The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

If stem cell-based therapies are developed, we will likely confront a difficult problem of justice: for biological reasons alone, the new therapies might benefit only a limited range of patients. In fact, they might benefit primarily white Americans, thereby exacerbating long-standing differences in health and health care.

David Lewis's modal realism claims that nothing can exist in more than one world or time, and that statements about how something would have been are to be analysed in terms of its counterpart. I first explain why the counterpart relation depends on de re modal statements in an intensional language, so that intuitive properties of similarity relations cannot be used to show that the counterpart relation is not an equivalence relation. I then look at test sentences in (the intensional) (...) natural language, and show that none of them provide compelling evidence that a counterpart semantics is needed. (shrink)

Adverbial modification is probably one of the least understood areas of linguistics. The essays in this volume all address the problem of how to give an analysis of adverbial modifiers within truth-conditional semantics. Chapters I-VI provide analyses of particular modifiers within a possible worlds framework, and were written between 1974 and 1981. Original publication details of these chapters may be found on p. vi. Of these, all but Chapter I make essential use of the idea that the time reference involved (...) in tensed sentences should be a time interval rather than a single instant. The final chapter (Chapter VII) was written especially for this volume and investigates the question of how the 'situation semantics' recently devised by Jon Barwise and John Perry, as a rival to possible-worlds semantics, might deal with adverbs. In addition I have included an appendix to Chapter III and an introduction which links all the chapters together. (shrink)

Semantic Indexicality shows how a simple syntax can be combined with a propositional language at the level of logical analysis. It is the adoption of such a base language which has not been attempted before, and it is this which constitutes the originality of the book. Cresswell's simple and direct style makes this book accessible to a wider audience than the somewhat specialized subject matter might initially suggest.

George Greenough was one of the influential group of early nineteenth-century English geologists who rejected both Hutton's and Werner's attempts to propound all-embracing geological theories, and followed a deliberately empirical approach. He travelled through Scotland in 1805, studying geological phenomena in the light of both the Plutonist and the Neptunist theories, and generally concluded that neither was entirely satisfactory as an explanation of the observable facts. He was also the first to suggest that the ‘Parallel Roads’ of Glen Roy were (...) the successive beach-levels of a former lake: this theory was later attacked by Darwin but ultimately vindicated by Agassiz's glacial theory. The more important geological passages from Greenough's MS. journal of the tour are reproduced and discussed in this paper. They illustrate some of the scientific problems that were involved in accepting either Hutton's or Werner's theory entire. (shrink)

Over a longer period than I sometimes care to contemplate I have worked on possible-worlds semantics. The earliest work was in modal logic, to which I keep returning, but a sabbatical in 1970 took me to UCLA, there to discover the work of Richard Montague in applying possible-worlds semantics to natural lan guage. My own version of this appeared in Cresswell (1973) and was followed up in a number of articles, most of which were collected in Cresswell (1985b). A central (...) problem for possible worlds semantics is how to accommodate propositional attitudes. This problem was addressed in Cresswell (1985a), and the three books mentioned so far represent a reasonably complete picture of my positive views on formal semantics. I have regarded the presentation of a positive view as more important than the criticism of alternatives, although the works referred to do contain many passages in which I have tried to defend my own views against those of others. But such criticism is important in that a crucial element in establishing the content of a theory is that we be able to evaluate it in relation to its com petitors. It is for that reason that I have collected in this volume a number of articles in which I attempt to defend the positive semantical picture I favour against objections and competing theories. (shrink)

Criticisms of the ethical justification of antidoping legislation are not uncommon in the literatures of medical ethics, sports ethics and sports medicine. Critics of antidoping point to inconsistencies of principle in the application of legislation and the unjustifiability of ethical postures enshrined in the World Anti-Doping Code, a new version of which came into effect in January 2009. This article explores the arguments concerning the apparent legal peculiarities of antidoping legislation and their ethically salient features in terms of: notions of (...) culpability, liability and guilt; aspects of potential duplication of punishments and the limitations of athlete privacy in antidoping practice and policy. It is noted that tensions still exist between legal and ethical principles and norms that require further critical attention. (shrink)

In celebrating Arthur Prior we celebrate what he gave to the world. Much of this is measured by what others have made of his ideas after his death. The focus of this paper is a little different. It looks at what Prior himself thought he was accomplishing. In particular it considers Prior’s attitude to the semantic metatheory of the logics that he was interested in. The paper sets out some characteristics of the metalogical study of intensional languages in terms of (...) an indexical theory of truth conditions stated in the language of set theory. In examining Prior’s work using these characteristics, it emerges that Prior had serious reservations about this way of studying modal and tense logics. (shrink)

The most common way of proving decidability in propositional modal logic is to shew that the system in question has the finite model property. This is not however the only way. Gabbay in [4] proves the decidability of many modal systems using Rabin's result in [8] on the decidability of the second-order theory of successor functions. In particular [4, pp. 258-265] he is able to prove the decidability of a system which lacks the finite model property. Gabbay's system is however (...) complete, in the sense of being characterized by a class of frames, and the question arises whether there is a decidable modal logic which is not complete. Since no incomplete modal logic has the finite model property [9, p. 33], any proof of decidability must employ some such method as Gabbay's. In this paper I use the Gabbay/Rabin technique to prove the decidability of a finitely axiomatized normal modal propositional logic which is not characterized by any class of frames. I am grateful to the referee for suggesting improvements in substance and presentation.The terminology I am using is standard in modal logic. By aframeis understood a pair 〈W, R〉 in whichWis a class (of “possible worlds”) andR⊆W2. To avoid confusion in what follows, a frame will henceforth be referred to as aKripkeframe. By contrast, ageneral frameis a pair 〈,Π〉 in whichis a Kripke frame andΠis a collection of subsets ofWclosed under the Boolean operations and satisfying the condition that ifAis inΠthen so isR−1“A. A model on a frame (of either kind) is obtained by adding a functionVwhich assigns sets of worlds to propositional variables. In the case of a general frame we require thatV(p) ∈Π. (shrink)