There is a paucity of treatment options for cognitively normal individuals with drug resistant genetic generalized epilepsy. Centromedian nucleus of the thalamus deep brain stimulation may be a viable treatment for GGE. Here, we present the case of a 27-year-old cognitively normal woman with drug resistant GGE, with childhood onset. Seizure semiology are absence seizures and generalized onset tonic clonic seizures. At baseline she had 4–8 GTC seizures per month and weekly absence seizures despite three antiseizure medications and vagus nerve (...) stimulation. A multidisciplinary committee recommended off-label use of CM DBS in this patient. Over 12-months of CM DBS she had two GTC seizure days, which were in the setting of medication withdrawal and illness, and no GTC seizures in the last 6 months. There was no significant change in the burden of absence seizures. Presently, just two studies clearly document CM DBS in cognitively normal individuals with GGE or idiopathic generalized epilepsy [in contrast to studies of cognitively impaired individuals with developmental and epileptic encephalopathies ]. Our results suggest that CM DBS can be an effective treatment for cognitively normal individuals with GGE and underscore the need for prospective studies of CM DBS. (shrink)

The U.S. stock market is one of the largest and most complex marketplaces in the global financial system. Over the past several decades, this market has evolved at multiple structural and temporal scales. New exchanges became active, and others stopped trading, regulations have been introduced and adapted, and technological innovations have pushed the pace of trading activity to blistering speeds. These developments have supported the growth of a rich machine-trading ecology that leads to qualitative differences in trading behavior at human (...) and machine time scales. We conduct a longitudinal analysis of comprehensive market data to quantify nonstationary dynamics throughout this system. We quantify the relationship between fluctuations in the number of active trading venues and realized opportunity costs experienced by market participants. We find that information asymmetries, in the form of quote dislocations, predict market-wide volatility indicators. Lastly, we uncover multiple micro-to-macro level pathways, including those exhibiting evidence of self-organized criticality. (shrink)

© 2015, Springer-Verlag Berlin Heidelberg.Genetic studies have identified single nucleotide polymorphisms associated with the risk of prostate cancer. It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score and aggressiveness. Statistical analyses were used to compare the frequency (...) of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 was significantly and inversely associated with aggressive and high-grade disease in European men. Similar associations with aggressive and high-grade disease were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness. (shrink)

Contrary to Lewis and Vihvelin, I argue that free will in a deterministic world is an ability to break a law of nature or to change the remote past. Even if it were true, as Lewis and Vihvelin think, that an agent who is predetermined to perform a particular act might not break a law or change the remote past by doing otherwise, it would nevertheless be true that he is able to do otherwise only if he is able to (...) break a law or to change the remote past. (shrink)

Pythagoras -- Confucius -- Heracleitus -- Parmenides -- Zeno of Elea -- Socrates -- Democritus -- Plato -- Aristotle -- Mencius -- Zhuangzi -- Pyrrhon of Elis -- Epicurus -- Zeno of Citium -- Philo Judaeus -- Marcus Aurelius -- Nagarjuna -- Plotinus -- Sextus Empiricus -- Saint Augustine -- Hypatia -- Anicius Manlius Severinus Boethius -- Śaṅkara -- Yaqūb ibn Ishāq aṣ-Ṣabāḥ al-Kindī -- Al-Fārābī -- Avicenna -- Rāmānuja -- Ibn Gabirol -- Saint Anselm of Canterbury -- al-Ghazālī -- (...) Peter Abelard -- Averroës -- Zhu Xi -- Moses Maimonides -- Ibn al-'Arabī -- Shinran -- Saint Thomas Aquinas -- John Duns Scotus -- William of Ockham -- Niccolò Machiavelli -- Wang Yangming -- Francis Bacon, Viscount Saint Alban (or Albans), Baron of Verulam -- Thomas Hobbes -- René Descartes -- John Locke -- Benedict de Spinoza -- Gottfried Wilhelm Leibniz -- Giambattista Vico -- George Berkeley -- Charles-Louis de Secondat, baron de La Brède et de Montesquieu -- David Hume -- Jean-Jacques Rousseau -- Immanuel Kant -- Moses Mendelssohn -- Marie-Jean-Antoine-Nicolas de Caritat, marquis de Condorcet -- Jeremy Bentham -- Georg Wilhelm Friedrich Hegel -- Arthur Schopenhauer -- Auguste Comte -- John Stuart Mill -- Søren Kierkegaard -- Karl Marx -- Herbert Spencer -- Wilhelm Dilthey -- William James -- Friedrich Nietzsche -- Friedrich Ludwig Gottlob Frege -- Edmund Husserl -- Henri Bergson -- John Dewey -- Alfred North Whitehead -- Benedetto Croce -- Nishida Kitarō -- Bertrand Russell -- G.E. Moore -- Martin Buber -- Ludwig Wittgenstein -- Martin Heidegger -- Rudolf Carnap -- Sir Karl Popper -- Theodor Wiesengrund Adorno -- Jean-Paul Sartre -- Hannah Arendt -- Simone de Beauvoir -- Willard Van Orman Quine -- Sir A.J. Ayer -- Wilfrid Sellars -- John Rawls -- Thomas S. Kuhn -- Michel Foucault -- Noam Chomsky -- Jürgeb Gabernas -- Sir Bernard Williams -- Jacques Derrida -- Richard Rorty -- Robert Nozick -- Saul Kripke -- David Kellogg Lewis -- Peter (Albert David) Singer. (shrink)

