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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.

The multiscale pore structure of a natural shale is obtained by three distinct imaging means. First, micro-tomography image data are extended to provide the spatial arrangement of the minerals and pores observable with a voxel size of 700 nm (denoted here as the macroscopic scale). Second, FIB/SEM provides a 3D representation of the porous clay matrix on the so-called mesoscopic scale (10-20 nm); a connected pore network, devoid of cracks, is obtained for two samples out of five, while the pore network is connected through cracks for two other samples out of five. Third, the nanometric pore network is characterized with tomographic STEM. Using these experimental pore structure data, permeability calculations are performed by the Lattice Boltzmann Method on the nanoscale, on the mesoscale, and on the combination of the two. Upscaling is finally done (by a finite volume approach) on the larger macroscopic scale. Calculations show that, in the absence of cracks, the contribution of the pore structure at the nanoscale, on the overall permeability, is similar to that of the mesoscale. The impact of the most recent tomographic STEM measurements on the overall transport properties is discussed.

Abstract Vanadium dioxide has attracted much interest due to the drastic change of the electrical and optical properties it exhibits during the transition from the semiconductor state to the metallic state, which takes place at a critical temperature of about 68 °C. Much study has been especially devoted to developing advanced fabrication methodologies to improve the performance of VO2 thin films for phase-change applications in optical devices. Films structural and morphological characterisation is normally performed with expensive and time consuming equipment, as x-ray diffractometers, electron microscopes and atomic force microscopes. Here we propose a purely optical approach which combines Polarized Raman Mapping and Phase-Transition by Continuous Wave Optical Excitation (PTCWE) to acquire through two simple measurements structural, morphological and thermal behaviour information on polycrystalline VO2 thin films. The combination of the two techniques allows to reconstruct a complete picture of the properties of the films in a fast and effective manner, and also to unveil an interesting stepped appearance of the hysteresis cycles probably induced by the progressive stabilization of rutile metallic domains embedded in the semiconducting monoclinic matrix.

Abstract Matching of various chalcogenide films shows the advantage of delivering multilayer heterostructures whose physical properties can be tuned with respect to the ones of the constituent single films. In this work, (Ge–Sb–Te)-based heterostructures were deposited by radio frequency sputtering on Si(100) substrates and annealed up to 400 °C. The as-deposited and annealed samples were studied by means of X-ray fluorescence, X-ray diffraction, scanning transmission electron microscopy, electron energy loss spectroscopy and Raman spectroscopy. The heterostructures, combining thermally stable thin layers (i. e. Ge-rich Ge5.5Sb2Te5, Ge) and films exhibiting fast switching dynamics (i. e. Sb2Te3), show, on the one side, higher crystallization-onset temperatures than the standard Ge2Sb2Te5 alloy and, on the other side, none to minimal Ge-segregation.

Abstract Background The recruitment-to-inflation ratio (R/I) has been recently proposed to bedside assess response to PEEP. The impact of PEEP on ventilator-induced lung injury depends on the extent of dynamic strain reduction. We hypothesized that R/I may reflect the potential for lung recruitment (i.e. recruitability) and, consequently, estimate the impact of PEEP on dynamic lung strain, both assessed through computed tomography scan. Methods Fourteen lung-damaged pigs (lipopolysaccharide infusion) underwent ventilation at low (5 cmH2O) and high PEEP (i.e., PEEP generating a plateau pressure of 28–30 cmH2O). R/I was measured through a one-breath derecruitment maneuver from high to low PEEP. PEEP-induced changes in dynamic lung strain, difference in nonaerated lung tissue weight (tissue recruitment) and amount of gas entering previously nonaerated lung units (gas recruitment) were assessed through computed tomography scan. Tissue and gas recruitment were normalized to the weight and gas volume of previously ventilated lung areas at low PEEP (normalized-tissue recruitment and normalized-gas recruitment, respectively). Results Between high (median [interquartile range] 20 cmH2O [18–21]) and low PEEP, median R/I was 1.08 [0.88–1.82], indicating high lung recruitability. Compared to low PEEP, tissue and gas recruitment at high PEEP were 246 g [182–288] and 385 ml [318–668], respectively. R/I was linearly related to normalized-gas recruitment (r = 0.90; [95% CI 0.71 to 0.97) and normalized-tissue recruitment (r = 0.69; [95% CI 0.25 to 0.89]). Dynamic lung strain was 0.37 [0.29–0.44] at high PEEP and 0.59 [0.46–0.80] at low PEEP (p

