Using the PACS and SPIRE spectrometers on-board the Herschel Space Observatory, we obtained spectra of two red supergiants (RSGs) in the Large Magellanic Cloud (LMC). Multiple rotational CO emission ...lines (J = 6–5 to 15-14) and 15 H2O lines were detected from IRAS 05280−6910, and one CO line was detected from WOH G64. This is the first time that CO rotational lines have been detected from evolved stars in the LMC. Their CO line intensities are as strong as those of the Galactic RSG, VY CMa. Modelling the CO lines and the spectral energy distribution results in an estimated mass-loss rate for IRAS 05280−6910 of 3 × 10−4 M⊙ yr−1. The model assumes a gas-to-dust ratio and a CO-to-H2 abundance ratio is estimated from the Galactic values scaled by the LMC metallicity (Fe/H ∼ −0.3), i.e. that the CO-to-dust ratio is constant for Galactic and LMC metallicities within the uncertainties of the model. The key factor determining the CO line intensities and the mass-loss rate found to be the stellar luminosity.
Recent studies using cell culture infection systems that recapitulate the entire life cycle of hepatitis C virus (HCV) indicate that several nonstructural viral proteins, including NS2, NS3, and ...NS5A, are involved in the process of viral assembly and release. Other recent work suggests that Ser-168 of NS2 is a target of CK2 kinase-mediated phosphorylation, and that this controls the stability of the genotype 1a NS2 protein. Here, we show that Ser-168 is a critical determinant in the production of infectious virus particles. Substitution of Ser-168 with Ala (or Gly) ablated production of infectious virus by cells transfected with a chimeric viral RNA (HJ3-5) containing core-NS2 sequences from the genotype 1a H77 virus within the background of genotype 2a JFH1 virus. An S168A substitution also impaired production of virus by cells transfected with JFH1 RNA. This mutation did not alter polyprotein processing or genome replication. This defect in virus production could be rescued by expression of wt NS2 in trans from an alphavirus replicon. The trans-complementing activities of NS2 from genotypes 1a and 2a demonstrated strong preferences for rescue of the homologous genotype. Importantly, the S168A mutation did not alter the association of core or NS5A proteins with host cell lipid droplets, nor prevent the assembly of core into particles with sedimentation and buoyant density properties similar to infectious virus, indicating that NS2 acts subsequent to the involvement of core, NS5A, and NS3 in particle assembly. Second-site mutations in NS2 as well as in NS5A can rescue the defect in virus production imposed by the S168G mutation. In aggregate, these results indicate that NS2 functions in trans, in a late-post assembly maturation step, perhaps in concert with NS5A, to confer infectivity to the HCV particle.
BackgroundTo gain maximum insight from large administrative healthcare datasets it is important to understand their data quality. Although a gold standard against which to assess criterion validity ...rarely exists for such datasets, internal consistency can be evaluated. We aimed to identify inconsistencies in the recording of mandatory International Statistical Classification of Diseases and Related Health Problems, tenth revision (ICD-10) codes within the Hospital Episodes Statistics dataset in England.MethodsThree exemplar medical conditions where recording is mandatory once diagnosed were chosen: autism, type II diabetes mellitus and Parkinson’s disease dementia. We identified the first occurrence of the condition ICD-10 code for a patient during the period April 2013 to March 2021 and in subsequent hospital spells. We designed and trained random forest classifiers to identify variables strongly associated with recording inconsistencies.ResultsFor autism, diabetes and Parkinson’s disease dementia respectively, 43.7%, 8.6% and 31.2% of subsequent spells had inconsistencies. Coding inconsistencies were highly correlated with non-coding of an underlying condition, a change in hospital trust and greater time between the spell with the first coded diagnosis and the subsequent spell. For patients with diabetes or Parkinson’s disease dementia, the code recording for spells without an overnight stay were found to have a higher rate of inconsistencies.ConclusionsData inconsistencies are relatively common for the three conditions considered. Where these mandatory diagnoses are not recorded in administrative datasets, and where clinical decisions are made based on such data, there is potential for this to impact patient care.
Older adults have worse outcomes following hospitalization with COVID-19, but within this group there is substantial variation. Although frailty and comorbidity are key determinants of mortality, it ...is less clear which specific manifestations of frailty and comorbidity are associated with the worst outcomes.
We aimed to identify the key comorbidities and domains of frailty that were associated with in-hospital mortality in older patients with COVID-19 using models developed for machine learning algorithms.
