Standardized Assessment of Hereditary Ataxia Patients in Clinical Studies.

BACKGROUND: Hereditary ataxias are a heterogeneous group of degenerative diseases of the cerebellum, brainstem, and spinal cord. They may present with isolated ataxia or with additional symptoms going beyond cerebellar deficits. There are an increasing number of clinical studies with the goal to define the natural history of these disorders, develop biomarkers, and investigate therapeutic interventions. Especially, early and preclinical disease stages are currently of particular interest. METHODS AND RESULTS: Evidence-based, we review standards for sampling and storage of biomaterials, clinical and neuropsychological assessment, as well as neurophysiology and neuroimaging and recommendations for standardized assessment of ataxia patients in multicenter studies. CONCLUSIONS: DNA, RNA, serum, and, if possible, cerebrospinal fluid samples should be processed following established standards. Clinical assessment in ataxia studies must include use of a validated clinical ataxia scale. There are several validated clinical ataxia scales available. There are no instruments that were specifically designed for assessing neuropsychological and psychiatric symptoms in ataxia disorders. We provide a list of tests that may prove valuable. Quantitative performance tests have the potential to supplement clinical scales. They provide additional objective and quantitative information. Posturography and quantitative movement analysis-despite valid approaches-require standardization before implemented in multicenter studies. Standardization of neurophysiological tools, as required for multicenter interventional trials, is still lacking. Future multicenter neuroimaging studies in ataxias should implement quality assurance measures as defined by the ADNI or other consortia. MRI protocols should allow morphometric analyses

Laminar Flame Combustion Diagnostics Using Imaging Fourier Transform Spectroscopy

Laminar flames are an important tool in combustion diagnostics with a host of pre-existing experimental research methods. Currently, however, no method captures time-resolved scalar profile estimates of temperature, and major species concentrations with a single measurement. This work provides IFTS with the capability to measure time-resolved 3D imaging of scalar values in laminar axisymmetric flames. This will make IFTS a useful tool for understanding combustion phenomenon, validating chemical kinetic models, verifying numerical simulations, and system performance estimate. Two algorithms are presented. The first reconstructs spectra as a function of flame period. Through selectively averaging over an ensemble of measurements, interferograms representing the scalar fields at t0 can be created. The second improves on traditional tomographic inversion methods to radially resolve multiple scalar values simultaneously in an axisymmetric flame. The combination of these two algorithms was applied to measurements of an unsteady laminar hydrogen flame. Temperature and water concentrations were successfully resolved radially at eight different snapshot times in the period of the flames harmonic motion. Measured results compared favorably with previously reported values and CFD simulations. Temperatures agree to within 11% and water concentration values agree to within 19%. This work demonstrates the ability of IFTS to make time-resolved 3-D maps of scalar values of harmonic laminar flame

A Study To Enhance The B-1B Targeting Pod Integration Developmental Processes

Recent United States combat operations required weapon systems to incorporate enhanced targeting capabilities to improve their effectiveness in weapons employment. The United States Air Force B-1B heavy bomber played a key role in releasing GPS guided munitions in Operation Enduring Freedom and Operation Iraqi Freedom without enhanced targeting capabilities. Future conflicts are expected to continue to address this requirement as the battlefield evolves. These operations highlighted the need for the B-1B to incorporate an advanced targeting pod (TGP) to provide positive identification of targets and allow for more precisely planned weapon releases without the aid of additional off-board resources. During 2004-2006 a concept demonstration electro-optical and infrared TGP program was developed and tested on the B-1B to address targeting limitations. The goal of the test program was to demonstrate a limited operational capability of the TGP using minimal testing resources. The concept demonstration highlighted areas for improvement in the final TGP implementation design. The improved alternatives were submitted as future design candidates and test procedures for the TGP development effort. The purpose of this thesis was to examine the concept demonstration test plan and planned test process and recommend improved testing processes and design enhancements for the fully integrated pod design. The planned testing included modeling and simulation of aerodynamics and structures, laboratory system functional testing, hardware development testing, ground vibration testing (GVT), electromagnetic interference compatibility testing (EMIC), crew operability testing, and flight envelope testing. Many of these elements were not planned to be thoroughly tested due to the limited demonstration constraints. The findings of this study indicate that a further evaluation of handling qualities are required, and pod related weapon separation testing should be expanded to include more release configurations and conditions. The Man Machine Interface (MMI) for the TGP future cockpit upgrade requires improvement while EMIC tests and related crew training should be increased during the final TGP System Developmental Design (SDD). No further increases in testing efforts relative to flight test instrumentation, GVT, logistics support, or aerodynamics are required

Studies on molecular and immune signatures for detection of pancreatic cancer and COVID-19

