Chronic myeloid leukemia (CML) is a cancer of the hematopoietic system initiated by a single genetic mutation which results in the oncogenic fusion protein Bcr-Abl. Untreated, patients pass through different phases of the disease beginning with the rather asymptomatic chronic phase and ultimately culminating into blast crisis, an acute leukemia resembling phase with a very high mortality. Although many processes underlying the chronic phase are well understood, the exact mechanisms of disease progression to blast crisis are not yet revealed. In (...) this paper we develop a mathematical model of CML based on causal Bayesian networks in order to study possible disease progression mechanisms. Our results indicate that an increase of Bcr-Abl levels alone is not sufficient to explain the phenotype of blast crisis and that secondary changes such as additional mutations are necessary to explain disease progression and the poor therapy response of patients in blast crisis. (shrink)

Background: Treating medication-refractory freezing of gait in Parkinson’s disease remains challenging despite several trials reporting improvements in motor symptoms using subthalamic nucleus or globus pallidus internus deep brain stimulation. Pedunculopontine nucleus region DBS has been used for medication-refractory FoG, with mixed findings. FoG, as a paroxysmal phenomenon, provides an ideal framework for the possibility of closed-loop DBS.Methods: In this clinical trial, five subjects with medication-refractory FoG underwent bilateral GPi DBS implantation to address levodopa-responsive PD symptoms with open-loop stimulation. Additionally, PPN (...) DBS leads were implanted for CL-DBS to treat FoG. The primary outcome of the study was a 40% improvement in medication-refractory FoG in 60% of subjects at 6 months when “on” PPN CL-DBS. Secondary outcomes included device feasibility to gauge the recruitment potential of this four-lead DBS approach for a potentially larger clinical trial. Safety was judged based on adverse events and explantation rate.Findings: The feasibility of this approach was demonstrated as we recruited five subjects with both “on” and “off” medication freezing. The safety for this population of patients receiving four DBS leads was suboptimal and associated with a high explantation rate of 40%. The primary clinical outcome in three of the five subjects was achieved at 6 months. However, the group analysis of the primary clinical outcome did not reveal any benefit.Interpretation: This study of a human PPN CL-DBS trial in medication-refractory FoG showed feasibility in recruitment, suboptimal safety, and a heterogeneous clinical effect in FoG outcomes. (shrink)

Despite the widely known Latin proverb, according to which about tastes it should not be discussed, concerning judgments of taste, we do dispute. However, based on what? If someone disagrees with our judgment, judging differently than us, we seek arguments to try to convince them otherwise. But by which arguments? The paper dwells on the issues about what underlies the arguments we use to justify our judgments of taste and how reliable these arguments are. From eighteenth-century philosophy to contemporary philosophy (...) of consciousness and mind, the aim here is to show that judgments of taste involve self-knowledge and that the question “how does it feel?”, at first glance simple, does not seem to be so easy to answer. (shrink)

Theories of discourse bring to realism new ideas about how knowledge develops and how representations of reality are influenced. We gain an understanding of the conceptual aspect of social life and the processes by which meaning is produced. This collection reflects the growing interest realist critics have shown towards forms of discourse theory and deconstruction. The diverse range of contributions address such issues as the work of Derrida and deconstruction, discourse theory, Eurocentrism and poststructuralism. What unites all of the contributions (...) is a sense that it is essential to provide a realist alternative to the hitherto dominance of social constructionism, hermeneutics and postmodernism, over many of the issues discussed. By developing a realist perspective the different authors attempt to embed discourse within the structured nature of the reality of the world. Realism can situate language, discourse and ideology within context specific, or 'causally efficacious' circumstances. Realism can help to uncover issues of power, representation, and subjectivity and how discursive and other social practices produce real effects. This can help us understand the manner in which social structures are reproduced through various forms of ideology and discourse. And by knowing this, we can start to address questions concerning human emancipation and how the world is to be transformed. (shrink)

This is a paradigmatic work of contemporary philosophy.

