The focus on translational research in clinical trials has the potential to generate clinically relevant genetic data that could have importance to patients. This raises challenging questions about communicating relevant genetic research results to individual patients. An exploratory pharmacogenetic analysis was conducted in the international ovarian cancer phase III trial, AGO-OVAR 16, which found that patients with clinically important germ-line BRCA1/2 mutations had improved progression-free survival prognosis. Mechanisms to communicate BRCA results were evaluated, because these findings may be beneficial to (...) patients and their families. Communicating individual BRCA results was not anticipated during clinical trial design. Consequently, options were not available for patients to indicate their preference for receiving their individual results when they signed pharmacogenetic informed consent. Differences in local requirements, clinical practice, and opinion regarding the ethical aspects of how to convey genetic results to patients are all potential barriers to returning individual BRCA results to patients. Communicating the aggregate BRCA result from this study provided clinical investigators with a mechanism to disseminate the overall study finding to patients while taking individual circumstances, local guidelines and clinical practice into account. This study illustrates the importance of increasing the clarity and scope of informed consent and the need for patient engagement to ensure clinical trial participants can indicate their preference regarding receipt of potentially important individual pharmacogenetic results. This study was registered in the NCT Clinical Trial Registry under NCT00866697 on March 19, 2009, following approval from participating ethics committees. (shrink)

Oxidative damage to DNA has been associated with neurodegenerative diseases. Developmental exposure to lead has been shown to elevate the Alzheimer's disease related beta-amyloid peptide , which is known to generate reactive oxygen species in the aging brain. This study measures the lifetime cerebral 8-hydroxy-2'-deoxyguanosine levels and the activity of the DNA repair enzyme 8-oxoguanine DNA glycosylase in rats developmentally exposed to Pb. Oxo8dG was transiently modulated early in life , but was later elevated 20 months after exposure to Pb (...) had ceased, while Ogg1 activity was not altered. Furthermore, an age-dependent loss in the inverse correlation between Ogg1 activity and oxo8dG accumulation was observed. The effect of Pb on oxo8dG levels did not occur if animals were exposed to Pb in old age. These increases in DNA damage occurred in the absence of any Pb-induced changes in copper/zinc-superoxide dismutase , manganese-SOD , and reduced-form glutathion . These data suggest that oxidative damage and neurodegeneration in the aging brain could be impacted by the developmental disturbances. (shrink)

Much of our understanding of human thinking is based on probabilistic models. This innovative book by Jerome R. Busemeyer and Peter D. Bruza argues that, actually, the underlying mathematical structures from quantum theory provide a much better account of human thinking than traditional models. They introduce the foundations for modelling probabilistic-dynamic systems using two aspects of quantum theory. The first, 'contextuality', is a way to understand interference effects found with inferences and decisions under conditions of uncertainty. The second, 'quantum (...) entanglement', allows cognitive phenomena to be modeled in non-reductionist ways. Employing these principles drawn from quantum theory allows us to view human cognition and decision in a totally new light. Introducing the basic principles in an easy-to-follow way, this book does not assume a physics background or a quantum brain and comes complete with a tutorial and fully worked-out applications in important areas of cognition and decision. (shrink)

A critical and constructive discussion of philosophical questions which have particular bearing on the formulation of educational aims.

It is argued that awareness of the distinction between dynamical and variational symmetries is crucial to understanding the significance of Noether's 1918 work. Specific attention is paid, by way of a number of striking examples, to Noether's first theorem, which establishes a correlation between dynamical symmetries and conservation principles.

Originating from work in operations research the cutting plane refutation systemCP is an extension of resolution, where unsatisfiable propositional logic formulas in conjunctive normal form are recognized by showing the non-existence of boolean solutions to associated families of linear inequalities. Polynomial sizeCP proofs are given for the undirecteds-t connectivity principle. The subsystemsCP q ofCP, forq≥2, are shown to be polynomially equivalent toCP, thus answering problem 19 from the list of open problems of [8]. We present a normal form theorem forCP (...) 2-proofs and thereby for arbitraryCP-proofs. As a corollary, we show that the coefficients and constant terms in arbitrary cutting plane proofs may be exponentially bounded by the number of steps in the proof, at the cost of an at most polynomial increase in the number of steps in the proof. The extensionCPLE +, introduced in [9] and there shown top-simulate Frege systems, is proved to be polynomially equivalent to Frege systems. Lastly, since linear inequalities are related to threshold gates, we introduce a new threshold logic and prove a completeness theorem. (shrink)

Internal global symmetries exist for the free non-relativistic Schrodinger particle, whose associated Noether charges---the space integrals of the wavefunction and the wavefunction multiplied by the spatial coordinate---are exhibited. Analogous symmetries in classical electromagnetism are also demonstrated.

