From the creation of the European research area in 2000 to a Mission on cancer in Europe in 2021-lessons learned and implications.

In the year 2000, cancer research in Europe had the potential to make a difference as it had several unique strengths, such as a strong foundation in biomedical science, good patient registries, infrastructures that spanned from biological repositories to bioinformatic hubs as well as thriving Comprehensive Cancer Centers (CCCs) and basic/preclinical cancer research institutions of high international standing. Research, however, was fragmented and lacked coordination. As a result, Europe could not harness its potential for translating basic research discoveries into a clinical setting for the patients' benefit. What was needed was a paradigm shift in cancer research that addressed the translational research continuum. Along these lines, in 2000, European Union (EU) Commissioner Philippe Busquin established the European Research Area (ERA) and in 2002 the European Cancer Research Area (ECRA), and their political approval was a powerful catalyst for the increased involvement of scientists in science policy in the EU. In this report, we briefly describe the actions embraced by the cancer community and cancer organizations in response to Busquin's proposals that led to the creation of the EU Mission on Cancer (MoC) in Horizon 2020 in 2021.

Culturable mycobiota of drinking water in Göteborg (Sweden) in comparison to Ljubljana (Slovenia) with implications on human health.

The European Union currently has no specific regulations on fungi in water. The only country where fungi are listed as the parameter is Sweden, with the maximal number of 100 CFU per 100 mL. The present study thus compared culturable mycobiota from Swedish drinking water with Slovenian, which has no specific requirements for fungi. Fungi were isolated with up to 38 CFU/L from 75% of Swedish samples. The most common were the genera Varicosporellopsis (27.3%), Paracremonium (14.5%), and black yeasts Cadophora, Cyphellophora, and Exophiala (18.2%). Using the same sampling and isolation methods, 90% of tap water samples in Slovenia were positive for fungi, with Aspergillus spp. (46%), Aureobasidium melanogenum (36%), and Exophiala spp. (24%) being the most common. The observed differences between countries are likely the consequence of geographical location, the use of different raw water sources, and water treatment methods. However, the core species and emerging fungi Aspergillus fumigatus, Candida parapsilosis sensu stricto, Exophiala phaeomuriformis, Bisifusarium dimerum, and Rhodotorula mucilaginosa were isolated in both studies. These findings point out the relevance of tracking the presence of emerging fungi with known effects on health in drinking water and encourage further studies on their transmission from raw water sources to the end-users.

The EU-funded I3LUNG Project: Integrative Science, Intelligent Data Platform for Individualized LUNG Cancer Care With Immunotherapy.

Although immunotherapy (IO) has changed the paradigm for the treatment of patients with advanced non-small cell lung cancers (aNSCLC), only around 30% to 50% of treated patients experience a long-term benefit from IO. Furthermore, the identification of the 30 to 50% of patients who respond remains a major challenge, as programmed Death-Ligand 1 (PD-L1) is currently the only biomarker used to predict the outcome of IO in NSCLC patients despite its limited efficacy. Considering the dynamic complexity of the immune system-tumor microenvironment (TME) and its interaction with the host's and patient's behavior, it is unlikely that a single biomarker will accurately predict a patient's outcomes. In this scenario, Artificial Intelligence (AI) and Machine Learning (ML) are becoming essential to the development of powerful decision-making tools that are able to deal with this high-complexity and provide individualized predictions to better match treatments to individual patients and thus improve patient outcomes and reduce the economic burden of aNSCLC on healthcare systems. I3LUNG is an international, multicenter, retrospective and prospective, observational study of patients with aNSCLC treated with IO, entirely funded by European Union (EU) under the Horizon 2020 (H2020) program. Using AI-based tools, the aim of this study is to promote individualized treatment in aNSCLC, with the goals of improving survival and quality of life, minimizing or preventing undue toxicity and promoting efficient resource allocation. The final objective of the project is the construction of a novel, integrated, AI-assisted data storage and elaboration platform to guide IO administration in aNSCLC, ensuring easy access and cost-effective use by healthcare providers and patients.

Evaluating comprehensive cancer networks; a review of standards and evaluation methods for care networks to inform a comparison with the OECI comprehensive cancer network standards.

