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Background: Exposomics, the study of the exposome, is flourishing, but the field is not well defined. The term "exposome" refers to all environmental influences and associated biological responses throughout the lifespan. However, this definition is very similar to that of the term "environment"-the external elements and conditions that surround and affect the life and development of an organism. Consequently, the exposome seems to be nothing more than a synonym for the environment, and exposomics a synonym for environmental research. As a result, some have rebranded their "standard" environmental health research with the neologistic exposome term, whereas others ignore or seek to abandon the seemingly redundant concept of the exposome., Objectives: We argue that exposomics needs to sharpen its mission focus to counteract this apparent redundancy. Exposomics should be defined as a research program in environmental health aimed at enabling a comprehensive and discovery-driven approach to identifying environmental determinants of human health. Similar to the aim of the Human Genome Project, exposomics aims to analyze the complete complexity of exposures and their corresponding biological responses. Exposomics' primary premise is that the existence of undiscovered, potentially interconnected, nongenetic (environmental) risk factors for health necessitates a comprehensive discovery-driven analysis approach., Discussion: We argue that exposomics researchers should adopt our reconceptualization of exposomics and focus on the productiveness and integrity of their research program: its purpose and principles. We suggest that exposomics researchers should coordinate the writing of reviews that assess the program's productiveness and integrity, as well as provide a platform for exposomics researchers to define their vision for the field. https://doi.org/10.1289/EHP14509.

AI-driven brain-computed interfaces aimed at restoring speech for individuals living with locked-in-syndrome are paired with ethical implications for user's autonomy, privacy and responsibility. Embedding options for sufficient levels of user-control in speech-BCI design has been proposed to mitigate these ethical challenges. However, how user-control in speech-BCIs is conceptualized and how it relates to these ethical challenges is underdetermined. In this narrative literature review, we aim to clarify and explicate the notion of user-control in speech-BCIs, to better understand in what way user-control could operationalize user's autonomy, privacy and responsibility and explore how such suggestions for increasing user-control can be translated to recommendations for the design or use of speech-BCIs. First, we identified types of user control, including executory control that can protect voluntariness of speech, and guidance control that can contribute to semantic accuracy. Second, we identified potential causes for a loss of user-control, including contributions of predictive language models, a lack of ability for neural control, or signal interference and external control. Such a loss of user control may have implications for semantic accuracy and mental privacy. Third we explored ways to design for user-control. While embedding initiation signals for users may increase executory control, they may conflict with other aims such as speed and continuity of speech. Design mechanisms for guidance control remain largely conceptual, similar trade-offs in design may be expected. We argue that preceding these trade-offs, the overarching aim of speech-BCIs needs to be defined, requiring input from current and potential users. Additionally, conceptual clarification of user-control and other (ethical) concepts in this debate has practical relevance for BCI researchers. For instance, different concepts of inner speech may have distinct ethical implications. Increased clarity of such concepts can improve anticipation of ethical implications of speech-BCIs and may help to steer design decisions., 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. MV declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 van Stuijvenberg, Samlal, Vansteensel, Broekman and Jongsma.)

Aim: This paper investigates the conditions for inclusive design of regenerative medicine interventions from a bioethical perspective, taking regenerative valve implants as a showcase. Methods: A value hierarchy is construed to translate the value of justice into norms and design requirements for inclusive design of regenerative valve implants. Results: Three norms are proposed and translated into design requirements: regenerative valve implants should be designed to promote equal opportunity to good health for all potential users; equal respect for all potential users should be shown; and the implants should be designed to be accessible to everyone in need. Conclusion: The norms and design requirements help to design regenerative valve implants that are appropriate, respectful and available for everyone in need.

