It has long been recognized that cancer onset and progression represent a type of reversion to an ancestral quasi‐unicellular phenotype. This general concept has been refined into the atavistic model of cancer that attempts to provide a quantitative analysis and testable predictions based on genomic data. Over the past decade, support for the multicellular‐to‐unicellular reversion predicted by the atavism model has come from phylostratigraphy. Here, we propose that cancer onset and progression involve more than a one‐off multicellular‐to‐unicellular reversion, and are (...) better described as a series of reversionary transitions. We make new predictions based on the chronology of the unicellular‐eukaryote‐to‐multicellular‐eukaryote transition. We also make new predictions based on three other evolutionary transitions that occurred in our lineage: eukaryogenesis, oxidative phosphorylation and the transition to adaptive immunity. We propose several modifications to current phylostratigraphy to improve age resolution to test these predictions. Also see the video abstract here: https://youtu.be/3unEu5JYJrQ. (shrink)

In their simplest form, hybrid languages are propositional modal languages which can refer to states. They were introduced by Arthur Prior, the inventor of tense logic, and played an important role in his work: because they make reference to specific times possible, they remove the most serious obstacle to developing modal approaches to temporal representation and reasoning. However very little is known about the computational complexity of hybrid temporal logics.In this paper we analyze the complexity of the satisfiability problem of (...) a number of hybrid temporal logics: the basic hybrid language over transitive trees; nominal Until logic; and referential interval logic. We discuss the effects of including nominals, the @ operator, the somewhere modality E, and the difference operator D. Adding nominals to tense logic leads for several frame-classes to an increase in complexity of the satisfiability problem from PSPACE to EXPTIME. On transitive trees, however, the satisfiability problem for this language can be decided in PSPACE. Along the way we make a detour through hybrid propositional dynamic logic: we establish upper bounds for a number of temporal logics by generalizing results due to Passy and Tinchev [29] and De Giacomo [16]. We conclude with some remarks on the relevance of our results to description logic, and draw attention to the utility of the spypoint technique for proving upper and lower bounds. (shrink)

\noindent\textbf{Introduction} Online interventions hold great potential for Therapeutic Change Process Research (TCPR), a field that aims to relate in-therapeutic change processes to the outcomes of interventions. Online a client is treated essentially through the language their counsellor uses, therefore the verbal interaction contains many important ingredients that bring about change. TCPR faces two challenges: how to derive meaningful change processes from texts, and secondly, how to assess these complex, varied and multi-layered processes? We advocate the use text mining and multi-level (...) models (MLMs): the former offers tools and methods to discovers patterns in texts; the latter can analyse these change processes as outcomes that vary at multiple levels. \noindent\textbf{Method} We (re-)used the data from \cite{Lamers2015} because it includes outcomes and the complete online intervention for clients with mild depressive symptoms. We used text mining to obtain basic text-variables from e-mails, that we analysed through MLMs. \noindent\textbf{Results} We found that we could relate outcomes of interventions to variables containing text-information. We conclude that we can indeed bridge text mining and MLMs for TCPR as it was possible to relate text-information (obtained through text mining) to multi-levelled TCPR outcomes (using a MLM). \noindent\textbf{Discussion} Text mining can be helpful to obtain change processes, which is also the main challenge for TCPR. We showed how MLMs and text mining can be combined, but our proposition leaves open how to obtain the most relevant textual operationalization of TCPR concepts. That requires interdisciplinary collaboration and discussion. The future does look bright: based on our proof-of-concept study we conclude that MLMs and text mining can indeed advance TCPR. (shrink)

Increasing ethical attention and debate is focusing on whether individuals who take part in clinical trials should be given access to post-trial care. However, the main focus of this debate has been upon drug trials undertaken in low-income settings. To broaden this debate, we report findings from interviews with individuals (n = 24) who participated in a clinical trial of a closed-loop system, which is a medical device under development for people with type 1 diabetes that automatically adjusts blood glucose (...) to help keep it within clinically recommended ranges. Individuals were recruited from UK sites and interviewed following trial close-out, at which point the closed-loop had been withdrawn. While individuals were stoical and accepting of the requirement to return the closed-loop, they also conveyed varying degrees of distress. Many described having relaxed diabetes management practices while using the closed-loop and having become deskilled as a consequence, which made reverting back to pre-trial regimens challenging. Participants also described unanticipated consequences arising from using a closed-loop. As well as deskilling, these included experiencing psychological and emotional benefits that could not be sustained after the closed-loop had been withdrawn and participants reevaluating their pre- and post-trial life in light of having used a closed-loop and now perceiving this life much more negatively. Participants also voiced frustrations about experiencing better blood glucose control using a closed-loop and then having to revert to using what they now saw as antiquated and imprecise self-management tools. We use these findings to argue that ethical debates about post-trial provisioning need to be broadened to consider potential psychological and emotional harms, and not just clinical harms, that may result from withdrawal of investigated treatments. We also suggest that individuals may benefit from information about potential nonclinical harms to help make informed decisions about trial participation. (shrink)

