Through their transcript products genes regulate the rates at which an immense variety of transcripts and subsequent proteins occur. Understanding the mechanisms that determine which genes are expressed, and when they are expressed, is one of the keys to genetic manipulation for many purposes, including the development of new treatments for disease. Viewing each gene in a genome as a distinct variable that is either on or off, or more realistically as a continuous variable, the values of some of these (...) variables influence the values of others through the regulatory proteins they express, including, of course, the possibility that the rate of expression of a gene at one time may, in various circumstances, influence the rate of expression of that same gene at a later time. If we imagine an arrow drawn from each gene expression variable at a given time to a gene variable whose expression it influences a short while after, the result is a network, technically a directed acyclic graph. For example, the DAG in Figure 1 is a representation of a system in which the expression level of gene G1 at time 1 ) causes the expression level of G2, which in turn causes the expression level of G3. The arrows in Figure 1 which do not have a variable at their tails are “error terms” which represent all of the causes of a variable other than the ones explicitly represented in the DAG. The DAG describes more than associations—it describes causal connections among gene expression rates. A shock to a cell—by mutation, heating, chemical treatment, etc. may alter the DAG describing the relations among gene expressions, for example by activating a gene that was otherwise not expressed, producing a cascade of new expression effects. Although “knockout” experiments can reveal some of the underlying causal network of gene expression levels, unless guided by information from other sources, such experiments are limited in how much of the network structure they can reveal, due to the sheer number of possible combinations of experimental manipulations of genes necessary to reveal the complete causal network. Recent developments have made it possible to compare quantitatively the expression of tens of thousands of genes in cells from different sources in a single experiment, and to trace gene expression over time in thousands of genes simultaneously. cDNA microarrays are already producing extensive data, much of it available on the web. Thus there are calls for analytic software that can be applied to microarray and other data to help infer regulatory networks. In this paper we will review current techniques that are available for searching for the causal relations between variables, describe algorithmic and data gathering obstacles to applying these techniques to gene expression levels, and describe the prospects for overcoming these obstacles. (shrink)

During the set-up phase of an international study of genetic influences on outcomes from sepsis, we aimed to characterise potential differences in ethics approval processes and outcomes in participating European countries. Between 2005 and 2007 of the FP6-funded international Genetics Of Sepsis and Septic Shock project, we asked national coordinators to complete a structured survey of research ethic committee approval structures and processes in their countries, and linked these data to outcomes. Survey findings were reconfirmed or modified in 2017. Eighteen (...) countries participated in the study, recruiting 2257 patients from 160 ICUs. National practices differed widely in terms of composition of RECs, procedures and duration of the ethics approval process. Eight countries used a single centralised process for approval, seven required approval by an ethics committee in each participating hospital, and three required both. Outcomes of the application process differed widely between countries because of differences in national legislation, and differed within countries because of interpretation of the ethics of conducting research in patients lacking capacity. The RECs in four countries had no lay representation. The median time from submission to final decision was 1.5 months; in nine approval was received within 1 month; six took over 6 months, and in one 24 months; had all countries been able to match the most efficient approvals processes, an additional 74 months of country or institution-level recruitment would have been available. In three countries, rejection of the application by some local RECs resulted in loss of centres; and one country rejected the application outright. The potential benefits of the single application portal offered by the European Clinical Trials Regulation will not be realised without harmonisation of research ethics committee practices as well as national legislation. (shrink)

In this thorough compendium, nineteen accomplished scholars explore, in some manner the values they find inherent in the world, their nature, and revelence through the thought of Frederick Ferré. These essays, informed by the insights of Ferré and coming from manifold perspectives—ethics, philosophy, theology, and environmental studies, advance an ambitious challenge to current intellectual and scholarly fashions.

