Deep brain stimulation of the subthalamic nucleus is a clinically effective tool for treating medically refractory Parkinson’s disease, but its neural mechanisms remain debated. Previous work has demonstrated that STN DBS results in evoked potentials in the primary motor cortex, suggesting that modulation of cortical physiology may be involved in its therapeutic effects. Due to technical challenges presented by high-amplitude DBS artifacts, these EPs are often measured in response to low-frequency stimulation, which is generally ineffective at PD symptom management. This (...) study aims to characterize STN-to-cortex EPs seen during clinically relevant high-frequency STN DBS for PD. Intraoperatively, we applied STN DBS to 6 PD patients while recording electrocorticography from an electrode strip over the ipsilateral central sulcus. Using recently published techniques, we removed large stimulation artifacts to enable quantification of STN-to-cortex EPs. Two cortical EPs were observed – one synchronized with DBS onset and persisting during ongoing stimulation, and one immediately following DBS offset, here termed the “start” and the “end” EPs respectively. The start EP is, to our knowledge, the first long-latency cortical EP reported during ongoing high-frequency DBS. The start and end EPs differ in magnitude and latency, and the end, but not the start, EP magnitude has a significant relationship to ongoing high gamma power during the EP. These contrasts may suggest mechanistic or circuit differences in EP production during the two time periods. This represents a potential framework for relating DBS clinical efficacy to the effects of a variety of stimulation parameters on EPs. (shrink)

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

This empirical study of Fortune 1000 firms assesses the degree to which those firms have adopted various practices associated with corporate ethics programs. The study examines the following aspects of formalized corporate ethics activity: ethics-oriented policy statements; formalization of management responsibilities for ethics; free-standing ethics offices; ethics and compliance telephone reporting/advice systems; top management and departmental involvement in ethics activities; usage of ethics training and other ethics awareness activities; investigatory functions; and evaluation of ethics program activities. Results show a high (...) degree of corporate adoption of ethics policies, but wide variability in the extent to which these policies are implemented by various supporting structures and managerial activities. In effect, the vast majority of firms have committed to the low cost, possibly symbolic side of ethics management (e.g., adoption of ethics codes and policies, etc.). But firms differ substantially in their efforts to see that those policies or codes actually are put into practice. (shrink)

Even if there were widespread cross-cultural agreement on the normative issues of business ethics, corporate ethics management initiatives (e.g., codes of conduct, ethics telephone lines, ethics offices) which are appropriate in one cultural setting still could fail to mesh with the management practices and cultural characteristics of a different setting. By uncritically adopting widely promoted American practices for managing corporate ethics, multinational businesses risk failure in pursuing the ostensible goals of corporate ethics initiatives. Pursuing shared ethical goals by means of (...) culturally inappropriate management practices, in short, can undermine the effectiveness of ethics management efforts. This article explicates how several important dimensions of culture can influence the effectiveness of common ethics initiatives, and recommends the development and application of a culture-structure contingency analysis in the task of encouraging ethical behavior in global businesses. (shrink)

Sodium monofluoroacetate (1080) is a mammalian pesticide used in different parts of the world for the control of mammalian pest species. In New Zealand it is used extensively and very successfully as a conservation management tool for the control of brushtail possums (Trichosurus vulpecula) – an introduced marsupial that has become a substantial agricultural and conservation management pest. Possums pose a threat to cattle farming in New Zealand as they are a vector for bovine tuberculosis. In protected natural areas, possum (...) browsing is responsible for large scale defoliation of native vegetation. As with many other pesticides, there has been some degree of popular concern about the use of this toxin and its safety, with particular reference to non-target effects. These concerns have been associated with potential non-target effects on human health, and the health of animals of recreational value (e.g., hunting dogs and game animals). This has led to the development of a strong “anti-1080” lobby in New Zealand. In contrast, this study encompasses a science-based risk analysis focusing on the potential risks to non-target native wildlife with a particular focus on chronic toxicity. It finds that there is evidence that 1080 may have endocrine disrupting capabilities (with potential relevance for non-target wildlife) but that this still needs more detailed investigation. This can be clarified by further targeted research. Further research is also needed to test the degradation rates of 1080 and its breakdown products at ecologically-relevant temperatures (i.e., winter stream temperatures – below 11 °C). Such research may demonstrate that some adjustment to 1080 risk management is warranted in New Zealand, or it may help to put to rest the current controversy over the use of this cost effective conservation management tool. (shrink)

This is a welcome reprint of a book that continues to grow in importance.

Two attitudes are possible: one, that the world is an absolute jungle and that the exercise of coercive power by rulers is only a manifestation of this; and the other, that it is both necessary and right that there should be this exercise of power, that through it the world is much less of a jungle than it could possibly be without it, so that one should in principle be glad of the existence of such power, and only take exception (...) to its unjust exercise. (shrink)

Modal propositional logic; Modal predicate logic; A survey of modal logic.

The author presents and defends three theses: (1) "the first is that it is not profitable for us at present to do moral philosophy; that should be laid aside at any rate until we have an adequate philosophy of psychology." (2) "the second is that the concepts of obligation, And duty... And of what is morally right and wrong, And of the moral sense of 'ought', Ought to be jettisoned if this is psychologically possible...." (3) "the third thesis is that (...) the differences between the well-Known english writers on moral philosophy from sidgwick to the present day are of little importance." (staff). (shrink)

The usual way for new cells to come into being is by division of old cells. So the zygote, which is a—new—single cell formed from two, the sperm and ovum, is an exception. Textbooks of human genetics usually say that this new cell is beginning of a new human individual. What this indicates is that they suddenly forget about identical twins.

Since psychiatry remains a descriptive discipline, it is essential for its practitioners to understand how the language of psychiatry came to be formed. This important book, written by a psychiatrist-historian, traces the genesis of the descriptive categories of psychopathology and examines their interaction with the psychological and philosophical context within which they arose. The author explores particularly the language and ideas that have characterised descriptive psychopathology from the mid-nineteenth century to the present day. He presents a masterful survey of the (...) history of the main psychiatric symptoms, from the metaphysics of classical antiquity to the operational criteria of today. Tracing the evolution of concepts such as memory, consciousness, will and personality, and of symptoms ranging from catalepsy and aboulia to anxiety and self-harm, this book provides fascinating insights into the subjective nature of mental illness, and into the ideas of British, Continental and American authorities who sought to clarify and define it. (shrink)

In 2005 St Andrews Studies published a volume of essays by Anscombe entitled Human Life, Action and Ethics, followed in 2008 by a second with the title Faith in a Hard Ground. Both books were highly praised. This third volume brings essays on the thought of historical philosophers in which Anscombe engages directly with their ideas and arguments. Many are published here for the first time and the collection provides further testimony to Anscombe's insight and intellectual imagination.

Normal propositional modal systems This first chapter has two main aims. One is to give a general account of the propositional modal systems that we shall ...

_Zettel, _ an en face bilingual edition, collects fragments from Wittgenstein's work between 1929 and 1948 on issues of the mind, mathematics, and language.