Primary progressive multiple sclerosis (PPMS) shows a highly variable disease progression with poor prognosis and a characteristic accumulation of disabilities in patients. These hallmarks of PPMS make it difficult to diagnose and currently impossible to efficiently treat. This study aimed to identify plasma metabolite profiles that allow diagnosis of PPMS and its differentiation from the relapsing-remitting subtype (RRMS), primary neurodegenerative disease (Parkinson’s disease, PD), and healthy controls (HCs) and that significantly change during the disease course and could serve as surrogate (...) markers of multiple sclerosis (MS)-associated neurodegeneration over time. We applied untargeted high-resolution metabolomics to plasma samples to identify PPMS-specific signatures, validated our findings in independent sex- and age-matched PPMS and HC cohorts and built discriminatory models by partial least square discriminant analysis (PLS-DA). This signature was compared to sex- and age-matched RRMS patients, to patients with PD and HC. Finally, we investigated these metabolites in a longitudinal cohort of PPMS patients over a 24-month period. PLS-DA yielded predictive models for classification along with a set of 20 PPMS-specific informative metabolite markers. These metabolites suggest disease-specific alterations in glycerophospholipid and linoleic acid pathways. Notably, the glycerophospholipid LysoPC(20:0) significantly decreased during the observation period. These findings show potential for diagnosis and disease course monitoring, and might serve as biomarkers to assess treatment efficacy in future clinical trials for neuroprotective MS therapies. (shrink)

Attentional control theory suggests that high cognitive demands impair the flexible deployment of attention control in anxious adults, particularly when paired with external threats. Extending this...

Clark has recently suggested that predictive processing advances a theory of neural function with the resources to put an ecumenical end to the “representation wars” of recent cognitive science. In this paper I defend and develop this suggestion. First, I broaden the representation wars to include three foundational challenges to representational cognitive science. Second, I articulate three features of predictive processing’s account of internal representation that distinguish it from more orthodox representationalist frameworks. Specifically, I argue that it posits a resemblance-based (...) representational architecture with organism-relative contents that functions in the service of pragmatic success, not veridical representation. Finally, I argue that internal representation so understood is either impervious to the three anti-representationalist challenges I outline or can actively embrace them. (shrink)

When the costs of acquiring knowledge outweigh the benefits of possessing it, ignorance is rational. In this paper I clarify and explore a related but more neglected phenomenon: cases in which ignorance is motivated by the anticipated costs of possessing knowledge, not acquiring it. The paper has four aims. First, I describe the psychological and social factors underlying this phenomenon of motivated ignorance. Second, I describe those conditions in which it is instrumentally rational. Third, I draw on evidence from the (...) social sciences to argue that this phenomenon of rational motivated ignorance plays an important but often unappreciated role in one of the most socially harmful forms of ignorance today: voter ignorance of societal risks such as climate change. Finally, I consider how to address the high social costs associated with rational motivated ignorance. (shrink)

Why do well‐functioning psychological systems sometimes give rise to absurd beliefs that are radically misaligned with reality? Drawing on signalling theory, I develop and explore the hypothesis that groups often embrace beliefs that are viewed as absurd by outsiders as a means of signalling ingroup commitment. I clarify the game‐theoretic and psychological underpinnings of this hypothesis, I contrast it with similar proposals about the signalling functions of beliefs, and I motivate several psychological and sociological predictions that could be used to (...) distinguish it from alternative explanations of irrational group beliefs. (shrink)

In this paper, I argue that explanations just ARE those sorts of things that, under the right circumstances and in the right sort of way, bring about understanding. This raises the question of why such a seemingly simple account of explanation, if correct, would not have been identified and agreed upon decades ago. The answer is that only recently has it been made possible to analyze explanation in terms of understanding without the risk of collapsing both to merely phenomenological states. (...) For the most part, theories of explanation were for 50 years held hostage to the historical accident that they far outstripped in sophistication corresponding accounts of understanding. (shrink)

Predictive processing has recently been advanced as a global cognitive architecture for the brain. I argue that its commitments concerning the nature and format of cognitive representation are inadequate to account for two basic characteristics of conceptual thought: first, its generality—the fact that we can think and flexibly reason about phenomena at any level of spatial and temporal scale and abstraction; second, its rich compositionality—the specific way in which concepts productively combine to yield our thoughts. I consider two strategies for (...) avoiding these objections and I argue that both confront formidable challenges. (shrink)

