Determining antimicrobial susceptibility in Salmonella enterica serovar Typhimurium through whole genome sequencing: a comparison against multiple phenotypic susceptibility testing methods

Background : UK public health organisations perform routine antimicrobial susceptibility tests (ASTs) to characterise the potential for antimicrobial resistance in Salmonella enterica serovars. Genetic determinants of these resistance mechanisms are detectable by whole genome sequencing (WGS), however the viability of WGS-based genotyping as an alternative resistance screening tool remains uncertain. We compared WGS-based genotyping, disk diffusion and agar dilution to the broth microdilution reference AST for 102 Salmonella enterica serovar Typhimurium (S. Typhimurium) isolates across 11 antimicrobial compounds. Results : Genotyping concordance, interpreted using epidemiological cut-offs (ECOFFs), was 89.8% (1007/1122) with 0.83 sensitivity and 0.96 specificity. For seven antimicrobials interpreted using Salmonella clinical breakpoints, genotyping produced 0.84 sensitivity and 0.88 specificity. Although less accurate than disk diffusion (0.94 sensitivity, 0.93 specificity) and agar dilution (0.83 sensitivity, 0.98 specificity), genotyping performance improved to 0.89 sensitivity and 0.97 specificity when two antimicrobials with relatively high very major error rates were excluded (streptomycin and sulfamethoxazole). Conclusions : An 89.8% concordance from WGS-based AST predictions using ECOFF interpretations suggest that WGS would serve as an effective screening tool for the tracking of antimicrobial resistance mechanisms in S. Typhimurium. For use as a standalone clinical diagnostic screen, further work is required to reduce the error rates for specific antimicrobials

Analysis of immune responses to attenuated alcelaphine herpesvirus 1 formulated with and without adjuvant

The experimental vaccine for bovine malignant catarrhal fever consists of viable attenuated alcelaphine herpesvirus 1 (AlHV-1) derived by extensive culture passage, combined with an oil-in-water adjuvant, delivered intramuscularly. This immunisation strategy was over 80% effective in previous experimental and field trials and protection appeared to be associated with induction of virus-neutralising antibodies. Whether the vaccine virus is required to be viable at the point of immunisation and whether adjuvant is required to induce the appropriate immune responses remains unclear. To address these issues two studies were performed, firstly to analyse immune responses in the presence and absence of adjuvant and secondly, to investigate immune responses to vaccines containing adjuvant plus viable or inactivated AlHV-1.The first study showed that viable attenuated AlHV-1 in the absence of adjuvant induced virus-specific antibodies but the titres of virus-neutralising antibodies were significantly lower than those induced by vaccine containing viable virus and adjuvant, suggesting adjuvant was required for optimal responses. In contrast, the second study found that the vaccine containing inactivated (>99.9%) AlHV-1 induced similar levels of virus-neutralising antibody to the equivalent formulation containing viable AlHV-1.Together these studies suggest that the MCF vaccine acts as an antigen depot for induction of immune responses, requiring adjuvant and a suitable antigen source, which need not be viable virus. These observations may help in directing the development of alternative MCF vaccine formulations for distribution in the absence of an extensive cold chain

An ALMA Survey of Submillimeter Galaxies in the Extended Chandra Deep Field South : The Redshift Distribution and Evolution of Submillimeter Galaxies

Accepted by ApJ. 45 pages, 16 figuresWe present the first photometric redshift distribution for a large unbiased sample of 870um selected submillimeter galaxies (SMGs) with robust identifications based on observations with the Atacama Large Millimeter Array (ALMA). In our analysis we consider 96 SMGs in the Extended Chandra Deep Field South, 77 of which have 4-19 band, optical-near-infrared, photometry. We model the Spectral Energy Distributions (SEDs) for these 77 SMGs, deriving a median photometric redshift of z=2.3+/-0.1. The remaining 19 SMGs have insufficient optical or near-infrared photometry to derive photometric redshifts, but a stacking analysis of IRAC and Herschel observations confirms they are not spurious. Assuming these sources have an absolute H-band magnitude distribution comparable to that of a complete sample of z~1-2 SMGs, we demonstrate that the undetected SMGs lie at higher redshifts, raising the median redshift for SMGs to z=2.5+/-0.2. More critically we show that the proportion of galaxies undergoing an SMG phase at z>3 is 35+/-5% of the total population. We derive a median stellar mass for SMGs of Mstar=(8+/-1)x10^10Mo, but caution that there are significant systematic uncertainties in our stellar mass estimate, up to x5 for individual sources. We compare our sample of SMGs to a volume-limited, morphologically classified sample of ellipticals in the local Universe. Assuming the star formation activity in SMGs has a timescale of ~100Myr we show that their descendants at z~0 would have a space density and M_H distribution which are in good agreement with those of local ellipticals. In addition the inferred mass-weighted ages of the local ellipticals broadly agree with the look-back times of the SMG events. Taken together, these results are consistent with a simple model that identifies SMGs as events that form most of the stars seen in the majority of luminous elliptical galaxies at the present day.Peer reviewe

