White matter and hypoxic hypobaria in humans.

Occupational exposure to hypobaria (low atmospheric pressure) is a risk factor for reduced white matter integrity, increased white matter hyperintensive burden, and decline in cognitive function. We tested the hypothesis that a discrete hypobaric exposure will have a transient impact on cerebral physiology. Cerebral blood flow, fractional anisotropy of water diffusion in cerebral white matter, white matter hyperintensity volume, and concentrations of neurochemicals were measured at baseline and 24 hr and 72 hr postexposure in N = 64 healthy aircrew undergoing standard US Air Force altitude chamber training and compared to N = 60 controls not exposed to hypobaria. We observed that hypobaric exposure led to a significant rise in white matter cerebral blood flow (CBF) 24 hr postexposure that remained elevated, albeit not significantly, at 72 hr. No significant changes were observed in structural measurements or gray matter CBF. Subjects with higher baseline concentrations of neurochemicals associated with neuroprotection and maintenance of normal white matter physiology (glutathione, N-acetylaspartate, glutamate/glutamine) showed proportionally less white matter CBF changes. Our findings suggest that discrete hypobaric exposure may provide a model to study white matter injury associated with occupational hypobaric exposure.

Evaluation of the accuracy and precision of the diffusion parameter EStImation with Gibbs and NoisE removal pipeline.

This work evaluates the accuracy and precision of the Diffusion parameter EStImation with Gibbs and NoisE Removal (DESIGNER) pipeline, developed to identify and minimize common sources of methodological variability including: thermal noise, Gibbs ringing artifacts, Rician bias, EPI and eddy current induced spatial distortions, and motion-related artifacts. Following this processing pipeline, iterative parameter estimation techniques were used to derive diffusion parameters of interest based on the diffusion tensor and kurtosis tensor. We evaluated accuracy using a software phantom based on 36 diffusion datasets from the Human Connectome project and tested the precision by analyzing data from 30 healthy volunteers scanned three times within one week. Preprocessing with both DESIGNER or a standard pipeline based on smoothing (instead of noise removal) improved parameter precision by up to a factor of 2 compared to preprocessing with motion correction alone. When evaluating accuracy, we report average decreases in bias (deviation from simulated parameters) over all included regions for fractional anisotropy, mean diffusivity, mean kurtosis, and axonal water fraction of 9.7%, 8.7%, 4.2%, and 7.6% using DESIGNER compared to the standard pipeline, demonstrating that preprocessing with DESIGNER improves accuracy compared to other processing methods.

Miniature pig magnetic resonance spectroscopy model of normal adolescent brain development.

BACKGROUND: We are developing the miniature pig (Sus scrofa domestica), an in-vivo translational, gyrencephalic model for brain development, as an alternative to laboratory rodents/non-human primates. We analyzed longitudinal changes in adolescent pigs using proton magnetic resonance spectroscopy (1H-MRS) and examined the relationship with white matter (WM) integrity derived from diffusion weighted imaging (DWI). NEW METHOD: Twelve female Sinclair™ pigs underwent three imaging/spectroscopy sessions every 23.95 ± 3.73 days beginning at three months of age using a clinical 3 T scanner. 1H-MRS data were collected using 1.2 × 1.0 × 3.0 cm voxels placed in left and right hemisphere WM using a Point Resolved Spectroscopy sequence (TR = 2000 ms, TE = 30 ms). Concentrations of N-acetylaspartate, myo-inositol (MI), glutamate + glutamine, choline, creatine, and macromolecules (MM) 09 and 14 were averaged from both hemispheres. DWI data were collected using 15 shells of b-values (b = 0-3500 s/mm2) with 32 directions/shell and fit using the WM Tract Integrity model to calculate fractional anisotropy (FA), kurtosis anisotropy (KA) and permeability-diffusivity index. RESULTS: MI and MM09 significantly declined with age. Increased FA and KA significantly correlated with decline in MI and MM09. Correlations lost significance once corrected for age. COMPARISON WITH EXISTING METHODS: MRI scanners/protocols can be used to collect 1H-MRS and DWI data in pigs. Pigs have a larger, more complex, gyrencephalic brain than laboratory rodents but are less complex than non-human primates, thus satisfying the "replacement" principle of animal research. CONCLUSIONS: Longitudinal effects in MRS measurements were similar to those reported in adolescent humans. MRS changes correlated with diffusion measurements indicating ongoing WM myelination/maturation.

