Return on investment in science: twenty years of European Commission funded research in Alzheimer's dementia, breast cancer and prostate cancer.

Alzheimer's disease (AD), breast cancer (BC) and prostate cancer (PC) continue to be high in the research and innovation agenda of the European Commission (EC). This is due to their exceptionally large burden to the national health systems, the profound economic effects of opportunity costs attributable to decreased working ability, premature mortality and the ever-increasing demand for both hospital and home-based medical care. Over the last two decades, the EC has been steadily increasing both the number of proposals being funded and the amounts of financial resources being allocated to these fields of research. This trend has continued throughout four consecutive science funding cycles, namely framework programme (FP)5, FP6, FP7 and Horizon 2020 (H2020). We performed a retrospective assessment of the outputs and outcomes of EC funding in AD, BC and PC research over the 1999-2019 period by means of selected indicators. These indicators were assessed for their ability to screen the past, present and future for an array of causal relationships and long-term trends in clinical, epidemiological and public health sphere, while considering also the broader socioeconomic impact of funded research on the society at large. This analysis shows that public-private partnerships with large industry and university-based consortia have led to some of the most impactful proposals being funded over the analysed time period. New pharmaceuticals, small molecules and monoclonal antibodies alike, along with screening and prevention, have been the most prominent sources of innovation in BC and PC, extending patients' survival and enhancing their quality of life. Unlike oncology, dementia drug development has been way less successful, with only minor improvements related to the quality of supportive medical care for symptoms and more sensitive diagnostics, without any ground-breaking disease-modifying treatment(s). Significant progresses in imaging diagnostics and nanotechnology have been largely driven by the participation of medical device industry multinational companies. Clinical trials funded by the EC were conducted, leading to the development of brand-new drug molecules featuring novel mechanisms of action. Some prominent cases of breakthrough discoveries serve as evidence for the European capability to generate cutting-edge technological innovation in biomedicine. Less productive areas of research may be reconsidered as priorities when shaping the new agenda for forthcoming science funding programmes.

Checkmating the Nutri-Score: Will Food Patriotism Prevent the Harmonization of Front-of-Pack Labeling Schemes within the EU?

Front-of-pack labeling schemes are an effective but contested regulatory approach to nudge consumers toward healthy food choices. The Nutri-Score, being implemented by eight European countries, is one of the most elaborated and evidence-based examples. Therefore, the Nutri-Score has been deemed as the front-runner within the European Commission's attempt to harmonize front-of-pack labeling among European Union (EU) member states under its Farm-to-Fork strategy by the end of 2022. However, the endeavor is on the brink of failure because of massive resistance by Mediterranean member states and parts of the food industry capitalizing on patriotic narratives (e.g., "Made in Italy"). This article investigates the Nutri-Score saga from a political and commercial determinants of health lens. It argues that an EU-wide rollout of the label hinges on the specific interplay between political structures and stakeholder agency. As shown, the EU's weak decision-making power has been exploited by the No-Nutri-Score alliance.

The European Kidney Health Alliance (EKHA) and the Decade of the KidneyTM.

The European Kidney Health Alliance (EKHA) is an advocacy organization that defends the case of the kidney patients and the nephrological community at the level of the European Union (EU), and from there, top to bottom, also at the national level of the EU member states and the EU-associated countries. The Decade of the KidneyTM is a global initiative launched by the American Association of Kidney Patients (AAKP) to create greater awareness and organize patient demands for long overdue innovation in kidney care. This article describes the medical and patient burden of kidney disease, the history of EKHA, its major activities and tools for policy action, and the need for innovation of kidney care. We then describe the Decade of the KidneyTM initiative, the rationale behind why EKHA joined this activity to emanate parallel action at the European side, the novel professionalized structure of EKHA, and its immediate targets. The final aim is to align all major stakeholders for an action plan on kidney disease comparable to Europe's successful Beating Cancer Plan, with the additional intent that the EKHA model is applied also by the respective national kidney-related societies to create a broad mobilization at all levels. The ultimate aims are that the EU considers chronic kidney disease (CKD) as a major health and health-economic problem, to consequently have CKD included as a key health research target by the European Commission, and to improve quality of life and outcomes for all kidney patients.

Is the EU chemicals strategy for sustainability a green deal?

