Evaluation of Host Protein Biomarkers by ELISA From Whole Lysed Peripheral Blood for Development of Diagnostic Tests for Active Tuberculosis

Tuberculosis (TB) remains a significant global health crisis and the number one cause of death for an infectious disease. The health consequences in high-burden countries are significant. Barriers to TB control and eradication are in part caused by difficulties in diagnosis. Improvements in diagnosis are required for organisations like the World Health Organisation (WHO) to meet their ambitious target of reducing the incidence of TB by 50% by the year 2025, which has become hard to reach due to the COVID-19 pandemic. Development of new tests for TB are key priorities of the WHO, as defined in their 2014 report for target product profiles (TPPs). Rapid triage and biomarker-based confirmatory tests would greatly enhance the diagnostic capability for identifying and diagnosing TB-infected individuals. Protein-based test methods e.g. lateral flow devices (LFDs) have a significant advantage over other technologies with regard to assay turnaround time (minutes as opposed to hours) field-ability, ease of use by relatively untrained staff and without the need for supporting laboratory infrastructure. Here we evaluate the diagnostic performance of nine biomarkers from our previously published biomarker qPCR validation study; CALCOCO2, CD274, CD52, GBP1, IFIT3, IFITM3, SAMD9L, SNX10 and TMEM49, as protein targets assayed by ELISA. This preliminary evaluation study was conducted to quantify the level of biomarker protein expression across latent, extra-pulmonary or pulmonary TB groups and negative controls, collected across the UK and India, in whole lysed blood samples (WLB). We also investigated associative correlations between the biomarkers and assessed their suitability for ongoing diagnostic test development, using receiver operating characteristic/area under the curve (ROC) analyses, singly and in panel combinations. The top performing single biomarkers for pulmonary TB versus controls were CALCOCO2, SAMD9L, GBP1, IFITM3, IFIT3 and SNX10. TMEM49 was also significantly differentially expressed but downregulated in TB groups. CD52 expression was not highly differentially expressed across most of the groups but may provide additional patient stratification information and some limited use for incipient latent TB infection. These show therefore great potential for diagnostic test development either in minimal configuration panels for rapid triage or more complex formulations to capture the diversity of disease presentations

The Murchison Widefield Array: Design Overview

The Murchison Widefield Array (MWA) is a dipole-based aperture array synthesis telescope designed to operate in the 80-300 MHz frequency range. It is capable of a wide range of science investigations, but is initially focused on three key science projects. These are detection and characterization of 3-dimensional brightness temperature fluctuations in the 21cm line of neutral hydrogen during the Epoch of Reionization (EoR) at redshifts from 6 to 10, solar imaging and remote sensing of the inner heliosphere via propagation effects on signals from distant background sources,and high-sensitivity exploration of the variable radio sky. The array design features 8192 dual-polarization broad-band active dipoles, arranged into 512 tiles comprising 16 dipoles each. The tiles are quasi-randomly distributed over an aperture 1.5km in diameter, with a small number of outliers extending to 3km. All tile-tile baselines are correlated in custom FPGA-based hardware, yielding a Nyquist-sampled instantaneous monochromatic uv coverage and unprecedented point spread function (PSF) quality. The correlated data are calibrated in real time using novel position-dependent self-calibration algorithms. The array is located in the Murchison region of outback Western Australia. This region is characterized by extremely low population density and a superbly radio-quiet environment,allowing full exploitation of the instrumental capabilities.Comment: 9 pages, 5 figures, 1 table. Accepted for publication in Proceedings of the IEE

Radio Astronomy

Contains table of contents for Section 4 and reports on eight research projects.National Science Foundation Grant AST 88-19848National Aeronautics and Space Administration Goddard Space Flight Center Grant NAGW-2310SM Systems and Research, IncNational Aeronautics and Space Administration Goddard Space Flight Center Grant NAG 5-537National Aeronautics and Space Administration Goddard Space Flight Center Grant NAG 5-10Leaders for Manufacturing ProgramNational Aeronautics and Space Administration Goddard Space Flight Center Grant NAS 5-3079

Field Deployment of Prototype Antenna Tiles for the Mileura Widefield Array--Low Frequency Demonstrator

