Research Infrastructure Research Articles

Strategies to decrease inequalities in cancer therapeutics, care and prevention: Proceedings on a conference organized by the Pontifical Academy of Sciences and the European Academy of Cancer Sciences, Vatican City, February 23-24, 2023.

Analyses of inequalities related to prevention and cancer therapeutics/care show disparities between countries with different economic standing, and within countries with high Gross Domestic Product. The development of basic technological and biological research provides clinical and prevention opportunities that make their implementation into healthcare systems more complex, mainly due to the growth of Personalized/Precision Cancer Medicine (PCM). Initiatives like the USA-Cancer Moonshot and the EU-Mission on Cancer and Europe's Beating Cancer Plan are initiated to boost cancer prevention and therapeutics/care innovation and to mitigate present inequalities. The conference organized by the Pontifical Academy of Sciences in collaboration with the European Academy of Cancer Sciences discussed the inequality problem, dependent on the economic status of a country, the increasing demands for infrastructure supportive of innovative research and its implementation in healthcare and prevention programs. Establishing translational research defined as a coherent cancer research continuum is still a challenge. Research has to cover the entire continuum from basic to outcomes research for clinical and prevention modalities. Comprehensive Cancer Centres (CCCs) are of critical importance for integrating research innovations to preclinical and clinical research, as for ensuring state-of-the-art patient care within healthcare systems. International collaborative networks between CCCs are necessary to reach the critical mass of infrastructures and patients for PCM research, and for introducing prevention modalities and new treatments effectively. Outcomes and health economics research are required to assess the cost-effectiveness of new interventions, currently a missing element in the research portfolio. Data sharing and critical mass are essential for innovative research to develop PCM. Despite advances in cancer research, cancer incidence and prevalence is growing. Making cancer research infrastructures accessible for all patients, considering the increasing inequalities, requires science policy actions incentivizing research aimed at prevention and cancer therapeutics/care with an increased focus on patients' needs and cost-effective healthcare.

Influence of rupture velocity on risk assessment of concrete moment frames: Supershear vs. subshear ruptures

The possibility of ground motions propagating at speeds greater than the Rayleigh wave speed was accepted not long ago, and thus studies on them are limited. These supershear motions are believed to damage specific kinds of infrastructure, and thus studying the risk associated is important. As a part of this investigation, we use state-of-the-art tools from the Natural Hazards Engineering Research Infrastructure to estimate normalized economic losses and injuries, by considering one particular building type and occupancy category listed in HAZUS-MH. Faults of similar dimensions are shown to replicate subshear and supershear earthquake instances with four groups of station points parallel to the fault and four more perpendicular to the fault. Both fault parallel and fault normal components of ground motion are stimulated. The economic loss % and injury is standardized in metrics of repair cost and population respectively and is estimated along with the associated uncertainty for 3, 6 and 9-story commercial concrete moment frame structures. Inclusion of complex phenomena such as supershear earthquake events in evaluating economic losses and risk will contribute to the United Nation Office for Disaster Risk Reduction (UNDRR) vision of disaster-resilient development goals.

Measurement uncertainties of scanning microwave radiometers and their influence on temperature profiling

Abstract. In order to improve observations of the atmospheric boundary layer (ABL), the European Meteorological Network, EUMETNET, and the Aerosol, Clouds, and Trace Gases Research Infrastructure, ACTRIS, are currently working on building networks of microwave radiometers (MWRs). Elevation-scanning MWRs are well suited to obtain temperature profiles of the atmosphere, especially within the ABL. Understanding and assessing measurement uncertainties of state-of-the-art scanning MWRs is therefore crucial for accurate temperature profiling. In this paper, we discuss measurement uncertainties due to the instrument setup and originating from external sources, namely (1) horizontal inhomogeneities of the atmosphere, (2) pointing errors or a tilt of the instrument, (3) physical obstacles in the line of sight of the instrument, and (4) radio frequency interference (RFI). Horizontal inhomogeneities from observations at the Jülich Observatory for Cloud Evolution (JOYCE) are shown to have a small impact on retrieved temperature profiles (<|0.22K| in the 25th and 75th percentiles below 3000 m). Typical instrument tilts, that could be caused by uncertainties during the instrument setup, also have a very small impact on temperature profiles and are smaller than 0.1 K below 3000 m for up to 1∘ of tilt. Physical obstacles at ambient temperatures and in the line of sight and filling the complete beam of the MWR at the lowest elevation angle of 5.4∘ have to be at least 600 m away from the instrument in order to have an impact of less than 0.1 K on obtained temperature profiles. If the obstacle is 5 K warmer than its surroundings then the obstacle should be at least 2700 m away. Finally, we present an approach on how to detect RFI with an MWR with azimuth and elevation-scanning capabilities. In this study, we detect RFIs in a water vapor channel that does not influence temperature retrievals but would be relevant if the MWR were used to detect horizontal humidity inhomogeneities.

