Physiological Fitness of U.S. Army Aviators Compared to the U.S. General Population.

INTRODUCTION: U.S. Army aviators are required to maintain a level of physiological fitness as part of their qualifying process, which suggests that they are generally physically healthy. However, it has not been statistically proven that they are more "physiologically fit" than the general population.METHODS: This retrospective study compares physiological measurements of U.S. Army aviators from the Aeromedical Electronic Resource Office database to the U.S. general population using the Center for Disease Control's National Health and Nutrition Examination Survey data. To enable an accurate comparison of physiological metrics between U.S. Army aviators and the U.S. general population, aviators were categorized into the same age groups and biological genders used for segmentation of the national population data.RESULTS: On average, pulse rate was 4.85 bpm lower in male aviators and 6.84 bpm lower in female aviators. Fasting glucose levels were, on average, 10.6 mg · dL-1 lower in aviators compared to the general population. Key metrics like pulse rate and fasting glucose were lower in aviators, indicating cardiovascular and metabolic advantages. However, parameters like cholesterol showed less consistent differences.DISCUSSION: While aviation physical demands and administrative policies selecting for elite physiological metrics produce improvements on some dimensions, a nuanced view accounting for the multitude of factors influencing an aviator's physiological fitness is still warranted. Implementing targeted health monitoring and maintenance programs based on assessments conducted more frequently than the current annual flight physical may optimize aviator safety and performance over the course of a career.D'Alessandro M, Mackie R, Wolf S, McGhee JS, Curry I. Physiological fitness of U.S. Army aviators compared to the U.S. general population. Aerosp Med Hum Perform. 2024; 95(4):175-186.

Assessing the variation in amount of pressure exerted by haemostatic pressure bandages: a volunteer study.

We assess the range of pressures exerted by haemostatic compression bandages on upper limb arterial injuries. Maintaining a pink hand can act as a safety marker to prevent excessive bandage pressure and avert compression injuries.

A Comparison of Nonhuman Primate Injuries in Horizontal Versus Vertical Sled +Gz (Head-to-Foot) Impact Accelerations.

INTRODUCTION: Accelerative events commonly expose military pilots to potentially injurious + Gz (axial, caudal to cranial) accelerations. The Naval Biodynamics Laboratory exposed nonhuman primates (NHPs) to + Gz loading in two subject orientations (supine or upright) to assess the effect of orientation and accelerations associated with injury at accelerations unsafe for human participation. MATERIALS AND METHODS: Archived care records, run records, and necropsy and pathology reports were used to identify acceleration-related injuries. Injuries were categorized as central nervous system (CNS), musculoskeletal (MSK) system, or thoracic (THR). The occurrence of injuries relative to corresponding peak sled acceleration (PSA) and subject orientation were compared. A t-test was applied within each injury category to test for a significant difference in mean PSA between orientations. RESULTS: For all 63 + Gz runs conducted, PSA ranged between 6 and 86 G. Of these runs, 17 (6 supine, 11 upright) resulted in acceleration-related injury. The lowest PSAs associated with injury for supine and upright were 69.8 G and 39.6 G, respectively. Individual injury occurrences for supine runs (CNS [n = 5], MSK [n = 6], and THR [n = 6]) occurred at/above 75.7 G, 69.8 G, and 69.8 G, respectively. For upright runs, injury occurrences (CNS [n = 3], MSK injuries [n = 9], and THR injuries [n = 6]) occurred at/above 60.1 G, 39.6 G, and 50.5 G, respectively. The applied t-test showed significant difference between the mean orientation accelerations within each category. Injuries to supine NHPs included compression fracture, organ damage, brain hemorrhage, spinal cord hemorrhage, cervical hemorrhage, paresis/paraplegia, and THR bruising, whereas injuries to upright NHPs included compression fracture, organ damage, spinal cord hemorrhage, paresis/paraplegia, THR bruising, and difficulty breathing. CONCLUSIONS: Axial loading to supine occupants produced more CNS injuries, whereas upright produced more MSK injuries. Both orientations produced equal THR injuries. NHP injuries reported reflected those reported following human + Gz acceleration events, highlighting the importance of orientation during acceleration to mitigate injury for next generation equipment design and testing.

