© 2015, Springer-Verlag Berlin Heidelberg.Genetic studies have identified single nucleotide polymorphisms associated with the risk of prostate cancer. It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score and aggressiveness. Statistical analyses were used to compare the frequency (...) of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 was significantly and inversely associated with aggressive and high-grade disease in European men. Similar associations with aggressive and high-grade disease were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness. (shrink)

While explaining a large proportion of any variance, accounts of the speed and accuracy of targetting movements use techniques (e.g., log transforms) that typically reduce variability before ''explaining'' the data. Therefore the predictive power of such accounts are important. We consider whether Plamondon's model can account for kinematics of targetting movements of clinical populations.

The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding semantic expressivity to (...) existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological and medical investigations and by importing parts of other biomedical ontologies such as GO, Chemical Entities of Biological Interest (ChEBI) and Phenotype Attribute and Trait Ontology (PATO) without altering their meaning. OBI is being used in a wide range of projects covering genomics, multi-omics, immunology, and catalogs of services. OBI has also spawned other ontologies (Information Artifact Ontology) and methods for importing parts of ontologies (Minimum information to reference an external ontology term (MIREOT)). The OBI project is an open cross-disciplinary collaborative effort, encompassing multiple research communities from around the globe. To date, OBI has created 2366 classes and 40 relations along with textual and formal definitions. The OBI Consortium maintains a web resource providing details on the people, policies, and issues being addressed in association with OBI. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Philosophy, Psychiatry, & Psychology 8.4 (2001) 343-346 [Access article in PDF] Kimura Bin on Schizophrenia James Phillips With "Cogito and I: A Bio-Logical Approach," Kimura has continued his research into the core disturbance in schizophrenia. In his work, he has combined an original phenomenological approach with some fundamental concepts taken from his native Japanese and Zen culture. As in the work of others in the tradition of (...) phenomenological psychiatry, he has focused on a basic disturbance that underlies the positive symptoms found in schizophrenic conditions. In what follows, I will attempt to relate this current effort to some of his previous work on schizophrenia. I will conclude this commentary with some remarks on what I find problematic in the treatment of Heidegger.In "Cogito and I," Kimura plunges us directly into the core ego disturbance of schizophrenic patients by quoting two patients who, each in his own words, describe a pathological split between what we may call a "subjective" and an "objective" I or self. The latter is the self that acts and is recognizable by others (and by the patient) as the agent acting in the world. The former, the subjective self, is the non-objectified sense of self or self-awareness that accompanies all our actions. The two must be integrated, and it is a failure of this integration that is at the basis of the schizophrenic's ego disturbance.We can gain further clarification of this central notion in Kimura's treatment of schizophrenia through reference to some of his other discussions of the topic. In "Reflection and Self in the Schizophrenic" (Kimura 1992b), he invokes Husserlian terminology to discuss the same polarity within the self. 1 In this study, he distinguishes "simultaneous reflection" (the subjective self) from "secondary reflection" (the objective self). In the latter, the self is a noematic object of reflection; it is the image of myself after the act, the I that has done something and can now be captured in reflection. While "Cogito and I" describes the schizophrenic split as between the noematic self and the noetic self of simultaneous reflection, "Reflection and Self in the Schizophrenic" locates the split further back within the noetic self. Kimura distinguishes in the noetic self an observing I from the I that is moving toward action, both prior to the noematic self of secondary reflection. "One could say that a subjective self here accompanies an other self no less subjective and observes it constantly 'from behind'. There is no objective, noematic self involved here; a sole noetic self splits into two simultaneous 'moments' which occupy alternitively the places of seeing and seen, and which nonetheless remain subjective-noetic" (Kimura 1992b, 118). Pélicier emphasizes this Husserlian analysis in his exposition of Kimura Bin's phenomenological treatment of schizophrenia: The Self is never grasped as an object, but rather experienced in a noetic mode. On the other hand, the representation (l'image), as an object of consciousness, and in a certain manner all representations (images), as objects of consciousness, are of the noematic [End Page 343] order in Husserl's sense. Kimura insists then on the difference between this auto-perception (jikaku) in the noetic register and its content, which, itself, is noematic. Starting from this analysis, Kimura poses to himself the question of the nature of schizophrenia.... (Pélicier 1984, 32) In still another treatment of the theme, "Pathology of the Immediate" (Kimura 1992c), Kimura Bin focuses on the role of language in the structure of the self. The circuit of simultaneous and secondary reflection described above is played out in the pre-linguistic and linguistic dimensions of the self. Simultaneous reflection is immediate and fugitive in a manner that escapes articulation but at the same time, very readily flows into a secondary reflection that exists only as a mediated, articulated, noematic self. As Kimura puts it, "As for the I, which seems apparently the most immediately given, this also, when it becomes conscious of itself as 'I,' is constituted equally as an experience mediated by a negative differentiation that inserts itself between the 'I' that is in the process of becoming... (shrink)