Adapting COVID-19 research infrastructure to capture influenza and respiratory syncytial virus alongside SARS-CoV-2 in UK healthcare workers winter 2022/23 and beyond: protocol for a pragmatic sub-study

Introduction During the COVID-19 pandemic, extensive research was conducted on SARS-CoV-2; however, important questions about other respiratory pathogens remain unanswered. A severe influenza season in 2022–2023 with simultaneous circulation of SARS-CoV2 and respiratory syncytial virus is anticipated. This sub-study aims to determine the incidence and impact of these respiratory viruses on healthcare workers, the symptoms they experienced, the effectiveness of both COVID-19 and influenza vaccination and the burden of these infections on the National Health Service (NHS) workforce. Methods and analysis This is a longitudinal prospective cohort sub-study, utilising the population and infrastructure of the SARS-CoV-2 Immunity & Reinfection Evaluation (SIREN) study, which focuses on hospital staff in the UK. Participants undergo fortnightly nucleic acid amplification testing on a multiplex assay including SARS-CoV-2, influenza A and B and RSV, regardless of symptoms. Questionnaires are completed every two weeks, capturing symptoms, sick days, exposures, and vaccination records. Serum samples are collected monthly or quarterly from participants associated with a SIREN site. This sub-study commenced on 28/11/22 to align with the predicted influenza season and participants’ influenza vaccine status. The SIREN Participant Involvement Panel shaped the aims and methods for the study, highlighting its acceptability. UK devolved administrations were supported to develop local protocols. Analysis plans include incidence of asymptomatic and symptomatic infection, comparisons of vaccination coverage, assessment of sick day burden, and effectiveness of seasonal influenza against infection and time off work. Data are also integrated into UKHSA nosocomial modelling. Ethics and dissemination The protocol was approved by the Berkshire Research Ethics Committee (IRAS ID 284460, REC Reference 20SC0230) on 14/11/2022. Participants were informed in advance. As the frequency and method of sampling remained the same, implied consent processes were approved by the committee. Participants returning to the study give informed consent. Regular reports to advisory groups and peer-reviewed publications are planned to disseminate findings and inform decision making. Clinical trial registration number: ISRCTN11041050; registration date: 12 January 2021. Sub study included in protocol version: v8.0, and amended in v9.0

Design and construction of the near-earth space plasma simulation system of the Space Plasma Environment Research Facility

Our earth is immersed in the near-earth space plasma environment, which plays a vital role in protecting our planet against the solar-wind impact and influencing space activities. It is significant to investigate the physical processes dominating the environment, for deepening our scientific understanding of it and improving the ability to forecast the space weather. As a crucial part of the National Major Scientific and Technological Infrastructure–Space Environment Simulation Research Infrastructure (SESRI) in Harbin, the Space Plasma Environment Research Facility (SPERF) builds a system to replicate the near-earth space plasma environment in the laboratory. The system aims to simulate the three-dimensional (3-D) structure and processes of the terrestrial magnetosphere for the first time in the world, providing a unique platform to reveal the physics of the 3-D asymmetric magnetic reconnection relevant to the earth's magnetopause, wave–particle interaction in the earth's radiation belt, particles’ dynamics during the geomagnetic storm, etc. The paper will present the engineering design and construction of the near-earth space plasma simulation system of the SPERF, with a focus on the critical technologies that have been resolved to achieve the scientific goals. Meanwhile, the possible physical issues that can be studied based on the apparatus are sketched briefly. The earth-based system is of great value in understanding the space plasma environment and supporting space exploration.