Trends in Metabolic Disorder in U.S. Army Aviators, 20162018.

INTRODUCTION: Recent epidemiological studies of U.S. Army aviators have suggested higher than anticipated rates of hyperlipidemia and metabolic disorder. The goal of this study was to determine whether this finding has persisted in 20162018 and to subsequently determine whether this trend is genuine and warrants further evaluation.METHODS: Data were requested from the U.S. Army Aeromedical Electronic Resource Office (AERO) and retrieved from the publicly available Defense Medical Surveillance System (DMSS) utilizing similar inclusion/exclusion criteria, where possible, as the earlier studies. For each year 20162018, incidence rates (per 1000 person years) for hyperlipidemia and metabolic syndrome were retrieved from DMSS, while percentages of aviators with these conditions were retrieved from AERO. The DMSS incidence rates were also age stratified. No formal analyses were conducted.RESULTS: Results from DMSS showed overall rates of hyperlipidemia ranging from 3.18 to 6.83 per 1000 person-years and for metabolic syndrome from 0.16 to 0.69 per 1000 person-years. The age stratified rates increased proportionally with age. AERO data showed a range of 0.81.5% of aviators had hyperlipidemia and for metabolic syndrome this ranged from 0.31 to 0.45%. These rates are broadly comparable to the previous studies findings.DISCUSSION: This studys findings suggest no continued increase in hyperlipidemia or metabolic disorder in aviators. While the exact cause is unknown, one could speculate a number of sources such as preferences in testing or encouragement from specific commanders or flight surgeons.Goldie C, McGhee J, Kelley AM. Trends in metabolic disorder in U.S. Army aviators, 20162018. Aerosp Med Hum Perform. 2021; 92(1):4346.

Aviation Maxillofacial Shields and Blunt Impact Protection in U.S. Army Helicopter Mishaps.

BACKGROUND: Maxillofacial shields (MFSs) are an available piece of aviation protective equipment designed to integrate into aircrew helmets and protect the face from wind and flying debris. Aviators have anecdotally reported that MFSs have provided blunt impact protection during impact events (i.e., a crash); however, no such cases have been formally documented in the literature.CASE REPORTS: Two cases were identified where aircrew wearing MFSs were involved in mishaps resulting in maxillofacial blunt impacts. In the first case, an OH-58 pilot struck the cyclic with his head/face during a crash. In the second case, a CH-47 crew chief was struck in the face by a maintenance panel dislodged from the aircraft. In both cases the MFS was damaged, but neither service member experienced injuries as a result of impact to the face.DISCUSSION: The cases illustrate the effectiveness of the MFS against blunt impact during aviation mishaps. While MFS use is currently optional for aircrew, it is believed that increased MFS use would result in fewer or less severe facial injuries as well as decrease the associated time and monetary losses due to injury.Weisenbach CA, McGhee JS. Aviation maxillofacial shields and blunt impact protection in U.S. Army helicopter mishaps. Aerosp Med Hum Perform. 2021; 92(1):5053.

Retrospective Assessment of U.S. Army Aviator Anthropometric Screening Process.

