According to the PubMed resource from the U.S. National Library of Medicine, over 750,000 scientific articles have been published in the ~5000 biomedical journals worldwide in the year 2007 alone. The vast majority of these publications include results from hypothesis-driven experimentation in overlapping biomedical research domains. Unfortunately, the sheer volume of information being generated by the biomedical research enterprise has made it virtually impossible for investigators to stay aware of the latest findings in their domain of interest, let alone to (...) be able to assimilate and mine data from related investigations for purposes of meta-analysis. While computers have the potential for assisting investigators in the extraction, management and analysis of these data, information contained in the traditional journal publication is still largely unstructured, free-text descriptions of study design, experimental application and results interpretation, making it difficult for computers to gain access to the content of what is being conveyed without significant manual intervention. In order to circumvent these roadblocks and make the most of the output from the biomedical research enterprise, a variety of related standards in knowledge representation are being developed, proposed and adopted in the biomedical community. In this chapter, we will explore the current status of efforts to develop minimum information standards for the representation of a biomedical experiment, ontologies composed of shared vocabularies assembled into subsumption hierarchical structures, and extensible relational data models that link the information components together in a machine-readable and human-useable framework for data mining purposes. (shrink)

Significant associations have been found between specific human leukocyte antigen (HLA) alleles and organ transplant rejection, autoimmune disease development, and the response to infection. Traditional searches for disease associations have conventionally measured risk associated with the presence of individual HLA alleles. However, given the high level of HLA polymorphism, the pattern of amino acid variability, and the fact that most of the HLA variation occurs at functionally important sites, it may be that a combination of variable amino acid sites shared (...) by several alleles (shared epitopes) are better descriptors of the actual causative genetic variants. Here we describe a novel approach to genetic association analysis in which genes/proteins are broken down into smaller sequence features and then variant types defined for each feature, allowing for independent analysis of disease association with each sequence feature variant type. We have used this approach to analyze a cohort of systemic sclerosis patients and show that a sequence feature composed of specific amino acid residues in peptide binding pockets 4 and 7 of HLA-DRB1 explains much of the molecular determinant of risk for systemic sclerosis. (shrink)

Human cognitive acts are directed towards entities of a wide range of different types. What follows is a new proposal for bringing order into this typological clutter. A categorial scheme for the objects of human cognition should be (1) critical and realistic. Cognitive subjects are liable to error, even to systematic error of the sort that is manifested by believers in the Pantheon of Olympian gods. Thus not all putative object-directed acts should be recognized as having objects of their own. (...) Broadly, the objects towards which human cognition is directed should be parts of reality in a sense that is at least consistent with the truths of natural science. But such a scheme should also be (2) comprehensive: it should do justice to each sort of object on its own terms, and not attempt to eliminate objects of one sort in favour of objects of other, more favoured sorts. Linguistic and other forms of idealism, as well as Meinongian theories, which assign to each and every referring expression or intentional act an object tailored to fit, yield categorial schemes which fail to satisfy (1). Physicalistic and other forms of reductionism yield categorial schemes which fail to satisfy (2). What follows is a categorial scheme that is both critically realistic and comprehensive. Thus it enjoys some of the benefits of linguistic idealism and physicalism, without (or so it is hoped) the corresponding disadvantages of each. (shrink)

Long-standing neglect of the chemical senses in the philosophy of perception is due, mostly, to their being regarded as ‘lower’ senses. Smell, taste, and chemically irritated touch are thought to produce mere bodily sensations. However, empirically informed theories of perception can show how these senses lead to perception of objective properties, and why they cannot be treated as special cases of perception modelled on vision. The senses of taste, touch, and smell also combine to create unified perceptions of flavour. The (...) nature of these multimodal experiences and the character of our awareness of them puts pressure on the traditional idea that each episode of perception goes one or other of the five senses. Thus, the chemical senses, far from being peripheral to the concerns of the philosophy of perception, may hold important clues to the multisensory nature of perception in general. (shrink)

The paper proposes a formal account of Aristotle's trichotomy of verbs, in terms of properties of their continuous tensings, into S(state)-verbs, K(kinesis)-verbs, and E-(energeia)-verbs. Within a Fregean tense framework in which predicates are relativized to times, an account of the continuous tenses is presented and a preliminary account of the trichotomy devised, which permits an illuminating analogy to be drawn between the temporal properties of E- and K-verbs and the spatial properties of stuffs and substances. This analogy is drawn upon (...) in constructing a sophisticated version of the preliminary theory accommodating more of the linguistic data. (shrink)

Examines the relevance of Foucault's work for developing an understanding of those issues which lie beyond the limits of Marxist theory and analysis - issues such as 'individualising' forms of power, power-knowledge relations, the rise of ...

