In this review, we discuss the application of mouse models to the identification and pre‐clinical validation of novel therapeutic targets in colorectal cancer, and to the search for early disease biomarkers. Large‐scale genomic, transcriptomic and epigenomic profiling of colorectal carcinomas has led to the identification of many candidate genes whose direct contribution to tumourigenesis is yet to be defined; we discuss the utility of cross‐species comparative ‘omics‐based approaches to this problem. We highlight recent progress in modelling late‐stage disease using mice, (...) and discuss ways in which mouse models could better recapitulate the complexity of human cancers to tackle the problem of therapeutic resistance and recurrence after surgical resection. (shrink)

In this article I distinguish the notion of there being something it is like to be a certain kind of creature from that of there being something it is like to have a certain kind of experience. Work on consciousness has typically dealt with the latter while employing the language of the former. I propose several ways of analyzing what it is like to be a certain kind of creature and find problems with them all. The upshot is that even (...) if there is something it is like to have certain kinds of experience, it does not follow that there is anything it is like to be a certain kind of creature. Skepticism about the existence of something that it is like to be an F is recommended. (shrink)

Inspired by Sara Ahmed’s notion of ‘queer use,’ I present and extend a neo-Aristotelian theory of artifacts to capture what I call ‘counter-use.’ The theory of artifacts is based on the idea that what they are, how they come to be, and what their functions are cannot be understood independently from each other. They come to exist when a maker imposes the concept of their substantial kind onto some matter by working on the matter to make an artifact of that (...) kind out of it. The extensions to this core theory that I describe are two. First, I show how using can be a kind of making and how disparate users may form what Benedict Anderson calls an imagined community. Second, I describe what I call an artifact’s historicity and suggest that, like its substantial kind, an artifact’s historicity is essential to it. On this basis, I characterize counter-use as use of an artifact by an imagined community that re-arranges an object’s historicity and hence brings into existence a numerically distinct object. Thus, politically motivated counter-use has genuine ontological implications. (shrink)

Background: Mental healthcare needs person-tailored interventions. Experience Sampling Method (ESM) can provide daily life monitoring of personal experiences. This study aims to operationalize and test a measure of momentary reward-related Quality of Life (rQoL). Intuitively, quality of life improves by spending more time on rewarding experiences. ESM clinical interventions can use this information to coach patients to find a realistic, optimal balance of positive experiences (maximize reward) in daily life. rQoL combines the frequency of engaging in a relevant context (a (...) ‘behavior setting’) with concurrent (positive) affect. High rQoL occurs when the most frequent behavior settings are combined with positive affect or infrequent behavior settings co-occur with low positive affect. Methods: Resampling procedures (Monte Carlo experiments) were applied to assess the reliability of rQoL using various behavior setting definitions under different sampling circumstances, for real or virtual subjects with low-, average- and high contextual variability. Furthermore, resampling was used to assess whether rQoL is a distinct concept from positive affect. Virtual ESM beep datasets were extracted from 1058 valid ESM observations for virtual and real subjects. Results: Behavior settings defined by Who-What contextual information were most informative. Simulations of at least 100 ESM observations are needed for reliable assessment. Virtual ESM beep datasets of a real subject can be defined by Who-What-Where behavior setting combinations. Large sample sizes are necessary for reliable rQoL assessments, except for subjects with low contextual variability. rQoL is distinct from positive affect. Conclusion: rQoL is a feasible concept. Monte Carlo experiments should be used to assess the reliable implementation of an ESM statistic. Future research in ESM should asses the behavior of summary statistics under different sampling situations. This exploration is especially relevant in clinical implementation, where often only small datasets are available. (shrink)

The American Journal of Bioethics, Volume 11, Issue 11, Page 42-43, November 2011.

Sleep enhances integration across multiple stimuli, abstraction of general rules, insight into hidden solutions and false memory formation. Newly learned information is better assimilated if compatible with an existing cognitive framework or schema. This article proposes a mechanism by which the reactivation of newly learned memories during sleep could actively underpin both schema formation and the addition of new knowledge to existing schemata. Under this model, the overlapping replay of related memories selectively strengthens shared elements. Repeated reactivation of memories in (...) different combinations progressively builds schematic representations of the relationships between stimuli. We argue that this selective strengthening forms the basis of cognitive abstraction, and explain how it facilitates insight and false memory formation. (shrink)

