At extreme altitude (>5,000 – 5,500 m), sustained hypoxia threatens human function and survival, and is associated with marked involuntary weight loss (cachexia). This seems to be a coordinated response: appetite and protein synthesis are suppressed, and muscle catabolism promoted. We hypothesise that, rather than simply being pathophysiological dysregulation, this cachexia is protective. Ketone bodies, synthesised during relative starvation, protect tissues such as the brain from reduced oxygen availability by mechanisms including the reduced generation of reactive oxygen species, improved mitochondrial (...) efficiency and activation of the ATP‐sensitive potassium (KATP) channel. Amino acids released from skeletal muscle also protect cells from hypoxia, and may interact synergistically with ketones to offer added protection. We thus propose that weight loss in hypoxia is an adaptive response: the amino acids and ketone bodies made available act not only as metabolic substrates, but as metabolic modulators, protecting cells from the hypoxic challenge.Also watch the Video Abstract. (shrink)

The growth factor progranulin (PGRN) regulates cell division, survival, and migration. PGRN is an extracellular glycoprotein bearing multiple copies of the cysteine‐rich granulin motif. With PGRN family members in plants and slime mold, it represents one of the most ancient of the extracellular regulatory proteins still extant in modern animals. PRGN has multiple biological roles. It contributes to the regulation of early embryogenesis, to adult tissue repair and inflammation. Elevated PGRN levels often occur in cancers, and PGRN immunotherapy inhibits the (...) growth of hepatic cancer xenografts in mice. Recent studies have demonstrated roles for PGRN in neurobiology. An autosomal dominant mutation in GRN, the gene for PGRN, leads to neuronal atrophy in the frontal and temporal lobes, resulting in the disease frontotemporal lobar dementia. In this review we will discuss current knowledge of the multifaceted biology of PGRN. (shrink)

Assessing mastery of bioethics in a graduate program requires careful attention not simply to the content knowledge and skill development of students but also to the principles of sound assessment processes. In this article, we describe the rationale, development process, and features of the comprehensive exam we created as a culminating experience of a master’s program in bioethics. The exam became the students’ opportunity to demonstrate the way they were able to integrate course, textual, and practical knowledge gained throughout the (...) experience of the program. Additionally, the exam assessed students’ proficiency in the field of bioethics and their ability to critically and constructively analyze bioethical issues. In this article, we offer tips to other exam creators regarding our experiences with question and answer development, scoring of the exam, and relationships between coursework and exam preparation and completion. We also include a sample rubric for others to see how we determined which student answers were satisfactory. (shrink)

Le visage est-il un phénomène simple ou complexe? Serait-il juste de le définir comme cet aspect de l’être humain qui dépasse tout effort de compréhension et de totalisation, ou bien y a-t-il d’autres caractéristiques de ce phénomène qu’il faut inclure dans toute définition ou description du visage? Le visage est un événement fondamental. Parmi les multiples manières d’approcher l’être, de se rapporter...

Population-level biomedical research offers new opportunities to improve population health, but also raises new challenges to traditional systems of research governance and ethical oversight. Partly in response to these challenges, various models of public involvement in research are being introduced. Yet, the ways in which public involvement should meet governance challenges are not well understood. We conducted a qualitative study with 36 experts and stakeholders using the World Café method to identify key governance challenges and explore how public involvement can (...) meet these challenges. This brief report discusses four cross-cutting themes from the study: the need to move beyond individual consent; issues in benefit and data sharing; the challenge of delineating and understanding publics; and the goal of clarifying justifications for public involvement. The report aims to provide a starting point for making sense of the relationship between public involvement and the governance of population-level biomedical research, showing connections, potential solutions and issues arising at their intersection. We suggest that, in population-level biomedical research, there is a pressing need for a shift away from conventional governance frameworks focused on the individual and towards a focus on collectives, as well as to foreground ethical issues around social justice and develop ways to address cultural diversity, value pluralism and competing stakeholder interests. There are many unresolved questions around how this shift could be realised, but these unresolved questions should form the basis for developing justificatory accounts and frameworks for suitable collective models of public involvement in population-level biomedical research governance. (shrink)