In the conclusion to this multi-part article I first review the discussions carried out around the six essential questions in psychiatric diagnosis – the position taken by Allen Frances on each question, the commentaries on the respective question along with Frances’ responses to the commentaries, and my own view of the multiple discussions. In this review I emphasize that the core question is the first – what is the nature of psychiatric illness – and that in some manner all further (...) questions follow from the first. Following this review I attempt to move the discussion forward, addressing the first question from the perspectives of natural kind analysis and complexity analysis. This reflection leads toward a view of psychiatric disorders – and future nosologies – as far more complex and uncertain than we have imagined. (shrink)

Scepticism about ought simpliciter is the view that there is no such thing as what one ought simpliciter to do. Instead, practical deliberation is governed by a plurality of normative standpoints, each authoritative from their own perspective but none authoritative simpliciter. This paper aims to resist such scepticism. After setting out the challenge in general terms, I argue that scepticism can be resisted by rejecting a key assumption in the sceptic’s argument. This is the assumption that standpoint-relative ought judgments bring (...) with them a commitment to act in accordance with those judgments. Instead, I propose an alternative account of our normative concepts according to which only ought simpliciter judgments commit one to acting in accordance with those judgments. In addition to answering the sceptical challenge, the proposal offers an independently motivated account of what makes a concept normatively authoritative. (shrink)

This paper examines the general prospects for conceptual role expressivism, expressivist theories that embrace conceptual role semantics. It has two main aims. The first aim is to provide a general characterisation of the view. The second aim is to raise a challenge for the general view. The challenge is to explain why normative concepts are not a species of defective concepts, where defective concepts are those that cannot meaningfully embed and participate in genuine inference. After rejecting existing attempts to answer (...) the challenge, I propose an alternative solution. However, the solution leaves conceptual role expressivism a far less distinctive and interesting position than its proponents claim. I conclude that we should be sceptical about how much expressivists gain by appealing to conceptual role semantics. (shrink)

Critical notice of Guy Fletcher's 'Dear Prudence: The Nature and Normativity of Prudential Discourse' and Dale Dorsey's 'A Theory of Prudence'.

Anthropology is a complex, wide-ranging, and ever-changing field. This clear, coherent, and well-crafted book is a revised version of a very successful text first published in 1986, designed to supplement standard textbooks and monographs. It covers the central concepts, distinctive methodologies, and philosophical as well as practical issues of cultural anthropology, and it is accessible to the anthropological novice, and of value to the professional. The updated version covers current issues in cultural anthropology, and includes topics such as globalization, gender, (...) post-modernism and public issues, and reflects changes in perspective and language. (shrink)

The concept of whole‐brain death is under attack again. Scholars are arguing that the concept of brain death per se—regardless of the focus on “higher,” “stem” or “whole”—is fundamentally flawed. These scholars have identified what they believe are serious discrepancies between the definition and criterion of brain death, and have pointed out that medical professionals and lay persons remain confused about its meaning. Yet whole‐brain death remains the standard for determining death in much of the Western world and its defenders (...) believe this concept best maps onto our everyday conception of death. (shrink)

The distinction between the "permanent" (will not reverse) and "irreversible" (cannot reverse) cessation of functions is critical to understand the meaning of a determination of death using circulatory–respiratory tests. Physicians determining death test only for the permanent cessation of circulation and respiration because they know that irreversible cessation follows rapidly and inevitably once circulation no longer will restore itself spontaneously and will not be restored medically. Although most statutes of death stipulate irreversible cessation of circulatory and respiratory functions, the accepted (...) medical standard is their permanent cessation because permanence is a perfect surrogate indicator for irreversibility, and using it permits a more timely declaration. Therefore, patients properly declared dead in donation after circulatory death (DCD) protocols satisfy the requirements of death statutes and do not violate the dead donor rule. The acronym DCD should represent organ "donation after circulatory death" to clarify that the death standard is the permanent cessation of circulation, not heartbeat. Heart donation in DCD does not retroactively negate the donor's death determination because circulation has ceased permanently. (shrink)

