42 research outputs found
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The Soft X-ray Imager (SXI) on the SMILE Mission
The Soft X-ray Imager (SXI) is part of the scientific payload of the Solar wind Magnetosphere Ionosphere Link Explorer (SMILE) mission. SMILE is a joint science mission between the European Space Agency (ESA) and the Chinese Academy of Sciences (CAS) and is due for launch in 2025. SXI is a compact X-ray telescope with a wide field-of-view (FOV) capable of encompassing large portions of Earth’s magnetosphere from the vantage point of the SMILE orbit. SXI is sensitive to the soft X-rays produced by the Solar Wind Charge eXchange (SWCX) process produced when heavy ions of solar wind origin interact with neutral particles in Earth’s exosphere. SWCX provides a mechanism for boundary detection within the magnetosphere, such as the position of Earth’s magnetopause, because the solar wind heavy ions have a very low density in regions of closed magnetic field lines. The sensitivity of the SXI is such that it can potentially track movements of the magnetopause on timescales of a few minutes and the orbit of SMILE will enable such movements to be tracked for segments lasting many hours. SXI is led by the University of Leicester in the United Kingdom (UK) with collaborating organisations on hardware, software and science support within the UK, Europe, China and the United States
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
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SILICON RADIATION DETECOTRS WITH OXIDE CHARGE STATE COMPENSATION
This paper discusses the use of boron implantation on high resistivity P-type silicon before oxide growth to compensate for the presence of charge states in the oxide and oxide/silicon interface. The presence of these charge states on high resistivity P-type silicon produces an inversion layer which causes high leakage currents on N/sup +/P junctions and high surface conductance. Compensating the surface region by boron implantation is shown to result in oxide passivated N/sup +/P junctions with very low leakage currents and with low surface conductance
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Use of semiconductor detectors with synchrotron radiation
Silicon and germanium semiconductor detectors are widely used as photon and charged-particle spectrometers. Semiconductor detectors combine wide energy bandwidth with good energy resolution to make useful spectrometers for use with the high-intensity x-ray sources available at synchrotron facilities. High-quality silicon and germanium single-crystal starting material is now available for the fabrication of large-volume detectors. Techniques have also been developed to reliably make detectors with passivated surfaces, thin windows and complex geometries. New low-noise preamplifiers and pulse-shaping networks allow higher counting rates and improved pulse throughput. For applications where accurate flux measurements of intense photon beams are required, a semiconductor detector with a current-measuring voltage-to-frequency converter provides a simple system which has excellent linearity and stability. Examples are given where semiconductor detectors have been used in experiments at synchrotron facilities
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PULSED FEEDBACK TECHNIQUES FOR SEMICONDUCTORS DETECTOR RADIATION SPECTROMETERS
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Status and problems of semiconductor detectors
A brief review is given of the types of silicon and germanium detectors used or presently being developed for nuclear experiments. Large-area silicon and germanium detector telescopes for use in long-range particle detection and identification are emphasized. Large area position-sensitive detectors are also described. Some results are presented regarding radiation damage and damage repair by annealing. Evidence is also presented for the importance of producing large area silicon crystals of adequate quality to reduce trapping problems to negligible proportions
Neural Mechanisms of Suboptimal Decisions
Making good decisions and adapting flexibly to environmental change are critical to the survival of animals. In this thesis, I investigated neural mechanisms underlying suboptimal decision making in humans and underlying behavioural adaptation in monkeys with the use of functional magnetic resonance imaging (fMRI) in both species.
In recent decades, in the neuroscience of decision making, there has been a prominent focus on binary decisions. Whether the presence of an additional third option could have an impact on behaviour and neural signals has been largely overlooked. I designed an experiment in which decisions were made between two options in the presence of a third option. A biophysical model simulation made surprising predictions that more suboptimal decisions were made in the presence of a very poor third alternative. Subsequent human behavioural testing showed consistent results with these predictions. In the ventromedial prefrontal cortex (vmPFC), I found that a value comparison signal that is critical for decision making became weaker in the presence of a poor value third option. The effect contrasts with another prominent potential mechanism during multi-alternative decision making – divisive normalization – the signatures of which were observed in the posterior parietal cortex.
It has long been thought that the orbitofrontal cortex (OFC) and amygdala mediate reward-guided behavioural adaptation. However, this viewpoint has been recently challenged. I recorded whole brain activity in macaques using fMRI while they performed an object discrimination reversal task over multiple testing sessions. I identified a lateral OFC (lOFC) region in which activity predicted adaptive win-stay/lose-shift behaviour. In contrast, anterior cingulate cortex (ACC) activity predicted future exploratory decisions regardless of reward outcome. Amygdala and lOFC activity was more strongly coupled for adaptive choice shifting and decoupled for task irrelevant reward memory. Day-to-day fluctuations in signals and signal coupling were correlated with day-to-day fluctuations in performance. These data demonstrate OFC, ACC, and amygdala each make unique contributions to flexible behaviour and credit assignment.This thesis is not currently available on ORA