Framework Programme Research Articles

Associations between training characteristics and change in peak oxygen consumption following exercise training in patients with heart failure with preserved ejection fraction

Abstract Introduction In heart failure with preserved ejection fraction (HFpEF), moderate continuous training (MCT) and high-intensity interval training (HIIT) are both effective in increasing peak oxygen uptake (peak V̇O2). Purpose The aim of this study was to investigate the association of training characteristics (i.e. average sessions/week, average duration/week, mean intensity) and change in peak V̇O2 following 3 months of MCT and HIIT in patients with HFpEF. Methods Among 120 patients who were randomized to MCT (5x40 min/week at 35–50% heart rate reserve [HRR]) or HIIT (3x38 min/week at 80–90% HRR), those who completed 3-month follow-up (N=107) were considered for this analysis. Training duration and heart rates [HR] were recorded with a smartphone application, evaluated with a customized software and manually checked for plausibility. If HR measurements were classified as invalid/unreliable (e.g. very strong fluctuations), patients were excluded from analysis. Intensities were calculated as average % HRR of total sessions in MCT and the average of the highest % HRR values of all intervals in HIIT. Associations between training characteristics and change in peak V̇O2 were evaluated using univariate and multivariate regression analyses. Individual HR-V̇O2 relationships were used to calculate and compare energy expenditure (MET-minutes) in MCT and HIIT. Results After excluding 16 patients due to invalid/unreliable HR data, 91 patients (67% female, 69±7 years) were included in this analysis. On average, MCT patients (N=45) performed 4.0±1.2 sessions/week (162±52 min/week) at 47.4±6.7% HRR, while HIIT patients (N=46) performed 2.4±0.8 sessions/week (96±40 min/week) at 81.8±11.8% HRR. Peak V̇O2 was improved by 1.70±2.35 ml/kg/min in MCT and 1.46±2.98 ml/kg/min in HIIT (difference: 0.24 [95% CI, −0.87 to 1.34], p=0.67). The associations between training characteristics and change in peak V̇O2 are shown in Fig.1. Mean % HRR was not significantly associated with the change in peak V̇O2 in the HIIT group, whereas in MCT, mean duration/week and mean intensity were of similar relative importance (standardized coefficients) and explained up to 26% of the variation in change in peak V̇O2 (Table 1). Average weekly MET-minutes above rest were 451±260 for MCT and 389±375 for HIIT (difference: 62 [95% CI, −71 to 195], p=0.36). After adjustment for MET-minutes, the difference in change in peak V̇O2 between groups diminished to 0.09 ml/kg/min (95% CI, −0.97 to 1.16; p=0.98). Conclusions Weekly duration and mean % HRR had a similar predictive ability for the change in peak V̇O2 following MCT with, interestingly, lower change in peak V̇O2 with increasing intensity. In HIIT, mean % HRR was not significantly associated with the change in peak V̇O2. After adjusting for energy expenditure, the difference in change in peak V̇O2 between training modes diminished, suggesting that MCT and HIIT were similarly effective. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Commission, Framework Program 7

Incremental utility of circulating biomarkers for cardiovascular risk prediction beyond the updated SCORE2 model