The newest addition to the successful Oxford Readings in Philosophy series, this collection contains the most important contributions to the recent debate on the philosophy of science. The contributors crystallize the often heated arguments of the last two decades, assessing the skeptical attitudes within philosophy of science and the counter-challenges of the scientific realists. Contributors include Nancy Cartwright, Brian Ellis, Arthur Fine, Clark Glymour, Larry Laudan, Peter Lipton, Alan Musgrave, Wesely C. Salmon, Lawrence Sklar, Bas C. van Fraassen, and (...) John Worrall. (shrink)

In Plato's Laws, the Athenian Stranger claims that the gods will smile only on a city where the law This passage is the origin of the slogan an abbreviation of which forms our phrase From Plato and Aristotle, through John Adams and John Marshall, down to us, no idea has proven more central to Western political and legal culture. Yet the slogan turns on a very dubious metaphor. Laws do not rule, and the is actually a specific form of rule (...) by men (including, nowadays, a few women). These rulers are not slaves to anything. Furthermore, the construction of the sloganhas unfortunate connotations. It suggests that the personal qualities of the human rulers required to secure the rule of law are nothing more than forbearance and disinterestedness—a resolution to stay out of law's way.Footnotes* I have received helpful comments and criticisms from a number of readers, including the other contributors to this volume and participants in the Georgetown University Law Center faculty workshop. In addition, I should like to thank Brian Bix, Ellen Frankel Paul, Fred Schauer, and Wibren van der Burg for extensive written comments on an earlier draft of this essay. (shrink)

Intuitively, a question is indeterminate just in case it is unsettled, not merely epistemically, but metaphysically. We ordinarily ascribe indeterminacy by saying that there is no fact of the matter. We say for instance that there is no fact of the matter how many clouds exist. The distribution of water droplets in the sky would appear to settle that there are some clouds, but not how many. ;On the one hand, it seems obvious that certain questions are indeterminate. On the (...) other hand, it seems easy to reduce an arbitrary ascription of indeterminacy to absurdity: Suppose that it is indeterminate---that is, metaphysically unsettled---whether Jud is bald. Because it is true that Jud is bald only if it is metaphysically settled that he is bald, and because it is true that Jud is not bald only if it is metaphysically settled that he is not bald, it is not true that Jud is bald and not true that Jud is not bald. Because Jud is bald only if it is true that he is bald, and because Jud is not bald only if it is true that he is not bald, Jud is not bald and Jud is not not bald. This is a contradiction. Hence, our supposition is false. Moreover, because the issue of whether Jud is bald was chosen arbitrarily, the argument generalizes: indeterminacy is impossible. ;We are faced with a dilemma: take the anti-indeterminacy argument at face value and look for a way to explain away our pro-indeterminacy intuitions, or take our intuitions at face value and look for a way to reject the argument. Many philosophers are inclined toward the latter route, but I want to take the first step toward justifying the former. ;After emphasizing the costs of rejecting the preceding sort of argument, I show how five of the most salient phenomena that give rise to pro-indeterminacy intuitions can be accounted for without postulating genuine indeterminacy. I examine explicitly incomplete definitions, hidden relativity, vagueness, comparatives, and subjunctive conditionals. In each case I suggest a way to account for the phenomenon without postulating indeterminacy. (shrink)

Research biobanks are heterogeneous and exist to manage diverse biosample types with the goal of facilitating and serving biomedical discovery. The perspectives of biobank managers are reviewed, and the perspectives of two biobank directors, one with experience in institutional biobanks and the other with national cooperative group banks, are presented. Most research biobanks are not designed, nor do they have the resources, to return research results and incidental findings to participants or their families.

