A logical analysis of T cell activation and anergy.
Interaction of the antigen-specific receptor of T lymphocytes with its antigenic ligand can lead either to cell activation or to a state of profound unresponsiveness (anergy). Although subtle changes in the nature of the ligand or of the antigen-presenting cell have been shown to affect the outcome of T cell receptor ligation, the mechanism by which the same receptor can induce alternative cellular responses is not completely understood. A model for explaining both positive (cell proliferation and cytokine production) and negative (anergy induction) signaling of T lymphocytes is described herein. This model relies on the autophosphorylative properties of the tyrosine kinases associated with the T cell receptor. One of its basic assumptions is that the kinase activity of these receptor-associated enzymes remains above background level after ligand removal and is responsible for cellular unresponsiveness. Using a simple Boolean formalism, we show how the timing of the binding and intracellular signal-transduction events can affect the properties of receptor signaling and determine the type of cellular response. The present approach integrates into a common framework a large body of experimental observations and allows specification of conditions leading to cellular activation or to anergy. (+info
Specific cognitive deficits in mild frontal variant frontotemporal dementia.
Eight patients with relatively mild frontal variant frontotemporal dementia (fvFTD) were compared with age- and IQ-matched control volunteers on tests of executive and mnemonic function. Tests of pattern and spatial recognition memory, spatial span, spatial working memory, planning, visual discrimination learning/attentional set-shifting and decision-making were employed. Patients with fvFTD were found to have deficits in the visual discrimination learning paradigm specific to the reversal stages. Furthermore, in the decision-making paradigm, patients were found to show genuine risk-taking behaviour with increased deliberation times rather than merely impulsive behaviour. It was especially notable that these patients demonstrated virtually no deficits in other tests that have also been shown to be sensitive to frontal lobe dysfunction, such as the spatial working memory and planning tasks. These results are discussed in relation to the possible underlying neuropathology, the anatomical connectivity and the hypothesized heterogeneous functions of areas of the prefrontal cortex. In particular, given the nature of the cognitive deficits demonstrated by these patients, we postulate that, relatively early in the course of the disease, the ventromedial (or orbitofrontal) cortex is a major locus of dysfunction and that this may relate to the behavioural presentation of these patients clinically described in the individual case histories. (+info
Autonomy, rationality and the wish to die.
Although suicide has traditionally carried a negative sanction in Western societies, this is now being challenged, and while there remains substantial public concern surrounding youth and elder suicide, there is a paradoxical push to relax the prohibition under certain circumstances. Central to the arguments behind this are the principles of respect for autonomy and the importance of rationality. It is argued here that the concepts of rationality and autonomy, while valuable, are not strong enough to substantiate a categorical "right to suicide" and that the concepts of "understandability" and "respect" are more useful and able to provide the foundation for responding to a person expressing a wish to die. Roman suicide, sometimes held as an example of "rational suicide", illustrates the effects of culture, tradition and values on the attitudes to, and the practice of, suicide. (+info
Arguments for zero tolerance of sexual contact between doctors and patients.
Some doctors do enter into sexual relationships with patients. These relationships can be damaging to the patient involved. One response available to both individual doctors and to disciplinary bodies is to prohibit sexual contact between doctors and patients ("zero tolerance"). This paper considers five ways of arguing for a zero tolerance policy. The first rests on an empirical claim that such contact is almost always harmful to the patient involved. The second is based on a "principles" approach while the third originates in "virtues" ethics. The fourth argues that zero tolerance is an "a priori" truth. These four attempt to establish that the behaviour is always wrong and ought, therefore, to be prohibited. The fifth argument is counterfactual. It claims a policy that allowed sexual contact would have unacceptable consequences. Given the responsibility of regulatory bodies to protect the public, zero tolerance is a natural policy to develop. (+info
The future of philosophy.
There is no sharp dividing line between science and philosophy, but philosophical problems tend to have three special features. First, they tend to concern large frameworks rather than specific questions within the framework. Second, they are questions for which there is no generally accepted method of solution. And third they tend to involve conceptual issues. For these reasons a philosophical problem such as the nature of life can become a scientific problem if it is put into a shape where it admits of scientific resolution. Philosophy in the 20th century was characterized by a concern with logic and language, which is markedly different from the concerns of earlier centuries of philosophy. However, it shared with the European philosophical tradition since the 17th century an excessive concern with issues in the theory of knowledge and with scepticism. As the century ends, we can see that scepticism no longer occupies centre stage, and this enables us to have a more constructive approach to philosophical problems than was possible for earlier generations. This situation is somewhat analogous to the shift from the sceptical concerns of Socrates and Plato to the constructive philosophical enterprise of Aristotle. With that in mind, we can discuss the prospects for the following six philosophical areas: (1) the traditional mind-body problem; (ii) the philosophy of mind and cognitive science; (iii) the philosophy of language; (iv) the philosophy of society; (v) ethics and practical reasons; (vi) the philosophy of science. The general theme of these investigations, I believe, is that the appraisal of the true significance of issues in the philosophy of knowledge enables us to have a more constructive account of various other philosophical problems than has typically been possible for the past three centuries. (+info
Illusions in reasoning about consistency.
Reasoners succumb to predictable illusions in evaluating whether sets of assertions are consistent. We report two studies of this computationally intractable task of "satisfiability." The results show that as the number of possibilities compatible with the assertions increases, the difficulty of the task increases, and that reasoners represent what is true according to assertions, not what is false. This procedure avoids overloading memory, but it yields illusions of consistency and of inconsistency. These illusions modify our picture of human rationality. (+info
Fairness versus reason in the ultimatum game.
In the Ultimatum Game, two players are offered a chance to win a certain sum of money. All they must do is divide it. The proposer suggests how to split the sum. The responder can accept or reject the deal. If the deal is rejected, neither player gets anything. The rational solution, suggested by game theory, is for the proposer to offer the smallest possible share and for the responder to accept it. If humans play the game, however, the most frequent outcome is a fair share. In this paper, we develop an evolutionary approach to the Ultimatum Game. We show that fairness will evolve if the proposer can obtain some information on what deals the responder has accepted in the past. Hence, the evolution of fairness, similarly to the evolution of cooperation, is linked to reputation. (+info
Modeling anatomical spatial relations with description logics.
Although spatial relations are essential for the anatomy domain, spatial reasoning is only weakly supported by medical knowledge representation systems. To remedy this shortcoming we express spatial relations that can intuitively be applied to anatomical objects (such as 'disconnected', 'externally connected', 'partial overlap' and 'proper part') within the formal framework of description logics. A special encoding of concept descriptions (in terms of SEP triplets) allows us to emulate spatial reasoning by classification-based reasoning. (+info