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)

PURPOSE: To evaluate the effects of social support on comprehension and recall of consent form information in a study of Parkinson disease patients and their caregivers.DESIGN and METHODS: Comparison of comprehension and recall outcomes among participants who read and signed the consent form accompanied by a family member/friend versus those of participants who read and signed the consent form unaccompanied. Comprehension and recall of consent form information were measured at one week and one month respectively, using Part A of the (...) Quality of Informed Consent Questionnaire .RESULTS: The mean age of the sample of 143 participants was 71 years . Analysis of covariance was used to compare QuIC scores between the intervention group and control group . In the 1-week model, no statistically significant intervention effect was found . However, the intervention status by patient status interaction was statistically significant . In the 1-month model, no statistically significant intervention effect was found . Again, however, the intervention status by patient status interaction was statistically significant . At both time periods, intervention group patients scored higher on the QuIC than did intervention group caregivers, and control group patients scored lower on the QuIC than did control group caregivers.IMPLICATIONS: Social support played a significant role in enhancing comprehension and recall of consent form information among patients. (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)

_The Budapest School: Beyond Marxism_ develops a systematic reconstruction of the post-Marxist projects of the Budapest School. It charts the evolution of these thinkers from their beginnings in the ‘renaissance of Marxism’ through to their contemporary critical theories of modernity.

Is it possible to interfere with individual decision-making while preserving freedom of choice? The purpose of this article is to assess whether ‘libertarian paternalism’, a set of political and ethical principles derived from the observations of behavioural sciences, can form the basis of a viable framework for the ethical analysis of public health interventions. First, the article situates libertarian libertarianism within the broader context of the law and economics movement. The main tenets of the approach are then presented and particular (...) attention is given to its operationalization through the notion of a ‘nudge’. Essentially, a ‘nudge’ consists in an intervention, which aims to suggest one choice over another by gently steering individual choices in welfare-enhancing directions yet without imposing any significant limit on available choices. Finally, the article concludes that, while it fails as an overreaching framework of ethical analysis, libertarian paternalism nonetheless constitutes a valuable addition to the conceptual toolbox of public health ethics. (shrink)

The posterior parietal cortex (PPC) is the most likely site where egocentric spatial relationships are represented in the brain. PPC cells receive visual, auditory, somaesthetic, and vestibular sensory inputs; oculomotor, head, limb, and body motor signals; and strong motivational projections from the limbic system. Their discharge increases not only when an animal moves towards a sensory target, but also when it directs its attention to it. PPC lesions have the opposite effect: sensory inattention and neglect. The PPC does not seem (...) to contain a “map” of the location of objects in space but a distributed neural network for transforming one set of sensory vectors into other sensory reference frames or into various motor coordinate systems. Which set of transformation rules is used probably depends on attention, which selectively enhances the synapses needed for making a particular sensory comparison or aiming a particular movement. (shrink)

Posidonivs was fortunate to be born in an age when the Romans had begun to recognize their own intellectual limitations, and had turned for guidance to a hitherto despised nation, admitted by themselves to be as much their superior in originality as it was inferior to them in practical matters. He was, moreover, the official exponent of a philosophical system which, destined as it was to exercise for hundreds of years the strongest moral influence over the world, had already taken (...) a firm hold on the more thoughtful minds at Rome. Probably any Greek teacher of ability had, in the time of Cicero, a good chance to make a name; Posidonius, who was a man of considerable intellectual gifts, great learning, and some originality, and who was, moreover, the accredited successor to Zeno and Chrysippus, obtained a reputation which lasted for some centuries. (shrink)

In the modal literature various notions of completeness have been studied for normal modal logics. Four of these are defined here, viz. (plain) completeness, first-order completeness, canonicity and possession of the finite model property — and their connections are studied. Up to one important exception, all possible inclusion relations are either proved or disproved. Hopefully, this helps to establish some order in the jungle of concepts concerning modal logics. In the course of the exposition, the interesting properties of first-order definability (...) and preservation under ultrafilter extensions are introduced and studied as well. (shrink)

Much ink has been spilt in consideration of the once pervasive reliance on military metaphors to depict the relationships between science and religion in the nineteenth century. This has resulted in historically sensitive treatments of secularization; and the realization that the relationship between science and religion was not a bloody war between intellectual nation states, but a protracted divorce of former partners. Moreover, historians of science have been encouraged to throw off the yoke of the internalism–externalism debate, and to explore (...) the cultural boundaries that impinged upon practitioners of a natural knowledge of the world. Within the historiography of nineteenth-century science, this has resulted in many new perspectives on science and natural knowledge in relation to cultural control and authority. (shrink)

We study reducts of Peano arithmetic for which conditions of saturation imply the corresponding conditions for the whole model. It is shown that very weak reducts (like pure order) have such a property for κ-saturation in every κ ≥ ω 1 . In contrast, other reducts do the job for ω and not for $\kappa > \omega_1$ . This solves negatively a conjecture of Chang.

