Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that (...) has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility. (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)

This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Biomedical Informatics: We Are What We Publish", written by Peter L. Elkin, Steven H. Brown, and Graham Wright. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the Elkin et al. paper. In subsequent issues the discussion can continue through letters to the editor.

The development of the Functional Genomics Investigation Ontology (FuGO) is a collaborative, international effort that will provide a resource for annotating functional genomics investigations, including the study design, protocols and instrumentation used, the data generated and the types of analysis performed on the data. FuGO will contain both terms that are universal to all functional genomics investigations and those that are domain specific. In this way, the ontology will serve as the “semantic glue” to provide a common understanding of data (...) from across these disparate data sources. In addition, FuGO will reference out to existing mature ontologies to avoid the need to duplicate these resources, and will do so in such a way as to enable their ease of use in annotation. This project is in the early stages of development; the paper will describe efforts to initiate the project, the scope and organization of the project, the work accomplished to date, and the challenges encountered, as well as future plans. (shrink)

The analytical philosophy of the last hundred years has been heavily influenced by a doctrine to the effect that the key to the correct understanding of reality is captured syntactically in the ‘Fa’ (or, in more sophisticated versions, in the ‘Rab’) of standard first order predicate logic. Here ‘F’ stands for what is general in reality and ‘a’ for what is individual. Hence “f(a)ntology”. Because predicate logic has exactly two syntactically different kinds of referring expressions—‘F’, ‘G’, ‘R’, etc., and ‘a’, (...) ‘b’, ‘c’, etc.—so reality must consist of exactly two correspondingly different kinds of entity: the general (properties, concepts) and the particular (things, objects). We describe the historical influence of this view, and also show how standard first-order predicate logic can be used for the logical formalization of a more adequate “six category ontology”, which recognizes, at the level of both particulars and universals, not only things or objects but also events and qualities. (shrink)

The central hypothesis of the collaboration between Language and Computing (L&C) and the Institute for Formal Ontology and Medical Information Science (IFOMIS) is that the methodology and conceptual rigor of a philosophically inspired formal ontology greatly benefits application ontologies. To this end r®, L&C’s ontology, which is designed to integrate and reason across various external databases simultaneously, has been submitted to the conceptual demands of IFOMIS’s Basic Formal Ontology (BFO). With this project we aim to move beyond the level of (...) controlled vocabularies to yield an ontology with the ability to support reasoning applications. Our general procedure has been the implementation of a meta-ontological definition space in which the definitions of all the concepts and relations in LinKBase® are standardized in a framework of first-order logic. In this paper we describe how this standardization has already led to an improvement in the LinKBase® structure that allows for a greater degree of internal coherence than ever before possible. We then show the use of this philosophical standardization for the purpose of mapping external databases to one another, using LinKBase® as translation hub, with a greater degree of success than possible hitherto. We demonstrate how this offers a genuine advance over other application ontologies that have not submitted themselves to the demands of philosophical scrutiny. LinKBase® is one of the world’s largest applications-oriented medical domain ontologies, and BFO is one of the world’s first philosophically driven reference ontologies. The collaboration of the two thus initiates a new phase in the quest to solve the so-called “Tower of Babel”. (shrink)

We provide an overview of Searle's contributions to speech act theory and the ontology of social reality, focusing on his theory of constitutive rules. In early versions of this theory, Searle proposed that all such rules have the form 'X counts as Y in context C' formula – as for example when Barack Obama (X) counts as President of the United States (Y) in the context of US political affairs. Crucially, the X and the Y terms are here identical. A (...) problem arises for this theory for cases involving 'free-standing Y terms', as for example in the case of money in a computerized bank account. Here there is no physical X to which a status function might be attached. We conclude by arguing that Searle's response to this problem creates difficulties for his naturalistic framework. (shrink)

Analytical philosophy of the last one hundred years has been heavily influenced by a doctrine to the effect that one can arrive at a correct ontology by paying attention to certain superficial (syntactic) features of first-order predicate logic as conceived by Frege and Russell. More specifically, it is a doctrine to the effect that the key to the ontological structure of reality is captured syntactically in the ‘Fa’ (or, in more sophisticated versions, in the ‘Rab’) of first-order logic, where ‘F’ (...) stands for what is general in reality and ‘a’ for what is individual. Hence “f(a)ntology”. Because predicate logic has exactly two syntactically different kinds of referring expressions—‘F’, ‘G’, ‘R’, etc., and ‘a’, ‘b’, ‘c’, etc.—so reality must consist of exactly two correspondingly different kinds of entity: the general (properties, concepts) and the particular (things, objects), the relation between these two kinds of entity being revealed in the predicate-argument structure of atomic formulas in first-order logic. (shrink)

These papers treat those issues involved in formulating a logic of propositional attitutudes and consider the relevance of the attitudes to the continuing study of both the philosophy of language and the philosophy of mind. Table of Contents: Introduction, by C. Anthony Anderson and Joseph Owens Quine on Quantifying In, by Kit Fine Prolegomena to a Structural Theory of Belief and Other Attitudes, by Hans Kemp A Study in Comparitive Semantics, by Ernest LePore and Barry Loewer Wherein is Language Social?, (...) by Tyler Burge Narrow Content, by Robert Stalnaker Cognitive Access and Semantic Puzzles, by Joseph Owens On Some Thought-Experiments About Mind and Meaning, by John Wallace and H. E. Mason Belief and the Indentity of Reference, by Keith S. Dennellan A Millian Heir Rejects the Wages of Sinn, by Nathan Salmon The Mode-of-Presentation Problem, by Stephen Schiffer Consciousness and Intentionality: Robots With and Without the Right Stuff, by Keith Gunderson Consciousness, Unconsciousness, and Intentionality, by John R. Searle. (shrink)

