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ABSTRACTDuring infectious disease emergencies, it may be necessary to deploy new therapies without conclusive evidence for their effectiveness. During the SARS-CoV-2 pandemic, several countries used registries to track the use of COVID-19 convalescent plasma (CCP). Those registries provided evidence that CCP was effective when used early and with high titer.

Background: Saliva has been considered a suitable sample material for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA testing, but uncertainty remained regarding sensitivity and reliability of different saliva collection methods. Objectives: This study aimed to investigate the potential utility of expectorated saliva (ES) and drooled saliva (DS) for community mass testing. Study design: Self-collected ES and DS samples were obtained in a prospective cohort study with 2,878 participants. The utility of saliva for SARS-CoV-2 qRT-PCR testing was assessed by comparing the capacity to detect SARS-CoV-2 positive cases with results for self-collected combined throat and nose (CTN) swabs. Additionally, quantification cycle (Cq) values were compared. Results: ES- and DS-based tests showed the same high level of concordance (98% vs 98%) with CTN swab-based results. Sensitivity was higher for DS (94%) than for ES (83%) or CTN swab (90%) but differences were statistically not significant. Comparing only symptomatic cases, however, a significantly higher sensitivity of DS (96%) than of ES (76%) or CTN swab (91%) was observed. Cq values of saliva and swab specimen were significantly correlated and appeared to be not impacted by age or other potentially confounding factors. Conclusions: Saliva-based SARS-CoV-2 RNA testing showed high diagnostic accuracy and can be considered an alternative where swabbing may not be tolerated or operationally feasible. DS yielded the same or better diagnostic performance compared to ES and may present a preferred option with reduced aerosol risk and increased compliance.

ABSTRACT The ability to measure neutralizing antibodies on large scale can be important for understanding features of the natural history and epidemiology of infection, as well as an aid in determining the efficacy of interventions, particularly in outbreaks such as the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Because of the assay’s rapid scalability and high efficiency, serology measurements that quantify the presence rather than function of serum antibodies often serve as proxies of immune protection. Here, we report the development of a high-throughput, automated fluorescence-based neutralization assay using SARS-CoV-2 virus to quantify neutralizing antibody activity in patient specimens. We performed large-scale testing of over 19,000 COVID-19 convalescent plasma (CCP) samples from patients who had been infected with SARS-CoV-2 between March and August 2020 across the United States. The neutralization capacity of the samples was moderately correlated with serological measurements of anti-receptor-binding domain (RBD) IgG levels. The neutralizing antibody levels within these convalescent-phase serum samples were highly variable against the original USA-WA1/2020 strain with almost 10% of individuals who had had PCR-confirmed SARS-CoV-2 infection having no detectable antibodies either by serology or neutralization, and ~1/3 having no or low neutralizing activity. Discordance between neutralization and serology measurements was mainly due to the presence of non-IgG RBD isotypes. Meanwhile, natural infection with the earliest SARS-CoV-2 strain USA-WA1/2020 resulted in weaker neutralization of subsequent B.1.1.7 (alpha) and the B.1.351 (beta) variants, with 88% of samples having no activity against the BA.1 (omicron) variant. IMPORTANCE The ability to directly measure neutralizing antibodies on live SARS-CoV-2 virus in individuals can play an important role in understanding the efficacy of therapeutic interventions or vaccines. In contrast to functional neutralization assays, serological assays only quantify the presence of antibodies as a proxy of immune protection. Here, we have developed a high-throughput, automated neutralization assay for SARS-CoV-2 and measured the neutralizing activity of ~19,000 COVID-19 convalescent plasma (CCP) samples collected across the United States between March and August of 2020. These data were used to support the FDA’s interpretation of CCP efficacy in patients with SARS-CoV-2 infection and their issuance of emergency use authorization of CCP in 2020.

Regional differences in SARS-CoV-2 variants may affect treatment outcome. Here, the authors show that near-sourced convalescent plasma has higher efficacy, as defined by death within 30 days of transfusion, than plasma sourced more than 150 miles away.

BackgroundThe United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma.Methods and findingsMayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (ConclusionsThese results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease.Trial registrationClinicalTrials.gov NCT#: NCT04338360.

UN-CODE is a web-based tool for structuring and visualizing collective decision-making processes using qualitative, case-based data. It offers a database management tool and visualization method in one. The structure of the database and the visualizations derive from a model that is rooted in evolutionary biology and that has been transformed for social scientists. It features three principal dimensions: problem and solution definitions (PSD), weighted connectedness (c_score) as a network measure, and fitness (FIT) to describe the probability of actors reaching their goals in the collective decision-making process. The results are visualized in a scalable 3D-environment that shows the main dynamics of such in one quick overview. Funding statement: This research has been funded by The Netherlands Organisation for Scientific Research research grant no. 451-10-022.

This special issue looks at the current debates on the coevolution of policy and innovation. We discuss the theoretical and empirical roots of this debate and provide an outlook to the papers within the special issue.

