Background: Treating medication-refractory freezing of gait in Parkinson’s disease remains challenging despite several trials reporting improvements in motor symptoms using subthalamic nucleus or globus pallidus internus deep brain stimulation. Pedunculopontine nucleus region DBS has been used for medication-refractory FoG, with mixed findings. FoG, as a paroxysmal phenomenon, provides an ideal framework for the possibility of closed-loop DBS.Methods: In this clinical trial, five subjects with medication-refractory FoG underwent bilateral GPi DBS implantation to address levodopa-responsive PD symptoms with open-loop stimulation. Additionally, PPN (...) DBS leads were implanted for CL-DBS to treat FoG. The primary outcome of the study was a 40% improvement in medication-refractory FoG in 60% of subjects at 6 months when “on” PPN CL-DBS. Secondary outcomes included device feasibility to gauge the recruitment potential of this four-lead DBS approach for a potentially larger clinical trial. Safety was judged based on adverse events and explantation rate.Findings: The feasibility of this approach was demonstrated as we recruited five subjects with both “on” and “off” medication freezing. The safety for this population of patients receiving four DBS leads was suboptimal and associated with a high explantation rate of 40%. The primary clinical outcome in three of the five subjects was achieved at 6 months. However, the group analysis of the primary clinical outcome did not reveal any benefit.Interpretation: This study of a human PPN CL-DBS trial in medication-refractory FoG showed feasibility in recruitment, suboptimal safety, and a heterogeneous clinical effect in FoG outcomes. (shrink)

Frequent evolutionary birth and death events have created a large quantity of biologically important, lineage‐specific DNA within mammalian genomes. The birth and death of DNA sequences is so frequent that the total number of these insertions and deletions in the human population remains unknown, although there are differences between these groups, e.g. transposable elements contribute predominantly to sequence insertion. Functional turnover – where the activity of a locus is specific to one lineage, but the underlying DNA remains conserved – can (...) also drive birth and death. However, this does not appear to be a major driver of divergent transcriptional regulation. Both sequence and functional turnover have contributed to the birth and death of thousands of functional promoters in the human and mouse genomes. These findings reveal the pervasive nature of evolutionary birth and death and suggest that lineage‐specific regions may play an important but previously underappreciated role in human biology and disease. (shrink)

Contemporary republicanism is characterized by three main ideas: free persons, who are not subject to the arbitrary power of others; free states, which try to protect their citizens from such power without exercising it themselves; and vigilant citizenship, as a means to limit states to their protective role. This book advances an economic model of such republicanism that is ideologically centre-left. It demands an exit-oriented state interventionism, one that would require an activist government to enhance competition and resource exit from (...) dominating relationships within markets of all types, be they marital, labour, or residential. The substantial intervention and redistribution necessitated by such an approach make it leftist, while its tendency to work with rather than against the grain of markets makes it centrist. It is, in short, a contribution to progressive republican political thought, but one that is less social-democratic than market-democratic in character. (shrink)

This edition of the Handbookfollows the first edition by 10 years.

With the publication of A Theory of Justice in 1971, John Rawls not only rejuvenated contemporary political philosophy but also defended a Kantian form of Enlightenment liberalism called “justice as fairness.” Enlightenment liberalism stresses the development and exercise of our capacity for autonomy, while Reformation liberalism emphasizes diversity and the toleration that encourages it. These two strands of liberalism are often mutually supporting, but they conflict in a surprising number of cases, whether over the accommodation of group difference, the design (...) of civic education, or the promotion of liberal values internationally. During the 1980’s, however, Rawls began to jettison key Kantian characteristics of his theory, a process culminating in the 1993 release of Political Liberalism and completing the transformation of justice as fairness into a Reformation liberalism. -/- Reconstructing Rawls argues that this transformation was a tragic mistake because it jeopardized the most important features of his theory, viz. the lexical priorities of right, liberty, and fair equality of opportunity as well as the difference principle. Controversially, this book contends that Rawls’s so-called “political turn,” motivated by a newfound interest in diversity and the accommodation of difference, has been unhealthy for autonomy-based liberalism and has pushed liberalism more broadly towards cultural relativism, be it in the guise of liberal multiculturalism or critiques of cosmopolitan distributive-justice theories. The book then demonstrates that the central elements of justice as fairness can only be defended within the context of a Kantian Enlightenment liberalism and that Rawls’s hope for a more pluralistic grounding for his theory, endorsed by a wide variety of belief systems present in modern democratic societies, is illusory. -/- Reconstructing Rawls is the first book to systematically compare Rawls’s and Kant’s theories and the first to offer an internal critique and reconstruction of justice as fairness, reconceiving it as a comprehensive, universalistic Kantian liberalism. By doing so, it gives us both the vision of a liberal world order—“a republicanism of all states, together and separately,” as Kant put it—and a mode of justification addressed to all men and women, not as members of particular nations, races, and faiths, but as human beings, as citizens of the world. In short, it reclaims Rawls for the Enlightenment. (shrink)