A fully integrated Chemicals Strategy for Sustainability (CSS) in respect of chemicals is crucial and must include: • An objective evaluation of the present situation including impacts of 'chemicals of concern' throughout their life cycle, that incorporates sustainability issues. • A framework that facilitates innovation of chemistry-based approaches to tackle each of the key sustainability issues. The EU CSS only addresses adverse impacts and mainly focusses on one aspect of risk assessment, the hazard to humans from individual industrial chemicals. The proposal removes consideration of the nature and amount of exposure, which is a critical determinant of risk. It can be presumed that this is solely to simplify, and hence speed up, regulatory decisions thereby enabling more chemicals to be assessed. The linkage of this proposed approach to address any of the major sustainability issues, such as environmental pollutants is obscure. For example, the well-recognised environmental problems caused by polymers such as plastics are not considered. The proposed change in the assessment methodology lacks any scientific justification and fails to address the sustainability issues the EU and the rest of the world are facing. The authors critically discuss a comprehensive innovative evaluation methodology for the impact of chemicals.

Everyday Digital Literacy Questionnaire for Older Adults: Instrument Development and Validation Study.

BACKGROUND: The need for digital literacy in aging populations is increasing in the digitalizing society. Digital literacy involves the identification, evaluation, and communication of information through various digital devices or relevant programs. OBJECTIVE: The aims of this study were to develop an Everyday Digital Literacy Questionnaire (EDLQ), a digital literacy assessment scale, and subsequently evaluate its psychometric properties using a population of community-dwelling older adults in South Korea. METHODS: The EDLQ was developed using an instrument development design. A nationwide survey was conducted, and the study included 1016 community-dwelling older adults (age ≥60 years). To evaluate the psychometric properties, the participants were randomly divided into 2 groups (n=508 each), and the internal consistency (Cronbach α and McDonald ω), structural validity (exploratory factor analysis and confirmatory factor analysis), hypothesis-testing construct validity using the eHealth Literacy Scale (eHEALS), and measurement invariance were analyzed. RESULTS: Among the initial 30 items of the EDLQ, 22 items with a 3-factor solution had a total explained variance of 77%. The domains included "information and communication" (9 items), "content creation and management" (4 items), and "safety and security" (9 items). Confirmatory factor analysis was conducted with this 3-factor solution (χ2206=345.1; normed χ2206=1.7; comparative fit index=0.997; Tucker-Lewis index=0.997; root-mean-square error of approximation=0.036; standardized root-mean-square residual=0.050; composite reliability=0.903-0.959; average variance extracted=0.699-0.724; R2=0.616-0.773). Hypothesis-testing construct validity with the eHEALS revealed a strong correlation (r=0.75). Cronbach α and McDonald ω coefficients were .98 and 0.98, respectively. The fit indices for measurement invariance, including the configural, metric, and scalar invariance models, demonstrated a satisfactory fit to the data. Our findings suggest that the psychometric properties of the 22-item EDLQ are valid and reliable for assessing digital literacy among older Korean adults. CONCLUSIONS: In this study, we developed a digital literacy measure with strong psychometric properties that made it suitable for assessing the digital literacy of community-dwelling older adults in Korea. To broaden its applicability, however, further assessment of its feasibility for use with different languages and cultures is necessary. Moreover, more empirical research on digital literacy and related factors in older adults can facilitate the development of personalized digital health care services and educational interventions in the digital society.

Artificial intelligence in laboratory medicine: fundamental ethical issues and normative key-points.

The contribution of laboratory medicine in delivering value-based care depends on active cooperation and trust between pathologist and clinician. The effectiveness of medicine more in general depends in turn on active cooperation and trust between clinician and patient. From the second half of the 20th century, the art of medicine is challenged by the spread of artificial intelligence (AI) technologies, recently showing comparable performances to flesh-and-bone doctors in some diagnostic specialties. Being the principle source of data in medicine, the laboratory is a natural ground where AI technologies can disclose the best of their potential. In order to maximize the expected outcomes and minimize risks, it is crucial to define ethical requirements for data collection and interpretation by-design, clarify whether they are enhanced or challenged by specific uses of AI technologies, and preserve these data under rigorous but feasible norms. From 2018 onwards, the European Commission (EC) is making efforts to lay the foundations of sustainable AI development among European countries and partners, both from a cultural and a normative perspective. Alongside with the work of the EC, the United Kingdom provided worthy-considering complementary advice in order to put science and technology at the service of patients and doctors. In this paper we discuss the main ethical challenges associated with the use of AI technologies in pathology and laboratory medicine, and summarize the most pertaining key-points from the guidelines and frameworks before-mentioned.

