Framework Programme Research Articles

Placental structural adaptation to maternal physical activity and sedentary behavior: findings of the DALI lifestyle study.

Are maternal levels of moderate-to-vigorous physical activity (MVPA) and sedentary time (ST) in obese pregnant women associated with placental structural adaptations for facilitating oxygen delivery to the fetus? Higher maternal MVPA and ST are associated with a higher density of villi, a proxy measure of placental surface area for oxygen delivery to the fetus, without further added placental vessels. Physical activity during pregnancy intermittently reduces uterine blood flow, potentially limiting placental and fetal oxygen supply. The placenta can mount several adaptive responses, including enlargement of the surface area of villi and/or feto-placental vessels to accommodate fetal needs. Early research on the morphology and growth of the placenta with exercise interventions has shown inconsistencies and is lacking, particularly in non-lean pregnant women. This study is a secondary longitudinal analysis of the vitamin D and lifestyle intervention for gestational diabetes prevention (DALI) randomized controlled trial. The prospective study was conducted between 2012 and 2015 in nine European countries at 11 different sites. In this analysis, 92 pregnant women with a BMI ≥ 29 kg/m2 were combined into one cohort. MVPA and percentage of time spent sedentary (% ST) were measured with accelerometers during gestation. Placental sections were immunostained for endothelial cell-specific CD34. Artificial intelligence (AI)-based stereology assessed villous density, number, and cross-sectional area of vessels on whole-slide images and in selected regions comprising peripheral villi only, where the majority of vascular adaptations occur. Expression of pro- and anti-angiogenic factors was quantified using molecular counting analysis. In multivariable regression, higher levels of maternal MVPA (min/day) were associated with a higher density of villi in both whole-slide images (beta 0.12; 95% CI 0.05, 0.2) and selected regions (0.17; CI 0.07, 0.26). Unexpectedly, ST was also positively associated with density of villi (0.23; CI 0.04, 0.43). MVPA and ST were not associated with vessel count/mm2 villous area, vessel area, or pro- and anti-angiogenic factor mRNA expression. All estimates and statistical significance of the sensitivity analyses excluding smokers, women who developed gestational diabetes or pre-eclampsia and/or pregnancy-induced hypertension were similar in the main analysis. The placenta is a complex organ undergoing dynamic changes. While various adjustments were made to account for different maternal contributing factors, in addition to the outcome measures, various other factors could impact oxygen delivery to the fetus. For the first time, we evaluated the association between placental structures quantified using an AI-based approach with objectively measured physical activity and ST at multiple time points in pregnant women with obesity. The observed adaptations contribute to the advancement of our understanding of the hemodynamics and adaptations of the placental unit in response to MVPA and ST. However, our results might not be generalizable to lean pregnant women. The DALI project has received funding from the European Community's 7th Framework Program (FP7/2007-2013) under grant agreement no. 242187. The funders had no role in study design, collection of data, analyses, writing of the article, or the decision to submit it for publication. The authors have no conflicts of interest to declare. ISRCTN70595832.

The solar cycle 25 multi-spacecraft solar energetic particle event catalog of the SERPENTINE project

The solar energetic particle analysis platform for the inner heliosphere (SERPENTINE) project, funded through the H2020-SPACE-2020 call of the European Union’s Horizon 2020 framework program, employs measurements of the new inner heliospheric spacecraft fleet to address several outstanding questions on the origin of solar energetic particle (SEP) events. The data products of SERPENTINE include event catalogs, which are provided to the scientific community. In this paper, we present SERPENTINE's new multi-spacecraft SEP event catalog for events observed in solar cycle 25. Observations from five different viewpoints are utilized, provided by Solar Orbiter, Parker Solar Probe, STEREO A, BepiColombo, and the near-Earth spacecraft Wind and SOHO. The catalog contains key SEP parameters for $25-40$ MeV protons, $ MeV electrons, and $ keV electrons. Furthermore, basic parameters of associated flares and type II radio bursts are listed, as are the coordinates of the observer and solar source locations. An event is included in the catalog if at least two spacecraft detect a significant proton event with energies of $25-40$ MeV. The SEP onset times were determined using the Poisson-CUSUM method. The SEP peak times and intensities refer to the global intensity maximum. If different viewing directions are available, we used the one with the earliest onset for the onset determination and the one with the highest peak intensity for the peak identification. We furthermore aimed to use a high time resolution to provide the most accurate event times. Therefore, we opted to use a 1-minute time resolution, and more time averaging of the SEP intensity data was only applied if necessary to determine clean event onsets and peaks. Associated flares were identified using observations from near Earth and Solar Orbiter. Associated type II radio bursts were determined from ground-based observations in the metric frequency range and from spacecraft observations in the decametric range. The current version of the catalog available at https://doi.org/10.5281/zenodo.10732268 contains 45 multi-spacecraft events observed in the period from November 2020 until May 2023, of which 13 events were found to be widespread (observed at longitudes separated by at least 80° from the associated flare location) and four could be classified as narrow-spread events (not observed at longitudes separated by at least 80° from the associated flare location). Using X-ray observations by GOES/XRS and Solar Orbiter/STIX, we were able to identify the associated flare in all but four events. Using ground-based and space-borne radio observations, we found an associated type II radio burst for 40 events. In total, the catalog contains 142 single event observations, of which 20 (45) have been observed at radial distances below 0.6 AU (0.8 AU). It is anticipated that the catalog will be extended in the future.

