Search

BackgroundIt is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID.MethodsNon-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo.FindingsParticipants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53-0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID.InterpretationAmubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID.FundingNational Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.

INTRODUCTION: Living kidney donor evaluation is a lengthy and complex process requiring in-person visits. Access to transplant centers, travel costs, lost wages, and dependent care arrangements are barriers to willing donors initiating evaluation. Telemedicine can help streamline and epedite the evaluation process. We aimed to deeply understand donor experiences and preferences using hybrid telemedicine video/in-person visits to ease access to donor evaluation or counseling. METHODS: We conducted in-depth, semistructured interviews with donors or donor candidates who completed their evaluation through telemedicine/in-person, or in-person only visits at a tertiary transplant center between November 27, 2019 and March 1, 2021. Enrollment continued until data saturation was reached (interviews with 20 participants) when no new information emerged from additional interviews. Transcripts were analyzed using inductive thematic analysis. RESULTS: Eight themes were identified as follows: (i) reducing financial and logistical burdens (minimizing travel time and travel-related expenses), (ii) enhancing flexibility with scheduling (less time off work and child or family caregiver arrangements), (iii) importance of a walkthrough and establishing shared understanding, (iv) supporting information with technology and visual aids, (v) key role of the coordinator, (vi) preferred visit by provider role (meeting donor surgeon in-person to create rapport and engaging primary care provider in donor evaluation/follow-up), (vii) comparing modality differences in human connection, and (viii) opportunity for family and support network engagement (allowing loved ones to be involved in telemedicine visits irrespective of geographic locations and pandemic restrictions). CONCLUSION: Telemedicine/in-person hybrid model can make donor evaluation more accessible and convenient. Our findings help inform about determinants that influence the adoption of telemedicine to initiate donor evaluation to motivate willing donors. In addition, our results call for policy and legislation that support telemedicine services for living donor kidney transplantation across states.

Present and future climatic trends are expected to markedly alter water fluxes and stores in the hydrologic cycle. In addition, water demand continues to grow due to increased human use and a growing population. Sustainably managing water resources requires a thorough understanding of water storage and flow in natural, agricultural, and urban ecosystems. Measurements of stable isotopes of water (hydrogen and oxygen) in the water cycle (atmosphere, soils, plants, surface water, and groundwater) can provide information on the transport pathways, sourcing, dynamics, ages, and storage pools of water that is difficult to obtain with other techniques. However, the potential of these techniques for practical questions has not been fully exploited yet. Here, we outline the benefits and limitations of potential applications of stable isotope methods useful to water managers, farmers, and other stakeholders. We also describe several case studies demonstrating how stable isotopes of water can support water management decision-making. Finally, we propose a workflow that guides users through a sequence of decisions required to apply stable isotope methods to examples of water management issues. We call for ongoing dialogue and a stronger connection between water management stakeholders and water stable isotope practitioners to identify the most pressing issues and develop best-practice guidelines to apply these techniques.

BACKGROUND: We sought to review our institutions experience with dental implant placement in free flap jaw reconstruction to determine factors impacting restoration of dental occlusion. METHODS: Exactly 48 patients underwent free flap jaw reconstruction with or without dental restoration from 2017 to 2022. Primary outcome was achievement of restored dental occlusion after jaw free flap reconstruction. RESULTS: A total of 48 patients with a mean age of 59.8 ± 16.4 years underwent jaw reconstruction from 2017 to 2022. Ten patients (20.8%) received osteointegrated dental implants. Two patients received a temporary dental prosthesis, 12 ± 4 months after initial reconstruction. Three patients received a final prosthesis, with a mean time to final prosthesis of 17.7 ± 12.4 months. Five patients did not receive any prosthesis despite placement of implants. CONCLUSION: A minority of patients received dental implant placement with free flap jaw reconstruction and only a small subset of these received a definitive dental prosthesis.

