41 research outputs found
Chemical telemetry of OH observed to measure interstellar magnetic fields
We present models for the chemistry in gas moving towards the ionization
front of an HII region. When it is far from the ionization front, the gas is
highly depleted of elements more massive than helium. However, as it approaches
the ionization front, ices are destroyed and species formed on the grain
surfaces are injected into the gas phase. Photodissociation removes gas phase
molecular species as the gas flows towards the ionization front. We identify
models for which the OH column densities are comparable to those measured in
observations undertaken to study the magnetic fields in star forming regions
and give results for the column densities of other species that should be
abundant if the observed OH arises through a combination of the liberation of
H2O from surfaces and photodissociation. They include CH3OH, H2CO, and H2S.
Observations of these other species may help establish the nature of the OH
spatial distribution in the clouds, which is important for the interpretation
of the magnetic field results.Comment: 11 pages, 2 figures, accepted by Astrophysics and Space Scienc
HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms
Background
Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS) which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy which impacts future treatment choices. Variations in human leukocyte antigen (HLA) class I in particular have been associated with serious T-cell mediated adverse drug reactions which has led to preventive screening strategies for some drugs.
Objective
To determine if variation in the HLA region is associated with vancomycin-induced DRESS.
Methods
Probable vancomycin DRESS cases were matched 1:2 with tolerant controls based on sex, race, and age using BioVU, Vanderbilt’s deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by conditional logistic regression. An extended sample set from BioVU was utilized to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele.
Results
Twenty-three individuals met inclusion criteria for vancomycin-associated DRESS. 19/23 (82.6%) cases carried HLA-A*32:01 compared to 0/46 (0%) of the matched vancomycin tolerant controls (p=1x10-8) and 6.3% of the BioVU population (n=54,249) (p=2x10-16). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01 positive group indicated that 19.2% developed DRESS and did so within four weeks.
Conclusions
HLA-A*32:01 is strongly associated with vancomycin DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug and preserve future treatment options with co-administered antibiotics
Star and Planet Formation with ALMA: an Overview
Submillimeter observations with ALMA will be the essential next step in our
understanding of how stars and planets form. Key projects range from detailed
imaging of the collapse of pre-stellar cores and measuring the accretion rate
of matter onto deeply embedded protostars, to unravelling the chemistry and
dynamics of high-mass star-forming clusters and high-spatial resolution studies
of protoplanetary disks down to the 1 AU scale.Comment: Invited review, 8 pages, 5 figures; to appear in the proceedings of
"Science with ALMA: a New Era for Astrophysics". Astrophysics & Space
Science, in pres
Studies of Dense Cores with ALMA
Dense cores are the simplest star-forming sites that we know, but despite
their simplicity, they still hold a number of mysteries that limit our
understanding of how solar-type stars form. ALMA promises to revolutionize our
knowledge of every stage in the life of a core, from the pre-stellar phase to
the final disruption by the newly born star. This contribution presents a brief
review of the evolution of dense cores and illustrates particular questions
that will greatly benefit from the increase in resolution and sensitivity
expected from ALMAComment: 6 pages, 2 figures, to appear in Astrophysics and Space Science,
special issue of "Science with ALMA: a new era for Astrophysics" conference,
ed. Dr. Bachille
Interstellar MHD Turbulence and Star Formation
This chapter reviews the nature of turbulence in the Galactic interstellar
medium (ISM) and its connections to the star formation (SF) process. The ISM is
turbulent, magnetized, self-gravitating, and is subject to heating and cooling
processes that control its thermodynamic behavior. The turbulence in the warm
and hot ionized components of the ISM appears to be trans- or subsonic, and
thus to behave nearly incompressibly. However, the neutral warm and cold
components are highly compressible, as a consequence of both thermal
instability in the atomic gas and of moderately-to-strongly supersonic motions
in the roughly isothermal cold atomic and molecular components. Within this
context, we discuss: i) the production and statistical distribution of
turbulent density fluctuations in both isothermal and polytropic media; ii) the
nature of the clumps produced by thermal instability, noting that, contrary to
classical ideas, they in general accrete mass from their environment; iii) the
density-magnetic field correlation (or lack thereof) in turbulent density
fluctuations, as a consequence of the superposition of the different wave modes