Robert Hanna presents a fresh view of the Kantian and analytic traditions that have dominated continental European and Anglo-American philosophy over the last two centuries, and of the connections between them. But this is not just a study in the history of philosophy, for out of this emerges Hanna's original approach to two much-contested theories that remain at the heart of contemporary philosophy. Hanna puts forward a new 'cognitive-semantic' interpretation of transcendental idealism, and a vigorous defense of Kant's theory (...) of analytic and synthetic necessary truth, making this compelling reading for all who are interested in these fundamental philosophical issues. (shrink)

Classical American pragmatism: the pragmatist -- Enlightenment-and its problematic semantics -- Analyzing pragmatism: pragmatics and pragmatisms -- A Kantian rationalist pragmatism: pragmatism -- Inferentialism, and modality in Sellars's arguments against -- Empiricism -- Linguistic pragmatism and pragmatism about norms: an arc of -- Thought from Rorty's eliminative materialism to his pragmatism -- Vocabularies of pragmatism: synthesizing naturalism and -- Historicism -- Towards an analytic pragmatism: meaning-use analysis -- Pragmatism, expressivism, and anti-representationalism: -- Local and global possibilities.

A sourcebook for developing and facilitating collaborative groups capable of continuously adapting to anticipate the evolving learning needs of students. Based on a theoretical foundation of schools as complex systems in which linear management models are no longer sufficient.

In order to carry out “a great and important piece of work, and that in a complete and lasting way”, Kant claims that one must join one’s “effort with that of the author”. The reading of a work, therefore, must try to embrace “the articulation or structure of the system, which yet matters most when it comes to judging its unity and soundness”. This structure and articulation, however, may not be so easily accessible; it may, rather, be latent under “bright (...) colours [that] paint over and make unrecognizable” the argument’s essence, often confusing the reader, who “cannot quickly enough attain a survey of the whole”. Now, it would be expected, then, that Kant, condemning such “ornaments”, would not employ those resources I n his writings. However, it is curious that not infrequently he makes use of such “bright colours”. The present paper aims at pointing out some passages of Kant's theoretical and practical philosophy in which it is possible to identify such “colouring”. (shrink)

Develops a theory of culture based on a metaphysics that elaborates on the Platonic and Confucian traditions. In Metaphysics of Goodness, Robert Cummings Neville extends Alfred North Whitehead’s project of cultural studies, which was based on a new metaphysics that Whitehead developed in Adventures of Ideas. Neville’s focus is value or goodness in many modes. The metaphysics treated in this book derive from the Platonic and Confucian traditions, with significant modifications of Whitehead, Peirce, Dewey, Confucius, Xunzi, and Zhou Dunyi. (...) Part one develops a theory of form based on a metaphysics of harmony. Part two elaborates a theory of art based on a metaphysics of beauty. Part three sketches a theory of personhood based on a metaphysics of obligation. Part four discusses civilization in a systematic way based on a metaphysics of flourishing. Throughout the book, Neville elaborates a theory of interpretation that is inspired by Peirce, Dewey, and Xunzi but is not limited to their ideas. While the reasoning of the book is concise, it employs methodologies from many kinds of philosophy, art criticism, ethics, and cultural studies, and sees philosophy as needing to learn from all these disciplines. “Neville’s work is informed by a lifelong engagement with the most important philosophers in history, including Plato, Aristotle, Whitehead, and Dewey. Here, he offers an important argument that there is beauty not only in how people see the world, but also in the world itself.” — Kevin Schilbrack, Appalachian State University. (shrink)