Determining directions for improving the legal regulation of technology transfer forms

The object of this study is the existing regulatory approaches to determining the forms of technology transfer in the legal systems of economically developed countries of the world, international treaties, and agreements. During the research and generalization of existing concepts, it was established that they are not unified and differ significantly from each other. It has been proven that this does not meet the needs of technology transfer participants and significantly destabilizes the technology transfer process. The expediency of improving the existing normative concept of determining the forms of technology transfer by fixing their single list has been substantiated. Recommendations on the list of the main forms of technology transfer have been formed based on a systematic analysis of legal acts that determine the peculiarities of the essence of technology. A classification of the main forms of technology transfer was proposed. Four main forms of technology transfer were identified as the transfer of rights to technology during its creation, within the framework of joint cooperation, within the framework of cooperation based on corporate and/or proprietary commercial principles. The expediency of dividing each form of transfer into separate subtypes was also substantiated. The need to make changes to the provisions of such international treaties and agreements as the World Trade Organization Agreements, the Recommendations of the World Organization for the Protection of Intellectual Property, the Oslo Guidelines, the UNCTAD Recommendations, and the framework program "Horizon Europe" has been proven. The study is aimed at forming general theoretical foundations for improving the essence of regulatory techniques for identifying forms of technology transfer. The research results could be used in the formation of international normative acts, recommendations of international institutions, acts of national legislation, and serve as a basis for further scientific research into these issues

Overview of T and D-T results in JET with ITER-like Wall

Abstract In 2021 JET exploited its unique capabilities to operate with T and D-T fuel with an ITER-like Be/W wall (JET-ILW). This second major JET D-T campaign (DTE2), after DTE1 in 1997, represented the culmination of a series of JET enhancements – new fusion diagnostics, new T injection capabilities, refurbishment of the T plant, increased auxiliary heating, in-vessel calibration of 14MeV neutron yield monitors – as well as significant advances in plasma theory and modelling in the fusion community. DTE2 was complemented by a sequence of isotope physics campaigns encompassing operation in pure tritium at high T-NBI power. Carefully conducted for safe operation with tritium, the new T and D-T experiments used 1 kg of T (vs 100 g in DTE1), yielding the most fusion reactor relevant D-T plasmas to date and expanding our understanding of isotopes and D-T mixture physics. Furthermore, since the JET T and DTE2 campaigns occurred almost 25 years after the last major D-T tokamak experiment, it was also a strategic goal of the European fusion programme to refresh operational experience of a nuclear tokamak to prepare staff for ITER operation. The key physics results of the JET T and DTE2 experiments, carried out within the EUROfusion JET1 work package, are reported in this paper. Progress in the technological exploitation of JET D-T operations, development and validation of nuclear codes, neutronic tools and techniques for ITER operations carried out by EUROfusion (started within the Horizon 2020 Framework Programme and continuing under the Horizon Europe FP) are reported in [1], while JET experience on T and D-T operations is presented in [2].

The collaborative framework for the management of tuberculosis and type 2 diabetes syndemic in low- and middle-income countries: a rapid review

IntroductionGiven the absence of international guidelines on the joint management and control of tuberculosis (TB) and type 2 diabetes mellitus (T2D), the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (The Union) launched in 2011 a policy framework to address the growing syndemic burden of TB-T2D. This review aimed at mapping the available evidence on the implementation of the Union-WHO Framework, explicitly, or bi-directional TB-T2D health programs as an initiative for co-management in patients in low- and middle-income countries (LMIC).MethodsA rapid review was performed based on a systematic search in PubMed and Web of Science electronic databases for peer-reviewed articles on The Union-WHO Framework and bi-directional interventions of TB and T2D in LMIC. The search was restricted to English language articles and from 01/08/2011 to 20/05/2022.ResultsA total of 24 articles from 16 LMIC met the inclusion criteria. Four described the implementation of The Union-WHO Framework and 20 on the bi-directional interventions of TB and T2D. Bi-directional activities were found valuable, feasible and effective following the Union-WHO recommendations. Limited knowledge and awareness on TB-T2D comorbidity was identified as one of the barriers to ensure a functional and effective integration of services.ConclusionsThis review revealed that it is valuable, feasible and effective to implement bi-directional TB and T2D activities (screening and management) according to the Union-WHO Framework recommendations, especially in countries that face TB-T2D syndemic. Additionally, it was apparent that gaps still exist in research aimed at providing evidence of costs to implement collaborative activities. There is need for TB and T2D services integration that should be done through the well-stablished TB programme. This integration of two vertical programmes, could ensure patient-centeredness, continuum of care and ultimately contribute for health systems strengthening.