Sex Differences in Training Loads during British Army Basic Training.

PURPOSE: To compare training loads between men and women during 14 wk of British Army standard entry basic training. METHODS: Thirty-one male (mean ± SD: age, 21 ± 4 yr; height, 1.78 ± 0.08 m; mass, 77.1 ± 10.5 kg) and 28 female (age, 22 ± 4 yr; height, 1.65 ± 0.05 m; mass, 63.9 ± 8.9 kg) British Army recruits had external (distance) and internal (HR, training impulse [TRIMP], RPE) training loads measured during weeks 1, 2, 6, 12, and 13 of basic training. Total energy expenditure was measured during weeks 1 to 2 and weeks 12 to 13. RESULTS: Daily distance was higher for men than women (13,508 ± 666 vs 11,866 ± 491 m, respectively, P < 0.001). Average daily HR (29% ± 3% vs 30% ± 3% HR reserve) and RPE (4 ± 1 vs 4 ± 1) were not different between men and women, respectively (P ≥ 0.495). Daily TRIMP was higher for women than men (492 ± 130 vs 261 ± 145 au, respectively, P < 0.001). Total energy expenditure was higher for men than women during weeks 1 to 2 (4020 ± 620 vs 2847 ± 323 kcal·d, respectively) and weeks 12 to 13 (4253 ± 556 kcal·d vs 3390 ± 344 kcal·d, respectively) (P < 0.001). Daily RPE, HR, and TRIMP were related to daily distance (R = 0.18-0.57, P ≤ 0.037), and daily RPE was related to daily TRIMP and HR (R = 0.37-0.77, P ≤ 0.001). CONCLUSIONS: Sex differences in training loads could contribute to the greater injury risk for women during basic training. Daily RPE appears a practical option for measuring internal training load during military training.

Patient Safety Climate: A Study of Southern California Healthcare Organizations.

EXECUTIVE SUMMARY: Human error remains the most important factor in unnecessary deaths and suffering in U.S. hospitals. Human error results from healthcare providers' attitudes and behaviors toward patients in different settings. Therefore, taking periodic snapshots of the attitudes and behaviors prevalent in an organization and manifested in its patient safety climate (PSC) is essential.We developed and tested a short survey instrument intended as an organization-level measure of PSC with good psychometric properties that can be used in hospitals, clinics, or other healthcare provider settings. Analysis of data from 61 Southern California healthcare organizations resulted in a PSC model with four distinct, reliable factors: (1) Assistance From Others and the Organization, (2) Leadership Messages of Support in Policy and Behavior, (3) Resources and Work Environment, and (4) Error Reporting Behavior. A PSC score, ranging from 0 to 100, was generated for each organization.For a subsample of hospitals in our study, preliminary results indicate a predictive quality of the model. The higher the PSC score, the lower the number of violations detected by the Centers for Medicare & Medicaid Services in complaint inspections, and the fewer the safety problems reported by The Leapfrog Group.Given the association between PSC and health outcomes, we urge healthcare leaders to use various means, such as our survey, to monitor the degree to which their organizations maintain a climate that fosters patient safety and use such data to pinpoint areas for improvement.

Estimates of Tibial Shock Magnitude in Men and Women at the Start and End of a Military Drill Training Program.

