Variations in levels of apolipoprotein E have been tied to the risk and progression of Alzheimer's disease . Our group has previously compared and contrasted the promoters of the mouse and human ApoE gene promoter sequences and found notable similarities and significant differences that suggest the importance of the APOE promoter's role in the human disease. We examine here three specific single-nucleotide polymorphisms within the human APOE promoter region, specifically at -491 , -427 , and at -219 upstream from the (...) +1 transcription start site. The -219 and -491 polymorphic variations have significant association with instance of AD, and -491AA has significant risk even when stratified for the APOEepsilon4 allele. We also show significant effects on reporter gene expression in neuronal cell cultures, and, notably, these effects are modified by species origin of the cells. The -491 and -219 polymorphisms may have an interactive effect in addition to any independent activity. DNA-protein interactions differ between each polymorphic state. We propose SP1 and GATA as candidates for regulatory control of the -491 and -219 polymorphic sites. This work's significance lies in drawing connection among APOE promoter polymorphisms' associations with AD to functional promoter activity differences and specific changes in DNA-protein interactions in cell culture-based assays. Taken together, these results suggest that APOE expression levels are a risk factor for AD irrespective of APOEepsilon4 allele status. (shrink)

Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

Aristotle and the sea battle, by G. E. M. Anscombe.--Aristotle's different possibilities, by K. J. J. Hintikka.--On Aristotle's square of opposition, by M. Thompson.--Categories in Aristotle and in Kant, by J. C. Wilson.--Aristotle's Categories, chapters I-V: translation and notes, by J. L. Ackrill--Aristotle's theory of categories, by J. M. E. Moravcsik.--Essence and accident, by I. M. Copi.--Tithenai ta phainomena, by G. E. L. Owen.--Matter and predication in Aristotle, by J. Owens.--Problems in Metaphysics Z, chapter 13, by M. J. Woods.--The meaning (...) of agathon in the Ethics of Aristotle, by H. A. Prichard.--Agathon and eudaimonia in the Ethics of Aristotle, by J. L. Austin.--The final good in Aristotle's Ethics, by W. F. R. Hardie.--Aristotle on pleasure, by J. O. Urmson.--Bibliography (p. 335-41). (shrink)

This new edition of Law and Medical Ethics continues to chart the ever-widening field that the topics cover. The interplay between the health caring professions and the public during the period intervening since the last edition has, perhaps, been mainly dominated by wide-ranging changes in the administration of the National Health Service and of the professions themselves but these have been paralleled by important developments in medical jurisprudence.

In this paper I describe and analyze an economic situation involving two competitive organizations. I put forth the argument that because of the systemic nature of decision making relative to managing the requirements of utilizing a descriptive equation that determines how many people an economic system can support, that even if all the players in the situation act ethically, the results will still be harmful, and necessarily so, to the system and to many innocent people. I will demonstrate that harming (...) innocent people is required and morally defensible given the choices available. The best one can do is slow down the increase in disutilities and possibly operate the system within a range of acceptable behavior that minimizes the resulting harm to innocent people, even if we cannot entirely remove this harm. In this context ethics becomes the study of the acceptable as opposed to the preferable. (shrink)

A set is said to be amorphous if it is infinite, but is not the disjoint union of two infinite subsets. Thus amorphous sets can exist only if the axiom of choice is false. We give a general study of the structure which an amorphous set can carry, with the object of eventually obtaining a complete classification. The principal types of amorphous set we distinguish are the following: amorphous sets not of projective type, either bounded or unbounded size of members (...) of partitions of the set into finite pieces), and amorphous sets of projective type, meaning that the set admits a non-degenerate pregeometry, over finite fields either of bounded cardinality or of unbounded cardinality. The hope is that all amorphous sets will be of one of these types. Examples of each sort are constructed, and a reconstruction result for bounded amorphous sets is presented, indicating that the amorphous sets of this kind constructed in the paper are the only possible ones. The final section examines some questions concerned with the resulting cardinal arithmetic. (shrink)

In the present research, two studies test the efficacy of an innovative procedure designed to reduce distortion and enhance communication of accurate childhood memories. One hundred two 7-year-olds participated in a staged activity and were randomly assigned to one of two treatment conditions . Two weeks later, half of the children participated in the innovative procedure designed to increase resistance to misleading questions by addressing sociolinguistic and socioemotional factors thought to promote acquiescence to misinformation. The other half of the children (...) participated in control sessions and were given motivating instructions to do their best. Then, memory for the staged activity was tested in an interview with an unfamiliar authority figure. The results of both studies suggest that the children who participated in the innovative procedure made significantly fewer errors in response to misleading questions than children in the control groups, hence diminishing acquiescence. This was accomplished without generating additional errors on the other question types. These findings are interpreted as a promising first step toward reducing the potential for distortion in the recall of childhood memories. Implications for adult recall of childhood trauma are discussed. (shrink)

Recently, new developments took place in the Dutch debate on the legislation of euthanasia. After a brief account of that debate, the article discusses a new government proposal for legislation in this field, which was submitted to the Dutch parliament in November 1991. This proposal relates not only to euthanasia but also to some other medical decisions concerning the end of life. The author concludes that, for several reasons, it is unsatisfactory.

This article revisits long-standing questions about consent, membership and emigration in Locke’s thought. Commentators such as A John Simmons have argued that Locke opens political membership to both express consenters and some kind of tacit consenters, and not just to the former, as some have suggested. Simmons’s reading seems to render Locke more sensible in that it does not exclude large numbers of people from membership or burden the few members with all the civic duties, and also in that it (...) allows at least tacit-consenting members the right to relocate, while this right is denied to express-consenting members. Against this reading, the article shows, by resolving seemingly conflicting claims in the text, that people become members only by express consent. It also responds to the criticism that the express-consent-only reading would limit membership to a few and so would render Locke’s account implausible from a practical point of view. The article then addresses the purported restriction Locke imposes on express consenters’ right to emigrate, arguing that the restriction concerns the change of membership and not the right to relocate. (shrink)

Originally published in 1926, this book attempts to state 'what has been believed with regard to God's incapacity for suffering'. Mozley charts the development of the doctrine from the Apostolic Fathers through the Reformation to the modern influence of metaphysical philosophy and concludes with six questions intended to prompt further theological discussion on this point. This book will be of value to anyone with an interest in the history of Christian theology.

Recent scholarship on technology-induced ‘conceptual disruption’ has spotlighted the notion of a conceptual gap. Conceptual gaps have also been discussed in scholarship on epistemic injustice, yet up until now these bodies of work have remained disconnected. This article shows that ‘gaps’ of interest to both bodies of literature are closely related, and argues that a joint examination of conceptual disruption and epistemic injustice is fruitful for both fields. I argue that hermeneutical marginalization—a skewed division of hermeneutical resources, which serves to (...) diminish the experiences of marginalized folk—does not only transpire because of conceptual gaps, but also because of two other kinds of conceptual disruption: conceptual overlaps and conceptual misalignments. Hence, there are multiple kinds of conceptual disruption that can be usefully studied through the normative lens of epistemic injustice. Technology can play different roles vis-a-vis epistemic injustices, both as a causal trigger of conceptual disruption, but also as a mediator of hermeneutical resources. Its role is normatively significant, in particular because socially disruptive technologies can have different epistemic implications for different groups: they may amplify the epistemic resources of some groups, while diminishing those of others. (shrink)

The literature on collective action largely ignores the constraints that moral principle places on action-prompting intentions. Here I suggest that neither individualism nor holism can account for the generality of intentional contents demanded by universalizability principles, respect for persons, or proactive altruism. Utilitarian and communitarian ethics are criticized for nominalism with respect to social intentions. The failure of individualism and holism as grounds for moral theory is confirmed by comparing Tuomela's reductivist analysis of we-intentions with Gilbert's analysis of social facts. (...) Tuomela's account founders over intentions to cooperate, and Gilbert's cannot accommodate legitimate authority, vicarious agency, or group structure. (shrink)

Mason and McCall Smith's classic textbook discusses the relationship of medical practice and ethics with the operation of the law. The subjects covered include natural and assisted reproduction, the impact of modern genetics on medicine, medical confidentiality, consent to medical treatment, the use of resources and problems surrounding death in the new medical era. It is of significance to anyone with an interest in the ethical and legal practice of medicine.

This paper traces the development of parental rights to accept or to refuse treatment for a defective newborn infant in the United Kingdom and in the United States of America; its main purpose is to explore the common trends from which an acceptable policy may be derived. It is probable that the British law on parental decision-making in respect of infants suffering from Down's syndrome is to be found in the civil case of In Re B rather than in the (...) criminal case of R v Arthur. United States court decisions are strongly influenced by constitutional law and reflect the right to personal privacy. The position on each side of the Atlantic seems very similar but this similarity includes a sense of uncertainty as to legal responsibility. There is a case for agreed guidelines and a suggested format is offered for consideration. (shrink)

In this paper an attempt is made to establish that the parties on both sides of the disputes concerning whether reasons are causes have mischaracterized or misdescribed what is involved in acting from a reason. A characterization of acting from a reason is provided, and, as a result, it is shown why contradictory positions have been and still are maintained by opposing parties. As a consequence of this account, an attempt is made to show why all parties have missed the (...) nature and significance of empathetic understanding. (shrink)

Background: The American Medical Association, the British Medical Association and the Canadian Medical Association have guidelines that specifically discourage physicians from self-prescribing or prescribing to family members, but only the BMA addresses informal prescription requests between colleagues. Objective: To examine the practices of paediatric providers regarding self-prescribing, curbsiding colleagues, and prescribing and refusing to prescribe to friends and family. Methods: 1086 paediatricians listed from the American Academy of Paediatrics 2007 web-based directory were surveyed. Results: 44% of eligible survey respondents returned (...) usable surveys. Almost half of respondents had prescribed for themselves. An equal number had informally requested a prescription from a colleague. Three-quarters stated they had been asked to prescribe a prescription drug for a first-degree or second-degree relative, and 51% had been asked by their spouse. Eighty-six per cent stated that they had refused to write a prescription on at least one occasion for a friend or family member. The following reasons “strongly influenced” their decision to refuse a prescription request: outside of provider’s expertise ; patient’s need for his or her own physician ; not medically indicated ; need for a physical examination. Conclusion: These data confirm that most physicians have engaged in self-prescribing or curbside requests for prescriptions. It can be argued that curbsiding is more morally problematic than self-prescribing because it implicates a third party, and should be discouraged regardless of whether the requester is a colleague, family member or friend. (shrink)