Abstract:This paper is a preliminary attempt to better understand the concept of legitimacy in stakeholder theory. The normative component of stakeholder theory plays a central role in the concept of legitimacy. Though the elaboration of legitimacy contained herein applies generally to all “normative cores” this paper relies on Phillips’s principle of stakeholder fairness and therefore begins with a brief description of this work. This is followed by a discussion of the importance of legitimacy to stakeholder theory as well as the (...) general ambiguity of the term. A distinction is then drawn between normative and derivative legitimacy. Reference to this distinction helps distinguish between a relationship with the organization based on direct moral obligation and one based on the power to help or harm the organization. It is concluded that stakeholders who retain the ability to affect the organization arelegitimate(derivatively), but that this legitimacy is derived from the moral obligation owed other (normative) stakeholders and that the two sorts of legitimacy are importantly different from one another. An example of the normative/derivative distinction at work in managerial decision making is elaborated upon and managerial and research implications are then suggested. (shrink)

Abstract:Should the responsibilities of business managers be understood independently of the social circumstances and “market forces” that surround them, or (in accord with empiricism and the social sciences) are agents and their choices shaped by their circumstances, free only insofar as they act in accordance with antecedently established dispositions, their “character”? Virtue ethics, of which I consider myself a proponent, shares with empiricism this emphasis on character as well as an affinity with the social sciences. But recent criticisms of both (...) empiricist and virtue ethical accounts of character deny even this apparent compromise between agency and environment. Here is an account of character that emphasizes dynamic interaction both in the formation and in the interplay between personal agency and responsibility on the one hand and social pressures and the environment on the other. (shrink)

The literature on theoretical reason has been dominated by epistemological concerns, treatments of practical reason by ethical concerns. This book overcomes the limitations of dealing with each separately. It sets out a comprehensive theory of rationality applicable to both practical and theoretical reason. In both domains, Audi explains how experience grounds rationality, delineates the structure of central elements, and attacks the egocentric conception of rationality. He establishes the rationality of altruism and thereby supports major moral principles. The concluding part describes (...) the pluralism and relativity his conception of rationality accommodates and, taking the unified account of theoretical and practical rationality in that light, constructs a theory of global rationality--the overall rationality of persons. Rich in narrative examples, intriguing analogies, and intuitively appealing arguments, this beautifully crafted book will spur advances in ethics and epistemology as well in philosophy of mind and action and the theory of rationality itself. (shrink)

This book is available either individually, or as part of the specially-priced Arguments of the Philosphers Collection.

The volume concludes by examining a critique of Hegel's metaphysical position from the perspective of the "continental" tradition, and in particular Gilles ...

A subtle and distinguished work by a philosopher renowned for his groundbreaking analysis of human emotions, About Love.

In “The Sources of Knowledge,” Robert Audi distinguishes what he calls the “four standard basic sources” by which we acquire knowledge or justified belief: perception, memory, consciousness, and reason. With the exception of memory, he distinguishes each of the above as a basic source of knowledge. Audi contrasts basic sources with nonbasic sources, concentrating on testimony. After clarifying the relationship between a source and a ground, or “what it is in virtue of which one knows or justifiedly believes,” Audi (...) evaluates the basic sources’ individual and collective autonomy as well as their vulnerability to defeasibility. He also examines the relationship of coherence to knowledge and justification, noting the distinction between a negative dependence on incoherence and a positive dependence on coherence. (shrink)

Looks at accounts by Locke, Fodor, Dretske, and Millikan concerning the nature of mental representation, and discusses connectionism and representation.

Robert Batterman examines a form of scientific reasoning called asymptotic reasoning, arguing that it has important consequences for our understanding of the scientific process as a whole. He maintains that asymptotic reasoning is essential for explaining what physicists call universal behavior. With clarity and rigor, he simplifies complex questions about universal behavior, demonstrating a profound understanding of the underlying structures that ground them. This book introduces a valuable new method that is certain to fill explanatory gaps across disciplines.

