Parkinson's disease (PD) is generally sporadic but a number of genetic diseases have parkinsonism as a clinical feature. Two dominant genes, α‐synuclein (SNCA) and leucine‐rich repeat kinase 2 (LRRK2), are important for understanding inherited and sporadic PD. SNCA is a major component of pathologic inclusions termed Lewy bodies found in PD. LRRK2 is found in a significant proportion of PD cases. These two proteins may be linked as most LRRK2 PD cases have SNCA‐positive Lewy bodies. Mutations in both proteins are (...) associated with toxic effects in model systems although mechanisms are unclear. LRRK2 is an intracellular signaling protein possessing both GTPase and kinase activities that may contribute to pathogenicity. A third protein, tau, is implicated as a risk factor for PD. We discuss the potential relationship between these genes and suggest a model for PD pathogenesis where LRRK2 is upstream of pathogenic effects through SNCA, tau, or both proteins. (shrink)

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)

Multiculturalism is higher on the daily political agenda than it has ever been. Leading politicians and public commentators speak with an unparalleled bluntness about the perceived limitations of multiculturalism while representatives of cultural, minorities express concern about marginalisation. This debate is taking place against a background of fear about terrorism, the integrity of national identities and a loosely construed ‘clash of civilizations’. Secularism is pitted against religious fundamentalism, respect for difference against the right of freedom of speech, integration against self-determination, (...) and duties of citizenship against minority rights. This book confronts the reality of moral conflict in the debate on multiculturalism while resisting the simplification which too frequently accompanies daily commentary on both sides of an increasingly polarised debate. The volume as a whole marks an important step in the attempt to examine the underlying concepts, of the nature and legitimate extent of disagreement, of secularism, the nature of power, the state and citizenship, which inevitably constitute key assumptions in the debate. Bringing together leading scholars on multiculturalism: Gerald Gaus, Peter Jones, John Horton, Tariq Modood, Chandran Kukathas, Bhikhu Parekh, Matthew Festenstein and Cecile Laborde, this book discusses the latest developments in the field. It will be of strong interest students and scholars of multiculturalism, political science, political theory, international relations, sociology, philosophy and anthropology. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:DESIRED POSSESSIONS: KARL POLANYI, RENÉ GIRARD, AND THE CRITIQUE OF THE MARKET ECONOMY Mark R. Anspach CREA, Paris! f '""phe most radical critique of liberal capitalism ever:" that is how JL Louis Dumont describes 7Ae Great Transformation, Karl Polanyi's classic work on the rise of the market system. But the French anthropologist goes on to observe that, when one confronts this same critique with the ethnography of tribal (...) societies, "one may ask whether Polanyi did not in fact come up short; having criticized the economy as an idea, he thought he could retain it as a thing..." (Dumont xiv, xvi). Is the economy indeed a "thing" that has always existed in some form everywhere, and if so, what manner of thing is it? In a word, what is an economyfor? Is there a particular aim that any economy must serve? A specific motive that it necessarily brings into play? We will begin by looking at Polanyi's answer to this question. "No human motive is per se economic," Polanyi tells us. "There is no such thing as a sui generis economic experience in the sense in which man may have a religious, aesthetic, or sexual experience." It is market society, with its dependence on a disembedded economic system, which fosters the illusion that the "economic" motives of hunger and gain necessarily underlie every economic system (1968, 63-4). In reality, however, "human beings will labor for a large variety of reasons as long as things are arranged accordingly." For example, "Monks traded for religious reasons... The KuIa trade ofthe Trobriand islanders... is mainly an aesthetic pursuit. Feudal economy was run on customary lines. With the Kwakiutl," industry appears to have been "a point of honor," and 1 82Mark R. Anspach so on (1968, 68). The trick, it seems, is to "arrange things accordingly." An economic system can be "run on noneconomic motives," Polanyi explains, without linking the process of production or distribution "to specific economic interests attached to the possession of goods," as long as "every single step in that process is geared to a number of social interests which eventually ensure that the required step be taken" (2001, 48). Now, there is a danger in this presentation. It could lead a reader to conclude that other societies arrange things cunningly so that all these social interests are harnessed to ensure the performance of the steps necessary to economic processes in a kind ofelaborate ruse—a ruse which the out-in-the-open operation ofthe economy in our society gives us the ability to see through. Very well, such a reader might acknowledge, the economy is an "instituted process," and, yes, the act of instituting it "shifts the place ofthe process in society" (Polanyi 1968, 148), but ifyou track it down to its hiding place and strip away the social contrivances in which it has been embedded, what you will find is still the economy as we know it—indeed, the economy which market society alone lays bare. In this reading, or rather misreading, the "real" economic aims that market society achieves directly are elsewhere accomplished only in the most cumbersomely indirect fashion. This kind of erroneous conclusion will likely be difficult to counter as long as one posits an opposition between multiple, variable and diffuse social interests, on the one hand, and the apparently straightforward individual interest in the possession of goods, on the other. Wherever the economy is submerged in social relationships, Polanyi says, a man "does not act so as to safeguard his individual interest in the possession ofmaterial goods; he acts so as to safeguard his social standing, his social claims, his social assets" (2001, 48). The problem with such an opposition between individual and social is that a market-minded theorist can overcome it simply by broadening the individual interest in the possession ofgoods to include the possession ofreified social goods. Once social interests are conceptualized as "social assets," to use Polanyi's own expression—or as "symbolic capital," to cite a more recent formulation—they lend themselves to "economizing" even in the formal sense, and Polanyi's carefully constructed distinction between the substantive and the formal collapses, apparently confirmingthe universality of the market... (shrink)

