When is directed deceased donation justified? Practical, ethical, and legal issues.

This paper explores whether directed deceased organ donation should be permitted, and if so under which conditions. While organ donation and allocation systems must be fair and transparent, might it be "one thought too many" to prevent directed donation within families? We proceed by providing a description of the medical and legal context, followed by identification of the main ethical issues involved in directed donation, and then explore these through a series of hypothetical cases similar to those encountered in practice. Ultimately, we set certain conditions under which directed deceased donation may be ethically acceptable. We restrict our discussion to the allocation of organs to recipients already on the waiting list.

Toward Transparency on Animal Experimentation in Switzerland: Seven Recommendations for the Provision of Public Information in Swiss Law.

In Switzerland, the importance of transparency in animal experimentation is emphasized by the Swiss Federal Council, recognizing the public's great interest in this matter. Federal reporting on animal experimentation indicates a total of 585,991 animals used in experiments in Switzerland in 2022. By Swiss law, the report enables the public to learn about many aspects such as the species and degree of suffering experienced by the animals, but some information of interest to the public is missing, such as the fate of the animals at the end of the experiment (e.g., euthanized, rehomed in a private home, reused in another experiment). When it comes to animals bred in facilities but not used in experiments, further information of interest is not required to be made public according to Swiss law, for example, the number and fate of "surplus" animals (i.e., animals bred but not used in experiments for a variety of reasons such as not carrying the phenotypical properties needed). Considering that the Swiss government has a duty to provide a full accounting of animal experimentation conducted on the public's behalf, further relevant information should be disclosed. While efforts toward transparency, such as the STAAR Agreement, have been made in the scientific community, these mostly reflect the legal requirements already in force. If Switzerland is to move toward more transparency in public information on animal experimentation, an update of the legal requirements is needed. In this article, we give recommendations for Swiss law to move toward more transparency in public information on seven aspects: (1) the fate of the animals at the end of the experiment; (2) the sources of funding for animal experimentation; (3) the harm-benefit analysis performed by researchers and ethics committees to justify an experiment using animals; (4) the number of breeding/surplus animals; (5) the fate of breeding/surplus animals; (6) the harms experienced by animals in facilities; and (7) the funding of animal facilities.

The "Magical Theory" of AI in Medicine: Thematic Narrative Analysis.

BACKGROUND: The discourse surrounding medical artificial intelligence (AI) often focuses on narratives that either hype the technology's potential or predict dystopian futures. AI narratives have a significant influence on the direction of research, funding, and public opinion and thus shape the future of medicine. OBJECTIVE: The paper aims to offer critical reflections on AI narratives, with a specific focus on medical AI, and to raise awareness as to how people working with medical AI talk about AI and discharge their "narrative responsibility." METHODS: Qualitative semistructured interviews were conducted with 41 participants from different disciplines who were exposed to medical AI in their profession. The research represents a secondary analysis of data using a thematic narrative approach. The analysis resulted in 2 main themes, each with 2 other subthemes. RESULTS: Stories about the AI-physician interaction depicted either a competitive or collaborative relationship. Some participants argued that AI might replace physicians, as it performs better than physicians. However, others believed that physicians should not be replaced and that AI should rather assist and support physicians. The idea of excessive technological deferral and automation bias was discussed, highlighting the risk of "losing" decisional power. The possibility that AI could relieve physicians from burnout and allow them to spend more time with patients was also considered. Finally, a few participants reported an extremely optimistic account of medical AI, while the majority criticized this type of story. The latter lamented the existence of a "magical theory" of medical AI, identified with techno-solutionist positions. CONCLUSIONS: Most of the participants reported a nuanced view of technology, recognizing both its benefits and challenges and avoiding polarized narratives. However, some participants did contribute to the hype surrounding medical AI, comparing it to human capabilities and depicting it as superior. Overall, the majority agreed that medical AI should assist rather than replace clinicians. The study concludes that a balanced narrative (that focuses on the technology's present capabilities and limitations) is necessary to fully realize the potential of medical AI while avoiding unrealistic expectations and hype.

Development of the Pneumococcal Genome Library, a core genome multilocus sequence typing scheme, and a taxonomic life identification number barcoding system to investigate and define pneumococcal population structure.

Investigating the genomic epidemiology of major bacterial pathogens is integral to understanding transmission, evolution, colonization, disease, antimicrobial resistance and vaccine impact. Furthermore, the recent accumulation of large numbers of whole genome sequences for many bacterial species enhances the development of robust genome-wide typing schemes to define the overall bacterial population structure and lineages within it. Using the previously published data, we developed the Pneumococcal Genome Library (PGL), a curated dataset of 30 976 genomes and contextual data for carriage and disease pneumococci recovered between 1916 and 2018 in 82 countries. We leveraged the size and diversity of the PGL to develop a core genome multilocus sequence typing (cgMLST) scheme comprised of 1222 loci. Finally, using multilevel single-linkage clustering, we stratified pneumococci into hierarchical clusters based on allelic similarity thresholds and defined these with a taxonomic life identification number (LIN) barcoding system. The PGL, cgMLST scheme and LIN barcodes represent a high-quality genomic resource and fine-scale clustering approaches for the analysis of pneumococcal populations, which support the genomic epidemiology and surveillance of this leading global pathogen.