Regenerative Medicine promises to develop treatments to regrow healthy tissues and cure the physical body. One of the emerging developments within this field is regenerative implants, such as jawbone or heart valve implants, that can be broken down by the body and are gradually replaced with living tissue. Yet challenges for embodiment are to be expected, given that the implants are designed to integrate deeply into the tissue of the living body, so that implant and body become one. In this paper, we explore how regenerative implants may affect the embodied experience of implant recipients. To this end, we take a phenomenological approach. First, we explore what insights the existing phenomenological and empirical literature on embodiment offers regarding the experience of illness and of living with regular (non-regenerative) implants and organ transplants. Second, we apply these insights to better understand how future implant recipients might experience living with regenerative implants. Third, we conclude that concepts and considerations from the existing phenomenological literature do not sufficiently address what it might be like to live with an implantable technology that, over time, becomes one with the living body. We argue that the interwovenness and intimate relationship of people living with regenerative implants should be understood in terms of 'entanglement'. Entanglement allows us to explore the complexities of human-technology relations, acknowledging the inseparability of humans and implantable technologies. Our theoretical foundations regarding the role of embodiment may be tested empirically once more people will be living with regenerative implants., (© 2024. The Author(s).)

Background: Clinical decision support systems (CDSSs) based on routine care data, using artificial intelligence (AI), are increasingly being developed. Previous studies focused largely on the technical aspects of using AI, but the acceptability of these technologies by patients remains unclear., Objective: We aimed to investigate whether patient-physician trust is affected when medical decision-making is supported by a CDSS., Methods: We conducted a vignette study among the patient panel (N=860) of the University Medical Center Utrecht, the Netherlands. Patients were randomly assigned into 4 groups-either the intervention or control groups of the high-risk or low-risk cases. In both the high-risk and low-risk case groups, a physician made a treatment decision with (intervention groups) or without (control groups) the support of a CDSS. Using a questionnaire with a 7-point Likert scale, with 1 indicating "strongly disagree" and 7 indicating "strongly agree," we collected data on patient-physician trust in 3 dimensions: competence, integrity, and benevolence. We assessed differences in patient-physician trust between the control and intervention groups per case using Mann-Whitney U tests and potential effect modification by the participant's sex, age, education level, general trust in health care, and general trust in technology using multivariate analyses of (co)variance., Results: In total, 398 patients participated. In the high-risk case, median perceived competence and integrity were lower in the intervention group compared to the control group but not statistically significant (5.8 vs 5.6; P=.16 and 6.3 vs 6.0; P=.06, respectively). However, the effect of a CDSS application on the perceived competence of the physician depended on the participant's sex (P=.03). Although no between-group differences were found in men, in women, the perception of the physician's competence and integrity was significantly lower in the intervention compared to the control group (P=.009 and P=.01, respectively). In the low-risk case, no differences in trust between the groups were found. However, increased trust in technology positively influenced the perceived benevolence and integrity in the low-risk case (P=.009 and P=.04, respectively)., Conclusions: We found that, in general, patient-physician trust was high. However, our findings indicate a potentially negative effect of AI applications on the patient-physician relationship, especially among women and in high-risk situations. Trust in technology, in general, might increase the likelihood of embracing the use of CDSSs by treating professionals., (©Anna G M Zondag, Raoul Rozestraten, Stephan G Grimmelikhuijsen, Karin R Jongsma, Wouter W van Solinge, Michiel L Bots, Robin W M Vernooij, Saskia Haitjema. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 28.05.2024.)

Exposome research is put forward as a major tool for solving the nature-versus-nurture debate because the exposome is said to represent "the nature of nurture." Against this influential idea, we argue that the adoption of the nature-versus-nurture debate into the exposome research program is a mistake that needs to be undone to allow for a proper bioethical assessment of exposome research. We first argue that this adoption is originally based on an equivocation between the traditional nature-versus-nurture debate and a debate about disease prediction/etiology. Second, due to this mistake, exposome research is pushed to adopt a limited conception of agential control that is harmful to one's thinking about the good that exposome research can do for human health and wellbeing. To fully excise the nature-versus-nurture debate from exposome research, we argue that exposome researchers and bioethicists need to think about the exposome afresh from the perspective of actionability. We define the concept of actionability and related concepts and show how these can be used to analyze the ethical aspects of the exposome. In particular, we focus on refuting the popular "gun analogy" in exposome research, returning results to study participants and risk-taking in the context of a well-lived life., (© 2024 The Authors. Bioethics published by John Wiley & Sons Ltd.)