A report on recommendations for the most suitable financial contribution model for the Distributed System of Scientific Collections Research Infrastructure (DiSSCo-RI)

A key consideration during the preparatory phase project DiSSCo Prepare – which laid the foundations for the future Research Infrastructure DiSSCo (Distributed System of Scientific Collections) – was the need to establish a small number of alternative viable financial contribution models and a scalable formula which could be presented to potential funders, with a view to obtaining the minimum financial contribution necessary for DiSSCo to operate, as well as considering how the RI could grow with increased national funding. This report briefly explains the ERIC funding framework – as chosen for DiSSCo – and its legal constraints, in order to explain the key role played by national member contributions in the viability of an ERIC. An essential annex of the statutes that will be signed by all members of the ERIC is the member fee calculation. A proposal for the DiSSCo member fee calculation is set out in this document and is based on three main indicators: economic power (GDP), annual spending in research and development and population size. In the context of DiSSCo – and to ensure the ERIC can function – these indicators are connected to a fixed baseline fee of €50,000, in order to guarantee a minimum significant annual contribution from each participating country and avoid contributions that will be more expensive to manage than to benefit from. This baseline is multiplied by contribution factors which propose different ways to weight the various indicators. The method is established on an ideal scenario, whereby all 27 EU members, as well as the UK, Iceland, Norway and Switzerland sign the DiSSCo statutes and agree to the proposed member contribution calculation, amounting to €4.5 million for the annual budget of the ERIC. This scenario remains highly unlikely; therefore, a scaled approach has been envisaged, meaning the initial engagement of some countries will allow DiSSCo to begin its operation and implement its business strategy, whilst the growth of the ERIC and its activities is likely to evolve proportionally to the number of national members it is able to engage. This report also looks at the ways in which funding could be distributed amongst the DiSSCo members in order to implement decentralised services.

DiSSCo Transition Abridged Grant Proposal

The Distributed System of Scientific Collections (DiSSCo) is a pan-European Research Infrastructure (RI) initiative. DiSSCo aims to bring together natural science collections from 175 museums, botanical gardens, universities and research institutes across 23 countries in a distributed infrastructure that makes these collections physically and digitally open and accessible for all forms of research and innovation. DiSSCo RI entered the ESFRI roadmap in 2018 and successfully concluded its Preparatory Phase in early 2023. The RI is now transitioning towards the constitution of its legal entity (an ERIC) and the start of its scaled-up construction (implementation) programme. This publication is an abridged version of the successful grant proposal for the DiSSCo Transition Project which has the goal of ensuring the seamless transition of the DiSSCo RI from its Preparatory Phase to the Construction Phase (expected to start in 2025). In this transition period, the Project will address five objectives building on the outcomes of the Preparatory Phase project: 1) Advance the DiSSCo ERIC process and complete its policy framework, ensuring the smooth early-phase Implementation of DISSCo; 2) Engage & support DiSSCo National Nodes to strengthen national commitments; 3) Advance the development of core e-services to avoid the accumulation of technical debt before the start of the Implementation Phase; 4) Continue international collaboration on standards & best practices needed for the DiSSCo service provision; and 5) Continue supporting DiSSCo RI interim governance bodies and transition them to the DiSSCo ERIC formal governance. The Project’s impact will be measured against the increase in the RI's overall Implementation Readiness Level (IRL). More specifically, we will monitor its impact towards reaching the required level of maturity in four of the five dimensions of the IRL that can benefit from further developments. These include the organisational, financial, technological and data readiness levels.

Establishing the ELIXIR Microbiome Community

Microbiome research has grown substantially over the past decade in terms of the range of biomes sampled, identified taxa, and the volume of data derived from the samples. In particular, experimental approaches such as metagenomics, metabarcoding, metatranscriptomics and metaproteomics have provided profound insights into the vast, hitherto unknown, microbial biodiversity. The ELIXIR Marine Metagenomics Community, initiated amongst researchers focusing on marine microbiomes, has concentrated on promoting standards around microbiome-derived sequence analysis, as well as understanding the gaps in methods and reference databases, and solutions to computational overheads of performing such analyses. Nevertheless, the methods used and the challenges faced are not confined to marine studies, but are broadly applicable to all other biomes. Thus, expanding this Community to a more inclusive ELIXIR Microbiome Community will enable it to encompass a broad range of biomes and link expertise across ‘omics technologies. Furthermore, engaging with a large number of researchers will improve the efficiency and sustainability of bioinformatics infrastructure and resources for microbiome research (standards, data, tools, workflows, training), which will enable a deeper understanding of the function and taxonomic composition of the different microbial communities.