A escolha adequada do instrumento para colecta é fundamental para que a pesquisa apresente resultados assertivos, confiáveis e úteis para a ciência e a sociedade. Assim, esta revisão de trabalhos de culminação de cursos universitários, tem por objectivo, analisar os tipos de instrumentos de recolha de dados adotados em pesquisas das Ciências Educacionais desenvolvidos em Universidades moçambicanas. Para o efeito, foram analisados 60 trabalhos tendo como foco o tipo de instrumentos, a natureza das questões e sua correlação com a pergunta e o objetivo da investigação. Os resultados indicaram a adoção de questionários, entrevistas e roteiros de observação. As três modalidades são amplamente reconhecidas e com uso consolidado no campo acadêmico da Educação/Ensino. Em alguns casos mais de um instrumento foi utilizado. Todos os instrumentos foram elaborados pelas autorias. No entanto, foi verificado que alguns dos instrumentos demonstraram baixa correlação com a questão e o objectivo da pesquisa, o que indica uma importante fragilidade na sua elaboração.

The professional identity of scientists has historically been cultivated to value research over teaching, which can undermine initiatives that aim to reform science education. Course-Based Research Experiences (CRE) and the inclusive Research and Education Communities (iREC) are two successful and impactful reform efforts that integrate research and teaching. The aim of this study is to explicate the professional identity of instructors who implement a CRE within an established iREC and to explore how this identity contributes to the success of these programs. 97 CRE instructors from the Science Education Alliance (SEA) iREC participated in a 2-year, multi-stage, qualitative research project that involved weekly reflective journaling, autoethnographic description, small group evaluation and writing, and large-scale community checking. The resulting description of professional identity consisted of shared values (inclusivity, student success, community membership, ownership/agency, science, overcoming failure, and persistence), specified roles (mentor, advocate, scientist, educator, motivator, collaborator, community builder, learner, evaluator and project manager) and a stated sense of self (dedicated, resilient, pride in students, multiskilled, valued, community member, responsible and overworked). Analysis of individual reflective diary entries revealed how a professional identity underpinned and facilitated the ways in which faculty addressed challenges that arose and worked toward the success of every student. It is the self-concept of the professional identity of the instructor in the context of the CRE classroom that directed the extended commitment and effort that these instructors evidently put into their work with students, which facilitated student engagement, student persistence, and their collective scientific output. The study concludes that a professional identity of STEM faculty in the context of a CRE and iREC combines being a researcher and educator, and that this integrated identity is central for current initiatives aimed at transforming undergraduate STEM education.

Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections (PANDAS) and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) are broad diagnoses that encompass a range of sudden-onset neuropsychiatric symptoms in children, which can include obsessive-compulsive disorder (OCD), tics, anxiety, emotional instability, and cognitive difficulties. Unlike PANDAS, PANS is not strictly linked to group A streptococcal infections but can be triggered by various infectious or environmental factors. Lights and shadows remain upon the management of children with PANS and PANDAS and there is no clear consensus regarding definition, diagnostic criteria, treatment, and follow-up. The aim of the present study was to evaluate the level of agreement on PANS and PANDAS definition, diagnostic criteria, treatment and follow-up and to assess on the basis of recent studies whether there is a need to modify the current recommendations used by primary care pediatricians and hospital pediatricians in clinical practice in order to improve outcomes. Using the Delphi method, this consensus provides shared indications on PANS and PANDAS management in pediatric age, based on the most updated literature. This work represents, in our opinion, the most complete and up-to-date information on the diagnosis of PANS and PANDAS, as well as consensus statements about several aspects of clinical care. Undoubtedly, more randomized and controlled trials are needed in the pediatric population to better define the best management, also in terms of adequate follow-up examinations and period of observation.

Objetivos: Descrever as reações adversas associadas a coletas de células mononucleares encontradas, a fim de monitorar o perfil de intercorrências no serviço de hemoterapia e planejar intervenções precoces, mitigando riscos. Material e métodos: Os dados foram obtidos através da planilha de registro dos procedimentos de aférese. A descrição das intercorrências foi extraída do sistema de gerenciamento da qualidade utilizado neste serviço. Critérios de exclusão: Reações adversas leves esperadas a infusão citrato e a mobilização em que não houve necessidade de administração de medicação não planejada e/ou avaliação médica. Resultados: No período entre janeiro de 2020 a dezembro de 2023 foram realizadas 609 coletas de células mononucleares: 457 coletas autólogas, 128 coletas alogênicas, 14 coletas para CAR-T e 10 coletas para DLI (Donor Lymphocyte Infusion). Foram utilizados dois equipamentos, sendo 585 procedimentos na Spectra Optia® e 24 na Cobe Spectra®. A solução anticoagulante utilizada foi o citrato de sódio e os métodos de mobilização utilizados incluíram fator estimulador de granulócitos (G-CSF), plerixafor ou quimioterapia. As coletas foram realizadas via acesso venoso periférico ou central. Foram observadas 28 intercorrências em 26 procedimentos. Das intercorrências, 15 (53,5%) foram relacionadas ao acesso venoso, 6 (21,4%) à mobilização, 03 (10,7%) episódios de hipotensão arterial, 02 (7,2%) à toxicidade pelo citrato, 01 (3,6%) episódio de hipertensão arterial e 01 (3,6%) coagulação do circuito. As intercorrências associadas ao acesso venoso foram: fluxo insuficiente do cateter (06), hematoma/sangramento (07) e acidente de punção (02). As reações adversas foram listadas e classificadas quanto à gravidade, sendo 16 (57,2%) leves, 10 (35,7%) moderadas e 02 (7,1%) graves. Discussão: Foi observada uma incidência de 4,59% de intercorrências no levantamento dos dados das coletas de células mononucleares ocorridas entre 2020 e 2023. Em sua maioria, foram consideradas reações leves e associadas a punção venosa profunda. Das 28 intercorrências, 04 resultaram em interrupção de procedimento: 01 tetania secundária a toxicidade ao citrato, 01 coagulação do circuito e 02 fluxos insuficientes no cateter. Apesar da interrupção da aférese, apenas em 01 caso foi necessário um segundo dia de coleta. A análise dos eventos adversos não evidenciou necessidade de ajustes nos processos internos que os mitigassem. Conclusão: Este trabalho teve como objetivo, levantar dados dos últimos 4 anos do serviço de hemoterapia a fim de analisar o perfil de reações adversas nas coletas periféricas de células mononucleares. Eventos adversos graves são raros e a interrupção da coleta em decorrência dos mesmos é incomum. Portanto, a coleta de células mononucleares periférica é um procedimento relativamente seguro e é uma etapa essencial no transplante de células tronco hematopoiéticas.

Summary: Background: It 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. Methods: Non-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. Findings: Participants 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. Interpretation: Amubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID. Funding: National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.

BackgroundDevelopment of safe and effective SARS-CoV-2 therapeutics is a high priority. Amubarvimab and romlusevimab are noncompeting anti-SARS-CoV-2 monoclonal antibodies with an extended half-life.ObjectiveTo assess the safety and efficacy of amubarvimab plus romlusevimab.DesignRandomized, placebo-controlled, phase 2 and 3 platform trial. (ClinicalTrials.gov: NCT04518410).SettingNonhospitalized patients with COVID-19 in the United States, Brazil, South Africa, Mexico, Argentina, and the Philippines.PatientsAdults within 10 days onset of symptomatic SARS-CoV-2 infection who are at high risk for clinical progression.InterventionCombination of monoclonal antibodies amubarvimab plus romlusevimab or placebo.MeasurementsNasopharyngeal and anterior nasal swabs for SARS-CoV-2, COVID-19 symptoms, safety, and progression to hospitalization or death.ResultsEight-hundred and seven participants who initiated the study intervention were included in the phase 3 analysis. Median age was 49 years (quartiles, 39 to 58); 51% were female, 18% were Black, and 50% were Hispanic or Latino. Median time from symptom onset at study entry was 6 days (quartiles, 4 to 7). Hospitalizations and/or death occurred in 9 (2.3%) participants in the amubarvimab plus romlusevimab group compared with 44 (10.7%) in the placebo group, with an estimated 79% reduction in events (P

Abstract Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.