Measuring neuronal activity with electrophysiological methods may be useful in detecting neurological dysfunctions, such as mild traumatic brain injury (mTBI). This approach may be particularly valuable for rapid detection in at-risk populations including military service members and athletes. Electrophysiological methods, such as quantitative electroencephalography (qEEG) and recording event-related potentials (ERPs) may be promising; however, the field is nascent and significant controversy exists on the efficacy and accuracy of the approaches as diagnostic tools. For example, the specific measures derived from an (...) electroencephalogram (EEG) that are most suitable as markers of dysfunction have not been clearly established. A study was conducted to summarize and evaluate the statistical rigor of evidence on the overall utility of qEEG as an mTBI detection tool. The analysis evaluated qEEG measures/parameters that may be most suitable as fieldable diagnostic tools, identified other types of EEG measures and analysis methods of promise, recommended specific measures and analysis methods for further development as mTBI detection tools, identified research gaps in the field, and recommended future research and development thrust areas. The qEEG study group formed the following conclusions: 1. Individual qEEG measures provide limited diagnostic utility for mTBI. However, many measures can be important features of qEEG discriminant functions, which do show significant promise as mTBI detection tools. 2. ERPs offer utility in mTBI detection. In fact, evidence indicates that ERPs can identify abnormalities in cases where EEGs alone are nondisclosing. 3. The standard mathematical procedures used in the characterization of mTBI EEGs should be expanded to incorporate newer methods of analysis including nonlinear dynamical analysis, complexity measures, analysis of causal interactions, graph theory and information dynamics. 4. and 5. are too long to include here. (shrink)

This volume presents twenty of the most important interviews the journal, Cogito conducted between 1987 and 1996. Covering a wide spectrum of intellectual inquiry, from logic to metaphysics to philosophy of mind, the interviews provide an excellent introduction to philosophy in the English speaking world at the end of the century. Interviews with: Michael Dummett Peter Strawson Alasdair MacIntyre David Gauthier Nancy Cartwright Mary Warnock Hilary Putnam Daniel Dennett Bernard Williams John Cottingham Willard Quine Stephen Korner Hugh Mellor Adam Morton (...) Jean Hampton Roger Scruton Richard Dawkins Richard Sorabji Derek Parfit Martha Nussbaum. (shrink)

Key Philosophers in Conversation is a fascinating collection of interviews presenting the ideas of some of the worlds leading contemporary philosophers. Each interview features a discussion with a key philosopher looking at philosophical issues such as; the philosophy of mind, ethics, science, political philosophy and the history of philosophy. Those interviewed are; W.V.O Quine, Michael Dummet, Mary Warnock, Hilary Putnam, Alasdair MacIntyre, Daniel Dennett, Martha Nussbaum, Roger Scruton, Bernard Williams, Jean Hampton, Richard Dawkins, Derek Parfit, Peter Strawson, David Gauthier, Hugh (...) Mellor, John Cottingham, Adam Morton, Stefan Korner, Richard Sorabji and Nancy Cartwright. This book offers an excellent insight to contemporary philosophy and is ideal for anyone seeking an introduction to what is happening in Philosophy today. (shrink)

Lenn E. Goodman is professor of philosophy and as the Andrew W. Mellon professor in the humanities at Vanderbilt University in Nashville, Tennessee. Trained in medieval Arabic and Hebrew philosophy and intellectual history, his prolific scholarship has covered the entire history of philosophy from antiquity to the present with a focus on medieval Jewish philosophy. A synthetic philosopher, Goodman has drawn on Jewish religious sources (e.g., Bible, Midrash, Mishnah, and Talmud) as well as philosophic sources (Jewish, Muslim, and Christian), (...) in an attempt to construct his own distinctive theory about the natural basis of morality and justice. Taking his cue from medieval Jewish philosophers such as Maimonides, Goodman offers a new theoretical framework for Jewish communal life that is attentive to contemporary philosophy and science. (shrink)

In a series of recent articles, Matthew Clayton, Andrew Williams and Rasmus Sommer Hansen and Soren Flinch Midtgaard argue that a key virtue of Ronald Dworkin’s account of distributive justice, Equality of Resources, is that it provides a distribution that is continuous with the evaluations of the individuals whom it ranges over. The idea of continuity, or as Williams calls it the ‘continuity test’, limits distributive claims in at least one important way: one person cannot claim compensation from another (...) when she does not believe she is worse off than him. In this article, I challenge whether an account of distributive justice should be continuous with the evaluations of the individuals whom it ranges over. My argument is that continuity competes with another consideration, namely, correctness. An account of distributive justice should track who actually is disadvantaged, not whether individuals believe they are disadvantaged. In addition, I offer an account of how we can get closer to a correct account of who is disadvantaged based on two sources of evidence. (shrink)

