Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial

BACKGROUND: Passive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited. METHODS: In this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581. FINDINGS: From Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77–1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66–1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14–4·29); for patients who were antibody negative, the OR was 0·51 (0·29–0·90; pinteraction=0·001). INTERPRETATION: When administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry. FUNDING: US National Institutes of Health

Unmanned Aerial Vehicle (UAV)-based remote sensing for early-stage detection of Ganoderma

Early detection of Basal Stem Rot (BSR) disease in oil palms is an important plantation management activity in Southeast Asia. Practical approaches for the best strategic approach toward the treatment of this disease that originated from Ganoderma Boninense require information about the status of infection. In spite of the availability of conventional methods to detect this disease, they are difficult to be used in plantation areas that are commonly large in terms of planting hectarage; therefore, there is an interest for a quick and delicate technique to facilitate the detection and monitoring of Ganoderma in its early stage. The main goal of this paper is to evaluate the use of remote sensing technique for the rapid detection of Ganoderma-infected oil palms using Unmanned Aerial Vehicle (UAV) imagery integrated with an Artificial Neural Network (ANN) model. Principally, we sought for the most representative mean and standard deviation values from green, red, and near-infrared bands, as well as the best palm circle radius, threshold limit, and the number of hidden neurons for different Ganoderma severity levels. With the obtained modified infrared UAV images at 0.026 m spatial resolution, early BSR infected oil palms were most satisfactorily detected with mean and standard deviation derived from a circle radius of 35 pixels of band green and near-infrared, 1/8 threshold limit, and ANN network by 219 hidden neurons, where the total classification accuracies achieved for training and testing the dataset were 97.52% and 72.73%, respectively. The results from this study signified the utilization of an affordable digital camera and UAV platforms in oil palm plantation, predominantly in disease management. The UAV images integrated with the Levenberg–Marquardt training algorithm illustrated its great potential as an aerial surveillance tool to detect early Ganoderma-infected oil palms in vast plantation areas in a rapid and inexpensive manner

A Geometrical Approach to a New Unified Field Theory

To identify the risk factors for development of peripapillary retinal splitting (schisis) in patients with glaucoma or suspicion of glaucoma.Glaucoma Clinic, Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, IL.In this institutional cross-sectional study, 495 patients (990 eyes) who had undergone spectral-domain optical coherence tomography (OCT Spectralis HRA-OCT, Heidelberg Engineering) optic nerve head (ONH) imaging and did not have identifiable optic nerve pits, pseudopits or coloboma were included. OCT scans were reviewed by two observers.Presence of peripapillary retinal splitting identified on OCT raster scans.Eleven of 990 glaucoma and glaucoma suspect eyes (1.1%) of 7 patients (2 females, 5 males, mean age 64.5 ± 9.2 years) had peripapillary retinal splitting. Two of these 11 eyes had extension of the splitting into the macula but none to the fovea. Of these 11 patients, 2 (28.6%) were glaucoma suspects, 3 (42.9%) had primary open-angle glaucoma, 1 (14.3%) had chronic angle-closure glaucoma and 1 (14.3%) had pigmentary glaucoma. 7/11 (63.6%) eyes had vitreous traction to the disc visualized on OCT and 6/11 eyes (54.5%) had beta-zone peripapillary atrophy.We observed peripapillary retinal splitting in 1.1% of a series of 990 glaucoma and glaucoma-suspect eyes. Evidence of adherent vitreous with traction and peripapillary atrophy was found in a majority of the involved eyes. A comparison to an age and axial length matched cohort is required to determine if this is a condition that is associated with glaucoma