Rawls offers three arguments for the priority of liberty in Theory, two of which share a common error: the belief that once we have shown the instrumental value of the basic liberties for some essential purpose (e.g., securing self-respect), we have automatically shown the reason for their lexical priority. The third argument, however, does not share this error and can be reconstructed along Kantian lines: beginning with the Kantian conception of autonomy endorsed by Rawls in section 40 of Theory, we (...) can explain our highest-order interest in rationality, justify the lexical priority of all basic liberties, and reinterpret Rawls’ threshold condition for the application of the priority of liberty. Perhaps unsurprisingly, this Kantian reconstruction will not work within the radically different framework of Political Liberalism. (shrink)

Historically, republicans were of different minds about markets: some, such as Rousseau, reviled them, while others, like Adam Smith, praised them. The recent republican resurgence has revived this issue. Classical liberals such as Gerald Gaus contend that neo-republicanism is inherently hostile to markets, while neo-republicans like Richard Dagger and Philip Pettit reject this characterization—though with less enthusiasm than one might expect. I argue here that the right republican attitude toward competitive markets is celebratory rather than acquiescent and that republicanism demands (...) such markets for the same reason it requires the rule of law: because both are essential institutions for protecting individuals from arbitrary interference. I reveal how competition restrains—and in the limit, even eradicates—market power and thereby helps us realize “market freedom,” i.e., freedom as non-domination in the context of economic exchange. Finally, I show that such freedom necessitates “Anglo-Nordic” economic policies. (shrink)

Jeremy Waldron has recently raised the question of whether there is anything approximating the creative self-authorship of personal autonomy in the writings of Immanuel Kant. After considering the possibility that Kantian prudential reasoning might serve as a conception of personal autonomy, I argue that the elements of a more suitable conception can be found in Kant’s Tugendlehre, or “Doctrine of Virtue”—specifically, in the imperfect duties of self-perfection and the practical love of others. This discovery is important for at least three (...) reasons: first, it elucidates the relationship among the various conceptions of autonomy employed by personal-autonomy theorists and contemporary Kantians; second, it brings to the surface previously unnoticed or undernoticed features of Kant’s moral theory; and third, it provides an essential line of defense against certain critiques of contemporary Kantian theories, especially that of John Rawls. (shrink)

Is “liberal socialism” an oxymoron? Not quite, but I will demonstrate here that it is a much more unstable and uncommon hybrid than scholars had previously thought and that almost all liberals should reject socialism, even in its most attractive form. More specifically, I will show that three leading varieties of liberalism—neutralist, plural-perfectionist, and deliberative-democratic—are incompatible with even a moderate form of socialism, viz., associational market socialism. My paper will also cast grave doubt on Rawls’s belief that justice as fairness (...) is consistent with liberal socialism. (shrink)

Robert S. Summers is a distinguished legal theorist whose work has had significant influence in Europe as well as the United States. The study of form and substance in law, the theme of this collection, marks many of his most distinctive contributions to law and legal philosophy over four decades.

Contemporary republicans have adopted a less-than-charitable attitude toward private beneficence, especially when it is directed to the poor, worrying that rich patrons may be in a position to exercise arbitrary power over their impoverished clients. These concerns have led them to support impartial public provision by way of state welfare programs, including an unconditional basic income (UBI). In contrast to this administrative model of public welfare, I will propose a competitive model in which the state regulates and subsidizes a decentralized (...) and nonstatist provision of support for the poor. This model will fix the historically objectionable features of private provision by having the state prevent collusion among private charities, deliver information to recipients about alternative sources of assistance, and give substantial grants to charities as well as tax incentives and vouchers to donors. I will contend that such an approach would do a better job of minimizing domination of the poor than traditional welfare states and may prove more politically feasible than a UBI, at least in the near term in certain national contexts. (shrink)

Many scholars, including G. A. Cohen, Daniel Attas, and George Brenkert, have denied that a Kantian defense of self-ownership is possible. Kant's ostensible hostility to self-ownership can be resolved, however, upon reexamination of the Groundwork and the Metaphysics of Morals. Moreover, two novel Kantian defenses of self-ownership (narrowly construed) can be devised. The first shows that maxims of exploitation and paternalism that violate self-ownership cannot be universalized, as this leads to contradictions in conception. The second shows that physical coercion against (...) rational agents involves a profound status wrong--namely, their treatment as children or animals--and that this system of differential status and treatment (including self-ownership rights for rational agents) can be morally justified by our capacity for autonomy. (shrink)

"Whole brain death" (neurological death) is well-established as a legal standard of death across the country. Recently, New Jersey became the first state to enact a statute recognizing a personal religious exemption (a conscience clause) protecting the rights of those who object to neurological death. The Act also mandates adoption through the regulatory process of uniform and up-to-date clinical criteria for determining neurological death.