Convergence of neural implants with artificial intelligence (AI) presents opportunities for the development of novel neural implants and improvement of existing neurotechnologies. While such technological innovation carries great promise for the restoration of neurological functions, they also raise ethical challenges. Developers of AI-driven neural implants possess valuable knowledge on the possibilities, limitations and challenges raised by these innovations; yet their perspectives are underrepresented in academic literature. This study aims to explore perspectives of developers of neurotechnology to outline ethical implications of three AI-driven neural implants: a cochlear implant, a visual neural implant, and a motor intention decoding speech-brain-computer-interface. We conducted semi-structured focus groups with developers (n = 19) of AI-driven neural implants. Respondents shared ethically relevant considerations about AI-driven neural implants that we clustered into three themes: (1) design aspects; (2) challenges in clinical trials; (3) impact on users and society. Developers considered accuracy and reliability of AI-driven neural implants conditional for users' safety, authenticity, and mental privacy. These needs were magnified by the convergence with AI. Yet, the need for accuracy and reliability may also conflict with potential benefits of AI in terms of efficiency and complex data interpretation. We discuss strategies to mitigate these challenges., (© 2024. The Author(s).)

Gene drive technologies (GDTs) have been proposed as a potential new way to alleviate the burden of malaria, yet have also raised ethical questions. A central ethical question regarding GDTs relates to whether it is morally permissible to intentionally modify or eradicate mosquitoes in this way and how the inherent worth of humans and non-human organisms should be factored into determining this. Existing analyses of this matter have thus far generally relied on anthropocentric and zoocentric perspectives and rejected an individualist biocentric outlook in which all living organisms are taken to matter morally for their own sake. In this paper, we reconsider the implications of taking a biocentric approach and highlight nuances that may not be evident at first glance. First, we shortly discuss biocentric perspectives in general, and then outline Paul Taylor's biocentric theory of respect for nature. Second, we explore how conflicting claims towards different organisms should be prioritised from this perspective and subsequently apply this to the context of malaria control using GDTs. Our ethical analysis shows that this context invokes the principle of self-defence, which could override the pro tanto concerns that a biocentrist would have against modifying malaria mosquitoes in this way if certain conditions are met. At the same time, the case study of GDTs underlines the relevance of previously posed questions and criticism regarding the internal consistency of Taylor's egalitarian biocentrism., Competing Interests: Competing interests: ALB is a member of the Dutch Senate. NdG and KRJ have no conflicts of interest to declare in relation to this research., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

It may soon become possible not just to replace, but to re-grow healthy tissues after injury or disease, because of innovations in the field of Regenerative Medicine. One particularly promising innovation is a regenerative valve implant to treat people with heart valve disease. These implants are fabricated from so-called 'smart', 'lifelike' materials. Implanted inside a heart, these implants stimulate re-growth of a healthy, living heart valve. While the technological development advances, the ethical implications of this new technology are still unclear and a clear conceptual understanding of the notions 'smart' and 'lifelike' is currently lacking. In this paper, we explore the conceptual and ethical implications of the development of smart lifelike materials for the design of regenerative implants, by analysing heart valve implants as a showcase. In our conceptual analysis, we show that the materials are considered 'smart' because they can communicate with human tissues, and 'lifelike' because they are structurally similar to these tissues. This shows that regenerative valve implants become intimately integrated in the living tissues of the human body. As such, they manifest the ontological entanglement of body and technology. In our ethical analysis, we argue this is ethically significant in at least two ways: It exacerbates the irreversibility of the implantation procedure, and it might affect the embodied experience of the implant recipient. With our conceptual and ethical analysis, we aim to contribute to responsible development of smart lifelike materials and regenerative implants., (© 2023. The Author(s).)