INTRODUCTION: To ensure that all citizens have equal access to high-quality cancer diagnosis and care, the EU4Health Programme, Europe's Beating Cancer Plan, and Horizon Europe's Cancer Mission propose Comprehensive Cancer Infrastructures in every European Union Member State. It is therefore important to establish the basic principles for high-performing cancer networks and a methodology for evaluating their quality and effectiveness. This article describes methods and standards/indicators for network evaluation found in literature, gives a comparative overview of the new OECI European Cancer Network Quality standards, and proposes principles for evaluating the performance of Comprehensive Cancer Networks as a basis for continuous improvement. MATERIALS AND METHODS: We performed a scoping literature review on methods and standards/indicators for care-network evaluation. We then compared the OECI set with literature findings, categorised standards that were similar, reflected on standards that were different, and deduced principles for quality standards for cancer networks. RESULTS: Of 1002 articles identified, 17 reported on evaluation methods and/or (mostly) qualitative indicators. Sixteen studies described indicators/standards for evaluating care networks, critical success factors or desirable outcomes. Of the 54 present OECI standards, 32 had a literature equivalent. No literature equivalent was found for 22 standards, especially on those related to the combination of care and research. The proposed OECI evaluation methods (survey, document review, and interviews) were all reported in the literature. From the conformity of these results, we deduced 8 principles for standards evaluating the effectiveness of Comprehensive Cancer Networks. CONCLUSIONS: Research on the evaluation of the effectiveness of care networks is scarce. Evaluation methods vary and are often single time-point assessments. The OECI set contributes to establishing clear principles and standards to evaluate the effectiveness of Comprehensive Cancer Networks.

[Analysis of the legal framework on food supplements for menopause in Spanish community pharmacies]. / Análisis del marco legal sobre complementos alimenticios para la menopausia en farmacias comunitarias españolas.

OBJECTIVE: To analyze the legal framework for the marketing of specific food supplements prescribed and indicated for menopause symptoms, so that it is verified if according to the effects on health that they produce, should be considered in the category of food supplements, or in others included in our legal system. METHOD: An exhaustive review of the legal frameworks applicable to food supplements used both in Spain and in Europe, collecting those aspects that are related to legal concepts such as the definition of medicine for human use, medicine based on medicinal plants, or the so-called "frontier products". RESULTS: There is a large number of products that can be called "frontier products", they can fit into different product categories, they can fit into different product categories, since some of the plants in their formulation are also authorized for use as industrial medicines or medicines based on traditional medicinal plants. CONCLUSIONS: There are currently specific food supplements for menopause that raise reasonable doubts about their inclusion in other legal categories, both as medicines for human use, or as herbal medicines, so the legislator would need to enable more agile mechanisms and more frequent reviews of the new certainties that science finds, and that can change the status of these products.

Resveratrol Food Supplement Products and the Challenges of Accurate Label Information to Ensure Food Safety for Consumers.

The food supplement market is growing as many consumers wish to complement their nutrient intake. Despite all the regulations in place to ensure food supplements safety, there are still many cases of irregularities reported especially connected to internet sales. Twenty resveratrol food supplement products sold on the Slovenian market were evaluated on their compliance of declared vs. determined resveratrol content, as well as the compliance of labels with the European Union (EU) and Slovenian regulatory requirements. Both the ingredient contents and food information are important parts of food safety. Analyses of 20 food supplements performed using high-performance thin-layer chromatography (HPTLC) coupled with densitometry showed that 95% of products had contents different from what was declared and 55% of products contained higher contents than declared. In 25% of the products the determined content per unit exceeded the maximum level (150 mg/day) specified in EU novel food conditions for food supplement with trans-resveratrol. Evaluation of the 20 food supplement labels included mandatory and voluntary food information, food supplement information, novel food information, health claims and nutrition claims. Most labels contained the necessary information, but multiple errors were observed ranging from typos to misleading practices. From a food safety perspective there is still a lot of improvement needed in the field of food supplements.

Evaluation of effects-based methods as monitoring tools for assessing ecological impacts of metals in aquatic ecosystems.