Henri Bergson (1859-1941) was once the most famous philosopher in the world, but his reputation waned in the latter half of the 20th century. Barry Allen here makes the case for Bergson as a great philosopher, one whose thought has much to contribute to contemporary philosophical questions. Living in Time presents chapters on each of Bergson's four major works, explaining his theories of time, perception, memory, and panpsychic consciousness, his innovative concept of virtual existence, his objection to Darwin, his (...) controversy with Einstein, his philosophy of creative evolution, and his social philosophy of closed and open society. In particular Allen focusses on Bergson's powerful ideas on time. Classical arguments for determinism fallaciously apply spatial concepts to consciousness; once we take time seriously, which means acknowledging its reality as duration and its difference from space, Bergson showed that the arguments for determinism become insupportable. Bergson's ideas on time and evolution offer a comparison with Nietzsche, which Allen develops, exposing both philosophical concurrence and systematic difference. The book's conclusion discusses the question of Bergson and naturalism and summarizes the ontology of the virtual that emerges as a core part of Bergson's thought. (shrink)

Barry Allen explores the concept of knowledge in Chinese thought over two millennia and compares the different philosophical imperatives that have driven Chinese and Western thought. Challenging the hyperspecialized epistemology of modern Western philosophy, he urges his readers toward an ethical appreciation of why knowledge is worth pursuing.

There are various ways of characterising Hume’s dictum that ‘you can’t get an ought from an is.’ Contributors to the literature directly addressing this question focus on logical characterisations of autonomy theses. Such theses maintain that certain logical relations do not obtain between ethical and non-ethical sentences, for instance that no non-ethical sentences logically entail an ethical sentence. I argue that this focus on logical autonomy is a mistake. The thesis so important to our metaethicists is not a logical thesis (...) but a metaphysical one. The relevant metaphysical autonomy thesis maintains that ethical facts are not fully grounded just in non-ethical facts. I defend this characterization. I also defend the converse thesis that all facts partly grounded in ethical facts are ethical facts. I then argue that this pair of theses can help with debates about the plausibility of nihilism and the classification of revisionary metaethical theses. (shrink)

We argue that a particular approach to satisfying the broad predictive ambitions of the sciences demands law confirmation. On this approach we confirm non-nomic generalizations by confirming there are no actually realized ways of causing disconfirming cases. This gives causal generalizations a crucial role in prediction. We then show how rational judgements of relevant causal similarity can be used to confirm that causal generalizations themselves have no actual disconfirmers, providing a distinctive and clearly viable methodology for inductively confirming them. Finally, (...) we argue that for agents in our epistemic position using this methodology to confirm causal generalizations of adequate breadth will commonly demand law confirmation. We make a prima facie assessment of the methodology’s fit with scientific practice and briefly consider the prospects for an associated analysis of laws. (shrink)

Many moral theories hold individuals responsible for their marginal impact on massive patterns (for instance overall value or equality of opportunity) or for following whichever rules would realise that pattern on the whole. But each of these injunctions is problematic. Intuitively, the first gives individuals responsibility for too much, and the second gives them responsibility for too little. I offer the outlines of a new approach to ethics in collective action contexts. I defend a new collaborative principle that assigns recognisably (...) worthwhile responsibilities to agencies wherever possible. This principle supports a fractal model of moral responsibility, one that favours restructuring divisions of labour in ways that enhance the prospects of recognition at every level of social organisation. This essay is programmatic: starting from a conjecture about the moral significance of recognition, it sketches a new way of approaching a range of collective action problems that combines the importance of the perspectives of both moral and political philosophy. (shrink)

There are several powerful motivations for neutral value‐based deontic theories such as Act Consequentialism. Traditionally, such theories have had great difficulty accounting for partiality towards one's personal relationships and projects. This paper presents a neutral value‐based theory that preserves the motivations for Act Consequentialism while vindicating some crucial intuitions about reasons to be partial. There are two central ideas. The first is that when it comes to working out what you ought to do, your friends’ interests, the needs of your (...) family, the significance of your own projects and ideals, etc. have more weight than the interests and needs of strangers. Your friends’ interests are not (thereby) more neutrally valuable than the interests of others. So there is a difference between the value of an outcome and its deontic significance. The second familiar idea is that reasons are modifiable. Reasons of partiality are reasons the weights of which are a function of the value of the relevant outcome modified by facts about the value of caring about the outcome in question. The resulting principle has various further explanatory advantages; in particular, it accounts for project‐ and relationship‐specific permissions and requirements, both at a time and across time. (shrink)

This ground breaking work explores the genealogical analysis of the discourses of reflection. Barry Sandywell traces the differences between the traditional discourses of reflection and the experiences of reflexivity in everyday, social and philosophical thought. Brilliantly organised and abounding with astonishing insights, Reflexivity and the Crisis of Western Reason offers a fundamental challenge to our normal ways of viewing social thought.

