A survey of genomic studies supports association of circadian clock genes with bipolar disorder spectrum illnesses and lithium response.Michael J. McCarthy,Caroline M. Nievergelt,John R.Kelsoe &David K. Welsh -unknowndetailsCircadian rhythm abnormalities in bipolar disorder have led to a search for genetic abnormalities in circadian "clock genes" associated with BD. However, no significant clock gene findings have emerged from genome-wide association studies. At least three factors could account for this discrepancy: complex traits are polygenic, the organization of the clock is more complex than previously recognized, and/or genetic risk for BD may be shared across multiple illnesses. To investigate these issues, we considered the clock gene network at three levels: (...) essential "core" clock genes, upstream circadian clock modulators, and downstream clock controlled genes. Using relaxed thresholds for GWAS statistical significance, we determined the rates of clock vs. control genetic associations with BD, and four additional illnesses that share clinical features and/or genetic risk with BD. Then we compared the results to a set of lithium-responsive genes. Associations with BD-spectrum illnesses and lithium-responsiveness were both enriched among core clock genes but not among upstream clock modulators. Associations with BD-spectrum illnesses and lithium-responsiveness were also enriched among pervasively rhythmic clock-controlled genes but not among genes that were less pervasively rhythmic or non-rhythmic. Our analysis reveals previously unrecognized associations between clock genes and BD-spectrum illnesses, partly reconciling previously discordant results from past GWAS and candidate gene studies. (shrink)
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Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia.Vladimir Vacic,Shane McCarthy,Dheeraj Malhotra,Fiona Murray,Hsun-Hua Chou,Aine Peoples,Vladimir Makarov,Seungtai Yoon,Abhishek Bhandari,Roser Corominas,Lilia M. Iakoucheva,Olga Krastoshevsky,Verena Krause,Verónica Larach-Walters,David K. Welsh,David Craig,John R.Kelsoe,Elliot S. Gershon,Suzanne M. Leal,Marie Dell Aquila,Derek W. Morris,Michael Gill,Aiden Corvin,Paul A. Insel,Jon McClellan,Mary-Claire King,Maria Karayiorgou,Deborah L. Levy,Lynn E. DeLisi &Jonathan Sebat -unknowndetailsRare copy number variants have a prominent role in the aetiology of schizophrenia and other neuropsychiatric disorders. Substantial risk for schizophrenia is conferred by large CNVs at several loci, including microdeletions at 1q21.1, 3q29, 15q13.3 and 22q11.2 and microduplication at 16p11.2. However, these CNVs collectively account for a small fraction of cases, and the relevant genes and neurobiological mechanisms are not well understood. Here we performed a large two-stage genome-wide scan of rare CNVs and report the significant association of copy (...) number gains at chromosome 7q36.3 with schizophrenia. Microduplications with variable breakpoints occurred within a 362-kilobase region and were detected in 29 of 8,290 patients versus 2 of 7,431 controls in the combined sample. All duplications overlapped or were located within 89 kilobases upstream of the vasoactive intestinal peptide receptor gene VIPR2. VIPR2 transcription and cyclic-AMP signalling were significantly increased in cultured lymphocytes from patients with microduplications of 7q36.3. These findings implicate altered vasoactive intestinal peptide signalling in the pathogenesis of schizophrenia and indicate the VPAC2 receptor as a potential target for the development of new antipsychotic drugs. © 2011 Macmillan Publishers Limited. All rights reserved. (shrink)
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Social Agency in International Business Practices: Perspectives on Principled Constructive Engagement.John R. Schermerhorn Jr &William B. Lamb -2008 -Proceedings of the International Association for Business and Society 19:74-79.detailsConstructive engagement in international business practice is defined as purpose-driven behavior in which economic contributions by the foreign investor also advance social progress in the host country. This paper distinguishes between amoral and moral social agency, and proposes a model of principled constructive engagement that describes a principled constructive engagement regime enacted in a disciplined, morally-directed manner.
Pragmatism.John R. Shook -2023 - Cambridge, Massachusetts: The MIT Press.detailsA concise, reader-friendly overview of pragmatism, the most influential school of American philosophical thought.