Abstract Background Accurate risk prediction for future cardiovascular disease (CVD) is crucial for timely initiation of preventive measures in high-risk individuals. Most risk scores, such as the recently updated SCORE2 risk-prediction model supported by the European Society of Cardiology, consider only traditional cardiovascular risk factors. Whether the addition of circulating biomarkers to the existing SCORE2 model may improve risk prediction is unclear. Purpose We aimed to evaluate the incremental utility of four widely available circulating biomarkers to improve the prediction of 10-year CVD-risk beyond SCORE2. Methods Data from ten prospective population-based cohorts from seven countries across Europe were collected if information on SCORE2-variables and at least one of the following four investigational biomarkers was available: high-sensitivity cardiac troponin I (hs-cTnI), NT-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP) and creatinine-based estimated glomerular filtration rate (eGFR). Primary outcome was incidence of CVD at 10 years, defined as the composite of cardiovascular mortality, non-fatal myocardial infarction and non-fatal stroke. We used Fine and Gray models adjusted for competing-risk and SCORE2-variables as well as penalized cubic splines to assess and visualize the association of individual biomarkers with incident CVD. In a multimarker approach, we performed backward selection to identify biomarkers providing independent predictive value beyond SCORE2-components. C-indices and category-free net reclassification index (cfNRI) were used to compare the performance of the original SCORE2 model to the biomarker-extended model. Results In 78'507 individuals, median age was 50 years and 50.3% were females. NT-proBNP, hs-CRP and hs-cTnI but not eGFR showed strong associations with 10-year CVD-risk when adjusted for SCORE2 and provided incremental predictive value when individually added to SCORE2 (Figure 1). In a multimarker approach, all three biomarkers remained independently associated with CVD beyond SCORE2 with strongest association of NT-proBNP, followed by hs-CRP and hs-cTnI (Table 1). The simultaneous addition of these three biomarkers to the SCORE2 model significantly increased discrimination (C-index; 0.782 [95% CI, 0.757, 0.806] versus 0.793 [95% CI, 0.768, 0.817], Delta 0.011 [95% CI, 0.005, 0.016]) and risk reclassification, driven by an improvement in non-events (cfNRIoverall 0.17 [95% CI, 0.12, 0.22], cfNRIevents 0.06 [95% CI, 0.02, 0.11], cfNRInon-events 0.11 [95% CI, 0.10, 0.11]). Conclusion NT-proBNP, hs-CRP and hs-cTnI but not eGFR provide incremental predictive value when added to the SCORE2 risk-prediction model and may help to further improve personalized CVD-risk prediction. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Community's Seventh Framework Programme (FP7/2007-2013)

T-wave alternans poorly prognostic in primary prophylactic ICD patients: a prospective EU-CERT-ICD study

Abstract Background New methods to identify patients who truly benefit from primary prophylactic implantable cardioverter defibrillation (ICD) are urgently needed. T-wave alternans (TWA) represents a beat-to-beat fluctuation in the morphology of the ST-segment and T-wave. It has been shown to associate with arrhythmogenesis of heart and sudden cardiac death [1]. We hypothised that TWA might associate with benefit from ICD implantation in primary prevention. Methods In EU-CERT-ICD study, we prospectively enrolled 2327 primary prophylactic ICD candidates from 15 European countries. A 24-hours Holter-monitoring was taken from all recruited patients at enrolment. TWA was assessed from Holter-monitoring using MMA method with Getemed Cardioday software. To assess the benefit from ICD treatment, we used outcomes all-cause mortality, appropriate shock and survival benefit. We conducted Cox regression model, competing risk regression model and propensity score adjusted Cox regression model. TWA was assessed both as contiguous variable and with cut-off points <47 μV and <60 μV. Results Final cohort included 1,734 valid T-wave alternans samples, 1,211 patients with ICD and 523 control patients with conservative treatment, with mean follow-up time 2.3 years. TWA <60 μV predicted lower all-cause mortality in ICD patients in univariate cox regression model (HR 1.484, 95% CI 1.024–2.151, p=0.0374). In multivariate models, TWA did not predict death or appropriate shocks in ICD patients. In addition, TWA did not predict death in control patients. In propensity score adjusted Cox regression model, TWA did not predict ICD benefit. Conclusion T-wave alternans is poorly prognostic in primary prophylactic ICD patients. Altough it may predict life-threatening arrhythmias and sudden cardiac death in several patient populations, it cannot be used in assessing benefit from implantable cardioverter defibrillator in primary prevention among patients with ejection fraction ≤35%. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Community's 7th Framework Program FP7/2007-2013

107P Ultra-sensitive monitoring mutations in cancer patients using superRCA mutation detection assays

107P Ultra-sensitive monitoring mutations in cancer patients using superRCA mutation detection assays

Comparison of two chemotherapy regimens in patients with newly diagnosed Ewing sarcoma (EE2012): an open-label, randomised, phase 3 trial