Experiments were performed with prototype antenna tiles for the Mileura Widefield Array--Low Frequency Demonstrator (MWA-LFD) to better understand the widefield, wideband properties of their design and to characterize the radio frequency interference (RFI) between 80 and 300 MHz at the site in Western Australia. Observations acquired during the six month deployment confirmed the predicted sensitivity of the antennas, sky-noise dominated system temperatures, and phase-coherent interferometric measurements. The radio spectrum is remarkably free of strong terrestrial signals, with the exception of two narrow frequency bands allocated to satellite downlinks and rare bursts due to ground-based transmissions being scattered from aircraft and meteor trails. Results indicate the potential of the MWA-LFD to make significant achievements in its three key science objectives: epoch of reionziation science, heliospheric science, and radio transient detection.Comment: Accepted by AJ. 17 pages with figure

Comparing Redundant and Sky-model-based Interferometric Calibration: A First Look with Phase II of the MWA

© 2018. The American Astronomical Society. All rights reserved.. Interferometric arrays seeking to measure the 21 cm signal from the epoch of reionization (EOR) must contend with overwhelmingly bright emission from foreground sources. Accurate recovery of the 21 cm signal will require precise calibration of the array, and several new avenues for calibration have been pursued in recent years, including methods using redundancy in the antenna configuration. The newly upgraded Phase II of Murchison Widefield Array (MWA) is the first interferometer that has large numbers of redundant baselines while retaining good instantaneous UV coverage. This array therefore provides a unique opportunity to compare redundant calibration with sky-model-based algorithms. In this paper, we present the first results from comparing both calibration approaches with MWA Phase II observations. For redundant calibration, we use the package OMNICAL and produce sky-based calibration solutions with the analysis package Fast Holographic Deconvolution (FHD). There are three principal results: (1) We report the success of OMNICAL on observations of ORBComm satellites, showing substantial agreement between redundant visibility measurements after calibration. (2) We directly compare OMNICAL calibration solutions with those from FHD and demonstrate that these two different calibration schemes give extremely similar results. (3) We explore improved calibration by combining OMNICAL and FHD. We evaluate these combined methods using power spectrum techniques developed for EOR analysis and find evidence for marginal improvements mitigating artifacts in the power spectrum. These results are likely limited by the signal-to-noise ratio in the 6 hr of data used, but they suggest future directions for combining these two calibration schemes

Radio Astronomy

Contains table of contents for Section 4 and reports on twelve research projects.National Science Foundation Grant AST 88-19848Jet Propulsion Laboratory Contract 957687National Aeronautics and Space Administration Grant NAGW 1386National Science Foundation Grant AST 88-19848Annie Jump Cannon AwardSM Systems and Research, Inc.U.S. Navy Office of Naval Research Contract N00014-88-K-2016NASA/Goddard Space Flight Center Grant NAG 5-537NASA/Goddard Space Flight Center Grant NAG 5-10Woods Hole Oceanographic Institution Contract SC-28860Leaders for Manufacturing Progra

Radio Astronomy

Contains table of contents for Section 4 and reports on nine research projects.National Science Foundation Grant AST 88-19848National Science Foundation Grant AST 90-22501Alfred P. Sloan FellowshipNational Science Foundation Presidential Young Investigator AwardNational Aeronautics and Space Administration Grant NAGW-2310David and Lucile Packard FellowshipSM Systems and Research CorporationNational Aeronautics and Space Administration/Goddard Space Flight Center Contract NAS 5-30791National Aeronautics and Space Administration/Goddard Space Flight Center Grant NAG5-10Leaders for Manufacturing Progra

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Low-Frequency Observations of the Moon with the Murchison Widefield Array

A new generation of low-frequency radio telescopes is seeking to observe the redshifted 21 cm signal from the epoch of reionization (EoR), requiring innovative methods of calibration and imaging to overcome the difficulties of wide-field low-frequency radio interferometry. Precise calibration will be required to separate the expected small EoR signal from the strong foreground emission at the frequencies of interest between 80 and 300 MHz. The Moon may be useful as a calibration source for detection of the EoR signature, as it should have a smooth and predictable thermal spectrum across the frequency band of interest. Initial observations of the Moon with the Murchison Widefield Array 32 tile prototype show that the Moon does exhibit a similar trend to that expected for a cool thermally emitting body in the observed frequency range, but that the spectrum is corrupted by reflected radio emission from Earth. In particular, there is an abrupt increase in the observed flux density of the Moon within the internationally recognized frequency modulated (FM) radio band. The observations have implications for future low-frequency surveys and EoR detection experiments that will need to take this reflected emission from the Moon into account. The results also allow us to estimate the equivalent isotropic power emitted by the Earth in the FM band and to determine how bright the Earth might appear at meter wavelengths to an observer beyond our own solar system