in the turbulent flow; iv) the evolution of the mass-to-magnetic flux ratio
(MFR) in density fluctuations as they are built up by dynamic compressions; v)
the formation of cold, dense clouds aided by thermal instability; vi) the
expectation that star-forming molecular clouds are likely to be undergoing
global gravitational contraction, rather than being near equilibrium, and vii)
the regulation of the star formation rate (SFR) in such gravitationally
contracting clouds by stellar feedback which, rather than keeping the clouds
from collapsing, evaporates and diperses them while they collapse.Comment: 43 pages. Invited chapter for the book "Magnetic Fields in Diffuse
Media", edited by Elisabete de Gouveia dal Pino and Alex Lazarian. Revised as
per referee's recommendation
Developing a predictive modelling capacity for a climate change-vulnerable blanket bog habitat: Assessing 1961-1990 baseline relationships
Aim: Understanding the spatial distribution of high priority habitats and
developing predictive models using climate and environmental variables to
replicate these distributions are desirable conservation goals. The aim of this
study was to model and elucidate the contributions of climate and topography to
the distribution of a priority blanket bog habitat in Ireland, and to examine how
this might inform the development of a climate change predictive capacity for
peat-lands in Ireland.
Methods: Ten climatic and two topographic variables were recorded for grid
cells with a spatial resolution of 1010 km, covering 87% of the mainland
land surface of Ireland. Presence-absence data were matched to these variables
and generalised linear models (GLMs) fitted to identify the main climatic and
terrain predictor variables for occurrence of the habitat. Candidate predictor
variables were screened for collinearity, and the accuracy of the final fitted GLM
was evaluated using fourfold cross-validation based on the area under the curve
(AUC) derived from a receiver operating characteristic (ROC) plot. The GLM
predicted habitat occurrence probability maps were mapped against the actual
distributions using GIS techniques.
Results: Despite the apparent parsimony of the initial GLM using only climatic
variables, further testing indicated collinearity among temperature and precipitation
variables for example. Subsequent elimination of the collinear variables and
inclusion of elevation data produced an excellent performance based on the AUC
scores of the final GLM. Mean annual temperature and total mean annual
precipitation in combination with elevation range were the most powerful
explanatory variable group among those explored for the presence of blanket
bog habitat.
Main conclusions: The results confirm that this habitat distribution in general
can be modelled well using the non-collinear climatic and terrain variables tested
at the grid resolution used. Mapping the GLM-predicted distribution to the
observed distribution produced useful results in replicating the projected
occurrence of the habitat distribution over an extensive area. The methods
developed will usefully inform future climate change predictive modelling for
Irelan
Physical Processes in Star Formation
© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s11214-020-00693-8.Star formation is a complex multi-scale phenomenon that is of significant importance for astrophysics in general. Stars and star formation are key pillars in observational astronomy from local star forming regions in the Milky Way up to high-redshift galaxies. From a theoretical perspective, star formation and feedback processes (radiation, winds, and supernovae) play a pivotal role in advancing our understanding of the physical processes at work, both individually and of their interactions. In this review we will give an overview of the main processes that are important for the understanding of star formation. We start with an observationally motivated view on star formation from a global perspective and outline the general paradigm of the life-cycle of molecular clouds, in which star formation is the key process to close the cycle. After that we focus on the thermal and chemical aspects in star forming regions, discuss turbulence and magnetic fields as well as gravitational forces. Finally, we review the most important stellar feedback mechanisms.Peer reviewedFinal Accepted Versio
Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Background:
In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation.
Methods:
This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).
Findings:
Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001).
Interpretation:
In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids.
Funding:
UK Research and Innovation (Medical Research Council) and National Institute of Health Research
Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial
Background:
Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19.
Methods:
This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.
Findings:
Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79).
Interpretation:
In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes.
Funding:
UK Research and Innovation (Medical Research Council) and National Institute of Health Research