Observation of a sudden cessation of a very-high-energy gamma-ray flare in PKS 1510-089 with H.E.S.S. and MAGIC in May 2016

The flat spectrum radio quasar (FSRQ) PKS 1510-089 is known for its complex multiwavelength behavior, and is one of only a few FSRQs detected at very high energy (VHE, E >100 GeV) -rays. VHE -ray observations with H.E.S.S. and MAGIC during late May and early June 2016 resulted in the detection of an unprecedented flare, which reveals for the first time VHE -ray intranight variability in this source. While a common variability timescale of 1.5 hr is found, there is a significant deviation near the end of the flare with a timescale of ∼ 20 min marking the cessation of the event. The peak flux is nearly two orders of magnitude above the low-level emission. For the first time, curvature is detected in the VHE -ray spectrum of PKS 1510-089, which is fully explained through absorption by the extragalactic background light. Optical R-band observations with ATOM reveal a counterpart of the -ray flare, even though the detailed flux evolution differs from the VHE lightcurve. Interestingly, a steep flux decrease is observed at the same time as the cessation of the VHE flare. In the high energy (HE, E >100 MeV) -ray band only a moderate flux increase is observed with Fermi-LAT, while the HE -ray spectrum significantly hardens up to a photon index of 1.6. A search for broad-line region (BLR) absorption features in the -ray spectrum indicates that the emission region is located outside of the BLR. Radio VLBI observations reveal a fast moving knot interacting with a standing jet feature around the time of the flare. As the standing feature is located ∼ 50 pc from the black hole, the emission region of the flare may have been located at a significant distance from the black hole. If this correlation is indeed true, VHE rays have been produced far down the jet where turbulent plasma crosses a standing shock.Accepted manuscrip

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

The clinical role of the hospital pharmacist in the United Kingdom National Health Service

In 2 vols.Available from British Library Document Supply Centre-DSC:DX196899 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Radionuclide sorption in Yucca Mountain tuffs with J-13 well water: Neptunium, uranium, and plutonium. Yucca Mountain site characterization program milestone 3338

We studied the retardation of actinides (neptunium, uranium, and plutonium) by sorption as a function of radionuclide concentration in water from Well J-13 and of tuffs from Yucca Mountain. Three major tuff types were examined: devitrified, vitric, and zeolitic. To identify the sorbing minerals in the tuffs, we conducted batch sorption experiments with pure mineral separates. These experiments were performed with water from Well J-13 (a sodium bicarbonate groundwater) under oxidizing conditions in the pH range from 7 to 8.5. The results indicate that all actinides studied sorb strongly to synthetic hematite and also that Np(V) and U(VI) do not sorb appreciably to devitrified or vitric tuffs, albite, or quartz. The sorption of neptunium onto clinoptilolite-rich tuffs and pure clinoptilolite can be fitted with a sorption distribution coefficient in the concentration range from 1 X 10{sup -7} to 3 X 10{sup -5} M. The sorption of uranium onto clinoptilolite-rich tuffs and pure clinoptilolite is not linear in the concentration range from 8 X 10{sup -8} to 1 X 10{sup -4} M, and it can be fitted with nonlinear isotherm models (such as the Langmuir or the Freundlich Isotherms). The sorption of neptunium and uranium onto clinoptilolite in J-13 well water increases with decreasing pH in the range from 7 to 8.5. The sorption of plutonium (initially in the Pu(V) oxidation state) onto tuffs and pure mineral separates in J-13 well water at pH 7 is significant. Plutonium sorption decreases as a function of tuff type in the order: zeolitic > vitric > devitrified; and as a function of mineralogy in the order: hematite > clinoptilolite > albite > quartz

Angiotensin converting enzyme inhibition patially prevents defecits in water maze performance, hippocampal synaptic plasticity and cerebral blood flow in streptozotocin-induced-diabetic rats

Vascular dysfunction is important in the pathogenesis of peripheral complications of diabetes. However, the effects of diabetes on cerebral blood flow and the role of vascular deficits in the pathogenesis of diabetic encephalopathy are still unknown. The present study examined whether experimental diabetes is associated with reduced cerebral blood flow and whether treatment with enalapril can improve cerebral perfusion and function (blood flow and functional cerebral deficits). Streptozotocin-diabetic rats were treated with the ACE inhibitor enalapril (24 mg/kg) from onset of diabetes. After 14 weeks of diabetes, 12 enalapril treated and 12 untreated diabetic rats, and 12 nondiabetic age-matched control rats were tested in a spatial version of the Morris water maze. After 16 weeks of diabetes, in the same groups, blood flow in the hippocampus and thalamus was measured by hydrogen clearance microelectrode polarography. In a separate study, hippocampal long-term potentiation was measured after 26 weeks of diabetes. Water maze performance and hippocampal long-term potentiation were impaired in diabetic rats. Furthermore, blood flow in diabetic rats was reduced by 30% (P<0.001) in the hippocampus and by 37% (P<0.005) in the thalamus compared to nondiabetic controls. Enalapril treatment significantly improved water maze performance (P<0.05), hippocampal long term potentiation (P<0.05) and hippocampal blood flow (P<0.05). Cerebral perfusion is reduced in diabetic rats compared to controls. Treatment aimed at the vasculature can improve cerebral blood flow, deficits in Morris maze performance and long term potentiation. These findings suggest that vasculopathy plays a role in the development of cerebral dysfunction in diabetic rats