Ethical, Legal, and Social Implications of Gene-Environment Interaction Research.

Many complex disorders are impacted by the interplay of genetic and environmental factors. In gene-environment interactions (GxE), an individual's genetic and epigenetic makeup impacts the response to environmental exposures. Understanding GxE can impact health at the individual, community, and population levels. The rapid expansion of GxE research in biomedical studies for complex diseases raises many unique ethical, legal, and social implications (ELSIs) that have not been extensively explored and addressed. This review article builds on discussions originating from a workshop held by the National Institute of Environmental Health Sciences (NIEHS) and the National Human Genome Research Institute (NHGRI) in January 2022, entitled: "Ethical, Legal, and Social Implications of Gene-Environment Interaction Research." We expand upon multiple key themes to inform broad recommendations and general guidance for addressing some of the most unique and challenging ELSI in GxE research. Key takeaways include strategies and approaches for establishing sustainable community partnerships, incorporating social determinants of health and environmental justice considerations into GxE research, effectively communicating and translating GxE findings, and addressing privacy and discrimination concerns in all GxE research going forward. Additional guidelines, resources, approaches, training, and capacity building are required to further support innovative GxE research and multidisciplinary GxE research teams.

The Moral Psychology of Artificial Intelligence.

Moral psychology was shaped around three categories of agents and patients: humans, other animals, and supernatural beings. Rapid progress in artificial intelligence has introduced a fourth category for our moral psychology to deal with: intelligent machines. Machines can perform as moral agents, making decisions that affect the outcomes of human patients or solving moral dilemmas without human supervision. Machines can be perceived as moral patients, whose outcomes can be affected by human decisions, with important consequences for human-machine cooperation. Machines can be moral proxies that human agents and patients send as their delegates to moral interactions or use as a disguise in these interactions. Here we review the experimental literature on machines as moral agents, moral patients, and moral proxies, with a focus on recent findings and the open questions that they suggest.

Prenatal and preimplantation testing for monogenic kidney disorders.

In recent years, advances in genetic sequencing techniques and the analysis of sequencing data have significantly improved our ability to diagnose genetic kidney diseases. Identification of the disease-causing genetic variant(s) is crucial not only for prognostication and personalized management, but also for providing genetic counseling and guiding family planning decisions. It is particularly important that patients desiring children receive advice on their reproductive choices early, ideally before conception. This concise review focuses on the options available for prenatal and preimplantation genetic testing in the context of monogenic kidney diseases, including the latest progress and the legal and ethical issues associated with these reproductive technologies. Although these tests could be performed for all monogenic disorders where the disease-causing variant(s) has been identified in the index patient, invasive prenatal testing is currently primarily performed for severe childhood-onset monogenic kidney disorders. Non-invasive prenatal diagnosis for monogenic disorders is a rapidly developing field that promises to provide an accurate and acceptable alternative to invasive procedures once several technical challenges have been addressed. Preimplantation genetic testing allows for the selection and implantation of embryos free from the disease-causing genetic variants, significantly lowering the risk of affected pregnancies. This option is becoming more popular among individuals with monogenic kidney diseases, particularly those with disorders that manifest later in life, such as autosomal dominant polycystic kidney disease. This review covers the procedure, its outcomes, and the technical, ethical and legal challenges of preimplantation genetic testing for monogenic kidney diseases.

The Genetic Discrimination Observatory: confronting novel issues in genetic discrimination.

Genetic discrimination (GD) is the differential or unfair profiling of an individual on the basis of genetic data. This article summarizes the actions of the Genetic Discrimination Observatory (GDO) in addressing GD and recent developments in GD since late 2020. It shows how GD can take many forms in today's rapidly evolving society.

The Emergence and Global Spread of Noninvasive Prenatal Testing.

Since its introduction in 2011, noninvasive prenatal testing (NIPT) has spread rapidly around the world. It carries numerous benefits but also raises challenges, often related to sociocultural, legal, and economic contexts. This article describes the implementation of NIPT in nine countries, each with its own unique characteristics: Australia, Canada, China and Hong Kong, India, Israel, Lebanon, the Netherlands, the United Kingdom, and the United States. Themes covered for each country include the structure of the healthcare system, how NIPT is offered, counseling needs and resources, and cultural and legal context regarding disability and pregnancytermination. Some common issues emerge, including cost as a barrier to equitable access, the complexity of decision-making about public funding, and a shortage of appropriate resources that promote informed choice. Conversely, sociocultural values that underlie the use of NIPT vary greatly among countries. The issues described will become even more challenging as NIPT evolves from a second-tier to a first-tier screening test with expanded use.