Despite the fact about colour, that it is one of the most obvious and conspicuous features of the world, there is a vast number of different theories about colour, theories which seem to be proliferating rather than decreasing. How is it possible that there can be so much disagreement about what colours are? Is it possible that these different theorists are not talking about the same thing? Could it be that more than one of them is right? Indeed some theorists, (...) e.g. Leo M. Hurvich, D. L. McAdam and K. Nassau, say that the term ‘colour’ is used to identify a range of different properties, e.g. pigments, properties of light, and sensations. Such a view has its attractions, but it raises the question of what it is that unites these various concepts – what is it that would make them all concepts of colour? What is it that justifies using the same terms, ‘yellow’, ‘blue’, ‘pink’, mauve’, and so on?This paper aims to address this question, arguing that its answer supports the conclusion that the best theory of colour is a form of anti‐realism: the Illusory theory of colours. There are two parts to this thesis, one negative, the other positive. The negative part is that there are no colours, as they are ordinarily conceived. The positive part is that, nevertheless, the world is such that ‘it is as if there are such colours’. Such a theory has important implications. One is that it doesn’t fall neatly into the usual taxonomy of philosophical theories. In particular, it does not deserve the label ‘eliminativist’. Another is that it allows some space for the views expressed by Hurvich, McAdam and Nassau, but not quite in the sense that they intend. (shrink)

There is no cure or vaccine for HIV/AIDS. The only life-prolonging treatment available is antiretroviral (ARV) therapy. WHO estimates, however, that less than 5 percent of those who require treatment in developing countries currently enjoy access to these medicines. In Africa fewer than 50,000 people–less than 2 percent of the people in need–currently receive ARV therapy. These facts have elicited strongly divergent reactions, and views about the appropriate response to this crisis have varied widely.The intensity of the debate concerning access (...) to life-prolonging medicines for the treatment of HIV/AIDS, and the heated rhetoric with which they are often conducted, suggest that these disagreements may be rooted in deeper disagreements of value. It is not obvious, however, what disagreements of value are at stake in this debate. By analyzing the statements of scholars, public officials, activist organizations, and private sector representatives, each of whom may endorse very different policy recommendations on access to HIV/AIDS drugs, we have identified and created a typology of the different sources of disagreement in the debate. We conclude that the central disagreements concerning access to medicines arise from competing understandings of how responsibilities for bringing remedy to hardships should be allocated to different agents and institutions. A central lesson that emerges from our analysis is that thinking about “health equity” must extend beyond the explanation and justification of goals, values, and ideals, and engage more honestly with the difficult question of how responsibilities for bringing remedy to health crises should be allocated in complex social contexts. (shrink)

Andrews explores spiritual practices that were the vital source from which everything else about Transcendentalism-texts, ideas, and social action-flowed. These practices are eminently available to spiritual seekers today, both those who are connected to conventional forms of religiosity and those who are allergic to 'religion.

ArgumentThe tension between theoretical and practical knowledge was particularly problematic for trainee physicians. Unlike civic apprenticeships in surgery and pharmacy, in early modern England there was no standard procedure for obtaining education in the practical aspects of the physician’s role, a very uncertain process of certification, and little regulation to ensure a suitable reward for their educational investment. For all the emphasis on academic learning and international travel, the majority of provincial physicians returned to practice in their home area, because (...) establishing a practice owed more to networks of kinship, patronage and credit than to formal qualifications. Only when (and where) practitioners had to rely solely on their professional qualification to establish their status as young practitioners that the community could trust would proposals to reform medical education, such as those put forward to address a crisis of medicine in Restoration London, which are examined here, be converted into national regulation of medical education in the early nineteenth century, although these proposals prefigured many informal developments in medical training in the eighteenth century. (shrink)

