406 research outputs found
Development of a Closed-Loop Strap Down Attitude System for an Ultrahigh Altitude Flight Experiment
A low-cost attitude system has been developed for an ultrahigh altitude flight experiment. The experiment uses a remotely piloted sailplane, with the wings modified for flight at altitudes greater than 100,000 ft. Mission requirements deem it necessary to measure the aircraft pitch and bank angles with accuracy better than 1.0 deg and heading with accuracy better than 5.0 deg. Vehicle cost restrictions and gross weight limits make installing a commercial inertial navigation system unfeasible. Instead, a low-cost attitude system was developed using strap down components. Monte Carlo analyses verified that two vector measurements, magnetic field and velocity, are required to completely stabilize the error equations. In the estimating algorithm, body-axis observations of the airspeed vector and the magnetic field are compared against the inertial velocity vector and a magnetic-field reference model. Residuals are fed back to stabilize integration of rate gyros. The effectiveness of the estimating algorithm was demonstrated using data from the NASA Dryden Flight Research Center Systems Research Aircraft (SRA) flight tests. The algorithm was applied with good results to a maximum 10' pitch and bank angles. Effects of wind shears were evaluated and, for most cases, can be safely ignored
Central Review of Amyloid-Related Imaging Abnormalities in Two Phase III Clinical Trials of Bapineuzumab in Mild-To-Moderate Alzheimer's Disease Patients
BACKGROUND: Amyloid-related imaging abnormalities (ARIA) consist of ARIA-E (with effusion or edema) and ARIA-H (hemosiderin deposits [HDs]).
OBJECTIVES: To address accurate ascertainment of ARIA identification, a final magnetic resonance imaging (MRI) reading was performed on patients with mild-to-moderate Alzheimer’s disease randomized to bapineuzumab IV or placebo during two Phase III trials (APOE ɛ4 allele carriers or noncarriers).
METHODS: Final MRI central review consisted of a systematic sequential locked, adjudicated read in 1,331 APOE ɛ4 noncarriers and 1,121 carriers by independent neuroradiologists. Assessment of ARIA-E, ARIA-H, intracerebral hemorrhages, and age-related white matter changes is described.
RESULTS: In the Final Read, treatment-emergent ARIA-E were identified in 242 patients including 76 additional cases not noted previously in real time. Overall, incidence proportion of ARIA-E was higher in carriers (active 21.2%; placebo 1.1%) than in noncarriers (pooled active 11.3%; placebo 0.6%), and was more often identified in homozygote APOE ɛ4 carriers than heterozygotes (34.5% versus 16.9%). Incidence rate of ARIA-E increased with increased dose in noncarriers. Frequency of ARIA-E first episodes was highest after the first and second bapineuzumab infusion and declined after repeated infusions. Incidence of total HDs <10 mm (cerebral microhemorrhages) was higher in active groups versus placebo.
CONCLUSION: ARIA was detected more often on MRI scans when every scan was reviewed by trained neuroradiologists and results adjudicated. There was increased incidence of ARIA-E in bapineuzumab-treated carriers who had a microhemorrhage at baseline. ARIA-E was a risk factor for incident ARIA-H and late onset ARIA-E was milder radiologically. Age-related white matter changes did not progress during the study
Development of a Sustainable Water Resource for the Big Creek Watershed
Proceedings of the 2001 Georgia Water Resources Conference, April 26 and 27, 2001, Athens, Georgia.The Big Creek Water Quality
Management Plan has been a cooperative effort of
Cherokee, Forsyth and Fulton Counties, as well as the
Cities of Alpharetta, Cumming and Roswell to develop
a mutually agreeable water quality protection Plan for
the Big Creek Watershed. The Big Creek Watershed
straddles the rapidly growing Georgia 400 Corridor in
the northern part of Metropolitan Atlanta. It is a water
supply for the City of Roswell and has an area of
about 99 square miles at the Roswell water intake. The
project purposes included: achieving and maintaining
a high quality water supply; minimizing flooding,
property damage and stream impacts; protecting
wetlands and establish greenways; meeting minimum
Georgia DNR water supply watershed criteria or
developing acceptable alternatives; understanding the
impacts of urbanization; and considering options for
and developing multi jurisdictional cooperation. The
study encompassed watershed characterization,
assessment of water quality and quantity issues,
assessment of habitat and social issues and the
selection of best management practices (BMP's) to
meet water quality, water quantity, habitat and social
goals. Study tasks included forecasting future land use
and impervious areas, assessing current and future
impacts and evaluating alternate management and