I explore the interrelations between the ontological and aesthetic issues raised by ready-mades such as Duchamp’s Fountain. I outline a hylomorphic metaphysics which has two central features. First, hylomorphically complex objects have matter to which they are not identical. Secondly, when such objects are artefacts (including artworks), it is essential to them that they are the products of creative work on their matter. Against this background, I suggest that ready-mades are of aesthetic interest because they pose a dilemma. Is there (...) really an object, a sculpture, that is distinct from its matter, a urinal, which object is created merely by the artist’s choice of the urinal? Or are we dealing with a case in which an artist passes off something, a urinal, as if it were a sculpture, even though it is not one? (shrink)

If science fiction is a genre, then attempts to think about the nature of science fiction will be affected by one’s understanding of what genres are. I shall examine two approaches to genre, one dominant but inadequate, the other better, but only occasionally making itself seen. I shall then discuss several important, interrelated issues, focusing particularly on science fiction : what it is for a work to belong to a genre, the semantics of genre names, the validity of attempts to (...) define genres, and the connections between genre and normativity. One important but neglected clue to the nature of genres lies in the kinds of disagreements they generate over the assignment of works to genres. I conclude by explaining why these disagreements tell us something about the nature of genres, and discussing in some detail two famous cases of disagreement about whether some work or works are science fiction. (shrink)

I argue that it is rational for a person to believe the conjunction of her beliefs. This involves responding to the Lottery and Preface Paradoxes. In addition, I suggest that in normal circumstances, what it is to believe a conjunction just is to believe its conjuncts.

This article researches how a corporate code of ethics (CCE) implemented in local government X has influenced the behavior of its employees, middle managers, and managers. Metaphors from the existing and desired CCE elicited by these three groups provided information on how to improve the effectiveness of the CCE. This method proved to be very fruitful. It appeared that continuous systematic attention needed to be paid to the CCE after the CCE had been implemented, particularly by management. Initiatives from management (...) to start discussions about relevant questions of integrity appeared to be also necessary to make the topic a “normal” topic which employees were no longer afraid to discuss. In this way, the possibility could be created to develop collectively a “practical” frame of reference concerning relevant questions of integrity that would help employees to make decisions in difficult situations during their work in the future. (shrink)

Memes, of the kind found often on the internet, are an increasingly significant medium of expressive activity. I develop a theory of their ontological nature and, in parallel, an analysis of the concept meme. On my view, memes are abstract artifacts made out of norms for production of instances. The norms say things like ‘use a certain image; add text of a certain kind; the text should be delivered in two chunks, one at the top of the image, one at (...) the bottom, etc.’ Instances of these memes are created when users follow these norms and publish the results. The concept meme is analyzed in terms of the notion of memographic practice, a historically situated form of activity within which memes are created and their instances produced and made public. (shrink)

The ability to reason independently from one's own goals or beliefs has long been recognised as a key characteristic of the development of formal operational thought. In this article we present the results of a study that examined the correlates of this ability in a group of 10-year-old children ( N = 61). Participants were presented with conditional and relational reasoning items, where the content was manipulated such that the conclusion to the arguments were either congruent, neutral, or incongruent with (...) beliefs, and either logically valid or logically invalid. Participants also received a measure of working memory capacity (the counting span task) and a measure of inhibitory control (the stop signal task). Indices of belief bias and logical reasoning on belief-based problems were predicted independently by both measures. In contrast logical reasoning on belief neutral problems was predicted by working memory alone. The findings suggest that executive functions play a key role in the development of children's ability to decontextualise their thinking. (shrink)

The objectives of this study were to develop a high-density chromosome bin map of homoeologous group 7 in hexaploid wheat, to identify gene distribution in these chromosomes, and to perform comparative studies of wheat with rice and barley. We mapped 2148 loci from 919 EST clones onto group 7 chromosomes of wheat. In the majority of cases the numbers of loci were significantly lower in the centromeric regions and tended to increase in the distal regions. The level of duplicated loci (...) in this group was 24% with most of these loci being localized toward the distal regions. One hundred nineteen EST probes that hybridized to three fragments and mapped to the three group 7 chromosomes were designated landmark probes and were used to construct a consensus homoeologous group 7 map. An additional 49 probes that mapped to 7AS, 7DS, and the ancestral translocated segment involving 7BS also were designated landmarks. Landmark probe orders and comparative maps of wheat, rice, and barley were produced on the basis of corresponding rice BAC/PAC and genetic markers that mapped on chromosomes 6 and 8 of rice. Identification of landmark ESTs and development of consensus maps may provide a framework of conserved coding regions predating the evolution of wheat genomes. (shrink)

Musical Platonists identify musical works with abstract sound structures but this implies that they are not created but only discovered. Jerrold Levinson adapts Platonism to allow for creation by identifying musical works with indicated sound structures. In this paper I explore the similarities between Levinson's view and Kit Fine's theory of qua objects. Fine offers the theory of qua objects as an account of constitution, as it obtains, for example, between a statue and the clay the statue is made out (...) of. I argue that Fine's theory does not adequately characterize the constitution relation and that the problems it faces extend to Levinson's account of musical works as indicated structures. I develop an alternative theory of constitution, based on the notion of being made out of. This approach to constitution enables me to offer an account of musical works as abstract objects that are constituted by sound structures. I argue that my account has several advantages over the Levinson/Fine approach. (shrink)

Constitution is the relation between something and what it is made of. Composition is the relation between something and its parts. I examine three different approaches to the relation between constitution and composition. One approach, associated with neo-Aristotelians like Mark Johnston and Kathrin Koslicki, identifies constitution with composition. A second, popular with those sympathetic to classical mereology such as Judith Thomson, defines constitution in terms of parthood. A third, advocated strongly by Lynne Baker, takes constitution to be somehow inconsistent with (...) relations of parthood. All of these approaches, I argue, face serious problems. I conclude, tentatively, that constitution and composition have nothing to do with each other. (shrink)

The Prologue offers an overview of the Reformation of method from Augustine of Hippo through to the Ramist movement, providing an orientation to the rest of the book. It highlights and explains an important nexus of Realism, exemplarism and illumination fundamental to Ramism. Beginning with Augustine it shows how these themes coalesced into a distinctive Christian philosophy taken up and refined by Franciscans such as Bonaventure of Bagnoregio and John Duns Scotus, as well as by Ramon Lull, the Franciscan-inspired encyclopaedist. (...) It traces the continuation of this methodological impulse into the Platonism and Christian humanism of the Renaissance, highlighting especially the topical and Realist (Scotistic) reform of logic pioneered by Lorenzo Valla and Rudolph Agricola. It concludes by showing the reception of this topical and biblical reform in Philipp Melanchthon and the movement of Reformed scholasticism, revealing Reformed Scotism and Christian philosophy as important preconditions for Ramism. (shrink)

This article revisits and further develops Mitchell et al.’s (Acad Manag Rev 22(4):853–886, 1997 ) theory of stakeholder identification and salience. Stakeholder salience holds considerable unrealized potential for understanding how organizations may best manage multiple stakeholder relationships. While the salience framework has been cited numerous times, attempts to develop it further have been relatively limited. We begin by reviewing the key contributions of other researchers. We then identify and seek to resolve three residual weaknesses in Mitchell et al.’s ( 1997 (...) ) framework, thereby strengthening its foundations for further development. We argue, first, that urgency is not relevant for identifying stakeholders; second, that it is primarily the moral legitimacy of the stakeholder’s claim that applies to stakeholder salience; and last, that the salience of stakeholders will vary as the degrees of the attributes vary. These insights inform revised definitions of stakeholder salience and legitimacy, and necessitate a new theoretical underpinning for the role of legitimacy. Finally, we present an extensive agenda for future research with the objective of refueling research in stakeholder salience. (shrink)

I argue for the thesis (UL) that there are certain logical abilities that any rational creature must have. Opposition to UL comes from naturalized epistemologists who hold that it is a purely empirical question which logical abilities a rational creature has. I provide arguments that any creatures meeting certain conditions—plausible necessary conditions on rationality—must have certain specific logical concepts and be able to use them in certain specific ways. For example, I argue that any creature able to grasp theories must (...) have a concept of conjunction subject to the usual introduction and elimination rules. I also deal with disjunction, conditionality and negation. Finally, I put UL to work in showing how it could be used to define a notion of logical obviousness that would be well suited to certain contexts—e.g. radical translation and epistemic logic—in which a concept of obviousness is often invoked. (shrink)

I argue that it is not ideally rational to believe that some of one's current beliefs are false, despite the impressive inductive evidence concerning others and our former selves. One's own current beliefs represent a commitment which would be undermined by taking some of them to be false. The nature of this commitment is examined in the light of Nagel's distinction between subjective and objective points of view. Finally, I suggest how we might acknowledge our fallibility consistently with this special (...) attitude to our own beliefs. (shrink)