The McNaughton rules for determining whether a person can be successfully defended on the grounds of mental incompetence were determined by a committee of the House of Lords in 1843. They arose as a consequence of the trial of Daniel McNaughton for the killing of Prime Minister Sir Robert Peel’s secretary. In retrospect it is clear that McNaughton suffered from schizophrenia. The successful defence of McNaughton on the grounds of mental incompetence by his advocate Sir Alexander Cockburn involved a profound (...) shift in the criteria for such a defence, and was largely based on the then recently published scientific thesis of the great US psychiatrist Isaac Ray, entitled A Treatise on the Medical Jurisprudence of Insanity. Subsequent discussion of this defence in the House of Lords led to the McNaughton rules, still the basis of the defence of mental incompetence in the courts of much of the English-speaking world. This essay considers one of these rules in the light of the discoveries of cognitive neuroscience made during the 160 years since Ray’s treatise. A major consideration is the relationship between the power of self-control and irresistible impulse as conceived by Cockburn on the one hand, and by cognitive neuroscience on the other. The essay concludes with an analysis of the notion of free will and of the extent to which a subject can exert restraint in the absence of particular synaptic connections in the brain. (shrink)

It is a pleasure to be able to pay tribute to Adam Potkay’s interesting and impressive book on two of the most important figures in the eighteenth century. It brings together the philosophical and the literary, the “anatomist” and the “painter” of the passions and the moral life, integrating worlds that, however isolated they may have become in the twentieth century, were not seen as all that distinct in the eighteenth. Having said this, the most remarkable feature of Potkay’s book (...) is that it unites two figures usually thought to be opposed—the irascible, domineering, and deeply Christian Johnson and the dispassionate, moderate, and pagan Hume. (shrink)

History of Cognitive Neuroscience documents the major neuroscientific experiments and theories over the last century and a half in the domain of cognitive neuroscience, and evaluates the cogency of the conclusions that have been drawn from them. Provides a companion work to the highly acclaimed Philosophical Foundations of Neuroscience – combining scientific detail with philosophical insights Views the evolution of brain science through the lens of its principal figures and experiments Addresses philosophical criticism of Bennett and Hacker?s previous book Accompanied (...) by more than 100 illustrations. (shrink)

Introduction / Jeffrey R. Di Leo, Peter Hitchcock, and Sophia A. McClennen -- Theory and history -- The rights to debt? / Sophia A. McClennen -- Kant at the Federal Reserve : on the aesthetics of quantitative easing / Peter Hitchcock -- Materialism : debt and sensuality / Christopher Breu -- The indebted man's cognitive mapping : boundaries and biohorror in the neoliberal debt economy / Liane Tanguay -- Living in the debt age -- The debt experience / (...) Jeffrey J. Williams -- Paying your debt to society : the neoliberal state and the logic of quid pro quo / Esther Peeren -- Indebted youth and neoliberalism / Tyler J. Pollard -- Austerity politics and the neoliberal target austerity politics and the neoliberal targeting of the body in public education / Kenneth J. Saltman -- Resisting the debt age -- On debt resistance / Jeffrey R. Di Leo -- Debt and financial literacy education : an ethics for capital or the other / Chris Arthur -- Student debt and the social functions of consolidation college / Christopher Newfield -- Confronting the creditor class / Andrew Ross -- Index. (shrink)

There are many benefits of using argumentation-based techniques in multi-agent systems, as clearly shown in the literature. Such benefits come not only from the expressiveness that argumentation-based techniques bring to agent communication but also from the reasoning and decision-making capabilities under conditions of conflicting and uncertain information that argumentation enables for autonomous agents. When developing multi-agent applications in which argumentation will be used to improve agent communication and reasoning, argumentation schemes are useful in addressing the requirements of the application domain (...) in regards to argumentation. In this work, we propose an argumentation framework that takes into account the particular structure of argumentation schemes at its core. This paper formally defines such a framework and experimentally evaluates its implementation for both argumentation-based reasoning and dialogues. (shrink)

We discuss the relation of the Theory of Event Coding (TEC) to a computational model of expert perception, CHREST, based on the chunking theory. TEC's status as a verbal theory leaves several questions unanswerable, such as the precise nature of internal representations used, or the degree of learning required to obtain a particular level of competence: CHREST may help answer such questions.

Over the last century, Alzheimer’s disease has proven a highly malleable concept. Initially an obscure diagnosis pertaining to rare cases of young onset dementia, by the latter half of the 20th cen...

