The Effect of Sensor Feature Inputs on Joint Angle Prediction across Simple Movements.

The use of wearable sensors, such as inertial measurement units (IMUs), and machine learning for human intent recognition in health-related areas has grown considerably. However, there is limited research exploring how IMU quantity and placement affect human movement intent prediction (HMIP) at the joint level. The objective of this study was to analyze various combinations of IMU input signals to maximize the machine learning prediction accuracy for multiple simple movements. We trained a Random Forest algorithm to predict future joint angles across these movements using various sensor features. We hypothesized that joint angle prediction accuracy would increase with the addition of IMUs attached to adjacent body segments and that non-adjacent IMUs would not increase the prediction accuracy. The results indicated that the addition of adjacent IMUs to current joint angle inputs did not significantly increase the prediction accuracy (RMSE of 1.92° vs. 3.32° at the ankle, 8.78° vs. 12.54° at the knee, and 5.48° vs. 9.67° at the hip). Additionally, including non-adjacent IMUs did not increase the prediction accuracy (RMSE of 5.35° vs. 5.55° at the ankle, 20.29° vs. 20.71° at the knee, and 14.86° vs. 13.55° at the hip). These results demonstrated how future joint angle prediction during simple movements did not improve with the addition of IMUs alongside current joint angle inputs.

Estimating Compressive and Shear Forces at L5-S1: Exploring the Effects of Load Weight, Asymmetry, and Height Using Optical and Inertial Motion Capture Systems.

This study assesses the agreement of compressive and shear force estimates at the L5-S1 joint using inertial motion capture (IMC) within a musculoskeletal simulation model during manual lifting tasks, compared against a top-down optical motion capture (OMC)-based model. Thirty-six participants completed lifting and lowering tasks while wearing a modified Plug-in Gait marker set for the OMC and a full-body IMC set-up consisting of 17 sensors. The study focused on tasks with variable load weights, lifting heights, and trunk rotation angles. It was found that the IMC system consistently underestimated the compressive forces by an average of 34% (975.16 N) and the shear forces by 30% (291.77 N) compared with the OMC system. A critical observation was the discrepancy in joint angle measurements, particularly in trunk flexion, where the IMC-based model underestimated the angles by 10.92-11.19 degrees on average, with the extremes reaching up to 28 degrees. This underestimation was more pronounced in tasks involving greater flexion, notably impacting the force estimates. Additionally, this study highlights significant differences in the distance from the spine to the box during these tasks. On average, the IMC system showed an 8 cm shorter distance on the X axis and a 12-13 cm shorter distance on the Z axis during lifting and lowering, respectively, indicating a consistent underestimation of the segment length compared with the OMC system. These discrepancies in the joint angles and distances suggest potential limitations of the IMC system's sensor placement and model scaling. The load weight emerged as the most significant factor affecting force estimates, particularly at lower lifting heights, which involved more pronounced flexion movements. This study concludes that while the IMC system offers utility in ergonomic assessments, sensor placement and anthropometric modeling accuracy enhancements are imperative for more reliable force and kinematic estimations in occupational settings.

Presumed Silicone Oil Droplets After Intravitreal Pegcetacoplan Injections.