One R or the other - an experimental bioethics approach to 3R dilemmas in animal research.

Sacrificial dilemmas such as the trolley problem play an important role in experimental philosophy (x-phi). But it is increasingly argued that, since we are not likely to encounter runaway trolleys in our daily life, the usefulness of such thought experiments for understanding moral judgments in more ecologically valid contexts may be limited. However, similar sacrificial dilemmas are experienced in real life by animal research decision makers. As part of their job, they must make decisions about the suffering, and often the death, of many non-human animals. For this reason, a context-specific investigation of so-called "3R dilemmas" (i.e., dilemmas where there is a conflict between the principles of replacement, reduction, and refinement of the use of animals in research) is essential to improve the situation of both non-human animals and human stakeholders. An approach well suited for such investigation is experimental philosophical bioethics ("bioxphi"), which draws on methods similar to x-phi to probe more realistic, practical scenarios with an eye to informing normative debates and ethical policy. In this article, we argue for a need to investigate 3R dilemmas among professional decision-makers using the tools of bioxphi. In a first step, we define 3R dilemmas and discuss previous investigations of professionals' attitudes in such cases. In a second step, we show how bioxphi is a promising method to investigate the whys and hows of professional decision-making in 3R dilemmas. In a last step, we provide a bioxphi template for 3R dilemmas, give recommendations on its use, explore the normative relevance of data collected by such means, and discuss important limitations.

Analytical and Functional Characterization of Plasmid DNA Topological Forms and Multimers.

Plasmid DNA (pDNA) is an essential tool in genetic engineering that has gained prevalence in cell and gene therapies. Plasmids exist as supercoiled (SC), open circular (OC), and linear forms. Plasmid multimerization can also occur during the manufacturing process. Even though the SC forms are thought to provide optimal knock-in (KI) efficiency, there is no strong consensus on the effect of the topological forms and multimers on the functional activity. In addition, the results obtained for conventional pDNAs (>5 kbp) do not necessarily translate to smaller pDNAs (∼3 kbp). In this study, a workflow was developed for the analytical and functional characterization of pDNA topological forms and multimers. An anion exchange chromatography (AEC) method was first developed to quantify the topological forms and multimers. Four AEC columns were initially compared, one of which was found to provide superior chromatographic performance. The effect of mobile phase pH, various salts, column temperature, and acetonitrile content on the separation performance was systematically studied. The method performance, including precision and accuracy, was evaluated. The final AEC method was compared to capillary gel electrophoresis (CGE) by analyzing several pDNA sequences and lots. A forced degradation study revealed unexpectedly high degradation of the SC forms. Finally, the KI efficiency was compared for the SC and OC forms, and the multimers.

AI Through Ethical Lenses: A Discourse Analysis of Guidelines for AI in Healthcare.

While the technologies that enable Artificial Intelligence (AI) continue to advance rapidly, there are increasing promises regarding AI's beneficial outputs and concerns about the challenges of human-computer interaction in healthcare. To address these concerns, institutions have increasingly resorted to publishing AI guidelines for healthcare, aiming to align AI with ethical practices. However, guidelines as a form of written language can be analyzed to recognize the reciprocal links between its textual communication and underlying societal ideas. From this perspective, we conducted a discourse analysis to understand how these guidelines construct, articulate, and frame ethics for AI in healthcare. We included eight guidelines and identified three prevalent and interwoven discourses: (1) AI is unavoidable and desirable; (2) AI needs to be guided with (some forms of) principles (3) trust in AI is instrumental and primary. These discourses signal an over-spillage of technical ideals to AI ethics, such as over-optimism and resulting hyper-criticism. This research provides insights into the underlying ideas present in AI guidelines and how guidelines influence the practice and alignment of AI with ethical, legal, and societal values expected to shape AI in healthcare.

Exploring the Health-Related Quality of Life and the Lived Experience of Adolescents Following Invasive Meningococcal Disease.

BACKGROUND: Data on the health-related quality of life (HRQoL) for invasive meningococcal disease (IMD) survivors, particularly among adolescents and young adults (AYAs), are limited. This study aimed to investigate the in-depth experiences and impacts of IMD on AYAs. METHODS: Participants were recruited from two Australian states, Victoria and South Australia. We conducted qualitative, semi-structured interviews with 30 patients diagnosed with IMD between 2016 and 2021. The interview transcripts were analyzed thematically. RESULTS: Of the participants, 53% were aged 15-19 years old, and 47% were aged 20-24. The majority (70%) were female. Seven themes relating to the participants' experience of IMD were identified: (1) underestimation of the initial symptoms and then rapid escalation of symptoms; (2) reliance on social support for emergency care access; (3) the symptoms prompting seeking medical care varied, with some key symptoms missed; (4) challenges in early medical diagnosis; (5) traumatic and life-changing experience; (6) a lingering impact on HRQoL; and (7) gaps in the continuity of care post-discharge. CONCLUSION: The themes raised by AYA IMD survivors identify multiple areas that can be addressed during their acute illness and recovery. Increasing awareness of meningococcal symptoms for AYAs may help reduce the time between the first symptoms and the first antibiotic dose, although this remains a challenging area for improvement. After the acute illness, conducting HRQoL assessments and providing multidisciplinary support will assist those who require more intensive and ongoing assistance during their recovery.