significance of other factors such as cavernoma size, family history, multiplicity, and the development of new lesions.DISCUSSION: A policy for the medical certification of aircrew with cavernomas that have presented with clinical symptoms and those that are detected incidentally is proposed.Jagathesan T, OBrien M. Aeromedical implications of cerebral cavernomas. Aerosp Med Hum Perform. 2021; 92(2):120123.

BACKGROUND: Charcot-Marie-Tooth disease (CMT) is a rare hereditary motor and sensory neuropathy. This is a report of a pilot with this condition with a discussion of the challenges for the regulator in the assessment for medical certification of pilots with a neurological disability.CASE REPORT: A pilot with CMTX1 declared his condition to the United Kingdom Civil Aviation Authority when his brother was diagnosed with the same condition. Apart from high arched feet and some difficulty playing sports, he had no problems until his mid-forties, when he very slowly developed increasing weakness with foot dorsiflexion and later wasting and weakness of the small hand muscles. He reported no problems with any flying activity. On clinical examination, it seemed likely that the disability would have an impact on his ability to undertake all the flying tasks of a commercial pilot, including those required in emergencies.DISCUSSION: A modified Medical Flight Test (MFT) specifically tailored by the regulator to test areas of functional impairment allowed the successful certificatory assessment of a pilot with this condition; an approach which could apply to any pilot with a rare neurological disability.Jagathesan T, OBrien M, Rattray A. Certification of a pilot with Charcot-Marie-Tooth disease. Aerosp Med Hum Perform. 2021; 92(2):124126.

INTRODUCTION: Noninferiority or equivalence testing are often used when comparing a novel pharmaceutical, operation, or procedure to the current standard designated as safe. Noninferiority and equivalence testing require estimates of a metric called delta: the margin of meaningful difference. Inappropriate delta margins can lead to invalid conclusions, thereby creating uncertainty about a studys scientific credibility. We recommend that a working group be convened with the following goals: 1) to evaluate delta values currently in use in aviation; 2) to determine if it is possible to develop a systematic, evidence-based, and replicable process to derive delta values based on statistical properties from population data, rather than a mixture of evidence- and opinion-based processes; and 3) based on the findings of the second goal, update the current delta values in use in aviation. This working group should include, at a minimum, government agencies and other key stakeholders using these values within operational settings.Lamp ACM, Rempe MJ, Belenky GL. Delta: the value that matters in fatigue risk management. Aerosp Med Hum Perform. 2021; 92(2):127128.

INTRODUCTION: In the 1990s, Canada, member states of the European Space Agency, Japan, the Russian Federation, and the United States entered into an international agreement Concerning Cooperation on the Civil International Space Station. Among the many unique infrastructure challenges, partners were to develop a comprehensive international medical system and related processes to enable crew medical certification and medical support for all phases of missions, in a framework to support a multilateral space program of unprecedented size, scope, and degree of integration. During the Shuttle/Mir Program, physicians and specialized experts from the United States and Russia studied prototype systems and developed and operated collaborative mechanisms. The 1998 NASA Memoranda of Understanding with each of the other four partners established the Multilateral Medial Policy Board, the Multilateral Space Medicine Board, and the Multilateral Medical Operations Panel as medical authority bodies to ensure International Space Station (ISS) crew health and performance. Since 1998, the medical system of the ISS Program has ensured health and excellent performance of the international crewsan essential prerequisite for the construction and operation of the ISSand prevented mission-impacting medical events and adverse health outcomes. As the ISS is completing its second decade of crewed operation, it is prudent to appraise its established medical framework for its utility moving forward in new space exploration initiatives. Not only the ISS Program participants, but other nations and space agencies as well, concomitant with commercial endeavors in human spaceflight, can benefit from this evidence for future human exploration programs.Doarn CR, Polk JD, Grigoriev A, Comtois J-M, Shimada K, Weerts G, Dervay JP, Taddeo TA, Sargsyan A. A framework for multinational medical support for the International Space Station: a model for exploration. Aerosp Med Hum Perform. 2021; 92(2):129134.