In 1956, W.B. Gallie introduced his idea of essentially contested concepts. In my paper, I offer a novel interpretation of his theory and argue that his theory, thus interpreted, is correct. The key to my interpretation lies in a condition Gallie places on essentially contested concepts that other interpreters downplay or dismiss: that the use of an essentially contested concept must be derived “from an original exemplar whose authority is acknowledged by all the contestant users of the concept.” This reveals (...) a similarity between Gallie’s views and the semantic externalist views of Hilary Putnam, and others, about natural kind terms like “water” and “tiger.” I argue that natural kind terms and terms for essentially contested concepts are two species of a single semantic genus. In the case of natural kind terms, a term refers to a natural kind, the exemplars are instances of that kind, and the relation between the exemplars and anything to which the term applies is co-membership of the kind. In the case of terms for essentially contested concepts, a term refers to an historical tradition, the exemplar is a stage or temporal part of that tradition, and the relation between the exemplar and anything to which the term refers is being the heir of. This allows me to understand the contests that alerted Gallie to the phenomenon of essentially contested concepts as contests over the ownership of historical traditions. (shrink)

I bring together social ontology and social epistemology by consideringsocial entities (``epistemic unities'') that are constituted by the holdingof epistemic relations between their members. In particular, I focus onthe relation of taking someone as an expert. Among the types of structuresexamined are ones with a single expert and one or more non-experts whomay or may not know of each other's situation; and ones with more thanone expert, including cases in which the relation between the experts ishierarchical and cases in which (...) it is symmetrical. These structures modela variety of social situations which can thus be given a unified treatment.Among the cases I discuss are persons, which I argue are multiple-expertunities of persons at times. Taking a person as a social unity like this offersa clear sense in which some groups can also be person-like. (shrink)

In recent years evidence has emerged of the considerable influence of Scotist metaphysics on the Reformed scholasticism of the seventeenth century. One of the figures often named in connection with this Scotist revival is Samuel Rutherford (1600–61), who was one of the most important Scottish theologians of the seventeenth century. Focussing on Rutherford’s maximalist doctrine of providence, this article demonstrates his profound debt to key Scotist philosophical devices. In structuring these concepts, however, it is demonstrated that Rutherford is influenced not (...) so much by Scotus directly but rather much more by the modified Scotism of Thomas Bradwardine, the fourteenth-century Augustinian theologian. In particular, Bradwardine is revealed as the key influence on Rutherford’s modal theory and his sophisticated account of divine concourse. The paper concludes by arguing that Bradwardine’s influence on Rutherford suggests the need to take a broader view of the late medieval influence on Reformed scholasticism than is currently the case. (shrink)

The Clinical Pastoral Education (CPE) model forthe provision of spiritual care represents theemergence of a secularized professionalpractice from a religiously-based theologicalpractice of chaplaincy. The transformation ofhospital chaplaincy into “spiritual careservices” is one means by which religioushealthcare ministry negotiates modernity, inthe particular forms of the secular realm ofbiomedicine and the pluralism of thecontemporary United States healthcaremarketplace. “Spiritual” is a labelstrategically deployed to extend the realm ofrelevance to any patient's “belief system,”regardless of his or her religious affiliation.“Theological” language is recast as a (...) tool forconceptualizing the “spiritual lens.” Suchmoves transform chaplaincy from a peripheralservice, applicable only to the few “religious”patients, into an integral element of patientcare for all. Such a secularized professionalpractice is necessary to demonstrate therelevance and utility of spiritual care for allhospital patients in an era of cost-containmentpriorities and managed care economics. (shrink)

We report the results of three experiments designed to assess the role of suppositions in human reasoning. Theories of reasoning based on formal rules propose that the ability to make suppositions is central to deductive reasoning. Our first experiment compared two types of problem that could be solved by a suppositional strategy. Our results showed no difference in difficulty between problems requiring affirmative or negative suppositions and very low logical solution rates throughout. Further analysis of the error data showed a (...) pattern of responses, which suggested that participants reason from a superficial representation of the premises in these arguments and this drives their choice of conclusion. Our second experiment employed a different set of suppositional problems but with extremely similar proofs in terms of the rules applied and number of inferential steps required. As predicted by our interpretation of reasoning strategies employed in Experiment 1, logical performance was very much higher on these problems. Our third experiment showed that problems that could be solved by constructing an initial representation of the premises were easier than problems in which this representation was not sufficient. This effect was independent of the suppositional structure of the problems. We discuss the implications of this research for theories of reasoning based on mental models and inference rules. (shrink)

The thesis of the paper is that persons are similar to a kind of group: multiple-expert epistemic unities (MEUs). MEUs are groups in which there are multiple experts on whom other members of the group model their opinion. An example would be a group of children playing Telephone. Any child nearer the source is an 'expert' for any child further away. I argue that, with certain important qualifications, it is both rational and necessary for persons to treat their future selves (...) as experts (i.e. to satisfy Bas Van Fraassen's Principle of Reflection). This makes a person a kind of MEU. (The paper "Epistemic Unities" gives more details about different kinds of epistemic unities.). (shrink)

A controversial claim in recent dual process accounts of reasoning is that intuitive processes not only lead to bias but are also sensitive to the logical status of an argument. The intuitive logic hypothesis draws upon evidence that reasoners take longer and are less confident on belief–logic conflict problems, irrespective of whether they give the correct logical response. In this paper, we examine conflict detection under conditions in which participants are asked to either judge the logical validity or believability of (...) a presented conclusion, accompanied by measures of eye movement and pupil dilation. The findings show an effect of conflict, under both types of instruction, on accuracy, latency, gaze shifts, and pupil dilation. Importantly, these effects extend to conflict trials in which participants give a belief‐based response (incorrectly under logic instructions or correctly under belief instructions) demonstrating both behavioral and physiological evidence in support of the logical intuition hypothesis. (shrink)

Taking as its point of departure Leder's phenomenological discussion of the `absent' body, this article explores the nature of human corporeality as a site of transgression. The body, I argue, using a process metaphysic, is first and foremost excessive, driven by human desire rather than animal need: a sensual mode of existence organized around the pleasure/pain axis. To be excessive/transgressive, however, implies the crossing of boundaries or limits which vary according to history and culture, time and place. These issues are (...) illustrated through a range of thinkers from Bakhtin to Kristeva, Irigaray to Deleuze and Guattari. A full-scale endorsement of the poststructuralist position is, however, rejected in favour of an approach which steers a middle ground between these transgressive, more fluid arguments and a foundationalist ontology of the emotional body as an ongoing structure of lived experience. The article concludes with some reflections on the complex pattern of corporeal `appearances', some more pleasant than others, which characterize our bodily-being-in-the-world. (shrink)

This paper offers two new arguments for a version of Reflection, the principle that says, roughly, that if one knew now what one would believe in the future, one ought to believe it now. The most prominent existing argument for the principle is the coherence-based Dutch Strategy argument advanced by Bas van Fraassen (and others). My two arguments are quite different. The first is a truth-based argument. On the basis of two substantive premises, that people’s beliefs generally get better over (...) time and that being a person requires having knowledge of this fact, it concludes that it is rational to treat your future selves as experts. The second argument is a transcendental one. Being a person requires being able to engage in plans and projects. But these cannot be meaningfully undertaken unless one has Reflection-like expectations about one’s future beliefs. Hence, satisfaction of Reflection is necessary for being a person. Together, the arguments show that satisfaction of Reflection is both rational and necessary for persons. (shrink)

George Du Maurier’s best-selling novel, Trilby (1894), is as important because of its defiance of social and cultural norms as it is for its apparent compliance with them. Trilby is a fiction that, like its eponymous heroine, attempts to negotiate the perilously fine line between the highbrow and the lowbrow, or to put it another way, between fine art and political commentary on one side, and pornography and sensationalism on the other. This article examines the way that Du Maurier engages (...) his readership in this textual tease – his seduction of the reader – by suggesting the possibility of a peep show where everything that Victorian respectability abhors may be on display, and then his narratological dressing of the text, to ensure that where there is sexual non-conformity there is also moralism, and where there is social confrontation there is also historical distance. Understanding the textual appeal of Trilby as a character, the artist’s model who enchanted the fin-de-siècle reading public, is essential to appreciating how the discourses of pornography and fine art interact and have consequently evolved. This article therefore examines why Trilby succeeded with the Victorians where other, similarly sexually active heroines – such as Thomas Hardy’s Sue Bridehead – failed. Trilby the novel and Trilby the woman are both broken down by their author into manageable parts, a pornographic fetishistic technique that simultaneously eroticises, and makes more palatable, the textual and the physical bodies. (shrink)

The concept of instinct espoused in psychology in the early 20th century and the contemporary concept of psychological adaptation invite comparison. Definitions of both employ the notions of inheritance, selection, functional specificity, and species typicality. This article examines how psychologists before the rise of behaviourism sought to establish instinct as a psychological phenomenon. One of the consequences of doing so was a decoupling of psychological and physiological forms of instinct. This led to a failure of constraint in the usage of (...) the term instinct and the abandonment of the project to establish it as foundational. I argue that the notion of psychological adaptations at the heart of contemporary evolutionary psychology as espoused by John Tooby and Leda Cosmides invites similar difficulties and may come to share a similar fate. (shrink)

A person who arrives at correct solutions via false premises is right and wrong simultaneously. Similarly, a person who generates “logical intuitions” through superficial heuristics can likewise be right and wrong at the same time. However, heuristics aren't guaranteed to deliver the logical solution, so the claim that system 1 can routinely produce the alleged system 2 response is unfounded.