The New Culture of Water (NCW) is a catalyst for sustainable transformation between political agreements and the unsustainability of the real world, thus requiring an integral participation for an efficient water management where the academy will try to make a substantial contribution. Therefore, this study aimed to design, implement and evaluate four competencies: Knowledge, Attitude, Perception and Practices (KAPP) of a formal program of Education for Sustainability (EfS) on the New Water Culture (NWC), addressing issues such as prevention of water quality, conservation and efficient use at home. To carry out the evaluation, a semi-structured survey of 47 items was conducted in three stages: at the beginning (diagnostic), during the development of the (EfS) (formative) and at the end (summative). A total of 103 nursing students participated in the (EfS), divided into two groups A and B, with the addition of group C as a control group. The results showed that group A had the best results, in general. Statistical tests to calculate the mean, standard deviation (SD) and a validation with the nonparametric Wilcoxon test showing a significant change in the participants of group A, which indicated an important impact of the (EfS). This study also provides an overview of the community situation that can help trigger early warnings to identify weaknesses in water management.

BackgroundOutpatient COVID-19 monoclonal antibody (mAb) treatment via subcutaneous delivery, if effective, overcomes the logistical burdens of intravenous administration.MethodsACTIV-2/A5401 was a randomized, masked placebo-controlled platform trial where participants with COVID-19 at low risk for progression were randomized 1:1 to subcutaneously administered BMS-986414 (C135-LS) 200 mg, plus BMS-986413 (C144-LS) 200 mg, (BMS mAbs), or placebo. Coprimary outcomes were time to symptom improvement through 28 days; nasopharyngeal SARS-CoV-2 RNA below the lower limit of quantification (LLoQ) on days 3, 7, or 14; and treatment-emergent grade 3 or higher adverse events (TEAEs) through 28 days.ResultsA total of 211 participants (105 BMS mAbs and 106 placebo) initiated study product. Time to symptom improvement favored the active therapy but was not significant (median 8 vs 10 days, P=0.19). There was no significant difference in the proportion with SARS-CoV-2 RNA ConclusionsWhile safe, the BMS mAbs delivered subcutaneously were not effective at treating COVID-19 at low risk for progression. The lack of clinically significant activity may relate to the pharmacokinetics of subcutaneous administration of mAbs.

Biallelic mutations in the gene that encodes the enzyme N-glycanase 1 (NGLY1) cause a rare disease with multi-symptomatic features including developmental delay, intellectual disability, neuropathy, and seizures. NGLY1s activity in human neural cells is currently not well understood. To understand how NGLY1 gene loss leads to the specific phenotypes of NGLY1 deficiency, we employed direct conversion of NGLY1 patient-derived induced pluripotent stem cells (iPSCs) to functional cortical neurons. Transcriptomic, proteomic, and functional studies of iPSC-derived neurons lacking NGLY1 function revealed several major cellular processes that were altered, including protein aggregate-clearing functionality, mitochondrial homeostasis, and synaptic dysfunctions. These phenotypes were rescued by introduction of a functional NGLY1 gene and were observed in iPSC-derived mature neurons but not astrocytes. Finally, laser capture microscopy followed by mass spectrometry provided detailed characterization of the composition of protein aggregates specific to NGLY1-deficient neurons. Future studies will harness this knowledge for therapeutic development.

The diversity of Rubus in South America is much understudied and a taxonomic framework needs to be established as a basis for future revisionary and phylogenetic work. Our review identified 110 names based on South American specimens which were published since 1767. Each name was then classified according to its botanical description and type material. Additionally, where necessary, we suggest appropriate lecto-, neo-, or epitypes. A comprehensive list of synonyms is provided and representative herbarium specimens for each country are cited to tentatively document geographical range. In total, we accept 46 species of Rubus recorded across South America, propose 19 new synonyms, restore R. organensis, previously a synonym of R. brasiliensis, provide a replacement name for the latter, and include new country records of R. azuayensis, R. laegaardii and R. rusbyi. This checklist serves as an essential starting point for future monographic and evolutionary studies on Rubus in South America.