Throughout the biological and biomedical sciences there is a growing need for, prescriptive ‘minimum information’ (MI) checklists specifying the key information to include when reporting experimental results are beginning to find favor with experimentalists, analysts, publishers and funders alike. Such checklists aim to ensure that methods, data, analyses and results are described to a level sufficient to support the unambiguous interpretation, sophisticated search, reanalysis and experimental corroboration and reuse of data sets, facilitating the extraction of maximum value from data sets (...) them. However, such ‘minimum information’ MI checklists are usually developed independently by groups working within representatives of particular biologically- or technologically-delineated domains. Consequently, an overview of the full range of checklists can be difficult to establish without intensive searching, and even tracking thetheir individual evolution of single checklists may be a non-trivial exercise. Checklists are also inevitably partially redundant when measured one against another, and where they overlap is far from straightforward. Furthermore, conflicts in scope and arbitrary decisions on wording and sub-structuring make integration difficult. This presents inhibit their use in combination. Overall, these issues present significant difficulties for the users of checklists, especially those in areas such as systems biology, who routinely combine information from multiple biological domains and technology platforms. To address all of the above, we present MIBBI (Minimum Information for Biological and Biomedical Investigations); a web-based communal resource for such checklists, designed to act as a ‘one-stop shop’ for those exploring the range of extant checklist projects, and to foster collaborative, integrative development and ultimately promote gradual integration of checklists. (shrink)

In this thorough compendium, nineteen accomplished scholars explore, in some manner the values they find inherent in the world, their nature, and revelence through the thought of Frederick FerrZ. These essays, informed by the insights of FerrZ and coming from manifold perspectives—ethics, philosophy, theology, and environmental studies, advance an ambitious challenge to current intellectual and scholarly fashions.

We outline two points of criticism. Firstly, we argue that robots do constitute a separate category of beings in people's minds rather than being mere depictions of non-robotic characters. Secondly, we find that (semi-)automatic processes underpinning communicative interaction play a greater role in shaping robot-directed speech than Clark and Fischer's theory of social robots as depictions indicate.