protection scenarios.Sponsored and Organized by: U.S. Geological Survey, Georgia Department of Natural Resources, Natural Resources Conservation Service, The University of Georgia, Georgia State University, Georgia Institute of TechnologyThis book was published by the Institute of Ecology, The University of Georgia, Athens, Georgia 30602-2202. The views and statements advanced in this publication are solely those of the authors and do not represent official views or policies of The University of Georgia, the U.S. Geological Survey, the Georgia Water Research Institute as authorized by the Water Resources Research Act of 1990 (P.L. 101-397) or the other conference sponsors
Initial results from the international double-blind phase III study of Dysport® in the treatment of adults with upper limb spasticity
The value of subtraction MRI in detection of amyloid-related imaging abnormalities with oedema or effusion in Alzheimer's patients: An interobserver study
BACKGROUND: Immunotherapeutic treatments targeting amyloid-β plaques in Alzheimer's disease (AD) are associated with the presence of amyloid-related imaging abnormalities with oedema or effusion (ARIA-E), whose detection and classification is crucial to evaluate subjects enrolled in clinical trials. PURPOSE: To investigate the applicability of subtraction MRI in the ARIA-E detection using an established ARIA-E-rating scale. METHODS: We included 75 AD patients receiving bapineuzumab treatment, including 29 ARIA-E cases. Five neuroradiologists rated their brain MRI-scans with and without subtraction images. The accuracy of evaluating the presence of ARIA-E, intraclass correlation coefficient (ICC) and specific agreement was calculated. RESULTS: Subtraction resulted in higher sensitivity (0.966) and lower specificity (0.970) than native images (0.959, 0.991, respectively). Individual rater detection was excellent. ICC scores ranged from excellent to good, except for gyral swelling (moderate). Excellent negative and good positive specific agreement among all ARIA-E imaging features was reported in both groups. Combining sulcal hyperintensity and gyral swelling significantly increased positive agreement for subtraction images. CONCLUSION: Subtraction MRI has potential as a visual aid increasing the sensitivity of ARIA-E assessment. However, in order to improve its usefulness isotropic acquisition and enhanced training are required. The ARIA-E rating scale may benefit from combining sulcal hyperintensity and swelling. KEY POINTS: • Subtraction technique can improve detection amyloid-related imaging-abnormalities with edema/effusion in Alzheimer's patients. • The value of ARIA-E detection, classification and monitoring using subtraction was assessed. • Validation of an established ARIA-E rating scale, recommendations for improvement are reported. • Complementary statistical methods were employed to measure accuracy, inter-rater-reliability and specific agreement
Rapid-onset dystonia-parkinsonism associated with the I758S mutation of the ATP1A3 gene: a neuropathologic and neuroanatomical study of four siblings
Rapid-onset dystonia-parkinsonism (RDP) is a movement disorder associated with mutations in the ATP1A3 gene. Signs and symptoms of RDP commonly occur in adolescence or early adulthood and can be triggered by physical or psychological stress. Mutations in ATP1A3 are also associated with alternating hemiplegia of childhood (AHC). The neuropathologic substrate of these conditions is unknown. The central nervous system of four siblings, three affected by RDP and one asymptomatic, all carrying the I758S mutation in the ATP1A3 gene, was analyzed. This neuropathologic study is the first carried out in ATP1A3 mutation carriers, whether affected by RDP or AHC. Symptoms began in the third decade of life for two subjects and in the fifth for another. The present investigation aimed at identifying, in mutation carriers, anatomical areas potentially affected and contributing to RDP pathogenesis. Comorbid conditions, including cerebrovascular disease and Alzheimer disease, were evident in all subjects. We evaluated areas that may be relevant to RDP separately from those affected by the comorbid conditions. Anatomical areas identified as potential targets of I758S mutation were globus pallidus, subthalamic nucleus, red nucleus, inferior olivary nucleus, cerebellar Purkinje and granule cell layers, and dentate nucleus. Involvement of subcortical white matter tracts was also evident. Furthermore, in the spinal cord, a loss of dorsal column fibers was noted. This study has identified RDP-associated pathology in neuronal populations, which are part of complex motor and sensory loops. Their involvement would cause an interruption of cerebral and cerebellar connections which are essential for maintenance of motor control. Electronic supplementary material The online version of this article (doi:10.1007/s00401-014-1279-x) contains supplementary material, which is available to authorized users
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International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.
The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations
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