For the purposes of the new text of Livy which Professor Conway and Professor C. F. Walters are preparing for the Oxford Series of Classical Texts, I undertook in 1908 to examine the Codex Leidensis, which contains Livy's first decade.

The text of Fronto is in a very corrupt state, and the startling discrepancies which exist between different collations, as well as the unintelligibility of many of the readings deciphered, seem to justify a good deal of conjectural emendation. I append some attempts to complete or restore the sense in some passages of the Greek letters which seem hitherto to have been left in an unsatisfactory state. Not having had access to the MS, I have relied on the collations of (...) Naber and others for a statement of what is to be found in the palimpsest. (shrink)

The idea of creaturely life has, in recent years, emerged as an important and illuminating category of literary and philosophical critique. In this paper I seek to contribute to this contemporary discourse by examining the references to the creaturely found in the writings of T.W. Adorno. Whilst much attention has been paid to Walter Benjamin’s reflections on creatureliness, Adorno, a thinker with whom Benjamin is often associated, has received comparatively little in this regard. I begin to redress this lacuna by (...) developing a reading of key passages of Dialectic of Enlightenment which orients itself towards Adorno’s remarks concerning the ‘inverse theology’ which he sees as grounding both his own, and Benjamin’s, thought. In placing theological core of Adorno’s philosophy in the foreground of my analysis, I argue that the notion of the creature, which I claim signifies a redemptive perspective on human existence, can be read as an important, if somewhat overlooked, concept in the normative framework of the Dialectic of Enlightenment. (shrink)

In the Laura Ashworth case in 2008, the Human Tissue Authority considered itself bound to overturn a deceased daughter's alleged wish that one of her kidneys should go to her mother, who at the time had end stage kidney failure and was on dialysis. 12 This was so even though Laura's earlier wish to be a living donor would most likely have been authorised, had the formal assessment process begun. The decision provoked much criticism. The recent Department of Health document (...) Requested Allocation of a Deceased Donor Organ, published 29 March 2010, developed by the UK health administrations together with the HTA and NHS Blood and Transplant , which is the main organ allocation body in the UK, seeks to resolve this ethical dilemma by setting out the circumstances in which requests for such deceased donations may be acceptable. 3 The most important conditions appear to be:a. the donation must be unconditional in nature;b. there must be …. (shrink)

Transplantation research on samples and organs from deceased donors in England, Wales and Northern Ireland is under threat. The key problems relate to difficulties encountered in gaining consent for research projects, as distinct from consent to donation for clinical transplantation. They are due partly to the terms of the Human Tissue Act 2004 (the 2004 Act), and partly to its interpretation by the Human Tissue Authority (HTA). They include excessive interaction with donor representatives regarding ‘informed consent’ to research projects, uncertainty (...) as to the scope and duration of a donor's ‘authority’ over an organ, and restrictions caused by the apparent need for licensing of transplantation research under the 2004 Act, combined with lack of certainty, or guidance, as to the distinction between ‘research’, which requires a licence, and ‘service development’, which does not. In our view this confusion hinders and deters Specialist Nurses for Organ Donation in approaching donor representatives and discussing possible research projects with them. It has also, as we have reported elsewhere, led to abandonment of research projects for fear of liability, despite both Research Ethics Committee (REC) approval and donor consent. Such problems do not seem to occur under the transplant laws of most other comparable jurisdictions. The Transplantation Ethics Symposium, ‘The ethics of organ retrieval: goals, rights and responsibilities’, hosted by the MRC Centre for Transplantation at King's College London in December 2010, revealed that many senior clinicians and researchers, administrators, and lawyers are both unclear and in disagreement concerning the effects of the 2004 Act and the extent to which it is adhered to or ignored in practice. In this paper we examine the difficulties encountered and suggest solutions based on a less restrictive interpretation of the 2004 Act, or, more probably, a regulatory change under its authority. We propose that, in the long term, a law which includes consent for REC-approved research within the general consent for organ donation and transplantation seems preferable to the present system, both ethically and in practical terms. (shrink)