Infection with chikungunya virus confers heterotypic cross-neutralizing antibodies and memory B-cells against other arthritogenic alphaviruses predominantly through the B domain of the E2 glycoprotein

Infections with Chikungunya virus, a mosquito-borne alphavirus, cause an acute febrile syndrome often followed by chronic arthritis that persists for months to years post-infection. Neutralizing antibodies are the primary immune correlate of protection elicited by infection, and the major goal of vaccinations in development. Using convalescent blood samples collected from both endemic and non-endemic human subjects at multiple timepoints following suspected or confirmed chikungunya infection, we identified antibodies with broad neutralizing properties against other alphaviruses within the Semliki Forest complex. Cross-neutralization generally did not extend to the Venezuelan Equine Encephalitis virus (VEEV) complex, although some subjects had low levels of VEEV-neutralizing antibodies. This suggests that broadly neutralizing antibodies elicited following natural infection are largely complex restricted. In addition to serology, we also performed memory B-cell analysis, finding chikungunya-specific memory B-cells in all subjects in this study as remotely as 24 years post-infection. We functionally assessed the ability of memory B-cell derived antibodies to bind to chikungunya virus, and related Mayaro virus, as well as the highly conserved B domain of the E2 glycoprotein thought to contribute to cross-reactivity between related Old-World alphaviruses. To specifically assess the role of the E2 B domain in cross-neutralization, we depleted Mayaro and Chikungunya virus E2 B domain specific antibodies from convalescent sera, finding E2B depletion significantly decreases Mayaro virus specific cross-neutralizing antibody titers with no significant effect on chikungunya virus neutralization, indicating that the E2 B domain is a key target of cross-neutralizing and potentially cross-protective neutralizing antibodies

Understanding Scientific Practices: The Role of Robustness Notions

This article explores the role of `robustness-notions¿ in an account of the engineering sciences. The engineering sciences aim at technological production of, and intervention with phenomena relevant to the (dis-)functioning of materials and technological devices, by means of scientific understanding thereof. It is proposed that different kinds of robustness-notions enable and guide scientific research: (1) Robustness is as a metaphysical belief that we have about the physical world ¿ i.e., we believe that the world is robust in the sense that the same physical conditions will always produce the same effects. (2) `Same conditions ¿ same effects¿ functions as a regulative principle that enables and guides scientific research because it points to, and justifies methodological notions. (3) Repetition, variance and multiple-determination function as methodological criteria for scientific methods that justify the acceptance of epistemological and ontological results. (4) Reproducibility and stability function as ontological criteria for the acceptance of phenomena described by A¿B. (5) Reliability functions as an epistemological criterion for the acceptance of epistemological results, in particular law¿like knowledge of a conditional form: ¿A¿B, provided Cdevice, and unless other known and/or unknown causally relevant conditions.¿ The crucial question is how different kinds of robustness¿notions are related and how they play their part in the production and acceptance of scientific results. Focus is on production and acceptance of physical phenomena and the rule-like knowledge thereof. Based on an analysis of how philosoophy of science tradtionally justified scientific knowledge, I propose a general schema that specifies how inferences to the claim that a scientific result has a certain epistem ological property (such as truth) are justified by scientific methods that meet specific methodological criteria. It is proposed that `same conditions ¿ same effects¿ as a regulative criterion justifies `repetition, variation and ultiple¿determination¿ as methodological criteria for the production and acceptance of (ontological and epistemological) scientific result

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries