A crisis continues to brew within the pharmaceutical research and development (R&D) enterprise: productivity continues declining as costs rise, despite ongoing, often dramatic scientific and technical advances. To reverse this trend, we offer various suggestions for both the expansion and broader adoption of modeling and simulation (M&S) methods. We suggest strategies and scenarios intended to enable new M&S use cases that directly engage R&D knowledge generation and build actionable mechanistic insight, thereby opening the door to enhanced productivity. What M&S requirements (...) must be satisfied to access and open the door, and begin reversing the productivity decline? Can current methods and tools fulfill the requirements, or are new methods necessary? We draw on the relevant, recent literature to provide and explore answers. In so doing, we identify essential, key roles for agent-based and other methods. We assemble a list of requirements necessary for M&S to meet the diverse needs distilled from a collection of research, review, and opinion articles. We argue that to realize its full potential, M&S should be actualized within a larger information technology framework—a dynamic knowledge repository—wherein models of various types execute, evolve, and increase in accuracy over time. We offer some details of the issues that must be addressed for such a repository to accrue the capabilities needed to reverse the productivity decline. (shrink)

There is a simple, intuitive theory of the semantic reference of proper names that has been unjustly neglected. This is the view that semantic reference is conventionalized speakers reference, i.e. the view that a name semantically refers to an object if, and only if, there exists a convention to use the name to speaker-refer to that object. The theory can be found in works dealing primarily with other issues (e.g. Stine in Philos Stud 33:319–337, 1977; Schiffer in Erkenntnis 13:171–206, 1978; (...) Sainsbury in Erkenntnis 80:195–214, 2015; Sainsbury, Thinking about things, Oxford University Press, 2018), yet these authors provide no sustained discussion of it. Devitt (Designation, Columbia University Press, 1981) did formulate a view on which semantic reference is conventionalized speaker’s reference, yet his views are assimilated to causalist views. This is a mistake. While the conventionalized speaker’s reference view captures much of what is plausible in descriptivism and causalism, it remains distinct from both. (shrink)

Kripke (1977) views Donnellan's (1966) misdescription cases as cases where semantic reference and speaker's reference come apart. Such cases, however, are also cases where semantic reference conflicts with a distinct species of reference I call "public reference", i.e. the object that the cues publicly available at the time of utterance indicate is the speaker's referent of the utterance. This raises the question: do the misdescription cases trade on the distinction between semantic reference and speaker's reference, or the distinction between semantic (...) reference and public reference? I argue that Kripke's own construal in terms of semantic reference and speaker's reference is at best incomplete, and probably wrong. I also explain the general importance of the notion of 'public reference'. (shrink)

This paper argues, based on Lewis’ claim that communication is a coordination game (Lewis in Minnesota studies in the philosophy of science, University of Minnesota Press, Minneapolis, pp 3–35, 1975), that we can account for the communicative function of demonstratives without assuming that they semantically refer. The appeal of such a game theoretical version of the case for non-referentialism is that the communicative role of demonstratives can be accounted for without entering the cul de sac of trying to construct conventions (...) of ever-increasing complexity. Instead communication via demonstratives is explained with reference to the general, non-domain specific ability of human beings to solve games of coordination. Furthermore, there is empirical support for such a view. Judgments concerning demonstrative reference have been shown to be sensitive to judgments concerning common ground (Clark et al. in J Verb Learn Verb Behav 22:245–258, 1983), which is exactly what the non-referentialist account would predict. The game theoretical account also allows for an intuitively plausible, non-referentialist treatment of Speaks’ ‘trumping argument’ (Speaks in Philos Stud 174:709–734, 2017), as well as the Carnap/Agnew puzzle (Kaplan in Syntax Semant 9:221–43, 1970). (shrink)

This is the first comprehensive study of Nietzsche's earliest (and extraordinary) book, The Birth of Tragedy (1872). When he wrote it, Nietzsche was a Greek scholar, a friend and champion of Wagner, and a philosopher in the making. His book has been very influential and widely read, but has always posed great difficulties for readers because of the particular way Nietzsche brings his ancient and modern interests together. The proper appreciation of such a work requires access to ideas that cross (...) the boundaries of conventional specialisms. This is now provided by M. S. Silk and J. P. Stern in their joint study of Nietzsche's book. They examine in detail its content, style and form; its strange genesis and hybrid status; its biographical background and the controversy engendered by its publication; its value as an account of ancient Greek culture and as a theory of tragedy and music; its relation to other theories of tragedy; and its place in the history of German ideas and in Nietzsche's own philosophical career. (shrink)