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Singular Analogy and Quantitative Inductive Logics.John R. Welch -1999 -Theoria: Revista de Teoría, Historia y Fundamentos de la Ciencia 14 (2):207-247.detailsThe paper explores the handling of singular analogy in quantitative inductive logics. It concentrates on two analogical patterns coextensive with the traditional argument from analogy: perfect and imperfect analogy. Each is examined within Carnap’s λ-continuum, Carnap’s and Stegmüller’s λ-η continuum, Carnap’s Basic System, Hintikka’s α-λ continuum, and Hintikka’s and Niiniluoto’s K-dimensional system. Itis argued that these logics handle perfect analogies with ease, and that imperfect analogies, while unmanageable in some logics, are quite manageable in others. The paper concludes with a (...) modification of the K-dimensional system that synthesizes independent proposals by Kuipers and Niiniluoto. (shrink)
Coping with Ethical Uncertainty.John R. Welch -2017 -Diametros 53:150-166.detailsMost ethical decisions are conditioned by formidable uncertainty. Decision makers may lack reliable information about relevant facts, the consequences of actions, and the reactions of other people. Resources for dealing with uncertainty are available from standard forms of decision theory, but successful application to decisions under risk requires a great deal of quantitative information: point-valued probabilities of states and point-valued utilities of outcomes. When this information is not available, this paper recommends the use of a form of decision theory that (...) operates on a bare minimum of information inputs: comparative plausibilities of states and comparative utilities of outcomes. In addition, it proposes a comparative strategy for dealing with second-order uncertainty. The paper illustrates its proposal with reference to a well-known ethical dilemma: Kant’s life-saving lie. (shrink)
The Radiance of Drift and Doubt: Zhuangzi and the Starting Point of Philosophical Discourse.John R. Williams -2017 -Dao: A Journal of Comparative Philosophy 16 (1):1-14.detailsIf one cannot establish givens, such as Platonic ideas, or determiners, such as Kantian categories, as a point of departure for philosophical inquiry, then how is philosophical inquiry to proceed in a non-question-begging manner? This, of course, is the familiar problem of grounding philosophical discourse. In this essay, I hope to offer a Zhuangzian solution—that is, a solution derived from analysis of the Zhuangzi 莊子 text—to this perennial philosophical problem. As a result, I hope to give the reader a critical (...) glimpse into a Zhuangzian philosophy without foundations, thereby providing a potential solution to the preceding problem while displaying the continued relevance of the Zhuangzi text. (shrink)
Genetic circuitry controlling motility behaviors of Myxococcus xanthus.Tâm Mignot &John R. Kirby -2008 -Bioessays 30 (8):733-743.detailsM. xanthus has a complex multicellular lifestyle including swarming, predation and development. These behaviors depend on the ability of the cells to achieve directed motility across solid surfaces. M. xanthus cells have evolved two motility systems including Type‐IV pili that act as grappling hooks and a controversial engine involving mucus secretion and fixed focal adhesion sites. The necessity for cells to coordinate the motility systems and to respond rapidly to environmental cues is reflected by a complex genetic network involving at (...) least three complete sets of chemosensory systems and eukaryotic‐like signaling proteins. In this review, we discuss recent advances suggesting that motor synchronization results from spatial oscillations of motility proteins. We further propose that these dynamics are modulated by the action of multiple upstream complementary signaling systems. M. xanthus is thus an exciting emerging model system to study the intricate processes of directed cell migration. BioEssays 30:733–743, 2008. © 2008 Wiley Periodicals, Inc. (shrink)
Emotion and Object.John R. S. Wilson -1972 - Cambridge,: Cambridge University Press.detailsA study in the philosophy of mind, centred on the problem of 'intentionality' the sense in which emotions can be said to have objects, their relation to these objects, and the implications of this relation for our understanding of human action and behaviour. Dr Wilson sets his enquiry against a broad historical background on what distinguishes man from inanimate objects by describing both Cartesian view of man is matter plus mind and the neo-Wittgensteinian view that there is a dynamic behavioural (...) difference – causal notions being often inapplicable to human action. Dr Wilson goes on to show the controversies and arguments that arise from the notion of intentionality cannot be analysed in causal terms. Dr Wilson believes that this notion can be shown causally and sets out to prove it. Finally, he brings this argument to a larger context mentioning that it has far-reaching effects in natural and social sciences. (shrink)
Qian Mu reads Zhuangzi: Regarding ‘there has not yet begun to be a “there has not yet begun to be nothing”’.John R. Williams -2022 -Asian Philosophy 32 (2):164-171.detailsTo advance our understanding of both the Book of Zhuāngzǐ 莊子 (c. fourth to third century BCE) and Qián Mù 錢穆 (1895–1990)’s Zhuāngzǐ studies 莊學, I aim to squarely face one of the more obscure passages in the former with recourse to an explanation from the latter. The passage in question is that from the second chapter beginning with the claim ‘there is a beginning’ (有始也者) and culminating with the claim that ‘there has not yet begun to be a “there (...) has not yet begun to be nothing”’ (有未始有夫未始有無也者). I hope to show that Qián offers a compelling and novel interpretation of this difficult passage worthy of our consideration. (shrink)
A Strict Finite Foundation for Geometric Constructions.John R. Burke -2022 -Axiomathes 32 (2):499-527.detailsStrict finitism is a minority view in the philosophy of mathematics. In this paper, we develop a strict finite axiomatic system for geometric constructions in which only constructions that are executable by simple tools in a small number of steps are permitted. We aim to demonstrate that as far as the applications of synthetic geometry to real-world constructions are concerned, there are viable strict finite alternatives to classical geometry where by one can prove analogs to fundamental results in classical geometry. (...) We consider this as one of many early steps investigating the extent to which strict finite foundations can be developed for the application of mathematics to the real-world. (shrink)
New tools for theory choice and theory diagnosis.John R. Welch -2013 -Studies in History and Philosophy of Science Part A 44 (3):318-329.detailsTheory choice can be approached in at least four ways. One of these calls for the application of decision theory, and this article endorses this approach. But applying standard forms of decision theory imposes an overly demanding standard of numeric information, supposedly satisfied by point-valued utility and probability functions. To ameliorate this difficulty, a version of decision theory that requires merely comparative utilities and plausibilities is proposed. After a brief summary of this alternative, the article illustrates how comparative decision theory (...) affords a rational reconstruction of decisions made by exemplary scientists in two cases of theory choice: Buffon’s law and the luminiferous ether. It also offers a rational reconstruction of two cases of theory diagnosis: Mendeleev’s anomalies and the Pioneer anomaly. (shrink)
Transcendence without reality.John R. Wright -2005 -Philosophy 80 (3):361-384.detailsThomas Nagel has held that transcendence requires attaining a point of view stripped of features unique to our perspective. The aim of transcendence on this view is to get at reality as it is, independent of our contributions to it. I show this notion of transcendence to be incoherent, yet defend a contrasting notion of transcendence. As conceived here, transcendence does not require striving for an external, objective viewpoint on nature or looking at matters from someone else's or an impartial (...) point of view. On my view, which builds on the work of Iris Murdoch, transcendence consists of a refinement of our concepts and sensibility to make them more adequate to the individuals we encounter. (Published Online October 13 2005). (shrink)
Llull and Leibniz: The Logic of Discovery.John R. Welch -1990 -Catalan Review 4:75-83.detailsLlull and Leibniz both subscribed to conceptual atomism: the belief that the majority of concepts are compounds constructed from a relatively small number of primitive concepts. Llull worked out techniques for finding the logically possible combinations of his primitives, but Leibniz criticized Llull’s execution of these techniques. This article argues that Leibniz was right about things being more complicated than Llull thought but that he was wrong about the details. The paper attempts to correct these details.
Cleansing the Doors of Perception: Aristotle on Induction.John R. Welch -2001 - In Konstantine Boudouris,Greek Philosophy and Epistemology. International Association for Greek Philosophy.detailsThis chapter has two objectives. The first is to clarify Aristotle’s view of the first principles of the sciences. The second is to stake out a critical position with respect to this view. The paper sketches an alternative to Aristotle’s intuitionism based in part on the use of quantitative inductive logics.
The Vanishing Wild Card: Challenges and Implications of Ziporyn's Zhuangzi.John R. Williams -2017 -Philosophy East and West 67 (1):177-191.detailsAnalyzing Zhuangzi’s Wild Card as presented by Brook Ziporyn, this essay aims (1) to clarify and draw out certain implications of Zhuangzi’s epistemological agnosticism and perspectivism (qua Ziporyn’s reading thereof), only (2) to problematize Zhuangzi’s response to this epistemological agnosticism and perspectivism (qua Ziporyn’s reading thereof). In turn, given the success of my argumentation, Zhuangzi will prove to be as pertinent (and unsettling) as ever.
Two Types of Moral Dilemma.John R. Welch -2001 - In Matti Häyry & Tuija Takala,The Future of Value Inquiry. Rodopi.detailsThis chapter identifies two types of moral dilemma. The first type is described as ethical clash: whether affirmative action is just or unjust, for example, or whether withholding information from an inquisitive relative is honest or dishonest. In these cases the dilemma takes the form of conflict between an ethical predicate and its complement. The second type of moral dilemma is ethical overlap. Instead of a clash between a single predicate and its complement, here two or more predicates apply. Dilemmas (...) associated with white lies, for example, often depart from the recognition that such acts are both dishonest and avoid inflicting pain. Similarly, social dilemmas over progressive taxation may arise despite agreement that progressive systems both decrease liberty and increase equality. Which predicate should take precedence? Strategies for dealing with both types of dilemma are proposed. (shrink)
Commissions and biomedical ethics: The canadian experience.John R. Williams -1989 -Journal of Medicine and Philosophy 14 (4):425-444.detailsCanadians frequently have recourse to public commissions as a means of dealing with contentious public policy issues. This essay examines the role of philosophers and philosophy in nine such commissions, all of which have dealt with issues in biomedical ethics. The principal findings of this essay are that philosophers have not been used extensively by these commissions, and that the philosophical aspects of the issues under investigation have been dealt with quite inadequately. The essay concludes with suggestions for an expanded (...) role for philosophers in such commissions. Keywords: bioethics, Canada, commissions, inquiries, philosophers CiteULike Connotea Del.icio.us What's this? (shrink)
Understanding Racism as an Ethical Ideology: An Approach to Critical Communication in a White Supremacist Society.John R. Wright -2001 -Social Philosophy Today 17:217-231.detailsTo be fully understood, contemporary forms of racism must be grasped as ethical ideologies rooted in an independent system of value classification. Racism does not merely result from an intrusion of strategic action on communicative action, as discourse ethicists might argue. In contemporary racism, the minority group is seen as perversely incapable of developing a capacity for the behavior that would constitute just moral reciprocity as decided in the contractual situation. Their standing as members of the moral community is thereby (...) qualilied To address racism discursively, the racist must be met with more than an abstract moral demand. Rather, racists must be confronted with the needs and capacities of the racial outsider, so that they might perceive her acts as virtuous and recognize the aptness of her use of value-concepts. (shrink)
The devil's own luck: Lucifer, luck, and moral responsibility.John R. Gilhooly -2022 - Lanham: Lexington Books.detailsThis book argues that the sin of the devil compels a view of moral responsibility that undermines concerns about luck. It surveys the biblical account of the primal sin, its major interpretation in the tradition, and navigates that interpretation through objections from the perspective of moral luck.
Commentary on “The strategic formulation of abductive arguments in everyday reasoning”.John R. Welch -2016 -Argumentation, Objectivity, and Bias: Proceedings of the 11th International Conference of the Ontario Society for the Study of Argumentation (OSSA).detailsHenrike Jansen’s “The strategic formulation of abductive arguments in everyday reasoning” insightfully explores the terrain of abductive argumentation. The purpose of this note is to continue the exploration along lines marked out by her paper. This further exploration proceeds in two stages. Section 2 of the paper addresses the nature of abductive inference by distinguishing two types of abduction, identifying some of abduction’s formal and nonformal properties, and relating abduction to enthymematic inference. Section 3 focuses on some of Jansen’s examples, (...) paying particular attention to the distinction between abduction and argument from sign. Whereas Jansen maintains that some arguments from sign are not abductive, the paper suggests an alternative perspective from which arguments from sign can generally be viewed as one sort of abductive inference. (shrink)
Plausibilistic coherence.John R. Welch -2014 -Synthese 191 (10):2239-2253.detailsWhy should coherence be an epistemic desideratum? One response is that coherence is truth-conducive: mutually coherent propositions are more likely to be true, ceteris paribus, than mutually incoherent ones. But some sets of propositions are more coherent, while others are less so. How could coherence be measured? Probabilistic measures of coherence exist; some are identical to probabilistic measures of confirmation, while others are extensions of such measures. Probabilistic measures of coherence are fine when applicable, but many situations are so information-poor (...) that the requisite probabilities cannot be determined. To measure coherence in these cognitively impoverished situations, this article proposes that the discussion be broadened to include plausibilistic measures of coherence. It shows how plausibilistic measures of coherence can be defined using plausibilistic measures of confirmation. It then illustrates how plausibilisic coherence can be measured in situations where probabilistic coherence cannot be determined. The coherence values obtained through the use of plausibilistic measures are often, though not always, comparable. The article also shows that coherence can be instantiated on different levels, one of which permits connections to inductive strength and deductive validity. (shrink)