The process of building European university alliances: a rhizomatic analysis of the European Universities Initiative.

Drawing upon French philosophy, this study offers a novel empirical and conceptual understanding of the newly launched European Universities Initiative. In 2019, higher education institutions across the European Union created 17 new alliances as part of the first pilot phase of the initiative. This is an experiment in European and global higher education. This paper offers a conceptual contribution to the field of higher education studies, making use of a rhizomatic analysis to explore how university alliances build what the European Commission refers to as the 'European universities of the future.' Based on the conceptual reflection and findings from a small-scale empirical study, this paper concludes that the alliances within the European Universities Initiative rely on pre-existing higher education and research partnerships while at the same time experimenting to foster a diversity of institutional forms to achieve the ambitious goal of creating 'European Universities.'

Land use efficiency of functional urban areas: Global pattern and evolution of development trajectories.

The application of last-generation spatial data modelling, integrating Earth Observation, population, economic and other spatially explicit data, enables insights into the sustainability of the global urbanisation processes with unprecedented detail, consistency, and international comparability. In this study, the land use efficiency indicator, as developed in the Sustainable Development Goals, is assessed globally for the first time at the level of Functional Urban Areas (FUAs). Each FUA includes the city and its commuting zone as inferred from statistical modelling of available spatial data. FUAs represent the economic area of influence of each urban centre. Hence, the analysis of land consumption within their boundary has significance in the fields of spatial planning and policy analyses as well as many other research areas. We utilize the boundaries of more than 9,000 FUAs to estimate the land use efficiency between 1990 and 2015, by using population and built-up area data extracted from the Global Human Settlement Layer. This analysis shows how, in the observed period, FUAs in low-income countries of the Global South evolved with rates of population growth surpassing the ones of land consumption. However, in almost all regions of the globe, more than half of the FUAs improved their land use efficiency in recent years (2000-2015) with respect to the previous decade (1990-2000). Our study concludes that the spatial expansion of urban areas within FUA boundaries is reducing compactness of settlements, and that settlements located within FUAs do not display higher land use efficiency than those outside FUAs.

Implementation of the new EU IVD regulation - urgent initiatives are needed to avert impending crisis.

Laboratory medicine in the European Union is at the dawn of a regulatory revolution as it reaches the end of the transition from IVDD 98/79/EC (https://eur-lex.eur-opa.eu/legal-content/EN/TXT/?uri=CELEX%3A31998L0079&qid=1628781352814) to IVDR 2017/746 https://eur-lex.europa.eu/eli/reg/2017/746. Without amendments and contingency plans, implementation of the IVDR in May 2022 will lead the healthcare sector into uncharted waters due to unpreparedness of the EU regulatory infrastructure. Prospective risk analyses were not made by the European Commission, and if nothing happens it can be anticipated that the consequences will impact all stakeholders of the medical test pipeline, may seriously harm patients and may prevent caregivers from making appropriate clinical decisions due to non-availability of medical tests. Finally, it also may discourage manufacturers and academia from developing specialty tests, thereby hampering innovation in medical diagnostic care. We hereby inform laboratory professionals about the imminent diagnostic collapse using testimonies from representative stakeholders of the diagnostic supply chain and from academia developing innovative in-house tests in domains of unmet clinical needs. Steps taken by the EFLM Task Force on European Regulatory Affairs, under the umbrella of the Biomedical Alliance in Europe, will be highlighted, as well as the search for solutions through dialogue with the European Commission. Although we recognize that the IVDR promotes positive goals such as increased clinical evidence, surveillance, and transparency, we need to ensure that the capabilities of the diagnostic sector are not damaged by infrastructural unpreparedness, while at the same time being forced to submit to a growing bureaucratic and unsupportive structure that will not support its "droit d'exister".

Contextual differences considered in the Tunisian ADOLOPMENT of the European guidelines on breast cancer screening.