Importance: Recently, intravitreal pegcetacoplan became the first drug to gain US Food and Drug Administration approval for the treatment of geographic atrophy associated with nonexudative age-related macular degeneration, but the administration of this medication may be associated with unanticipated posttreatment complications. Objective: To assess the prevalence of presumed silicone oil droplets in the vitreous cavity after intravitreal injection of pegcetacoplan. Design, Setting, and Participants: This case series study involved a retrospective record review of all 55 patients treated with intravitreal pegcetacoplan, 0.1 mL in 150-mg/mL solution, between March 24 and June 5, 2023, at a single specialty retina practice. All injections were done using needles from the kit supplied by Apellis Pharmaceuticals on a 1-mL McKesson Luer lock syringe. Main Outcomes and Measures: The presence or absence of presumed silicone bubbles detected during dilated biomicroscopic fundus examination and/or on color fundus photographs, the presence or absence of symptoms, change in visual acuity, and/or increase in intraocular pressure. Results: A total of 62 intravitreal pegcetacoplan injections were given to 55 patients (mean [SD] age, 83.8 [7.8] years; 33 women [60%]) from March 24 to June 5, 2023. Of the 55 patients, 16 (29%; mean [SD] age, 83.8 [7.4] years; 9 women [56%]) had presumed intravitreal silicone droplets discovered 2 to 4 weeks after treatment, 3 of which were documented on color fundus photographs. Of the 16 patients, 14 (88%) were symptomatic for new floaters that they described as persistent, while 2 (13%) were asymptomatic. There were no signs of inflammation or infection, no increases in intraocular pressure, and no changes in visual acuity for all 16 patients. Conclusions and Relevance: A substantial percentage of patients had symptomatic floaters from presumed intravitreal silicone oil droplets after injections of pegcetacoplan using a McKesson 1-mL Luer lock syringe. These findings support consideration of informing patients of this potential adverse effect, avoiding use of the McKesson syringe, and considering use of silicone-free syringes for pegcetacoplan injections.

Drift-Free Joint Angle Calculation Using Inertial Measurement Units without Magnetometers: An Exploration of Sensor Fusion Methods for the Elbow and Wrist.

Joint angles of the lower extremities have been calculated using gyroscope and accelerometer measurements from inertial measurement units (IMUs) without sensor drift by leveraging kinematic constraints. However, it is unknown whether these methods are generalizable to the upper extremity due to differences in motion dynamics. Furthermore, the extent that post-processed sensor fusion algorithms can improve measurement accuracy relative to more commonly used Kalman filter-based methods remains unknown. This study calculated the elbow and wrist joint angles of 13 participants performing a simple ≥30 min material transfer task at three rates (slow, medium, fast) using IMUs and kinematic constraints. The best-performing sensor fusion algorithm produced total root mean square errors (i.e., encompassing all three motion planes) of 6.6°, 3.6°, and 2.0° for the slow, medium, and fast transfer rates for the elbow and 2.2°, 1.7°, and 1.5° for the wrist, respectively.

Cardiovascular Protective Effects of NP-6A4, a Drug with the FDA Designation for Pediatric Cardiomyopathy, in Female Rats with Obesity and Pre-Diabetes.

BACKGROUND: Obese and pre-diabetic women have a higher risk for cardiovascular death than age-matched men with the same symptoms, and there are no effective treatments. We reported that obese and pre-diabetic female Zucker Diabetic Fatty (ZDF-F) rats recapitulate metabolic and cardiac pathology of young obese and pre-diabetic women and exhibit suppression of cardio-reparative AT2R. Here, we investigated whether NP-6A4, a new AT2R agonist with the FDA designation for pediatric cardiomyopathy, mitigate heart disease in ZDF-F rats by restoring AT2R expression. METHODS: ZDF-F rats on a high-fat diet (to induce hyperglycemia) were treated with saline, NP-6A4 (10 mg/kg/day), or NP-6A4 + PD123319 (AT2R-specific antagonist, 5 mg/kg/day) for 4 weeks (n = 21). Cardiac functions, structure, and signaling were assessed by echocardiography, histology, immunohistochemistry, immunoblotting, and cardiac proteome analysis. RESULTS: NP-6A4 treatment attenuated cardiac dysfunction, microvascular damage (-625%) and cardiomyocyte hypertrophy (-263%), and increased capillary density (200%) and AT2R expression (240%) (p < 0.05). NP-6A4 activated a new 8-protein autophagy network and increased autophagy marker LC3-II but suppressed autophagy receptor p62 and autophagy inhibitor Rubicon. Co-treatment with AT2R antagonist PD123319 suppressed NP-6A4's protective effects, confirming that NP-6A4 acts through AT2R. NP-6A4-AT2R-induced cardioprotection was independent of changes in body weight, hyperglycemia, hyperinsulinemia, or blood pressure. CONCLUSIONS: Cardiac autophagy impairment underlies heart disease induced by obesity and pre-diabetes, and there are no drugs to re-activate autophagy. We propose that NP-6A4 can be an effective drug to reactivate cardiac autophagy and treat obesity- and pre-diabetes-induced heart disease, particularly for young and obese women.

