The AppNL-G-F mouse retina is a site for preclinical Alzheimer's disease diagnosis and research

In this study, we report the results of a comprehensive phenotyping of the retina of the AppNL-G-F mouse. We demonstrate that soluble Aβ accumulation is present in the retina of these mice early in life and progresses to Aβ plaque formation by midlife. This rising Aβ burden coincides with local microglia reactivity, astrogliosis, and abnormalities in retinal vein morphology. Electrophysiological recordings revealed signs of neuronal dysfunction yet no overt neurodegeneration was observed and visual performance outcomes were unafected in the AppNL-G-F mouse. Furthermore, we show that hyperspectral imaging can be used to quantify retinal Aβ, underscoring its potential as a biomarker for AD diagnosis and monitoring. These fndings suggest that the AppNL-G-F retina mimics the early, preclinical stages of AD, and, together with retinal imaging techniques, ofers unique opportunities for drug discovery and fundamental research into preclinical AD

A method for real-time classification of insect vectors of mosaic and brown streak disease in cassava plants for future implementation within a low-cost, handheld, in-field multispectral imaging sensor

Background The paper introduces a multispectral imaging system and data-processing approach for the identification and discrimination of morphologically indistinguishable cryptic species of the destructive crop pest, the whitefly Bemisia tabaci. This investigation and the corresponding system design, was undertaken in two phases under controlled laboratory conditions. The first exploited a prototype benchtop variant of the proposed sensor system to analyse four cryptic species of whitefly reared under similar conditions. The second phase, of the methodology development, employed a commercial high-precision laboratory hyperspectral imager to recover reference data from five cryptic species of whitefly, immobilized through flash freezing, and taken from across four feeding environments. Results The initial results, for the single feeding environment, showed that a correct species classification could be achieved in 85–95% of cases, utilising linear Partial Least Squares approaches. The robustness of the classification approach was then extended both in terms of the automated spatial extraction of the most pertinent insect body parts, to assist with the spectral classification model, as well as the incorporation of a non-linear Support Vector Classifier to maintain the overall classification accuracy at 88–98%, irrespective of the feeding and crop environment. Conclusion This study demonstrates that through an integration of both the spatial data, associated with the multispectral images being used to separate different regions of the insect, and subsequent spectral analysis of those sub-regions, that B. tabaci viral vectors can be differentiated from other cryptic species, that appear morphologically indistinguishable to a human observer, with an accuracy of up to 98%. The implications for the engineering design for an in-field, handheld, sensor system is discussed with respect to the learning gained from this initial stage of the methodology development

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

JMAK model applied on the κ-carbide precipitation in FeMnAlC steels

Different lightweight steels alloys have been treated by different isothermal treatments in order to understand the basics of precipitation kinetics of κ-carbide for such class of new steel grades featured by high concentration of Mn and Al. The κ-carbide precipitation plays a significant role to induce the strengthening of these steel grades that maintain a significant ductility up to the fracture as a consequence of their duplex ferrite-austenite structure that exploits the twinning mechanism of austenite during the plastic deformation. In this paper the results about isothermal transformations involving the κ-carbide precipitation have been discussed. In order to deepen the comprehension of the mechanisms involved in precipitation of κ-carbides, the study has been performed by isothermal (Temperature Transformation Treatment) experiments applying different temperatures and holding times. The observed transformations have been measured and it has been possible to apply the JMAK model to fit such results. In addition, it has been observed a relationship between the steel composition and the activation energy for the transformation

γ Decomposition in Fe–Mn–Al–C lightweight steels

In the last few decades the steelmaking industry has been focusing on lightweight steel development and the Fe–Mn–Al–C system has been put under the spotlight. In fact, this quaternary alloy has been shown to be able to lower common steel density by more than 20 wt.%. In addition, these steels may also be suitable for cryogenic applications, corrosion and high-temperature oxidation resistance and wear resistance. Austenite plays an important role in Fe–Mn–Al–C steels because of its possible evolutions. Each configuration derived from y reaction has its own specific properties and/or drawbacks, which need to be mastered in order to develop valuable products. The aim of this paper is to study the different austenite decomposition reactions at different temperatures for different chemical compositions: the microstructures obtained have been characterized by means of optical and SEM microscopy with the support of Vickers macro-hardness tests, SEM-EDS and phase volume fraction diagrams. Results have made it possible to characterize four different y transformations. Limiting conditions for triggering each reaction have been established, in terms of the chemical composition driving force, thermal energy input and thermodynamic stability of austenite. Discontinuous precipitation occurred at 600 ◦C and in a medium Mn, high Al and high C combination. Cellular transformation developed at 800 ◦C annealing between 9–12% Al. For 1% C spinodal decomposition was triggered at the expense of cellular transformation, as far as austenite stability is influenced by the k-carbide driving force as well

γ Decomposition in Fe–Mn–Al–C lightweight steels

Abstract In the last few decades the steelmaking industry has been focusing on lightweight steel development and the Fe–Mn–Al–C system has been put under the spotlight. In fact, this quaternary alloy has been shown to be able to lower common steel density by more than 20 wt.%. In addition, these steels may also be suitable for cryogenic applications, corrosion and high-temperature oxidation resistance and wear resistance. Austenite plays an important role in Fe–Mn–Al–C steels because of its possible evolutions. Each configuration derived from γ reaction has its own specific properties and/or drawbacks, which need to be mastered in order to develop valuable products. The aim of this paper is to study the different austenite decomposition reactions at different temperatures for different chemical compositions: the microstructures obtained have been characterized by means of optical and SEM microscopy with the support of Vickers macro-hardness tests, SEM-EDS and phase volume fraction diagrams. Results have made it possible to characterize four different γ transformations. Limiting conditions for triggering each reaction have been established, in terms of the chemical composition driving force, thermal energy input and thermodynamic stability of austenite. Discontinuous precipitation occurred at 600 °C and in a medium Mn, high Al and high C combination. Cellular transformation developed at 800 °C annealing between 9–12% Al. For 1% C spinodal decomposition was triggered at the expense of cellular transformation, as far as austenite stability is influenced by the κ-carbide driving force as well

Prediction of Martensite Start Temperature for Lightweight Fe–Mn–Al–C Steels

A tailor-made thermodynamic database of the Fe-Mn-Al-C system was developed using the CALPHAD approach. The database enables predicting phase equilibria and thereby assessing the resulting microstructures of Fe-Mn-Al-C alloys. Available information on the martensite start (Ms) temperature was reviewed. By employing the Ms property model in the Thermo-Calc software together with the new thermodynamic database and experimental Ms temperatures, a set of model parameters for the Fe-Mn-Al-C system in the Ms model was optimised. Employing the newly evaluated parameters, the calculated Ms temperatures of the alloys in the Fe-Mn-Al-C system were compared with the available measured Ms temperatures. Predictions of Ms temperatures were performed for the alloys, Fe-10, 15 and 20 wt. Mn-xAl-yC. The predictability of the Ms model can be further validated when new experimental Ms temperatures of the Fe-Mn-Al-C system are available. © 2018, The Author(s)