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STUDY QUESTION Would the different regulatory approaches for preimplantation genetic testing (PGT) in Europe permit the implementation of preimplantation genetic testing using polygenic risk scores (PGT-P)? SUMMARY ANSWER While the regulatory approaches for PGT differ between countries, the space provided for potential implementation of PGT-P seems limited in all three regulatory models. WHAT IS KNOWN ALREADY PGT is a reproductive genetic technology that allows the testing for hereditary genetic disorders and chromosome abnormalities in embryos before implantation. Throughout its history, PGT has largely been regarded as an ethically sensitive technology. For example, ethical questions have been raised regarding the use of PGT for adult-onset conditions, non-medical sex selection, and human leukocyte antigen typing for the benefit of existing siblings. Countries in which PGT is offered each have their own approach of regulating the clinical application of PGT, and a clear overview of legal and practical regulation of PGT in Europe is lacking. An emerging development within the field of PGT, namely PGT-P, is currently bringing new ethical tensions to the forefront. It is unclear whether PGT-P may be applied within the current regulatory frameworks in Europe. Therefore, it is important to investigate current regulatory frameworks in Europe and determine whether PGT-P fits within these frameworks. STUDY DESIGN, SIZE, DURATION The aim of this study was to provide an overview of the legal and practical regulation of the use of PGT in seven selected European countries (Belgium, France, Germany, Italy, the Netherlands, Spain, and the UK) and critically analyse the different approaches with regards to regulatory possibilities for PGT-P. Between July and September 2023, we performed a thorough and extensive search of websites of governments and governmental agencies, websites of scientific and professional organizations, and academic articles in which laws and regulations are described. PARTICIPANTS/MATERIALS, SETTING, METHODS We investigated the legal and regulatory aspects of PGT by analysing legal documents, regulatory frameworks, scientific articles, and guidelines from scientific organizations and regulatory bodies to gather relevant information about each included country. The main sources of information were national laws relating to PGT. MAIN RESULTS AND THE ROLE OF CHANCE We divided the PGT regulation approaches into three models. The regulation of PGT differs per country, with some countries requiring central approval of PGT for each new indication (the medical indication model: the UK, the Netherlands), other countries evaluating each individual PGT request at the local level (the individual requests model: France, Germany), and countries largely leaving decision-making about clinical application of PGT to healthcare professionals (the clinical assessment model: Belgium, Italy, Spain). In the countries surveyed that use the medical indication model and the individual requests model, current legal frameworks and PGT criteria seem to exclude PGT-P. In countries using the clinical assessment model, the fact that healthcare professionals and scientific organizations in Europe are generally negative about implementation of PGT-P due to scientific and socio-ethical concerns, implies that, even if it were legally possible, the chance that PGT-P would be offered in the near future might be low. LIMITATIONS, REASONS FOR CAUTION The results are based on our interpretation of publicly available written information and documents, therefore not all potential discrepancies between law and practice might have been identified. In addition, our analysis focuses on seven—and not all—European countries. However, since these countries are relevant players within PGT in Europe and since they have distinct PGT regulations, the insights gathered give relevant insights into diverse ways of PGT regulation. WIDER IMPLICATIONS OF THE FINDINGS To the best of our knowledge, this is the first paper that provides a thorough overview of the legal and practical regulation of PGT in Europe. Our analysis of how PGT-P fits within current regulation models provides guidance for healthcare professionals and policymakers in navigating the possible future implementation of PGT-P within Europe. STUDY FUNDING/COMPETING INTEREST(s) This project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 813707. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Developments in prenatal testing allow the detection of more findings. SNP arrays in prenatal diagnosis (PND) can be analyzed at 0.5 Mb resolution detecting more clinically relevant anomalies, or at 5 Mb resolution. We investigated whether women had sufficient knowledge to make informed choices regarding the scope of their prenatal test that were consistent with their attitude. Pregnant women could choose between testing at 5 or at 0.5 Mb array. Consenting women (N = 69) received pre-test genetic counseling by phone and filled out the Measure of Informed Choice questionnaire designed for this study. Choices based on sufficient knowledge and consistent with attitude were considered informed. Sixty-two percent of the women made an adequately informed choice, based on sufficient knowledge and attitude-consistent with their choice of microarray resolution. Women who made an informed choice, opted for 0.5 Mb array resolution more often. There were no differences between women making adequately informed or less informed choices regarding level of experienced anxiety or doubts. Over time on T0 and T1, anxiety and doubts significantly decreased. While previous studies demonstrated that knowledge is an important component in informed decision-making, this study underlines that a consistent attitude might be equally important for decision-making. We advocate more focus on attitude-consistency and deliberation as compared to only a strong focus on knowledge. [ABSTRACT FROM AUTHOR]