Safety and immunogenicity of the co-administered Na-APR-1 and Na-GST-1 hookworm vaccines in school-aged children in Gabon: a randomised, controlled, observer-blind, phase 1, dose-escalation trial.

A human hookworm vaccine is being developed to protect children against iron deficiency and anaemia associated with chronic infection with hookworms. Necator americanus aspartic protease-1 (Na-APR-1) and N americanus glutathione S-transferase-1 (Na-GST-1) are components of the blood digestion pathway critical to hookworm survival in the host. Recombinant Na-GST-1 and catalytically inactive Na-APR-1 (Na-APR-1[M74]) adsorbed to Alhydrogel were safe and immunogenic when delivered separately or co-administered to adults in phase 1 trials in non-endemic and endemic areas. We aimed to investigate the safety and immunogenicity of these antigens in healthy children in a hookworm-endemic area. This was a randomised, controlled, observer-blind, phase 1, dose-escalation trial, conducted in a clinical research centre, in 60 children aged six to ten years in Lambaréné, a hookworm-endemic region of Gabon. Healthy children (determined by clinical examination and safety laboratory testing) were randomised 4:1 to receive co-administered Na-GST-1 on Alhydrogel plus Na-APR-1(M74) on Alhydrogel and glucopyranosyl lipid A in aqueous formulation (GLA-AF), or co-administered ENGERIX-B hepatitis B vaccine (HBV) and saline placebo, injected into the deltoid of each arm. Allocation to vaccine groups was observer-masked. In each vaccine group, children were randomised 1:1 to receive intramuscular injections into each deltoid on two vaccine schedules, one at months 0, 2, and 4 or at months 0, 2, and 6. 10 μg, 30 μg, and 100 μg of each antigen were administered in the first, second, and third cohorts, respectively. The intention-to-treat population was used for safety analyses; while for immunogenicity analyses, the per-protocol population was used (children who received all scheduled vaccinations). The primary outcome was to evaluate the vaccines' safety and reactogenicity in healthy children aged between six and ten years. The secondary outcome was to measure antigen-specific serum IgG antibody levels at pre-vaccination and post-vaccination timepoints by qualified ELISAs. The trial is registered with ClinicalTrials.gov, NCT02839161, and is completed. Between Jan 23 and Oct 3, 2017, 137 children were screened, of whom 76 were eligible for this trial. 60 children were recruited, and allocated to either 10 μg of the co-administered antigens (n=8 for each injection schedule), 30 μg (n=8 for each schedule), 100 μg (n=8 for each schedule), or HBV and placebo (n=6 for each schedule) in three sequential cohorts. Co-administration of the vaccines was well tolerated; the most frequent solicited adverse events were mild-to-moderate injection-site pain, observed in up to 12 (75%) of 16 participants per vaccine group, and mild headache (12 [25%] of 48) and fever (11 [23%] of 48). No vaccine-related serious adverse events were observed. Significant anti-Na-APR-1(M74) and anti-Na-GST-1 IgG levels were induced in a dose-dependent manner, with peaks seen 14 days after the third vaccinations, regardless of dose (for Na-APR-1[M74], geometric mean levels [GML]=2295·97 arbitrary units [AU] and 726·89 AU, while for Na-GST-1, GMLs=331·2 AU and 21·4 AU for the month 0, 2, and 6 and month 0, 2, and 4 schedules, respectively). The month 0, 2, and 6 schedule induced significantly higher IgG responses to both antigens (p=0·01 and p=0·04 for Na-APR-1[M74] and Na-GST-1, respectively). Co-administration of recombinant Na-APR-1(M74) and Na-GST-1 to school-aged Gabonese children was well tolerated and induced significant IgG responses. These results justify further evaluation of this antigen combination in proof-of-concept controlled-infection and efficacy studies in hookworm-endemic areas. European Union Seventh Framework Programme.

Sunitinib for metastatic progressive phaeochromocytomas and paragangliomas: results from FIRSTMAPPP, an academic, multicentre, international, randomised, placebo-controlled, double-blind, phase 2 trial