Part 1 of this exchange consists in a critique by Smith of Searle’s The Construction of Social Reality focusing on Searle’s use of the formula ‘X counts as Y in context C’. Smith argues that this formula works well for social objects such as dollar bills and presidents where the corresponding X terms (pieces of paper, human beings) are easy to identify. In cases such as debts and prices and money in a banks computers, however, the formula fails, because these (...) are cases of what he calls ‘free-standing Y terms’, since there is here no X which can count as the corresponding Y. In his response in Part 2, Searle argues that Smith’s critique rests on three misunderstandings: 1. in wrongly presupposing that Searle is trying to analyze the nature of what he calls “social objects”, rather than of social facts; 2. in thinking that the counts as formula is intended as a definition, rather than as a mere mnemonic; and 3. in neglecting the naturalism of Searle’s account. (shrink)

We are often told that we are morally obligated to produce equal opportunity for all. Therefore, it seems we should examine what power we have to produce that desirable state. For it would be nonsense to say we are required to provide what is beyond our power to provide. When we examine this question, we find our power limited by two sets of constraints. One set comprises formal constraints upon the idea itself of equal opportunity. We cannot do the logically (...) impossible. The other set comprises limits upon our ability to produce the directed socio-economic change, getting known outputs for known inputs. I illustrate the formal constraints by outlining the work of Douglas Rae. The constraints upon our abilities I illustrate with evidence from sociology and politics. At the end, we shall discover that our power to make opportunities equal is sharply though not unbearably limited. A critical but unbaised survey will reveal that in the past fifty years we have gone remarkably far towards doing all that we are presently capable of doing to equalize opportunities. Perhaps we shall go even farther when we learn how. The word ‘real’ in the title is opposed to ‘ideal’ or even ‘chimerical'. It may seem an interesting question what equality of opportunity should consist in were we able to produce directed socio-economic change at will. But we are not. Therefore, a more interesting and more important question is what equality of opportunity consists in given the very large number of constraints within which we must work to achieve it. (shrink)

‘Mysticism means to isolate the eternal from the originated.’ This is not my definition of the word ‘mysticism’ but that of the founder of the ‘orthodox’ school of Muslim mysticism, Al-Junayd of Baghdad who flourished in the ninth century a.d . In actual fact it is not a definition of mysticism at all but of the Arabic word tawḥīd which means primarily ‘the affirmation of unity’; and that surely is an essential ingredient of any form of mysticism: it is the (...) affirmation through personal experience of unity either absolutely or in some qualified sense. (shrink)

As everyone knows, since the end of the Second World War there has been a sensational revival of interest in the non-Christian religions particularly in the United States and in this country. The revival has taken two forms, the one popular, the other academic. The first of these has turned almost exclusively to Hindu and Buddhist mysticism and can be seen as an energetic reaction against the dogmatic and until very recently rigid structure of institutionalised Christianity and a search for (...) a lived experience of the freedom of the spirit which is held to be the true content of mysticism, obscured in Christianity by the basic dogma of a transcendent God, the ‘wholly Other’ of Rudolf Otto and his numerous followers, but wholly untrammelled by any such concept in the higher reaches of Vedanta and Buddhism, particularly in its Zen manifestation. On the academic side the picture is less clear. There is, of course, the claim that the study of religion, like any other academic study, must be subjected to and controlled by the same principles of ‘scientific’ objectivity to which the other ‘arts’ subjects have been subjected, to their own undoing. But even here there would seem to be a bias in favour of the religions of India and the Far East as against Islam, largely, one supposes, in response to popular demand. (shrink)

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into (...) two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop. (shrink)

Pain is undertreated in the American health-care system at all levels: physician offices, hospitals, long-term care facilities. The result is needless suffering for patients, complications that cause further injury or death, and added costs in treatment overall. The health-care system's failure to respond to patient pain needs corrective action. Excuses for such shortcomings are simply not acceptable any longer.Physicians have long been accused of poor pain management for their patient. The term “opiophobia” has been coined to describe this remarkable clinical (...) aversion to the proper use of opioids to control pain. If the professional mandate of the health-care professional is to relieve suffering, then physicians are falling far short of their obligations by accepting myths about the use of opioids in the face of evidence to the contrary. (shrink)

Scientific discovery and scientific progress are made by scientists, not philosophers. Philosophers sometimes overlook this fact. It appears to be completely ignored by those who call themselves feminist philosophers of science. A favored claim among them is that the production of a feminist epistemology, or of a feminist society, or of both together, will produce something called ‘feminist science’. Feminist science will be different, they say, from the science we now have. One leading proponent of this view, Sandra Harding, writes: (...) “[t]he sciences that gain world ascendancy in the future are unlikely to be so distinctively Western and androcentric as are the dominant tendencies today.” But just how will they differ? Like all utopians these feminists are short on specifics and we are never told what such a science as science would look like, even in outline, much less in detail, nor how it is likely to differ as science from swnh. (shrink)

Physicians and institutional providers face expanding liability exposure today, in spite of state tort reform legislation and public awareness of the costs of malpractice for providers. Standards of practice are evolving rapidly; new medical technologies are being introduced at a rapid rate; information is proliferating as to treatment efficacy, patient risk, and diseases generally. Tort standards mirror this change. As medical standards of care evolve, they provide a benchmark against which to measure provider failure. The liability exposure of physicians is (...) affected by the generation of data, including outcomes data usable to profile physician practice, and statistical data that allows for predictions as to treatment efficacy, and patient prognosis; obligations to inform patients and third parties of risk created by contagious disease and other sources of harm; obligations of physicians to disclose risks that the provider creates for the patient; obligations to disclose conflicts of interest arising out of the practice setting; and duties arising from new epidemiological knowledge. (shrink)