Development and Assessment of a Diagnostic DNA Oligonucleotide Microarray for Detection and Typing of Meningitis-Associated Bacterial Species.

Meningitis is commonly caused by infection with a variety of bacterial or viral pathogens. Acute bacterial meningitis (ABM) can cause severe disease, which can progress rapidly to a critical life-threatening condition. Rapid diagnosis of ABM is critical, as this is most commonly associated with severe sequelae with associated high mortality and morbidity rates compared to viral meningitis, which is less severe and self-limiting. We have designed a microarray for detection and diagnosis of ABM. This has been validated using randomly amplified DNA targets (RADT), comparing buffers with or without formamide, in glass slide format or on the Alere ArrayTubeTM (Alere Technologies GmbH) microarray platform. Pathogen-specific signals were observed using purified bacterial nucleic acids and to a lesser extent using patient cerebral spinal fluid (CSF) samples, with some technical issues observed using RADT and glass slides. Repurposing the array onto the Alere ArrayTubeTM platform and using a targeted amplification system increased specific and reduced nonspecific hybridization signals using both pathogen nucleic and patient CSF DNA targets, better revealing pathogen-specific signals although sensitivity was still reduced in the latter. This diagnostic microarray is useful as a laboratory diagnostic tool for species and strain designation for ABM, rather than for primary diagnosis

Improvements in forecasting intense rainfall: results from the FRANC (forecasting rainfall exploiting new data assimilation techniques and novel observations of convection) project

The FRANC project (Forecasting Rainfall exploiting new data Assimilation techniques and Novel observations of Convection) has researched improvements in numerical weather prediction of convective rainfall via the reduction of initial condition uncertainty. This article provides an overview of the project’s achievements. We highlight new radar techniques: correcting for attenuation of the radar return; correction for beams that are over 90% blocked by trees or towers close to the radar; and direct assimilation of radar reflectivity and refractivity. We discuss the treatment of uncertainty in data assimilation: new methods for estimation of observation uncertainties with novel applications to Doppler radar winds, Atmospheric Motion Vectors, and satellite radiances; a new algorithm for implementation of spatially-correlated observation error statistics in operational data assimilation; and innovative treatment of moist processes in the background error covariance model. We present results indicating a link between the spatial predictability of convection and convective regimes, with potential to allow improved forecast interpretation. The research was carried out as a partnership between University researchers and the Met Office (UK). We discuss the benefits of this approach and the impact of our research, which has helped to improve operational forecasts for convective rainfall event

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

The spectroscopy of DA white dwarfs at high resolution

This thesis is concerned with the spectroscopy of hot, hydrogen-rich white dwarfs, and the development of instrumentation with which to further their study. It begins with a review of white dwarf research, and a summary of results from some notable Extreme-Ultraviolet (EUV) missions. The absence of helium in hot hydrogen-rich white dwarfs is introduced, and the need to precisely determine their composition is explained. These issues provide motivation for the Joint Astrophysical Plasmadynamic Experiment (J-PEX). Using normal incidence, multilayer coated optics and a high resolution focal plane detector, this spectrometer offers a substantial improvement in effective area and spectral resolution over current instrumentation. The design and development of a microchannel plate (MCP) detector for J-PEX is discussed, and a study of MCP sensitivity enhancement processes presented. A CsI photocathode is found to offer superior performance in the 225 - 245 Å band covered by J-PEX. The low quantum efficiencies recently measured for MCPs are also discussed. A preliminary analysis of data from the first successful flight of J-PEX, on board a sounding rocket, is described. Techniques are devised to overcome uncertainties in wavelength calibration, leading to production of the highest resolution EUV spectrum currently available for an astronomical object. These data reveal the presence of helium along the line of sight to the white dwarf G191-B2B, and prove the value of the J-PEX design. Data from the Hubble Space Telescope and the International Ultraviolet Explorer are used to search for white dwarfs with highly ionised, non-photospheric absorption features. Three new identifications are made, in the white dwarfs REJ 1738+665, REJ 0558+165 and WD 2218+706. Possible explanations, including absorption by planetary nebulæ, are suggested. The spectra are of longer wavelength, but higher resolution than currently obtainable by J-PEX, and complement the latter instrument by resolving multiple velocity components along the line-of-sight. The importance of these measurements in the context of J-PEX results, is demonstrated

Isolating the 130.4 nm and 135.6 nm emissions in Ganymede’s aurora using broadband optics

