Aircraft Exceedances Vary According to Time of Day and Workload

The Flight Operational Quality Assurance (FOQA) programs have been implemented in US and Europe to identify anomalous flights based on data recorded on board an aircraft in an effort to improve flight safety. Numerous methods have been developed to support the analysis of FOQA data. However, it is unclear how FOQA data relates to the performance of the pilot. We sought to characterize the frequency and type of flight exceedances extracted from FOQA data during a controlled pilot schedule in order to determine whether patterns of exceedances related to human control of the aircraft would change according to scheduling factors

Clinicopathological evaluation of chronic traumatic encephalopathy in players of American football

IMPORTANCE: Players of American football may be at increased risk of long-term neurological conditions, particularly chronic traumatic encephalopathy (CTE). OBJECTIVE: To determine the neuropathological and clinical features of deceased football players with CTE. DESIGN, SETTING, AND PARTICIPANTS: Case series of 202 football players whose brains were donated for research. Neuropathological evaluations and retrospective telephone clinical assessments (including head trauma history) with informants were performed blinded. Online questionnaires ascertained athletic and military history. EXPOSURES: Participation in American football at any level of play. MAIN OUTCOMES AND MEASURES: Neuropathological diagnoses of neurodegenerative diseases, including CTE, based on defined diagnostic criteria; CTE neuropathological severity (stages I to IV or dichotomized into mild [stages I and II] and severe [stages III and IV]); informant-reported athletic history and, for players who died in 2014 or later, clinical presentation, including behavior, mood, and cognitive symptoms and dementia. RESULTS: Among 202 deceased former football players (median age at death, 66 years [interquartile range, 47-76 years]), CTE was neuropathologically diagnosed in 177 players (87%; median age at death, 67 years [interquartile range, 52-77 years]; mean years of football participation, 15.1 [SD, 5.2]), including 0 of 2 pre–high school, 3 of 14 high school (21%), 48 of 53 college (91%), 9 of 14 semiprofessional (64%), 7 of 8 Canadian Football League (88%), and 110 of 111 National Football League (99%) players. Neuropathological severity of CTE was distributed across the highest level of play, with all 3 former high school players having mild pathology and the majority of former college (27 [56%]), semiprofessional (5 [56%]), and professional (101 [86%]) players having severe pathology. Among 27 participants with mild CTE pathology, 26 (96%) had behavioral or mood symptoms or both, 23 (85%) had cognitive symptoms, and 9 (33%) had signs of dementia. Among 84 participants with severe CTE pathology, 75 (89%) had behavioral or mood symptoms or both, 80 (95%) had cognitive symptoms, and 71 (85%) had signs of dementia. CONCLUSIONS AND RELEVANCE: In a convenience sample of deceased football players who donated their brains for research, a high proportion had neuropathological evidence of CTE, suggesting that CTE may be related to prior participation in football.This study received support from NINDS (grants U01 NS086659, R01 NS078337, R56 NS078337, U01 NS093334, and F32 NS096803), the National Institute on Aging (grants K23 AG046377, P30AG13846 and supplement 0572063345-5, R01 AG1649), the US Department of Defense (grant W81XWH-13-2-0064), the US Department of Veterans Affairs (I01 CX001038), the Veterans Affairs Biorepository (CSP 501), the Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (grant B6796-C), the Department of Defense Peer Reviewed Alzheimer’s Research Program (grant 13267017), the National Operating Committee on Standards for Athletic Equipment, the Alzheimer’s Association (grants NIRG-15-362697 and NIRG-305779), the Concussion Legacy Foundation, the Andlinger Family Foundation, the WWE, and the NFL

Changes in the neurochemistry of athletes with repetitive brain trauma: preliminary results using localized correlated spectroscopy