No randomised controlled trial has ever been done in patients with metastatic phaeochromocytomas and paragangliomas. Preclinical and first clinical evidence suggested beneficial effects of sunitinib. We aimed to evaluate the safety and efficacy of sunitinib in patients with metastatic phaeochromocytomas and paragangliomas. FIRSTMAPPP is a multicentre, international, randomised, placebo-controlled, double-blind, phase 2 trial done at 14 academic centres across four European countries. Eligible participants were adults (aged ≥18 years) with sporadic or inherited progressive metastatic phaeochromocytomas and paragangliomas. Patients were randomly assigned (1:1) to receive either oral sunitinib (37·5 mg per day) or placebo. Randomisation was stratified according to SDHB status (mutation present vs wild type) and number of previous systemic therapies (0 vs ≥1). Primary endpoint was the rate of progression-free survival at 12 months according to real-time central review (Response Evaluation Criteria in Solid Tumours version 1.1). On the basis of a two-step Simon model, we aimed for the accrual of 78 patients, assuming a 20% improvement of the 12-month progression-free survival rate from 20% to 40%, to conclude that sunitinib is effective. Crossover from the placebo group was allowed. This trial is registered with ClinicalTrials.gov, number NCT01371201, and is closed for enrolment. From Dec 1, 2011, to Jan 31, 2019, a total of 78 patients with progressive metastatic phaeochromocytomas and paragangliomas were enrolled (39 patients per group). 25 (32%) of 78 patients had germline SDHx variants and 54 (69%) had used previous therapies. The primary endpoint was met, with a 12-month progression-free survival in 14 of 39 patients (36% [90% CI 23-50]) in the sunitinib group. In the placebo group, the 12-month progression-free survival in seven of 39 patients was 19% (90% CI 11-31), validating the hypotheses of our study design. The most frequent grade 3 or 4 adverse events were asthenia (seven [18%] of 39 and one [3%] of 39), hypertension (five [13%] and four [10%]), and back or bone pain (one [3%] and three [8%]) in the sunitinib and placebo groups, respectively. Three deaths occurred in the sunitinib group: these deaths were due to respiratory insufficiency, amyotrophic lateral sclerosis, and rectal bleeding. Only the latter event was considered drug related. Two deaths occurred in the placebo group due to aspiration pneumonia and septic shock. This first randomised trial supports the use of sunitinib as the medical option with the highest level of evidence for anti-tumour efficacy in progressive metastatic phaeochromocytomas and paragangliomas. French Ministry of Health, through the National Institute for Cancer, German Ministry of Education and Research, and the German Research Foundation within the CRC/Transregio 205/2, EU Seventh Framework Programme, and a private donator grant.

Overview of the EUROfusion Tokamak Exploitation programme in support of ITER and DEMO

Abstract Within the 9th European Framework programme, since 2021 EUROfusion is operating five tokamaks under the auspices of a single Task Force called "Tokamak Exploitation”. The goal is to benefit from the complementary capabilities of each machine in a coordinated way and help in developing a scientific output scalable to future largre machines. The programme of this Task Force ensures that ASDEX Upgrade, MAST-U, TCV, WEST and JET (since 2022) work together to achieve the objectives of Missions 1 and 2 of the EUROfusion Roadmap: i) demonstrate plasma scenarios that increase the success margin of ITER and satisfy the requirements of DEMO and, ii) demonstrate an integrated approach that can handle the large power leaving ITER and DEMO plasmas. The Tokamak Exploitation task force has therefore organized experiments on these two missions with the goal to strengthen the physics and operational basis for the ITER baseline scenario and for exploiting the recent plasma exhaust enhancements in all four devices (PEX: Plasma EXhaust) for exploring the solution for handling heat and particle exhaust in ITER and develop the conceptual solutions for DEMO. The ITER Baseline scenario has been developed in a similar way in ASDEX Upgrade, TCV and JET. Key risks for ITER such as disruptions and run-aways have been also investigated in TCV, ASDEX Upgrade and JET. Experiments have explored successfully different divertor configurations (standard, super-X, snowflakes) in MAST-U and TCV and studied tungsten melting in WEST and ASDEX Upgrade. The input from the smaller devices to JET has also been proven successful to set-up novel control schemes on disruption avoidance and detachment.

Regional and sectoral variations in the ability to attract funding from the European Union’s Seventh Framework Program and Horizon 2020

The funding from the European Union’s Framework Programs for Research and Innovation (EU FPs) is skewed across European countries and institutions. The goal of this article is to deepen our understanding of this skewness by incorporating a regional (NUTS-2) and a sectoral (higher education sector and private sector) perspective when studying the ability to attract 71.6 billion euros of research funding distributed by the EU Framework Programs between 2007 and 2020, and to explore how it changed from FP7 to Horizon 2020. We explore the ability to attract grant funding per unit of R&D personnel, and how it is affected by a region’s volume of research personnel, R&D investments, research intensity, level of development, and mediated by the amount of funding requested. In the private sector, we find that several Southern European regions are highly capable of attracting funding, primarily through a high proposal intensity, e.g., large amounts of funding requested. In the higher education sector, regions in the so-called “blue banana” are particularly able to attract funding, due to high levels of R&D investments, strong research intensity, and a high amount of funding requested. From FP7 to Horizon 2020, we observe increasing divergence in the ability to attract funding in the private sector, in favor of peripheral regions, which aligns with the aims of the European Commission's cohesion policy.

Research priorities and considerations for nutrition research: methods of sex and gender analysis for biomedical and nutrition research.