In “Conditions and Analyses of Knowledge”, Robert Shope focuses on the conditions that must be satisfied for a person to have knowledge, specifically knowledge that something is so. Traditionally, knowledge has been analyzed in terms of justified true belief. Shope addresses philosophers’ disagreements concerning the truth and belief conditions. After introducing the justification condition, he presents challenges that have provoked several attempts to replace or to supplement the justification condition for knowledge. Shope presents and assesses several of these, including (...) early causal theories, the nonaccidentality requirement, reliable process and conditional analyses, the reliable‐indicator analysis, the conclusive reasons analysis, defeasibility analyses, analyses in terms of cognitive or intellectual virtues, and proper functionalism as well as his own account of knowledge. (shrink)

"This is an important new Cummins work.

From the ferment of recent debates about the intellectual virtues, Roberts and Wood develop an approach they call 'regulative epistemology', exploring the connection between knowledge and intellectual virtue. In the course of their argument they analyse particular virtues of intellectual life - such as courage, generosity, and humility - in detail.

Introduction -- Modes of settling: settling down, settling in, settling up, settling for, settling one's affairs, settling on -- The value of settling: settling as an aid to planning and agency, settling, commitment, trust, and confidence, settling the social fabric -- What settling is not: settling is not just compromising, settling is not just conservatism, settling is not just resignation -- Settling in aid of striving: settling in order to strive, what strivings require settling, and why, when to switch between (...) one and the other, and why -- Conclusions. (shrink)

ABSTRACT:Utilitarianism is commonly defined in very different ways, sometimes in a single text. There is wide agreement that it mandates maximizing some kind of good, but many formulations also require a pattern of distribution. The most common of these take utilitarianism to characterize right acts as those that achieve “the greatest good for the greatest number.” This paper shows important ambiguities in this formulation and contrasts it (on any plausible interpretation of it) with the kinds of utilitarian views actually defended (...) by major proponents of utilitarianism. The aim is not to defend any of these views but to formulate them in a way that facilitates using them—or, more likely, some revised version suggested by the paper—in guiding decisions in business. The analysis provided here should also facilitate appraisal of utilitarianism, contribute to clarity in discussions of business ethics, and suggest a range of ethical standards that merit consideration for certain kinds of decision. If the results of the analysis are correct, a distributive reading of utilitarianism is at best misleading as a representation of its central thrust; it should not be described as the view that ethics calls for achieving “the greatest good for the greatest number”; and, understood as its major proponents take it, utilitarianism differs more from Kantian ethics than distributive readings imply and is more difficult to defend than it appears to be when viewed as intrinsically distributive. (shrink)

Robert Stern investigates how scepticism can be countered by using transcendental arguments concerning the necessary conditions for the possibility of experience, language, or thought. He shows that the most damaging sceptical questions concern neither the certainty of our beliefs nor the reliability of our belief-forming methods, but rather how we can justify our beliefs.

This collection of 21 essays explores the creative interaction among the cognitive neurosciences, philosophy, and theology. It is the result of an international research conference co-sponsored by the Vatican Observatory, Rome, and the Center for Theology and the Natural Sciences, Berkeley.

Are historians storytellers? Is it possible to tell true stories about the past? These are just a couple of the questions raised in this comprehensive collection of texts about philosophy, theory, and methodology of writing history. Drawing together seminal texts from philosophers and historians, this volume presents the great debate over the narrative character of history from the 1960s onwards. The History and Narrative Reader combines theory with practice to offer a unique overview of this debate and illuminates the practical (...) implications of these philosophical debates for the writing of history. The editor's introduction offers a succinct survey of the subject to support the readings, which explore the role of narrative in everything from historical understanding and human action to linguistics and the practice of history. Including the work of F. R. Ankersmit, David Carr, Hayden White, W. H. Dray, and Frederick Olafson; a detailed bibliography; and a glossary of key concepts, this collection will prove an invaluable resource for students of historical theory and methodology. (shrink)

