Internal representations of smell in the Drosophila brain

Recent advances in sensory neuroscience using Drosophila olfaction as a model system have revealed brain maps representing the external world. Once we understand how the brain's built-in capability generates the internal olfactory maps, we can then elaborate how the brain computes and makes decision to elicit complex behaviors. Here, we review current progress in mapping Drosophila olfactory circuits and discuss their relationships with innate olfactory behaviors

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

Effects of carbides on fatigue characteristics of austempered ductile iron

Crack initiation and growth behavior of an austempered ductile iron (ADI) austenitized at 800 °C and austempered at 260 °C have been assessed under three-point bend fatigue conditions. Initiation sites have been identified as carbides remaining from the as-cast ductile iron due to insufficient austenization. The number of carbides cracking on loading to stresses greater than 275 MPa is critical in determining the failure mechanism. In general, high carbide area fractions promote coalescence-dominated fatigue crack failure, while low area fractions promote propagation-dominated fatigue crack failure. Individual carbides have been characterized using finite body tessellation (FBT) and adaptive numerical modeling (SUpport vector Parsimonious ANalysis Of VAriance (SUPANOVA)) techniques in an attempt to quantify the factors promoting carbide fracture. This indicated that large or long and thin carbides on the whole appear to be susceptible to fracture, and carbides that are locally clustered and aligned perpendicular to the tensile axis are particularly susceptible to fracture

Reducing beam hardening effects and metal artefacts using Medipix3RX: With applications from biomaterial science

This paper discusses methods for reducing beam hardening effects using spectral data for biomaterial applications. A small-animal spectral scanner operating in the diagnostic energy range was used. We investigate the use of photon-processing features of the Medipix3RX ASIC in reducing beam hardening and associated artefacts. A fully operational charge summing mode was used during the imaging routine. We present spectral data collected for metal alloy samples, its analysis using algebraic 3D reconstruction software and volume visualisation using a custom volume rendering software. Narrow high energy acquisition using the photon-processing detector revealed substantial reduction in beam hardening effects and metal artefacts

Effect of thermal residual stresses on fatigue crack opening and propagation behavior in an Al/SiC p metal matrix composite

The effects of a thermal residual stress field on fatigue crack growth in a silicon carbide particle-reinforced aluminium alloy have been measured. Stress fields were introduced into plates of material by means of a quench from a solution heat treatment temperature. Measurements using neutron diffraction have shown that this introduces an approximately parabolic stress field into the plates, varying from compressive at the surfaces to tensile in the centre. Long fatigue cracks were grown in specimens cut from as-quenched plates, and in specimens which were given a stress-relieving overageing heat treatment prior to testing. Crack closure levels for these cracks were determined as a function of the position of the crack tip in the residual stress field, and these are shown to differ between as-quenched and stress-relieved samples. By monitoring the compliance of the specimens during fatigue cycling, the degree to which the residual stresses close the crack has been evaluated

Residual Stresses Distribution Through Thick HVOF Sprayed Inconel 718 Coatings

Residual stress build up in thick thermal spray coatings is a property of concern. Coating adhesion to the substrate is influenced by residual stresses that are generated during the coating deposition process. In the HVOF spray process, significant peening stresses are generated during impact of semi molten particles on the substrate. The combination of these peening stresses together with quenching and thermal mismatch stresses can be of significant importance. Both numerical Finite Element Method (FEM), to calculate peening, quenching stresses, and experimental methods, i.e. Modified Layer Removal Method (MLRM) and Neutron Diffraction, have been utilised in this work. The investigation was performed on thick Inconel 718 coatings on Inconel 718 substrates. Combined, these numerical and experimental techniques yield a deeper understanding of residual stress formation in the HVOF process and thus a tool for process optimisation. The relationship between the stress state and deposit/substrate thickness ratio is given particular interest