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 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)

Research necessarily entails the close interrelation of concepts and arguments, including solutions to a range of meta-questions, whether acknowledged explicitly or not. Despite this, few detailed accounts currently exist that support researchers to develop their complex conceptual architectures, especially in critical realist spheres. Indeed, many published accounts often omit much of this ‘messiness’ that sits behind, yet is foundational to, research projects. Those accounts that do seek to portray how/why researchers have made decisions (e.g. about connections between research philosophy, methodology, (...) methods, theory and empirical evidence) tend to focus on one set of meta-questions, or occasionally on the relationships between two sets, at a time. Therefore, this paper presents a flexible framework – supported by specific examples from studies – that we hope will be useful in supporting researchers from all traditions, but especially critical realists, to carefully think through and develop more holistic connections in their conceptual architecture. (shrink)

J J Schwieso, N J Hastings; Explanations and Practice: behaviour modification in education, Journal of Philosophy of Education, Volume 20, Issue 1, 30 May 2006.

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)

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.

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)

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 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)

Ontologies aim to represent what is general, by means of universal statements. In contrast, dispositional predications capture knowledge about what is likely to happen if a certain set of circumstances obtain, which is crucial in investigative research such as in drug discovery and systems biology, where entities which are constitutionally dissimilar can nevertheless have similar behavior in a biological context. While such dispositional properties are increasingly included in biomedical ontologies, the circumstances under which the dispositions are realized are seldom explicitly (...) modeled, and doing so is problematic due to the necessary restriction to binary relations in OWL ontologies. In this paper we address this shortcoming, focusing on the bioactivity of small molecules at varying levels of concentration within a living organism as our problem domain, although our approach is generalizable to other problems. We discuss the ontological nature and representation of dispositions and their realization; consider the nature of concentrations and their representation; and finally we detail an approach to linking dispositions to the conditions for their realization which regards conditions as triggers for the process in which the disposition is realized. (shrink)

While genomic and proteomic information describe the overall cellular machinery available to an organism, the metabolic profile of an individual at a given time provides a canvas as to the current physiological state. Concentration levels of relevant metabolites vary under different conditions, in particular, in the presence or absence of different disorders. Metabolite concentrations thus mediate an important link between chemistry and biology, contributing to a systems-wide understanding of biological processes and pathways. However, there are a number of challenges in (...) the ontological representation of such information. Firstly, concentration information is numeric and ranges over continuous values, while ontologies consist of discrete classes. Secondly, ontologies usually model only what is certain, and their logical formalisms are adapted to reasoning from certain axioms to logical deductions, however, the link between chemicals and diseases via concentration levels, like many threshold phenomena, is both uncertain and vague. In this paper we evaluate the representation of this knowledge using a combination of concrete domains and probabilistic reasoning. We parse concentration values from HMDB and create an ontology able to distinguish normal from abnormal concentrations and able to evaluate a probabilistic risk category for the presence of an associated disorder. (shrink)

This volume contains thirteen papers that were presented at the 2017 Annual Meeting of the Canadian Society for History and Philosophy of Mathematics/Société canadienne d’histoire et de philosophie des mathématiques, which was held at Ryerson University in Toronto. It showcases rigorously reviewed modern scholarship on an interesting variety of topics in the history and philosophy of mathematics from Ancient Greece to the twentieth century. A series of chapters all set in the eighteenth century consider topics such as John Marsh’s techniques (...) for the computation of decimal fractions, Euler’s efforts to compute the surface area of scalene cones, a little-known work by John Playfair on the practical aspects of mathematics, and Monge’s use of descriptive geometry. After a brief stop in the nineteenth century to consider the culture of research mathematics in 1860s Prussia, the book moves into the twentieth century with an examination of the historical context within which the Axiom of Choice was developed and a paper discussing Anatoly Vlasov’s adaptation of the Boltzmann equation to ionized gases. The remaining chapters deal with the philosophy of twentieth-century mathematics through topics such as an historically informed discussion of finitism and its limits; a reexamination of Mary Leng’s defenses of mathematical fictionalism through an alternative, anti-realist approach to mathematics; and a look at the reasons that mathematicians select specific problems to pursue. Written by leading scholars in the field, these papers are accessible to not only mathematicians and students of the history and philosophy of mathematics, but also anyone with a general interest in mathematics. (shrink)