The value-free ideal for science prohibits noncognitive values from influencing the practice of science. After all, a scientist should not reject an empirical theory on religious grounds. But while motivated by reasonable concerns, VFI overlooks legitimate roles for noncognitive values in science. Contra VFI, Hugh Lacey explains that noncognitive values can promote scientific aims by grounding new methodologies that may lead to novel theories and extend to new domains. Yet, Lacey agrees with one aspect of VFI: noncognitive values should not (...) serve as grounds in the empirical evaluation of theories. This has led some critics to misidentify his view merely as an updated version of VFI. I argue that views of the kind Lacey endorses, which I call Dialectical Empiricism, deserve further investigation. They capture what VFI gets right; but they also show that noncognitive values are essential to good science. Throughout the dissertation I explore variants of DE, demonstrating its potential and flexibility. Furthermore, I defend DE against its critics, especially those who mistake it for a version of VFI. In stark opposition to VFI, DE reveals how the illusion of value-freedom sometimes blinds us to promising alternatives to mainstream scientific approaches. I demonstrate this by applying the framework of DE to contemporary research in agricultural and nutritional science. These case studies show that noncognitive values really do influence scientific practices. And, most importantly, they demonstrate how embracing a value-laden view of science can open our eyes to promising alternative approaches that may have the potential to increase our knowledge of the world and of possibilities for human flourishing. (shrink)

In this paper I discuss a recent exchange of articles between Hugh McLachlan and John Coggon on the relationship between omissions, causation, and moral responsibility. My aim is to contribute to their debate by isolating a presupposition I believe they both share and by questioning that presupposition. The presupposition is that, at any given moment, there are countless things that I am omitting to do. This leads both McLachlan and Coggon to give a distorted account of the relationship between causation (...) and moral or (as the case may be) legal responsibility and, in the case of Coggon, to claim that the law’s conception of causation is a fiction based on policy. Once it is seen that this presupposition is faulty, we can attain a more accurate view of the logical relationship between causation and moral responsibility in the case of omissions. This is important because it will enable us, in turn, to understand why the law continues to regard omissions as different, both logically and morally, from acts, and why the law seeks to track that logical and moral difference in the legal distinction it draws between withholding life-sustaining measures and euthanasia. (shrink)

Hugh LaFollette proposed parental licensing in 1980 (and 2010)--not as a requirement for pregnancy, but for raising a child. If you have a baby, are not licensed, and do not get licensed, the baby would be put up for adoption. Despite the intervention required in an extremely personal area of life, I argue that those who endorse the harm principle ought to endorse parental licensing of this sort. Put differently, I show how the harm principle strengthens the case for parental (...) licensing. (shrink)

Kirsten Macfarlane’s Biblical Scholarship in an Age of Controversy: The Polemical World of Hugh Broughton (1549–1612) is a work of deep erudition, graceful narration, and trenchant argumentation. M...

This is an opinionated guide to the literature on epistemic dilemmas. It discusses seven kinds of situations where epistemic dilemmas appear to arise; dilemmic, dilemmish, and non-dilemmic takes on them; and objections to dilemmic views along with dilemmist’s replies to them.

Daniel Greco (forthcoming) argues that there cannot be epistemic dilemmas. I argue that he is wrong. I then look in detail at a would-be epistemic dilemma and argue that no non-dilemmic approach to it can be made to work. Along the way, there is discussion of octopuses, lobsters, and other ‘inscrutable cognizers’; the relationship between evaluative and prescriptive norms; a failed attempt to steal a Brueghel; epistemic and moral blame and residue; an unbearable guy who thinks he’s God’s gift to (...) women; excuses; stupid games involving hats; radical permissivism; how I’ll never be able to afford to buy a house in Hampstead; and many other exciting topics. (shrink)