For some 20 years, science funding bodies have been asking for the integration of sex- and gender-related factors into the content of research and innovation. The rationale for those requirements has been the accumulated evidence that sex and gender are important determinants of health and disease. The European Commission (EC) has been the first, since 2002, to seriously ask for the integration of sex and gender into research and innovation in the context of their multi-annual framework programmes. When introduced, this condition was not immediately applauded by the research community, who perhaps lacked training in methods for the integration of sex- and gender-related factors. The EC Expert Group on Gendered Innovations sought to fill this gap. This review describes the work of this international collaborative project which has resulted in the development of general and field-specific methods for sex and gender analysis and 38 case studies for various research domains (science, health and medicine, environment, engineering) to illustrate how, by applying methods of sex and gender analysis, new knowledge could be created. Since 2010, science funding bodies in Canada, the USA and several EU member states have followed the example of the EC issuing similar conditions. Although the effects of nutritional patterns on a range of (physiological and health) outcomes may differ for men and women, sex and gender analyses are rarely conducted in nutrition research. In this review, we provide examples of how gender is connected to dietary intake, and how advancing gender analysis may inform gender-sensitive policies and dietary recommendations.

Less-advanced regions in EU innovation networks: Could nanotechnology represent a possible trigger for path upgrading?

This paper examines whether nanotechnology projects funded under the European Union (EU) Framework Programmes (FPs) are a possible trigger for path upgrading (i.e., infusion of new technologies in existing traditional sectors) in less-advanced regions. First, the adoption of cluster analysis and a set of key indicators (i.e., technological intensity, scientific excellence, human capital, and research and development expenditure) allowed us to distinguish between 79 more-advanced and 127 less-advanced EU regions. Subsequently, through social network analysis and nonparametric testing we were able to demonstrate how the less-advanced EU regions (average degree centrality: 40.5) play a marginal role compared with the more-advanced ones (average degree centrality: 98.5) in the nanotechnology network created within Horizon 2020-i.e., the EU programming cycle implemented in the 2014-2020 period. Despite this, we observed that a few less-advanced regions (33 out of 127) were able to score higher than the EU median in terms of participation in the targeted nanotechnology network, thus benefiting from relevant knowledge flows potentially leading to re-industrialization processes. The adoption of qualitative comparative analysis allowed us to determine which combinations of key innovation, scientific and socioeconomic factors could facilitate such beneficial interregional interactions and related knowledge exchange in these types of regions (i.e., primarily what we defined as "relative innovativeness," excellence in nanotechnology research and a comparatively high level of gross domestic product per capita). Our empirical results provided some clear policy implications. For instance, the necessity to I) remove the barriers impeding a more balanced participation to promote a widespread renewal of traditional industries in less-advanced regions and II) implement coordinated EU and domestic actions designed to encourage the involvement of the great majority of the less-advanced regions, which remain marginal in the periodically launched FPs.

Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial

BackgroundTreatment with benznidazole for chronic Chagas disease is associated with low cure rates and substantial toxicity. We aimed to compare the parasitological efficacy and safety of 3 different benznidazole regimens in adult patients with chronic Chagas disease. MethodsThe MULTIBENZ trial was an international, randomised, double-blind, phase 2b trial performed in Argentina, Brazil, Colombia, and Spain. We included participants aged 18 years and older diagnosed with Chagas disease with two different serological tests and detectable T cruzi DNA by qPCR in blood. Previously treated people, pregnant women, and people with severe cardiac forms were excluded. Participants were randomly assigned 1:1:1, using a balanced block randomisation scheme stratified by country, to receive benznidazole at three different doses: 300 mg/day for 60 days (control group), 150 mg/day for 60 days (low dose group), or 400 mg/day for 15 days (short treatment group). The primary outcome was the proportion of patients with a sustained parasitological negativity by qPCR during a follow-up period of 12 months. The primary safety outcome was the proportion of people who permanently discontinued the treatment. Both primary efficacy analysis and primary safety analysis were done in the intention-to-treat population. The trial is registered with EudraCT, 2016-003789-21, and ClinicalTrials.gov, NCT03191162, and is completed. FindingsFrom April 20, 2017, to Sept 20, 2020, 245 people were enrolled, and 234 were randomly assigned: 78 to the control group, 77 to the low dose group, and 79 to the short treatment group. Sustained parasitological negativity was observed in 42 (54%) of 78 participants in the control group, 47 (61%) of 77 in the low dose group, and 46 (58%) of 79 in the short treatment group. Odds ratios were 1·41 (95% CI 0·69–2·88; p=0·34) when comparing the low dose and control groups and 1·23 (0·61–2·50; p=0·55) when comparing short treatment and control groups. 177 participants (76%) had an adverse event: 62 (79%) in the control group, 56 (73%) in the low dose group, and 59 (77%) in the short treatment group. However, discontinuations were less frequent in the short treatment group compared with the control group (2 [2%] vs 11 [14%]; OR 0·20, 95% CI 0·04–0·95; p=0·044). InterpretationParticipants had a similar parasitological responses. However, reducing the usual treatment from 8 weeks to 2 weeks might maintain the same response while facilitating adherence and increasing treatment coverage. These findings should be confirmed in a phase 3 clinical trial. FundingEuropean Community's 7th Framework Programme.