As with other fields of applied ethics, philosophers engaged in business ethics struggle to carry out substantive philosophical reflection in a way that mirrors the practical reasoning that goes on within business management itself. One manifestation of the philosopher’s struggle is the field’s division into approaches that emphasize moral philosophy and those grounded in the methods of social science. I claim here that the task for those who come to business ethics with philosophical training is to avoid unintentionally widening the (...) gap between philosophical theory and business management by emphasizing the centrality of practical wisdom to both good managment and to the moral life. Distinguishing my own approach from recent emphases on phronesis in management literature, I draw on the concepts of social practice and of narrative to tie practical reasoning to a company’s unique story. Practical reason, social practices and narrative are employed together to give an account of the art of management at Patagonia. The essay hopes to both provide a way for philosophers engaged with business ethics to see family resemblances between their practices and those of business management and to offer a pedagogical example useful for those in any discipline interested in viewing businesses ethically. (shrink)

Chow's one-tailed null-hypothesis significance-test procedure, with its rationale based on the elimination of chance influences, is not appropriate for theory-corroboration experiments. Estimated effect sizes and their associated standard errors or confidence limits will always suffice.

Approximately 1,500 years ago John Philoponus proposed a simple argument for the existence of God. The argument runs thus: Whatever comes to be has a cause of its coming to be. The universe came to be. Therefore, the universe has a cause of its coming to be. ;Due to the influence of William Lane Craig, this argument and the family of arguments that support it have come to be known as the "kalam" cosmological argument . Craig's account of the KCA (...) incorporates features that serve to distinguish his version as a significant advance. First, conceptual advances in mathematics now permit a clearer presentation of the argument than was previously possible. Second, contemporary Big Bang cosmology confirms the central contention of the KCA, namely, that the past existence of the universe is finite. Reflection upon the implications of using Cantorian transfinite mathematics to model physical processes allowed Craig to develop a distinctively philosophical version of the KCA which is relatively independent of changes in contemporary scientific cosmology. This dissertation is intended as a critical investigation and development of this philosophical strand of the KCA. The literature relating to the KCA has grown however to a significant bulk, and there is now danger of duplication and misassessment due to the plurality of interpretations that the argument has received. Part I of the dissertation addresses this need by laying bare the underlying logical structure of the KCA and by providing a comprehensive "state of the question" . Part II of the dissertation, comprising chapters 3 through 6, focuses upon an important species of objection made to the KCA. This species of objection relies upon thought-experiments designed to show that an actual infinity is possible. I reply: this objection is effectively answered by introducing a metaphysics of substances. In the course of presenting a systematic response I develop an interpretation of the notion of substance that is useful for analytic philosophy, present a general account of the logical requirements of KCA thought-experiments, and outline a theory of logical modality suited to the metaphysical requirements of the KCA. (shrink)

The most interesting and completely overlooked aspect of Ludwig von Mises’s theory of probability is the total absence of any explicit definition for probability in his theory. This paper examines Mises’s theory of probability in light of the fact that his theory possesses no definition for probability. It is argued, first, that Mises’s theory differs in important respects from his brother’s famous theory of probability. A defense of the subjective definition for probability is then provided, which is subsequently used to (...) critique Ludwig von Mises’s theory. It is argued that only the subjective definition for probability comports with Mises’s other philosophical positions. Since Mises did not provide an explicit definition for probability, it is suggested that he ought to have adopted a subjective definition. (shrink)