Entry of new organizations, including multinational enterprises from emerging markets, raises the ethical question of will they benefit society. The concept of legitimacy answers this question because it is the overall assessment of the appropriateness of organizational ends and means. Moreover, gaining legitimacy enables EMNEs to succeed in new host countries. Past work examined collective level indicators of the legitimacy of MNEs, but recent research recognizes the importance of individuals’ perceptions as the micro-foundation of legitimacy. This study first uses new (...) pragmatism, deontology, and utilitarianism to demonstrate that legitimacy is fundamentally an ethical concept—a perspective that has been overlooked in management research. Second, this study uses a seven-step procedure to develop and validate a measure of individuals’ perceptions of the legitimacy of Chinese EMNEs operating in The Netherlands, a developed country. Six dimensions of legitimacy were identified. The study also finds support for this legitimacy judgment process linking the dimensions: validating knowledge → propriety judgments → generalized judgment. This work provides additional micro-foundations to research on legitimacy and contributes to the ongoing process of construct validation. Future research could use the validated measure in other settings and use specific ethical theories in depth to refine the concept of legitimacy. (shrink)

This paper presents methods and challenges attendant on the use of protocol analysis to develop a model of heuristic processing applied to research ethics. Participants are exposed to ethically complex scenarios and asked to verbalize their thoughts as they formulate a requested decision. The model identifies functional parts of the decision-making task: interpretation, retrieval, judgment and editing and seeks to reliably code participant verbalizations to those tasks as well as to a set of cognitive tools generally useful in such work. (...) Important difficulties in the reliability and external validity of measurement are evaluated and a small set of illustrative data is used in support of that discussion. Results indicate that both intuitive emotional but also more deliberative cognition is present which is consistent with work in related literatures in expertise and in neuropsychology. Finally, the theoretical and practical potential of the approach is elaborated, particularly through links to a framing in Aristotelian ethics. (shrink)

This study explores the role that news coverage plays in the allocation of Japanese development aid. Conceptually, it is expected that democratic foreign policy officials, including those working in bureaucratic governmental structures will try to match the magnitude of their actions with what they expect is the public's perception of the importance of the recipient. News media salience serves an easily accessible indicator of that domestic political importance and, in the case of foreign aid, this suggests that higher levels of (...) news coverage of a less-developed country will lead to higher aid commitments. The statistical analysis demonstrates that the level of news coverage is a statistically significant factor in Japanese aid distributions. More significantly, the analysis demonstrates that separating grant aid from other forms of aid is critical for the empirical examination of the determinants of Japanese aid. (shrink)

The past twenty years have witnessed extensive collaborative research between computer scientists, logicians, linguists, philosophers, and psychologists. These interdisciplinary studies stem from the realization that researchers drawn from all fields are studying the same problem. Specifically, a common concern amongst researchers today is how logic sheds light on the nature of information. Ancient questions concerning how humans communicate, reason and decide, and modern questions about how computers should communicate, reason and decide are of prime interest to researchers in various disciplines. (...) _Words, Proofs and Diagrams_ is a collection of papers covering active research areas at the interface of logic, computer science, and linguistics. Readers of the volume will find traditional research on process logics, issues in formal semantics, and language processing. In addition, the volume also highlights a particularly new area where all three disciplines meet—the study of images and graphics as information carriers and the diagrammatic reasoning supported by them. (shrink)

Scholars of early Chinese philosophy frequently point to the nontranscendent, organismic conception of the cosmos in early China as the source of China's unique perspective and distinctive values. One would expect recent works in Confucian ethics to capitalize on this idea. Reviewing recent works in Confucian ethics by P. J. Ivanhoe, David Nivison, R. P. Peerenboom, Henry Rosemont, and Tu Wei-Ming, the author analyzes these new studies in terms of the extent to which their representation of Confucian ethics reflects (...) and is consistent with the view that in early China the cosmos was conceived to be organismic, nontranscendent, and nondualistic. (shrink)

In this article, we report on eight grand challenges for value sensitive design, which were developed at a one-week workshop, Value Sensitive Design: Charting the Next Decade, Lorentz Center, Leiden, The Netherlands, November 14–18, 2016. A grand challenge is a substantial problem, opportunity, or question that motives sustained research and design activity. The eight grand challenges are: Accounting for Power, Evaluating Value Sensitive Design, Framing and Prioritizing Values, Professional and Industry Appropriation, Tech policy, Values and Human Emotions, Value Sensitive Design (...) and Intelligent Algorithms, and Value Tensions. Each grand challenge consists of a discussion of its importance and a set of tractable key questions. (shrink)