Effects-based methods (EBMs) are considered part of a more integrative strategy for regulating substances of concern under the European Union Water Framework Directive. In general, EBMs have been demonstrated as useful indicators of effects on biota, although links to population and community-level effects are sometimes uncertain. When EBMs are sufficiently specific and sensitive, and links between measured endpoints and apical or higher level effects are established, they can be a useful tool in assessing effects from a specific toxicant or class of toxicants. This is particularly valuable for toxicants that are difficult to measure and for assessing the effects of toxicant mixtures. This paper evaluates 12 EBMs that have been proposed for potential use in the assessment of metals. Each EBM was evaluated with respect to metal specificity and sensitivity, sensitivity to other classes of toxicants, and the strength of the relationship between EBM endpoints and effects observed at the whole organism or population levels of biological organization. The evaluation concluded that none of the EBMs evaluated meet all three criteria of being sensitive to metals, insensitive to other classes of toxicants, and a strong indicator of effects at the whole organism or population level. Given the lack of suitable EBMs for metals, we recommended that the continued development of mixture biotic ligand models (mBLMs) may be the most effective way to achieve the goal of a more holistic approach to regulating metals in aquatic ecosystems. Given the need to further develop and validate mBLMs, we suggest an interim weight-of-evidence approach that includes mBLMs, macroinvertebrate community bioassessment, and measurement of metals in key macroinvertebrate species. This approach provides a near-term solution and simultaneously generates data needed for the refinement and validation of mBLMs. Once validated, it should be possible to rely primarily on mBLMs as an alternative to EBMs for metals. Integr Environ Assess Manag 2023;19:24-31.  © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Quality Requirements for Medicinal Cannabis and Respective Products in the European Union - Status Quo.

Medicinal cannabis and respective products have been available in EU member states as single-patient prescriptions without regular marketing authorizations for a couple of years. The Netherlands was the first member state to realize this; in the meantime other member states have followed. Today, aside from the Netherlands, Germany is the most important market for such products. The regulatory framework for the approval of medicinal cannabis and its distribution to patients in the EU member states is, however, not harmonized at all, and there are distinct national regulations. Regarding the quality of such products, the general requirements for herbal medicinal products as defined in the European Pharmacopoeia, national pharmacopoeias, and the EMA guidance documents in place beside GMP requirements in the EU are applicable. However, for a couple of aspects, every EU member state follows its own interpretation of these requirements. To facilitate free distribution of such products between EU member states in future and to harmonize requirements for quality and GMP, an EU-wide approach is needed. As a first step, this should be realized by implementing monographs for cannabis medicinal products in the European Pharmacopoeia.

Opportunities and hurdles to European market access for multi-herbal traditional Chinese medicine products: An analysis of EU regulations for combination herbal medicinal products.

TCM herbal remedies are popular among European patients. However, a very limited number of TCM products have been approved as herbal medicinal products (HMPs) in Europe. Multi-herbal TCM products, the most prevalent form of medication in TCM practice, are even rare. This indicates multi-herbal TCM products are facing considerable obstacles in the access to EU market. To further identify such obstacles, we make a systematic analysis of current advances in both EU herbal monographs and combination HMPs granted in member states and present main features of the regulation as well as challenges for multi-herbal TCM products. The results show the EU is open to combination HMPs based on TCM or other non-European traditions. The regulation allows appropriate flexibility in the range of drug extraction rations, variation in concentrations of extraction solvent and number of herbal drugs presented in the product, if plausible pharmacological effects could be justified. Meanwhile, to guarantee the safety and efficacy based on medicinal usage, especially to justify the rationale or plausibility of the combination, is the key element for well-established use or traditional use combination HMPs. Additionally, EU herbal monographs also have great value in their marketing procedure. Nonetheless, there are many challenges in the European market access of multi-herbal TCM products which lies in quality control, safety and efficacy evaluation and others e.g., practical standard for full marketing authorization. Enforced scientific research and communication among research institutions, industries and authorities are necessary to further facilitate the access of multi-herbal TCM products to EU market. The results of this article may provide guidance for HMPs based on TCM or other non-European traditions with intention to entering EU market.

Impact assessment of the EU import ban on Indonesian palm oil: Using environmental extended multi-scale MRIO.