On June 11, 1963, in a dramatic gesture that caught the nation's attention, Governor George Wallace physically blocked the entrance to Foster Auditorium on the University of Alabama's campus. His intent was to defy Attorney General Nicholas Katzenbach, sent on behalf of the Kennedy administration to force Alabama to accept court-ordered desegregation. After a tense confrontation, President Kennedy federalized the Alabama National Guard and Wallace backed down, allowing Vivian Malone and James Hood to become the first African Americans to enroll (...) successfully at their state's flagship university. That night, John F. Kennedy went on television to declare civil rights a "moral issue" and to commit his administration to this cause. That same night, Medgar Evers was shot dead. In The Schoolhouse Door, E. Culpepper Clark provides a riveting account of the events that led to Wallace's historic stand, tracing a tangle of intrigue and resistance that stretched from the 1940s, when the university rejected black applicants outright, to the post-Brown v. Board of Education era. We are there in July 1955 when Thurgood Marshall and lawyers at the NAACP Legal Defense Fund win for Autherine Lucy and "all similarly situated" the right to enroll at the university. We are in the car with Lucy in February 1956 as university officials escort her to class, shielding her from a mob jeering "Lynch the nigger," "Keep 'Bama white," and "hit the nigger whore." Clark exposes the many means, including threats and intimidation, used by university and state officials to discourage black applicants following the Lucy episode. And he explains how University of Alabama president Frank Anthony Rose eventually cooperated with the Kennedy administration to ensure a smooth transition toward desegregation. We also witness Robert Kennedy's remarkable face-to-face plea for Wallace's cooperation and the governor's adamant refusal: "I will never submit voluntarily to any integration in a school system in Alabama." As Clark writes, Wallace's carefully orchestrated surrender would leave the forces of white supremacy free to fight another day. And the Kennedys' public embrace of the civil rights movement would set in motion a political transformation that changed the presidential base of the Democratic party for the next thirty years. In these pages, full of courageous black applicants, fist-shaking demonstrators, and powerful politicians, Clark captures the dramatic confrontations that transformed the University of Alabama into a proving ground for the civil rights movement and gave the nation unforgettable symbols for its struggle to achieve racial justice. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:“The Whole Internal World His Own”: Locke and Metaphor ReconsideredS. H. ClarkWhy need I name thy Boyle, whose pious search, Amid the dark recesses of his works, The great Creator sought? And why thy Locke, Who made the whole internal world his own?Oh decus! Anglicae certe oh lux altera gentis!... Tu caecas rerum causas, fontemque severum Pande, Pater; tibi enim, tibi, veri magne Sacerdos, Corda patent hominum, atque altae (...) penetralia Mentis.Fourfold Annihilation & at the clangor of the Arrows of Intellect The innumerable Chariots of the Almighty appeard in Heaven And Bacon & Newton & Locke, & Milton & Shakespear & Chaucer1Two features of these encomia to John Locke, composed by James Thomson, Thomas Gray, and William Blake, are immediately striking. Firstly, they are delivered by poets in a tradition customarily seen as a reaction to the intellectual climate induced by Locke’s Essay, a book which Blake famously claimed to regard with “Contempt and Abhorrence.” 2 Secondly, the familiar and somewhat hackneyed characterizations of Locke as philosopher of common-sense, [End Page 241] empiricism, and liberal ideology are refreshingly absent. For Gray he is “veri magne Sacerdos,” great priest of truth; Thomson places him in a pantheon including Shakespeare, Milton, Spenser, and Chaucer; and this ranking is explicitly endorsed in Blake’s “Milton & Shakspear & Chaucer.” Comparable praise of Locke’s imaginative power is conspicuously absent from even the most generous tributes of recent commentators. 3Even if Locke’s philosophical contribution to a variety of debates is fully acknowledged, the question remains of why his major work, An Essay concerning Human Understanding, was held in such high popular esteem—veneration is not too strong a word—during the subsequent century. The text itself appears an improbable candidate for such canonization: George Saintsbury accused its prose of being “positively mean in every point of style,” 4 and certainly in comparison with the poised and lucid ironies of Berkeley and Hume, it cannot but appear prolix, diffuse, and repetitive. The chief (and frequently only) merit grudgingly accorded to it is of disarming informality. Rosalie Colie’s emphasis on the “exploitation of the generic and rhetorical possibilities in the essay form itself “ highlights the conscious manipulation of authorial distance through which Locke creates the effect of sprawling inclusiveness and incom-pletion, but at the expense of conceding that “in exchange for the frankness with which the essayist appeared to present his thinking self, he was allowed certain liberties from logical rigour.” 5 Though the suggestion that a major philosophical text seeks to evade “logical rigour” might seem damning enough, there is a still more insidious equation of Locke’s “middle-style,” his desire “to make, what I have to say, as easie and intelligible to all sort of Readers as I can,” with a complicity with the expectations of his audience. 6 Other critics, notably John Richetti, have put a more positive gloss on the “simple and fortuitously concocted circle of friends” to whom the Essay is addressed, but even these accounts have been obliged to stress the representative and consensual nature of Locke’s thought. 7 This view is perhaps most elegantly expressed by Leslie Stephen: “Locke ruled the thought of his own and the coming period [End Page 242] because he interpreted so completely the fundamental beliefs which had been worked out at this time. He ruled, that is, by obeying.” 8William Walker correctly observes that “identifying and interpreting metaphors of mind” in the Essay are “standard practices of mainstream philosophical commentary from Leibniz to Rorty,” but also notes that these analyses are usually concerned with the degree to which Locke’s reliance on figuration was at variance with and compromised his epistemological doctrine. 9 I would argue that the poetic tributes previously quoted offer a more suggestive and adequate guide to the original impact of his work. In order to substantiate this claim, I shall begin by examining Locke’s apparent renunciation of, yet paradoxical dependence upon metaphor; go on to look at the connection of the “Horizon” to the elegiac presentation of memory and the ethic of mental “Labour”; and conclude by analyzing the complex interdependence of candle and sun within the light imagery employed in the... (shrink)

It is widely alleged that metaphysical possibility is “absolute” possibility Conceivability and possibility, Clarendon, Oxford, 2002, p 16; Stalnaker, in: Stalnaker Ways a world might be: metaphysical and anti-metaphysical essays, Oxford University Press, Oxford, 2003, pp 201–215; Williamson in Can J Philos 46:453–492, 2016). Kripke calls metaphysical necessity “necessity in the highest degree”. Van Inwagen claims that if P is metaphysically possible, then it is possible “tout court. Possible simpliciter. Possible period…. possib without qualification.” And Stalnaker writes, “we can agree (...) with Frank Jackson, David Chalmers, Saul Kripke, David Lewis, and most others who allow themselves to talk about possible worlds at all, that metaphysical necessity is necessity in the widest sense.” What exactly does the thesis that metaphysical possibility is absolute amount to? Is it true? In this article, I argue that, assuming that the thesis is not merely terminological, and lacking in any metaphysical interest, it is an article of faith. I conclude with the suggestion that metaphysical possibility may lack the metaphysical significance that is widely attributed to it. (shrink)