INTRODUCTION: The current U.S. Army aviator anthropometric screening process for rotary-wing cockpit compatibility was codified over 30 yr ago. Critical to the process are the anthropometric standards that define what is acceptable for U.S. Army flight school applicants. The purpose of this study was to assess and optimize the efficiency of the standards in screening for anthropometric cockpit compatibility while maintaining safety.METHODS: A retrospective analysis was performed. Anthropometry and disposition data of flight school applicants from 2005 to 2014 were taken from the Aeromedical Electronic Resource Office database to determine efficiency of the process. Data on mishaps from 1972 to 2017 were retrieved from the Risk Management Information System database to determine the safety benchmark of the existing process, to which adjusted standards would be held. Adjustments to standards were modeled that would more efficiently pass applicants over the period studied without exceeding the established acceptable safety level.RESULTS: There were 40,136 (98.28%) applicants who passed the standards, while 702 (1.72%) failed. Most (98.52%) applicants who failed the standards and applied for an anthropometry exception to policy (ETP) received one. The models would pass up to 396 (99.25%) applicants who received ETPs without exceeding the established number of mishaps attributable to the anthropometry standards, which was found to be zero.DISCUSSION: The screening process is efficient and effective, but could be improved. Adjusting the standards could increase process efficiency by passing more applicants during their flight physical and widening the applicant pool, while maintaining the current level of safety.Moczynski AN, Weisenbach CA, McGhee JS. Retrospective assessment of U.S. Army aviator anthropometric screening process. Aerosp Med Hum Perform. 2020; 91(9):725731.

How affinity of the ELT-2 GATA factor binding to cis-acting regulatory sites controls Caenorhabditis elegans intestinal gene transcription.

We define a quantitative relationship between the affinity with which the intestine-specific GATA factor ELT-2 binds to cis-acting regulatory motifs and the resulting transcription of asp-1, a target gene representative of genes involved in Caenorhabditis elegans intestine differentiation. By establishing an experimental system that allows unknown parameters (e.g. the influence of chromatin) to effectively cancel out, we show that levels of asp-1 transcripts increase monotonically with increasing binding affinity of ELT-2 to variant promoter TGATAA sites. The shape of the response curve reveals that the product of the unbound ELT-2 concentration in vivo [i.e. (ELT-2free) or ELT-2 'activity'] and the largest ELT-XXTGATAAXX association constant (Kmax) lies between five and ten. We suggest that this (unitless) product [Kmax×(ELT-2free) or the equivalent product for any other transcription factor] provides an important quantitative descriptor of transcription-factor/regulatory-motif interaction in development, evolution and genetic disease. A more complicated model than simple binding affinity is necessary to explain the fact that ELT-2 appears to discriminate in vivo against equal-affinity binding sites that contain AGATAA instead of TGATAA.

Common mental disorders among US army aviation personnel: Prevalence and return to duty.

OBJECTIVES: Assess the prevalence of US Army aviation personnel with common mental disorders, the percentage that return to duty following mental health treatment, and predictors of return to duty. METHODS: Examined the prevalence over a 5-year period. The percentage of personnel who were granted a waiver to return to flying duty following treatment was also determined. RESULTS: The results revealed a 5-year prevalence of 0.036 (95% CI = 0.034-0.038) for personnel experiencing one or more of the mental disorders (N = 1,155). Prevalence was highest for adjustment disorders and for nonpilot participants. Overall, personnel were granted a waiver 55.3% of the time and suspended or disqualified 44.7% of the time. Waivers were more likely to be granted for an adjustment disorder and for pilots. CONCLUSIONS: Discussion focuses on the importance of aviation personnel receiving mental health treatment when problems are not severe to maximize the likelihood of returning to duty.

A Strategy To Isolate Modifiers of Caenorhabditis elegans Lethal Mutations: Investigating the Endoderm Specifying Ability of the Intestinal Differentiation GATA Factor ELT-2.