Under the Renewable Energy Directive (RED) II, the EU will phase out the use of palm oil for biodiesel feedstock. Environmental concerns are the main reasons for the EU to implement this initiative. This study analyzes the economic and environmental impact of EU import ban to Indonesia at provincial level, using 2 scenarios (a direct and direct-indirect import ban). The analysis is performed using a global-subnational Multi-Regional Input-Output (MRIO) with environmental extensions. This study shows that a direct (combined) import ban of palm oil by the EU will reduce Indonesia's GDP by -0.2 % (-0.26 %) and employment by -0.12 % (-0.54 %) from baseline. At provincial level, Riau, North Sumatra, Lampung, Central Kalimantan and South Kalimantan experience the highest impact on their domestic product (more than -0.5 %). Under a direct import ban, job losses mostly happen in outside Java (96.26 %) and in the oilseeds sector (75.21 %). Low and middle skilled jobs decline more than high skilled jobs and count for 95 % of the total loss. This study also shows that a direct (combined) import ban reduces national GHG emissions by -0.19 % (-0.24 %) and total land use by -0.48 % (-0.6 %). Potential carbon sequestration can be 34.55 (42.27) million tons C equivalent to 149.74 (182.67) million tons CO2e under assumption a full rewilding from the reduction of land use in oilseed. Our study shows that an EU import ban on Indonesian palm oil has relatively small economic and environmental impacts at national and provincial level. Yet, this policy can create potential carbon sequestration that can absorb CO2 by vegetation and soil.

Review: Bioavailability of trace elements in farm animals: definition and practical considerations for improved assessment of efficacy and safety.

Currently, the authorisation procedure of trace elements as feed additives in the European Union according to Regulation (EC) No. 1831/2003 does not consider the bioavailability of trace element sources. This manuscript provides framework conditions for in vivo experiments that aim to estimate differences in the relative bioavailability between supplements of essential trace elements. Framework conditions encompass necessary technical information on the test substance, the experimental design and diet composition as well as the suitability of status parameters that allow for relative comparisons of regression variables. This manuscript evolves recommendations for researchers to conduct solid and reliable experiments on the matter as well as decision makers to interpret the value of studies submitted with authorisation applications regarding a certain trace element supplement.

Bridging the (Brexit) divide: Effects of a brief befriending meditation on affective polarization.

The European Union Brexit referendum has divided the British electorate, with high levels of animosity between those who affiliate with the Remain side (Remainers) and the Leave side (Leavers) of the debate. Previous research has shown that a brief befriending meditation reduces affective polarization among Democrats and Republicans in the United States, but the results have not been replicated in a non-US sample and the psychological mechanisms underlying the effects have yet to be examined. The present study therefore used a post-test only randomized controlled design to investigate the effects of a brief befriending meditation on affective polarization among Remainers and Leavers (n = 922). Results showed that participants in the befriending condition scored modestly lower on affective polarization than participants in the attentional control condition (t(921) = 2.17, p = .030, d = 0.14) and that perceived commonality with the political outgroup mediated the effects. In sum, audio-guided befriending practices may be a highly scalable means to reduce high levels of affective polarization through increasing perceived commonality.

The European Union's development assistance for health (DAH) in Vietnam: any other purposes than health improvement?

Development Assistance for health (DAH) has increased dramatically these last two decades. While according to the official rhetoric, it aims at 'health improvement' and 'poverty reduction', such apolitical purposes have been questioned by scholars who identified other major objectives. However, few studies have sought to uncover the motivations behind EU's health assistance.To fill such academic gap, this article explores the main drivers that have guided the EU's DAH in Vietnam where the EU celebrated in 2020 its 25 years of health cooperation. Opting for a 'multiple sources of foreign aid model' that considers that no single factor can explain foreign aid decision, and adopting a 'holistic approach' that focuses on the modalities, the narratives, the allocation, and the terms of health assistance, as well as the international and domestic contexts in which it has taken place, this study identifies four major purposes: (a) the confirmation of EU's identities within the global health community. (b) the defense of the relevance of its approach of health assistance to influence international norms framing international health aid, (c) its support to the leading role of the WHO in global health, and (d) the facilitation of trade and investment opportunities for European companies.

Geographical authentication of virgin olive oil by GC-MS sesquiterpene hydrocarbon fingerprint: Verifying EU and single country label-declaration.