INTRODUCTION: Foot drill is a key component of military training and is characterized by frequent heel stamping, likely resulting in high tibial shock magnitudes. Higher tibial shock during running has previously been associated with risk of lower limb stress fractures, which are prevalent among military populations. Quantification of tibial shock during drill training is, therefore, warranted. This study aimed to provide estimates of tibial shock during military drill in British Army Basic training. The study also aimed to compare values between men and women, and to identify any differences between the first and final sessions of training. MATERIALS AND METHODS: Tibial accelerometers were secured on the right medial, distal shank of 10 British Army recruits (n = 5 men; n = 5 women) throughout a scheduled drill training session in week 1 and week 12 of basic military training. Peak positive accelerations, the average magnitude above given thresholds, and the rate at which each threshold was exceeded were quantified. RESULTS: Mean (SD) peak positive acceleration was 20.8 (2.2) g across all sessions, which is considerably higher than values typically observed during high impact physical activity. Magnitudes of tibial shock were higher in men than women, and higher in week 12 compared with week 1 of training. CONCLUSIONS: This study provides the first estimates of tibial shock magnitude during military drill training in the field. The high values suggest that military drill is a demanding activity and this should be considered when developing and evaluating military training programs. Further exploration is required to understand the response of the lower limb to military drill training and the etiology of these responses in the development of lower limb stress fractures.

Sex differences in neuromuscular fatigability in response to load carriage in the field in British Army recruits.

OBJECTIVES: Women are resistant to neuromuscular fatigue compared to men in response to a range of exercise tasks. The sex differences in the neuromuscular responses to load carriage have yet to be investigated. DESIGN: Prospective cohort study. METHODS: Twenty-three male and 19 female British Army recruits completed a 9.7km loaded march within 90min, with the weight carried dependent on military trade (16±2kg for men and 15±1kg for women). Isometric maximal voluntary contraction (MVC) force of the knee extensors and vertical jump (VJ) height were examined pre- and post-loaded march to examine neuromuscular fatigue. Heart rate (HR) was recorded throughout and ratings of perceived exertion (RPE) was recorded following the march. RESULTS: HR was higher for women (173±9bmin-1, 83±6% heart rate reserve) than men (158±8bmin-1, 72±6% heart rate reserve) (p≤0.001). RPE following the march was also higher for women than men (6±2 vs 4±2, respectively, p<0.001). The loss in MVC force was greater for men than women (-12±9% vs -9±13%, respectively, p=0.031), however VJ height was impaired to a similar extent (-5±11% vs -5±6%, respectively, p=0.582). CONCLUSIONS: The greater physiological stress during load carriage for women compared to men did not translate to a greater severity of knee extensor muscle fatigue, with women demonstrating fatigue resistance.

Miniature pig model of human adolescent brain white matter development.

BACKGROUND: Neuroscience research in brain development and disorders can benefit from an in vivo animal model that portrays normal white matter (WM) development trajectories and has a sufficiently large cerebrum for imaging with human MRI scanners and protocols. NEW METHOD: Twelve three-month-old Sinclair™ miniature pigs (Sus scrofa domestica) were longitudinally evaluated during adolescent development using advanced diffusion weighted imaging (DWI) focused on cerebral WM. Animals had three MRI scans every 23.95 ±â€¯3.73 days using a 3-T scanner. The DWI imaging protocol closely modeled advanced human structural protocols and consisted of fifteen b-shells (b = 0-3500 s/mm2) with 32-directions/shell. DWI data were analyzed using diffusion kurtosis and bi-exponential modeling that provided measurements that included fractional anisotropy (FA), radial kurtosis, kurtosis anisotropy (KA), axial kurtosis, tortuosity, and permeability-diffusivity index (PDI). RESULTS: Significant longitudinal effects of brain development were observed for whole-brain average FA, KA, and PDI (all p < 0.001). There were expected regional differences in trends, with corpus callosum fibers showing the highest rate of change. COMPARISON WITH EXISTING METHOD(S): Pigs have a large, gyrencephalic brain that can be studied using clinical MRI scanners/protocols. Pigs are less complex than non-human primates thus satisfying the "replacement" principle of animal research. CONCLUSIONS: Longitudinal effects were observed for whole-brain and regional diffusion measurements. The changes in diffusion measurements were interepreted as evidence for ongoing myelination and maturation of cerebral WM. Corpus callosum and superficial cortical WM showed the expected higher rates of change, mirroring results in humans.

Utilization of MRI for Cerebral White Matter Injury in a Hypobaric Swine Model-Validation of Technique.