Expressivists about normative thought and discourse traditionally deny that there are nondeflationary normative propositions. However, it has recently been suggested that expressivists might avoid a number of problems by providing a theory of normative propositions compatible with expressivism. This paper explores the prospects for developing an expressivist theory of propositions within the framework of cognitive act theories of propositions. First, I argue that the only extant expressivist theory of cognitive propositions—Michael Ridge's ‘ecumenical expressivist’ theory—fails to explain identity conditions for normative (...) propositions. Second, I argue that this failure motivates a general constraint—the ‘unity requirement’—that any expressivist theory of propositions must provide a unified nonrepresentational explanation of that in virtue of which propositional attitudes have the content that they have. Third, I argue that conceptual role accounts of content provide a promising framework in which to develop an expressivist theory of cognitive propositions. (shrink)

The definition of death is one of the oldest and most enduring problems in biophilosophy and bioethics. Serious controversies over formally defining death began with the invention of the positive-pressure mechanical ventilator in the 1950s. For the first time, physicians could maintain ventilation and, hence, circulation on patients who had sustained what had been previously lethal brain damage. Prior to the development of mechanical ventilators, brain injuries severe enough to induce apnea quickly progressed to cardiac arrest from hypoxemia. Before the (...) 1950s, the loss of spontaneous breathing and heartbeat were perfect predictors of death because the functioning of the brain and of all other organs ceased rapidly and nearly simultaneously thereafter, producing a unitary death phenomenon. In the pretechnological era, physicians and philosophers did not have to consider whether a human being who had lost certain “vital functions” but had retained others was alive, because such cases were technically impossible. (shrink)

Abstract:Disturbing cases continue to be published of patients declared brain dead who later were found to have a few intact brain functions. We address the reasons for the mismatch between the whole-brain criterion and brain death tests, and suggest solutions. Many of the cases result from diagnostic errors in brain death determination. Others probably result from a tiny amount of residual blood flow to the brain despite intracranial circulatory arrest. Strategies to lessen the mismatch include improving brain death determination training (...) for physicians, mandating a test showing complete intracranial circulatory arrest, or revising the whole-brain criterion. (shrink)

The shape of a life hypothesis holds that the temporal sequence of good or bad times in a life can itself be a valuable feature of that life. This is generally thought to be incompatible with additivism about lifetime well-being, which holds that lifetime well-being is fully determined by momentary well-being. This discussion examines Dale Dorsey’s recent argument that these views are in fact compatible. I argue that accepting the conjunction of these views requires stronger commitments than Dorsey recognizes. After (...) arguing that these commitments are problematic, I conclude that we should reject the compatibility claim. (shrink)

A combination of emerging life support technologies and entrenched organ donation practices are complicating the physician's task of determining death. On the one hand, technologies that support or replace ventilation and circulation may render the diagnosis of death ambiguous. On the other, transplantation of vital organs requires timely and accurate declaration of death of the donor to keep the organs as healthy as possible. These two factors have led to disagreements among physicians and scholars on the precise moment of death. (...) In this article, I suggest that the debate about exactly when a person dies can benefit from distinguishing the strict biological concept of death from the medical standards for determining human death, and I show how an appreciation of the difference between the permanent and irreversible cessation of circulation is helpful in understanding the reasons for the two approaches to determining when death should be declared. (shrink)

The publicity surrounding the recent McMath and Muñoz cases has rekindled public interest in brain death: the familiar term for human death determination by showing the irreversible cessation of clinical brain functions. The concept of brain death was developed decades ago to permit withdrawal of therapy in hopeless cases and to permit organ donation. It has become widely established medical practice, and laws permit it in all U.S. jurisdictions. Brain death has a biophilosophical justification as a standard for determining human (...) death but remains poorly understood by the public and by health professionals. The current controversies over brain death are largely restricted to the academy, but some practitioners express ambivalence over whether brain death is equivalent to human death. Brain death remains an accepted and sound concept, but more work is necessary to establish its biophilosophical justification and to educate health professionals and the public. (shrink)

Nair-Collins and Joffe (2023) highlighted the noncongruence between the language of the Uniform Determination of Death Act (UDDA) and the accepted brain death bedside testing standard by showing th...