BACKGROUND: Breast cancer is a common disease in Tunisia and is associated with high mortality rates. The "Instance Nationale de l'Evaluation et de l'Accréditation en Santé" (INEAS) and the Tunisian Society of Oncology decided to develop practice guidelines on the subject. While the development of de novo guidelines on breast cancer screening is a demanding process, guideline adaptation appears more appropriate and context sensitive. The objective of this paper is to describe the adaptation process of the European Guidelines on Breast Cancer Screening and Diagnosis to the Tunisian setting in terms of the methodological process, contextual differences between the source and adoloped guideline, and changes in the recommendations. METHODS: We used the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE)-ADOLOPMENT methodology to prioritize the topic, select the source guideline, and prioritize the questions and the outcomes. Once the source guideline was selected-the European Breast Cancer Guidelines-the European Commission´s Joint Research Centre shared with the project team in Tunisia all relevant documents and files. In parallel, the project team searched for local studies on the disease prevalence, associated outcomes' baseline risks, patients' values and preferences, cost, cost-effectiveness, acceptability, and feasibility. Then, the adoloping panel reviewed the GRADE evidence tables and the Evidence to Decision tables and discussed whether their own judgments were consistent with those from the source guideline or not. They based their judgments on the evidence on health effects, the contextual evidence, and their own experiences. RESULTS: The most relevant contextual differences between the source and adoloped guidelines were related to the perspective, scope, prioritized questions, rating of outcome importance, baseline risks, and indirectness of the evidence. The ADOLOPMENT process resulted in keeping 5 out of 6 recommendations unmodified. One recommendation addressing "screening versus no screening with ultrasound in women with high breast density on mammography screening" was modified from 'conditional against' to 'conditional for either' due to more favorable ratings by the adoloping panel in terms of equity and feasibility. CONCLUSION: This process illustrates both the feasibility of GRADE-ADOLOPMENT approach and the importance of consideration of contextual evidence. It also highlights the value of collaboration with the organization that developed the source guideline.

Reactions of euro area government yields to Covid-19 related policy measure announcements by the European Commission and the European Central Bank.

This paper evaluates the impact of announcements of Covid-19 related monetary and fiscal policy measures by the European Central Bank and the European Commission. Applying an event study, we find that the announcements predominantly affect the government bond yields of more solvent countries such as Germany and the Netherlands. Since this finding mainly holds for the announcements of fiscal measures, we conclude that the investors are primarily concerned about the future fiscal burden that has to be shouldered by those solvent countries within the euro area.

A good career start can open doors: the plusses and minuses of an international graduate student program-a student's perspective.

There are many Ph.D. programs from various funding agencies that provide excellent starts to a scientific career. Multinational Ph.D. positions attract students because they provide students with much-required exposure to the international scientific community at an early stage of the career. For this reason, multinational Ph.D. positions can be considered as a better career opportunity over Ph.D. positions confined to a single country. In addition, these multidisciplinary research programs connect different organizations to deal with the problems of global interest. One of these multi-disciplinary research programs is the viral and bacterial adhesion network training-innovative training network (ViBrANT). ViBrANT is a multifaceted platform that develops the required skillsets in young researchers and thereby also contributes to building a multidisciplinary research community. Is this the only parameter to be considered or are there other factors that can also stimulate one's career development? In this perspective article, I will discuss the key reasons why I chose a multinational Ph.D. program along with the merits of being part of ViBrANT. I also discuss the challenges I faced while moving from India to the United Kingdom.

The fourth edition of the European Network for Health Technology Assessment Forum: highlights and outcomes.

The European Network for Health Technology Assessment (EUnetHTA) organizes an annual Forum with stakeholders to receive feedback on its activities, processes, and outputs produced. The fourth edition of the EUnetHTA Forum brought together representatives of HTA bodies, patient organizations, healthcare professionals (HCPs), academia, payers, regulators, and industry. The aim of this paper is to provide an overview of the highlights presented at the 2019 EUnetHTA Forum, reporting the main items and themes discussed in the plenary panel and breakout sessions. The leading topic was the concept of unmet medical need seen from different stakeholders' perspectives. Breakout sessions covered the joint production of assessment reports and engagement with payers, patients, and HCPs. Synergies, pragmatism, and inclusiveness across Member States and stakeholders were emphasized as leading factors to put in place a collaboration that serves the interest of patients and public health in a truly European spirit.