In this article, we introduce the Special Issue, Value Sensitive Design: Charting the Next Decade, which arose from a week-long workshop hosted by Lorentz Center, Leiden, The Netherlands, November 14–18, 2016. Forty-one researchers and designers, ranging in seniority from doctoral students to full professors, from Australia, Europe, and North America, and representing a wide range of academic fields participated in the workshop. The first article in the special issue puts forward eight grand challenges for value sensitive design to help guide (...) and shape the field. It is followed by 16 articles consisting of value sensitive design nuggets—short pieces of writing on a new idea, method, challenge, application, or other concept that engages some aspect of value sensitive design. The nuggets are grouped into three clusters: theory, method, and applications. Taken together the grand challenges and nuggets point the way forward for value sensitive design into the next decade and beyond. (shrink)

Evidence suggests that psychedelics bring about their therapeutic outcomes in part through the subjective or qualitative effects they engender and how the individual interprets the resulting experiences. However, psychedelics are contraindicated for individuals who have been diagnosed with certain mental illnesses, on the grounds that these subjective effects may be disturbing or otherwise counter-therapeutic. Substantial resources are therefore currently being devoted to creating psychedelic substances that produce many of the same biological changes as psychedelics, but without their characteristic subjective effects. (...) In this article, we consider ethical issues arising from the prospect of such potential “nonsubjective” psychedelics. We are broadly supportive of efforts to produce such substances for both scientific and clinical reasons. However, we argue that such nonsubjective psychedelics should be reserved for those special cases in which the subjective effects of psychedelics are specifically contraindicated, whereas classic psychedelics that affect subjective experience should be considered the default and standard of care. After reviewing evidence regarding the subjective effects of psychedelics, we raise a number of ethical concerns around the prospect of withholding such typically positive, meaningful, and therapeutic experiences from most patients. (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)

Graeme Forbes (2011) raises some problems for two-dimensional semantic theories. The problems concern nested environments: linguistic environments where sentences are nested under both modal and epistemic operators. Closely related problems involving nested environments have been raised by Scott Soames (2005) and Josh Dever (2007). Soames goes so far as to say that nested environments pose the “chief technical problem” for strong two-dimensionalism. We call the problem of handling nested environments within two-dimensional semantics “the nesting problem”. We show that the two-dimensional (...) semantics for attitude ascriptions developed in Chalmers (2011a) has no trouble accommodating certain forms of the nesting problem that involve factive verbs such as “know” or “establish”. A certain form of the nesting problem involving apriority and necessity operators does raise an interesting puzzle, but we show how a generalized version of the nesting problem arises independently of two-dimensional semantics—it arises, in fact, for anyone who accepts the contingent a priori. We, then, provide a two-dimensional treatment of the apriority operator that fits the two-dimensional treatment of attitude verbs and apply it to the generalized nesting problem. We conclude that two-dimensionalism is not seriously threatened by cases involving the nesting of epistemic and modal operators. (shrink)

For many years essentialism was considered beyond the pale in philosophy, a relic of discredited Aristotelianism. This is no longer so. Kripke and Putnam have made belief in essential natures respectable once more. Harré and Madden have argued against Hume's theory of causation and developed an alternative theory based on the assumption that there are genuine causal powers in nature. Dretske, Tooley, Armstrong, Swoyer, and Carroll have all developed strong alternatives to Hume's theory of the laws of nature. And Shoemaker (...) has developed a thoroughly non-Humean theory of properties. The "new essentialism" has evolved from these beginnings and can now reasonably claim to be a metaphysic for a modern scientific understanding of the world - one that challenges the conception of the world as comprising passive entities whose interactions are to be explained by appeal to contingent laws of nature externally imposed. (shrink)

When making substituted judgments for incapacitated patients, surrogates often struggle to guess what the patient would want if they had capacity. Surrogates may also agonize over having the (sole) responsibility of making such a determination. To address such concerns, a Patient Preference Predictor (PPP) has been proposed that would use an algorithm to infer the treatment preferences of individual patients from population-level data about the known preferences of people with similar demographic characteristics. However, critics have suggested that even if such (...) a PPP were more accurate, on average, than human surrogates in identifying patient preferences, the proposed algorithm would nevertheless fail to respect the patient’s (former) autonomy since it draws on the ‘wrong’ kind of data: namely, data that are not specific to the individual patient and which therefore may not reflect their actual values, or their reasons for having the preferences they do. Taking such criticisms on board, we here propose a new approach: the Personalized Patient Preference Predictor (P4). The P4 is based on recent advances in machine learning, which allow technologies including large language models to be more cheaply and efficiently ‘fine-tuned’ on person-specific data. The P4, unlike the PPP, would be able to infer an individual patient’s preferences from material (e.g., prior treatment decisions) that is in fact specific to them. Thus, we argue, in addition to being potentially more accurate at the individual level than the previously proposed PPP, the predictions of a P4 would also more directly reflect each patient’s own reasons and values. In this article, we review recent discoveries in artificial intelligence research that suggest a P4 is technically feasible, and argue that, if it is developed and appropriately deployed, it should assuage some of the main autonomy-based concerns of critics of the original PPP. We then consider various objections to our proposal and offer some tentative replies. (shrink)