This book examines what makes someone an evil person and how evil people are different from merely bad people. Rather than focusing on the "problem of evil" that occupies philosophers of religion, Barry looks instead to moral psychology—the intersection of ethics and psychology. He provides both a philosophical account of what evil people are like and considers the implications of that account for social, legal, and criminal institutions. He also engages in traditional philosophical reasoning strongly informed by psychological research, (...) especially abnormal and social psychology. In response to the popularity of phrases like "the axis of evil" and the ease with which politicians and others describe their opponents as "evil," Barry sets out to make clear just what it is to be an evil person. (shrink)

Consent remains a crucial, yet challenging, cornerstone of clinical practice. The ethical, legal and professional understandings of this construct have evolved away from a doctor-centred act to a patient-centred process that encompasses the patient’s values, beliefs and goals. This alignment of consent with the philosophy of shared decision-making was affirmed in a recent high-profile Supreme Court ruling in England. The communication of information is central to this model of health care delivery but it can be difficult for doctors to gauge (...) the information needs of the individual patient. The aim of this paper is to describe ‘core information sets’ which are defined as a minimum set of consensus-derived information about a given procedure to be discussed with all patients. Importantly, they are intended to catalyse discussion of subjective importance to individuals. The model described in this paper applies health services research and Delphi consensus-building methods to an idea orginally proposed 30 years ago. The hypothesis is that, first, large amounts of potentially-important information are distilled down to discrete information domains. These are then, secondly, rated by key stakeholders in multiple iterations, so that core information of agreed importance can be defined. We argue that this scientific approach is key to identifying information important to all stakeholders, which may otherwise be communicated poorly or omitted from discussions entirely. Our methods apply systematic review, qualitative, survey and consensus-building techniques to define this ‘core information’. We propose that such information addresses the ‘reasonable patient’ standard for information disclosure but, more importantly, can serve as a spring board for high-value discussion of importance to the individual patient. The application of established research methods can define information of core importance to informed consent. Further work will establish how best to incorporate this model in routine practice. (shrink)

Cyclic nucleotides can regulate the sensitivity of retinal rods to light through phosducin. The phosphorylation state of phosducin determines the amount of G available for activation by Rho*. Phosducin phosphorylation is regulated by cyclic nucleotides through their activation of cAMP-dependent protein kinase. The regulation of phosphodiesterase activity by the noncatalytic cGMP binding sites as well as Ca2+/calmodulin dependent regulation of cGMP binding to the cation channel are also discussed.

Is relativism about truth ever a coherent doctrine? Some people have argued that an answer to this question depends on whether there can be cases of genuine disagreement where those who disagree hold confl icting beliefs towards the same proposition and yet are each entitled to say that what they believe is true. These have been called cases of faultless disagreement and are often explored by considering the case of disagreements about taste. However, this is not the right way to (...) formulate the relativist’s doctrine, and the discussions of taste are often based on a faulty view about the nature of taste and about the workings of predicates of taste. I examine the taste case in more detail and consider the prospects for a genuine form of truth relativism. Key words: relativism, truth, taste, predicates of taste. (shrink)

David Lewis claims that his theory of modality successfully reduces modal items to nonmodal items. This essay will clarify this claim and argue that it is true. This is largely an exercise within ‘Ludovician Polycosmology’: I hope to show that a certain intuitive resistance to the reduction and a set of related objections misunderstand the nature of the Ludovician project. But these results are of broad interest since they show that would-be reductionists have more formidable argumentative resources than is often (...) thought. Lewis’s reduction depends on a set of methodological commitments each of which is fairly plausible or at least currently popular, and none of which is particular to modality. The choice of which of these commitments to reject I leave to the discerning antireductionist. The essay proceeds as follows: §1 discusses reduction generally and one or two relevant puzzles; §2 discusses Lewis’s reduction in particular; the longest section, §3 replies to four objections. (shrink)

In Reflexivity and the Crisis of Western Reason Barry Sandywell outlined and defended a central place for reflexivity in the human sciences. In this second equally outstanding and challenging volume of Logological Investigations, he reconstructs the origins of "European" reflection. The author's central claim is that the world does not exist independently of us, but that it is constituted through the terms of our discursive categories. Rather than research being a triumphant exploration, it is more fully understood as agonized (...) self-reflection on the grounds of knowledge production. Sandywell argues that this approach has been inherent throughout Western philosophy and in so doing, he shows that the reflexive character of human experience in Western Culture can be traced through the desire for intelligibility that animated Greek drama, poetry, philosophy and science as explorations of the cosmos, body-politics and the soul. (shrink)