Internationally, a single standard chemotherapy treatment for Ewing sarcoma is not defined. Because different chemotherapy regimens were standard in Europe and the USA for newly diagnosed Ewing sarcoma, and in the absence of novel agents to investigate, we aimed to compare these two strategies. EURO EWING 2012 was a European investigator-initiated, open-label, randomised, controlled phase 3 trial done in 10 countries. We included patients aged 2-49 years, with any histologically and genetically confirmed Ewing sarcoma of bone or soft tissue, or Ewing-like sarcomas. The eligibility criteria originally excluded patients with extrapulmonary metastatic disease, but this was amended in the protocol (version 3.0) in September, 2016. Patients were randomly assigned (1:1) to either the European regimen of vincristine, ifosfamide, doxorubicin, and etoposide induction, and consolidation using vincristine, actinomycin D, with ifosfamide or cyclophosphamide, or busulfan and melphalan (group 1); or the US regimen of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide induction, plus ifosfamide and etoposide, and consolidation using vincristine and cyclophosphamide, or vincristine, actinomycin D, and ifosfamide, with busulfan and melphalan (group 2). All drugs were administered intravenously. The primary outcome measure was event-free survival. We used a Bayesian approach for the design, analysis, and interpretation of the results. Patients who received at least one dose of study treatment were considered in the safety analysis. The trial was registered with EudraCT, 2012-002107-17, and ISRCTN, 54540667. Between March 21, 2014, and May 1, 2019, 640 patients were entered into EE2012, 320 (50%) randomly allocated to each group. Median follow-up of surviving patients was 47 months (range 0-84). Event-free survival at 3 years was 61% with group 1 and 67% with group 2 (adjusted hazard ratio [HR] 0·71 [95% credible interval 0·55-0·92 in favour of group 1). The probability that the true HR was less than 1·0 was greater than 0·99. Febrile neutropenia as a grade 3-5 treatment toxicity occurred in 234 (74%) patients in group 1 and in 183 (58%) patients in group 2. More patients in group 1 (n=205 [64%]) required at least one platelet transfusion compared with those in group 2 (n=138 [43%]). Conversely, more patients required blood transfusions in group 2 (n=286 [89%]) than in group 1 (n=277 [87%]). Dose-intensive chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide is more effective, less toxic, and shorter in duration for all stages of newly diagnosed Ewing sarcoma than vincristine, ifosfamide, doxorubicin, and etoposide induction and should now be the standard of care for Ewing sarcoma. The European Union's Seventh Framework Programme for Research, Technological Development, and Demonstration; The National Coordinating Centre in France, Centre Léon Bérard; SFCE; Ligue contre le cancer; Cancer Research UK.

Використання міжнародних грантових програм Horizon 2020 та Horizon Europe в цифровій економіці

The work reveals the status and prospects of using international grant programs of Horizon 2020 and Horizon Europe in the digital economy cluster. It is shown that despite the existence of a large number of international grant projects, in particular within the framework programs of Horizon 2020 and Horizon Europe, the problem of increasing the number of participants from among Ukrainian scientists and scientific teams in these projects remains open. It is shown that there is a gap between the Ukrainian scientific and technical community and the world in the field of obtaining funding for grant projects. The analysis of the features of the use of international framework programs of Horizon 2020 and Horizon Europe in the digital economy cluster was carried out. In particular, a detailed analysis of the supported grant projects in the Horizon 2020 program was carried out with the participation of Ukrainian scientific teams and the role of Ukraine as a project coordinator. The specifics of the topic and the choice of the cluster of funded grant projects were studied. In particular, in the field of digitalization, the research was conducted in the context of such clusters as H2020-EU.2/H2020-EU.2.1 and H2020-EU.2.3.1, which accounted for 12.8% of all funded grant projects within the eighth framework program of Horizon 2020. As for the Horizon Europe program, the research was conducted under all grant projects in which Ukraine participated, including the Euratom program. The budget of the cluster programs in the field of digitalization, which are most in demand by Ukrainian scientists, was also analyzed, the priority areas of providing grants in the ninth framework program of Horizon Europe were determined, and the main key factors of supporting grant projects in the framework program of Horizon 2020 were identified. It is shown that the European Commission, when choosing competitive projects, gives Ukrainian teams more chances to receive funding for a grant project if it is related to the goals of the European Union.