This article criticizes radical labor republicanism on republican grounds. I show that its demand for universal workplace democracy via workers’ cooperatives conflicts with republican freedom along three different dimensions: first, freedom to choose an occupation…and not to choose one; second, freedom within the very cooperatives that workers are to democratically govern; and third, freedom within the newly proletarian state. In the conclusion, I ask whether these criticisms apply, at least in part, to the more modest, incrementalist strand of labor republicanism. (...) To the extent that they do, delaboring republicanism might be the best response. (shrink)

Against several recent interpretations, I argue in this chapter that Immanuel Kant's support for enlightened absolutism was a permanent feature of his political thought that fit comfortably within his larger philosophy, though he saw such rule as part of a transition to democratic self-government initiated by the absolute monarch himself. I support these contentions with (1) a detailed exegesis of Kant’s essay "What is Enlightenment?" (2) an argument that Kantian republicanism requires not merely a separation of powers but also a (...) representative democratic legislature, and (3) a demonstration that each stage of a democratic transition can potentially be in an absolute monarch’s short-run self-interest. (shrink)

In the wake of both the semiotic and the psychoanalytic revolutions, how is it possible to describe the object of religious worship in realist terms? Semioticians argue that each object is known only insofar as it gives birth to a series of signs and interpretants (new signs). From the psychoanalytic side, religious beliefs are seen to belong to transference energies and projections that contaminate the religious object with all-too-human complexes. In Nature's Religion, distinguished theologian and philosopher Robert S. Corrington (...) weaves together the concept of infinite semiosis with that of the transference to show that the self does have access to something in nature that is intrinsically religious. Corrington argues that signs and our various transference fields can and do connect us with fully natural religious powers that are not of our own making, thereby opening up a path past the Western monotheisms to a capacious religion of nature. With a foreword by Robert C. Neville, Nature's Religion is essential reading for philosophers of religion, scholars of the psychology of religion, and theologians. (shrink)

The republican tradition has long been ambivalent about markets and commercial society more generally: from the contrasting positions of Rousseau and Smith in the eighteenth century to recent neorepublican debates about capitalism, republicans have staked out diverse positions on fundamental issues of political economy. Rather than offering a systematic historical survey of these discussions, this chapter will instead focus on the leading neo-republican theory—that of Philip Pettit—and consider its implications for market society. As I will argue, Pettit’s theory is even (...) friendlier to markets than most have believed: far from condemning commercial society, his theory recognizes that competitive markets and their institutional preconditions are an alternative means to limit arbitrary power across the domestic, economic, and even political spheres. While most republican theorists have focused on political means to limit such power—including both constitutional means (e.g., separation of powers, judicial review, the rule of law, federalism) and participatory ones (democratic elections and oversight)—I will examine here an economic model of republicanism that can complement, substitute for, and at times displace the standard political model. Whether we look at spousal markets, labor markets, or residential markets within federal systems, state policies that heighten competition among their participants and resource exit from abusive relationships within them can advance freedom as non-domination as effectively or even more effectively than social-democratic approaches that have recently gained enthusiasts among republicans. These conclusions suggest that democracy, be it social or political, is just one means among others for restraining arbitrary power and is consequently less central to (certain versions of) republicanism than we may have expected. So long as they counteract domination, economic inroads into notionally democratic territory are no more worrisome than constitutional ones. (shrink)

The story of this book of 'materials on Ludwik Fleck' is also the story of the reception of Ludwik Fleck. In this volume, some essential materials which have been produced by that reception have been gathered together.

Cet article propose une brève discussion de la représentation des arbres et des grottes dans l’art grec, en soulignant la tendance de ces deux motifs paysagers à se recouvrir ou à se confondre sur un plan formel.The article offers a brief discussion of tree and cave representations in Greek art, tracing a tendency of these two landscape motifs to overlap or appear in conflated form.

This 10th book in the series addresses automaticity and how it relates to social behavior.

One powerful argument against self-ownership is that it degrades personhood by leading individuals to view themselves and others as mere instrumental goods, alienable commodities to be exchanged in markets like other products and services. In general terms, this line of criticism (called the “commodification argument”) maintains that a direct and causal relationship exists between certain legal institutions (self-ownership) and certain attitudes (instrumentalism) and that the undesirability of the latter justifies restrictions on the former. In this article, I will critically examine (...) Margaret Jane Radin’s book Contested Commodities (1996), which presents a well-developed, compelling version of the commodification argument. I will advance three central points over the course of the article: first, the purported causal connection between self-ownership and instrumentalism is either weak or nonexistent; second, the commodification argument does little independent moral work, tending instead to be parasitic on arguments against economic, racial, and gender inequality; and third, what independent moral work it does do seems to be directed not so much at self-ownership as at liberal neutrality. I will conclude by showing that the weaknesses of Radin’s diverse defenses of the commodification argument cast doubt upon the anticommodificationist enterprise as a whole. (shrink)