We discuss a technique for isolating the two main Far Ultraviolet emission lines in Ganymede’s aurora by adding flight proven transmission filters to a broad- band, wide-field imager design. We find that the ra- tio of OI emissions at 135.6 nm and 130.4 nm can be recovered if the transmission of the filters and other optical elements are well known. This ratio allows constraints to be placed on the relative abundances of O atoms and O2 molecules within Ganymede’s at- mosphere, leading to more accurate models of atmo- spheric composition

Autofluorescence Signatures of Seven Pathogens: Preliminary in Vitro Investigations of a Potential Diagnostic for Acanthamoeba Keratitis

PURPOSE: Acanthamoeba keratitis can cause devastating damage to the human cornea and is often difficult to diagnose by routine clinical methods. In this preliminary study, we investigated whether Acanthamoeba may be distinguished from other common corneal pathogens through its autofluorescence response. Although only a small number of pathogens were studied, the identification of a unique Acanthamoeba signature would indicate that autofluorescence spectroscopy as a diagnostic method merits further investigation. METHODS: Samples of 7 common pathogens (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Elizabethkingia miricola, Achromobacter ruhlandii, Candida albicans, and Acanthamoeba castellanii) in solution were excited with ultraviolet light at a number of successive, narrow wavebands between 260 and 400 nm, and their fluorescence response recorded. Principal Component Analysis was used to allow better visualization of the differences in response to UV light for different species. RESULTS: Acanthamoeba was found to possess a characteristic autofluorescence response and was easily distinguished from E. coli, S. aureus, P. aeruginosa, E. miricola, A. ruhlandii, and C. albicans over a wide range of excitation wavelengths. We also found a clear discrimination between E. coli, C. albicans, and P. aeruginosa at an excitation wavelength of 274 nm, whereas E. miricola, S. aureus, and A. ruhlandii could be separated using an excitation wavelength of 308 nm. CONCLUSIONS: Our results, although preliminary, indicate that autofluorescence spectroscopy shows promise as a diagnostic technique for keratitis. We intend to expand the set of pathogens studied before assessing the feasibility of the technique in vivo by introducing cultures onto pig corneas

The Lunar X-ray Observatory (LXO)

X-ray emission from charge exchange recombination between the highly ionized solar wind and neutral material in Earth's magnetosheath has complicated x-ray observations of celestial objects with x-ray observatories including ROSAT, Chandra, XMM-Newton, and Suzaku. However, the charge-exchange emission can also be used as an important diagnostic of the solar-wind interacting with the magnetosheath. Soft x-ray observations from low-earth orbit or even the highly eccentric orbits of Chandra and XMM-Newton are likely superpositions of the celestial object of interest, the true extra-solar soft x-ray background, geospheric charge exchange, and heliospheric charge exchange. We show that with a small x-ray telescope placed either on the moon, in a similar vein as the Apollo ALSEP instruments, or in a stable orbit at a similar distance from the earth, we can begin to disentangle the complicated emission structure in the soft x-ray band. Here we present initial results of a feasibility study recently funded by NASA to place a small x-ray telescope on the lunar surface. The telescope operates during lunar night to observe charge exchange interactions between the solar wind and magnetosphic neutrals, between the solar wind and the lunar atmosphere, and an unobstructed view of the soft x-ray background without the geospheric component

Isolating auroral FUV emission lines using compact, broadband instrumentation

Images of auroral emissions at far ultraviolet (FUV, 122–200 nm) wavelengths are useful tools with which to study magnetospheric–ionospheric coupling, as the scattered sunlight background in this region is low, allowing both dayside and nightside auroras to be imaged simultaneously. The ratio of intensities between certain FUV emission lines or regions can be used to characterise the precipitating particles responsible for auroral emissions, and hence is a useful diagnostic of magnetospheric dynamics. Here, we describe how the addition of simple transmission filters to a compact broadband imager design allows far ultraviolet emission ratios to be deduced while also providing large-scale instantaneous images of the aurora. The low mass and volume of such an instrument would make it well-suited for both small satellite Earth-orbiting missions and larger outer planet missions from which it could be used to characterise the tenuous atmospheres observed at several moons, as well as studying the auroral emissions of the gas giants. We present a study to investigate the accuracy of a technique to allow emission line ratio retrieval, as applied to the OI 130.4 nm and 135.6 nm emissions at Ganymede. The ratio of these emissions provides information about the atmospheric composition, specifically the relative abundances of O and O2. Using modelled FUV spectra representative of Ganymede׳s atmosphere, based on observations by the Hubble Space Telescope (HST) Space Telescope Imaging Spectrograph (STIS), we find that the accuracy of the retrieved ratios is a function of the magnitude of the ratio, with the best measurements corresponding to a ratio of ~1.