This paper examines the idea of objective phenomenology, or a way of understanding the phenomenal character of conscious experiences that doesn’t require one to have had the kinds of experiences under consideration. My central thesis is that structural facts about experience—facts that characterize purely how conscious experiences are structured—are objective phenomenal facts. I begin by precisifying the idea of objective phenomenology and diagnosing what makes any given phenomenal fact subjective. Then I defend the view that structural facts about experience are (...) objective. I also argue that structural facts about experience, despite being objective, nevertheless still give rise to an explanatory gap. (shrink)

As the principle of natural selection is generalized to explain (adaptive) patterns of human behavior, it becomes less clear what the selective environment empirically refers to. While the environment and individual are relatively separable in the non-human biological context, they are highly entangled in the context of moral, social, and institutional evolution. This chapter brings attention to the problem of generalizing the selective environment, and argues that it is ontologically disunified and definable only through its explanatory function. What unifies the (...) selective environment is that it explains adaptation in a non-agential way, by screening off various forms of agency, whether divine, organismic, or human. This explanatory function of the selective environment helps avoid some sources of confusion when the theory of natural selection is applied to humanities and social sciences. (shrink)

Philosophers often claim that humility is a dependent virtue: a virtue that depends on another virtue for its value. I consider three views about this relation: Specific Dependence, Unspecific Dependence, and Fittingness. I argue that, since humility cannot uniquely depend on another virtue, and since this uniqueness is desirable, we should reject Specific and Unspecific Dependence. I defend a Fittingness view, according to which the humble person possesses some objectively good quality fitting for humility. I show beyond Slote’s original characterization (...) of the dependence relation that, even if humility’s value depends on having objectively good qualities, humility itself can be one such quality. So, humility can depend on itself. I call this view Bootstrapped Fittingness. (shrink)

Some accounts of moral responsibility hold that an agent's responsibility is completely determined by some aspect of the agent's mental life at the time of action. For example, some hold that an agent is responsible if and only if there is an appropriate mesh among the agent's particular psychological elements. It is often objected that the particular features of the agent's mental life to which these theorists appeal (such as a particular structure or mesh) are not necessary for responsibility. This (...) is because there appear to be cases in which an agent acts at an earlier time which causes her to lack the appropriate psychological features at some later time and yet, intuitively, she is responsible at that later .. (shrink)

Perception is riddled with cases of reliable misperception. These are cases in which a perceptual state is tokened inaccurately any time it is tokened under normal conditions. On the face of it, this fact causes trouble for theories that provide an analysis of perceptual content in non-semantic, non-intentional, and non-phenomenal terms, such as those found in Millikan (1984), Fodor (1990), Neander (2017), and Schellenberg (2018). I show how such theories can be extended so that they cover such cases without giving (...) up their core commitments. (shrink)

Recasts Plutarch's Lives as a work of political philosophy emerging from the imperial encounter of Greece and Rome.

This volume is a philosophical introduction and exploration of the nature and value of personal relationships. It is an ideal text for introductory philosophy, ethics, or applied ethics courses.

In this article we discuss two divergent accounts of non-human animals as analog models of human biomedical phenomena. Using a classical account of analogical reasoning, toxicologists and teratologists claim that if the model and subject modeled are substantially similar, then test results in non-human animals are likely applicable to humans. However, the same toxicologists report that different species often react very differently to the same chemical stimuli. The best way to understand their findings is to abandon the classical view of (...) analogical - i.e., linear - reasoning, and replace it with a version informed by chaos theory. We briefly outline the current understanding of chaos, and trace its implications for toxicology and teratology. (shrink)

We are all familiar with the phenomenon of a proposition seeming true. Many think that these seeming states can yield justified beliefs. Very few have seriously explored what these seeming states are. I argue that seeming states are not plausibly analyzed in terms of beliefs, partial beliefs, attractions to believe, or inclinations to believe. Given that the main candidates for analyzing seeming states are unsatisfactory, I argue for a brute view of seemings that treats seeming states as irreducible propositional attitudes.

This is a discussion of the state of discussion on pragmatic reasons for belief.

This book brings together an international group of scholars to discuss the ramifications of Heidegger's Black Notebooks for philosophy and the humanities. In contrast to both those who seek to exonerate Heidegger and those who simply condemn him, they urge careful reading and rereading of his work to turn Heideggerian thought against itself.