Immortality is a subject which has long been explored and imagined by science fiction writers. In his intriguing new study, Stephen R.L.Clark argues that the genre of science fiction writing allows investigation of philosophical questions about immortality without the constraints of academic philosophy. He reveals how fantasy accounts of issues such as resurrection, disembodied survival, reincarnation and devices or drugs for preserving life can be used as an important resource for philosophical inquiry and examines how a society of immortals might (...) function through a reading of the vampire myth. _How to Live Forever_ is a compelling study which introduces students and professional philosophers to the possibilities of using science fiction in their work. It includes extensive suggestions for further reading, both fictional and philosophical, and examines the work of such major science fiction authors as _Arthur C. Clarke, Frank Herbert, Larry Niven, William Gibson_, and _Colin Wilson_. (shrink)

This article takes as its starting point the recent work of Frank Ankersmit on subjective historical experience. Such an experience, which Ankersmit describes as a ‘sudden obliteration of the rift between present and past’ is connected strongly with the Deweyan theory of art as experiential, which contains an account of aesthetic experience as affording a similar breakdown in the polarization of the subject and object of experience. The article shows how other ideas deriving from the phenomenological tradition and the (...) philosophy of perception can fruitfully be applied to the same terrain, and an account of aesthetic experience is built up that stresses embodied, differential and virtual aspects in the perception of aesthetic objects. The disruption and/or enhancement of these aisthetic aspects of perception, coupled with the self-conscious reflection thereby occasioned, is put forward as an account of aesthetic experience that links Ankersmit’s ideas with those of others, and a critical reading is made of a section of Ankersmit’s Sublime Historical Experience that centers on his experience of a painting by Francesco Guardi. The fijinal section aims at strengthening aspects of Ankersmit’s ideas and renews his critique of the radical constructivism of Oakeshott. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Consenting for Novel and Dangerous Surgical Procedures with Minimal Supporting EvidenceMichelle J. ClarkeFrank1 was a 19–year–old man referred to me after a workup for back pain led to the discovery of a large, aggressive tumor in his sacrum. The tumor wrapped around the nerves controlling bowel, bladder, and leg function. We performed a needle biopsy and learned that the tumor was an angiosarcoma, an extremely aggressive and usually deadly (...) form of cancer. However, the tumor was unique in that it theoretically could be cured if removed in one piece. But, to do so would necessitate sacrificing the nerves, leaving the patient irreversibly incontinent, lacking sexual function, and confined to a wheelchair.Once we knew the diagnosis, Frank came to the office with his family to discuss treatment options. He appeared terrified and was almost silent through the appointment, deferring most questions to his parents. Due to the speed of tumor growth, we discussed palliative therapy, conventional treatment, and the one–piece or “en bloc” surgery, which was new and unproven for his disease. Based on the remarkable tumor growth we noted during the work–up, with palliative treatment the patient would likely survive for less than six months. Conventional treatment, in which surgery is done to remove part of the tumor while sparing the nerves to bowel and bladder function, was known to have a high rate of recurrence and death. Further, this tumor didn’t respond well to radiation and chemotherapy, so chance of survival was limited, although his life might have been extended for a short period. Thus our conversation turned to the novel “en bloc” procedure.The en bloc procedure offered a hope of long–term survival unlike the other options. However, this came with an enormous cost. The surgery itself would be planned to occur over three days with five separate surgical teams and a very real chance of major complications or death. Nerves to bowel and bladder would be cut, irreversibly leaving the patient without sexual function, and completely incontinent with a urinary catheter and colostomy. Walking was expected to be disrupted or potentially impossible due to the nerve resection. We went to great lengths over the course of many visits to describe the impact of the surgery on the patient’s function, and the impact on his quality of life. To make matters more challenging, as this procedure was so new and the tumor so rare, research did not yet exist to quantify his likelihood of long–term survival.Personally I was very uncomfortable with the situation. From a medical standpoint, the surgery offered was the best distillation of research and professional experience. En bloc surgery offered the best—if not the only—chance for survival in [End Page 5] this young man. Additionally, having treated many spine–injured patients I was aware that many patients with similar deficits led happy and productive lives following an emotional and physical adjustment period. However the surgery was also extreme. I worried that we would not be able to accomplish the goal of a one–piece resection and would accidentally spill some of the tumor, creating all of the deficits but no survival benefit. Frankly, I thought there was a 25% chance that would happen, which was explained to the family preoperatively. Were we overreaching our abilities and making a dying patient’s life worse by proceeding?Second, I was uneasy about the social situation. The patient’s family was very supportive, traveling with him to all appointments and assisting with his care. The patient himself usually deferred all scheduling to his mother, which wasn’t entirely unusual for such a young man. However it was difficult to grasp how much the patient understood of his disease or supported the plan. We attempted to delve more deeply into his thoughts, including without his parents present, but got only short answers, which revealed little. While the family appeared to have accepted the diagnosis and wanted to get to the business of treatment, the patient seemed to me to still carry the shock of his recent cancer diagnosis. Pushed by the rapid tumor growth, we were limited in how long we could wait for... (shrink)