Introduction: The goal was to identify which neurochemicals differ in professional athletes with repetitive brain trauma (RBT) when compared to healthy controls using a relatively new technology, in vivo Localized COrrelated SpectroscopY (L-COSY). Methods: To achieve this, L-COSY was used to examine five former professional male athletes with 11 to 28 years of exposure to contact sports. Each athlete who had had multiple symptomatic concussions and repetitive sub concussive trauma during their career was assessed by an experienced neuropsychologist. All athletes had clinical symptoms including headaches, memory loss, confusion, impaired judgment, impulse control problems, aggression, and depression. Five healthy men, age and weight matched to the athlete cohort and with no history of brain trauma, were recruited as controls. Data were collected from the posterior cingulate gyrus using a 3 T clinical magnetic resonance scanner equipped with a 32 channel head coil. Results: The variation of the method was calculated by repeated examination of a healthy control and phantom and found to be 10% and 5%, respectively, or less. The L-COSY measured large and statistically significant differences (P ≤0.05), between healthy controls and those athletes with RBT. Men with RBT showed higher levels of glutamine/glutamate (31%), choline (65%), fucosylated molecules (60%) and phenylalanine (46%). The results were evaluated and the sample size of five found to achieve a significance level P = 0.05 and a power of 90%. Differences in N-acetyl aspartate and myo-inositol between RBT and controls were small and were not statistically significance. Conclusions: A study of a small cohort of professional athletes, with a history of RBT and symptoms of chronic traumatic encephalopathy when compared with healthy controls using 2D L-COSY, showed elevations in brain glutamate/glutamine and choline as recorded previously for early traumatic brain injury. For the first time increases in phenylalanine and fucose are recorded in the brains of athletes with RBT. Larger studies utilizing the L-COSY method may offer an in-life method of diagnosis and personalized approach for monitoring the acute effects of mild traumatic brain injury and the chronic effects of RBT

Intranasal oxytocin in children and adolescents with autism spectrum disorder

BACKGROUND Experimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder. METHODS We conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ. RESULTS Of the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was −3.7 in the oxytocin group and −3.5 in the placebo group (least-squares mean difference, −0.2; 95% confidence interval, −1.5 to 1.0; P=0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONS This placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks

A Photo Score for Aesthetic Outcome in Sagittal Synostosis:An ERN CRANIO Collaboration

European Reference Network (ERN) CRANIO is focused on optimizing care for patients with rare or complex craniofacial anomalies, including craniosynostosis and/or rare ear, nose, and throat disorders. The main goal of ERN CRANIO is to collect uniform data on treatment outcomes for multicenter comparison. We aimed to develop a reproducible and reliable suture-specific photo score that can be used for cross-center comparison of phenotypical severity of sagittal synostosis and aesthetic outcome of treatment. We conducted a retrospective study among nonsyndromic sagittal synostosis patients aged &lt;19 years. We included preoperative and postoperative photo sets from 6 ERN CRANIO centers. Photo sets included bird's eye, lateral, and anterior-posterior views. The sagittal synostosis photo score was discussed in the working group, and consensus was obtained on its contents. Interrater agreement was assessed with weighted Fleiss' Kappa and intraclass correlation coefficients.The photo score consisted of frontal bossing, elongated skull, biparietal narrowness, temporal hollowing, vertex line depression, occipital bullet, and overall phenotype. Each item was scored as normal, mild, moderate, or severe. Results from 36 scaphocephaly patients scored by 20 raters showed kappa values ranging from 0.38 [95% bootstrap CI: 0.31, 0.45] for biparietal narrowness to 0.56 [95% bootstrap CI: 0.47, 0.64] for frontal bossing. Agreement was highest for the sum score of individual items [intraclass correlation coefficients agreement 0.69 [95% CI: 0.57, 0.82]. This is the first large-scale multicenter study in which experts investigated a photo score to assess the severity of sagittal synostosis phenotypical characteristics. Agreement on phenotypical characteristics was suboptimal (fair-moderate agreement) and highest for the summed score of individual photo score items (substantial agreement), indicating that although experts interpret phenotypical characteristics differently, there is consensus on overall phenotypical severity.</p