The ELT-2 GATA factor normally functions in differentiation of the C. elegans endoderm, downstream of endoderm specification. We have previously shown that, if ELT-2 is expressed sufficiently early, it is also able to specify the endoderm and to replace all other members of the core GATA-factor transcriptional cascade (END-1, END-3, ELT-7). However, such rescue requires multiple copies (and presumably overexpression) of the end-1p::elt-2 cDNA transgene; a single copy of the transgene does not rescue. We have made this observation the basis of a genetic screen to search for genetic modifiers that allow a single copy of the end-1p::elt-2 cDNA transgene to rescue the lethality of the end-1 end-3 double mutant. We performed this screen on a strain that has a single copy insertion of the transgene in an end-1 end-3 background. These animals are kept alive by virtue of an extrachromosomal array containing multiple copies of the rescuing transgene; the extrachromosomal array also contains a toxin under heat shock control to counterselect for mutagenized survivors that have been able to lose the rescuing array. A screen of ∼14,000 mutagenized haploid genomes produced 17 independent surviving strains. Whole genome sequencing was performed to identify genes that incurred independent mutations in more than one surviving strain. The C. elegans gene tasp-1 was mutated in four independent strains. tasp-1 encodes the C. elegans homolog of Taspase, a threonine-aspartic acid protease that has been found, in both mammals and insects, to cleave several proteins involved in transcription, in particular MLL1/trithorax and TFIIA. A second gene, pqn-82, was mutated in two independent strains and encodes a glutamine-asparagine rich protein. tasp-1 and pqn-82 were verified as loss-of-function modifiers of the end-1p::elt-2 transgene by RNAi and by CRISPR/Cas9-induced mutations. In both cases, gene loss leads to modest increases in the level of ELT-2 protein in the early endoderm although ELT-2 levels do not strictly correlate with rescue. We suggest that tasp-1 and pqn-82 represent a class of genes acting in the early embryo to modulate levels of critical transcription factors or to modulate the responsiveness of critical target genes. The screen's design, rescuing lethality with an extrachromosomal transgene followed by counterselection, has a background survival rate of <10-4 without mutagenesis and should be readily adapted to the general problem of identifying suppressors of C. elegans lethal mutations.

Initial analysis of archived non-human primate frontal and rear impact data from the biodynamics data resource.

OBJECTIVE: The research objective was to conduct an initial analysis of non-human primate (NHP) data from frontal and rear impact events archived in the Biodynamics Data Resource (BDR) records of the Naval Biodynamics Laboratory (NBDL). These rare data, collected between 1973 and 1989, will inform the safety community of upper-end tolerance limits of NHP and may be related to severe crash scenarios. METHODS: Data from frontal and rear acceleration tests to 93 macaque NHP were examined. Each NHP was fully torso restrained, whereas the head-neck complex was unrestrained. Each NHP underwent between 1 and 21 total runs; 2 total runs was most common-a low-level run and then a high-level run. Following each impact exposure, the NHP was evaluated using a series of medical examinations. Now part of the legacy collection in the BDR, these evaluations were used to assess NHP exposures to be in one of 3 categories: noninjurious, injurious, or fatal. Using reported peak sled acceleration values, data were amenable to survival analysis statistical methodology to derive injury probability curves (IPCs). IPCs were derived for injury and fatality outcomes. RESULTS: Fatal injuries for both frontal and rear impacts were mostly at the cranio-vertebral junction. In addition to hemorrhage, fatal frontal and rear impact tests both produced predominantly atlanto-occipital dislocations, with and without spinal cord transection. After exclusions, IPCs were derived for frontal and rear impact for both (1) fatal outcome and (2) injurious outcome (any injury including fatal injury). For frontal impact, 53 NHP qualified with 5, 25, and 50% risk for fatality at 89, 105, and 114 peak sled Gs, respectively, and for injurious outcome at 70, 92, and 106 Gs, respectively. For rear impact, 34 NHP qualified with 5, 25, and 50% risk for fatality at 96, 122, 138 peak sled Gs, respectively, and for injurious outcome at 75, 99, and 115 Gs, respectively. CONCLUSIONS: The majority of injuries were at the cranio-vertebral junction, indicating that the inertial head mass caused a tensile loading mechanism to the cervical spine. These data may be used in conjunction with finite element modeling to estimate risks to the human population. The most direct application in the automotive environment could be to the well-restrained child. The Nij neck injury criteria, currently based on data from piglet studies, could also benefit because the NHP is a more accurate human surrogate. These types of tests are likely to never be repeated and will form an upper bound of tolerance information valuable to safety system designers.