BACKGROUND: Repetitive hypobaric exposure in humans induces subcortical white matter change, observable on magnetic resonance imaging (MRI) and associated with cognitive impairment. Similar findings occur in traumatic brain injury (TBI). We are developing a swine MRI-driven model to understand the pathophysiology and to develop treatment interventions. METHODS: Five miniature pigs (Sus scrofa domestica) were repetitively exposed to nonhypoxic hypobaria (30,000 feet/FIO2 100%/transcutaneous PO2 >90%) while under general anesthesia. Three pigs served as controls. Pre-exposure and postexposure MRIs were obtained that included structural sequences, dynamic contrast perfusion, and diffusion tensor quantification. Statistical comparison of individual subject and group change was performed utilizing a two-tailed t test. FINDINGS: No structural imaging change was noted on T2-weighted or three-dimensional fluid-attenuated inversion recovery imaging between MRI 1 and MRI 2. No absolute difference in dynamic contrast perfusion was observed. A trend (p = 0.084) toward increase in interstitial extra-axonal fluid was noted. When individual subjects were examined, this trend toward increased extra-axonal fluid paralleled a decrease in contrast perfusion rate. DISCUSSION/IMPACT/RECOMMENDATIONS: This study demonstrates high reproducibility of quantitative noninvasive MRI, suggesting MRI is an appropriate assessment tool for TBI and hypobaric-induced injury research in swine. The lack of fluid-attenuated inversion recovery change may be multifactorial and requires further investigation. A trend toward increased extra-axonal water content that negatively correlates with dynamic contrast perfusion implies generalized axonal injury was induced. This study suggests this is a potential model for hypobaric-induced injury as well as potentially other axonal injuries such as TBI in which similar subcortical white matter change occurs. Further development of this model is necessary.

Reproducibility of quantitative structural and physiological MRI measurements.

INTRODUCTION: Quantitative longitudinal magnetic resonance imaging and spectroscopy (MRI/S) is used to assess progress of brain disorders and treatment effects. Understanding the significance of MRI/S changes requires knowledge of the inherent technical and physiological consistency of these measurements. This longitudinal study examined the variance and reproducibility of commonly used quantitative MRI/S measurements in healthy subjects while controlling physiological and technical parameters. METHODS: Twenty-five subjects were imaged three times over 5 days on a Siemens 3T Verio scanner equipped with a 32-channel phase array coil. Structural (T1, T2-weighted, and diffusion-weighted imaging) and physiological (pseudocontinuous arterial spin labeling, proton magnetic resonance spectroscopy) data were collected. Consistency of repeated images was evaluated with mean relative difference, mean coefficient of variation, and intraclass correlation (ICC). Finally, a "reproducibility rating" was calculated based on the number of subjects needed for a 3% and 10% difference. RESULTS: Structural measurements generally demonstrated excellent reproducibility (ICCs 0.872-0.998) with a few exceptions. Moderate-to-low reproducibility was observed for fractional anisotropy measurements in fornix and corticospinal tracts, for cortical gray matter thickness in the entorhinal, insula, and medial orbitofrontal regions, and for the count of the periependymal hyperintensive white matter regions. The reproducibility of physiological measurements ranged from excellent for most of the magnetic resonance spectroscopy measurements to moderate for permeability-diffusivity coefficients in cingulate gray matter to low for regional blood flow in gray and white matter. DISCUSSION: This study demonstrates a high degree of longitudinal consistency across structural and physiological measurements in healthy subjects, defining the inherent variability in these commonly used sequences. Additionally, this study identifies those areas where caution should be exercised in interpretation. Understanding this variability can serve as the basis for interpretation of MRI/S data in the assessment of neurological disorders and treatment effects.

Training in Readmission Reduction in an Indonesian Hospital.

The authors implemented a new discharge protocol to reduce readmission rates in a hospital in West Java, Indonesia. Forty nurses were trained in the use of the protocol. Results indicate that posttest group readmission rates were significantly lower after the implementation of protocol, from 6.11% to 4.21%. The protocol was effective in reducing readmissions for patients discharged from internal medicine, pulmonology, and women. Differences were also found by type of insurance or payment method, generally suggesting that the lower the socioeconomic status of the patients was, the more effective the discharge protocol was.

Reproducibility of tract-based white matter microstructural measures using the ENIGMA-DTI protocol.

