Demonstrating public value to funders and other stakeholders—the journey of ELIXIR, a virtual and distributed research infrastructure for life science data

Open Science is a founding principle of ELIXIR, a pan-European research infrastructure for life science data, with 21 Member countries plus the European Molecular Biology Laboratory. The mission of ELIXIR is to coordinate bioinformatics resources so that they form a single, integrated and pan-European infrastructure, which can be used freely by academic and private-sector researchers across the globe. As a recipient of public and charitable funding, ELIXIR must demonstrate its value, and the need to produce evidence in support of this is intensifying. Our practice-led journey towards demonstrating public value is articulated around five main challenges and, for each, we present our pragmatic approach for tackling it. We begin by showing how we are working towards demystifying what research infrastructures do. We then shed light on the sort of evidence our funders and other stakeholders are asking us for, how this evidence varies in nature and scope, and our tactics to satisfy them. We follow-on by providing our thoughts on possible barriers and solutions to embedding impact evaluation in our activities. Finally, we provide lessons learned, which we believe are sufficiently transferable and will be inspirational to other research infrastructures as they embark on their own journeys to demonstrate public value.publishedVersio

Navigating institutional pressure in state-socialist and democratic regimes: The case of movement brontosaurus

Using the case of Movement Brontosaurus, a Czech organization founded in state socialist times, this article investigates how civic associations and nongovernmental organizations seeking to promote alternatives to the status quo respond to institutional pressures in different political and social contexts. The case shows that under state socialism, Brontosaurus appeared to conform to state mandates and societal expectations. However, its formal structure was decoupled from many activities to obscure its oppositional intent.After the transition to democracy, the organization was only able to maintain its place in society after it aligned its structure and practices with each other and openly expressed its alternative agenda. The findings demonstrate how social change and alternative lifestyle organizations vary their responses to institutional pressure in ways that enable them to realize their values and pursue their missions while accounting for the political and social contexts in which they are embedded

Changes in the Diagnosis of Stroke and Cardiovascular Conditions in Primary Care During First 2 COVID-19 Waves in the Netherlands

BACKGROUND AND OBJECTIVES: Although there is evidence of disruption in acute cerebrovascular and cardiovascular care during the coronavirus disease 2019 (COVID-19) pandemic, its downstream effect in primary care is less clear. We investigated how the pandemic affected utilization of cerebrovascular and cardiovascular care in general practices (GPs) and determined changes in GP-recorded diagnoses of selected cerebrovascular and cardiovascular outcomes. METHODS: From electronic health records of 166,929 primary care patients aged 30 or over within the Rotterdam region, the Netherlands, we extracted the number of consultations related to cerebrovascular and cardiovascular care, and first diagnoses of selected cerebrovascular and cardiovascular risk factors (hypertension, diabetes, lipid disorders), conditions, and events (angina, atrial fibrillation, TIA, myocardial infarction, stroke). We quantified changes in those outcomes during the first COVID-19 wave (March–May 2020) and thereafter (June–December 2020) by comparing them to the same period in 2016–2019. We also estimated the number of potentially missed diagnoses for each outcome. RESULTS: The number of GP consultations related to cerebrovascular and cardiovascular care declined by 38% (0.62, 95% confidence interval 0.56–0.68) during the first wave, as compared to expected counts based on prepandemic levels. Substantial declines in the number of new diagnoses were observed for cerebrovascular events: 37% for TIA (0.63, 0.41–0.96) and 29% for stroke (0.71, 0.59–0.84), while no significant changes were observed for cardiovascular events (myocardial infarction [0.91, 0.74–1.14], angina [0.77, 0.48–1.25]). The counts across individual diagnoses recovered following June 2020, but the number of GP consultations related to cerebrovascular and cardiovascular care remained lower than expected throughout the June to December period (0.93, 0.88–0.98). DISCUSSION: While new diagnoses of acute cardiovascular events remained stable during the COVID-19 pandemic, diagnoses of cerebrovascular events declined substantially compared to prepandemic levels, possibly due to incorrect perception of risk by patients. These findings emphasize the need to improve symptom recognition of cerebrovascular events among the general public and to encourage urgent presentation despite any physical distancing measures

Protein-Engineered Proteinase of Myeloblastosis Associated Virus, An Enzyme of High Activity and HIV-1 Proteinase-Like Specificity

All proteinases of avian and mammalian retroviruses belong to the family of aspartic proteinases, are of similar size and of homologous primary structure; they all act catalytically in the form of highly symmetric molecular dimers.1 Detailed studies of retroviral proteinases were carried out on two almost identical proteinases of MAV2,3 and RS V4 (representing the group of avian retroviruses) and on the HIV proteinase.5,6 The knowledge of the 3D structure,2,4,5 catalytic activity and substrate specifity3,6 of the MAV and the HIV proteinase has changed the notion of their general similarity since several features that distinguish each proteinase from the other were revealed. The HIV-1 proteinase has a considerably higher activity3,6 which reflects the different conditions of the expression and action of this enzyme in vivo: 7 The “coding strategy” of MAV allows the expression of the proteinase from the first (gag) open reading frame and provides for the high (i.e. stoichiometrical) level of the relatively “weak” enzyme whereas the smaller amount of the more active HIV enzyme is a result of infrequent translational frameshift events that occur in the overlapping region of the gag and pol reading frames.8 The substrate specificities of retroviral proteinases seem complex and the requirement for a side chain in an individual subsite of a substrate is an outcome of the combination of residues occupying other closely located subsites.3 The two proteinases (MAV and HIV) show rather promiscuous substrate specificity, nevertheless several differences can be traced. We made an attempt to use protein engineering of the MAV proteinase to tackle directly problems of structural basis of these differences and, vice versa, to make more precise conclusions on the functional importance of the individual elements of its three dimensional structure. This article describes mutation of the MAV proteinase which resulted not only in an alteration of its substrate specificity but also in an increase of its enzymic activity — a rare case in protein engineering