Abstract Pleistocene environments are among the most studied issues in paleoecology and human evolution research in eastern Africa. Many data have been recorded from archaeological sites located at low and medium elevations (≤ 1500 m), whereas few contexts are known at 2000 m and above. Here, we present a substantial isotopic study from Melka Kunture, a complex of prehistoric sites located at 2000—2200 m above sea level in the central Ethiopian highlands. We analyzed the stable carbon and oxygen isotopic composition of 308 faunal tooth enamel samples from sites dated between 2.02 and 0.6 Ma to investigate the animal diets and habitats. The carbon isotopic results indicate that the analyzed taxa had C4-dominated and mixed C3-C4 diets with no significant diachronic changes in feeding behavior with time. This is consistent with faunal and phytolith analyses, which suggested environments characterized by open grasslands (with both C3 and C4 grasses), patches of bushes and thickets, and aquatic vegetation. However, palynological data previously documented mountain forests, woodlands, and high-elevation grasslands. Additionally, the carbon isotopic comparison with other eastern African localities shows that differences in elevation did not influence animal feeding strategies and habitat partitioning, even though plant species vary according to altitudinal gradients. In contrast, the oxygen isotopic comparison suggests significant differences consistent with the altitude effect. Our approach allows us to detect diverse aspects of animal behavior, habitat, and vegetation that should be considered when reconstructing past environments.

Over the last two decades, there have been numerous initiatives to improve undergraduate student outcomes in STEM. One model for scalable reform is the inclusive Research Education Community (iREC). In an iREC, STEM faculty from colleges and universities across the nation are supported to adopt and sustainably implement course-based research – a form of science pedagogy that enhances student learning and persistence in science. In this study, we used pathway modeling to develop a qualitative description that explicates the HHMI Science Education Alliance (SEA) iREC as a model for facilitating the successful adoption and continued advancement of new curricular content and pedagogy. In particular, outcomes that faculty realize through their participation in the SEA iREC were identified, organized by time, and functionally linked. The resulting pathway model was then revised and refined based on several rounds of feedback from over 100 faculty members in the SEA iREC who participated in the study. Our results show that in an iREC, STEM faculty organized as a long-standing community of practice leverage one another, outside expertise, and data to adopt, implement, and iteratively advance their pedagogy. The opportunity to collaborate in this manner and, additionally, to be recognized for pedagogical contributions sustainably engages STEM faculty in the advancement of their pedagogy. Here, we present a detailed pathway model of SEA that, together with underpinning features of an iREC identified in this study, offers a framework to facilitate transformations in undergraduate science education.

Introduction: Historically, difficult-to-treat areas in psoriasis included face, scalp, folds, genitalia, nails and palmoplantar region. Recent studies have found that lower limbs behave like a “new” difficult-to-treat area, as it can be the only site of residual disease even in patients undergoing biologic therapies. Objectives: We aimed to evaluate whether legs had different response rates and response times to treatment with a new biologic drug, risankizumab, than other body sites. Methods: We conducted a real-life, observational, retrospective, multicentric study, including patients affected by moderate-to-severe psoriasis with legs involvement and undergoing biological therapy with risankizumab for more than 16 weeks. The Psoriasis Area Severity Index (PASI) and Leg-PASI were collected at T0 and at week 16, 28, 40, 52, 64 and 76. Statistical analysis using T student test and linear regression analysis were performed. Results: A total of 124 patients were included. The difference between the improvement percentage respect to baseline was statistically significant at week 16 and 28, demonstrating that Leg-PASI improved less than PASI. From the linear regression it was deduced that the slope is statistically less steep for Leg-PASI than for overall PASI, confirming that this site responds more slowly to the therapy. Conclusions: Leg response to risankizumab appears to differ significantly from other body-sites in the first weeks of treatment, even if after 28 weeks statistical significance is lost. Our preliminary finding suggests that risankizumab can be considered an effective treatment for legs psoriasis, but with longer response times than other areas demonstrating the relative nature of resistance to treatment of this district.