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)

The aim of this paper is to provide a conceptual framework that will help in understanding and evaluating, along social and ethical lines, the issue of killing day-old male chicks and two alternative directions of responsible innovations to solve this issue. The following research questions are addressed: Why is the killing of day-old chicks morally problematic? Are the proposed alternatives morally sound? To what extent do the alternatives lead to responsible innovation? The conceptual framework demonstrates clearly that there is a (...) moral “lock-in”, and why the killing of day-old chicks is indeed an issue. Furthermore, it is shown that both alternative directions address some important objections with regard to the killing of day-old chicks, but that they also raise new dilemmas. It also becomes clear that the framework enables and secures anticipation, reflection, deliberation with and responsiveness to stakeholders, the four dimensions of responsible innovation, in a structured way. (shrink)

Much epistemological theorizing is the attempt to specify what makes for meritorious cognition, but epistemologists have not, despite meritorious effort, achieved unity when it comes to picking out the feature and principles that are distinctive of epistemic normativity. In this essay we explain why this is the inevitable outcome. We isolate important but overlooked variations in the link between epistemological theorizing and the idea of epistemic unification, and then argue that much epistemological theorizing is misguided because it aims toward complete (...) epistemic unification when only partial epistemic unification, at best, is possible. But our arguments — based on work in moral epistemology and philosophical psychology — stop short of epistemological eliminativism, and thus we stake out a middle ground between philosophers such as Descartes, the earlier Alston, Audi, and the earlier BonJour on one hand and Rorty, Fish, and Patricia Churchland on the other. (shrink)

New dimensions in different ethical scenarios following genetic information require new medical-ethical Action Guides for physician-patient interaction. This paper discusses the ambiguity in moral choice between a “right not to know” and “a duty to know”, regarding parental decisionmaking pro or contra selective abortion following prenatal screening for autosomal dominant polycystic kidney disease (Potter III) and related public policy issues.

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)

During the decades following the publication of Darwin's Origin of species in 1859, religious belief in England and in particular the Church of England experienced some of the most intense criticism in its history. The early 1860s saw the appearance of Lyell's Evidence of the antiquity of man , Tylor's research on the early history of mankind , Renan's Vie de Jésus , Pius IX's encyclical, Quanta cura, and the accompanying Syllabus errarum, John Henry Newman's Apologia , and Swinburne's notorious (...) Atalanta in Calydon ; it was in this period also that Arthur Stanley was appointed Dean of Westminster, and that Bills were introduced in Parliament to amend or repeal the ‘Test Acts’ as they affected universities. They were the years that witnessed Lyell present the case for geology at the British Association at Bath , the first meeting of the X-Club , and the award of the Royal Society's Copley Medal to Charles Darwin. These were the years in which, as Owen Chadwick has put it, ‘the controversy between “science” and “religion” took fire’. (shrink)

Rationing healthcare is a difficult task, which includes preventing patients from accessing potentially beneficial treatments. Proponents of implicit rationing argue that politicians cannot resist pressure from strong patient groups for treatments and conclude that physicians should ration without informing patients or the public. The authors subdivide this specific programme of implicit rationing, or “hidden rationing”, into local hidden rationing, unsophisticated global hidden rationing and sophisticated global hidden rationing. They evaluate the appropriateness of these methods of rationing from the perspectives of (...) individual and political autonomy and conclude that local hidden rationing and unsophisticated global hidden rationing clearly violate patients’ individual autonomy, that is, their right to participate in medical decision-making. While sophisticated global hidden rationing avoids this charge, the authors point out that it nonetheless violates the political autonomy of patients, that is, their right to engage in public affairs as citizens. A defence of any of the forms of hidden rationing is therefore considered to be incompatible with a defence of autonomy. (shrink)

We consider the simple case of a nonrelativistic charged harmonic oscillator in one dimension, to investigate how to take into account the radiation reaction and vacuum fluctuation forces within the Schrödinger equation. The effects of both zero-point and thermal classical electromagnetic vacuum fields, characteristic of stochastic electrodynamics, are separately considered. Our study confirms that the zero-point electromagnetic fluctuations are dynamically related to the momentum operator p=−i ℏ ∂/∂ x used in the Schrödinger equation.

OBJECTIVES: To determine the epidemiology and the underlying pathological conditions of natural deaths among motor vehicle drivers. Sudden death while driving may cause damage to properties, other vehicles or road users. Although the Medical Commission on Accident Prevention recommended restrictions to drivers at risk of sudden death due to their medical conditions, these restrictions are useless if they do not result in greater safety to the public. DESIGN: A retrospective study of natural deaths of motor vehicle drivers. SETTING: Natural deaths (...) of motor vehicle drivers reported to the coroner for Birmingham and Solihull. SUBJECTS: 86 consecutive natural deaths of motor vehicle drivers in a five-year period between 1984 and 1988. RESULTS: Of the 86 fatalities reviewed, 80 (93%) sudden deaths were caused by ischaemic heart disease. Fifty vehicles were involved in collision with 32 properties, 20 other vehicles and six pedestrians. Fifty-one out of 80 cardiac deaths had past cardiac history and three had reported chest pain prior to the sudden death. CONCLUSION: An applied normative ethical assessment based on the basic moral principles of autonomy, justice, beneficence and non-maleficence are discussed. We conclude that medical screening of drivers has little benefit for the drivers or other persons. (shrink)

We make a brief review of the Kramers escape rate theory for the probabilistic motion of a particle in a potential well U(x), and under the influence of classical fluctuation forces. The Kramers theory is extended in order to take into account the action of the thermal and zero-point random electromagnetic fields on a charged particle. The result is physically relevant because we get a non-null escape rate over the potential barrier at low temperatures (T → 0). It is found (...) that, even if the mean energy is much smaller than the barrier height, the classical particle can escape from the potential well due to the action of the zero-point fluctuating fields. These stochastic effects can be used to give a classical interpretation to some quantum tunneling phenomena. Relevant experimental data are used to illustrate the theoretical results. (shrink)

This volume offers the first-ever complete English translation of Leibniz’s Dissertatio De Arte Combinatoria together with a critical edition of the original Latin text on fa...