Abstract Silica cell-wall formation in diatoms is a showcase for the ability of organisms to control inorganic mineralization. The process of silicification by these unicellular algae is tightly regulated within a membrane-bound organelle, the silica deposition vesicle (SDV). Two opposing scenarios were proposed to explain the tight regulation of this intracellular process: a template-mediated process that relies on preformed scaffolds, or a template-independent self-assembly process. The present work points to a third scenario, where the SDV membrane is a dynamic mold that shapes the forming silica. We use in-cell cryo-electron tomography to visualize the silicification process in situ, in its native-state, and with a nanometer-scale resolution. This reveals that the plasma membrane interacts with the SDV membrane via physical tethering at membrane contact sites, where the curvature of the tethered side of the SDV membrane mirrors the intricate silica topography. We propose that silica growth and morphogenesis result from the biophysical properties of the SDV and plasma membranes.

Kindergarten teachers' work is unique because they juggle the roles of caregiver to young children, tending to their physical, emotional and educational needs, and managing their kindergarten unit. The year of internship and transition into teaching is particularly intense. For new kindergarten teachers (NKTs) to fully integrate in the kindergarten and pursue a teaching career, they need varied support schemes. This study is part of an international project supported by the Erasmus+ program. A total of 230 and 80 kindergarten mentors answered survey questionnaires. Findings show that NKTs are satisfied with their induction program and report a high level of integration into the education system and in the workplace. This study identifies relationships between a high level of NKT integration in the workplace and varied support schemes. The significance of self-efficacy as a major resource for support and mentors' contribution specific to the kindergarten setting are highlighted and discussed.

The normal lives of schools were significantly affected by the recent global pandemic. Some countries closed all schools nationally, others such as the USA closed at a local level according to state law. Much of the focus of research in this area is on the effect on children and learning loss, but this paper uses secondary analysis of data from a project on primary/secondary school transition in England to examine the experience of teaching in a pandemic, with a particular focus on pedagogy and professionalism. It presents our findings of a significant impact on teachers' professional lives in England; from the pedagogic difficulties of teaching online, dealing with the anxieties and fears of themselves and others, providing support in ways hitherto beyond their experience, increased and different workloads. Some embraced the positive challenge, but many found their mental health suffered.

The current study compared the reading growth of (a) students who received targeted interventions, (b) students who received typical school interventions, and (c) students who were proficient readers at the study's onset. The participants were 1,513 students in first through fifth grades who attended one of three treatment schools or one of three control schools. Students who received a targeted intervention had higher adjusted mean growth scores from fall to winter than students who received the typical school intervention, after controlling for grade and free or reduced-price lunch status, but had relatively equal mean growth score as the proficient readers. The data supported previous research but found positive effects for interventions that were selected and implemented by school personnel in an applied setting.

BackgroundWith the emergence of SARS-CoV-2 variants resistant to monoclonal antibody therapies and limited global access to therapeutics, the evaluation of novel therapeutics to prevent progression to severe COVID-19 remains a critical need.MethodsSafety, clinical and antiviral efficacy of inhaled interferon-β1a (SNG001) were evaluated in a phase II randomized controlled trial on the ACTIV-2/A5401 platform (ClinicalTrials.govNCT04518410). Adult outpatients with confirmed SARS-CoV-2 infection within 10 days of symptom onset were randomized and initiated either orally inhaled nebulized SNG001 given once daily for 14 days (n = 110) or blinded pooled placebo (n = 110) between February 10 and August 18, 2021.FindingsThe proportion of participants reporting premature treatment discontinuation was 9% among SNG001 and 13% among placebo participants. There were no differences between participants who received SNG001 or placebo in the primary outcomes of treatment emergent Grade 3 or higher adverse events (3.6% and 8.2%, respectively), time to symptom improvement (median 13 and 9 days, respectively), or proportion with unquantifiable nasopharyngeal SARS-CoV-2 RNA at days 3 (28% [26/93] vs. 39% [37/94], respectively), 7 (65% [60/93] vs. 66% [62/94]) and 14 (91% [86/95] vs. 91% [83/81]). There were fewer hospitalizations with SNG001 (n = 1; 1%) compared with placebo (n = 7; 6%), representing an 86% relative risk reduction (p = 0.07). There were no deaths in either arm.InterpretationIn this trial, SNG001 was safe and associated with a non-statistically significant decrease in hospitalization for COVID-19 pneumonia.FundingThe ACTIV-2 platform study is funded by the NIH. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1 AI068634, UM1 AI068636 and UM1 AI106701. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.