Ariane Lewis provided an insightful review of several controversial cases of death by neurologic criteria (“brain death”) in the UK, focusing on Archie Battersbee, a boy whose tragic illness provok...

Among the old and new controversies over brain death, none is more fundamental than whether brain death is equivalent to the biological phenomenon of human death. Here, I defend this equivalency by offering a brief conceptual justification for this view of brain death, a subject that Andrew Huang and I recently analyzed elsewhere in greater detail. My defense of the concept of brain death has evolved since Bernard Gert, Charles Culver, and I first addressed it in 1981, a development that (...) paralleled advances in intensive care unit treatment. The century‐old concept of the organism as a whole provides the fundamental justification for the equivalency of brain death and human death. In our technological age, in which increasing numbers of components and systems of an organism can be kept alive, and for longer intervals, the permanent cessation of functioning of the organism as a whole is the phenomenon that best corresponds to its death. (shrink)

Notwithstanding these wise pronouncements, my project here is to characterize the biological phenomenon of death of the higher animal species, such as vertebrates. My claim is that the formulation of “whole- brain death ” provides the most congruent map for our correct understanding of the concept of death. This essay builds upon the foundation my colleagues and I have laid since 1981 to characterize the concept of death and refine when this event occurs. Although our society's well-accepted program of multiple (...) organ procurement for transplantation requires the organ donor first to be dead, the concept of brain death is not merely a social contrivance to permit us to obtain the benefits of organ procurement. Rather, the concept of whole- brain death stands independently as the most accurate biological representation of the demise of the human organism. (shrink)

Over the past quarter century, organ donation after the circulatory determination of death (DCD) has grown in acceptance and prevalence throughout the world (Domínguez-Gil et al. 2021). Notwithstan...

The locked-in syndrome is a state of profound paralysis with preserved awareness of self and environment who typically results from a brain stem stroke. Although patients in LIS have great difficulty communicating, their consciousness, cognition, and language usually remain intact. Medical decision-making by LIS patients is compromised, not by cognitive impairment, but by severe communication impairment. Former systems of communication that permitted LIS patients to make only “yes” or “no” responses to questions was sufficient to validate their consent for simple (...) medical decisions but not for consequential medical decisions such as whether to refuse further life-sustaining therapy. Emerging technologies including computer-tracking assistance of retained partial motor function and brain-computer interfaces promise to improve the communication ability of LIS patients and, when better developed, will allow them to fully exercise their right to actively participate in consequential medical decisions about their own medical care. Although so-called “covert cognition” patients clinically diagnosed as vegetative state that are shown to be aware by functional neuroimaging maybe metaphorically considered locked-in, it is nosologically more coherent not to categorize them formally as LIS. (shrink)

Hirsch’s revision results from his attempt to think through the difficult question that underlies the whole essay: How does the movement of time and circumstance affect the stability of meaning? The first part of his answer is that the relation between original meaning and subsequent understanding or applications of that meaning is analogous to the relation between a concept and its extension. For example, if he reads Shakespeare’s sonnet 55 and applies it to his beloved, and one of us reads (...) it and applies it to his beloved, “that does not make the meaning of the sonnet different for us, assuming that we both understand that the text’s meaning is not limited to any particular exemplification but rather embraces many, many exemplifications” . That is, the sonnet has a status analogous to that of the concept “bicycle,” and the two applications have a status analogous to that of a three-speed and a ten-speed bicycle. Whereas Hirsch formerly considered such exemplifications part of a text’s significance, he now considers them part of its meaning. This revision indicates that for Hirsch meaning is not the product of a consciousness producing an intrinsic genre but of a consciousness communicating something broader and more general than an intrinsic genre—an intention-concept that can have numerous extensions or exemplifications, including many that the originating consciousness could not have anticipated. Formerly, Hirsch used intrinsic genre to describe that sense of the whole which governed the horizon of developing meaning and which, when the work was completed—when all the blanks were filled in—gave the work its specific determinate meaning. That is, determinacy of meaning was in large part a function of narrowing the class of implications; when the work was completed, the class of implications was restricted to those synonymous with expressed meaning. In short, in the old theory, meaning-intention is a “narrow,” not a broad “concept.” James L. Battersby, professor of English at Ohio State University, is the author of Rational Praise and Natural Lamentation: Johnson, Lycidas, and Principles of Criticism and Elder Olson: An Annotated Bibliography. He is currently at work on a study of the relationship between “thought” and structure in various genres. James Phelan is associate professor English at Ohio State University and the author of Worlds from Words: A Theory of language in Fiction. His work in progress concerns character and narrative progression. (shrink)