Recent years have seen a substantial increase in alternative agrifood initiatives that attempt to use the market to curtail the negative social and environmental effects of production and trade in a globalized food system. These alternatives pose a challenge to capital accumulation and the externalization of environmental costs by large agribusiness, trading and retail firms. Yet the success of these alternatives also makes them an inviting target for corporate participation. This article examines these dynamics through a case study of the (...) two most significant such food system alternatives—organics and fair trade—focusing on corporate involvement in establishing and renegotiating the standards undergirding these initiatives. We compare the development of and contestation over the standards for both certified organic and certified fair trade, with particular attention to the U.S. context. We provide a brief history of their parallel processes of rapid growth and market mainstreaming. We examine claims of cooptation by movement participants, as well as the divergences and similarities between the organic and fair trade cases. Analyzing these two cases provides useful insights into the strategic approaches that corporate firms have deployed to further capital accumulation and to defuse threats to their profit margins and to status quo production, pricing, labor, trading and retailing practices. It can also offer valuable lessons regarding the most effective means of responding to such counter-reforms and of protecting or reasserting the more transformative elements at the heart of these alternative systems. (shrink)

Two striking claims are advanced on behalf of the free energy principle in cognitive science and philosophy: that it identifies a condition of the possibility of existence for self-organising systems; and that it has important implications for our understanding of how the brain works, defining a set of process theories—roughly, theories of the structure and functions of neural mechanisms—consistent with the free energy minimising imperative that it derives as a necessary feature of all self-organising systems. I argue that the conjunction (...) of claims and rests on a fallacy of equivocation. The FEP can be interpreted in two ways: as a claim about how it is possible to redescribe the existence of self-organising systems, and as a claim about how such systems maintain their existence. Although the Descriptive FEP plausibly does identify a condition of the possibility of existence for self-organising systems, it has no important implications for our understanding of how the brain works. Although the Explanatory FEP would have such implications if it were true, it does not identify a condition of the possibility of existence for self-organising systems. I consider various ways of responding to this conclusion, and I explore its implications for the role and importance of the FEP in cognitive science and philosophy. (shrink)

Recent medical and bioethics literature shows a growing concern for practitioners’ emotional experience and the ethical environment in the workplace. Moral distress, in particular, is often said to result from the difficult decisions made and the troubling situations regularly encountered in health care contexts. It has been identified as a leading cause of professional dissatisfaction and burnout, which, in turn, contribute to inadequate attention and increased pain for patients. Given the natural desire to avoid these negative effects, it seems to (...) most authors that systematic efforts should be made to drastically reduce moral distress, if not altogether eliminate it from the lives of vulnerable practitioners. Such efforts, however, may be problematic, as moral distress is not adequately understood, nor is there agreement among the leading accounts regarding how to conceptualize the experience. With this article I make clear what a robust account of moral distress should be able to explain and how the most common notions in the existing literature leave significant explanatory gaps. I present several cases of interest and, with careful reflection upon their distinguishing features, I establish important desiderata for an explanatorily satisfying account. With these fundamental demands left unsatisfied by the leading accounts, we see the persisting need for a conception of moral distress that can capture and delimit the range of cases of interest. (shrink)

The notion of ‘revealed preference’ is unclear and should be abandoned. Defenders of the theory of revealed preference have misinterpreted legitimate concerns about the testability of economics as the demand that economists eschew reference to (unobservable) subjective states. As attempts to apply revealed-preference theory to game theory illustrate with particular vividness, this demand is mistaken.

In this paper, I am going to explore some of the moral considerations relating to smoking licences. And I shall offer a limited defence of licences as a replacement for sales tax on tobacco products. This defence will include some moral arguments in favour of one particular licence design over others.