Perception of Polish patients with cancer of the ethical and legal issues related to biobank research.

BACKGROUND: Although biobanks have become fundamental to many research centers and contribute to medical development, they generate many ethical and legal issues that may discourage patients from donating. MATERIALS AND METHODS: To understand patients' perception of ethical and legal issues related to biobanks we conducted a survey among 548 Polish patients with cancer. RESULTS: While 93.1% of patients with cancer declared themselves willing to donate biospecimens left over after a medical procedure to a biobank, most opted for one-time consent or study-specific consent, blanket consent being less frequently preferred. Many patients believed that future use of previously collected tissues require second contact. Most patients preferred pseudonymization over anonymization of the data, and supported donors' right to withdraw informed consent at any given moment. Finally, while personal health information was the most expected form of compensation for donation, most patients suggested that all parties, including the biobank concerned, the sponsors of the research, and the donors, should own the rights to cancer tissues donated and profit from the biobank research. Patients' opinions on the ethical and legal issues related to biobank research were associated with age, sex, religiosity, education level, and place of residence. CONCLUSIONS: Since biobanks generate ethical and legal issues related to informed consent, data protection and storage, as well as the sharing of biosamples, tissue ownership, and profit sharing, that may discourage patients from donation, when asking a patient for a donation, healthcare professionals should communicate in a donor-centered manner and address patients' ethical and moral concerns related to donation and offer resources to help manage these concerns.

Preclinical research (on rare diseases): we need to talk about health equity.

There is a thriving, worldwide, biomedical research community working to understand the molecular bases of diseases of all types, continuously driving improved diagnostics and therapies. Developments in genetics and experimental medicine are yielding novel genetic therapies that were hardly dreamt of 40 years ago. But along with these scientific achievements, there exist challenges in ensuring that 21st century medical interventions are accessible to all who need them. This perspective will discuss how preclinical research, with a focus on rare diseases, can better contribute to healthcare ecosystems that are oriented towards greater health equity. This contribution may require changes to the prevailing scientific research culture that will need support from relevant institutions and the wider community.

Generative Adversarial Networks in Digital Histopathology: Current Applications, Limitations, Ethical Considerations, and Future Directions.

Generative adversarial networks (GANs) have gained significant attention in the field of image synthesis, particularly in computer vision. GANs consist of a generative model and a discriminative model trained in an adversarial setting to generate realistic and novel data. In the context of image synthesis, the generator produces synthetic images, whereas the discriminator determines their authenticity by comparing them with real examples. Through iterative training, the generator allows the creation of images that are indistinguishable from real ones, leading to high-quality image generation. Considering their success in computer vision, GANs hold great potential for medical diagnostic applications. In the medical field, GANs can generate images of rare diseases, aid in learning, and be used as visualization tools. GANs can leverage unlabeled medical images, which are large in size, numerous in quantity, and challenging to annotate manually. GANs have demonstrated remarkable capabilities in image synthesis and have the potential to significantly impact digital histopathology. This review article focuses on the emerging use of GANs in digital histopathology, examining their applications and potential challenges. Histopathology plays a crucial role in disease diagnosis, and GANs can contribute by generating realistic microscopic images. However, ethical considerations arise because of the reliance on synthetic or pseudogenerated images. Therefore, the manuscript also explores the current limitations and highlights the ethical considerations associated with the use of this technology. In conclusion, digital histopathology has seen an emerging use of GANs for image enhancement, such as color (stain) normalization, virtual staining, and ink/marker removal. GANs offer significant potential in transforming digital pathology when applied to specific and narrow tasks (preprocessing enhancements). Evaluating data quality, addressing biases, protecting privacy, ensuring accountability and transparency, and developing regulation are imperative to ensure the ethical application of GANs.

The nexus of fertility and politics: exploring the influence of social tolerance, religiosity, and political conservatism on the acceptance of assisted reproduction in Spain.