Using cultured canine cardiac slices to model the autophagic flux with doxorubicin.

Chemotherapy-induced impairment of autophagy is implicated in cardiac toxicity induced by anti-cancer drugs. Imperfect translation from rodent models and lack of in vitro models of toxicity has limited investigation of autophagic flux dysregulation, preventing design of novel cardioprotective strategies based on autophagy control. Development of an adult heart tissue culture technique from a translational model will improve investigation of cardiac toxicity. We aimed to optimize a canine cardiac slice culture system for exploration of cancer therapy impact on intact cardiac tissue, creating a translatable model that maintains autophagy in culture and is amenable to autophagy modulation. Canine cardiac tissue slices (350 µm) were generated from left ventricular free wall collected from euthanized client-owned dogs (n = 7) free of cardiovascular disease at the Foster Hospital for Small Animals at Tufts University. Cell viability and apoptosis were quantified with MTT assay and TUNEL staining. Cardiac slices were challenged with doxorubicin and an autophagy activator (rapamycin) or inhibitor (chloroquine). Autophagic flux components (LC3, p62) were quantified by western blot. Cardiac slices retained high cell viability for >7 days in culture and basal levels of autophagic markers remained unchanged. Doxorubicin treatment resulted in perturbation of the autophagic flux and cell death, while rapamycin co-treatment restored normal autophagic flux and maintained cell survival. We developed an adult canine cardiac slice culture system appropriate for studying the effects of autophagic flux that may be applicable to drug toxicity evaluations.

Gyroscope vector magnitude: A proposed method for measuring angular velocities.

High movement velocities are among the primary risk factors for work-related musculoskeletal disorders (MSDs). Ergonomists have commonly used two methods to calculate angular movement velocities of the upper arms using inertial measurement units (accelerometers and gyroscopes). Generalized velocity is the speed of movement traveled on the unit sphere per unit time. Inclination velocity is the derivative of the postural inclination angle relative to gravity with respect to time. Neither method captures the full extent of upper arm angular velocity. We propose a new method, the gyroscope vector magnitude (GVM), and demonstrate how GVM captures angular velocities around all motion axes and more accurately represents the true angular velocities of the upper arm. We use optical motion capture data to demonstrate that the previous methods for calculating angular velocities capture 89% and 77% relative to our proposed method.

A nanoparticle probe for the imaging of autophagic flux in live mice via magnetic resonance and near-infrared fluorescence.

Autophagy-the lysosomal degradation of cytoplasmic components via their sequestration into double-membraned autophagosomes-has not been detected non-invasively. Here we show that the flux of autophagosomes can be measured via magnetic resonance imaging or serial near-infrared fluorescence imaging of intravenously injected iron oxide nanoparticles decorated with cathepsin-cleavable arginine-rich peptides functionalized with the near-infrared fluorochrome Cy5.5 (the peptides facilitate the uptake of the nanoparticles by early autophagosomes, and are then cleaved by cathepsins in lysosomes). In the heart tissue of live mice, the nanoparticles enabled quantitative measurements of changes in autophagic flux, upregulated genetically, by ischaemia-reperfusion injury or via starvation, or inhibited via the administration of a chemotherapeutic or the antibiotic bafilomycin. In mice receiving doxorubicin, pre-starvation improved cardiac function and overall survival, suggesting that bursts of increased autophagic flux may have cardioprotective effects during chemotherapy. Autophagy-detecting nanoparticle probes may facilitate the further understanding of the roles of autophagy in disease.