In AI We Trust: Ethics, Artificial Intelligence, and Reliability.

One of the main difficulties in assessing artificial intelligence (AI) is the tendency for people to anthropomorphise it. This becomes particularly problematic when we attach human moral activities to AI. For example, the European Commission's High-level Expert Group on AI (HLEG) have adopted the position that we should establish a relationship of trust with AI and should cultivate trustworthy AI (HLEG AI Ethics guidelines for trustworthy AI, 2019, p. 35). Trust is one of the most important and defining activities in human relationships, so proposing that AI should be trusted, is a very serious claim. This paper will show that AI cannot be something that has the capacity to be trusted according to the most prevalent definitions of trust because it does not possess emotive states or can be held responsible for their actions-requirements of the affective and normative accounts of trust. While AI meets all of the requirements of the rational account of trust, it will be shown that this is not actually a type of trust at all, but is instead, a form of reliance. Ultimately, even complex machines such as AI should not be viewed as trustworthy as this undermines the value of interpersonal trust, anthropomorphises AI, and diverts responsibility from those developing and using them.

Novel indicators to better monitor the collection and recovery of (critical) raw materials in WEEE: Focus on screens.

Currently, in the European Union (EU), e-waste chain performance is assessed by technical indicators that aim to ensure system compliance with collection and recovery targets set by the WEEE Directive. This study proposes indicators to improve WEEE flow monitoring beyond the current overall weight-based approach, including complementary flows and treatment performance. A case study focused on the screen category in France is presented. In 2017, the collection rate of cathode-ray tube screens (CRT) was 68%, while for flat panel display (FPD) generated only 14% was collected. CRT screens have less precious and critical materials than FDP. Thus, elements like cobalt and gold highly concentrated in FPD, have a collection rate two to four times lower than elements such as copper (37%) which represents a high proportion in CRTs. Recycling is the main treatment in France. Nevertheless, the recycling rate per element varies significantly due to the low collection, and also the lack of technology and/or secondary raw materials market. The elements with higher recycling rates are base metals such as copper (28%), followed by precious metals like silver (23%), and gold (13%). Except for palladium, the recycling rate of the critical raw materials targeted in the study ranged from 6% (cobalt) to 0% (e.g. neodymium and indium). The results stress the need for indicators to support the development of WEEE chain from waste management to secondary (critical) raw materials suppliers.

The EFSA Health Claim on Olive Oil Polyphenols: Acid Hydrolysis Validation and Total Hydroxytyrosol and Tyrosol Determination in Italian Virgin Olive Oils.

The health claims of olive oil represent an important marketing lever in raising the willingness to pay for a product, but world producers of extra virgin olive oil (EVOO) do not take advantage of it because there are still obstacles to their use. Among these, one issue is the lack of an official method for determination of all free and linked forms derived from secoiridoidic structures of hydroxytyrosol and tyrosol. In this study, different acidic hydrolytic procedures for analyzing the linked forms were tested. The best method was validated and then applied to more than 100 EVOOs. The content of oleuropein and ligstroside derivatives in EVOOs was indirectly evaluated comparing the amount of phenols before and after hydrolysis. After acidic hydrolysis, a high content of total tyrosol was found in most of the EVOOs. The use of a suitable corrective factor for the evaluation of hydroxytyrosol allows an accurate determination only using pure tyrosol as a standard. Further knowledge on the concentration of total hydroxytyrosol will assist in forecasting the resistance of oils against aging, its antioxidant potential and to better control its quality over time.

In House Validated UHPLC Protocol for the Determination of the Total Hydroxytyrosol and Tyrosol Content in Virgin Olive Oil Fit for the Purpose of the Health Claim Introduced by the EC Regulation 432/2012 for "Olive Oil Polyphenols".