Abstract Background Companies are currently marketing personal genome tests directly-to-consumer that provide genetic susceptibility testing for a range of multifactorial diseases simultaneously. As these tests comprise multiple risk analyses for multiple diseases, they may be difficult to evaluate. Insight into morally relevant differences between diseases will assist researchers, healthcare professionals, policy-makers and other stakeholders in the ethical evaluation of personal genome tests. Discussion In this paper, we identify and discuss four disease characteristics - severity, actionability, age of onset, and the somatic/psychiatric nature of disease - and show how these lead to specific ethical issues. By way of illustration, we apply this framework to genetic susceptibility testing for three diseases: type 2 diabetes, age-related macular degeneration and clinical depression. For these three diseases, we point out the ethical issues that are relevant to the question whether it is morally justifiable to offer genetic susceptibility testing to adults or to children or minors, and on what conditions. Summary We conclude that the ethical evaluation of personal genome tests is challenging, for the ethical issues differ with the diseases tested for. An understanding of the ethical significance of disease characteristics will improve the ethical, legal and societal debate on personal genome testing.

Abstract Background As genetics technology proceeds, practices of genetic testing have become more heterogeneous: many different types of tests are finding their way to the public in different settings and for a variety of purposes. This diversification is relevant to the discourse on ethical, legal and societal issues (ELSI) surrounding genetic testing, which must evolve to encompass these differences. One important development is the rise of personal genome testing on the basis of genetic profiling: the testing of multiple genetic variants simultaneously for the prediction of common multifactorial diseases. Currently, an increasing number of companies are offering personal genome tests directly to consumers and are spurring ELSI-discussions, which stand in need of clarification. This paper presents a systematic approach to the ELSI-evaluation of personal genome testing for multifactorial diseases along the lines of its test characteristics. Discussion This paper addresses four test characteristics of personal genome testing: its being a non-targeted type of testing, its high analytical validity, low clinical validity and problematic clinical utility. These characteristics raise their own specific ELSI, for example: non-targeted genetic profiling poses serious problems for information provision and informed consent. Questions about the quantity and quality of the necessary information, as well as about moral responsibilities with regard to the provision of information are therefore becoming central themes within ELSI-discussions of personal genome testing. Further, the current low level of clinical validity of genetic profiles raises questions concerning societal risks and regulatory requirements, whereas simultaneously it causes traditional ELSI-issues of clinical genetics, such as psychological and health risks, discrimination, and stigmatization, to lose part of their relevance. Also, classic notions of clinical utility are challenged by the newer notion of 'personal utility.' Summary Consideration of test characteristics is essential to any valuable discourse on the ELSI of personal genome testing for multifactorial diseases. Four key characteristics of the test - targeted/non-targeted testing, analytical validity, clinical validity and clinical utility - together determine the applicability and the relevance of ELSI to specific tests. The paper identifies and discusses four areas of interest for the ELSI-debate on personal genome testing: informational problems, risks, regulatory issues, and the notion of personal utility.

