Persistent identification of instruments

Instruments play an essential role in creating research data. Given the importance of instruments and associated metadata to the assessment of data quality and data reuse, globally unique, persistent and resolvable identification of instruments is crucial. The Research Data Alliance Working Group Persistent Identification of Instruments (PIDINST) developed a community-driven solution for persistent identification of instruments which we present and discuss in this paper. Based on an analysis of 10 use cases, PIDINST developed a metadata schema and prototyped schema implementation with DataCite and ePIC as representative persistent identifier infrastructures and with HZB (Helmholtz-Zentrum Berlin für Materialien und Energie) and BODC (British Oceanographic Data Centre) as representative institutional instrument providers. These implementations demonstrate the viability of the proposed solution in practice. Moving forward, PIDINST will further catalyse adoption and consolidate the schema by addressing new stakeholder requirements

Persistent Identification Of Instruments

Instruments play an essential role in creating research data. Given the importance of instruments and associated metadata to the assessment of data quality and data reuse, globally unique, persistent and resolvable identification of instruments is crucial. The Research Data Alliance Working Group Persistent Identification of Instruments (PIDINST) developed a community-driven solution for persistent identification of instruments which we present and discuss in this paper. Based on an analysis of 10 use cases, PIDINST developed a metadata schema and prototyped schema implementation with DataCite and ePIC as representative persistent identifier infrastructures and with HZB (Helmholtz-Zentrum Berlin für Materialien und Energie) and BODC (British Oceanographic Data Centre) as representative institutional instrument providers. These implementations demonstrate the viability of the proposed solution in practice. Moving forward, PIDINST will further catalyse adoption and consolidate the schema by addressing new stakeholder requirements

Sinking Organic Particles in the Ocean—Flux Estimates From in situ Optical Devices

Optical particle measurements are emerging as an important technique for understanding the ocean carbon cycle, including contributions to estimates of their downward flux, which sequesters carbon dioxide (CO2) in the deep sea. Optical instruments can be used from ships or installed on autonomous platforms, delivering much greater spatial and temporal coverage of particles in the mesopelagic zone of the ocean than traditional techniques, such as sediment traps. Technologies to image particles have advanced greatly over the last two decades, but the quantitative translation of these immense datasets into biogeochemical properties remains a challenge. In particular, advances are needed to enable the optimal translation of imaged objects into carbon content and sinking velocities. In addition, different devices often measure different optical properties, leading to difficulties in comparing results. Here we provide a practical overview of the challenges and potential of using these instruments, as a step toward improvement and expansion of their applications

Coastal wave overtopping: New Nowcast and monitoring technologies

It is projected that global mean sea level could rise up to 1 m this century with a strong regional pattern. It is estimated that 20% of England's coastal defenses could fail under just half this rise. Ambitious climate mitigation and adaptation plans may protect 400,000 - 500,000 people, but flood and coastal erosion risks cannot be fully eliminated. Building coastal climate resilience requires accurate wave overtopping prediction tools and nowcast information to prepare for and respond to coastal hazards. In Dawlish, SW England, a new monitoring system to measure concurrent beach level and wave overtopping conditions over a 1-year period was installed. The system obtains in-situ measurements of the inland wave overtopping distribution across a public walkway and railway line, and issues near real-time overtopping data to the British Oceanographic Data Centre, making it accessible online within 15 minutes of detection. This public web service also ingests near-real time wave and water level data from existing national coastal monitoring networks, providing a full dataset to validate and calibrate an operational wave, water-level and overtopping forecast system. Using these data, the numerical forecasts have been refined by incorporating recent beach levels to reduce the uncertainty in the wave overtopping predictions due to seasonal variability in the beach level at the toe of the sea wall

Ocean data product integration through innovation-the next level of data interoperability

In the next decade the pressures on ocean systems and the communities that rely on them will increase along with impacts from the multiple stressors of climate change and human activities. Our ability to manage and sustain our oceans will depend on the data we collect and the information and knowledge derived from it. Much of the uptake of this knowledge will be outside the ocean domain, for example by policy makers, local Governments, custodians, and other organizations, so it is imperative that we democratize or open the access and use of ocean data. This paper looks at how technologies, scoped by standards, best practice and communities of practice, can be deployed to change the way that ocean data is accessed, utilized, augmented and transformed into information and knowledge. The current portal-download model which requires the user to know what data exists, where it is stored, in what format and with what processing, limits the uptake and use of ocean data. Using examples from a range of disciplines, a web services model of data and information flows is presented. A framework is described, including the systems, processes and human components, which delivers a radical rethink about the delivery of knowledge from ocean data. A series of statements describe parts of the future vision along with recommendations about how this may be achieved. The paper recommends the development of virtual test-beds for end-to-end development of new data workflows and knowledge pathways. This supports the continued development, rationalization and uptake of standards, creates a platform around which a community of practice can be developed, promotes cross discipline engagement from ocean science through to ocean policy, allows for the commercial sector, including the informatics sector, to partner in delivering outcomes and provides a focus to leverage long term sustained funding. The next 10 years will be “make or break” for many ocean systems. The decadal challenge is to develop the governance and co-operative mechanisms to harness emerging information technology to deliver on the goal of generating the information and knowledge required to sustain oceans into the future

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Using standards to model delayed mode sensor processes

Ocean data are expensive to collect. Data reuse saves time and accelerates the pace of scientific discovery. For data to be re-usable the FAIR principles reassert the need for rich metadata and documentation that meet relevant community standards and provide information about provenance. Approaches on sensor observations, are often inadequate at meeting FAIR; prescriptive with a limited set of attributes, while providing little or no provision for really important metadata about sensor observations later in the data lifecycle. As part of the EU ENVRIplus project, our work aimed at capturing the delayed mode, data curation process taking place at the National Oceanography Centre’s British Oceanography Data Centre (BODC). Our solution uses Unique URIs, OGC SWE standards and controlled vocabularies, commencing from the submitted originators input and ending by the archived and published dataset. The BODC delayed mode process is an example of a physical system that is composed of several components like sensors and other computations processes such as an algorithm to compute salinity or absolute winds. All components are described in sensorML identified by unique URIs and associated with the relevant datastreams, which in turn are exposed on the web via ERDDAP using unique URIs. In this paper we intend to share our experience in using OGC standards and ERDDAP to model the above mentioned process and publish the associated datasets in a unified way. The benefits attained, allow greater automation of data transferring, easy access to large volumes of data from a chosen sensor, more precise capturing of data provenance, standardization, and pave the way towards greater FAIRness of the sensor data and metadata, focusing on the delayed mode processing