An ongoing challenge in olive oil analytics is the development of a reliable procedure that can draw the consensus of all interested parties regarding the quantification of concentrations above the required minimum value of 5 mg of bioactive "olive oil polyphenols" per 20 g of the oil, to fulfill the health claim introduced by the European Commission (EC) Regulation 432/2012. An in-house validated ultra-high performance liquid chromatography (UHPLC) protocol fit for this purpose is proposed. It relies on quantification of the total hydroxytyrsol (Htyr) and tyrosol (Tyr) content in the virgin olive oil (VOO) polar fraction (PF) before and after acidic hydrolysis of their bound forms. PF extraction and hydrolysis conditions were as previously reported. The chromatographic run lasts ~1/3 of the time needed under high performance liquid chromatography (HPLC) conditions, this was also examined. Eluent consumption for the same piece of information was 6-fold less. Apart from being cost effective, a larger number of samples can be analyzed daily with less environmental impact. Two external curves, detection at 280 nm and correction factors for molecular weight difference are proposed. The method, which is fit for purpose, is selective, robust with satisfactory precision (percentage relative standard deviation (%RSD) values < 11%) and recoveries higher than 87.6% for the target analytes (Htyr, Tyr). Standard operational procedures are easy to apply in the olive oil sector.

Toward a Harmonized and Standardized Protocol for the Determination of Total Hydroxytyrosol and Tyrosol Content in Virgin Olive Oil (VOO). The Pros of a Fit for the Purpose Ultra High Performance Liquid Chromatography (UHPLC) Procedure.

Τoward a harmonized and standardized procedure for the determination of total hydroxytyrosol and tyrosol content in virgin olive oil (VOO), the pros of a recently published in house validated ultra high performance liquid chromatography (UHPLC) protocol are discussed comparatively with those of other procedures that determine directly or indirectly the compounds hosted under the health claim on "olive oil polyphenols" (EC regulation 432/2012). Authentic VOOs were analyzed with five different liquid chromatographic separation protocols and 1H-NMR one in five different laboratories with expertise in VOO phenol analysis within three months. Data comparison indicated differences in absolute values. Method comparison using appropriate tools (Passing-Bablok regression and Bland Altman analyses) for all protocols vs. the UHPLC one indicated slight or statistically significant differences. The results were also discussed in terms of cost effectiveness, detection means, standard requirements and ways to calculate the total hydroxytyrosol and tyrosol content. Findings point out that the in-house validated fit for the purpose UHPLC protocol presents certain pros that should be exploited by the interested parties. These are the simplicity of sample preparation, fast elution time that increase the number of samples analyzed per day and integration of well-resolved peaks with the aid of only two commercially available external standards. Importance of correction factors in the calculations is stressed.

European Union implementation of Article 5.3 of the Framework Convention on Tobacco Control.

BACKGROUND: Article 5.3 of the World Health Organization's Framework Convention on Tobacco Control (FCTC) requires Parties to the agreement to take proactive measures to protect health policy from the vested interests of the tobacco industry. Parties to the FCTC are required to submit periodic reports to the Convention Secretariat on the efforts undertaken to implement it. Previous analyses of national compliance with the FCTC suggest that Article 5.3 implementation is piecemeal and insufficient in many contexts, with governments relying on general transparency and other existing policies for the purpose of Article 5.3 implementation. No in-depth study of Article 5.3 compliance within the European Union (EU) - a signatory to the Convention - has been undertaken. This study seeks to assess the extent of Article 5.3 compliance in European Union institutions, through an analysis of the mechanisms in place in the European Commission and European Parliament. It analyses EU documents relevant to Article 5.3 compliance, as well as semi-structured interviews with policy actors in the EU institutions and the field of tobacco control. RESULTS: As with many national governments, Article 5.3 compliance within EU institutions is partial and incomplete. Much of the compliance activity cited in EU reports is derived from general codes of conduct for EU staff and the Juncker Commission's transparency agenda. Interview respondents reveal widespread lack of knowledge about the existence of the FCTC and Article 5.3 amongst key policy actors across the institutions. Within the Commission policies vary greatly between Directorates General, and issues surrounding the conceptualisation of the role of Members of the European Parliament affect implementation in that context. While there is growing awareness of the issue in both the Commission and the Parliament, in large part as a result of the experience of lobbying over the Tobacco Products Directive, there remains considerable resistance in both institutions to further substantive action to implement Article 5.3. CONCLUSIONS: We recommend that a binding and comprehensive policy and code of conduct, specifically designed for the implementation of Article 5.3 and based on the World Health Organization's guidelines, be created to cover the activities of all employees of all EU institutions. Crucially, such guidelines would need to deal explicitly with third parties acting for the tobacco industry.