Aims: Healthcare professionals are relevant stakeholders because of their gatekeeper role in the clinic. This study aims to explore their perspectives on the potential future clinical implementation of the bio-artificial pancreas (BAP) for people with type 1 diabetes, and suitable target groups., Methods: Semi-structured interviews were conducted with 17 healthcare professionals, including endocrinologists, nurses, and pancreas transplant surgeons. Inclusion was stopped once data saturation was reached. The audiotaped interviews were transcribed verbatim. Qualitative content analysis using an inductive approach was conducted to develop themes within a coding framework., Results: Three main themes emerged: (1) hoped-for benefits, which included improved clinical outcomes, enhanced sense of normality, reduced mental burden for patients and their significant others, greater societal participation, and lower costs; (2) concerns, which included safety and effectiveness, inequitable access, accurate information, control over self-management, and organizational challenges; and (3) allocating the BAP during initial implementation, which included prioritizing people who lack effective treatment options, people with mental health issues, and vulnerable people., Conclusions: The results of this study are important for researchers and practitioners involved in the development of the BAP, so that they can align its design and the process of clinical implementation with healthcare professionals' perspectives., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dide de Jongh reports financial support was provided by European Commission. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Whole genome sequencing (WGS) of a tumour may sometimes reveal additional potential targets for medical treatment. Practice variation in the use of WGS is therefore a source of unequal access to targeted therapies and, as a consequence, of disparities in health outcomes. Moreover, this may even be more significant if patients seek access to WGS by paying a relatively limited amount of money out of pocket, and sometimes effectively buy themselves a ticket to (very) expensive publicly funded treatments. Should resulting unequal access to WGS be considered unfair? Drawing from current practice in the Dutch healthcare system, known as egalitarian, we argue that differences in employment of WGS between hospitals are the consequence of the fact that medical innovation and its subsequent uptake inevitably takes time. Consequently, temporal inequalities in access can be deemed acceptable, or at least tolerated, because and insofar as, ultimately, all patients benefit. However, we argue against allowing a practice of out-of-pocket payments for WGS in publicly funded healthcare systems, for four reasons: because allowing private spending favours patients with higher socio-economic status significantly more than practice variation between hospitals does, may lead to displacement of publicly funded health care, does not help to ultimately benefit all, and may undermine the solidaristic ethos essential for egalitarian healthcare systems., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Eline Bunnik is a member of the Data Access Board of the Hartwig Medical Foundation, a non-profit national DNA sequencing centre in the Netherlands for cancer diagnosis and research. As a member of the Data Access Board, Eline reviews requests for access to the research database maintained by the Hartwig Medical Foundation, from research groups around the world., (Copyright © 2024. Published by Elsevier Ltd.)

The shortage of organs for transplantations is increasing in Europe as well as globally. Many initiatives to the organ shortage, such as opt-out systems for deceased donation and expanding living donation, have been insufficient to meet the rising demand for organs. In recurrent discussions on how to reduce organ shortage, financial incentives and removal of disincentives, have been proposed to stimulate living organ donation and increase the pool of available donor organs. It is important to understand not only the ethical acceptability of (dis)incentives for organ donation, but also its societal acceptance. In this review, we propose a research agenda to help guide future empirical studies on public preferences in Europe towards the removal of disincentives and introduction of incentives for organ donation. We first present a systematic literature review on public opinions concerning (financial) (dis)incentives for organ donation in European countries. Next, we describe the results of a randomized survey experiment conducted in the United States. This experiment is crucial because it suggests that societal support for incentivizing organ donation depends on the specific features and institutional design of the proposed incentive scheme. We conclude by proposing this experiment's framework as a blueprint for European research on this topic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ambagtsheer, Bunnik, Pengel, Reinders, Elias, Lacetera and Macis.)

Epigenetic research has brought several important technological achievements, including identifying epigenetic clocks and signatures, and developing epigenetic editing. The potential military applications of such technologies we discuss are stratifying soldiers' health, exposure to trauma using epigenetic testing, information about biological clocks, confirming child soldiers' minor status using epigenetic clocks, and inducing epigenetic modifications in soldiers. These uses could become a reality. This article presents a comprehensive literature review, and analysis by interdisciplinary experts of the scientific, legal, ethical, and societal issues surrounding epigenetics and the military. Notwithstanding the potential benefit from these applications, our findings indicate that the current lack of scientific validation for epigenetic technologies suggests a careful scientific review and the establishment of a robust governance framework before consideration for use in the military. In this article, we highlight general concerns about the application of epigenetic technologies in the military context, especially discrimination and data privacy issues if soldiers are used as research subjects. We also highlight the potential of epigenetic clocks to support child soldiers' rights and ethical questions about using epigenetic engineering for soldiers' enhancement and conclude with considerations for an ethical framework for epigenetic applications in the military, defense, and security contexts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Duke University School of Law, Harvard Law School, Oxford University Press, and Stanford Law School.)