Persons registered to vote in Seattle, Washington for the November, 1986 general election and a September, 1987 primary election were randomly assigned to treatments in two telephoneconducted experiments that sought to increase voter tumout. The experiments applied and extended a "self-prophecy” technique, in which respondents are asked simply to predict whether or not they will perform a target action. In the present studies, voting registrants were asked to predict whether or not they would vote in an election that was less (...) than 48 hours away. This technique, which previously increased turnout in a small study done during the 1984 U.S. Presidential election, was again effective among moderate prior-turnout voters in the second of the present much larger experiments. The failure of the effect in Experiment 1 was plausibly a ceiling effect due to very high turnout for a U.S. Senate contest in the 1986 election. Successful applications of the self· prophecy technique are facilitated by social desirability of the target action (which leads subjects to predict that they will perform it). However, social desirability of the target behavior is not a sufficient condition for the effect, as indicated by an unexpected nonoccurrence of the effect among low prior-tumout voters in Experiment 2. (shrink)

A decade has now passed since the House of Lords removed the immunity from suit in negligence previously enjoyed by advocates in England and Wales. The small number of cases decided against barristers since the removal of the immunity indicates that the closeness of the relationship between barristers and the judiciary may give rise to issues of perceived judicial impartiality. This paper argues that the standard of care applied to barristers may be more generous than that applied to other professions. (...) This is because the courts emphasise the importance of barristers' independence and the judiciary also have a direct interest in avoiding defensive practices on the part of barristers. Expert evidence is uncommon in negligence claims against barristers, placing the judge in the dual role of expert and adjudicator. The paper also considers the principles developed to address actual, apparent and presumed bias on the part of judges and the principles enshrined in Article 6 of the European Convention for the Protection of Human Rights and Fundamental Freedoms. In concluding, possibilities are explored for redressing the balance in barristers' negligence claims and removing the perception of bias which may currently taint such claims. (shrink)

This special issue of HEC Forum includes articles on a wide range of specific topics that make significant contributions to conscientious objection scholarship. In this commentary, it is not feasible to provide a comprehensive analysis of each of the articles; and I have not attempted to do so. Instead, for each article, I have selected specific issues and arguments on which to comment.

Despite the preponderance of advance fee fraud scams, many in society still fall victim to such con games. The internet has provided scammers with an opportunity to perpetrate fraud on a global scale. In particular, the 419 email scam has become a popular tool used by scammers to entice their victims. Our purpose is to establish rhetorical moves that exist in these 419 messages, and then analyze the intention of the scammers behind each move — a scam must shake the (...) potential victim out of the status quo behavior. In other words, how is the content of particular moves able to facilitate change in a potential victim’s mind, goading him or her to unwise action? After examining each move in light of features considered necessary for mind change, it was determined that the scammers are most concerned about building solidarity with the mark and playing to a mark’s egocentrism, both of which keep the mark from making well-informed decisions. (shrink)

Volume 20, Issue 7, July 2020, Page 122-124.

Childbearing is an increasingly complicated matter, which has evolved significantly over the past several decades. Treatment options for infertility have expanded. Prenatal testing and treatment have led to an evolution in obstetrical decision-making, wherein the risks and benefits to the fetus and future child are better understood and more strongly considered in medical management of the pregnant woman. Obstetrics appears to be increasingly interventional; one in three babies in the United States is now born by cesarean section. Neonatal intensive care (...) has markedly improved outcomes for premature babies. A pregnant woman may now be presented with many options— obstetrician or midwife, home or hospital delivery, choices among prenatal testing and monitoring, early induction of labor, cesarean delivery. Health care professionals face similar decisions with regard to what they recommend and the boundaries of safe and responsible care they should make available. Preterm Babies, Fetal Patients, and Childbearing Choices, by John D. Lantos and Diane S. Lauderdale, provides an excellent overview of the available information relevant to these questions. (shrink)

Historically associated with military service, conscientious objection has become a significant phenomenon in health care. Mark Wicclair offers a comprehensive ethical analysis of conscientious objection in three representative health care professions: medicine, nursing and pharmacy. He critically examines two extreme positions: the 'incompatibility thesis', that it is contrary to the professional obligations of practitioners to refuse provision of any service within the scope of their professional competence; and 'conscience absolutism', that they should be exempted from performing any action contrary (...) to their conscience. He argues for a compromise approach that accommodates conscience-based refusals within the limits of specified ethical constraints. He also explores conscientious objection by students in each of the three professions, discusses conscience protection legislation and conscience-based refusals by pharmacies and hospitals, and analyzes several cases. His book is a valuable resource for scholars, professionals, trainees, students, and anyone interested in this increasingly important aspect of health care. (shrink)

If you really could have a conversation with God--it might sound like this!