The role of City Climate Networks in Promoting Citizen Participation in Municipalities: A Critical Multi-Case Analysis

BackgroundAt the COP21, cities were recognised as key actors in combatting climate change. In supporting cities, climate city networks such as transnational climate networks (TCNs) and national climate networks (NCNs) have emerged to enable cities in building capacities and formulating climate policy whilst also encouraging citizen engagement and participation in public decision-making. This paper addresses the question whether and how TCN or NCN membership enables municipalities to implement citizen participation in public decision-making. Six propositions are presented addressing: presumed influence of TCN membership on citizen participation, organization of citizen participation, initiator capacity, goal setting, involvement of stakeholders, participatory methods used, and planning processes. A multi-case study research design is used to verify these propositions, comprising of four medium-sized cities in the Netherlands and three in Belgium.ResultsResults of the analysis of four cities in The Netherlands show that municipalities having membership to climate city networks only to a low extent empower citizen participation via local climate agendas. Citizen participation emerges rather bottom-up via local initiatives or capacity building via EU framework programs—outside TCNs or NCNs—that better suit financial needs and provide more immediate benefits to municipalities. None of the six propositions were confirmed. A more positive image resulted from the Belgian cases that moderately confirmed four out of six propositions (i.e., organizing citizen participation, goal setting, selection of methods, and planning), and featured indirect empowerment via externally funded implementation projects following firm integration of participation in local climate policy through TCN influence.ConclusionsIn terms of citizen participation selected municipalities in the Netherlands having TCN and/or NCN membership only to a small extent differ from those not having membership. This is partly due to poor implementation of TCNs and NCNs—with Covenant of Mayors and ‘Klimaatverbond’ lacking support structure and capacity—having lost importance during the past years. However, there is reason to believe that context makes a difference as revealed by the cases from Belgium, which revealed more positive results.

Ethics reviews in the European Union. Implications for the governance of scientific research in times of data science and Artificial Intelligence

ABSTRACT This article builds on discussions on peer review in science and the role of ethics in the governance of technologies to achieve a two-fold goal. First, it shows the process of co-production of the European Commission’s (EC’s) standardised ‘ethics appraisal process’ with the development of the EC’s Framework Programmes (FPs), by looking at the standardisation of the process and the mutual shaping of data protection law and risk-based discourses around Artificial Intelligence. Second, it investigates the political and epistemic implications arising from this process for the EU governance of scientific research regarding (1) sponsorship of science and technology by the EU and (2) how many limitations or constraints researchers have in practice when carrying out their research. After sketching the origins of the ethics appraisal process and its co-production with data protection law and risk-based jargon, the article outlines the implications for the governance of scientific research and draws recommendations.

Digital Archiving in Archaeology: Assessing the State of the Art

The Saving European Archaeology from Digital Dark Age (SEADDA) COST Action (CA18128) is funded by the Horizon 2020 Framework Programme of the European Union and aims to create a network for archaeologists and digital specialists to build capacity for the long-term preservation of digital data for archaeology. More than 20 countries are involved in SEADDA, and have undertaken surveys, publications, workshops, STSMs (Short Term Scientific Missions) and other activities carried out to increase awareness and share expertise. Within the scope of the project, Internet Archeology 58 2021, titled "Digital Archiving in Archeology: Assessing the State of the Art", and then Internet Archeology 63 2023, titled "Digital Archiving in Archeology: Additional State of the Art and Further Analyzes" were published. This article will give a brief introduction to SEADDA but will focus primarily on what we are learning from Internet Archaeology 58 and Internet Archaeology 63, how it is helping us to understand digital archaeological data around the world. In this study, 37 articles from 31 different countries were examined, according to three main categories: administrative structure, physical and digital archives for archaeological data. In the light of the data obtained, it is difficult to generalize about archaeological data processes and management; however, different countries and regions are applying different methods to create repositories. Legislation, budgets, and human resources are all factors which affect these processes for preserving digital archaeological data for future generations. But, all countries need to share expertise, and engage in capacity building, especially around legislations, human resources, standards and guidelines, whilst financial support needs to be prioritized.

Meld Exploring the Feasibility of a Framework-less Framework

HEP data-processing frameworks are essential ingredients in getting from raw data to physics results. But they are often tricky to use well, and they present a significant learning barrier for the beginning HEP physicist. In addition, existing frameworks typically support rigid, collider-based data models, which do not map well to neutrino-physics experiments like DUNE. Neutrino physicists thus expend significant effort working around framework limitations instead of using a framework that directly supports their needs. Presented here is Meld, a Fermilab R&D project, which intends to address these limitations. By leveraging modern C++ capabilities, state-of-the-art concurrency libraries, and a flexible data model, it is possible for beginning (and seasoned) HEP physicists to execute framework programs easily and efficiently, with minimal coupling to framework-specific constructs. Meld aims to directly support the frameworks needs of neutrino experiments like DUNE as well as the more common collider-based experiments.