An ALMA Survey of Submillimeter Galaxies in the Extended Chandra Deep Field South : The Redshift Distribution and Evolution of Submillimeter Galaxies

Accepted by ApJ. 45 pages, 16 figuresWe present the first photometric redshift distribution for a large unbiased sample of 870um selected submillimeter galaxies (SMGs) with robust identifications based on observations with the Atacama Large Millimeter Array (ALMA). In our analysis we consider 96 SMGs in the Extended Chandra Deep Field South, 77 of which have 4-19 band, optical-near-infrared, photometry. We model the Spectral Energy Distributions (SEDs) for these 77 SMGs, deriving a median photometric redshift of z=2.3+/-0.1. The remaining 19 SMGs have insufficient optical or near-infrared photometry to derive photometric redshifts, but a stacking analysis of IRAC and Herschel observations confirms they are not spurious. Assuming these sources have an absolute H-band magnitude distribution comparable to that of a complete sample of z~1-2 SMGs, we demonstrate that the undetected SMGs lie at higher redshifts, raising the median redshift for SMGs to z=2.5+/-0.2. More critically we show that the proportion of galaxies undergoing an SMG phase at z>3 is 35+/-5% of the total population. We derive a median stellar mass for SMGs of Mstar=(8+/-1)x10^10Mo, but caution that there are significant systematic uncertainties in our stellar mass estimate, up to x5 for individual sources. We compare our sample of SMGs to a volume-limited, morphologically classified sample of ellipticals in the local Universe. Assuming the star formation activity in SMGs has a timescale of ~100Myr we show that their descendants at z~0 would have a space density and M_H distribution which are in good agreement with those of local ellipticals. In addition the inferred mass-weighted ages of the local ellipticals broadly agree with the look-back times of the SMG events. Taken together, these results are consistent with a simple model that identifies SMGs as events that form most of the stars seen in the majority of luminous elliptical galaxies at the present day.Peer reviewe

Polr3b heterozygosity in mice induces both beneficial and deleterious effects on health during ageing with no effect on lifespan

The genetic pathways that modulate ageing in multicellular organisms are typically highly conserved across wide evolutionary distances. Recently RNA polymerase III (Pol III) was shown to promote ageing in yeast, C. elegans and D. melanogaster. In this study we investigated the role of Pol III in mammalian ageing using C57BL/6N mice heterozygous for Pol III (Polr3b+/−). We identified sexually dimorphic, organ-specific beneficial as well as detrimental effects of the Polr3b+/− mutation on health. Female Polr3b+/− mice displayed improved bone health during ageing, but their ability to maintain an effective gut barrier function was compromised and they were susceptible to idiopathic dermatitis (ID). In contrast, male Polr3b+/− mice were lighter than wild-type (WT) males and had a significantly improved gut barrier function in old age. Several metabolic parameters were affected by both age and sex, but no genotype differences were detected. Neither male nor female Polr3b+/− mice were long-lived compared to WT controls. Overall, we find no evidence that a reduced Pol III activity extends mouse lifespan but we do find some potential organ- and sex-specific benefits for old-age health

Disability Rights as a Necessary Framework for Crisis Standards of Care and the Future of Health Care

In this essay, we suggest practical ways to shift the framing of crisis standards of care toward disability justice. We elaborate on the vision statement provided in the 2010 Institute of Medicine (National Academy of Medicine) “Summary of Guidance for Establishing Crisis Standards of Care for Use in Disaster Situations,” which emphasizes fairness; equitable processes; community and provider engagement, education, and communication; and the rule of law. We argue that interpreting these elements through disability justice entails a commitment to both distributive and recognitive justice. The disability rights movement\u27s demand “Nothing about us, without us” requires substantive inclusion of disabled people in decision-making related to their interests, including in crisis planning before, during, and after a pandemic like Covid-19

COVID-19 in patients undergoing chronic kidney replacement therapy and kidney transplant recipients in Scotland: findings and experience from the Scottish Renal Registry

