Mitotic recombination is a repair process which is known to repair double strand breaks and to fill double‐strand gaps by copying a homologous sequence. Meiotic recombination is a process of heteroduplex formation which sometimes generates crossovers. Evidence is presented that the later stages of meiotic recombination have some characteristics of mitotic repair recombination, leading to the conclusion that mismatch repair may be a recombinogenic repair process. The evidence suggests that the recombinational repair process generates hetero‐duplex bubbles which can move. Some (...) bubbles become crossovers. Others cease to exist, perhaps because topoisomerase activity breaks them down. (shrink)

Evolutionary theory assumed that mutations occur constantly, gradually, and randomly over time. This formulation from the “modern synthesis” of the 1930s was embraced decades before molecular understanding of genes or mutations. Since then, our labs and others have elucidated mutation mechanisms activated by stress responses. Stress‐induced mutation mechanisms produce mutations, potentially accelerating evolution, specifically when cells are maladapted to their environment, that is, when they are stressed. The mechanisms of stress‐induced mutation that are being revealed experimentally in laboratory settings provide (...) compelling models for mutagenesis that propels pathogen–host adaptation, antibiotic resistance, cancer progression and resistance, and perhaps much of evolution generally. We discuss double‐strand‐break‐dependent stress‐induced mutation in Escherichia coli. Recent results illustrate how a stress response activates mutagenesis and demonstrate this mechanism's generality and importance to spontaneous mutation. New data also suggest a possible harmony between previous, apparently opposed, models for the molecular mechanism. They additionally strengthen the case for anti‐evolvability therapeutics for infectious disease and cancer. (shrink)

An educational provision for young children with autism that offers intensive behavioural intervention based on the principles of Applied Behaviour Analysis (ABA), within an early years mainstream school setting in the UK, is described. The ABA Class at Westwood School is a collaborative project between the School of Psychology, Bangor University, two Local Education Authorities in North East Wales (Flintshire and Wrexham) and the local NHS Trust. Using two case examples, two important features of mainstream education for children with autism (...) are considered: access to the National Curriculum, and inclusion with peers in mainstream settings. Standardised test data on outcomes for these children over the initial 12 months of their educational placements are also provided. (shrink)

Most donated organs in the United States come from brain dead donors, while a small percentage come from patients who die in “controlled,” or expected, circumstances, typically after the family or surrogate makes a decision to withdraw life support. The number of organs available for transplant could be substantially if donations were permitted in “uncontrolled” circumstances–that is, from people who die unexpectedly, often outside the hospital. According to projections from the Institute of Medicine, establishing programs permitting “uncontrolled donation after circulatory (...) determination of death,” or uDCDD, throughout the United States has the potential to provide 22,000 more donation opportunities annually. In contrast, U.S. controlled donation after circulatory determination of death, or cDCDD, cases have increased progressively over the past decade from 87 to 848 donors, but currently account for only 10.6 percent of all deceased donors. Following the IOM recommendations, several projects exploring the feasibility of uDCDD were funded by the federal government, including a grant from the Health Resources and Services Administration that supported a pilot project in New York City in which the authors of this article participated.A key feature of our protocol, and indeed of many uDCDD protocols, is the initiation of preservation methods such as chest compressions and extracorporeal membrane oxygenation shortly after death in order to perfuse and preserve the donor's organs. Critics of uDCDD argue that the means of determining death deviates from generally ascribed principles. They assert that reinstituting circulation in order to preserve organs has the effect of “undoing” the prior determination of death. The result is that cDCDD is widely accepted and practiced routinely even though it only marginally increases the number of organs available for transplantation, and uDCDD is widely considered unacceptable despite being ethically embraced and proven to significantly increase organ donation opportunities in other countries. This article explores the evolution of this counterintuitive state of affairs and calls for a policy that, in line with the IOM report, allows for both cDCDD and uDCDD protocols. (shrink)

The authors respond to a letter by Mitchell Berger in the March‐April 2024 issue of the Hastings Center Report concerning their essay “Securing the Trustworthiness of the FDA to Build Public Trust in Vaccines.”.