In utero exposures to perfluoroalkyl substances and the human fetal liver metabolome in Scotland: a cross-sectional study

Perfluoroalkyl and polyfluoroalkyl substances are classed as endocrine disrupting compounds but continue to be used in many products such as firefighting foams, flame retardants, utensil coatings, and waterproofing of food packaging. Perfluoroalkyl exposure aberrantly modulates lipid, metabolite, and bile acid levels, increasing susceptibility to onset and severity of metabolic diseases, such as diabetes and metabolic dysfunction-associated steatotic liver disease. To date, most studies in humans have focused on perfluoroalkyl-exposure effects in adults. In this study we aimed to show if perfluoroalkyls are present in the human fetal liver and if they have metabolic consequences for the human fetus. In this cross-sectional study, human fetal livers from elective termination of pregnancies at the Aberdeen Pregnancy Counselling Service, Aberdeen, UK, were analysed by both targeted (bile acids and perfluoroalkyl substances) and combined targeted and untargeted (lipids and polar metabolites) mass spectrometry based metabolomic analyses, as well as with RNA-Seq. Only fetuses from normally progressing pregnancies (determined at ultrasound scan before termination), terminated for non-medical reasons, from women older than 16 years, fluent in English, and between 11 and 21 weeks of gestation were collected. Women exhibiting considerable emotional distress or whose fetuses had anomalies identified at ultrasound scan were excluded. Stringent bioinformatic and statistical methods such as partial correlation network analysis, linear regression, and pathway analysis were applied to this data to investigate the association of perfluoroalkyl exposure with hepatic metabolic pathways. Fetuses included in this study were collected between Dec 2, 2004, and Oct 27, 2014. 78 fetuses were included in the study: all 78 fetuses were included in the metabolomics analysis (40 female and 38 male) and 57 fetuses were included in the RNA-Seq analysis (28 female and 29 male). Metabolites associated with perfluoroalkyl were identified in the fetal liver and these varied with gestational age. Conjugated bile acids were markedly positively associated with fetal age. 23 amino acids, fatty acids, and sugar derivatives in fetal livers were inversely associated with perfluoroalkyl exposure, and the bile acid glycolithocholic acid was markedly positively associated with all quantified perfluoroalkyl. Furthermore, 7α-hydroxy-4-cholesten-3-one, a marker of bile acid synthesis rate, was strongly positively associated with perfluoroalkyl levels and was detectable as early as gestational week 12. Our study shows direct evidence for the in utero effects of perfluoroalkyl exposure on specific key hepatic products. Our results provide evidence that perfluoroalkyl exposure, with potential future consequences, manifests in the human fetus as early as the first trimester of gestation. Furthermore, the profiles of metabolic changes resemble those observed in perinatal perfluoroalkyl exposures. Such exposures are already linked with susceptibility, initiation, progression, and exacerbation of a wide range of metabolic diseases. UK Medical Research Council, Horizon Europe Program of the European Union, Seventh Framework Programme of the European Union, NHS Grampian Endowments grants, European Partnership for the Assessment of Risks from Chemicals, Swedish Research Council, Formas, Novo Nordisk Foundation, and the Academy of Finland.

Improving transparency and corneal wound healing in rare diseases by promoting corneal nerve regeneration

Corneal nerves play a crucial role in maintaining the integrity of corneal tissue, as well as the proper regulation of tearing and blinking. When activated, corneal nerves release locally several factors, including neuropeptides, that contribute to the trophic maintenance of corneal tissues. So that, the reduction or absence of corneal nerves led to impaired corneal wound healing in addition to a loss of sensory input, resulting in lack of sensitivity and alterations in tearing and blinking rate. Such consequences are seen clinically in several rare diseases where severe nerve deficit is a prominent factor such as in neurotrophic keratopathy, where the cornea spontaneously ulcerates due to its inability to renew the epithelium and to heal epithelial wounds, leading to loss of corneal transparency. An advanced molecular therapy to increase corneal nerve regeneration and support the corneal neurotrophic environment in such ocular rare diseases is proposed.(Supported by RESTORE VISION – 101 080 611, Horizon Europe Framework Programme, European Commission)

The Association between Long-Term DDT or DDE Exposures and an Altered Sperm Epigenome-a Cross-Sectional Study of Greenlandic Inuit and South African VhaVenda Men.