BackgroundInfection with the severe acute respiratory coronavirus 2 (SARS-CoV-2) has led to a worldwide pandemic with coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2, overwhelming healthcare systems globally. Preliminary reports suggest a high incidence of infection and mortality with SARS-CoV-2 in patients receiving kidney replacement therapy (KRT). The aims of this study are to report characteristics, rates and outcomes of all patients affected by infection with SARS-CoV-2 undergoing KRT in Scotland.MethodsStudy design was an observational cohort study. Data were linked between the Scottish Renal Registry, Health Protection Scotland and the Scottish Intensive Care Society Audit Group national data sets using a unique patient identifier (Community Health Index (CHI)) for each individual by the Public Health and Intelligence unit of Public Health, Scotland. Descriptive statistics and survival analyses were performed.Results During the period 1st March 2020 to 31st May 2020, 110 patients receiving KRT tested positive for SARS-CoV-2 amounting to 2% of the prevalent KRT population. Of those affected, 86 were receiving haemodialysis or peritoneal dialysis and 24 had a renal transplant. Patients who tested positive were older and more likely to reside in more deprived postcodes. Mortality was high at 26.7% in the dialysis patients and 29.2% in the transplant patients. ConclusionThe rate of detected SARS-CoV-2 in people receiving KRT in Scotland was relatively low but with a high mortality for those demonstrating infection. Although impossible to confirm, it appears that the measures taken within dialysis units coupled with the national shielding policy, have been effective in protecting this population from infection. <br/

Validation of a priori CME arrival predictions made using real-time heliospheric imager observations

Between December 2010 and March 2013, volunteers for the Solar Stormwatch (SSW) Citizen Science project have identified and analyzed coronal mass ejections (CMEs) in the near real-time Solar Terrestrial Relations Observatory Heliospheric Imager observations, in order to make “Fearless Forecasts” of CME arrival times and speeds at Earth. Of the 60 predictions of Earth-directed CMEs, 20 resulted in an identifiable Interplanetary CME (ICME) at Earth within 1.5–6 days, with an average error in predicted transit time of 22 h, and average transit time of 82.3 h. The average error in predicting arrival speed is 151 km s−1, with an average arrival speed of 425km s−1. In the same time period, there were 44 CMEs for which there are no corresponding SSW predictions, and there were 600 days on which there was neither a CME predicted nor observed. A number of metrics show that the SSW predictions do have useful forecast skill; however, there is still much room for improvement. We investigate potential improvements by using SSW inputs in three models of ICME propagation: two of constant acceleration and one of aerodynamic drag. We find that taking account of interplanetary acceleration can improve the average errors of transit time to 19 h and arrival speed to 77 km s−1

Ice and ocean velocity in the Arctic marginal ice zone: Ice roughness and momentum transfer

The interplay between sea ice concentration, sea ice roughness, ocean stratification, and momentum transfer to the ice and ocean is subject to seasonal and decadal variations that are crucial to understanding the present and future air-ice-ocean system in the Arctic. In this study, continuous observations in the Canada Basin from March through December 2014 were used to investigate spatial differences and temporal changes in under-ice roughness and momentum transfer as the ice cover evolved seasonally. Observations of wind, ice, and ocean properties from four clusters of drifting instrument systems were complemented by direct drill-hole measurements and instrumented overhead flights by NASA operation IceBridge in March, as well as satellite remote sensing imagery about the instrument clusters. Spatially, directly estimated ice-ocean drag coefficients varied by a factor of three with rougher ice associated with smaller multi-year ice floe sizes embedded within the first-year-ice/multi-year-ice conglomerate. Temporal differences in the ice-ocean drag coefficient of 20–30% were observed prior to the mixed layer shoaling in summer and were associated with ice concentrations falling below 100%. The ice-ocean drag coefficient parameterization was found to be invalid in September with low ice concentrations and small ice floe sizes. Maximum momentum transfer to the ice occurred for moderate ice concentrations, and transfer to the ocean for the lowest ice concentrations and shallowest stratification. Wind work and ocean work on the ice were the dominant terms in the kinetic energy budget of the ice throughout the melt season, consistent with free drift conditions. Overall, ice topography, ice concentration, and the shallow summer mixed layer all influenced mixed layer currents and the transfer of momentum within the air-ice-ocean system. The observed changes in momentum transfer show that care must be taken to determine appropriate parameterizations of momentum transfer, and imply that the future Arctic system could become increasingly seasonal

Missing information, unresponsive authors, experimental flaws: the impossibility of assessing the reproducibility of previous human evaluations in NLP

We report our efforts in identifying a set of previous humane valuations in NLP that would be suitable for a coordinated study examining what makes human evaluations in NLP more/less reproducible. We present our results and findings, which include that just13% of papers had (i) sufficiently low barriers to reproduction, and (ii) enough obtainable information, to be considered for reproduction, and that all but one of the experiments we selected for reproduction was discovered to have flaws that made the meaningfulness of conducting are production questionable. As a result, we had to change our coordinated study design from a reproduce approach to a standardise-then-reproduce-twice approach. Our overall (negative)finding that the great majority of human evaluations in NLP is not repeatable and/or not reproducible and/or too flawed to justify reproduction, paints a dire picture, but presents an opportunity for a rethink about how to design and report human evaluations in NL