The role of healthcare leaders in implementing equitable clinical academic pathways for nurses: An integrative review.

To identify and synthesize empirical evidence on the role of healthcare leaders in the development of equitable clinical academic pathways for nurses. Integrative literature review. Literature was searched using CINAHL, PubMed, ProQuest and Google Scholar databases. A total of 114 eligible articles published between 2010 and2022 were screened, 16 papers were selected. Results highlighted the need for consistent national, regional, and organizational policy approaches to developing clinical academic careers for nurses. Government health departments and National Health boards must focus on increasing engagement in research and evidence-based nursing practice for high-quality patient care. Discriminatory practices and attitudes were identified as barriers. Discrimination due to gender was evident, while the impact of race, ethnicity, and other social categories of identity are under-researched. Educational leaders must unravel misconceptions about research, highlighting its relevance to patient care and bedside nurses' work. Academic leaders together with executive nurses, research funders and professional nursing bodies must create appropriately remunerated career structures. Transformative approaches are required to develop the clinical academic nurse role and understand its value in clinical practice. Multiple elements exist within complex systems that healthcare leaders can navigate collaboratively to develop and implement clinical nurse academic roles. This requires vision, acknowledgement of the value of nursing research and the importance of evidence-based research infrastructures. Findings highlight the collaborative role of healthcare leaders as critical to the success of critical academic careers for nurses. This review can inform those still to formalize this innovative role for nurses. The review complies with the PRISMA guidelines for reporting systematic reviews. This paper contributes evidence about the healthcare leader's role in developing clinical academic pathways for nurses to the wider global clinical community. No patient or public contribution was included in this review.

Engineering Meter-scale Porous Media Flow Experiments for Quantitative Studies of Geological Carbon Sequestration

This technical note describes the FluidFlower concept, a new laboratory infrastructure for geological carbon storage research. The highly controlled and adjustable system produces a strikingly visual physical ground truth of studied processes for model validation, comparison and forecasting, including detailed physical studies of the behavior and storage mechanisms of carbon dioxide and its derivative forms in relevant geological settings for subsurface carbon storage. The design, instrumentation, structural aspects and methodology are described. Furthermore, we share engineering insights into construction, operation, fluid considerations and fluid resetting in the porous media. The new infrastructure enables researchers to study variability between repeated CO2 injections, making the FluidFlower concept a suitable tool for sensitivity studies on a range of determining carbon storage parameters in varying geological formations.

Emerging roles and responsibilities of libraries in support of reproducible research

Ensuring the reproducibility of research is a multi-stakeholder effort that comes with challenges and opportunities for individual researchers and research communities, librarians, publishers, funders and service providers. These emerge at various steps of the research process, and, in particular, at the publication stage. Previous work by Knowledge Exchange highlighted that, while there is growing awareness among researchers, reproducible publication practices have been slow to change. Importantly, research reproducibility has not yet reached institutional agendas: this work seeks to highlight the rationale for libraries to initiate and/or step up their engagement with this topic, which we argue is well aligned with their core values and strategic priorities. We draw on secondary analysis of data gathered by Knowledge Exchange, focusing on the literature identified as well as interviews held with librarians. We extend this through further investigation of the literature and by integrating the findings of discussions held at the 2022 LIBER conference, to provide an updated picture of how libraries engage with research reproducibility. Libraries have a significant role in promoting responsible research practices, including transparency and reproducibility, by leveraging their connections to academic communities and collaborating with stakeholders like research funders and publishers. Our recommendations for libraries include: i) partnering with researchers to promote a research culture that values transparency and reproducibility, ii) enhancing existing research infrastructure and support; and iii) investing in raising awareness and developing skills and capacities related to these principles.

Landscape Analysis of Neurodevelopmental Comorbidities in Newborn Screening Conditions: Challenges and Opportunities.