Transdermal Delivery of High Molecular Weight Antibiotics to Deep Tissue Infections via Droplette Micromist Technology Device (DMTD).

Wound infection by multidrug-resistant (MDR) bacteria is a major disease burden. Systemic administration of broad-spectrum antibiotics colistin methanesulfonate (CMS) and vancomycin are the last lines of defense against deep wound infections by MDR bacteria. However, systemic administration of CMS and vancomycin are linked to life-threatening vital organ damage. Currently there are no effective topical application strategies to deliver these high molecular weight antibiotics across the stratum corneum. To overcome this difficulty, we tested if high molecular weight antibiotics delivered by Droplette micromist technology device (DMTD), a transdermal delivery device that generates a micromist capable of packaging large molecules, could attenuate deep skin tissue infections. Using green fluorescent protein-tagged E. coli and live tissue imaging, we show that (1) the extent of attenuation of deep-skin E. coli infection was similar when treated with topical DMTD- or systemic IP (intraperitoneal)-delivered CMS; (2) DMTD-delivered micromist did not spread the infection deeper; (3) topical DMTD delivery and IP delivery resulted in similar levels of vancomycin in the skin after a 2 h washout period; and (4) IP-delivered vancomycin was about 1000-fold higher in kidney and plasma than DMTD-delivered vancomycin indicating systemic toxicity. Thus, topical DMTD delivery of these antibiotics is a safe treatment for the difficult-to-treat deep skin tissue infections by MDR bacteria.

Manufacturing worker perceptions of using wearable inertial sensors for multiple work shifts.

Wearable inertial sensors may be used to objectively quantify exposure to some physical risk factors associated with musculoskeletal disorders. However, concerns regarding their potential negative effects on user safety and satisfaction remain. This study characterized the self-reported daily discomfort, distraction, and burden associated with wearing inertial sensors on the upper arms, trunk, and dominant wrist of 31 manufacturing workers collected over 15 full work shifts. Results indicated that the workers considered the devices as generally comfortable to wear, not distracting, and not burdensome to use. Exposure to non-neutral postures (discomfort, right arm, beta = 0.02; trunk, beta = -0.01), non-cyclic tasks (distraction, beta = -0.26), and higher body mass indices (discomfort, beta = 0.05; distraction, beta = 0.02) contributed to statistically significant (p < 0.05), albeit practically small increases in undesirable ratings. For instance, for each additional percentage of time working with the right arm elevated ≥60°, self-reported discomfort ratings increased 0.02 cm on a standard 10 cm visual analog scale. Female workers reported less discomfort and distraction while wearing the sensors at work than males (discomfort, beta = -0.93; distraction, beta = -0.3). In general, the low ratings of discomfort, distraction, and burden associated with wearing the devices during work suggests that inertial sensors may be suitable for extended use among manufacturing workers.

Lysyl oxidase regulation and protein aldehydes in the injured newborn lung.

During newborn lung injury, excessive activity of lysyl oxidases (LOXs) disrupts extracellular matrix (ECM) formation. Previous studies indicate that TGFß activation in the O2-injured mouse pup lung increases lysyl oxidase (LOX) expression. But how TGFß regulates this, and whether the LOXs generate excess pulmonary aldehydes are unknown. First, we determined that O2-mediated lung injury increases LOX protein expression in TGFß-stimulated pup lung interstitial fibroblasts. This regulation appeared to be direct; this is because TGFß treatment also increased LOX protein expression in isolated pup lung fibroblasts. Then using a fibroblast cell line, we determined that TGFß stimulates LOX expression at a transcriptional level via Smad2/3-dependent signaling. LOX is translated as a pro-protein that requires secretion and extracellular cleavage before assuming amine oxidase activity and, in some cells, reuptake with nuclear localization. We found that pro-LOX is processed in the newborn mouse pup lung. Also, O2-mediated injury was determined to increase pro-LOX secretion and nuclear LOX immunoreactivity particularly in areas populated with interstitial fibroblasts and exhibiting malformed ECM. Then, using molecular probes, we detected increased aldehyde levels in vivo in O2-injured pup lungs, which mapped to areas of increased pro-LOX secretion in lung sections. Increased activity of LOXs plays a critical role in the aldehyde generation; an inhibitor of LOXs prevented the elevation of aldehydes in the O2-injured pup lung. These results reveal new mechanisms of TGFß and LOX in newborn lung disease and suggest that aldehyde-reactive probes might have utility in sensing the activation of LOXs in vivo during lung injury.