Forsyth (J Pers Soc Psychol 39(1): 175-184, 1980) argued that ethical ideology includes the two orthogonal dimensions of relativism and idealism. Relativists determine morality by looking at the complexities of the situation rather than relying on universal moral rules, while idealists believe that positive consequences can always be obtained without harming others. This study examined the role of ethical ideology as a moderator between justice and constructive and deviant reactions to injustice. Students with work experience (N = 200) completed Bennett (...) and Robinson's (J Appl Psychol 85(3): 349-360, 2000) measure of Workplace Deviance, Gill's (Reactions to injustice: Development and validation of a measure. Unpublished doctoral dissertation, University of Western Ontario, 2005) Reactions to Injustice measure, and the Ethics Position Questionnaire (Forsyth, 1980), and provided ratings of justice in their own workplace. Hierarchical regressions revealed a significant main effect of idealism on deviance and constructive behaviors, and three-way interactions between idealism, relativism, and some types of justice. These findings suggest that ethical ideology plays a significant role in predicting responses to injustice. (shrink)

In his paper ‘Has the Ontological Argument Been Refuted?’, 97–110) William F. Vallicella argues that my attempt to show that the Ontological Argument begs the question is unsuccessful. 1 I believe he is wrong about this, but before endeavouring to vindicate my position I must first make clear what precisely is the point at issue between us. The Ontological Argument is not a single argument, but a family of arguments. Newly devised formulations of the argument are frequently put forward by (...) philosophers in an effort to avoid difficulties that have been pointed out in previous versions. As a consequence there is no possibility of a conclusive proof that every form of the argument embodies the same fallacy. Nevertheless, one can, I believe, prove that all the standard versions of the argument embody a certain fallacy and that, given the nature of the argument, it is therefore unlikely that the argument can be formulated in such a way as to avoid this difficulty. What I tried to show in my paper is that the six best-known versions of the argument all beg the question and that they do so at the same point in the argument, namely when it is asserted that it is possible that an absolutely perfect being exists. It is difficult to see how an ontological argument could be formulated without including this claim as one of its premises, since the distinguishing badge of the argument is the inference from the possibility of an absolutely perfect being to its actuality. It must be unlikely then, if my criticism of these six versions is correct, that there is any way of formulating the argument that avoids this fallacy. (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.

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.

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)

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

Hume's 'Natural History of Religion' offers a naturalized account of the causes of religious thought, an investigation into its 'origins' rather than its 'foundation in reason'. Hume thinks that if we consider only the causes of religious belief, we are provided with a reason to suspend the belief. I seek to explain why this is so, and what role the argument plays in Hume's wider campaign against the rational acceptability of religious belief. In particular, I argue that the work threatens (...) a form of fideism which maintains that it is rationally permissible to maintain religious belief in the absence of evidence or of arguments in its favour. I also discuss the 'argument from common consent', and the relative superiority of Hume's account of the origins of religious belief. (shrink)

Multidisciplinary healthcare committees meet regularly to discuss patients’ candidacy for emerging functional neurosurgical procedures, such as Deep Brain Stimulation . Through debate and discussion around the surgical candidacy of particular patients, functional neurosurgery programs begin to mold practice and policy supported both by scientific evidence and clear value choices. These neurosurgical decisions have special considerations not found in non-neurologic committees. The professional time used to resolve these conflicts provides opportunities for the emergence of careful, ethical practices simultaneous with the expansion (...) of therapy applications. (shrink)

This paper discusses the metaphor of projection in relation to Hume’s treatment of causal necessity. I argue that the best understanding of projection shows it to be compatible with taking Hume to be a ‘sceptical realist’ about causal necessity, albeit an agnostic one.

There have been two recent attempts to disentangle the evidence for the procedures in fourth-century Athens for the enactment and revision of nomoi, by D. M. MacDowell and by M. H. Hansen. I have learned from both, but think that further progress can be made. MacDowell distinguishes five separate measures: The Old Legislation Law, requiring action at a specified time, advance publicity for the new proposal, concurrent repeal of any existing law with which the new proposal conflicts, and a decision (...) by nomothetae who are omomokotes, men who have sworn the dicastic oath : this is described as a παλαις νόμος, and as the law καθ' ν σαν ο πρότεροι νομοθέαι. Replacing that c. 370, the New Legislation Law, no longer requiring action at a specified time, advance publicity, concurrent repeal, or that the nomothetae should be omomokotes: as a result of the change conflicting laws have been enacted, and for some time continuing to the mid 350s commissioners have had to be elected to sort out the conflicts. Still valid in the 350s, the Review Law, requiring an annual epicheirotonia of the laws in four subject divisions in the assembly on 11 Hecatombaeon , advance publicity for new proposals, and at the third assembly after 11 Hecatombaeon the appointment of nomothetae who are omomokotes to decide between the existing laws and the new proposals. (shrink)