STUDY QUESTION: How do individual religious, political, and social tolerance orientations influence the acceptance of ART among Spanish citizens? SUMMARY ANSWER: Social tolerance and religiosity are predictive factors for the acceptance of ART, with more tolerant individuals and those with lower levels of religiosity being more accepting of ART; political conservatism mediates the relationship between social tolerance and acceptance of ART, particularly for left-leaning individuals. WHAT IS KNOWN ALREADY: The rapid advancement of ART has raised questions about its societal acceptance, especially in the context of religious, political, and social beliefs. STUDY DESIGN, SIZE, DURATION: The analysis utilized data from the combined Europe Values Study and World Values Survey, comprising cross-sectional national surveys from 1981 to 2021. Each country's population was surveyed a maximum of seven times and a minimum of two times during this period. This study uses the cross-sectional data of 2021. After filtering for Spanish citizens and deleting cases with missing key variables, a sample of 1030 valid responses from Spanish citizens was obtained. Quotas were set for sex, age, and educational level, following guidance from the Spanish Statistics Institute. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study surveyed participants' attitudes towards ART, their religious and political orientations, and collected demographic information. The sample consisted of 51.7% women, most respondents were married or in common-law partnerships, and 61.6% had children. Catholicism was the dominant religion (53.0%) and a majority had completed secondary education (66.2%), with half earning over 1400 euros per month. MAIN RESULTS AND THE ROLE OF CHANCE: Using two linear models to test hypotheses, the study found that social tolerance and religiosity significantly predict acceptance of ART, with more tolerant and less religious individuals being more accepting. Political conservatism mediated the relationship between social tolerance and ART acceptance, particularly among left-leaning individuals. LIMITATIONS, REASONS FOR CAUTION: This study is cross-sectional and based on self-reported data, which may have limitations. Additionally, the findings are based on a Spanish sample and may not be universally applicable. WIDER IMPLICATIONS OF THE FINDINGS: The results have significant implications for policymakers and healthcare professionals in the field of reproductive technologies. They also contribute to public debates on ethical considerations surrounding ART. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Mineco-FrontVida Program, Frontiers of Life, Social Change, and Changing Values Around the Beginning and End of Life (grant number PID2019-106882RB-I00), as part of the State Program for Knowledge Generation and Scientific and Technological Strengthening, and the State R&D Program Oriented to the Challenges of Society, 2019, Ministry of Science, Innovation, and Universities of Spain. 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. TRIAL REGISTRATION NUMBER: N/A.

Ethical choice reversals.

Understanding the systematic ways that human decision making departs from normative principles has been important in the development of cognitive theory across multiple decision domains. We focus here on whether such seemingly "irrational" decisions occur in ethical decisions that impose difficult tradeoffs between the welfare and interests of different individuals or groups. Across three sets of experiments and in multiple decision scenarios, we provide clear evidence that contextual choice reversals arise in multiples types of ethical choice settings, in just the way that they do in other domains ranging from economic gambles to perceptual judgments (Trueblood et al., 2013; Wedell, 1991). Specifically, we find within-participant evidence for attraction effects in which choices between two options systematically vary as a function of features of a third dominated and unchosen option-a prima facie violation of rational choice axioms that demand consistency. Unlike economic gambles and most domains in which such effects have been studied, many of our ethical scenarios involve features that are not presented numerically, and features for which there is no clear majority-endorsed ranking. We provide empirical evidence and a novel modeling analysis based on individual differences of feature rankings within attributes to show that such individual variations partly explains observed variation in the attraction effects. We conclude by discussing how recent computational analyses of attraction effects may provide a basis for understanding how the observed patterns of choices reflect boundedly rational decision processes.

Role and ethics of cynomolgus monkey (Macaca fascicularis) blastoids in primate developmental biology research.

This review on cynomolgus monkey (Macaca fascicularis) blastoids discusses a breakthrough in modeling early non-human primate embryogenesis, offering insights into embryonic development and implantation processes. It acknowledges ethical challenges and animal welfare considerations in developmental biology, suggests potential applications in human reproductive medicine, and highlights the need for ongoing ethical and technical refinement.

Rising adoption of artificial intelligence in scientific publishing: evaluating the role, risks, and ethical implications in paper drafting and review process.