According to the last report from the European Union (EU) Food Fraud Network, olive oil tops the list of the most notified products. Current EU regulation states geographical origin as mandatory for virgin olive oils, even though an official analytical method is still lacking. Verifying the compliance of label-declared EU oils should be addressed with the highest priority level. Hence, the present work tackles this issue by developing a classification model (PLS-DA) based on the sesquiterpene hydrocarbon fingerprint of 400 samples obtained by HS-SPME-GC-MS to discriminate between EU and non-EU olive oils, obtaining an 89.6% of correct classification for the external validation (three iterations), with a sensitivity of 0.81 and a specificity of 0.95. Subsequently, multi-class discrimination models for EU and non-EU countries were developed and externally validated (with three different validation sets) with successful results (average of 92.2% of correct classification for EU and 96.0% for non-EU countries).

Vaccine Liability in the Light of Covid-19: A Defence of Risk-Benefit.

Vaccines have played an essential role in advancing medical treatment in the twentieth and twenty-first centuries. However, no medical intervention is risk free, and vaccines are no exception to that rule. This article considers how lawyers have confronted or eschewed risk-benefit in the context of determining defectiveness in vaccine liability, with emphasis on the UK, European Union, and US experiences. It explores the potential role that risk-benefit may play in assessing liability for vaccines against the COVID-19 pandemic. It argues that a holistic, flexible approach to determining defectiveness embracing risk-benefit allows consideration of the overwhelming public interest derived from the continued availability and supply of vaccines, as well as immunity conferring benefits on both the individual and the community. If cases do emerge concerning the liability of a COVID-19 vaccine, immunity conferring benefits on both the individual and the community of the COVID-19 vaccines should be relevant in any determination of defectiveness. Such a holistic, flexible approach to defectiveness embracing risk-benefit can be used effectively to determine the entitled safety of a vaccine and may help to mitigate against the dangers of weakening confidence in the public's vaccine uptake.

Pesticide residues in honeybee-collected pollen: does the EU regulation protect honeybees from pesticides?

Researchers globally identify pesticides as one of the main reasons for pollinator decline. In the European Union (EU), extensive legislation is implemented to protect pollinators from harmful pesticide exposure. The aim of our study was to discover whether the pesticide residue levels in honeybee matrices, such as nectar and pollen, exceeded the chronic or acute toxicity levels when beehives were located next to fields treated with specific insecticides. The insecticides were used according to the EU legislation and its national implementation. The experiments were conducted in turnip rape, oilseed rape, and caraway fields in southern Finland during the years 2019 and 2020. The pesticides used in the experiments contained the active substances lambda-cyhalothrin (2019), esfenvalerate (2020), and tau-fluvalinate (2020). However, the honeybee-collected pollen and nectar were analyzed for residues of more than 100 active substances. The results showed that the pesticide residue levels clearly remained under the oral acute toxicity for honeybees, although we found high levels of thiacloprid residues in the pollen collected in 2019. The pesticide residues in nectar were below LOQ values, which was most likely due to the rainy weather conditions together with the chosen sampling method. No statistically significant differences were observed between the insecticide-treated and untreated fields. In light of our research, the EU legislation protected honeybees from oral acute toxicity during the years 2019 and 2020. However, potential sublethal effects of thiacloprid and other pesticide compounds found in the collected pollen cannot be ruled out. In the future, constant monitoring of pesticide exposure of honeybees and wild pollinators should be established to ensure that pesticide legislation, and its implementation across the EU successfully protects pollinators and their services in agricultural environments.

The need for European harmonization of Nutrivigilance in a public health perspective: a comprehensive review.

According to the European Union regulation, some countries have established a pre-market notification system for food supplements while others have not. As this regulation is unfulfilled, a notified and marketed food supplement ingredient in one country may be forbidden in another. Even though food supplements shall not be placed on the market if unsafe, some products may still expose the consumers to risks. The risk is increased by easier access due to worldwide dissemination fostered by the internet and free movement of goods in the European Union. The Rapid Alert System for Food and Feed and the Emerging Risks Exchange Network are described. To date, the European Union legislation does not include a provision to establish a dedicated vigilance system for food supplements (Nutrivigilance). Six European Union countries have nevertheless set up national systems, which are presented. The present lack of European Union data collection harmonization, does not allow easy cooperation between countries. This article advocates for creating a coordinated European Nutrivigilance System to detect and scrutinize adverse effects of food supplements. This, to help in directing science-based risk assessments and reinforce the science-based decision of policy makers to improve public health safety.