For years now, unionization has been under vigorous attack. Membership has been steadily declining, and with it union bargaining power. As a result, unions may soon lose their ability to protect workers from economic and personal abuse, as well as their significance as a political force. In the Name of Liberty responds to this worrying state of affairs by presenting a new argument for unionization, one that derives an argument for universal unionization in both the private and public sector from (...) concepts of liberty that we already accept. In short, In the Name of Liberty reclaims the argument for liberty from the political right, and shows how liberty not only requires the unionization of every workplace as a matter of background justice, but also supports a wide variety of other progressive policies. (shrink)

Modern accounts of Sicilian history in the late fifth century b.c.e. and its relations with Athens often follow Thucydides’ Athenocentric narrative closely, largely ignoring the Sicilian background. This article instead foregrounds the actions and concerns of two important Sicilian cities, Segesta and Leontini, whose perspectives Thucydides chose to leave out or downplay. In particular, Segesta was involved in the complex cross-cultural dynamics of western Sicily, while Leontini demonstrated resilience in its resistance to Syracusan imperialism. Both cities’ relations with Athens emerged (...) from their pre-existing policies and strategies. This article thus develops an alternate narrative of these events that complements Thucydides’ Athenocentric one. To accomplish this, it argues for a more nuanced approach to Thucydides’ narrative: reading it against the grain, supplementing it with data from Diodorus and epigraphy, and placing it in its Sicilian historical and cultural context. In this way, the article develops a new approach to the methodological issues involved in writing the history of poleis that are not emphasized in major extant narrative sources. Recognizing Segesta and Leontini as political actors with their own goals and agendas enables both a new reading of Thucydides and a less Athenocentric account of late fifth-century Sicilian history. (shrink)

The use of intuition abounds in modern analytic philosophy. In particular, intuition is considered evidence that is used in the analysis of concepts, often in an attempt to find the individually necessary and jointly sufficient conditions of the concept under consideration. Alternatively, intuition is used as evidence that one or more of the proposed necessary conditions is unacceptable, as in Gettier counterexamples to the classical analysis of knowledge. This view of intuition can be thought of as a form of rationalism. (...) However, in the middle part of the 20th century intuition cam under attack through the influence of Quine's project of naturalizing philosophy. The two very general positions on intuition are: intuition provides evidence, but only of necessary truths or intuition does not provide evidence at all. ;I critically analyze the philosophical positions on intuition of many modern philosophers. I pay particular attention to the defense of moderate rationalism presented by Bealer and Bonjour, who place intuition at the heart of rationalism. I criticize their respective views by arguing that their defenses are viciously circular because they overtly appeal to intuition in order to defend intuition as a source of evidence. I further criticize the inability of the moderate rationalists to defend their stipulation that intuition must be of apparent necessary truths. ;On the positive side, I defend that intuition is best thought of as a basic source of evidence that provides evidence for both necessary and some contingent truths. This is how I split the difference between and from above. This view has many virtues, with one if its primary virtues being its ability to account for contingent, grammatical intuitions of he sort used in modern day linguistics. Finally, I argue that my view is more amenable to modern evolutionary psychology by giving a genealogy of intuition. (shrink)

Unfortunately, many people today see the regulation of lies, disinformation, hate speech, and fake news as an infringement of free speech, at least when such speech is ‘political,’ despite the damage that such speech can do. But this very protective attitude toward speech rests on a mistaken understanding of the role of free speech in a liberal society. The right to free speech is based on the liberal value of freedom, and as such can be no broader than freedom itself. (...) And freedom has always been subject to reasonable limits in a liberal society. Indeed, while the principles of toleration and neutrality are often cited as supporting a broad interpretation of the right to free speech, they also tell us that certain limits apply to that right. We need not tolerate speech that encourages intolerance, and while government should be neutral between reasonable conceptions of the good, it need not be neutral between reasonable and unreasonable conceptions. These ideas form the framework of liberal society, and as I shall show, also provide a guide for understanding what kind of speech is protected in a liberal society and what it is not. (shrink)

This state-of-the-science volume brings together an array of leading authorities to comprehensively review theory and research in this burgeoning area.

The persistent failure of public schooling in low-income communities constitutes one of our nation's most pressing civil rights and social justice issues. Many school reformers recognize that poverty, racism, and a lack of power held by these communities undermine children's education and development, but few know what to do about it. A Match on Dry Grass argues that community organizing represents a fresh and promising approach to school reform as part of a broader agenda to build power for low-income communities (...) and address the profound social inequalities that affect the education of children. Based on a comprehensive national study, the book presents rich and compelling case studies of prominent organizing efforts in Chicago, New York City, Los Angeles, Denver, San Jose, and the Mississippi Delta. The authors show how organizing groups build the participation and leadership of parents and students so they can become powerful actors in school improvement efforts. They also identify promising ways to overcome divisions and create the collaborations between educators and community residents required for deep and sustainable school reform. Identifying the key processes that create strong connections between schools and communities, Warren, Mapp, and their collaborators show how community organizing builds powerful relationships that lead to the transformational change necessary to advance educational equity and a robust democracy. (shrink)