The field of transplantation has witnessed the emergence of Advanced Therapy Medicinal Products (ATMPs) as highly promising solutions to address the challenges associated with organ and tissue transplantation. ATMPs encompass gene therapy, cell therapy, and tissue-engineered products, hold immense potential for breakthroughs in overcoming the obstacles of rejection and the limited availability of donor organs. However, the development and academic research access to ATMPs face significant bottlenecks that hinder progress. This opinion paper emphasizes the importance of addressing bottlenecks in the development and academic research access to ATMPs by implementing several key strategies. These include the establishment of streamlined regulatory processes, securing increased funding for ATMP research, fostering collaborations and partnerships, setting up centralized ATMP facilities, and actively engaging with patient groups. Advocacy at the policy level is essential to provide support for the development and accessibility of ATMPs, thereby driving advancements in transplantation and enhancing patient outcomes. By adopting these strategies, the field of transplantation can pave the way for the introduction of innovative and efficacious ATMP therapies, while simultaneously fostering a nurturing environment for academic research., Competing Interests: Authors MM, KP-K, and PK were employed by Kugelmeiers Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Piemonti, Scholz, de Jongh, Kerr-Conte, van Apeldoorn, Shaw, Engelse, Bunnik, Mühlemann, Pal-Kutas, Scott, Magalon, Kugelmeier and Berishvili.)

Background: Genomic research on neurodevelopmental disorders (NDDs), particularly involving minors, combines and amplifies existing research ethics issues for biomedical research. We performed a review of the literature on the ethical issues associated with genomic research involving children affected by NDDs as an aid to researchers to better anticipate and address ethical concerns., Results: Qualitative thematic analysis of the included articles revealed themes in three main areas: research design and ethics review, inclusion of research participants, and communication of research results. Ethical issues known to be associated with genomic research in general, such as privacy risks and informed consent/assent, seem especially pressing for NDD participants because of their potentially decreased cognitive abilities, increased vulnerability, and stigma associated with mental health problems. Additionally, there are informational risks: learning genetic information about NDD may have psychological and social impact, not only for the research participant but also for family members. However, there are potential benefits associated with research participation, too: by enrolling in research, the participants may access genetic testing and thus increase their chances of receiving a (genetic) diagnosis for their neurodevelopmental symptoms, prognostic or predictive information about disease progression or the risk of concurrent future disorders. Based on the results of our review, we developed an ethics checklist for genomic research involving children affected by NDDs., Conclusions: In setting up and designing genomic research efforts in NDD, researchers should partner with communities of persons with NDDs. Particular attention should be paid to preventing disproportional burdens of research participation of children with NDDs and their siblings, parents and other family members. Researchers should carefully tailor the information and informed consent procedures to avoid therapeutic and diagnostic misconception in NDD research. To better anticipate and address ethical issues in specific NDD studies, we suggest researchers to use the ethics checklist for genomic research involving children affected by NDDs presented in this paper.

Biomedical research aimed at the development of therapies for chronic and late-onset conditions increasingly concentrates on the early treatment of symptom-less disease. This broad trend is evidenced in prominent shifts in contemporary dementia research. Revised diagnostic criteria and new approaches to clinical trials propose a focus on earlier stages of disease and prompt concerns about the implications of communicating test results associated with the risk of developing dementia when no effective treatments are available. This article examines expectations of the implications of learning test results related to dementia risk, based on focus group research conducted in the UK and Spain. It points to the extended social and temporal aspects of the dementia risk experience. Three key dimensions of this risk experience are elaborated: living 'at risk', represented in efforts to reduce risk and plan for the future; 'with risk', through vigilance towards cognitive health and earlier or prolonged contact with healthcare services; and finally, 'beyond risk' through a cessation of the self in its current social, legal and financial form. A virtual abstract of this paper can be viewed at: https://www.youtube.com/channel/UC_979cmCmR9rLrKuD7z0ycA., (© 2018 Foundation for the Sociology of Health & Illness.)