Habitability Models for Astrobiology.

Habitability has been generally defined as the capability of an environment to support life. Ecologists have been using Habitat Suitability Models (HSMs) for more than four decades to study the habitability of Earth from local to global scales. Astrobiologists have been proposing different habitability models for some time, with little integration and consistency among them, being different in function to those used by ecologists. Habitability models are not only used to determine whether environments are habitable, but they also are used to characterize what key factors are responsible for the gradual transition from low to high habitability states. Here we review and compare some of the different models used by ecologists and astrobiologists and suggest how they could be integrated into new habitability standards. Such standards will help improve the comparison and characterization of potentially habitable environments, prioritize target selections, and study correlations between habitability and biosignatures. Habitability models are the foundation of planetary habitability science, and the synergy between ecologists and astrobiologists is necessary to expand our understanding of the habitability of Earth, the Solar System, and extrasolar planets.

EMG and Joint Angle-Based Machine Learning to Predict Future Joint Angles at the Knee.

Electromyography (EMG) is commonly used to measure electrical activity of the skeletal muscles. As exoskeleton technology advances, these signals may be used to predict human intent for control purposes. This study used an artificial neural network trained and tested with knee flexion angles and knee muscle EMG signals to predict knee flexion angles during gait at 50, 100, 150, and 200 ms into the future. The hypothesis of this study was that the algorithm's prediction accuracy would only be affected by time into the future, not subject, gender or side, and that as time into the future increased, the prediction accuracy would decrease. A secondary hypothesis was that as the number of algorithm training trials increased, the prediction accuracy of the artificial neural network (ANN) would increase. The results of this study indicate that only time into the future affected the accuracy of knee flexion angle prediction (p < 0.001), whereby greater time resulted in reduced accuracy (0.68 to 4.62 degrees root mean square error (RMSE) from 50 to 200 ms). Additionally, increased number of training trials resulted in increased angle prediction accuracy.

Comparing upper arm and trunk kinematics between manufacturing workers performing predominantly cyclic and non-cyclic work tasks.

Musculoskeletal disorders (MSDs) are common among manufacturing workers. Exposure to non-neutral postures and high movement speeds associated with MSDs among manufacturing workers may depend on the extent of the variability in the work tasks performed (i.e., predominantly "cyclic" versus "non-cyclic" work). The objectives of this study were to (i) compare mean levels of full-shift exposure summary metrics based on both posture and movement speed between manufacturing workers performing predominantly cyclic (n = 18) and non-cyclic (n = 17) tasks, and (ii) explore patterns of between- and within-worker exposure variance and between-minute (within-shift) exposure level and variation within each group. Inertial sensors were used to measure exposures for up to 15 full shifts per participant. Results indicated (i) substantially higher upper arm and trunk movement speeds among workers performing predominantly cyclic tasks relative to workers performing non-cyclic tasks despite similar postures, and (ii) greater exposure variability both between and within workers in the non-cyclic group.

Measuring upper arm elevation using an inertial measurement unit: An exploration of sensor fusion algorithms and gyroscope models.