Despite widespread and worldwide efforts to eradicate vector-borne diseases such as malaria, these diseases continue to have an enormous negative impact on public health. For this reason, scientists are working on novel control strategies, such as gene drive technologies (GDTs). As GDT research advances, researchers are contemplating the potential next step of conducting field trials. An important point of discussion regarding these field trials relates to who should be informed, consulted, and involved in decision-making about their design and launch. It is generally argued that community members have a particularly strong claim to be engaged, and yet, disagreement and lack of clarity exist about how this "community" should be defined and delineated. In this paper, we shed light on this "boundary problem": the problem of determining how boundaries of inclusion and exclusion in (GDT) community engagement should be drawn. As our analysis demonstrates, the process of defining and delineating a community is itself normative. First, we explicate why it is important to define and delineate the community. Second, we demonstrate that different definitions of community are used and intermingled in the debate on GDTs, and argue in favor of distinguishing geographical, affected, cultural, and political communities. Finally, we propose initial guidance for deciding who should (not) be engaged in decision-making about GDT field trials, by arguing that the definition and delineation of the community should depend on the rationale for engagement and that the characteristics of the community itself can guide the effective design of community engagement strategies., (© 2023 The Authors. Bioethics published by John Wiley & Sons Ltd.)

Purpose: To explore cataract patients' experiences with an e-health tool for self-assessing visual function (ie, a web-based eye test), and to formulate recommendations for its successful adoption in routine cataract care., Setting: Clinics in the Netherlands, Germany, and Austria., Design: Mixed-methods study., Methods: 22 participants were included in this study; in-depth interviews were conducted with 12. Questionnaires and in-depth semi-structured interviews were conducted alongside a multicenter randomized controlled trial evaluating the validity, safety and cost-effectiveness of remote care after cataract surgery (Cataract Online Refraction Evaluation, a Randomized Controlled Trial). Results were analyzed thematically., Results: Participants reported positively about performing the web-based eye test at home. 4 overarching themes were identified in the interviews. First, participants were inventive in overcoming practical barriers encountered while conducting the test. Second, participants desired a clear presentation of test results and their meaning. Third, the ability to self-monitor visual function was appreciated. Fourth, most participants preferred to keep the option to contact their eyecare professional (ECP) postoperatively, especially when experiencing symptoms. Most would be satisfied with a phone consultation or an e-consult. Participants reported positive experiences with the web-based eye test. Barriers for successful adoption were identified, including insecurity about correctly performing the test, incomplete information on how to interpret test results, and a feeling that in-hospital assessments were superior to remote assessments., Conclusions: It is recommended to focus on building trust in remote eyecare delivery and that access to the ECP be retained when medically indicated or deemed necessary by the patient., (Copyright © 2023 The Author(s).Published by Wolters Kluwer Health, Inc. on behalf of ASCRS and ESCRS.)

It is of paramount importance that healthcare professionals can participate in the academic and societal debate surrounding medical AI. To realise this critical-constructive guidance of AI, it is necessary to be able to distinguish between different types of AI, different applications of AI and to paint the different shades of grey in the current black-and-white debate. This article describes and nuances eight misconceptions that currently dominate the public debate surrounding AI in healthcare. By asking ourselves as healthcare professionals 'what specifically defines our line of work?' we must define what aspects of our occupation we want to have AI either carry out or support, and in what way.

In recent years, exposome research has been put forward as the next frontier for the study of human health and disease. Exposome research entails the analysis of the totality of environmental exposures and their corresponding biological responses within the human body. Increasingly, this is operationalized by big-data approaches to map the effects of internal as well as external exposures using smart sensors and multiomics technologies. However, the ethical implications of exposome research are still only rarely discussed in the literature. Therefore, we conducted a systematic review of the academic literature regarding both the exposome and underlying research fields and approaches, to map the ethical aspects that are relevant to exposome research. We identify five ethical themes that are prominent in ethics discussions: the goals of exposome research, its standards, its tools, how it relates to study participants, and the consequences of its products. Furthermore, we provide a number of general principles for how future ethics research can best make use of our comprehensive overview of the ethical aspects of exposome research. Lastly, we highlight three aspects of exposome research that are most in need of ethical reflection: the actionability of its findings, the epidemiological or clinical norms applicable to exposome research, and the meaning and action-implications of bias., Competing Interests: Conflict of interest statement None declared.