Widespread exposure to Crimean-Congo haemorrhagic fever in Uganda might be driven by transmission from Rhipicephalus ticks: Evidence from cross-sectional and modelling studies

Crimean-Congo haemorrhagic fever (CCHF) is a widespread tick-borne viral infection, present across Africa and Eurasia, which might pose a cryptic public health problem in Uganda. We aimed to understand the magnitude and distribution of CCHF risk in humans, livestock and ticks across Uganda by synthesising epidemiological (cross-sectional) and ecological (modelling) studies. We conducted a cross-sectional study at three urban abattoirs receiving cattle from across Uganda. We sampled humans (n=478), livestock (n=419) and ticks (n=1065) and used commercially-available kits to detect human and livestock CCHF virus (CCHFV) antibodies and antigen in tick pools. We developed boosted regression tree models to evaluate the correlates and geographical distribution of expected tick and wildlife hosts, and of human CCHF exposures, drawing on continent-wide data. The cross-sectional study found CCHFV IgG/IgM seroprevalence in humans of 10·3% (7·8-13·3), with antibody detection positively associated with reported history of tick bite (age-adjusted odds ratio=2·09 (1·09-3·98)). Cattle had a seroprevalence of 69·7% (65·1-73·4). Only one Hyalomma tick (CCHFV-negative) was found. However, CCHFV antigen was detected in Rhipicephalus (5·9% of 304 pools) and Amblyomma (2·9% of 34 pools) species. Modelling predicted high human CCHF risk across much of Uganda, low environmental suitability for Hyalomma, and high suitability for Rhipicephalus and Amblyomma. Our epidemiological and ecological studies provide complementary evidence that CCHF exposure risk is widespread across Uganda. We challenge the idea that Hyalomma ticks are consistently the principal reservoir and vector for CCHFV, and postulate that Rhipicephalus might be important for CCHFV transmission in Uganda, due to high frequency of infected ticks and predicted environmental suitability. UCL Global Challenges Research Fund (GCRF) and Pan-African Network on Emerging and Re-Emerging Infections (PANDORA-ID-NET) funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) under the EU Horizon 2020 Framework Programme for Research and Innovation.

The policy of open access to the results of scientific research projects, enforced in research and development contracts: the experience of European countries, the USA and its possible implementation in Ukrainе