BACKGROUND: In the rapid evolving landscape of artificial intelligence (AI), scientific publishing is experiencing significant transformations. AI tools, while offering unparalleled efficiencies in paper drafting and peer review, also introduce notable ethical concerns. CONTENT: This study delineates AI's dual role in scientific publishing: as a co-creator in the writing and review of scientific papers and as an ethical challenge. We first explore the potential of AI as an enhancer of efficiency, efficacy, and quality in creating scientific papers. A critical assessment follows, evaluating the risks vs. rewards for researchers, especially those early in their careers, emphasizing the need to maintain a balance between AI's capabilities and fostering independent reasoning and creativity. Subsequently, we delve into the ethical dilemmas of AI's involvement, particularly concerning originality, plagiarism, and preserving the genuine essence of scientific discourse. The evolving dynamics further highlight an overlooked aspect: the inadequate recognition of human reviewers in the academic community. With the increasing volume of scientific literature, tangible metrics and incentives for reviewers are proposed as essential to ensure a balanced academic environment. SUMMARY: AI's incorporation in scientific publishing is promising yet comes with significant ethical and operational challenges. The role of human reviewers is accentuated, ensuring authenticity in an AI-influenced environment. OUTLOOK: As the scientific community treads the path of AI integration, a balanced symbiosis between AI's efficiency and human discernment is pivotal. Emphasizing human expertise, while exploit artificial intelligence responsibly, will determine the trajectory of an ethically sound and efficient AI-augmented future in scientific publishing.

Should it stay, or swerve? Trading off lives in dilemma situations involving autonomous cars.

Using a representative survey with 1317 individuals and 12,815 moral decisions, we elicit Swedish citizens' preferences on how algorithms for self-driving cars should be programmed in cases of unavoidable harm to humans. Participants' choices in different dilemma situations (treatments) show that, at the margin, the average respondent values the lives of passengers and pedestrians equally when both groups are homogeneous and no group is to blame for the dilemma. In comparison, the respondent values the lives of passengers more when the pedestrians violate a social norm, and less when the pedestrians are children. Furthermore, we explain why the average respondent in the control treatment needs to be compensated with two to six passengers spared in order to sacrifice the first pedestrian, even though she values the lives of passengers and pedestrians equally at the margin. We conclude that respondents' choices are highly contextual and consider the age of the persons involved and whether these persons have complied with social norms.

Examining where to go: pediatric psychology trainees' perception of their graduate training in culture and diversity.

OBJECTIVE: Culture and diversity-related training is critical to the development of competent pediatric psychologists. Evaluation of training efforts have been conducted at the program level, yet evaluation of trainee experiences in culture and diversity-related training remains unassessed. This trainee-led study was the first formal assessment of pediatric psychology trainee experiences of culture and diversity-related training and the impact of training on their own cultural humility. METHODS: Study overview and a survey link was distributed across 2 listservs associated with the American Psychological Association (Division 53, Division 54) and sent directly to directors of graduate, internship, and fellowship training programs with a request to share with trainees. Surveys assessing integration of cultural training and trainee cultural humility were completed. Trainees also provided qualitative feedback regarding their multicultural training and development. RESULTS: Pediatric psychology trainees (N = 90) reported inconsistent integration of culture and diversity topics into their training. Of the 34 training areas assessed, 10 were perceived as thoroughly integrated into formal training by at least half of the respondents. Trainees often sought independent cultural training outside of their programs, and no relationship was detected between perceived integration of cultural training and trainee cultural competence. DISCUSSION: Results indicate room for improvement regarding integration of cultural training and a need to better understand driving forces behind trainees independently seeking training outside of their formal training programs. Moreover, understanding the aspects of training that are most contributory to trainee development is needed given that no relationship between training and development emerged in the current study.

Female Affective Perception of Mainstream and Paraphilic Pornography: Associations with Sexual and Psychological Intrapersonal Variables.