Target Identification for Stereotactic Thalamotomy Using Diffusion Tractography

BACKGROUND: Stereotactic targets for thalamotomy are usually derived from population-based coordinates. Individual anatomy is used only to scale the coordinates based on the location of some internal guide points. While on conventional MR imaging the thalamic nuclei are indistinguishable, recently it has become possible to identify individual thalamic nuclei using different connectivity profiles, as defined by MR diffusion tractography. METHODOLOGY AND PRINCIPAL FINDINGS: Here we investigated the inter-individual variation of the location of target nuclei for thalamotomy: the putative ventralis oralis posterior (Vop) and the ventral intermedius (Vim) nucleus as defined by probabilistic tractography. We showed that the mean inter-individual distance of the peak Vop location is 7.33 mm and 7.42 mm for Vim. The mean overlap between individual Vop nuclei was 40.2% and it was 31.8% for Vim nuclei. As a proof of concept, we also present a patient who underwent Vop thalamotomy for untreatable tremor caused by traumatic brain injury and another patient who underwent Vim thalamotomy for essential tremor. The probabilistic tractography indicated that the successful tremor control was achieved with lesions in the Vop and Vim respectively. CONCLUSIONS: Our data call attention to the need for a better appreciation of the individual anatomy when planning stereotactic functional neurosurgery

Enzyme replacement reverses abnormal cerebrovascular responses in Fabry disease

BACKGROUND: Fabry disease is a lysosomal X-linked enzyme deficiency of α-galactosidase A associated with an increased mortality and morbidity due to renal failure, cardiac disease and early onset stroke. METHODS: We examined the functional blood flow response of the brain after visual stimulation (reversing checkerboard pattern), and cerebral vasoreactivity following acetazolamide (15 mg/kg) with [(15)O]H(2)O and positron emission tomography (PET) in Fabry disease. Twenty-six hemizygous patients (age range 19–47 years) were enrolled in a randomized double-blind placebo-controlled 6-month trial of enzyme replacement therapy administered by intravenous infusion every two weeks. Regional cerebral blood flow (rCBF) was measured with PET at the beginning and end of the trial. RESULTS: Fabry patients had a significantly greater increase in rCBF following visual stimulation and acetazolamide challenge compared to controls. Visual reactivity was normal. The time for recovery of the cerebral vasculature following acetazolamide was prolonged in Fabry patients compared to controls. The abnormal rCBF response induced by visual stimulation and acetazolamide decreased significantly following enzyme replacement therapy, as did the prolonged recovery of the cerebral vasculature. CONCLUSIONS: Enzyme replacement therapy reverses the exaggerated cerebrovascular response in Fabry disease

Subtle oculomotor difficulties and their relation to motor skill in children with autism spectrum disorder

Objectives Sensorimotor difficulties are often reported in autism spectrum disorders (ASD). Visual and motor skills are linked in that the processing of visual information can help in guiding motor movements. The present study investigated oculomotor skill and its relation to general motor skill in ASD by providing a comprehensive assessment of oculomotor control. Methods Fifty children (25 ASD; 25 typically developing [TD]), aged 7–10 years, completed a motor assessment (comprising fine and gross motor tasks) and oculomotor battery (comprising fixation, smooth pursuit, prosaccade and antisaccade tasks). Results No group differences were found for antisaccade errors, nor saccade latencies in prosaccade and antisaccade tasks, but increased saccade amplitude variability was observed in children with ASD, suggesting a reduced consistency in saccade accuracy. Children with ASD also demonstrated poorer fixation stability than their peers and spent less time in pursuit of a moving target. Motor skill was not correlated with saccade amplitude variability. However, regression analyses revealed that motor skill (and not diagnosis) accounted for variance in fixation performance and fast smooth pursuit. Conclusions The findings highlight the importance of considering oculomotor paradigms to inform the functional impact of neuropathologies in ASD and also assessing the presentation of co-occurring difficulties to further our understanding of ASD. Avenues for future research are suggested