Many sensor fusion algorithms for analyzing human motion information collected with inertial measurement units have been reported in the scientific literature. Selecting which algorithm to use can be a challenge for ergonomists that may be unfamiliar with the strengths and limitations of the various options. In this paper, we describe fundamental differences among several algorithms, including differences in sensor fusion approach (e.g., complementary filter vs. Kalman Filter) and gyroscope error modeling (i.e., inclusion or exclusion of gyroscope bias). We then compare different sensor fusion algorithms considering the fundamentals discussed using laboratory-based measurements of upper arm elevation collected under three motion speeds. Results indicate peak displacement errors of <4.5° with a computationally efficient, non-proprietary complementary filter that did not account for gyroscope bias during each of the one-minute trials. Controlling for gyroscope bias reduced peak displacement errors to <3.0°. The complementary filters were comparable (<1° peak displacement difference) to the more complex Kalman filters.

A novel tracer for in vivo optical imaging of fatty acid metabolism in the heart and brown adipose tissue.

Multiplexed imaging is essential for the evaluation of substrate utilization in metabolically active organs, such as the heart and brown adipose tissue (BAT), where substrate preference changes in pathophysiologic states. Optical imaging provides a useful platform because of its low cost, high throughput and intrinsic ability to perform composite readouts. However, the paucity of probes available for in vivo use has limited optical methods to image substrate metabolism. Here, we present a novel near-infrared (NIR) free fatty acid (FFA) tracer suitable for in vivo imaging of deep tissues such as the heart. Using click chemistry, Alexa Fluor 647 DIBO Alkyne was conjugated to palmitic acid. Mice injected with 0.05 nmol/g bodyweight of the conjugate (AlexaFFA) were subjected to conditions known to increase FFA uptake in the heart (fasting) and BAT [cold exposure and injection with the ß3 adrenergic agonist CL 316, 243(CL)]. Organs were subsequently imaged both ex vivo and in vivo to quantify AlexaFFA uptake. The blood kinetics of AlexaFFA followed a two-compartment model with an initial fast compartment half-life of 0.14 h and a subsequent slow compartment half-life of 5.2 h, consistent with reversible protein binding. Ex vivo fluorescence imaging after overnight cold exposure and fasting produced a significant increase in AlexaFFA uptake in the heart (58 ± 12%) and BAT (278 ± 19%) compared to warm/fed animals. In vivo imaging of the heart and BAT after exposure to CL and fasting showed a significant increase in AlexaFFA uptake in the heart (48 ± 20%) and BAT (40 ± 10%) compared to saline-injected/fed mice. We present a novel near-infrared FFA tracer, AlexaFFA, that is suitable for in vivo quantification of FFA metabolism and can be applied in the context of a low cost, high throughput, and multiplexed optical imaging platform.

Pro-Senescence and Anti-Senescence Mechanisms of Cardiovascular Aging: Cardiac MicroRNA Regulation of Longevity Drug-Induced Autophagy.

Chronological aging as well as biological aging accelerated by various pathologies such as diabetes and obesity contribute to cardiovascular aging, and structural and functional tissue damage of the heart and vasculature. Cardiovascular aging in humans is characterized by structural pathologic remodeling including cardiac and vascular fibrosis, hypertrophy, stiffness, micro- and macro-circulatory impairment, left ventricular diastolic dysfunction precipitating heart failure with either reduced or preserved ejection fraction, and cardiovascular cell death. Cellular senescence, an important hallmark of aging, is a critical factor that impairs repair and regeneration of damaged cells in cardiovascular tissues whereas autophagy, an intracellular catabolic process is an essential inherent mechanism that removes senescent cells throughout life time in all tissues. Several recent reviews have highlighted the fact that all longevity treatment paradigms to mitigate progression of aging-related pathologies converge in induction of autophagy, activation of AMP kinase (AMPK) and Sirtuin pathway, and inhibition of mechanistic target of rapamycin (mTOR). These longevity treatments include health style changes such as caloric restriction, and drug treatments using rapamycin, the first FDA-approved longevity drug, as well as other experimental longevity drugs such as metformin, rapamycin, aspirin, and resveratrol. However, in the heart tissue, autophagy induction has to be tightly regulated since evidence show excessive autophagy results in cardiomyopathy and heart failure. Here we discuss emerging evidence for microRNA-mediated tight regulation of autophagy in the heart in response to treatment with rapamycin, and novel approaches to monitor autophagy progression in a temporal manner to diagnose and regulate autophagy induction by longevity treatments.