The article analyzes experience of the EU and the USA in implementing the open access policy to the results of scientific researches. There are determined approaches to the formation of a policy of open access during joint projects with the participation of scientific research institutions and Universities, as well as its implementation into the provisions of contracts on research and development, available in Europe and the United States; also, recommendations for implementation of the open access policy in the provisions of contracts for conducting R&D with the participation of Ukrainian scientists are proposed.Statement of the problem: Ukraine, following the countries of Europe and America, is actively implementing the “Open Science” policy, which consists of 3 main elements: open access to publications, open data, and open discussion of the scientific research process and its results. At the same time, a whole list of issues related, in particular, to the functioning of open access to scientific publications and other materials containing the results of scientific research (the absence of an appropriate open access policy in scientific institutions and Universities, legally undefined status of free access licenses according to Ukrainian legislation, etc.). Another issue arises, related to open access to the results of scientific research and development: namely, the appropriate consolidation of the mechanisms of open access to such results of joint international or interdepartmental (interinstitutional) projects in research contracts (hereinafter – Research and Development Contracts (DR Agreements)). The article examines existing open access mechanisms used by scientists and researchers in European countries, mechanisms established at the EU level in the Framework Program for Scientific Research “Horizon Europe”, and also examines the experience of the USA (the level of federal institutions and the practice of universities). Recommendations are offered on setting out an open access policy when concluding DR contracts with Ukrainian and foreign partners.Results of the analysis of scientific publications. The study of the foreign practice of implementing open science, and, in particular, the policy of open access to scientific publications is quite active in Ukraine, but it is of interest to specialists, mainly, as an example for the implementation of such a policy in their research institutes, scientific publishing houses, higher educational institutions. Accordingly, the vast majority of domestic publications on this subject contain the exposition of the open access policy of institutions in Europe and the USA, as well as the definition of such policy in international documents (Didenko Y., Egorov I., ), some publications are devoted to a certain criticism of the process of implementing open access in Ukraine (articles by Yaroshenko T., Haustov V., Hryga V., Ryzhenko Yu.). At the same time, attention is paid to the only aspect – the successive steps of fulfilling the conditions of free access to scientific publications. Other significant aspects of the implementation of free access, namely, the combination of requirements for open access to the results of scientific research and their patent protection, and the legal consolidation of the open access policy of scientific institutions in contracts for conducting scientific research and development with partners and customers have not been clarified by the Ukrainian legal scholars (although certain works in this field have been published and related to the use of Creative Commons open access licenses when using scientific journals, book editions placed in the electronic environment by leading publishing houses (articles by Y.M. Kapitsa, K.S. Shahbazyan), the issue of copyright protection and detection of plagiarism (publications by V. Trotska, K. Shahbazyan, O. Sobin, O. Golikova, O. Samelyuk).

Fostering the Adoption of DMP in Small Research Projects through a Collaborative Approach

In order to promote sound management of research data the European Commission, under the Horizon 2020 framework program, is promoting the adoption of a Data Management Plan (DMP) in research projects. Despite the value of a DMP to make data findable, accessible, interoperable and reusable (FAIR) through time, the development and implementation of DMPs is not yet a common practice in health research. Raising the awareness of researchers in small projects to the benefits of early adoption of a DMP is, therefore, a motivator for others to follow suit. In this paper we describe an approach to engage researchers in the writing of a DMP, in an ongoing project, FrailSurvey, in which researchers are collecting data through a mobile application for self-assessment of fragility. The case study is supported by interviews, a metadata creation session, as well as the validation of recommendations by researchers. With the outline of our process we also outline tools and services that supported the development of the DMP in this small project, particularly since there were no institutional services available to researchers

Editorial introductions.

Editorial introductions.

241.3: Generation of Prevascularized Endocrine Constructs to Treat Type 1 Diabetes

Introduction: The goal of our study was to generate a functional, prevascularized endocrine constructs utilizing amniotic membrane derived hydrogel, islets and blood outgrowth endothelial cells (BOECs) to be transplanted in diabetic hosts. Methods: Human amniotic membranes were dissected from placentas decellularized, lyophilized, and solubilized to obtain hydrogels. DNA quantification and scanning electron microscopy showed complete removal of cellular components and preserved extracellular matrix. Characterization studies demonstrated widespread distribution of all essential structural proteins, including collagen, GAGs and laminin. The islets and BOECs were admixed in amnion derived hydrogels and cultured in specially designed media to enhance endothelial cell assembly into tubular, vascular-like structures. Constructs were kept under culture for 3 days. Glucose stimulated insulin secretion (GSIS) tests showed an adequate insulin secretion in response to high glucose stimulation, confirming the functional activity of the prevascularized endocrine constructs. Results: To test in vivo biocompatibility and function, the vascularized constructs generated from 500 IEQ rat islets and 2× 105 human derived BOECs were implanted under the skin of the diabetic NSG mice. Transplantation of the constructs led to rapid and long-term (90 days) normalization of blood glucose levels. Removal of the grafts led to recurrence of hyperglycemia within 24 hours, indicating that the transplanted constructs was responsible for normalized glucose levels. Histological analysis of the explanted grafts revealed healthy islet morphology and perfect revascularization. Grafts stained positive for insulin and human specific CD 31 indicating presence of human endothelial cells in newly formed intra-islet micro vessels. Conclusion: Our findings show that amnion derived hydrogel seeded with endocrine pancreatic tissue and endothelial cells could be used for functional, preveascularized endocrine construct bioengineering. This work is supported by grants from the European Commission (Horizon 2020 Framework Program; VANGUARD grant 874700), the European Foundation for the Study of Diabetes (EFSD), the Juvenile Diabetes Research Foundation (JDRF; grant 3-SRA-2020-926-S-B) and the Shota Rustaveli National Science Foundation (grant FR-19-19760).