Despite the controversial nature of studies of reproductive phenomena, a major center of reproductive biology emerged and coalesced in the Department of Zoology at the University of Chicago circa 1892–1940. Led by Frank R. Lillie, several small groups of researchers pioneered the study of sex determination and sex hormones, pursuing these via a Chicago approach to framing biological practice at both cellular and organismic levels. They worked in an interdisciplinary manner, however much in tandem, and drew strongly on local (...) resources—from the stockyards to local philanthropy. Most remarkably, Lillie redirected the mission of the major National Research Council Committee for Research Problems of Sex to address the biology of sex and then garnered about a fifth of its funds for Chicago. He thus guided Chicago biology into the fully modern era of external support for on-campus research and elaborate national scientific networks via promising biological solutions to social problems. (shrink)

This book considers the significance of this confluence through an examination of myths in the writings of H. G. Wells, Arthur C. Clarke, Philip K. Dick and Frank Herbert. Presenting fresh insights into their works, the author brings to light the tendency of science fiction narratives to reaffirm spiritual myths.

Do we directly perceive physical objects? What is the significance of the qualification ‘directly’ here? Austin famously denied that there was a unique interpretation by which we could make sense of the traditional debate in the philosophy of perception. I look here at Thompson Clarke’s discussion of G. E. Moore and surface perception to answer Austin’s scepticism.

It is widely agreed that the intelligibility of modal metaphysics has been vindicated. Quine's arguments to the contrary supposedly confused analyticity with metaphysical necessity, and rigid with non-rigid designators.2 But even if modal metaphysics is intelligible, it could be misconceived. It could be that metaphysical necessity is not absolute necessity – the strictest real notion of necessity – and that no proposition of traditional metaphysical interest is necessary in every real sense. If there were nothing otherwise “uniquely metaphysically significant” about (...) metaphysical necessity, then paradigmatic metaphysical necessities would be necessary in one sense of “necessary”, not necessary in another, and that would be it. The question of whether they were necessary simpliciter would be like the question of whether the Parallel Postulate is true simpliciter – understood as a pure mathematical conjecture, rather than as a hypothesis about physical spacetime. In a sense, the latter question has no objective answer. In this article, I argue that paradigmatic questions of modal metaphysics are like the Parallel Postulate question. I then discuss the deflationary ramifications of this argument. I conclude with an alternative conception of the space of possibility. According to this conception, there is no objective boundary between possibility and impossibility. Along the way, I sketch an analogy between modal metaphysics and set theory. (shrink)

Jerry Fodor deemed informational encapsulation ‘the essence’ of a system’s modularity and argued that human perceptual processing comprises modular systems, thus construed. Nowadays, his conclusion is widely challenged. Often, this is because experimental work is seen to somehow demonstrate the cognitive penetrability of perceptual processing, where this is assumed to conflict with the informational encapsulation of perceptual systems. Here, I deny the conflict, proposing that cognitive penetration need not have any straightforward bearing on the conjecture that perceptual processing is composed (...) of nothing but informationally encapsulated modules, the conjecture that each and every perceptual computation is performed by an informationally encapsulated module, and the consequences perceptual encapsulation was traditionally expected to have for a perception-cognition border, the epistemology of perception and cognitive science. With these points in view, I propose that particularly plausible cases of cognitive penetration would actually seem to evince the encapsulation of perceptual systems rather than refute/problematize this conjecture. (shrink)

The approximate number system (ANS) enables organisms to represent the approximate number of items in an observed collection, quickly and independently of natural language. Recently, it has been proposed that the ANS goes beyond representing natural numbers by extracting and representing rational numbers (Clarke & Beck, 2021a). Prior work demonstrates that adults and children discriminate ratios in an approximate and ratio-dependent manner, consistent with the hallmarks of the ANS. Here, we use a well-known “connectedness illusion” to provide evidence that (...) these ratio-dependent ratio discriminations are (a) based on the perceived number of items in seen displays (and not just non-numerical confounds), (b) are not dependent on verbal working memory, or explicit counting routines, and (c) involve representations with a part-whole (or subset-superset) format, like a fraction, rather than a part-part format, like a ratio. These results vindicate key predictions of the hypothesis that the ANS represents rational numbers. (shrink)