ABSTRACT The term “applied science,” as it came to be popularly used in the 1870s, was a hybrid of three earlier concepts. The phrase “applied science” itself had been coined by Samuel Taylor Coleridge in 1817, translating the German Kantian term “angewandte Wissenschaft.” It was popularized through the Encyclopaedia Metropolitana, which was structured on principles inherited from Coleridge and edited by men with sympathetic views. Their concept of empirical as opposed to a priori science was hybridized with an earlier English (...) concept of “practical science” and with “science applied to the arts,” adopted from the French. Charles Dupin had favored the latter concept and promoted it in the reconstruction of the Conservatoire Nationale des Arts et Métiers. The process of hybridization took place from the 1850s, in the wake of the Great Exhibition, as a new technocratic government favored scientific education. “Applied science” subsequently was used as the epistemic basis for technical education and the formation of new colleges in the 1870s. (shrink)

Robert Stalnaker draws together in this volume his seminal work in metaphysics. The central theme is the role of possible worlds in articulating our various metaphysical commitments. The book begins with reflections on the general idea of a possible world, and then uses the framework of possible worlds to formulate and clarify some questions about properties and individuals, reference, thought, and experience. The essays also reflect on the nature of metaphysics, and on the relation between questions about what there (...) is and questions about how we talk and think about what there is. Two of the fourteen essays, plus an extensive introduction that sets the papers in context and draws out the essays' common threads, are published here for the first time. (shrink)

Introduction -- Trapped by oneself in Jacques Tourneur's Out of the past -- "A deliberate, intentional fool" in Orson Welles's The lady from Shanghai -- Sexual agency in Fritz Lang's Scarlet Street -- "Why didn't you shoot again, baby?": concluding remarks.

This article discusses minimal model explanations, which we argue are distinct from various causal, mechanical, difference-making, and so on, strategies prominent in the philosophical literature. We contend that what accounts for the explanatory power of these models is not that they have certain features in common with real systems. Rather, the models are explanatory because of a story about why a class of systems will all display the same large-scale behavior because the details that distinguish them are irrelevant. This story (...) explains patterns across extremely diverse systems and shows how minimal models can be used to understand real systems. (shrink)

This work, first published in 1985, offers a general interpretation of Hume's Treatise of Human Nature. Most Hume scholarship has either neglected or downplayed an important aspect of Hume's position - his scepticism. This book puts that right, examining in close detail the sceptical arguments in Hume's philosophy.

This book is a lively and provoking introduction to film theory.

Cushman (1913-93) was a systematic theologian at Duke University. He looks at Plato's philosophy as a whole and single system, but also reappraises the basis of his pervasive and unyielding conviction that metaphysical relations actually obtain for people's finite existence, whether recognized or not, and that it is upon those relations that their present and ultimate hope rests. The 1958 edition was published by the University of North Carolina Press. Michae Henry (philosophy, St. John's U.) contributes a new introduction. c. (...) Book News Inc. (shrink)

It is a near truism of philosophy of language that sentences are prior to words--that they are the only things that fundamentally have meaning. Robert's Stainton's study interrogates this idea, drawing on a wide body of evidence to argue that speakers can and do use mere words, not sentences, to communicate complex thoughts.

This paper articulates and responds to a challenge to contemporary compatibilist views of free will. Despite the popularity and appeal of compatibilist theories, many are left with lingering doubts about compatibilism. This paper explains this doubt in terms of the absurdity challenge: because a compatibilist accepts that they do not have causal access to all the actual sufficient causal sources of their own agency, the compatibilist can find their own agency absurd. By taking a cue from political philosophy, this paper (...) argues that a non-ideal construction of the problem of free will allows compatibilists to overcome this existential-metaphysical challenge, and by doing so, perhaps adopt a metaphysically progressive picture of human agency. (shrink)

The Federalist, justifying the Electoral College to elect the president, claimed that a small group of more informed individuals would make a better decision than the general mass. But the Condorcet Jury Theorem tells us that the more independent, better-than-random voters there are, the more likely it will be that the majority among them will be correct. The question thus arises as to how much better, on average, members of the smaller group would have to be to compensate for the (...) epistemic costs of making decisions on the basis of that many fewer votes. This question is explored in the contexts of referendum democracy, delegate-style representative democracy, and trustee-style representative democracy. (shrink)