This paper argues that radical enactivism (RE) offers a framework with the required nuance needed for understanding of the full range of the various forms of pretense. In particular, its multi-storey account of cognition, which holds that psychological attitudes can be both contentless and contentful, enables it to appropriately account for both the most basic and most advanced varieties of pretense. By comparison with other existing accounts of pretense, RE is shown to avoid the pitfalls of representationalist theories while also (...) allowing us to combine the best elements of the praxeological enactivist (Weichold & Rucińska, 2021 ) and Langland-Hassan’s ( 2020, 2021 ) proposals about pretense, while avoiding their key shortcomings. (shrink)

Plato's dialogues frequently criticize traditional Greek myth, yet Plato also integrates myth with his writing. Daniel S. Werner confronts this paradox through an in-depth analysis of the Phaedrus, Plato's most mythical dialogue. Werner argues that the myths of the Phaedrus serve several complex functions: they bring nonphilosophers into the philosophical life; they offer a starting point for philosophical inquiry; they unify the dialogue as a literary and dramatic whole; they draw attention to the limits of language and the limits (...) of knowledge; and they allow Plato to co-opt cultural authority as a way of defining and legitimating the practice of philosophy. Platonic myth, as a species of traditional tale, is thus both distinct from philosophical dialectic and similar to it. Ultimately, the most powerful effect of Platonic myth is the way in which it leads readers to participate in Plato's dialogues and to engage in a process of self-examination. (shrink)

Bruineberg et al. provide compelling clarity on the roles Markov blankets could (and perhaps should) play in the study of life and mind. However, here we draw attention to a further role blankets might play: as a hypothesis about cognition itself. People and other animals may use blanket-like representations to model the boundary between themselves and their worlds.

Sex differences in mortality rates stem from genetic, physiological, behavioral, and social causes that are best understood when integrated in an evolutionary life history framework. This paper investigates the Male-to-Female Mortality Ratio (M:F MR) from external and internal causes and across contexts to illustrate how sex differences shaped by sexual selection interact with the environment to yield a pattern with some consistency, but also with expected variations due to socioeconomic and other factors.

In slapstick comedy, the worst thing that could happen usually does: The person with a sore toe manages to stub it, sometimes twice. Such errors also arise in daily life, and research traces the tendency to do precisely the worst thing to ironic processes of mental control. These monitoring processes keep us watchful for errors of thought, speech, and action and enable us to avoid the worst thing in most situations, but they also increase the likelihood of such errors when (...) we attempt to exert control under mental load (stress, time pressure, or distraction). Ironic errors in attention and memory occur with identifiable brain activity and prompt recurrent unwanted thoughts; attraction to forbidden desires; expression of objectionable social prejudices; production of movement errors; and rebounds of negative experiences such as anxiety, pain, and depression. Such ironies can be overcome when effective control strategies are deployed and mental load is minimized. (shrink)

Mandatory minimum sentencing provisions have been a feature of the US justice system since 1790. But they have expanded considerably under the war on drugs, and their use has expanded considerably under the Trump Administration; some states are also poised to expand drug-related mandatory minimums further in efforts to fight the current opioid epidemic. In this chapter I outline and evaluate three prominent arguments for and against the use of mandatory minimums in the war on drugs—they appeal, respectively, to proportionality, (...) consistency, and efficiency. I ultimately defend the view that the use of mandatory minimums in the war on drugs is unjust. (shrink)

In a critique of my work on ‘taking the blame’ as a response to medical errors, my position on the potential goods of individual responsibility and blame is challenged. It is suggested that medicine is a ‘team sport’ and several rich examples are provided to support the possible harms of practitioner self-blame. Yet, it appears that my critics have misunderstood my demands and to whom they are directed. With this response, I offer several clarifications of my account, as well as (...) a reiteration on the role of self-blame after medical error. (shrink)

Contextualists about knowledge ascriptions perceive an analogy between the semantics they posit for “know(s)” and the semantics of comparative terms like “tall” and “flat”. Jason Stanley has recently raised a number of objections to this view. This paper offers a response by way of an alternative analogy with modified comparatives, which resolves most of Stanley’s objections. Rather than being ad hoc, this new analogy in fact fits better with platitudes about knowledge and facilitates a better understanding of the semantics of (...) gradability, such that an explanation of most of Stanley’s disanalogies becomes available. In addition, I argue that there are reasons to doubt Stanley’s claim that “knows(s)” cannot switch its content within a discourse, due to what may happen when we ascribe knowledge of more than one proposition. (shrink)