David DeGrazia’s stated purposes for Taking Animals Seriously are to apply a coherentist methodology to animal ethics, to do the philosophical work necessary for discussing animal minds, and to fill in some of the gaps in the existing literature on animal ethics.

This book presents a major statement on the dominant philosophy of science by one of the world's leading metaphysicians. Brian Ellis's new book develops the metaphysics of scientific realism to the point where it begins to take on the characteristics of a first philosophy. As most people understand it, scientific realism is not yet such a theory. It is not sufficiently general, and has no plausible applications in fields other than the well-established sciences. Nevertheless, Ellis demonstrates that the original (...) arguments that led to scientific realism may be deployed more widely than they originally were to fill out a more complete picture of what there is. Ellis shows that realistic theories of quantum mechanics, time, causality and human freedom can all be developed satisfactorily, and moral theory can be recast to fit within this comprehensive metaphysical framework. (shrink)

The study of perception and the role of the senses have recently risen to prominence in philosophy and are now a major area of study and research. However, the philosophical history of the senses remains a relatively neglected subject. Moving beyond the current philosophical canon, this outstanding collection offers a wide-ranging and diverse philosophical exploration of the senses, from the classical period to the present day. Written by a team of international contributors, it is divided into six parts: -/- Perception (...) from Non-Western Perspectives Perception in the Ancient Period Perception in the Medieval Latin/Arabic Period Perception in the Early Modern Period Perception in the Post-Kantian Period Perception in the Contemporary Period. The volume challenges conventional philosophical study of perception by covering a wide range of significant, as well as hitherto overlooked, topics, such as perceptual judgment, temporal and motion illusions, mirror and picture perception, animal senses and cross-modal integration. By investigating the history of the senses in thinkers such as Plotinus, Auriol, Berkeley and Cavendish; and considering the history of the senses in diverse philosophical traditions, including Chinese, Indian, Byzantine, Greek and Latin it brings a fresh approach to studying the history of philosophy itself. -/- Including a thorough introduction as well as introductions to each section by the editors, The Senses and the History of Philosophy is essential reading for students and researchers in the history of philosophy, perception, philosophy of mind, philosophical psychology, aesthetics and eastern and non-western philosophy. It will also be extremely useful for those in related disciplines such as psychology, religion, sociology, intellectual history and cognitive sciences. (shrink)

This article provides current Schwartz Values Survey (SVS) data from samples of business managers and professionals across 50 societies that are culturally and socioeconomically diverse. We report the society scores for SVS values dimensions for both individual- and societal-level analyses. At the individual-level, we report on the ten circumplex values sub-dimensions and two sets of values dimensions (collectivism and individualism; openness to change, conservation, self-enhancement, and self-transcendence). At the societal-level, we report on the values dimensions of embeddedness, hierarchy, mastery, affective (...) autonomy, intellectual autonomy, egalitarianism, and harmony. For each society, we report the Cronbach’s α statistics for each values dimension scale to assess their internal consistency (reliability) as well as report interrater agreement (IRA) analyses to assess the acceptability of using aggregated individual level values scores to represent country values. We also examined whether societal development level is related to systematic variation in the measurement and importance of values. Thus, the contributions of our evaluation of the SVS values dimensions are two-fold. First, we identify the SVS dimensions that have cross-culturally internally reliable structures and within-society agreement for business professionals. Second, we report the society cultural values scores developed from the twenty-first century data that can be used as macro-level predictors in multilevel and single-level international business research. (shrink)

In a range of contexts, one comes across processes resembling inference, but where input propositions are not in general included among outputs, and the operation is not in any way reversible. Examples arise in contexts of conditional obligations, goals, ideals, preferences, actions, and beliefs. Our purpose is to develop a theory of such input/output operations. Four are singled out: simple-minded, basic (making intelligent use of disjunctive inputs), simple-minded reusable (in which outputs may be recycled as inputs), and basic reusable. They (...) are defined semantically and characterised by derivation rules, as well as in terms of relabeling procedures and modal operators. Their behaviour is studied on both semantic and syntactic levels. (shrink)