Although Broad published many books in his lifetime, this volume is unique in presenting some of his most interesting unpublished writings. Divided into five clear sections, the following figures and topics are covered: Autobiography, Hegel and the nature of philosophy, Francis Bacon, Hume's philosophy of the self and belief, F. H. Bradley, The historical development of scientific thought from Pythagoras to Newton, Causation, Change and continuity, Quantitative methods, Poltergeists, Paranormal phenomena. -/- Each section is introduced and placed in context by (...) the editor, Joel Walmsley. The volume also includes an engaging and informative foreword by Simon Blackburn. It will be of great value to those studying and researching the history of twentieth-century philosophy, metaphysics, and the recent history and philosophy of science, as well as anyone interested in Broad's philosophical thought and his place in the history of philosophy. (shrink)

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that (...) has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility. (shrink)

This article describes the spiritual formation training program for counseling students at Richmont Graduate University, an evangelical institution providing Master’s-level instruction for counselors and ministers. This model of spiritual formation has a dual foundation which includes the centrality of love to the Christian life and the importance of attachment to the development of persons. The training is intentionally designed to invite students to pursue a more secure attachment to God, healthier relationships with others, and a more grace-based self-awareness. Integrative and (...) clinical instruction, and experiences that foster establishment of secure attachment are described. Co-curricular efforts in research and student advisement focus on grace and wellness, as well as opportunities for service, and these serve to further contribute to a supportive environment for spiritual formation. (shrink)

Simon Blackburn. 1985. Garrett, Don. Cognition and Commitment in Hume's Philosophy. Oxford: Oxford University Press, 1997. Gaskin, J.C. A. Hume's Philosophy of Religion, 2nd ed. Basingstoke: Macmillan, 1988. Holden, T.The Architecture ...

Lewis has argued that quasi-realism is fictionalism. Blackburn denies this, offering reasons which rely on a descriptive reading of quasi-realism. This note offers a different, more general argument against Lewis's claim, available to prescriptive as well as descriptive quasi-realists.

I argue that mind-independence realism should be characterised in terms of what I call 'essential', rather than 'modal', independence from our mental lives. I explore the connections between the two kinds of independence, and argue that characterizations in terms of essence respect more intuitions about what realism is, harmonize better with standard characterizations of anti-realism, and avert the threat of subversion from Blackburn's quasi-realist.

Are the relations between the property of a thing and its related disposition to react in certain ways, and between the triggering of that disposition and the consequent effect, necessary? Harré and Madden, in their analysis of causal powers, said they are, but their arguments are not persuasive. Humeans like Simon Blackburn deny it. I criticize the Humean position, and argue afresh for their necessity. I note that David Lewis' analysis of causation requires their necessity, though as a confessed (...) Humean he has not admitted this. (shrink)

We can describe certain actions as defective in a particular virtue, for example, as “unjust” or “intemperate.” We can take the additional step of describing such actions as “morally wrong” or “contrary to moral obligation.” A key claim of Elizabeth Anscombe's “Modern Moral Philosophy” is that if we choose to describe virtue-defective actions as “morally wrong,” because we are “obliged” or “bound” or “required” not to do them, we are in fact taking an additional step and that this step stands (...) in need of explanation. Just what, if anything, is added to the description of an action as “unjust” when we say there is an obligation not to do it? Anscombe thinks “the answer is in history: between Aristotle and us came Christianity, with its law conception of ethics.” 1 In this paper, I shall confront this question in two parts. First, I will consider the possibility, argued for by Simon Blackburn, that Anscombe's historical explanation cannot answer this question because her history is based on the false premise that the Greeks do not possess the “moral ought.” Describing an action as contrary to obligation may still add something to “unjust,” but historical genealogy of Anscombe's sort will not shed any light on the question. Since I think that Blackburn's arguments, although important, are not conclusive, I will proceed to consider the implications of Anscombe's own view of what talk about obligation adds to descriptions of actions as defective in virtue. This will require elaboration of her cryptic Wittgensteinian remark that “it really does add something to the description ‘unjust’ to say there is an obligation not to do it; for what obliges is the divine law—as rules oblige in a game.” 2. (shrink)