Quantitating transcription factor redundancy: The relative roles of the ELT-2 and ELT-7 GATA factors in the C. elegans endoderm.

The two GATA transcription factors ELT-2 and ELT-7 function in the differentiation of the C. elegans intestine. ELT-2 loss causes lethality. ELT-7 loss causes no obvious phenotype but enhances the elt-2(-) intestinal phenotype. Thus, ELT-2 and ELT-7 appear partially redundant, with ELT-2 being more influential. To investigate the different regulatory roles of ELT-2 and ELT-7, we compared the transcriptional profiles of pure populations of wild-type, elt-2(-), elt-7(-), and elt-7(-); elt-2(-) double mutant L1-stage larvae. Consistent with the mutant phenotypes, loss of ELT-2 had a>25 fold greater influence on the number of significantly altered transcripts compared to the loss of ELT-7; nonetheless, the levels of numerous transcripts changed upon loss of ELT-7 in the elt-2(-) background. The quantitative responses of individual genes revealed a more complicated behaviour than simple redundancy/partial redundancy. In particular, genes expressed only in the intestine showed three distinguishable classes of response in the different mutant backgrounds. One class of genes responded as if ELT-2 is the major transcriptional activator and ELT-7 provides variable compensatory input. For a second class, transcript levels increased upon loss of ELT-2 but decreased upon further loss of ELT-7, suggesting that ELT-7 actually overcompensates for the loss of ELT-2. For a third class, transcript levels also increased upon loss of ELT-2 but remained elevated upon further loss of ELT-7, suggesting overcompensation by some other intestinal transcription factor(s). In spite of its minor loss-of-function phenotype and its limited sequence similarity to ELT-2, ELT-7 expressed under control of the elt-2 promoter is able to rescue elt-2(-) lethality. Indeed, appropriately expressed ELT-7, like appropriately expressed ELT-2, is able to replace all other core GATA factors in the C. elegans endodermal pathway. Overall, this study focuses attention on the quantitative intricacies behind apparent redundancy or partial redundancy of two related transcription factors.

Evaluation of Head and Brain Injury Risk Functions Using Sub-Injurious Human Volunteer Data.

Risk assessment models are developed to estimate the probability of brain injury during head impact using mechanical response variables such as head kinematics and brain tissue deformation. Existing injury risk functions have been developed using different datasets based on human volunteer and scaled animal injury responses to impact. However, many of these functions have not been independently evaluated with respect to laboratory-controlled human response data. In this study, the specificity of 14 existing brain injury risk functions was assessed by evaluating their ability to correctly predict non-injurious response using previously conducted sled tests with well-instrumented human research volunteers. Six degrees-of-freedom head kinematics data were obtained for 335 sled tests involving subjects in frontal, lateral, and oblique sled conditions up to 16 Gs peak sled acceleration. A review of the medical reports associated with each individual test indicated no clinical diagnosis of mild or moderate brain injury in any of the cases evaluated. Kinematic-based head and brain injury risk probabilities were calculated directly from the kinematic data, while strain-based risks were determined through finite element model simulation of the 335 tests. Several injury risk functions substantially over predict the likelihood of concussion and diffuse axonal injury; proposed maximum principal strain-based injury risk functions predicted nearly 80 concussions and 14 cases of severe diffuse axonal injury out of the 335 non-injurious cases. This work is an important first step in assessing the efficacy of existing brain risk functions and highlights the need for more predictive injury assessment models.

Probing and rearranging the transcription factor network controlling the C. elegans endoderm.