Exactness of Parrilo’s Conic Approximations for Copositive Matrices and Associated Low Order Bounds for the Stability Number of a Graph

De Klerk and Pasechnik introduced in 2002 semidefinite bounds [Formula: see text] for the stability number [Formula: see text] of a graph G and conjectured their exactness at order [Formula: see text]. These bounds rely on the conic approximations [Formula: see text] introduced by Parrilo in 2000 for the copositive cone [Formula: see text]. A difficulty in the convergence analysis of the bounds is the bad behavior of Parrilo’s cones under adding a zero row/column: when applied to a matrix not in [Formula: see text] this gives a matrix that does not lie in any of Parrilo’s cones, thereby showing that their union is a strict subset of the copositive cone for any [Formula: see text]. We investigate the graphs for which the bound of order r≤1 is exact: we algorithmically reduce testing exactness of [Formula: see text] to acritical graphs, we characterize the critical graphs with [Formula: see text] exact, and we exhibit graphs for which exactness of [Formula: see text] is not preserved under adding an isolated node. This disproves a conjecture posed by Gvozdenović and Laurent in 2007, which, if true, would have implied the above conjecture by de Klerk and Pasechnik. Funding: This work is supported by the European Union’s Framework Programme for Research and Innovation Horizon 2020 under the Marie Skłodowska-Curie Actions Grant Agreement Polynomial Optimization, Efficiency through Moments and Algebra [Grant 813211].

VECTORS OF STATE REGULATION OF COMPETENT APPROACH IN THE EDUCATION SYSTEM OF UKRAINE FROM THE PERSPECTIVE OF JOINING THE EUROPE

The main idea of the competence approach is the formation of education system depending on proposed requirements of society, that is, on the expected result. The content of key competencies includes not only knowledge, but also the willingness to apply knowledge in various situations. Thus, the competence approach allows in the process of education to form a person’s readiness and ability to independently and responsibly solve professional and personal problems related to the ability to acquire and qualitatively use knowledge, applying it in real situations, to develop flexibility, mobility, which contributes to self-development and self-realization personality. Nevertheless, the reality is that in practice, the implementation of the competence approach in the education system acquires, to a greater extent, only a declarative character. In addition, there are large differences in the application of the approach in our country and the countries of the European Union. This indicates the need to find modern vectors of state regulation of the competence approach in education system of Ukraine based on European practices, taking into account our prospects for joining the European Union. The purpose of the article is to study Ukrainian and European ways of implementing the competence approach in the education system. The methodological basis of the research is the methods of logical generalization, systematic analysis and synthesis. The article examines the evolution of the concept of «competence» in education. The key ideas of the competence approach are defined, in particular, the importance of the influence on the development of competences not only of education, but also of family, friends, work, politics, religion, etc. is analyzed. It is the entire set of influencing factors that forms the system of value orientations that become the basis for formation of new competencies. The competence approach is characterized in a systematized form, based on the mission of education. The mechanisms of implementation of the competence approach in education system were studied, in particular, through measures to determine the own achievements of both teachers and students of education. The key positions of the Framework Program of Key Competences for Lifelong Learning by the European Parliament and the Council of the European Union are highlighted. Based on this, the main vectors of the development of the competence approach in the European Union were formed. As a result of the conducted research, it is proposed to start work on a comprehensive state program for the development of key competencies at all levels of education, including both children’s and adult education, which should be based on the requirements of social development, the European integration vector and Ukrainian traditions.