Biomechanical factors during common agricultural activities: Results of on-farm exposure assessments using direct measurement methods.

Agricultural work is associated with increased risk of adverse musculoskeletal health outcomes. The purpose of this study was to quantify exposure to biomechanical factors among a sample (n = 55) of farmers in the Midwest region of the U.S. while they performed a variety of routine agricultural activities, and to compare exposure levels between these activities. Surface electromyography was used to estimate activity levels of the erector spinae, upper trapezius, forearm flexor, and forearm extensor muscle groups. Simultaneously, inertial sensors were used to measure kinematics of the trunk, upper arm, and wrist. In general, lower muscle activity levels, less extreme postures, and slower movement speeds were observed during activities that involved primarily the use of agricultural machinery in comparison to manual activities, suggesting a potential advantage of mechanization relative to musculoskeletal health. Median wrist movement speeds exceeding recently proposed exposure thresholds were also observed during many manual activities, such as milking animals and repairing equipment. Upper arm postures and movement speeds did not appear to confer excessive risk for shoulder-related outcomes (on the whole), but interpretation of the results is limited by a sampling approach that may not have captured the full extent of exposure variation. Not surprisingly, substantial variation in exposure levels were observed within each agricultural activity, which is related to substantial variation in the equipment, tools, and work practices used by participants. Ultimately, the results of this study contribute to an emerging literature in which the physical demands of routine agricultural work have been described on the basis of sensor-based measurements rather than more common self-report or observation-based approaches.

Elevated Environmental Carbon Dioxide Exposure Confounding Physiologic Events in Aviators?

INTRODUCTION: Physiological events (PEs) are a growing problem for US military aviation with detrimental risks to safety and mission readiness. Seeking causative factors is, therefore, of high importance. There is no evidence to date associating carbon dioxide (CO2) pre-flight exposure and decompression sickness (DCS) in aviators. MATERIALS AND METHODS: This study is a case series of six aviators with PE after being exposed to a rapid decompression event (RDE) with symptoms consistent with type II DCS. The analysis includes retrospective review of flight and environmental data to further assess a possible link between CO2 levels and altitude physiologic events (PEs). IRB approval was obtained for this study. RESULTS: This case series presents six aviators with PE after being exposed to a rapid decompression event (RDE) with symptoms consistent with type II DCS. Another three aviators were also exposed to a RDE, but remained asymptomatic. All events involved tactical jet aircraft flying at an average of 35,600' Mean Sea Level (MSL) when a RDE occurred, Retrospective reviews led to the discovery that the affected individuals were exposed, pre-flight, to poor indoor air quality demonstrated by elevated levels of measured CO2. CONCLUSION: PEs are a growing safety concern for the aviation community in the military. As such, increasing measures are taken to ensure safety of flight and completion of the mission. To date, there is no correlation of CO2 exposure and altitude DCS. While elevated CO2 levels cannot be conclusively implicated as causative, this case series suggests a potential role of CO2 in altitude DCS through CO2 direct involvement with emboli gas composition, as well as pro-inflammatory cascade. Aviators exposed to elevated CO2 in poorly ventilated rooms developed PE symptoms consistent with DCS, while at the same command, aviators that were exposed to a well ventilated room did not. This report is far from an answer, but does demonstrate an interesting case series that draws some questions about CO2's role in these aviator's DCS experience. Other explanations are plausible, including the accurate diagnosis of DCS, health variables amongst the aviators, and differences in aircraft and On-Board Oxygen Generation Systems (OBOGS). For a better understanding, the role of environmental CO2 and pre-flight exposure as a risk of DCS should be reviewed.