In “Weighing Up Weighted Lotteries: Scarcity, Overlap Cases, and Fair Inequalities of Chance”, Gerard Vong addresses intriguing problems in which it is impossible to give an equal chance of receiving a good to a set of equal claimants, because goods can be distributed only via groups which have overlapping membership. Vong proposes a rule for distributing chances that he argues is sensitive to both comparative and absolute fairness. This comment discusses some formal difficulties with Vong’s proposal and argues that it (...) is better to separate the two concerns and to allow the tradeoffs between them to depend on characteristics of the goods to be distributed. (shrink)

It is well known that Aristotle tries to make room for self-motion – an idea he inherits to some extent from Plato – within his other commitments to causal determinism while at the same time modifying the idea. However, one argument in Physics VII 1 seems to pose a problem for the bare possibility of self-motion; in it he seems to argue that everything that moves must be moved by something else. The text in which this argument appears is itself (...) vexed on a number of fronts, because it is not clear how Physics VII fits with the rest of the Physics, and also because there are two distinct manuscript traditions for Physics VII. So the argument in Physics VII 1 has not been adequately taken into account in discussions of self-motion. I argue for a new and charitable reading of Aristotle’s Physics VII 1 α241b35-242a49 / β241b25-242a15. I show that the argument is compatible with Aristotle’s endorsements of self-motion; I defend the argument’s most controversial premise; and I argue that my reading has some useful implications for understanding Aristotelian self-motion. (shrink)

Einstein’s razor, a corollary of Ockham’s razor, is often paraphrased as follows: make everything as simple as possible, but not simpler. This rule of thumb describes the challenge that designers of a legal system face—to craft simple laws that produce desired ends, but not to pursue simplicity so far as to undermine those ends. Complexity, simplicity’s inverse, taxes cognition and increases the likelihood of suboptimal decisions. In addition, unnecessary legal complexity can drive a misallocation of human capital toward comprehending and (...) complying with legal rules and away from other productive ends. While many scholars have offered descriptive accounts or theoretical models of legal complexity, most empirical research to date has been limited to simple measures of size, such as the number of pages in a bill. No extant research rigorously applies a meaningful model to real data. As a consequence, we have no reliable means to determine whether a new bill, regulation, order, or precedent substantially effects legal complexity. In this paper, we begin to address this need by developing a proposed empirical framework for measuring relative legal complexity. This framework is based on “knowledge acquisition”, an approach at the intersection of psychology and computer science, which can take into account the structure, language, and interdependence of law. We then demonstrate the descriptive value of this framework by applying it to the U.S. Code’s Titles, scoring and ranking them by their relative complexity. We measure various features of a title including its structural size, the net flow of its intra-title citations and its linguistic entropy. Our framework is flexible, intuitive, and transparent, and we offer this approach as a first step in developing a practical methodology for assessing legal complexity. (shrink)

The past twenty years have been an incredibly productive period in science studies. Still, because recent work in science studies puts a spotlight on agency and enabling situa tions, many practitioners in the field ignore, underplay, or dismiss the possibility that historically established, structurally stable attributes of the world may systemically shape practice at the laboratory level. This article questions this general position. Draw ing on data from a participant observation study of a university biology laboratory, it describes five features (...) of the institutional landscape that shape this laboratory's practice. (shrink)

Widespread commercial use of the internet has significantly increased the volume and scope of data being collected by organisations. ‘Big data’ has emerged as a term to encapsulate both the technical and commercial aspects of this growing data collection activity. To date, much of the discussion of big data has centred upon its transformational potential for innovation and efficiency, yet there has been less reflection on its wider implications beyond commercial value creation. This paper builds upon normal accident theory to (...) analyse the broader ethical implications of big data. It argues that the strategies behind big data require organisational systems that leave them vulnerable to normal accidents, that is to say some form of accident or disaster that is both unanticipated and inevitable. Whilst NAT has previously focused on the consequences of physical accidents, this paper suggests a new form of system accident that we label data accidents. These have distinct, less tangible and more complex characteristics and raise significant questions over the role of individual privacy in a ‘data society’. The paper concludes by considering the ways in which the risks of such data accidents might be managed or mitigated. (shrink)

The ancient background -- Weiss and the pursuit of bodily excellence -- Huizinga and the homo ludens hypothesis -- Feezell, moderation, and irony -- The process of becoming virtuous.