BACKGROUND: In preparation for longitudinal analyses of white matter development in youths with family histories of substance use disorders (FH+) or without such histories (FH-), we examined the reproducibility and reliability of global and regional measures of fractional anisotropy (FA) values, measured using the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA)-diffusion tensor imaging (DTI) protocol. Highly reliable measures are necessary to detect any subtle differences in brain development. METHODS: First, we analyzed reproducibility data in a sample of 12 healthy young adults (ages 20-28) imaged three times within a week. Next, we calculated the same metrics in data collected 1-year apart in the sample of 68 FH+ and 21 FH- adolescents. This is a timeframe where within subject changes in white matter microstructure are small compared to between subject variance. Reproducibility was estimated by examining mean coefficients of variation (MCV), mean absolute differences (MAD), and intraclass correlations (ICC) for global and tract-specific FA values. RESULTS: We found excellent reproducibility for whole-brain DTI-FA values and most of the white matter tracts, except for the corticospinal tract and the fornix in both adults and youths. There was no significant effect of FH-group on reproducibility (p = .4). Reproducibility metrics were not significantly different between adolescents and adults (all p > .2). In post hoc analyses, the reproducibility metrics for regional FA values showed a strong positive correlation (r = .6) with the regional FA heritability measures previously reported by ENIGMA-DTI. CONCLUSION: Overall, this study demonstrated an excellent reproducibility of ENIGMA-DTI FA, positing it as viable analysis tools for longitudinal studies and other protocols that repeatedly assess white matter microstructure.

White Matter Integrity in High-Altitude Pilots Exposed to Hypobaria.

INTRODUCTION: Nonhypoxic hypobaric (low atmospheric pressure) occupational exposure, such as experienced by U.S. Air Force U-2 pilots and safety personnel operating inside altitude chambers, is associated with increased subcortical white matter hyperintensity (WMH) burden. The pathophysiological mechanisms underlying this discrete WMH change remain unknown. The objectives of this study were to demonstrate that occupational exposure to nonhypoxic hypobaria is associated with altered white matter integrity as quantified by fractional anisotropy (FA) measured using diffusion tensor imaging and relate these findings to WMH burden and neurocognitive ability. METHODS: There were 102 U-2 pilots and 114 age- and gender-controlled, health-matched controls who underwent magnetic resonance imaging. All pilots performed neurocognitive assessment. Whole-brain and tract-wise average FA values were compared between pilots and controls, followed by comparison within pilots separated into high and low WMH burden groups. Neurocognitive measurements were used to help interpret group difference in FA values. RESULTS: Pilots had significantly lower average FA values than controls (0.489/0.500, respectively). Regionally, pilots had higher FA values in the fronto-occipital tract where FA values positively correlated with visual-spatial performance scores (0.603/0.586, respectively). There was a trend for high burden pilots to have lower FA values than low burden pilots. DISCUSSION: Nonhypoxic hypobaric exposure is associated with significantly lower average FA in young, healthy U-2 pilots. This suggests that recurrent hypobaric exposure causes diffuse axonal injury in addition to focal white matter changes.McGuire SA, Boone GRE, Sherman PM, Tate DF, Wood JD, Patel B, Eskandar G, Wijtenburg SA, Rowland LM, Clarke GD, Grogan PM, Sladky JH, Kochunov PV. White matter integrity in high-altitude pilots exposed to hypobaria. Aerosp Med Hum Perform. 2016; 87(12):983-988.

Physiological Responses During Multiplay Exergaming in Young Adult Males are Game-Dependent.