Conspicuous consumption associated with status reinforcement behavior can be explained in terms of costly signaling, or strategic handicap theory, first articulated by Zahavi and later formalized by Grafen. A theory is introduced which suggests that the evolutionary raison d’être of status reinforcement behavior lies not only in its effects on lifetime reproductive success, but in its positive effects on the probability of survival through infrequent, unpredictable demographic bottlenecks. Under some circumstances, such “wasteful” displays may take the form of displays of (...) altruistic behavior and generosity on the part of high status individuals, in that is signals the ability to bear the short-term costs of being generous or “cooperative,” while at the same time reinforcing the long-term benefits of higher status. (shrink)

In this work, a neo-classical relativistic mechanics theory is presented where the spin of an electron is an inherent part of its world space-time path as a point particle. The fourth-order equation of motion corresponds to the same covariant Lagrangian function in proper time as in special relativity except for an additional spin energy term. The theory provides a hidden-variable model of the electron where the dynamic variables give a complete description of its motion, giving a classical mechanics explanation of (...) the electron’s spin, its dipole moments, and Schrödinger’s zitterbewegung, These features are also described mathematically by quantum mechanics theory, of course, but without any physical picture of an underlying reality. The total motion of the electron can be decomposed into a sum of a local spin motion about a point and a global motion of this point, called here the spin center. The global motion is sub-luminal and described by Newton’s Second Law in proper time, the time for a clock fixed at the spin center, while the total motion occurs at the speed of light c, consistent with the eigenvalues of Dirac’s velocity operators having magnitude c. The local spin motion is an inherent perpetual motion, which for a free electron is periodic at the ultra-high zitterbewegung frequency and its path is circular in a spin-center reference frame. In an electro-magnetic field, this spin motion generates magnetic and electric dipole energies through the Lorentz force on the electron’s point charge. The electric dipole energy corresponds to the spin-orbit coupling term involving the electric field that appears in the corrected Pauli non-relativistic Hamiltonian, which has long been used to explain the doublet structure of the spectral lines of the excited hydrogen atom. Pauli’s spin-orbit term is usually derived, however, from his magnetic dipole energy term, including also the effect of Thomas precession, which halves this energy. The magnetic dipole energy from Pauli’s and Dirac’s theory is twice that in the neo-classical theory, a discrepancy that has not been resolved. By defining a spin tensor as the angular momentum of the electron’s total motion about its spin center, the fundamental equations of motion can be re-written in an identical form to those of the Barut–Zanghi electron theory. This allows the equations of motion to be expressed in an equivalent form involving operators applied to a state function of proper time satisfying a neo-classical Dirac–Schrödinger spinor equation. This state function produces the dynamic variables from the same operators as in Dirac’s theory for the electron but without any probability implications. It leads to a neo-classical wave function that satisfies Dirac’s relativistic wave equation for the free electron by applying the Lorentz transformation to express proper time in the state function in terms of an observer’s space-time coordinates, showing that there is a close connection between the neo-classical theory and quantum mechanics theory for the electron’s dynamics. (shrink)

Despite the popularity, success, and growth of programs of organ donation after the circulatory determination of death (DCDD), a long‐standing controversy persists over whether the organ donor is truly dead at the moment physicians declare death, usually following five minutes of circulatory and respiratory arrest. Advocates of the prevailing death determination standard claim that the donor is dead when declared because of permanent cessation of respiration and circulation. Critics of this standard argue that while the cessation of respiration and circulation (...) may be permanent, it may not be irreversible at the moment death is declared because, if cardiopulmonary resuscitation were performed, it might succeed. And because irreversibility of cessation of respiration and circulation is required by both the statute and the biological concept of death, the donor must be alive. Who is correct?Making two related distinctions clarifies the cause of the disagreement over whether the DCDD donor is dead and points to a possible resolution. First, in a determination of death, there is an important distinction between the permanent and the irreversible cessation of circulation and respiration—two associated phenomena that are often confounded. Second, there is an important distinction between the medical practice standard for death determination, in which physicians certify the permanent cessation of vital functions as sufficient for death declaration, and the underlying biological concept of death that requires the irreversible cessation of vital functions because death, by definition, is an irreversible event. (shrink)