Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

In the introductory chapter of his essay on Utilitarianism, John Stuart Mill says his aim is to contribute towards the understanding of utilitarianism and towards ‘such proof as it is susceptible of’. He immediately adds that ‘this cannot be proof in the ordinary and popular meaning of the term’ because ‘ultimate ends are not amenable to direct proof’. A proof that something is good has to show that it is ‘a means to something admitted to be good without proof’. But, (...) he goes on, this does not imply that a formula of ultimate ends can only be accepted on ‘blind impulse, or arbitrary choice’. It can be rationally discussed and subjected to proof in a wider sense of that word. ‘Considerations may be presented capable of determining the intellect either to give or withhold its assent to the doctrine; and this is equivalent to proof.’. (shrink)

Garrod, Smith and the contributors of the volume envisage the longue durée poetics of an early modern genre. They interpret its poetics alongside its various epistemic agenda and make a case for the literary status of natural history.

Mental causation has been a hotly disputed topic in recent years, with reductive and non-reductive physicalists vying with each other and with dualists over how to accommodate, or else to challenge, two widely accepted metaphysical principles—the principle of the causal closure of the physical domain and the principle of causal non-overdetermination—which together appear to support reductive physicalism, despite the latter’s lack of intuitive appeal. Current debate about these matters appears to have reached something of an impasse, prompting the question of (...) why this should be so. One possibility well worth exploring is that, while this debate makes extensive use of ontological vocabulary—by talking, for instance, of substances, events, states, properties, powers, and relations—relatively little attempt has been made within the debate itself to achieve either clarity or agreement about what, precisely, such terms should be taken to mean. Hence, the debate has become somewhat detached from broader developments in metaphysics and ontology, which have lately been proceeding apace, providing us with an increasingly rich and refined set of ontological categories upon which to draw, as well as a much deeper understanding of how they are related to one another. In preparing this volume, the editors invited leading metaphysicians and philosophers of mind to reflect afresh upon the problem of mental causation in the light of some of these recent developments, with a view to making new headway with one of the most challenging and seemingly intractable issues in contemporary philosophy. (shrink)

Even though anthropogenic climate change is largely caused by industrialized nations, its burden is distributed unevenly with poor developing countries suffering the most. A common response to livelihood insecurities and destruction is migration. Using Peter Singer's ‘historical principle’, this paper argues that a morally just evaluation requires taking causality between climate change and migration under consideration. The historical principle is employed to emphasize shortcomings in commonly made philosophical arguments to oppose immigration. The article concludes that none of these arguments is (...) able to override the moral responsibility of industrialized countries to compensate for harms that their actions have caused. (shrink)

The essay examines the impact of thought insertion on typical conceptions of self-consciousness. Stephens and Graham have recently argued that thought insertion is compatible with the inseparability thesis, which maintains that with regard to self-consciousness subjectivity is a proper part of introspection--introspection and subjectivity are inseparable. They argue that thought insertion is an error of agency and not an error of subjectivity. The essay contends that even if they are correct in their interpretation that thought insertion is an error of (...) agency rather than subjectivity, which is unlikely, they are incorrect to maintain that it is not also an error of subjectivity. Evidence is put forth to indicate that thought insertion is, at best, a mistake of agency and subjectivity. It is concluded that thought insertion is incompatible with the inseparability thesis, and a new inseparability thesis is thereby postulated. (shrink)

Advances in molecular biological research in the latter half of the twentieth century have made the story of the gene vastly complicated: the more we learn about genes, the less sure we are of what a gene really is. Knowledge about the structure and functioning of genes abounds, but the gene has also become curiously intangible. This collection of essays renews the question: what are genes? Philosophers, historians and working scientists re-evaluate the question in this volume, treating the gene as (...) a focal point of interdisciplinary and international research. It will be of interest to professionals and students in the philosophy and history of science, genetics and molecular biology. (shrink)

This book explores a range of traditional and contemporary metaphysical themes that figure in the writings of E. J. Lowe, whose powerful and influential work was still developing at the time of his death in 2015. Leading philosophers present new essays on topics to do with ontology, necessity, existence, and mental causation.

Power and authority in terms of the Ten Commandments (TCs) are discussed. The paper reviews the TCs in Christianity, Judaism, and Islam. The treatment and basis for power and authority in each religion are clarified. Implications of power and authority using the perspective of the TCs are provided. The paper suggests that in today's business environment people tend to be selective in identifying only with certain elements of the TCs that fit their interest and that the TCs should be viewed (...) as general moral guidelines. (shrink)

The dominant approach to the study of dynamic preference is to generate preference change by manipulating aspects of decision-problem presentation (problem description, task procedure, contextual options). The predisposing approach instead manipulates the decision maker’s mental state while holding problem presentation constant. Three illustrative studies are outlined here. The first modified preferences for ambitious consumption by manipulating subjects’ consumption energy. The second modified preferences for immediate consumption by manipulating subjects’ hedonic resources. The third modified preferences for consumption itself by manipulating subjects’ (...) desire proneness. Whereas framing is thought to affect perception, predisposing apparently can affect tastes and so involves a special kind of preference dynamism. (shrink)

Lankford’s (2013) essential empirical argument, which is based on evidence such as psychological autopsies, is that suicide attacks are caused by suicidality. By operationalizing this causal claim in a hypothetical experiment, I show the claim to be provable, and I contend that its truth is supported by Lankford’s data. However, I question the success of his follow-on arguments about beauty and goodness.

The current debate on “free agency” seems to highlight the romantic aspects of free agent and considers it a genuine response to changing economic conditions (e.g., high-unemployment rate, importance of knowledge in the labor market, the eclipse of organizational loyalty, and self pride). Little attention, if any, has been given to the religious root of the free agency concept and its persistent existence across history. In this paper, the current discourse on free agency and the conditions that have led to (...) its emergence are briefly discussed. The paper focuses on the theological perspectives of Judaism, Christianity, and Islam on the concept. Implications for management and business organizations are provided. (shrink)

The essay opens with some background information about the period in which J.S. Mill wrote. The discussion revolves around the concept of blasphemy which Mill considered to be highly problematic. Tagging unpopular views as ‘blasphemous’ amounted to abuse of governmental powers and infringed on the basic liberties of the out-of-favour speakers. The discussion on blasphemy sets the scene to the understanding of Mill's concerns, his priorities and consequently his emphasis on the widest possible liberty of expression. Section 2 presents the (...) Millian principles that are pertinent to his philosophy of free speech: liberty and truth. Section 3 analyzes Mill's very limited boundaries to freedom of expression, asserting that the consequentialist reasoning had led Mill to ignore present tangible harm. It is argued that democracy is required to develop protective mechanisms against harm-facilitating speech. (shrink)

As the federal government distributed remdesivir to some of the states COVID-19 hit hardest, policymakers scrambled to develop criteria to allocate the drug to their hospitals. Our state, Michigan, was among those states to receive an initial quantity of the drug from the U.S. government. The disparities in burden of disease in Michigan are striking. Detroit has a death rate more than three times the state average. Our recommendation to the state was that it should prioritize the communities that bear (...) a disproportionate burden of suffering in the allocation of the new potential treatment. This recommendation is justified not only for new drugs with uncertain effects, but also for drugs of certain benefit or vaccines. For states with significant health disparities, such as Michigan, this allocation priority may help to repair them. In fact, any other allocation strategy may make them worse. (shrink)