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)

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)

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.

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)

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)

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 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)

Inleidend overzicht van de wijsgerige ethiek.

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.”.

In response to criticisms of the use of the Ideological Surround Model to analyze Tolerance of Ambiguity, emphasis is placed on how the methodologies of this model operate from Christian pacifist assumptions. This model seeks to promote social scientific methodologies that will allow competing perspectives to obtain increasing clarity on points of conflict.

This study assessed the possibility that the Budner Intolerance of Ambiguity Scale can offer an ideologically biased understanding of religious commitments. In a large sample of university undergraduates , Budner Scale correlations with Religious Interest, Religious Orientation, Need for Cognition, and Response Uncertainty supported the conclusion that religion predicts an inability to cope with uncertainty. At the same time, however, special procedures were used to create new scales expressing a Christian Tolerance of Ambiguity by translating Budner Scale items into a (...) language that was more compatible with religious beliefs. These Christian Tolerance of Ambiguity measures revealed that religiousness was associated with an ability rather than an inability to cope with uncertainty. Conflicting results between these Christian and nonreligious Tolerance of Ambiguity measures yielded additional support for the Ideological Surround Model of the psychology of religion. (shrink)

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)

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.

It is the impression of neurologists who deal with cancer patients that the incidence of neurologic complications of cancer is increasing (Posner 1995). ...

The metaphysical problem of individuation requires an answer to two different but intimately related questions: 1) How are we to characterize individuality ontologically? To what ontological category or logical type does individuality belong? 2) What sort of distinction is there between the individuality and nature of an individual, e.g., a real distinction, a modal distinction, a distinction of reason, or some other distinction My purpose in this article is to clarify a bare particular account of individuation and respond to objections (...) that have been raised against bare particulars as individuators. (shrink)

Between 1787, and the end of his life in 1832, Bentham turned his attention to the development and application of economic ideas and principles within the general structure of his legislative project. For seventeen years this interest was manifested through a number of books and pamphlets, most of which remained in manuscript form, that develop a distinctive approach to economic questions. Although Bentham was influenced by Adam Smith's An Inquiry into the Nature and Causes of the Wealth of Nations, he (...) neither adopted a Smithian vocabulary for addressing questions of economic principle and policy, nor did he accept many of the distinctive features of Smith's economic theory. One consequence of this was that Bentham played almost no part in the development of the emerging science of political economy in the early nineteenth century. The standard histories of economics all emphasize how little he contributed to the mainstream of late eighteenth and early nineteenth-century debate by concentrating attention on his utilitarianism and the psychology of hedonism on which it is premised. Others have argued that the calculating nature of his theory of practical reason reduced the whole legislative project to a crude attempt to apply economics to all aspects of social and political life. Put at its simplest this argument amounts to the erroneous claim that Bentham's science of legislation is reducible to the science of political economy. A different but equally dangerous error would be to argue that because Bentham's conception of the science of legislation comprehends all the basic forms of social relationships, there can be no science of political economy as there is no autonomous sphere of activity governed by the principles of economics. This approach is no doubt attractive from an historical point of view given that the major premise of this argument is true, and that many of Bentham's ‘economic’ arguments are couched in terms of his theory of legislation. Yet it fails to account for the undoubted importance of political economy within Bentham's writings, not just on finance, economic policy, colonies and preventive police, but also in other aspects of his utilitarian public policy such as prison reform, pauper management, and even constitutional reform. All of these works reflect a conception of political economy in its broadest terms. However, this conception of political economy differs in many respects from that of Bentham's contemporaries, and for this reason Bentham's distinctive approach to problems of economics and political economy has largely been misunderstood. (shrink)

Theism, according to David O'Connor, has in recent centuries been on trial for its life, the charge being that the existence of so much evil in the world is incompatible with belief in a benevolent creator. But this trial, he claims is incapable of producing a reasoned verdict.

This essay explores a variety of important Chinese conceptions of the actual and ideal relationship between human beings and the rest of the natural world. It presents views from the earliest period of historical China, the latter part of the Shang dynasty (ca. 1200–1050 bce), and from representative thinkers of other periods, extending down to the last imperial era, the Qing dynasty (1644–1911 ce). There is a fairly clear line of development from the earliest period, when the Chinese saw the (...) natural realm as chaotic, dangerous and largely inscrutable, to a later view of the world as well ordered, inclined toward human good and more open to understanding. This later view was first expressed during the “Eastern Zhou” (770–221 bce), and reached a mature and systematic form in the following Han dynasty (206 bce–220 ce). Subsequent periods saw remarkable variation in the specific features of this view but its general form – a belief in a well ordered and manageable world, inclined toward human good and open to human understanding – remained dominant throughout subsequent Chinese history. (shrink)