Tissue Engineering (TE) is a branch of Regenerative Medicine (RM) that combines stem cells and biomaterial scaffolds to create living tissue constructs to restore patients' organs after injury or disease. Over the last decade, emerging technologies such as 3D bioprinting, biofabrication, supramolecular materials, induced pluripotent stem cells, and organoids have entered the field. While this rapidly evolving field is expected to have great therapeutic potential, its development from bench to bedside presents several ethical and societal challenges. To make sure TE will reach its ultimate goal of improving patient welfare, these challenges should be mapped out and evaluated. Therefore, we performed a systematic review of the ethical implications of the development and application of TE for regenerative purposes, as mentioned in the academic literature. A search query in PubMed, Embase, Scopus, and PhilPapers yielded 2451 unique articles. After systematic screening, 237 relevant ethical and biomedical articles published between 2008 and 2021 were included in our review. We identified a broad range of ethical implications that could be categorized under 10 themes. Seven themes trace the development from bench to bedside: (1) animal experimentation, (2) handling human tissue, (3) informed consent, (4) therapeutic potential, (5) risk and safety, (6) clinical translation, and (7) societal impact. Three themes represent ethical safeguards relevant to all developmental phases: (8) scientific integrity, (9) regulation, and (10) patient and public involvement. This review reveals that since 2008 a significant body of literature has emerged on how to design clinical trials for TE in a responsible manner. However, several topics remain in need of more attention. These include the acceptability of alternative translational pathways outside clinical trials, soft impacts on society and questions of ownership over engineered tissues. Overall, this overview of the ethical and societal implications of the field will help promote responsible development of new interventions in TE and RM. It can also serve as a valuable resource and educational tool for scientists, engineers, and clinicians in the field by providing an overview of the ethical considerations relevant to their work. Impact statement To our knowledge, this is the first time that the ethical implications of Tissue Engineering (TE) have been reviewed systematically. By gathering existing scholarly work and identifying knowledge gaps, this review facilitates further research into the ethical and societal implications of TE and Regenerative Medicine (RM) and other emerging biomedical technologies. Moreover, it will serve as a valuable resource and educational tool for scientists, engineers, and clinicians in the field by providing an overview of the ethical considerations relevant to their work. As such, our review may promote successful and responsible development of new strategies in TE and RM.

The rise of precision medicine has led to an unprecedented focus on human biological material in biomedical research. In addition, rapid advances in stem cell technology, regenerative medicine and synthetic biology are leading to more complex human tissue structures and new applications with tremendous potential for medicine. While promising, these developments also raise several ethical and practical challenges which have been the subject of extensive academic debate. These debates have led to increasing calls for longitudinal governance arrangements between tissue providers and biobanks that go beyond the initial moment of obtaining consent, such as closer involvement of tissue providers in what happens to their tissue, and more active participatory approaches to the governance of biobanks. However, in spite of these calls, such measures are being adopted slowly in practice, and there remains a strong tendency to focus on the consent procedure as the tool for addressing the ethical challenges of contemporary biobanking. In this paper, we argue that one of the barriers to this transition is the dominant language pervading the field of human tissue research, in which the provision of tissue is phrased as a 'donation' or 'gift', and tissue providers are referred to as 'donors'. Because of the performative qualities of language, the effect of using 'donation' and 'donor' shapes a professional culture in which biobank participants are perceived as passive providers of tissue free from further considerations or entitlements. This hampers the kind of participatory approaches to governance that are deemed necessary to adequately address the ethical challenges currently faced in human tissue research. Rather than reinforcing this idea through language, we need to pave the way for the kind of participatory approaches to governance that are being extensively argued for by starting with the appropriate terminology., (© 2022. The Author(s).)

Background: The perspectives of researchers and patients regarding roles and responsibilities in stem cell research are rarely studied, but these could offer insights about responsible research conduct. Method: We have conducted a qualitative study consisting of focus groups with both early- (n = 7) and late-career stem cell researchers (n = 11) that are primarily based in Europe, and with Dutch patients with chronic lower back pain (n = 9). These focus groups have been analyzed thematically. Results: Four themes were identified: 1) roles and responsibilities in the laboratory, 2) responsibilities of and toward patients and the public, 3) the role of regulation and 4) structural hurdles for responsibility. Discussion: The results suggest that responsible research conduct could be improved by addressing grant application procedures, publication pressure and by providing support of dissemination activities for researchers. Conclusion: Responsibility in stem cell research could be enhanced by embracing open science initiatives and targeted training.