In this paper we outline the activities of young girls in a Toba community of northern Argentina and examine the effect of girl helpers on time allocation of nursing women. Activity budgets were obtained for 41 girls aged 3 to 15 using spot observations. Girls spent substantial portions of observations engaged in helping behaviors. Individual values varied with age, anthropometric characteristics, and birth order. Activity budgets of 21 nursing women were obtained through focal observation sessions. Women living in households with (...) girls aged 7 to 15 allocated 17% less time to domestic work and 9% more time to socializing during afternoon observation sessions. For nursing women in this community, direct childcare (provided by the infant’s own mother) seemed to be a priority. Living with a girl helper did not have any measurable effect on the frequency or duration of nursing, or on the time that women spent caring for their infants. Based on these findings, hypotheses are outlined for future work on the effect of girl helpers on women’s fertility. (shrink)

Addressing both collegiate and professional sports, the updated edition of Fair Play: The Ethics of Sport explores the ethical presuppositions of competitive athletics and their connection both to ethical theory and to concrete moral dilemmas that arise in actual athletic competition. This fourth edition has been updated with new examples, including a discussion of Spygate by the New England Patriots and recent discoveries on the use of performance enhancing drugs by top athletes. Two additional authors, Cesar R. Torres and (...) class='Hi'>Peter F. Hager, bring to this edition a discussion of the moral issues involved in youth sports and the ethics of being a fan, as well as a fresh perspective on the theories of broad internalism and the quest for excellence. Furthermore, major criticisms of broad internalism by philosophers William J. Morgan and Scott Kretchmar add a new dimension to the discussion on the moral foundations of winning. (shrink)

Peter Anstey presents a thorough and innovative study of John Locke's views on the method and content of natural philosophy. Focusing on Locke's Essay concerning Human Understanding, but also drawing extensively from his other writings and manuscript remains, Anstey argues that Locke was an advocate of the Experimental Philosophy: the new approach to natural philosophy championed by Robert Boyle and the early Royal Society who were opposed to speculative philosophy. On the question of method, Anstey shows how Locke's pessimism (...) about the prospects for a demonstrative science of nature led him, in the Essay, to promote Francis Bacon's method of natural history, and to downplay the value of hypotheses and analogical reasoning in science. But, according to Anstey, Locke never abandoned the ideal of a demonstrative natural philosophy, for he believed that if we could discover the primary qualities of the tiny corpuscles that constitute material bodies, we could then establish a kind of corpuscular metric that would allow us a genuine science of nature. It was only after the publication of the Essay, however, that Locke came to realize that Newton's Principia provided a model for the role of demonstrative reasoning in science based on principles established upon observation, and this led him to make significant revisions to his views in the 1690s. On the content of Locke's natural philosophy, it is argued that even though Locke adhered to the Experimental Philosophy, he was not averse to speculation about the corpuscular nature of matter. Anstey takes us into new terrain and new interpretations of Locke's thought in his explorations of his mercurialist transmutational chymistry, his theory of generation by seminal principles, and his conventionalism about species. (shrink)

Humans hunt and kill many different species of animals, but whales are our biggest prey. In the North Atlantic, a male long-fi nned pilot whale (Globiceph- ala melaena), a large relative of the dolphins, can grow as large as 6.5 meters and weigh as much as 2.5 tons. As whales go, these are not particularly large, but there are more than 750,000 pilot whales in the North Atlantic, traveling in groups, “pods,” that range from just a few individuals to a (...) thousand or more. Each pod is led by an individual known as the “pilot,” who appears to set the course of travel for the rest of the group. This pilot is both an asset and a weakness to the pod. The average pilot whale will yield about a half ton of meat and blubber, and North Atlantic societies including Ireland, Iceland, and the Shetlands used to manipulate the pilot to drive the entire pod ashore. In the Faroe Islands, a group of 18 grassy rocks due north of Scotland, pilot whale hunts have continued for the last 1200 years, at least. The permanent residents of these islands, the Faroese, previously killed an average of 900 whales each year, yielding about 500 tons of meat and fat that was consumed by local residents. Hunts have declined in recent years. From 2001 to 2005, about 3400 whales were killed, yielding about 890 metric tons of blubber and 990 metric tons of meat. The whale kill, or grindadráp in the Faroese language, begins when a fi shing boat spots a pod close enough to a suitable shore, on a suitably clear day. A single boat, or even a small group of fi shermen, is not suffi cient to trap a.. (shrink)

Philosophy and Kafka is a collection of original essays interrogating the relationship of literature and philosophy. The essays either discuss specific philosophical commentaries on Kafka’s work, consider the possible relevance of certain philosophical outlooks for examining Kafka’s writings, or examine Kafka’s writings in terms of a specific philosophical theme, such as communication and subjectivity, language and meaning, knowledge and truth, the human/animal divide, justice, and freedom.