Consciousness is an active area of both philosophical debates and scientific research. Consciousness Quest, rather than covering the broad spectrum of consciousness spread over multiple scientific disciplines, refocuses the quest for consciousness on a specific area where Eastern contemplative traditions, mostly in Hindu and Buddhist theories of mind, meet Western empirical research. This book is an introduction to current scientific thinking and research on consciousness and at the same time acquaints readers with the spectrum of classical and modern philosophical notions (...) on consciousness. (shrink)

'Johann Sommerville's is an impeccable textbook. Simply written, it provides exposition of Hobbes' arguments in the context of English and continental thought'. P. Springborg, University of Sydney, Political Studies, Vol. XL1, No 2 6/93 Thomas Hobbes was probably the greatest of British political theorists. Too often commentators have failed to grasp his meaning because they have ignored the historical context in which he wrote. Drawing on much recent scholarship and on many little-known seventeenth century sources, this book presents a lucid (...) and jargon-free examination of Hobbes' arguments, setting them against a background of the ideas of his contemporaries and of the political events of his lifetime. By viewing Hobbes in his context, the book both clarifies his theories and illuminates European thinking at a critical stage in the development of modern political ideas. (shrink)

Contractarians aim to derive moral principles from the dictates of instrumental rationality alone. But it is well-known that contractarian moral theories struggle to identify normative principles that are both uniquely rational and morally compelling. Michael Moehler's recent book, *Minimal Morality* seeks to avoid these difficulties by developing a novel "two-level" social contract theory, which restricts the scope of contractarian morality to cases of deep and persistent moral disagreement. Yet Moehler remains ambitious, arguing that a restricted version of Kant's categorical imperative (...) is a uniquely rational principle of conflict resolution. We develop a formal model of Moehler's informal game-theoretic argument, which reconstructs a valid argument for Moehler's conclusion. This model, in turn, enables us to expose how a successful argument for Moehler's contractarian principle rests on assumptions that can only be justified by subtle yet significant departures from the standard conception of rationality. We thus extend our understanding of familiar contractarian difficulties by showing how they arise even if we restrict the scope of contractarian morality to a domain where its application seems both promising and necessary. We show that the problem lies not in contractarians' immodest ambitions but in the modest resources rationality can offer to satisfy them. (shrink)

This paper is devoted to the study of some subvarieties of the variety Qof Q-Heyting algebras, that is, Heyting algebras with a quantifier. In particular, a deeper investigation is carried out in the variety Q 3 of three-valued Q-Heyting algebras to show that the structure of the lattice of subvarieties of Qis far more complicated that the lattice of subvarieties of Heyting algebras. We determine the simple and subdirectly irreducible algebras in Q 3 and we construct the lattice of subvarieties (...) (Q 3 ) of the variety Q 3. (shrink)

This paper is devoted to the study of some subvarieties of the variety Q of Q-Heyting algebras, that is, Heyting algebras with a quantifier. In particular, a deeper investigation is carried out in the variety Q subscript 3 of three-valued Q-Heyting algebras to show that the structure of the lattice of subvarieties of Q is far more complicated that the lattice of subvarieties of Heyting algebras. We determine the simple and subdirectly irreducible algebras in Q subscript 3 and we construct (...) the lattice of subvarieties lambda (Q subscript 3) of the variety Q subscript 3. (shrink)

The achievements of the textile industry in Roman Britain are often underestimated as a result of the meagreness of our available evidence. The Edict on maximum prices issued by Diocletian in A.D. 301 shows that British capes commanded high prices on the markets of the Empire, and that in the late third century A.D. British rugs were the best in the world. In view of the competition from the traditional centres of rug manufacture in the East, this is an astonishing (...) achievement. (shrink)

The received translation and interpretation of many of the technical terms current in the textile industry of the Roman Empire are inaccurate, because lexicographers have either fought shy of being precise, or have thought that they recognized in the ancient world technical processes which originated at a much later date. The evidence is often equivocal or insufficient, but may still yield details that have been overlooked. The textile expression scutulatus, to take an example, deserves more attention than Blümner has devoted (...) to it. When it refers to the appearance of a garment, Lewis and Short, s.v. scutulatus, translate ‘diamond or lozenge-shaped, checkered’. It seems worth while to attempt a more precise translation, and, if possible, to estimate the significance in context of the goods so designated. (shrink)