Understanding affective perceptual processes can further contribute to the explanation of motivation and actions, as well as sexual risk behaviors. Pornography can be considered salient emotional content and is popular, also among females. Yet, the female perspective on pornography has often been overlooked and it remains unclear how individual variables may be associated with the affective perception of pornography and could provide a risk profile. Possible associations between several sexual and psychological intrapersonal variables and the affective perception of various forms of pornography were analyzed from the female perspective. A sample of 231 females (M = 21.87 years; SD = 3.9 years) provided ratings of affective valence, arousal, disgust, and moral and ethical acceptance for mainstream pornographic and paraphilic images of dominance, submission, or sexual violence. Paraphilic pornography was perceived as less pleasant, arousing, and moral and ethically acceptable, but more disgusting compared to mainstream pornography. This was more pronounced among females who had never consumed pornography. Results further suggest that the female affective perception of pornography was associated with the following sexual intrapersonal variables: sexual sensation seeking for physical sensations, erotophilia, lack of sexual control, problematic pornography consumption, and sexual disgust sensitivity. Of the assessed psychological intrapersonal variables, only anxiety was negatively associated with disgust for paraphilic pornography. It is important to further analyze the female affective perception of pornography and associated variables to include them in strategies for prevention and for addressing problematic consequences of the acceptance of specific sexual content and behaviors, especially related to sexualized violence.

Ethical assessment of genome resource banking (GRB) in wildlife conservation.

Genome Resources Banks (GRBs) represent vital repositories for the systematic collection, storage, and management of genetic material across various taxa, with a primary objective of safeguarding genetic diversity for research and practical applications. Alongside the development of assisted reproductive techniques (ART), GRBs have evolved into indispensable tools in conservation, offering opportunities for species preservation, mitigating inbreeding risks, and facilitating genetic management across fragmented populations. By preserving genetic information in a suspended state, GRBs serve as backups against population vulnerabilities, potentially aiding in the restoration of endangered species and extending their genetic lifespan. While evidence demonstrates the efficacy of GRBs, ethical considerations surrounding biobanking procedures for wildlife conservation remain largely unexplored. In this article, we will discuss possible ethical issues related to GRBs and the need to ethically monitor biobanking procedures in wildlife conservation. We will then propose a methodological tool, ETHAS, already in use for the ethical self-assessment of assisted reproduction techniques, to assess also biobanking procedures. ETHAS can make it possible to monitor a GRB from its design phase to its actual operation, helping to build biobanking procedures that meet high ethical standards.

Exploring the Ethical, Legal, and Social Implications of ChatGPT in Urology.

PURPOSE OF THE REVIEW: ChatGPT is programmed to generate responses based on pattern recognition. With this vast popularity and exponential growth, the question arises of moral issues, security and legitimacy. In this review article, we aim to analyze the ethical and legal implications of using ChatGPT in Urology and explore potential solutions addressing these concerns. RECENT FINDINGS: There are many potential applications of ChatGPT in urology, and the extent to which it might improve healthcare may cause a profound shift in the way we deliver our services to patients and the overall healthcare system. This encompasses diagnosis and treatment planning, clinical workflow, patient education, augmenting consultations, and urological research. The ethical and legal considerations include patient autonomy and informed consent, privacy and confidentiality, bias and fairness, human oversight and accountability, trust and transparency, liability and malpractice, intellectual property rights, and regulatory framework. The application of ChatGPT in urology has shown great potential to improve patient care and assist urologists in various aspects of clinical practice, research, and education. Complying with data security and privacy regulations, and ensuring human oversight and accountability are some potential solutions to these legal and ethical concerns. Overall, the benefits and risks of using ChatGPT in urology must be weighed carefully, and a cautious approach must be taken to ensure that its use aligns with human values and advances patient care ethically and responsibly.

Community views on the secondary use of general practice data: Findings from a mixed-methods study.