Background and objectives Etiological factors and accurate diagnostic biomarkers have remained elusive to pancreatic cancer, a disease with > 90% five-years mortality rate. The recent understanding of microbiome interaction with host organs has opened new research avenues on the potential role of microbiota in the tumor microenvironment. The objectives in Study I and II aim to investigate molecular and microbiome related biomarkers in plasma, saliva, pancreatic fluid and tissues from patient groups diagnosed with pancreatic cystic neoplasms, and their correlation with pancreatic neoplastic grade. The COVID-19 outbreak occurred in an unprecedented transmission rate which necessitate diagnostic biomarkers to manage the pandemic. The objective in Study III aims to investigate the potential use of saliva as a non-invasive approach for assessment of immune exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results Study I shows that elevated bacterial 16S DNA copies and IL-1β levels in pancreas cysts correlate with high neoplastic grade. Analysis of the intracystic pancreas microbiome shows co-occurrence and enrichment of oral bacterial species. Bacteria DNA level in pancreas is also associated to prior exposure to invasive endoscopic procedures. Study II shows that elevated plasma and salivary antibody reactivity to oral pathogens (particularly F. nucleatum or Fap2 of F. nucleatum) is associated with intraductal papillary mucinous neoplasm (IPMN) diagnosis showing high-grade dysplasia or invasive cancer. Study III shows that salivary antibody reactivity to SARS-CoV-2 spike and capsid antigens persist up to 9 months after mild COVID-19 with a new multiplex antibody assay. Presence of specific salivary antibodies also correlates to COVID-19 like symptoms in a second undiagnosed cohort. The virus-specific IgG in saliva appears stable and tolerates temperature and detergent pre-treatments. Conclusion Collectively, the results indicate that oral microbes have a role in disease progression of pancreatic cystic neoplasms. Reducing the inflammatory microbiome may be a potential therapeutic strategy. The salivary antibody testing against oral pathogens holds interesting promise for early identification of high-risk pancreatic tumors. Furthermore, salivary antibody testings on a multiplex platform perform well and can support immune diagnostics of COVID-19. By combining at-home sample collection and the multiplex strategy, salivary diagnostics can be a sensitive and non-invasive alternative to conventional tests currently availabl

Cloud impacts on photochemistry: building a climatology of photolysis rates from the Atmospheric Tomography mission

Measurements from actinic flux spectroradiometers on board the NASA DC-8 during the Atmospheric Tomography (ATom) mission provide an extensive set of statistics on how clouds alter photolysis rates (J values) throughout the remote Pacific and Atlantic Ocean basins. J values control tropospheric ozone and methane abundances, and thus clouds have been included for more than three decades in tropospheric chemistry modeling. ATom made four profiling circumnavigations of the troposphere capturing each of the seasons during 2016–2018. This work examines J values from the Pacific Ocean flights of the first deployment, but publishes the complete Atom-1 data set (29 July to 23 August 2016). We compare the observed J values (every 3&thinsp;s along flight track) with those calculated by nine global chemistry–climate/transport models (globally gridded, hourly, for a mid-August day). To compare these disparate data sets, we build a commensurate statistical picture of the impact of clouds on J values using the ratio of J-cloudy (standard, sometimes cloudy conditions) to J-clear (artificially cleared of clouds). The range of modeled cloud effects is inconsistently large but they fall into two distinct classes: (1) models with large cloud effects showing mostly enhanced J values aloft and or diminished at the surface and (2) models with small effects having nearly clear-sky J values much of the time. The ATom-1 measurements generally favor large cloud effects but are not precise or robust enough to point out the best cloud-modeling approach. The models here have resolutions of 50–200&thinsp;km and thus reduce the occurrence of clear sky when averaging over grid cells. In situ measurements also average scattered sunlight over a mixed cloud field, but only out to scales of tens of kilometers. A primary uncertainty remains in the role of clouds in chemistry, in particular, how models average over cloud fields, and how such averages can simulate measurements.</p

Wide-Field InfrarRed Survey Telescope-Astrophysics Focused Telescope Assets WFIRST-AFTA 2015 Report

This report describes the 2014 study by the Science Definition Team (SDT) of the Wide-Field Infrared Survey Telescope (WFIRST) mission. It is a space observatory that will address the most compelling scientific problems in dark energy, exoplanets and general astrophysics using a 2.4-m telescope with a wide-field infrared instrument and an optical coronagraph. The Astro2010 Decadal Survey recommended a Wide Field Infrared Survey Telescope as its top priority for a new large space mission. As conceived by the decadal survey, WFIRST would carry out a dark energy science program, a microlensing program to determine the demographics of exoplanets, and a general observing program utilizing its ultra wide field. In October 2012, NASA chartered a Science Definition Team (SDT) to produce, in collaboration with the WFIRST Study Office at GSFC and the Program Office at JPL, a Design Reference Mission (DRM) for an implementation of WFIRST using one of the 2.4-m, Hubble-quality telescope assemblies recently made available to NASA. This DRM builds on the work of the earlier WFIRST SDT, reported by Green et al. (2012) and the previous WFIRST-2.4 DRM, reported by Spergel et. (2013). The 2.4-m primary mirror enables a mission with greater sensitivity and higher angular resolution than the 1.3-m and 1.1-m designs considered previously, increasing both the science return of the primary surveys and the capabilities of WFIRST as a Guest Observer facility. The addition of an on-axis coronagraphic instrument to the baseline design enables imaging and spectroscopic studies of planets around nearby stars.Comment: This report describes the 2014 study by the Science Definition Team of the Wide-Field Infrared Survey Telescope mission. 319 pages; corrected a misspelled name in the authors list and a typo in the abstrac