Main-stream evaluations of failed policies are geared towards finding a limited set of factors that are deemed to have caused the problem. This is particularly so in the case of high-profile public projects such as in technology and infrastructure development. While justified from the point of political accountability, this article presents an alternative view. Following insights from evolutionary economics and complex systems about the embedded nature of technological systems and the role of chance next to purposeful planning, we demonstrate that traditional policy evaluations are misguided when geared towards simplistic cause-and-effect relations. To this end, we analyze the reasons for the mixed results in the Dutch high-speed railway case. The findings show that, contrary to popular opinions in the political domain, technological progress did take place. However, misalignment between social practices and technological systems masked that progress.

OBJECTIVE: One of the major and devastating complications of the coronary artery bypass grafting (CABG) is the stroke. Avoiding cardiopulmonary bypass (CPB) may reduce this neurological complication. In the past years there was an increased interest in the off-pump coronary artery grafting (OPCAB). The benefit of this method of revascularization in term of stroke and mortality is controversially discussed. METHODS: A retrospective analysis of collected data from 252 patients were operated without cardiopulmonary bypass out of 1516 CABG procedures from January 2004 through May 2006. The mean age of the patient population was 70±11years, within a range of 27-88 years. Forty-eight (19%) patients were older than 80 years and there were 172 (69%) males. Mean graft per patient was 1.78±0.79. The internal mammary artery (IMA) graft was used in 95% of the patients. For eight (3.17%) patients this was the second procedure. RESULTS: Hospital mortality was 3.17%; Mean EuroSCORE in these patients was 10.36±6.67. No neurological complications occurred, six (2.38%) patients had temporary psycho syndrome. Postoperative myocardial infarction occurred in three (1.19%) patients. Two patients required rethoracotomy as a result of bleeding. Thirty-eight (15%) patients needed postoperative therapy for atrial fibrillation. CONCLUSION: CABG with OPCAB technique has the benefit of low mortality and morbidity in terms of stroke. The advantages of this technique depends on the patient's general condition at the time of the operation, the sufficiency of pump function and coronary morphology, as well as on the surgeon's experience.OBJETIVO: Uma das principais e devastadoras complicações da revascularização do miocárdio é o acidente cerebrovascular. Evitar a circulação extracorpórea (CEC) pode reduzir essa complicação neurológica. No passado, houve um interesse crescente na cirurgia de revascularização do miocárdio sem circulação extracorpórea. O benefício deste método de revascularização com relação ao acidente cerebrovascular e à mortalidade ainda é discutido de forma controversa. MÉTODOS: Uma análise retrospectiva dos dados coletados de 1.516 pacientes submetidos à cirurgia de revascularização do miocárdio, de janeiro de 2004 a maio de 2006, dos quais 252 pacientes que foram operados sem circulação extracorpórea. A média de idade da população da amostra foi de 70±11 anos, variando de 27 a 88 anos. Quarenta e oito pacientes (19%) tinham mais de 80 anos e 172 pacientes (69%) eram homens. O número médio de transplante por paciente foi de 1,78±0,79. A artéria torácica interna (ATI) foi usada em 95% dos pacientes, enquanto que para oito pacientes a ATI foi o segunda procedimento. RESULTADOS: A mortalidade hospitalar foi de 3,17%; o EuroScore médio nesses pacientes foi de 10,36±6,67. Não ocorreram complicações neurológicas, porém, seis pacientes (2,38%) tiveram psicossíndrome temporária. Infarto do miocárdio ocorreu em três pacientes (1,19%) após a cirurgia. Dois pacientes precisaram fazer uma nova toracotomia por motivo de sangramento e 38 (15%) de tratamento para fibrilação atrial após a cirurgia. CONCLUSÃO: A cirurgia de revascularização do miocárdio sem circulação extracorpórea apresenta o benefício da baixa mortalidade e morbidade com relação ao acidente cerebrovascular. As vantagens dessa técnica dependem da condição geral do paciente na época da cirurgia, da suficiência da função da bomba e da morfologia coronária, bem como da experiência do cirurgião.

Literary modernism often exhibits the opposing impulses of cross-cultural pollination on the one hand, and exile and dislocation on the other. Writers wrestled with the problem of representing these complex cultural and political forces, especially as manifested in such European metropolises as Paris, Vienna, and London. D. H. Lawrence, in some ways an archetypal modem writer, differed from many modernist contemporaries in rejecting their Eurocentric viewpoint. Both his life and his writing display a search for fresh meanings, forms, and lifestyles in the so-called New World. This essay concentrates on two neglected, often heavily criticised novels of the 1920s, Aaron's Rod and Kangaroo, examining how each maps the distinct journeys of protagonists through and beyond a Europe terminally blighted by war. Lawrence recasts Europe as spiritually and culturally empty, but fundamentally unaware of its critical state. Aaron's Rod tracks the picaresque adventures of its eponymous hero from an English mining town, through the dulled world of western Europe to his apparent spiritual rebirth in Florence. Kangaroo records the more planned flight of Richard and Harriet Somers from a Europe they both detest to the supposed sanctuary of Australia. In neither novel is the search resolved: Aaron is pointed beyond Europe by his mentor, Lilly, while the Somers reject what they see as the unreflective ease of Australian democracy, journeying on to the untamed places of America. Both works overtly criticise the dead hand of post-war Europe from the margins of that culture, and beyond. At the same time, each is a literary experiment, an attempt by Lawrence to perform radical surgery on the novel form. As such they are worthy of consideration in discussion both of the eseentially European focus of much modernist literature and the diversity of literary essentially newness which marked it.