This was a retrospective study that used the Hospital Episode Statistics administrative data set from March 1, 2020, to February 28, 2021, for hospitalized patients in England aged 65 years or older. The data set was split into separate training (70%), test (15%), and validation (15%) data sets during model development. Global frailty was assessed using the Hospital Frailty Risk Score (HFRS) and specific domains of frailty were identified using the Global Frailty Scale (GFS). Comorbidity was assessed using the Charlson Comorbidity Index (CCI). Additional features employed in the random forest algorithms included age, sex, deprivation, ethnicity, discharge month and year, geographical region, hospital trust, disease severity, and International Statistical Classification of Disease, 10th Edition codes recorded during the admission. Features were selected, preprocessed, and input into a series of random forest classification algorithms developed to identify factors strongly associated with in-hospital mortality. Two models were developed; the first model included the demographic, hospital-related, and disease-related items described above, as well as individual GFS domains and CCI items. The second model was similar to the first but replaced the GFS domains and CCI items with the HFRS as a global measure of frailty. Model performance was assessed using the area under the receiver operating characteristic (AUROC) curve and measures of model accuracy.
In total, 215,831 patients were included. The model using the individual GFS domains and CCI items had an AUROC curve for in-hospital mortality of 90% and a predictive accuracy of 83%. The model using the HFRS had similar performance (AUROC curve 90%, predictive accuracy 82%). The most important frailty items in the GFS were dementia/delirium, falls/fractures, and pressure ulcers/weight loss. The most important comorbidity items in the CCI were cancer, heart failure, and renal disease.
The physical manifestations of frailty and comorbidity, particularly a history of cognitive impairment and falls, may be useful in identification of patients who need additional support during hospitalization with COVID-19.
ABSTRACT
Radiative transfer is a key component in almost all astrophysical and cosmological simulations. We present magritte: a modern open-source software library for 3D radiative transfer. It uses ...a deterministic ray-tracer and formal solver, i.e. it computes the radiation field by tracing rays through the model and solving the radiative transfer equation in its second-order form along a fixed set of rays originating from each point. magritte can handle structured and unstructured input meshes, as well as smoothed-particle hydrodynamics (SPH) particle data. In this first paper, we describe the numerical implementation, semi-analytic tests and cross-code benchmarks for the non-LTE line radiative transfer module of magritte. This module uses the radiative transfer solver to self-consistently determine the populations of the quantized energy levels of atoms and molecules using an accelerated Lambda iteration (ALI) scheme. We compare magritte with the established radiative transfer solvers ratran (1D) and lime (3D) on the van Zadelhoff benchmark and present a first application to a simple Keplerian disc model. Comparing with lime, we conclude that magritte produces more accurate and more precise results, especially at high optical depth, and that it is faster.
We present new Herschel photometric and spectroscopic observations of Supernova 1987A, carried out in 2012. Our dedicated photometric measurements provide new 70 mu m data and improved imaging ...quality at 100 and 160 mu m compared to previous observations in 2010. Our Herschel spectra show only weak CO line emission, and provide an upper limit for the 63 mu m OI line flux, eliminating the possibility that line contaminations distort the previously estimated dust mass. The far-infrared spectral energy distribution (SED) is well fitted by thermal emission from cold dust. The newly measured 70 mu m flux constrains the dust temperature, limiting it to nearly a single temperature. The far-infrared emission can be fitted by 0.5 + or - 0.1 M sub(middot in circle) of amorphous carbon, about a factor of two larger than the current nucleosynthetic mass prediction for carbon. The observation of SiO molecules at early and late phases suggests that silicates may also have formed and we could fit the SED with a combination of 0.3 M sub(middot in circle) of amorphous carbon and 0.5 M sub(middot in circle) of silicates, totalling 0.8 M sub(middot in circle) of dust. Our analysis thus supports the presence of a large dust reservoir in the ejecta of SN 1987A. The inferred dust mass suggests that supernovae can be an important source of dust in the interstellar medium, from local to high-redshift galaxies.
In order to investigate the origin and the structure of the low-velocity, chemically rich clumps observed along the lobes of low- and intermediate-mass outflows, we construct a detailed model of the ...S1 clump along the CB3 outflow. We use a time-dependent chemical model coupled with a radiative transfer model to reproduce the observed line profile for a direct comparison with previous observations of this clump. We find that the simultaneous fitting of multiple species and transitions is a powerful tool in constraining the physical parameters of the gas. Different scenarios for the clump formation have been investigated. The models that better reproduce all the observed lines are those where the clump is formed, at least partially, before the advent of the outflow; with the advent of the outflow the clump undergoes a short period of non-dissociative shock and the consequent release of the icy mantle together with the high-temperature chemistry leads to the observed chemical enrichment. Our results also suggest the presence of substructure within the clump: a more extended component traced by CS, SO and the lower-energy transitions (3K-2K and 2K-1K) of CH3OH, and a more compact component traced by H2CO, SO2 and the higher-energy transitions (5K-4K) of CH3OH.
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