In list-method directed forgetting, reexposure to forgotten List 1 items has been shown to reduce directed forgetting. proposed that reexposure to a few List 1 items only during a direct test of memory reinstates the entire List 1 episode. In the present experiments, part-list reexposure in the context of indirect as well as direct memory tests reduced directed forgetting. Directed forgetting was reduced when 50% or more of the items were reexposed, and was intact when only 25% were reexposed. Furthermore, (...) part-list reexposure appeared to reinstate only reexposed items-not the entire List 1 episode. (shrink)

In list-method directed forgetting, reexposure to forgotten List 1 items has been shown to reduce directed forgetting. proposed that reexposure to a few List 1 items only during a direct test of memory reinstates the entire List 1 episode. In the present experiments, part-list reexposure in the context of indirect as well as direct memory tests reduced directed forgetting. Directed forgetting was reduced when 50% or more of the items were reexposed, and was intact when only 25% were reexposed. Furthermore, (...) part-list reexposure appeared to reinstate only reexposed items-not the entire List 1 episode. (shrink)

This volume is a collection of original essays by eminent philosophers written for R. B. Braithwaite's eightieth birthday to celebrate his work and teaching. In one way or another, all the essays reflect his central concern with the impact of science on our beliefs about the world and the responses appropriate to that. Together they testify to the signal importance of his contributions in areas of philosophy bearing on this concern: the philosophy of science, especially of the statistical sciences, theories (...) of belief and of probability, decision theory and games theory. This book, which includes a full bibliography of Professor Braithwaite's work, will interest advanced students and professionals in the fields of philosophy and psychology. (shrink)

Objectives: To analyse legislation and medical professional positions concerning the doctor’s role in assisted dying in western Europe, and to discuss their implications for doctors.Method: This paper is based on country-specific reports by experts from European countries where assisted dying is legalised , or openly practiced , or where it is illegal .Results: Laws on assisted dying in The Netherlands and Belgium are restricted to doctors. In principle, assisted suicide is not illegal in either Germany or Switzerland, but a doctor’s (...) participation in Germany would violate the code of professional medical conduct and might contravene of a doctor’s legal duty to save life. The Assisted Dying for the Terminally Ill Bill proposed in the UK in 2005 focused on doctors, whereas the Proposal on Assisted Dying of the Norwegian Penal Code Commission minority in 2002 did not.Professional medical organisations in all these countries except The Netherlands maintain the position that medical assistance in dying conflicts with the basic role of doctors. However, in Belgium and Switzerland, and for a time in the UK, these organisations dropped their opposition to new legislation. Today, they regard the issue as primarily a matter for society and politics. This “neutral” stance differs from the official position of the Royal Dutch Medical Association which has played a key role in developing the Dutch practice of euthanasia as a “medical end-of-life decision” since the 1970s.Conclusion: A society moving towards an open approach to assisted dying should carefully identify tasks to assign exclusively to medical doctors, and distinguish those possibly better performed by other professions. (shrink)

0-categorical o-minimal structures were completely described by Pillay and Steinhorn 565–592), and are essentially built up from copies of the rationals as an ordered set by ‘cutting and copying’. Here we investigate the possible structures which an 0-categorical weakly o-minimal set may carry, and find that there are some rather more interesting examples. We show that even here the possibilities are limited. We subdivide our study into the following principal cases: the structure is 1-indiscernible, in which case all possibilities are (...) classified up to binary structure; the structure is 2-indiscernible, classified up to ternary structure; the structure is 3-indiscernible, in which case we show that it is k-indiscernible for every finite k. We also make some remarks about the possible structures of higher arities which an 0-categorical weakly o-minimal structure may carry. (shrink)

Oxidative damage to DNA has been associated with neurodegenerative diseases. Developmental exposure to lead has been shown to elevate the Alzheimer's disease related beta-amyloid peptide , which is known to generate reactive oxygen species in the aging brain. This study measures the lifetime cerebral 8-hydroxy-2'-deoxyguanosine levels and the activity of the DNA repair enzyme 8-oxoguanine DNA glycosylase in rats developmentally exposed to Pb. Oxo8dG was transiently modulated early in life , but was later elevated 20 months after exposure to Pb (...) had ceased, while Ogg1 activity was not altered. Furthermore, an age-dependent loss in the inverse correlation between Ogg1 activity and oxo8dG accumulation was observed. The effect of Pb on oxo8dG levels did not occur if animals were exposed to Pb in old age. These increases in DNA damage occurred in the absence of any Pb-induced changes in copper/zinc-superoxide dismutase , manganese-SOD , and reduced-form glutathion . These data suggest that oxidative damage and neurodegeneration in the aging brain could be impacted by the developmental disturbances. (shrink)

Alzheimer's disease is characterized by amyloid-beta peptide -loaded plaques in the brain. Abeta is a cleavage fragment of amyloid-beta protein precursor and over production of APP may lead to amyloidogenesis. The regulatory region of the APP gene contains consensus sites recognized by the transcription factor, specificity protein 1 , which has been shown to be required for the regulation of APP and Abeta. To understand the role of SP1 in APP biogenesis, herein we have characterized the relative distribution and localization (...) of SP1, APP, and Abeta in various brain regions of rodent and primate models using immunohistochemistry. We observed that overall distribution and cellular localization of SP1, APP, and Abeta are similar and neuronal in origin. Their distribution is abundant in various layers of neocortex, but restricted to the Purkinje cell layer of the cerebellum, and the pyramidal cell layer of hippocampus. These findings suggest that overproduction of Abeta in vivo may be associated with transcriptional pathways involving SP1 and the APP gene. (shrink)

The FDA's new table of surrogate endpoints used for drug approvals is an important step forward for overseeing the use of biomarkers in clinical trials. Nevertheless, we present several ways in which the table can be improved.

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)

Coastal ecosystems are increasingly dominated by humans. Consequently, the human dimensions of sustainability science have become an integral part of emerging coastal governance and management practices. But if we are to avoid the harsh lessons of land management, coastal decision makers must recognize that humans are one of the more coastally dependent species in the biosphere. Management responses must therefore confront both the temporal urgency and the very real compromises and sacrifices that will be necessary to achieve a sustainable coastal (...) ecosystem, one that is economically feasible, socially just, and ecologically sound. (shrink)