Best Practices for Remediation in Pulmonary and Critical Care Medicine Fellowship Training

BackgroundRemediation of struggling learners in pulmonary and critical care fellowship programs is a challenge, even for experienced medical educators.ObjectiveThis evidence-based narrative review provides a framework program leaders may use to address fellows having difficulty achieving competency during fellowship training.MethodsThe relevant evidence for approaches on the basis of each learner’s needs is reviewed and interpreted in the context of fellowship training in pulmonary medicine and critical care. Issues addressed include bias in fellow assessments and remediation, the impacts of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the specific challenges of pulmonary and critical care fellowship programs, a brief review of relevant legal issues, guidance on building and leveraging program resources, and a discussion of learner outcomes.ResultsThis results in a concise, evidence-based toolkit for program leaders based around four pillars: early identification, fellow assessment, collaborative intervention, and reassessment. Important concepts also include the need for documentation, clear and written communication, and fellow-directed approaches to the creation of achievable goals.ConclusionEvidence-based remediation helps struggling learners in pulmonary and critical care fellowship to improve their ability to meet Accreditation Council for Graduate Medical Education (ACGME) milestones.

A 3D particle-based simulation of heat and mass transfer behavior in the EAGLE ID1 in-pile test

The ID1 test was the final target test of the EAGLE experimental framework program. It was used to verify that during a core disruptive accident, the molten fuel could be discharged via wall failure of an inner duct in FAIDUS, a design concept for the sodium-cooled fast reactor. The ID1 results revealed that the wall failure behavior owed to the large heat flow from the surrounding fuel/steel mixture. The present study numerically investigated the heat transfer mechanisms in the test using the finite volume particle method in the three-dimensional domain. The thermal hydraulic behaviors during wall failure were reproduced reasonably. The present three-dimensional simulation mitigated inherent defects of our previous two-dimensional calculation and clarified that the solid fuel and liquid steel close to the outer surface of the duct can expose the duct to high thermal loads, resulting in the wall failure.

Mechanisms and Features of Academic Career Development in Universities

The article emphasizes the importance of creating and implementing policies at the national and institutional levels for the development of an academic career in the context of European integration processes. On the basis of a comparative analysis of national and European policies, the essence and components of academic career development in universities are revealed, attention is focused on the need to reform domestic higher education in the context of Ukraine's integration into the European Research Area.
 It was established that the main features of an academic career are stages, external and internal factors of influence and planning. An academic career is considered as a certain type of professional activity in the field of higher education and science, in which the formation, development and development of researchers, disclosure of research potential, achievement of established quantitative and qualitative requirements for research, successful promotion through certain steps (positions), acquisition of high social status and authority in the academic sphere.
 It was determined that the mechanisms of the academic career include evaluation (criteria: publication activity, quality and results of research, social influence and reputation, expert activity, research ethics and integrity, teaching based on research and innovation), academic mobility (participation in framework programs , projects and other EU initiatives, strengthening the research capacity of universities), support and motivation (the presence of structural units and developed policies in the university to meet the needs of researchers in support at the beginning of their careers, improving research competence, leadership and communication skills, mastering digital technologies).

Experiences of Adolescents with Cancer Attending a Tertiary Care Cancer Centre: A Thematic Analysis.

Adolescents with cancer experience several psychosocial concerns. Cancer among adolescents contributes to one-fifth of cancers in India. Most of the published empirical literature on adolescents' views about their cancer experience is from high-income countries.The objectives of the study were to explore the experiences of adolescents with cancer in India. Twenty-eight adolescents were purposively recruited and participated in prospectively conducted qualitative interviews conducted at the Tata Memorial Hospital, Mumbai, between 2013 and 2015. Interview data were transcribed and analysed using Braun and Clarke's reflexive thematic analysis. Two themes and several subthemes were generated during the analysis. The transition to the new reality of illness was traumatic. It embodied fear about the unknown, disease and symptoms. The experience was isolating and disfigurement further led to peer separation. Inadequate information made the adolescents anxious and worried, and children and parents experienced moments of severe distress. The love and support received from parents, siblings and extended family facilitated positive coping. Peer support was reassuring and enabled them to have a normalising experience. Discovering their inner strength, acceptance of the situation and faith in God made them resilient and hopeful. Adolescents with cancer experience significant emotional concerns, which are often unexplored and unaddressed. An adolescent-specific communication framework and psychosocial programme contextual to the Indian setting may be developed based on the study findings.