First published in 1982, this reissue contains a critical exposition of the views of Frege, Dedekind and Peano on the foundations of arithmetic. The last quarter of the 19th century witnessed a remarkable growth of interest in the foundations of arithmetic. This work analyses both the reasons for this growth of interest within both mathematics and philosophy and the ways in which this study of the foundations of arithmetic led to new insights in philosophy and striking advances in logic. This (...) historical-critical study provides an excellent introduction to the problems of the philosophy of mathematics - problems which have wide implications for philosophy as a whole. This reissue will appeal to students of both mathematics and philosophy who wish to improve their knowledge of logic. (shrink)

Doctors’ strikes are legally permissible in the UK, with the situation differing in other countries. But are they morally permissible? Doug McConnell and Darren Mann have systematically attempted to dismiss the arguments for the moral impermissibility of doctors’ strikes and creatively attempted to provide further moral justification for them. Unfortunately for striking doctors, they fail to achieve this. Meanwhile, junior doctors’ strikes have continued in the UK through 2023 and have now extended into 2024. In this response, which focuses on (...) the UK situation and specifically junior doctors’ strikes in the National Health Service (NHS) in England, I will demonstrate a central problem with their arguments—namely that they underplay the harms caused by prolonged doctors’ strikes by ignoring the harms to patients with cancer. This weakens their conclusion that strikes are morally permissible in terms of the conditions and thresholds they set. I then provide a psychological critique of their justification for strikes in terms of the interests of the public. It follows that invoking the controversial concept of supererogatory action is ungrounded but also absurd when you consider time-critical cancer care. If those representing striking doctors wish to maintain a modicum of moral respectability, they should mitigate for patients with cancer and negotiate reasonably and with urgency. (shrink)

Human conflict and its resolution is obviously a subject of great practical importance. Equally obviously, it is a vast subject, ranging from total war at one end of the spectrum to negotiated settlement at its other end. The literature on the subject is correspondingly vast and, in recent times, technical, thanks to the valuable contributions made to it by game theorists, economists, and writers on industrial and international relations. In this essay, however, I shall discuss only one familiar form of (...) conflict-resolution. There is room for such a discussion, because philosophers have lately neglected compromise, despite the interest shown in it by the aforementioned experts, and despite the classic treatments of it by Halifax, Burke and Morley. Truly, ‘…compromise is not so widely discussed by philosophers as one might expect’, and ‘…the idea of compromise has been largely neglected by Anglo-American jurisprudence’. (shrink)

First published in 1982, this reissue contains a critical exposition of the views of Frege, Dedekind and Peano on the foundations of arithmetic. The last quarter of the 19th century witnessed a remarkable growth of interest in the foundations of arithmetic. This work analyses both the reasons for this growth of interest within both mathematics and philosophy and the ways in which this study of the foundations of arithmetic led to new insights in philosophy and striking advances in logic. This (...) historical-critical study provides an excellent introduction to the problems of the philosophy of mathematics - problems which have wide implications for philosophy as a whole. This reissue will appeal to students of both mathematics and philosophy who wish to improve their knowledge of logic. (shrink)

After describing Heidegger's critique of metaphysics as ontotheology, I unpack the metaphysical assumptions of several transhumanist philosophers. I claim that they deploy an ontology of power and that they also deploy a kind of theology, as Heidegger meant it. I also describe the way in which this metaphysics begets its own politics and ethics. In order to transcend the human condition, they must transgress the human.

Humanity does not gradually progress from combat to combat until it arrives at universal reciprocity, where the rule of law finally replaces warfare; humanity installs each of its violences in a system of rules and thus proceeds from domination to domination. (Foucault, 1984, 85)In this essay, I take a note from Michel Foucault regarding the notion of biopolitics. For Foucault, biopolitics has both repressive and constitutive properties. Foucault's claim is that with the rise of modern government, the state became exceedingly (...) concerned about the body politic, the bodies that make up the polis, including the health of those bodies. However, Giorgio Agamben claims that Foucault and all western political philosophy misses the relationship between power and Sovereignty, with disastrous results and totalizing tendencies. I explore the case of Terri Schiavo claiming that the social conservatives have attempted to politicize bare life in its legal maneuverings, but I also show how the social liberals open an uncontrollable space between life and death. Both the left and the right miss the aporia at the heart of western political philosophy, and bioethics is complicit in the totalizing effects of contemporary medicine. (shrink)