[Enlightenment of international pharmacovigilance system on establishment of pharmacovigilance system of Chinese medicine].

Pharmacovigilance system is an extension of the original adverse drug reactions monitoring and reporting system as well as an internationally recognized basic system that must be matched with the whole life cycle supervision of drugs. European Union(EU)pharmacovigilance system, World Health Orgnization(WHO) Uppsala Monitoring Center system and ICH system are internationally recognized pharmacovigilance systems. They all have their own pharmacovigilance characteristics and could provide guarantee for clinical safe drug use. With the deepening of international communication, pharmacovigilance has also been developed in China. Pharmacovigilance of Chinese medicine is a new concept based on the existing pharmacovigilance system of chemical medicine and the characteristics of Chinese medicine. In ancient China, Chinese medicine also had its own ways of early warning. Ancient medical books have records on the toxicity classification, clinical pharmacovigilance and intoxication rescue of Chinese medicine. With the increase of public recognition of Chinese medicine in recent years, especially since the government issued the 13 th Five-Year Plan for the development of Chinese medicine, the pharmaceutical industry in China has paid more and more attention to the pharmacovigilance of Chinese medicine.However, the pharmacovigilance system of Chinese medicine has not yet been established, and it still needs to be explored and improved.Therefore, it is very necessary to develop the system to standardize pharmacovigilance-related activities of Chinese medicine. In this context, this study analyzed and learned the characteristics of pharmacovigilance systems of EU, ICH, and WHO Uppsala Monitoring Center, so as to provide some enlightenment for the establishment and improvement of pharmacovigilance system of Chinese medicine.

[Big Data in health: a new paradigm to regulate, a challenge for social justice.] / Big Data en salud: Un nuevo paradigma para regular, un desafío para la justicia social.

In addition to the opportunities posed by the use of Big Data in health, it also generates important challenges in the field of research, especially from the point of view of its management and ethical considerations. The European Union has been promoting different initiatives that allow the exploitation of this data in the context of the knowledge economy. The UNESCO Ethics Committee has identified three ethical principles to take into account regarding the application of Big Data in Health: independence, privacy and justice. The protection of privacy and patient safety is questioned in a context where cybersecurity is far to be complete. In addition, an imbalance in the exploitation of these data by the public and private sectors could generate inequalities that would represent a significant problem of social justice. This article follows a qualitative methodology based on the documentary analysis of current legislative texts, especially the recently approved General Data Protection Regulation (GDPR), as well as non-legislative documents of projects and parliamentary communications throughout the last two legislatures, with the aim of analyzing them and evaluating how they conform to the principles outlined by UNESCO, especially with respect to the principle of social justice. The most representative national projects that have started to be adopted are also reviewed.

Además de las oportunidades que supone el uso de Big Data en salud, también genera desafíos importantes en el campo de la investigación, especialmente desde el punto de vista de su gestión y de las consideraciones éticas. La Unión Europea ha estado promoviendo diferentes iniciativas que permitan la explotación de estos datos en el contexto de la economía del conocimiento. El Comité de Ética de la UNESCO ha identificado tres principios éticos a tener en cuenta sobre la aplicación de Big Data en Salud: independencia, privacidad y justicia. La protección de la privacidad y la seguridad de los pacientes se cuestiona en un contexto en el que la ciberseguridad está lejos de ser completa. Además, un desequilibrio en la explotación de estos datos por parte de los sectores público y privado podría generar inequidades que significarían un problema importante de justicia social. Este artículo sigue una metodología cualitativa basada en el análisis documental de los textos legislativos vigentes, especialmente el recientemente aprobado reglamento general de protección de datos (RGPD), así como documentos no legislativos de proyectos y comunicaciones parlamentarias a lo largo de las dos últimas legislaturas, con el objetivo es analizarlas y evaluar cómo se ajustan a los principios esbozados por la UNESCO, especialmente con respecto al principio de justicia social. También se revisan los proyectos nacionales más representativos que han empezado a adoptarse.