Regular moderate-intensity exercise provides health benefits. The aim of this study was to examine whether the selected exercise intensity and physiological responses during exergaming in a single and multiplayer mode in the same physical space were game-dependent. Ten males (mean ±SD, age: 23 ±5 years, body mass: 84.2 ±15.6 kg, body height: 180 ±7 cm, body mass index: 26.0 ±4.0 kg·m(-2)) played the games Kinect football, boxing and track & field (3 × âˆ¼10 min, ∼ 2 min rest periods) in similar time sequence in two sessions. Physiological responses were measured with the portable Cosmed K4b(2) pulmonary gas exchange system. Single play demands were used to match with a competitive opponent in a multiplay mode. A within-subjects crossover design was used with one-way ANOVA and a post-hoc t-test for analysis (p<0.05). Minute ventilation, oxygen uptake and the heart rate were at least 18% higher during a multiplayer mode for Kinect football and boxing but not for track & field. Energy expenditure was 21% higher during multiplay football. Single play track & field had higher metabolic equivalent than single play football (5.7 ±1.6, range: 3.2-8.6 vs 4.1 ±1.0, range: 3.0-6.1, p<0.05). Exergaming in a multiplayer mode can provide higher physiological demands but the effects are game-dependent. It seems that exergaming with low intensity in a multiplayer mode may provide a greater physical challenge for participants than in a single play mode but may not consistently provide sufficient intensity to acquire health benefits when played regularly as part of a programme to promote and maintain health in young adults.

White matter hyperintensities and hypobaric exposure.

OBJECTIVE: Demonstrate that occupational exposure to nonhypoxic hypobaria is associated with subcortical white matter hyperintensities (WMHs) on fluid-attenuated inversion recovery magnetic resonance imaging (MRI). METHODS: Eighty-three altitude chamber personnel (PHY), 105 U-2 pilots (U2P), and 148 age- controlled and health-matched doctorate degree controls (DOC) underwent high-resolution MRI. Subcortical WMH burden was quantified as count and volume of subcortical WMH lesions after transformation of images to the Talairach atlas-based stereotactic frame. RESULTS: Subcortical WMHs were more prevalent in PHY (volume p = 0.011/count p = 0.019) and U2P (volume p < 0.001/count p < 0.001) when compared to DOC, whereas PHY were not significantly different than U2P. INTERPRETATION: This study provides strong evidence that nonhypoxic hypobaric exposure may induce subcortical WMHs in a young, healthy population lacking other risk factors for WMHs and adds this occupational exposure to other environmentally related potential causes of WMHs. Ann Neurol 2014;76:719-726.

Lower neurocognitive function in U-2 pilots: Relationship to white matter hyperintensities.

OBJECTIVE: Determine whether United States Air Force (USAF) U-2 pilots (U2Ps) with occupational exposure to repeated hypobaria had lower neurocognitive performance compared to pilots without repeated hypobaric exposure and whether U2P neurocognitive performance correlated with white matter hyperintensity (WMH) burden. METHODS: We collected Multidimensional Aptitude Battery-II (MAB-II) and MicroCog: Assessment of Cognitive Functioning (MicroCog) neurocognitive data on USAF U2Ps with a history of repeated occupational exposure to hypobaria and compared these with control data collected from USAF pilots (AFPs) without repeated hypobaric exposure (U2Ps/AFPs MAB-II 87/83; MicroCog 93/80). Additional comparisons were performed between U2Ps with high vs low WMH burden. RESULTS: U2Ps with repeated hypobaric exposure had significantly lower scores than control pilots on reasoning/calculation (U2Ps/AFPs 99.4/106.5), memory (105.5/110.9), information processing accuracy (102.1/105.8), and general cognitive functioning (103.5/108.5). In addition, U2Ps with high whole-brain WMH count showed significantly lower scores on reasoning/calculation (high/low 96.8/104.1), memory (102.9/110.2), general cognitive functioning (101.5/107.2), and general cognitive proficiency (103.6/108.8) than U2Ps with low WMH burden (high/low WMH mean volume 0.213/0.003 cm(3) and mean count 14.2/0.4). CONCLUSION: In these otherwise healthy, highly functioning individuals, pilots with occupational exposure to repeated hypobaria demonstrated lower neurocognitive performance, albeit demonstrable on only some tests, than pilots without repeated exposure. Furthermore, within the U2P population, higher WMH burden was associated with lower neurocognitive test performance. Hypobaric exposure may be a risk factor for subtle changes in neurocognition.

Combining diffusion tensor imaging and magnetic resonance spectroscopy to study reduced frontal white matter integrity in youths with family histories of substance use disorders.