On a now orthodox view, humans and many other animals possess a “number sense,” or approximate number system, that represents number. Recently, this orthodox view has been subject to numerous critiques that question whether the ANS genuinely represents number. We distinguish three lines of critique – the arguments from congruency, confounds, and imprecision – and show that none succeed. We then provide positive reasons to think that the ANS genuinely represents numbers, and not just non-numerical confounds or exotic substitutes for (...) number, such as “numerosities” or “quanticals,” as critics propose. In so doing, we raise a neglected question: numbers of what kind? Proponents of the orthodox view have been remarkably coy on this issue. But this is unsatisfactory since the predictions of the orthodox view, including the situations in which the ANS is expected to succeed or fail, turn on the kind of number being represented. In response, we propose that the ANS represents not only natural numbers, but also non-natural rational numbers. It does not represent irrational numbers, however, and thereby fails to represent the real numbers more generally. This distances our proposal from existing conjectures, refines our understanding of the ANS, and paves the way for future research. (shrink)

It is often assumed that adaptation — a temporary change in sensitivity to a perceptual dimension following exposure to that dimension — is a litmus test for what is and is not a “primary visual attribute”. Thus, papers purporting to find evidence of number adaptation motivate a claim of great philosophical significance: That number is something that can be seen in much the way that canonical visual features, like color, contrast, size, and speed, can. Fifteen years after its reported discovery, (...) number adaptation’s existence seems to be nearly undisputed, with dozens of papers documenting support for the phenomenon. The aim of this paper is to offer a counterweight — to critically assess the evidence for and against number adaptation. After surveying the many reasons for thinking that number adaptation exists, we introduce several lesser-known reasons to be skeptical. We then advance an alternative account — the old news hypothesis — which can accommodate previously published findings while explaining various (otherwise unexplained) anomalies in the existing literature. Next, we describe the results of eight pre-registered experiments which pit our novel old news hypothesis against the received number adaptation hypothesis. Collectively, the results of these experiments undermine the number adaptation hypothesis on several fronts, whilst consistently supporting the old news hypothesis. More broadly our work raises questions about the status of adaptation itself as a means of discerning what is and is not a visual attribute. (shrink)

Although Aristotle (Metaphysics, Book IV, Chapter 2) was perhaps the first person to consider the part-whole relationship to be a proper subject matter for philosophic inquiry, the Polish logician Stanislow Lesniewski [15] is generally given credit for the first formal treatment of the subject matter in his Mereology.1 Woodger [30] and Tarski [24] made use of a specific adaptation of Lesniewski's work as a basis for a formal theory of physical things and their parts. The term 'calculus of individuals' was (...) introduced by Leonard and Goodman [14] in their presentation of a system very similar to Tarski's adaptation of Lesniewski's Mereology. Contemporaneously with Lesniewski's development of his Mereology, Whitehead [27] and [28] was developing a theory of extensive abstraction based on the two-place predicate, 'x extends over y\ which is the converse of 'x is a part of y\ This system, according to Russell [22], was to have been the fourth volume of their Pήncipia Mathematica, the never-published volume on geometry. Both Lesniewski [15] and Tarski [25] have recognized the similarities between Whitehead's early work and Lesniewski's Mereology. Between the publication of Whitehead's early work and the publication of Process and Reality [29], Theodore de Laguna [7] published a suggestive alternative basis for Whitehead's theory. This led Whitehead, in Process and Reality, to publish a revised form of his theory based on the two-place predicate, 'x is extensionally connected with y\ It is the purpose of this paper to present a calculus of individuals based on this new Whiteheadian primitive predicate. (shrink)

Scanlon’s Being Realistic about Reasons (BRR) is a beautiful book – sleek, sophisticated, and programmatic. One of its key aims is to demystify knowledge of normative and mathematical truths. In this article, I develop an epistemological problem that Scanlon fails to explicitly address. I argue that his “metaphysical pluralism” can be understood as a response to that problem. However, it resolves the problem only if it undercuts the objectivity of normative and mathematical inquiry.