INTRODUCTION: General practice data, particularly when combined with hospital and other health service data through data linkage, are increasingly being used for quality assurance, evaluation, health service planning and research. In this study, we explored community views on sharing general practice data for secondary purposes, including research, to establish what concerns and conditions need to be addressed in the process of developing a social licence to support such use. METHODS: We used a mixed-methods approach with focus groups (November-December 2021), followed by a cross-sectional survey (March-April 2022). RESULTS: The participants in this study strongly supported sharing general practice data with the clinicians responsible for their care, and where there were direct benefits for individual patients. Over 90% of survey participants (N = 2604) were willing to share their general practice information to directly support their health care, that is, for the primary purpose of collection. There was less support for sharing data for secondary purposes such as research and health service planning (36% and 45% respectively in broad agreement) or for linking general practice data to data in the education, social services and criminal justice systems (30%-36%). A substantial minority of participants were unsure or could not see how benefits would arise from sharing data for secondary purposes. Participants were concerned about the potential for privacy breaches, discrimination and data misuse and they wanted greater transparency and an opportunity to consent to data release. CONCLUSION: The findings of this study suggest that the public may be more concerned about sharing general practice data for secondary purposes than they are about sharing data collected in other settings. Sharing general practice data more broadly will require careful attention to patient and public concerns, including focusing on the factors that will sustain trust and legitimacy in general practice and GPs. PATIENT AND PUBLIC CONTRIBUTION: Members of the public were participants in the study. Data produced from their participation generated study findings. CLINICAL TRIAL REGISTRATION: Not applicable.

Reflexive control in emergency medicine.

Emergency physicians (EPs) navigate high-pressure environments, making rapid decisions amidst ambiguity. Their choices are informed by a complex interplay of experience, information, and external forces. While cognitive shortcuts (heuristics) expedite assessments, there are multiple ways they can be subtly manipulated, potentially leading to reflexive control: external actors steering EPs' decisions for their own benefit. Pharmaceutical companies, device manufacturers, and media narratives are among the numerous factors that influence the EPs' information landscape. Using tactics such as selective data dissemination, framing, and financial incentives, these actors can exploit pre-existing cognitive biases like anchoring, confirmation, and availability. This creates fertile ground for reflexive control, where EPs may believe they are acting independently while unknowingly serving the goals of external influencers. The consequences of manipulated decision making can be severe: misdiagnoses, inappropriate treatments, and increased healthcare costs. Ethical dilemmas arise when external pressures conflict with patient well-being. Recognizing these dangers empowers EPs to resist reflexive control through (1) critical thinking: examining information for potential biases and prioritizing evidence-based practices, (2) continuous education: learning about cognitive biases and mitigation strategies, and (3) institutional policies: implementing regulations to reduce external influence and to promote transparency. This vulnerability of emergency medicine decision making highlights the need for awareness, education, and robust ethical frameworks. Understanding reflexive control techniques is crucial for safeguarding patient care and promoting independent, ethical decision making in emergency medicine.

Perceptions and beliefs of community gatekeepers about genomic risk information in African cleft research.

BACKGROUND: A fundamental ethical issue in African genomics research is how socio-cultural factors impact perspectives, acceptance, and utility of genomic information, especially in stigmatizing conditions like orofacial clefts (OFCs). Previous research has shown that gatekeepers (e.g., religious, political, family or community leaders) wield considerable influence on the decision-making capabilities of their members, including health issues. Thus, their perspectives can inform the design of engagement strategies and increase exposure to the benefits of genomics testing/research. This is especially important for Africans underrepresented in genomic research. Our study aims to investigate the perspectives of gatekeepers concerning genomic risk information (GRI) in the presence of OFCs in a sub-Saharan African cohort. METHODS: Twenty-five focus group discussions (FGDs) consisting of 214 gatekeepers (religious, community, ethnic leaders, and traditional birth attendants) in Lagos, Nigeria, explored the opinions of participants on genomic risk information (GRI), OFC experience, and the possibility of involvement in collaborative decision-making in Lagos, Nigeria. Transcripts generated from audio recordings were coded and analyzed in NVivo using thematic analysis. RESULTS: Three main themes-knowledge, beliefs, and willingness to act-emerged from exploring the perspective of gatekeepers about GRI in this group. We observed mixed opinions regarding the acceptance of GRI. Many participants believed their role is to guide and support members when they receive results; this is based on the level of trust their members have in them. However, participants felt they would need to be trained by medical experts to do this. Also, religious and cultural beliefs were crucial to determining participants' understanding of OFCs and the acceptance and utilization of GRI. CONCLUSIONS: Incorporating cultural sensitivity into public engagement could help develop appropriate strategies to manage conflicting ideologies surrounding genomic information in African communities. This will allow for more widespread access to the advances in genomics research in underrepresented populations. We also recommend a synergistic relationship between community health specialists/scientists, and community leaders, including spiritual providers to better understand and utilize GRI.