Objective: The James Lind Alliance (JLA) offers a method for better aligning health and care agenda's with the needs of patients, carers and clinicians by bringing them together in a Priority Setting Partnership (PSP). In this paper, we draw attention to crucial lessons learnt when establishing such a shared research agenda., Key Arguments: Having specific strategies and plans in place for maximising dialogic processes in a PSP can help facilitate and maintain trust, innovation and equal inclusion., Conclusion: Eight lessons learnt have been formulated, based on our observations and reflections on the JLA PSP and our expertise on patient participation and participatory research., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective . The aim of this review was to systematically identify the ethical implications of visual neuroprostheses. Approach . A systematic search was performed in both PubMed and Embase using a search string that combined synonyms for visual neuroprostheses, brain-computer interfaces (BCIs), cochlear implants (CIs), and ethics. We chose to include literature on BCIs and CIs, because of their ethically relavant similarities and functional parallels with visual neuroprostheses. Main results . We included 84 articles in total. Six focused specifically on visual prostheses. The other articles focused more broadly on neurotechnologies, on BCIs or CIs. We identified 169 ethical implications that have been categorized under seven main themes: (a) benefits for health and well-being; (b) harm and risk; (c) autonomy; (d) societal effects; (e) clinical research; (f) regulation and governance; and (g) involvement of experts, patients and the public. Significance . The development and clinical use of visual neuroprostheses is accompanied by ethical issues that should be considered early in the technological development process. Though there is ample literature on the ethical implications of other types of neuroprostheses, such as motor neuroprostheses and CIs, there is a significant gap in the literature regarding the ethical implications of visual neuroprostheses. Our findings can serve as a starting point for further research and normative analysis., (Creative Commons Attribution license.)

Competing Interests: Competing interests: None declared.

Background: Gene drive technologies (GDTs) bias the inheritance of a genetic element within a population of non-human organisms, promoting its progressive spread across this population. If successful, GDTs may be used to counter intractable problems such as vector-borne diseases. A key issue in the debate on GDTs relates to what governance is appropriate for these technologies. While governance mechanisms for GDTs are to a significant extent proposed and shaped by professional experts, the perspectives of these experts have not been explored in depth., Methods: A total of 33 GDT experts from different professional disciplines were interviewed to identify, better understand, and juxtapose their perspectives on GDT governance. The pseudonymized transcripts were analyzed thematically., Results: Three main themes were identified: (1) engagement of communities, stakeholders, and publics; (2) power dynamics, and (3) decision-making. There was broad consensus amongst respondents that it is important to engage communities, stakeholders, and publics. Nonetheless, respondents had diverging views on the reasons for doing so and the timing and design of engagement. Respondents also outlined complexities and challenges related to engagement. Moreover, they brought up the power dynamics that are present in GDT research. Respondents stressed the importance of preventing the recurrence of historical injustices and reflected on dilemmas regarding whether and to what extent (foreign) researchers can legitimately make demands regarding local governance. Finally, respondents had diverging views on whether decisions about GDTs should be made in the same way as decisions about other environmental interventions, and on the decision-making model that should be used to decide about GDT deployment., Conclusions: The insights obtained in this interview study give rise to recommendations for the design and evaluation of GDT governance. Moreover, these insights point to unresolved normative questions that need to be addressed to move from general commitments to concrete obligations.

Medical AI is increasingly being developed and tested to improve medical diagnosis, prediction and treatment of a wide array of medical conditions. Despite worries about the explainability and accuracy of such medical AI systems, it is reasonable to assume that they will be increasingly implemented in medical practice. Current ethical debates focus mainly on design requirements and suggest embedding certain values such as transparency, fairness, and explainability in the design of medical AI systems. Aside from concerns about their design, medical AI systems also raise questions with regard to physicians' responsibilities once these technologies are being implemented and used. How do physicians' responsibilities change with the implementation of medical AI? Which set of competencies do physicians have to learn to responsibly interact with medical AI? In the present article, we will introduce the notion of forward-looking responsibility and enumerate through this conceptual lens a number of competencies and duties that physicians ought to employ to responsibly utilize medical AI in practice. Those include amongst others understanding the range of reasonable outputs, being aware of own experience and skill decline, and monitoring potential accuracy decline of the AI systems., (© 2021 John Wiley & Sons Ltd.)