A new semi-analytical treatment of the effect of supernovae on ULIRG spectral energy distributions.

This work presents a method for generating synthetic spectra of Ultra-Luminous Infrared Galaxies (ULIRGS) using AGN, HII region and supernovae source functions. The AGN element represents the far-infrared contribution to the ULIRG spectrum from an energetic central engine. It is modelled using a quasar source embedded in an axi-symmetric dusty torus. The radiative transfer of flux (RT) is then simulated and the AGN emergent spectral energy distributions (SEDs) generated. The HII region solution is then developed. A stellar evolutionary synthesis code is used to generate instantaneous burst (ISB) source functions which decay in time. The evolution of the gas and dust density in a spherically-symmetric, dense GMC, under the influence of a time-dependent ionizing source flux, is derived. Having irradiated the dust distribution with the source cluster SED, the RT is calculated and the HII region SEDs obtained. The impact of supernovae energy on a GMC already ionized by stellar flux is then considered. Using the standard pressure-driven expansion model of e.g., Weaver et al. (1977) the radial evolution of a superbubble expanding under the influence of a continuous super novae energy function is derived. The superbubble is modelled in both an adiabatic rapid expansion phase and in an isothermal momentum-conserving phase. As the superbubble expands, upstream gas is swept into a thin shell trapped on its surface and the gas density enhancement is modelled using simple shock physics. Having generated expressions for the evolution of the shell gas temperature, it is linked to the dust density via a temperature dependent condensation factor. Finally expressions are developed to quantify the evolution of the optical depth along a line of sight. It is found that the star formation efficiency (SFE) has a profound effect on the radial evolution of the optical depth distributions in GMCs generating marked differences in behaviour between and high and low SFEs. Low SFE models have shells below the dust condensation temperature at the GMC boundary R2w and the extinction, having initially been in decline, recovers to more substantial values in a dust reformation scenario. These systems tend to be optically thick for most of their evolution. Those models classified high SFE have supershell temperatures in excess of the dust condensation temperature at R2w and the extinction distribution drops precipitously and reaches very low values (< 1) at R2w- It then remains low for some time before a small recovery in extinction occurs as the shell dust condenses out. These systems tend to be optically thin for most of their life-times. It is the more powerful supernovae source functions included in the modelled space which generate the high SFE extinction behaviour and vice versa. Having derived the dust density distributions they are irradiated by the appropriate central source cluster SED and the RT simulated to generate the emergent SEDs. These are similarly categorised as low and high SFE. The low SFE model SEDs appear to be representative of systems where the dust acts as an enshrouding bolometer and most it not all UV and optical radiation is reprocessed and re-emitted into the infrared. Conversely, the high SFE model SEDs are optically revealed and exhibit substantial, only mildly attenuated source flux at short wavelengths for the majority of their evolution. The emergent AGN and starburst (ISB HII region and supernovae) SEDs are then combined in pairs to form a ULIRG SED Library. These SEDs are matched to the published data for a sample of six nearby (redshift z < 1) ULIRGS. No model ULIRG SED is found to have a better than 40% probability of belonging to the same population distribution as the published data. This is found to be most likely the result of using an ISB source function. The starburst SED library is therefore extended to approximate constant star formation (CSFRA) using a time decay parameterization and the ULIRGs refitted. In each case a model ULIRG SED was found to match the observations with a better than 5% probability of non-random fit, which suggests that a constant rather than ISB star formation mode is perhaps more appropriate in ULIRGs. Using the CSFRA component of the best-fitting model ULIRG SED, estimates are made for the star formation rate, starburst age and the implied merger and interaction state for each ULIRG. In all case these quantities agree favourably with the literature. Each ULIRG was fitted with a CSFRA SED element originating in the high SFE group of models. This was found to be a direct result of fitting the upper limits to the short wavelength (A < 3m) flux data points, as it is the high SFE SEDs that are optically revealed. (Abstract shortened by UMI.)

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 &lt;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&lt;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&lt;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

The vesicular monoamine transporter (VMAT-2) inhibitor tetrabenazine induces tremulous jaw movements in rodents: Implications for pharmacological models of parkinsonian tremor

Tetrabenazine (TBZ) is a reversible inhibitor of vesicular monoamine storage that is used to treat Huntington’s disease. TBZ preferentially depletes striatal dopamine (DA), and patients being treated with TBZ often experience parkinsonian side effects. The present studies were conducted to investigate the ability of TBZ to induce tremulous jaw movements (TJMs), which are a rodent model of parkinsonian tremor, and to determine if interference with adenosine A2A receptor transmission can attenuate TJMs and other motor effects of TBZ. In rats, TBZ (0.25–2.0 mg/kg) significantly induced TJMs, which primarily occurred in the 3.0–7.5-Hz frequency range. The adenosine A2A antagonist MSX-3 (1.25–10.0 mg/kg) significantly attenuated the TJMs induced by 2.0 mg/kg TBZ in rats, and also significantly reduced the display of catalepsy and locomotor suppression induced by TBZ. In mice, TBZ (2.5–10.0 mg/kg) dose dependently induced TJMs, and adenosine A2A receptor knockout mice showed significantly fewer TJMs compared to wild-type controls. MSX-3 (2.5–10.0 mg/kg) also significantly reduced TBZ-induced TJMs in CD1 mice. To provide a cellular marker of these pharmacological conditions, we examined c-Fos expression in the ventrolateral neostriatum (VLS). TBZ (2.0 mg/kg) significantly increased the number of c-Fos-positive cells in the VLS, which is indicative of reduced DA D2 receptor transmission, and 10.0 mg/kg MSX-3 significantly attenuated the TBZ-induced c-Fos expression. These results indicate that TBZ induces tremor as measured by the TJM model, and that pharmacological antagonism and genetic deletion of adenosine A2A receptors are capable of attenuating this oral tremor