The report by Barbara Bierer and Mark Barnes highlights the complexities experienced by institutions that conduct Public Health Service‐funded research involving human subjects and that need to negotiate the requirements of two sets of federal regulations: 45 C.F.R. 46, covering protections for human research subjects, and 42 C.F.R. 93, the PHS policies on research misconduct. As the nation's single largest sponsor of biomedical and behavioral research, the National Institutes of Health seeks to exemplify and promote human research protections and the (...) highest level of scientific integrity, public accountability, and social responsibility in the conduct of science. The NIH is committed to protecting the rights and welfare of research participants and to upholding integrity standards for research supported with public funds. However, human subjects protections must always take priority. (shrink)

The release of genetically engineered organisms into the shared environment raises scientific, ethical, and societal issues. Using some form of democratic deliberation to provide the public with a voice on the policies that govern these technologies is important, but there has not been enough attention to how we should connect public deliberation to the existing regulatory process. Drawing on lessons from previous public deliberative efforts by U.S. federal agencies, we identify several practical issues that will need to be addressed if (...) relevant federal agencies are to undertake public deliberative activities to inform decision‐making about gene editing in the wild. We argue that, while agencies may have institutional capacity to undertake public deliberative activities, there may not be sufficient political support for them to do so. Advocates of public deliberation need to make a stronger case to Congress about why federal agencies should be encouraged and supported to conduct public deliberations. (shrink)

The Covid‐19 pandemic highlighted the need to examine public trust in the U.S. Food and Drug Administration (FDA) vaccine approval process and the role of political influence in the FDA's decisions. Ensuring that the FDA is itself trustworthy is important for justifying public trust in its actions, like vaccine approvals, thereby promoting public health. We propose five conditions of trustworthiness that the FDA should meet when it reviews vaccines, even during emergencies: consistency with rules, proper expert or political decision‐makers, proper (...) decision‐making and noninterference, connection to public preference, and transparency of both reasons and procedures. The five conditions provide a road map of procedural and substantive requirements, which the FDA has variably implemented, focused on ensuring appropriate influence of political interests. While being a trustworthy agency cannot guarantee the public's trust, implementing these conditions builds a groundwork for public trust. (shrink)

This article is the lead piece in a special report that presents the results of a bioethical investigation into chimeric research, which involves the insertion of human cells into nonhuman animals and nonhuman animal embryos, including into their brains. Rapid scientific developments in this field may advance knowledge and could lead to new therapies for humans. They also reveal the conceptual, ethical, and procedural limitations of existing ethics guidance for human‐nonhuman chimeric research. Led by bioethics researchers working closely with an (...) interdisciplinary work group, the investigation focused on generating conceptual clarity and identifying improvements to governance approaches, with the goal of helping scholars, funders, scientists, institutional leaders, and oversight bodies (embryonic stem cell research oversight [ESCRO] committees and institutional animal care and use committees [IACUCs]) deliver principled and trustworthy oversight of this area of science. The article, which focuses on human‐nonhuman animal chimeric research that is stem cell based, identifies key ethical issues in and offers ten recommendations regarding the ethics and oversight of this research. Turning from bioethics’ previous focus on human‐centered questions about the ethics of “humanization” and this research's potential impact on concepts like human dignity, this article emphasizes the importance of nonhuman animal welfare concerns in chimeric research and argues for less‐siloed governance and oversight and more‐comprehensive public communication. (shrink)

Book reviewed in this article: The Gene Factory. By John Elkington. In the Name of Eugenics: Genetics and the Uses of Human Heredity. By Daniel J. Kevles. Broken Code: The Exploitation of DNA. By Marc Lappé.

Inleidend overzicht van de wijsgerige ethiek.

Philip J. Ivanhoe's richly annotated translation of this classic work is accompanied by his engaging interpretation and commentary, a lucid introduction, and a Language Appendix that compares eight classic translations of the opening passage of the work and invites the reader to consider the principles upon which each was rendered.

This new edition offers expanded selections from the works of Kongzi, Mengzi, Zhuangzi, and Xunzi ; two new works, the dialogues _Robber Zhi_ and _White Horse_; a concise general introduction; brief introductions to, and selective bibliographies for, each work; and four appendices that shed light on important figures, periods, texts, and terms in Chinese thought.

Religion and the external world -- Projection, religion, and the external world -- The senses, reason and the imagination -- Realism, meaning and justification : the external world and religious belief -- Modality, projection and realism -- 'Our profound ignorance' : causal realism, and the failure to detect necessity -- Spreading the mind : projection, necessity and realism -- Into the labyrinth : persons, modality, and Hume's undoing -- Value, projection, and realism -- Gilding : projection, value and secondary qualities (...) -- The gold : good, evil, belief and desire -- The golden : relational values, realism and a moral sense. (shrink)

Commentators have generally been content to cite parallels for the phrase iucunda uoluptas at Propertius 1.10.3 without drawing attention to an interesting resonance which it may evoke.