Newborn screening (NBS) is a large-scale public health program in the US that screens 3.8 million newborns for up to 81 genetic conditions each year. Many of these conditions have comorbidities, including neurodevelopmental disorders (NDDs). These comorbidities can have a significant impact on health outcomes across the lifespan. Most screened conditions are inborn errors of metabolism. PKU, the first condition identified by NBS, is an inherited metabolic disorder that can cause developmental delays and intellectual/developmental disabilities if not treated. The Newborn Screening Translational Research Network (NBSTRN) is a program that has been funded by the National Institute of Child Health and Human Development since 2008. NBSTRN is charged with developing, maintaining, and enhancing tools, resources, and expertise supporting NBS research. One of the tasks led by NBSTRN is to provide direction for developing question/answer sets used in the Longitudinal Pediatric Data Resource (LPDR) to create consensus-based and standardized common data elements (CDEs) for NBS conditions. There is growing interest in the NBS community in assessing neurodevelopmental trajectories through long-term follow-up studies. This could be streamlined by employing uniform CDEs. To address this unmet need, we conducted a landscape analysis to (1) explore the co-occurrence of NDD-related comorbidities and NBS conditions using text mining in MedGen, (2) compile a list of NDD-related CDEs from existing repositories as well as LPDR data dictionaries, and (3) identify challenges and knowledge gaps hindering the early identification of risks for NDDs in NBS conditions. Our findings can inform future efforts toward advancing the research infrastructure for this established public health program. The renewed awareness of the risk of NDDs after a positive NBS and diagnosis could lead to improved treatment guidelines for mental health conditions.

Unlocking the potential of genetic research in pulmonary arterial hypertension: Insights from clinicians, researchers, and study team.

Genetic research and testing are increasingly important for understanding and treating pulmonary arterial hypertension. We aimed to explore how attitudes toward genetic research among clinical and research teams impacted the engagement in genetic research and the integration of genetic insights into clinical practice. We conducted 53 semistructured interviews and focus groups with patients, clinicians, and researchers from nine UK Pulmonary Hypertension centers, who had genetic research experience. Transcripts were thematically coded using inductive analysis. In this study, we focus on the researchers', clinicians', and study team's perspectives. From the interview data, several key themes emerged, ranging from study design, recruitment, and consent procedures to the return of individual genetic results. Additionally, participants reflected on both the successes of these studies and the future directions of genetic research. The analysis highlighted the critical importance of fostering collaborative networks firmly rooted in existing clinical and research infrastructure in rare disease study setups. Furthermore, the significance of trust-building, personalized communication, and transparency among stakeholders was underscored. The study offered valuable insights into the motivating and hindering factors to participant recruitment and consent procedures. Lastly, the findings gathered from processes surrounding the return of individual genetic results, genetic counselling, and the recruitment of relatives provided invaluable lessons regarding the integration of genetics into clinical practice. This in-depth analysis yields a crucial understanding of attitudes to genetic research among various stakeholders and sheds light on the complexities of genetic research and the evidence-practice gap.

Learning the Autoimmune Pathogenesis Through the Study of Aire.

One of the difficulties in studying the pathogenesis of autoimmune diseases is that the disease is multifactorial involving sex, age, MHC, environment, and some genetic factors. Because deficiency of Aire, a transcriptional regulator, is an autoimmune disease caused by a single gene abnormality, Aire is an ideal research target for approaching the enigma of autoimmunity, e.g., the mechanisms underlying Aire deficiency can be studied using genetically modified animals. Nevertheless, the exact mechanisms of the breakdown of self-tolerance due to Aire's dysfunction have not yet been fully clarified. This is due, at least in part, to the lack of information on the exact target genes controlled by Aire. State-of-the-art research infrastructures such as single-cell analysis are now in place to elucidate the essential function of Aire. The knowledge gained through the study of Aire-mediated tolerance should help our understanding of the pathogenesis of autoimmune disease in general.