In clinical trials which target pathophysiological mechanisms associated with Alzheimer's disease, research participants who are recruited based on biomarker test results should be informed about their increased risk of developing Alzheimer's dementia. This paper presents the results of a qualitative focus group study of attitudes and concerns toward learning information about biomarker-based risk status among healthy research participants in the United Kingdom and Spain and people with dementia and their supporters/caregivers from countries represented in the European Working Group of People with Dementia of Alzheimer Europe. The study identified expectations related to learning risk status and preferences related to the content, quality, and follow-up of the disclosure process. The latter emphasize distinctions between risk and diagnoses, the importance of clear information about risk, and suggestions for risk reduction, as well as expectations for follow up and support. The implications of these preferences for practice are discussed. Providing details of research participants' experience and views may serve as a guide for the development of processes for the responsible disclosure of Alzheimer's disease biomarkers.

Genetic, epidemiological and experimental evidence suggest that the major histocompatibility complex (MHC) is critical in controlling human immunodeficiency virus (HIV) infection. The objectives of this study were to determine whether novel recombinant Mamu MHC constructs would elicit protection against rectal challenge with heterologous simian-human immunodeficiency virus (SHIV) strain SF162.P4 in rhesus macaques. Mamu class I and II gene products were linked together with HIV gp140, simian immunodeficiency virus (SIV) p27 and heat-shock protein 70 to dextran. The vaccine was administered to two groups, each consisting of nine macaques, either subcutaneously (SC), or rectally and boosted by SC immunization. The controls were untreated or adjuvant-treated animals. Repetitive rectal challenges with up to ten doses of SHIV SF162.P4 showed a significant decrease in the peak and sequential viral RNA concentrations, and three macaques remained uninfected, in the nine SC-immunized animals, compared with infection in all nine controls. Macaques immunized rectally followed by SC boosters showed a less significant decrease in both sequential and peak viral loads compared with the SC-immunized animals, and all were infected following rectal challenge with SHIV SF162.P4. Plasma and mucosal IgG and IgA antibodies to Mamu class I alleles and HIV gp120, as well as to RANTES (regulated upon activation, normal T-cell expressed, and secreted; CCR5) were increased, and showed significant inverse correlations with the peak viral load. These results suggested that allo-immunization with recombinant MHC constructs linked to HIV-SIV antigens merits further investigation in preventing HIV-1 infection.

We evaluated the ability of intravenous immunoglobulin (IVIG) to diminish immune hyperactivation, which is considered a major cause of CD4+ T cell loss during chronic HIV-1 infection and whether this affected CD4+ T cell counts and plasma HIV-1 RNA (pVL). Therefore, we treated six chronically HIV-1-infected, antiretroviral-therapy-naive patients with IVIG (0.4 g/kg) at weeks 0 and 4, with a follow-up of 12 weeks after the second dosage during which pVL, T cell numbers, and T cell activation were measured. At baseline median CD4+ T cell counts were 300 (range 200-460) x 10(6)/liter and median pVL was 5.0 (range 3.2-5.2) log10 copies/ml. IgG plasma levels peaked during the first days after administration. We observed a decrease in the percentage of activated (CD38+ HLA-DR+) CD4+ and CD8+ T cells [3.5% (range 1-7%) and 5% (1-10%), respectively (p = 0.027)], but no effect on the fraction of proliferating CD4+ or CD8+ T cells as measured by Ki67 expression. CD4+ T cell counts were significantly increased on day 4 (median +55 cells, range 0-150, p = 0.043). pVL was significantly increased on day 1 after IVIG infusion (median +0.13 log10, range 0.01-0.55, p = 0.028). All these parameters returned to baseline levels within 1 week after infusion. In conclusion, administration of IVIG caused a temporary decrease in T cell activation and an increase in CD4+ T cell counts, despite an increase in pVL. Our results support the hypothesis that T cell activation, rather than direct HIV-1 infection, mediates the loss of CD4+ T cells and suggest that immunomodulating therapy in HIV-1 infection could indeed be effective.