The organochlorine dichlorodiphenyltrichloroethane (DDT) is banned worldwide owing to its negative health effects. It is exceptionally used as an insecticide for malaria control. Exposure occurs in regions where DDT is applied, as well as in the Arctic, where its endocrine disrupting metabolite, -dichlorodiphenyldichloroethylene (-DDE) accumulates in marine mammals and fish. DDT and -DDE exposures are linked to birth defects, infertility, cancer, and neurodevelopmental delays. Of particular concern is the potential of DDT use to impact the health of generations to come via the heritable sperm epigenome. The objective of this study was to assess the sperm epigenome in relation to -DDE serum levels between geographically diverse populations. In the Limpopo Province of South Africa, we recruited 247 VhaVenda South African men and selected 50 paired blood serum and semen samples, and 47 Greenlandic Inuit blood and semen paired samples were selected from a total of 193 samples from the biobank of the INUENDO cohort, an EU Fifth Framework Programme Research and Development project. Sample selection was based on obtaining a range of -DDE serum levels (). We assessed the sperm epigenome in relation to serum -DDE levels using MethylC-Capture-sequencing (MCC-seq) and chromatin immunoprecipitation followed by sequencing (ChIP-seq). We identified genomic regions with altered DNA methylation (DNAme) and differential enrichment of histone H3 lysine 4 trimethylation (H3K4me3) in sperm. Differences in DNAme and H3K4me3 enrichment were identified at transposable elements and regulatory regions involved in fertility, disease, development, and neurofunction. A subset of regions with sperm DNAme and H3K4me3 that differed between exposure groups was predicted to persist in the preimplantation embryo and to be associated with embryonic gene expression. These findings suggest that DDT and -DDE exposure impacts the sperm epigenome in a dose-response-like manner and may negatively impact the health of future generations through epigenetic mechanisms. Confounding factors, such as other environmental exposures, genetic diversity, and selection bias, cannot be ruled out. https://doi.org/10.1289/EHP12013.

(Invited) Lithium Plating as a Critical Ageing Mechanism in Lithium-Ion Batteries – Detection by Advanced Methods and Mitigation

The cycle life of Li-ion batteries is limited by aging on the material and electrode level. Prolonging the battery life helps increasing sustainability, reducing the dependency from critical raw materials, and safes costs. The first step in extending battery life is to understand the underlying degradation mechanisms. Post-Mortem analysis of commercial and pilot-line made cells showed that Lithium plating is a very relevant and severe aging mechanism which can lead to high aging rates and decrease safety properties.1 In this talk, we analyse the aging mechanism of Lithium plating on cell and electrode level.On cell level, capacity fade per time yields aging rates, which are temperature dependent. This temperature dependency is analyzed via Arrhenius plots. The Arrhenius plots for cycling aging show a typical V-shape with a low and a high temperature branch.2–4 A minimum in the Arrhenius plot corresponds to the maximum cycle life of the battery, while the low temperature branch indicates Lithium plating. Interestingly, the minimum in the Arrhenius plot shifts with the charging C-rate, the battery type,3,4 and – in case of non-linear capacity fade curves – with aging.4 In the last years, our group developed new semi-quantitative methods based on glow discharge optical emission spectroscopy (GD-OES) depth profiling for detection of Lithium plating on graphite5 and on Si/graphite composite anodes.6 Furthermore, a new in situ optical microscopy method with cross-sectioned full cells allows direct observations of the electrodes during charging and discharging.7,8 The color change of lithiated graphite in combination with simultaneous electrochemical data gives insight into the charging behavior of anodes. Under slow charging conditions (0.1C), the lithiation of the anode is observed to be homogeneously. Most interestingly, at 1C transport limitations come into play and lithiation fronts moving from the anode surface to the current collector can be directly observed and quantified by image analysis. Our results of both methods5,6,8 and in full consistence with simulations by others9 show that Lithium is mainly deposited on the anode surface, i.e. near the separator (see Figure).Finally, we show that Lithium deposition can be prevented by avoiding anode potentials < 0 V vs. Li/Li+ in commercial cells and cells from our pilot-line. Interestingly, Si/graphite anodes in pouch full cells show a lower susceptibility to Lithium plating at low temperatures with increasing Si content and the same anode areal capacity and N/P ratio. This suggests that the transport limitations in the pores of these Si/graphite anodes are reduced due to lower anode coating thickness. References T. Waldmann, B.-I. Hogg, and M. Wohlfahrt-Mehrens, J. Power Sources, 384, 107–124 (2018).T. Waldmann, M. Wilka, M. Kasper, M. Fleischhammer, and M. Wohlfahrt-Mehrens, J. Power Sources, 262, 129–135 (2014).X.-G. Yang and C.-Y. Wang, J. Power Sources, 402, 489–498 (2018).G. Kucinskis et al., J. Power Sources, 549, 232129 (2022).N. Ghanbari, T. Waldmann, M. Kasper, P. Axmann, and M. Wohlfahrt-Mehrens, J. Phys. Chem. C, 120, 22225–22234 (2016).M. Flügel, K. Richter, M. Wohlfahrt-Mehrens, and T. Waldmann, J. Electrochem. Soc., 169, 050533 (2022).C. Hogrefe et al., J. Electrochem. Soc., 169, 050519 (2022).C. Hogrefe, T. Waldmann, M. Hölzle, and M. Wohlfahrt-Mehrens, J. Power Sources, 556, 232391 (2023).S. Hein and A. Latz, Electrochimica Acta, 201, 354–365 (2016). Acknowledgement The authors would like to acknowledge the Federal Ministry for Economic Affairs and Climate Action (BMWK) for financial support of the Structur.e project (03ETE018E), the German Federal Ministry of Education and Research (BMBF) for funding of the project CharLiSiKo (03XP0333A) and the TEESMAT project (Horizon 2020 E.U. Framework Program, Grant Agreement N° 814106, http://www.teesmat.eu). Figure 1