Dark Matter Science Project

Dark Matter Science Project

1983 Exploring barriers to recruiting older people to a white-coat hypertension study

Abstract Introduction There is a recognised association between white coat hypertension (WCH) and adverse cardiovascular outcomes in older adults. However, there is no consensus on the management of WCH in this group. The objective of the Hypertension in the Very Elderly Trial (HYVET-2) study was to assess the feasibility of randomising 100 patients >75years with WCH from General Practice in the UK to treatment or usual care. The study did not randomise any patients. In this follow up study, we sought to explore the reasons for not recruiting. Methods Using a mixed-methods study design, staff from 29 General Practice (GP) sites and the Clinical Research Network (CRN) in Kent, Surrey, and Sussex (KSS) were sent an online questionnaire about local research facilities and infrastructure, and HYVET-2 study methodology and target population demographics. Results Nineteen (19) individuals responded the questionnaires (15 primary care staff, 4 CRN staff). Using a framework approach, we identified six themes summarising challenges to HYVET-2 recruitment. These themes were: established approaches of primary care towards managing WCH in older people, target patient demographics, study design complexity, patient-facing study documents, limited research resources in primary care and identification of eligible patients using existing coding. Conclusion Our experience showed that recruiting older people to a WCH study from primary care was not feasible. A national scoping survey amongst primary care physicians in the UK, and a robust patient and public involvement (PPI) targeting older people with WCH might improve recruitment in future studies of WCH in older people.

Developing partnerships for academic data science consulting and collaboration units

Data science consulting and collaboration units (DSUs) are core infrastructure for research at universities. Activities span data management, study design, data analysis, data visualization, predictive modelling, preparing reports, manuscript writing and advising on statistical methods and may include an experiential or teaching component. Partnerships are needed for a thriving DSU as an active part of the larger university network. Guidance for identifying, developing and managing successful partnerships for DSUs can be summarized in six rules: (1) align with institutional strategic plans, (2) cultivate partnerships that fit your mission, (3) ensure sustainability and prepare for growth, (4) define clear expectations in a partnership agreement, (5) communicate and (6) expect the unexpected. While these rules are not exhaustive, they are derived from experiences in a diverse set of DSUs, which vary by administrative home, mission, staffing and funding model. As examples in this paper illustrate, these rules can be adapted to different organizational models for DSUs. Clear expectations in partnership agreements are essential for high quality and consistent collaborations and address core activities, duration, staffing, cost and evaluation. A DSU is an organizational asset that should involve thoughtful investment if the institution is to gain real value.

Czech national e-infrastructure services for HEP

Czech national e-infrastructure services for HEP

The KM3NeT4RR project in Bologna

KM3NeT4RR is a project for the Kilometre Cube Neutrino Telescope (KM3NeT), which is a large European research infrastructure composed of two underwater large-scale neutrino telescopes, ARCA and ORCA, located in the Mediterranean Sea off-shore Portopalo di Capo Passero (Sicily, Italy) and Toulon (Provence, France) respectively. The telescopes are mainly designed for studying cosmic neutrinos and neutrino properties, but the observatory infrastructure also offers opportunity for geological and marine sciences research, providing instrumentation connections for long-term, high-bandwidth and continuous data collection. The KM3NeT4RR project, led by the Italian Istituto Nazionale di Fisica Nucleare, has started at the end of 2022 and during the following 30 months it includes a set of activities aimed at extending the ARCA seafloor network and the Italian on-shore facilities, building and operating an additional significant number of detection elements, thus significantly advancing the final completion of the infrastructure. Within this project, the KM3NeT laboratories present at the INFN-Bologna section are going to be expanded and a new setup will be created that will serve for both the detectors calibration studies and for deep-sea environmental research.

Energy saving magnets for beam lines

Beam lines magnets for high rigidity particles can have a large power dissipation. In presence of a high duty cycle, this translates in a considerable amount of energy waste. The call for sustainability of large research infrastructures, like particle accelerator centers, and the recent increase of the cost of energy, require to take measures to reduce the energy consumption, even at cost of moderate investment. A study program called ESABLIM (Energy SAving Beam LIne Magnets) has been set up at the LASA lab of University and INFN Milano, aimed at revamping existing normal-conducting magnets for beam lines with the target of cutting the peak power by a factor 10 to 20 and reducing the energy consumption by factor 5 or more. The idea is to replace the water cooled coils of iron-dominated magnets with new superconducting coils cooled at 10-20 K by means of a cryocooler, while to reusing the iron yoke pole assembly. We envisage using MgB2 for its moderate cost, however, high temperature superconductors (HTS) will also be considered as conductor. We present the first advanced design for revamping of a large bending dipole in a hadron therapy center, and the conceptual design for magnets in a nuclear physics laboratory and we try to define the domain where this transformation of normal-conducting into super-ferric magnets can be technically and economically advantageous.