Individuals with a family history of substance use disorder (FH+) show impaired frontal white matter as indicated by diffusion tensor imaging (DTI). This impairment may be due to impaired or delayed development of myelin in frontal regions, potentially contributing to this population's increased risk for developing substance use disorders. In this study, we examined high angular resolution DTI and proton magnetic resonance spectroscopy data from the anterior corona radiata were collected in 80 FH+ and 34 FH- youths (12.9 ± 1.0 years old). White matter integrity indices included fractional anisotropy (FA), N-acetylaspartate (NAA), and total choline (tCho). Lower FA suggests decreased myelination. Decreased NAA coupled with higher tCho suggests impaired build-up and maintenance of cerebral myelin and consequently greater breakdown of cellular membranes. We found FH+ youths had lower FA (P < 0.0001) and NAA (P = 0.017) and higher tCho (P = 0.04). FH density (number of parents and grandparents with substance use disorders) was negatively correlated with FA (P < 0.0001) and NAA (P = 0.011) and positively correlated with tCho (P = 0.001). FA was independently predicted by both FH density (P = 0.006) and NAA (P = 0.002), and NAA and tCho were both independent predictors of FH density (P < 0.001). Our finding of lower frontal FA in FH+ youths corresponding to lower NAA and increased tCho is consistent with delayed or impaired development of frontal white matter in FH+ youths. Longitudinal studies are needed to determine how these differences relate to substance use outcomes.

White matter hyperintensities on MRI in high-altitude U-2 pilots.

OBJECTIVE: To demonstrate that U-2 pilot occupational exposure to hypobaria leads to increased incidence of white matter hyperintensities (WMH) with a more uniform distribution throughout the brain irrespective of clinical neurologic decompression sickness history. METHODS: We evaluated imaging findings in 102 U-2 pilots and 91 controls matched for age, health, and education levels. Three-dimensional, T2-weighted, high-resolution (1-mm isotropic) imaging data were collected using fluid-attenuated inversion recovery sequence on a 3-tesla MRI scanner. Whole-brain and regional WMH volume and number were compared between groups using a 2-tailed Wilcoxon rank sum test. RESULTS: U-2 pilots demonstrated an increase in volume (394%; p = 0.004) and number (295%; p < 0.001) of WMH. Analysis of regional distribution demonstrated WMH more uniformly distributed throughout the brain in U-2 pilots compared with mainly frontal distribution in controls. CONCLUSION: Pilots with occupational exposure to hypobaria showed a significant increase in WMH lesion volume and number. Unlike the healthy controls with predominantly WMH in the frontal white matter, WMH in pilots were more uniformly distributed throughout the brain. This is consistent with our hypothesized pattern of damage produced by interaction between microemboli and cerebral tissue, leading to thrombosis, coagulation, inflammation, and/or activation of innate immune response, although further studies will be necessary to clarify the pathologic mechanisms responsible.

Aeromedical decision making and seizure risk after traumatic brain injury: longitudinal outcome.

INTRODUCTION: Traumatic brain injury (TBI) is common in young adults and therefore of significant concern to an aircrew population. This paper reports the occurrences of seizures in U.S. Air Force (USAF) aircrew following receipt of an aeromedical waiver for TBI. METHODS: Using both an aeromedical waiver tracking system database and medical records, we identified surrogate seizure markers such as all episodes of subsequent TBI, seizure, loss of consciousness, or prescription of anticonvulsant medications from the time of initial TBI until the last medical visit or entry recorded in either the database or medical records for our study population. RESULTS: The seizure rate for aircrew who met USAF waiver criteria was 24.53/100,000 person-years. One pilot experienced a major motor seizure 14.9 yr following a severe TBI for an incidence of 308.64/100,000 person-years. DISCUSSION: The USAF waiver process following TBI was sufficiently effective in removing aircrew with elevated risk for seizure following TBI. While our rates of post-traumatic seizure appear to be lower than previously published civilian population rates, direct comparison cannot be made secondary to differences in study design and selection criteria. Further areas of study could involve a more detailed analysis of aircrew neurocognitive status following TBI for subtle changes, crosschecking USAF Safety Center data for changes in accident rates among post-TBI aircrew, and analysis of lost aircrew flying time as a result of TBI and the degree of burden that loss places on the flying mission. CONCLUSION: Application of these stringent criteria is sufficient to fulfill aeromedical safety standards, but costs remain undetermined.