Exemplary Persons and Ethics.John R. White -2005 -American Catholic Philosophical Quarterly 79 (1):57-90.detailsFor Max Scheler, St. Francis represented perhaps the highest ideal of the moral life, an ideal he felt compelled to articulate throughout his philosophical work. In this paper, I examine the significance of the person of St. Francis for Scheler’s philosophy. I begin by developing Scheler’s notion of “exemplary person,” the idea that persons act as influences on moral life and thought. I then hypothesize that St. Francis functioned as an exemplary person for Scheler. Finally, I attempt to justify that (...) hypothesis by examining Scheler’s discussion of Francis in Sympathy and by comparing Scheler’s philosophy to elements of the thought of Bonaventure and of Scotus. I conclude with a discussion of the significance of using exemplary persons for understanding the history of philosophy. (shrink)
Ecological Value Cognition and the American Capitalist Ethos.John R. White -2006 -Environmental Philosophy 3 (2):44-51.detailsIn this paper, I investigate what I call “ecological value cognition,” a term designating a cognitive process by which one understands: (1) a value or set of values which pertain to the environment, (2) that such values are morally relevant, and (3) that these values may invite or even require virtues, attitudes or actions with respect to them and the entities which bear them. I seek, in this paper, to elucidate the nature of ecological value cognition and suggest specific challenges (...) that the American capitalist ethos poses for understanding these values and therefore for developing a sound environmental ethics and policy. (shrink)
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A Monistic Interpretation of Whitehead’s Creativity.John R. Wilcox -1991 -Process Studies 20 (3):162-174.detailsCreativity in Whitehead is analogous to prime matter in Aristotle; both principles serve as the counterpart of form. A fundamental difference is that whereas prime matter is purely passive, creativity is pure activity. ;My dissertation focuses on the question whether creativity in some sense exists as numerically one running throughout the entire universe, or only as numerically many in the many individual actual entities which are the basis of his avowed ontological pluralism? ;The most common view in the literature is (...) that creativity exists only as many . Four leading commentators are examined, and each is seen to face a problem with creativity's on-goingness. If creativity exists only in its individuals, then why do new individuals continue to come into existence? Two of the commentators attempt to answer this question by appealing, each in a slightly different way, to creativity's universality; but in both cases it is argued that this form of answer is circular for the pluralist must show that creativity is universal in the future. ;Two other interpreters of creativity are examined who emphasize creativity's causal role in perpetuating the universe. Analysis of their interpretations shows that each in fact requires creativity to be something numerically one throughout the universe , though this view is not made explicit. ;A monistic interpretation is then put forward and defended against a common criticism; namely, that it is inconsistent with Whitehead's ontological pluralism. It is argued that creativity implies process and process implies a plurality of stages. The monistic creativity is not more real than its plurality of stages, since these stages are essential to its being a creating activity. Creativity is merely the counterpart of form; each stage of creativity's process has its own ingredient eternal objects and its own subjective aim at satisfaction in terms of which it is a novel atomic individual . A monistic creativity does not imply ontological monism. Furthermore, since it solves the problem of on-goingness, it should replace the received pluralistic interpretation. (shrink)
Parmenides, B 8. 4.John R. Wilson -1970 -Classical Quarterly 20 (01):32-.detailsThe text of Parmenides 8. 4 is unusually corrupt. Most recent critics, however, agree that Plutarch's printed in the later editions of DielsKranz, Die Fragmente der Vorsokratiker, should be excluded in favour of As G. E. L. Owen remarks , ‘[Plutarch's] is inappropriate since is to be proved from and not vice versa’.
The ethics activities of the world medical association.John R. Williams -2005 -Science and Engineering Ethics 11 (1):7-12.detailsSince its formation in 1947, the World Medical Association (WMA) has been a leading voice in international medical ethics. The WMA’s principal ethics activity over the years has been policy development on a wide variety of issues in medical research, medical practice and health care delivery. With the establishment of a dedicated Ethics Unit in 2003, the WMA’s ethics activities have intensified in the areas of liaison, outreach and product development. Initial priorities for the Ethics Unit have been the review (...) of paragraph 30 of the Declaration of Helsinki, the expansion of the Ethics Unit section of the WMA website and the development of an ethics manual for medical students everywhere. (shrink)
The physician’s role in the protection of human research subjects.John R. Williams -2006 -Science and Engineering Ethics 12 (1):5-12.detailsResponsibility for the protection of human research subjects is shared by investigators, research ethics committees, sponsors/funders, research institutions, governments and, the focus of this article, physicians who enrol patients in clinical trials. The article describes the general principles of the patient-physician relationship that should regulate the participation of physicians in clinical trials and proposes guidelines for determining when and how such participation should proceed. The guidelines deal with the following stages of the trial: when first considering participation, when deciding whether (...) to enrol patients, when asking patients to participate, when the trial is underway and when it is completed. (shrink)