Many assume that whenever government is entitled to make a law, it is entitled to enforce that law coercively. I argue that the justification of legal authority and the justification of governmental coercion come apart. Both in ideal theory and in actual human societies, governments are sometimes entitled to make laws that they are not entitled to enforce coercively.

For Kant, knowledge involves certainty. If “certainty” requires that the grounds for a given propositional attitude guarantee its truth, then this is an infallibilist view of epistemic justification. Such a view says you can’t have epistemic justification for an attitude unless the attitude is also true. Here I want to defend an alternative fallibilist interpretation. Even if a subject has grounds that would be sufficient for knowledge if the proposition were true, the proposition might not be true. And so there (...) is sometimes still rational room for doubt. The goal of this paper is to present four different models of what “certainty” amounts to, for Kant, each of which is compatible with fallibilism. (shrink)

In his 1978 paper “Mathematical Explanation”, Mark Steiner attempts to modernize the Aristotelian idea that to explain a mathematical statement is to deduce it from the essence of entities figuring in the statement, by replacing talk of essences with talk of “characterizing properties”. The language Steiner uses is reminiscent of language used for proofs deemed “pure”, such as Selberg and Erdős’ elementary proofs of the prime number theorem avoiding the complex analysis of earlier proofs. Hilbert characterized pure proofs as those (...) that use only “means that are suggested by the content of the theorem”, a characterization we have elsewhere called “topical purity”. In this paper we will examine the connection between Steiner’s account of mathematical explanation and topical purity. Are Steiner-explanatory proofs necessarily topically pure? Are topically pure proofs necessarily Steiner-explanatory? Answers to these questions will shed light on the general question of the relation between purity and explanatory power. (shrink)

The aim of the Analytic of Concepts is to derive and deduce a set of pure concepts of the understanding, the categories, which play a central role in Kant’s explanation of the possibility of synthetic a priori cognition and judgment. This chapter is structured around two questions. First, what is a pure concept of the understanding? Second, what is involved in a deduction of a pure concept of the understanding? In answering the first, we focus on how the categories differ (...) from the pure forms of sensibility and examine whether they are known only to be the pure forms of human thinking or rather the forms of discursive cognition as such. In answering the second, we draw a distinction between the application and the exemplification of the categories and use it to identify different ways of understanding Kant’s project in the Transcendental Deduction of the Categories. These questions connect because the answer to the first determines how we should understand the kind of entitlement which is to be established in the Deduction. (shrink)

While many aspects of cognition have been shown to be shared between humans and non-human animals, there remains controversy regarding whether the capacity to mentally time travel is a uniquely human one. In this paper, we argue that there are four ways of representing when some event happened: four kinds of temporal representation. Distinguishing these four kinds of temporal representation has five benefits. First, it puts us in a position to determine the particular benefits these distinct temporal representations afford an (...) organism. Second, it provides the conceptual resources to foster a discussion about which of these representations is necessary for an organism to count as having the capacity to mentally time travel. Third, it enables us to distinguish stricter from more liberal views of mental time travel that differ regarding which kind(s) of temporal representation is taken to be necessary for mental time travel. Fourth, it allows us to determine the benefits of taking a stricter or more liberal view of mental time travel. Finally, it ensures that disagreement about whether some species can mentally time travel is not merely the product of unrecognised disagreement about which temporal representation is necessary for mental time travel. We argue for a more liberal view, on the grounds that it allows us to view mental time travel as an evolutionarily continuous phenomenon, and to recognise that differences in the ways that organisms mentally time travel might reflect different temporal representations, or combinations thereof, that they employ. Our ultimate aim, however, is to create the conceptual framework for further discussion regarding what sorts of temporal representations are required for mental time travel. (shrink)

The utterance “I am humble” is thought to be paradoxical because a speaker implies that they know they are virtuous or reveals an aim to impress others – a decidedly non-humble aim. Such worries lead to the seemingly absurd conclusion that a humble person cannot properly assert that they are humble. In this paper, I reconstruct and evaluate three purported paradoxes of humility concerning its self-attribution, knowledge and belief about our own virtue, and humility's value. I argue that humility is (...) not genuinely paradoxical and that these puzzles do not have meaningful implications for its conceptual analyses. I instead offer error theoretical explanations of humility's apparent paradoxicality. (shrink)