Incremental prognostic value of acute serum biomarkers for functional outcome after traumatic brain injury (CENTER-TBI): an observational cohort study

Several studies have reported an association between serum biomarker values and functional outcome following traumatic brain injury. We aimed to examine the incremental (added) prognostic value of serum biomarkers over demographic, clinical, and radiological characteristics and over established prognostic models, such as IMPACT and CRASH, for prediction of functional outcome. We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study. We included patients aged 14 years or older who had blood sampling within 24 h of injury, results from a CT scan, and outcome assessment according to the Glasgow Outcome Scale-Extended (GOSE) at 6 months. Amounts in serum of six biomarkers (S100 calcium-binding protein B, neuron-specific enolase, glial fibrillary acidic protein, ubiquitin C-terminal hydrolase L1 [UCH-L1], neurofilament protein-light, and total tau) were measured. The incremental prognostic value of these biomarkers was determined separately and in combination. The primary outcome was the GOSE 6 months after injury. Incremental prognostic value, using proportional odds and a dichotomised analysis, was assessed by delta C-statistic and delta R2 between models with and without serum biomarkers, corrected for optimism with a bootstrapping procedure. Serum biomarker values and 6-month GOSE were available for 2283 of 4509 patients. Higher biomarker levels were associated with worse outcome. Adding biomarkers improved the C-statistic by 0·014 (95% CI 0·009-0·020) and R2 by 4·9% (3·6-6·5) for predicting GOSE compared with demographic, clinical, and radiological characteristics. UCH-L1 had the greatest incremental prognostic value. Adding biomarkers to established prognostic models resulted in a relative increase in R2 of 48-65% for IMPACT and 30-34% for CRASH prognostic models. Serum biomarkers have incremental prognostic value for functional outcome after traumatic brain injury. Our findings support integration of biomarkers-particularly UCH-L1-in established prognostic models. European Union's Seventh Framework Programme, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences, and NeuroTrauma Sciences.

Anti-transparency within the EU shift to open science

Abstract In 2014, the European Commission initiated a process to strengthen science 2.0 as a core research policy concept. However, this turned into a substantial ideational shift. The concept of science 2.0 was dropped. Instead, open science became established as one of the three pillars of the €94 billion research framework programme Horizon Europe. This article scrutinises the official narrative regarding the shift of concepts, identifying transparency issues, specifically misrepresentation of concepts and data, and the redaction of key material. This can be characterised as problems of input legitimacy. A public consultation did take place, but numerous transparency issues can be found. From science 2.0 to open science, the ideational shift was portrayed as simply a matter of exchanging two synonymous concepts. However, science 2.0 is a descriptive concept referring to science being transformed by digitalisation. In contrast, open science involves normative assumptions about how science should work and be governed.

Challenges in the implementation of responsible research and innovation across Horizon 2020

ABSTRACT In the last decade, the European Commission (EC) developed an ambitious strategy to promote RRI across the Horizon 2020 Framework Programme for Research and Innovation (H2020). This effort resulted in a significant number of European-funded projects that substantially expanded the available knowledge of the theory, methods and implementation of RRI. However, various evaluations and studies revealed a limited and diffuse implementation of the concept. In this article, we aim to shed some light on this matter with a study covering eight programme lines of H2020 (ERC, MSCA, LEIT, FOOD, ENV, SEC, WIDENING and EURATOM). We employ an extensive policy document analysis and 112 semi-structured interviews carried out with various stakeholders. We argue that the limited implementation of RRI in H2020 is the result of conflicts with existing values, science cultures, economic objectives, restricted resources for its implementation and a lack of clarification around what RRI means.