The ELT-2 GATA factor is the predominant transcription factor regulating gene expression in the C. elegans intestine, following endoderm specification. We comment on our previous study (Wiesenfahrt et al., 2016) that investigated how the elt-2 gene is controlled by END-1, END-3 and ELT-7, the 3 endoderm specific GATA factors that lie upstream in the regulatory hierarchy. We also discuss the unexpected result that ELT-2, if expressed sufficiently early and at sufficiently high levels, can specify the C. elegans endoderm, replacing the normal functions of END-1 and END-3.

A 44 bp intestine-specific hermaphrodite-specific enhancer from the C. elegans vit-2 vitellogenin gene is directly regulated by ELT-2, MAB-3, FKH-9 and DAF-16 and indirectly regulated by the germline, by daf-2/insulin signaling and by the TGF-ß/Sma/Mab pathway.

The Caenorhabditis elegans vitellogenin genes are transcribed in the intestine of adult hermaphrodites but not of males. A 44-bp region from the vit-2 gene promoter is able largely to reconstitute this tissue-, stage- and sex-specific-expression. This "enhancer" contains a binding site for the DM-domain factor MAB-3, the male-specific repressor of vitellogenesis, as well as an activator site that we show is the direct target of the intestinal GATA factor ELT-2. We further show that the enhancer is directly activated by the winged-helix/forkhead-factor FKH-9, (whose gene has been shown by others to be a direct target of DAF-16), by an unknown activator binding to the MAB-3 site, and by the full C. elegans TGF-ß/Sma/Mab pathway acting within the intestine. The vit-2 gene has been shown by others to be repressed by the daf-2/daf-16 insulin signaling pathway, which so strongly influences aging and longevity in C. elegans. We show that the activity of the 44 bp vit-2 enhancer is abolished by loss of daf-2 but is restored by simultaneous loss of daf-16. DAF-2 acts from outside of the intestine but DAF-16 acts both from outside of the intestine and from within the intestine where it binds directly to the same non-canonical target site that interacts with FKH-9. Activity of the 44 bp vit-2 enhancer is also inhibited by loss of the germline, in a manner that is only weakly influenced by DAF-16 but that is strongly influenced by KRI-1, a key downstream effector in the pathway by which germline loss increases C. elegans lifespan. The complex behavior of this enhancer presumably allows vitellogenin gene transcription to adjust to demands of body size, germline proliferation and nutritional state but we suggest that the apparent involvement of this enhancer in aging and longevity "pathways" could be incidental.

The function and regulation of the GATA factor ELT-2 in the C. elegans endoderm.

ELT-2 is the major regulator of genes involved in differentiation, maintenance and function of C. elegans intestine from the early embryo to mature adult. elt-2 responds to overexpression of the GATA transcription factors END-1 and END-3, which specify the intestine, as well as to overexpression of the two GATA factors that are normally involved in intestinal differentiation, ELT-7 and ELT-2 itself. Little is known about the molecular mechanisms underlying these interactions, how ELT-2 levels are maintained throughout development or how such systems respond to developmental perturbations. Here, we analyse elt-2 gene regulation through transgenic reporter assays, ELT-2 ChIP and characterisation of in vitro DNA-protein interactions. Our results indicate that elt-2 is controlled by three discrete regulatory regions conserved between C. elegans and C. briggsae that span >4 kb of 5' flanking sequence. These regions are superficially interchangeable but have quantitatively different enhancer properties, and their combined activities indicate inter-region synergies. Their regulatory activity is mediated by a small number of conserved TGATAA sites that are largely interchangeable and interact with different endodermal GATA factors with only modest differences in affinity. The redundant molecular mechanism that forms the elt-2 regulatory network is robust and flexible, as loss of end-3 halves ELT-2 levels in the early embryo but levels fully recover by the time of hatching. When ELT-2 is expressed under the control of end-1 regulatory elements, in addition to its own endogenous promoter, it can replace the complete set of endoderm-specific GATA factors: END-1, END-3, ELT-7 and (the probably non-functional) ELT-4. Thus, in addition to controlling gene expression during differentiation, ELT-2 is capable of specifying the entire C. elegans endoderm.