This volume contains twelve essays by friends, colleagues, and former students of Philippa Foot: Anscombe, Blackburn, Hursthouse, Kenny, Lawrence, McDowell, Quinn, Sachs, Scanlon, Michael Thompson, Wiggins, and Williams. The essays concern issues relevant to or raised by Foot's work in moral philosophy, only sometimes specifically addressing her views. Unfortunately, there is no contribution by Foot herself, either in the form of replies or a new paper. This certainly lessens the interest of the volume. Perhaps Foot was driven by modesty (...) in not wanting the focus to be on her comments, or by the need to conserve her time for larger ongoing projects. Whatever the explanation, readers would have benefited from the chance to hear her latest thinking on the issues raised in some of these papers (especially those by Blackburn and McDowell). (shrink)

Collections of essays and conference papers are always liable to two defects. One is that the essays are not all of the same quality. The other is that the collection is ad hoc with no structural unity or organized purpose. The present collection—arising from the 1997 Claremont conference on the philosophy of religion—almost unavoidably exemplifies the first defect. I myself would pick out the contributions of Simon Blackburn, D. Z. Phillips R. W. Beardsmore, Jane McIntyre, Antony Flew, and Peter (...) Jones as the most interesting. Many of the others are well worth the attention of Hume scholars, but two or three are turgid, over-annotated examples of argument by authority of the sort “Wittgenstein tells us...” compounded with emotive appeals to what is alleged to be Hume’s insufferable moral narrowness. But as I say, the uneven quality of contributions is a standard hazard of conference collections. The second hazard—lack of structure—is much less in evidence. There is a real coherence of subject and purpose in the eighteen sections that make up this book, and an effort has been made to relate the articles to each other. An odd omission is, however, the absence of any standard system of reference to agreed editions of Hume’s works. It happens, for example, that most contributors refer to the Selby-Bigge edition of the Enquiries, but this is an accident of common usage not a virtue of editorial policy. There is a general index. (shrink)

This modern, advanced textbook reviews modal logic, a field which caught the attention of computer scientists in the late 1970's.

This bestselling dictionary is written by one of the leading philosophers of our time, and it is widely recognized as the best dictionary of its kind. Comprehensive and authoritative, it covers every aspect of philosophy from Aristotle to Zen. With clear and concise definitions, it provides lively and accessible coverage of not only Western philosophical traditions, but also themes from Chinese, Indian, Islamic, and Jewish philosophy. New entries on philosophy of economics, social theory, neuroscience, philosophy of the mind, and moral (...) conceptions, bring this authoritative third edition up to date. It is the ideal introduction to philosophy for anyone with an interest in the subject, and it is an indispensable work of reference for students and teachers. (shrink)

The UK Genethics Club was established in November 2001 in order to provide a national forum of ethics support for the profession of clinical genetics in the UK. The forum brings together health professionals, medical ethicists and lawyers and support is provided through detailed discussion of cases and sharing of good practice. Clinical genetics professionals had previously voiced concerns about making extremely difficult ethical decisions, with profound implications, in something of a vacuum. Professionals saw a lack of guidance in the (...) area and lack of time for discussion of difficult cases as reasons for this. This paper describes the origins of the group and gives (anonymized) examples of some of the types of issues discussed. (shrink)

One of the major issues in the debate about the future of health care is how to keep costs under control while meeting growing demands for care. Addressing that, especially on an international scale, is far from easy. How are we to determine what the demands for care will most likely be? Even if it is not possible to estimate the future number of dependent elderly persons with any precision, it is hard to ignore the most probable scenario: a substantial (...) increase in the number of the oldest old. (shrink)

Expressivism is the view that the function of normative sentences is not to represent a kind of fact, but to avow attitudes, prescribe behavior, or the like. The idea can be found in David Hume. In the 20th century, G.E. Moore’s Open Question Argument provided important support for the view. Elizabeth Anscombe introduced the notion of “direction of fit,” which helped distinguish expressivism from a kind of naive subjectivism. The central advantage of expressivism is that it easily explains the motivational (...) force of moral conviction. Its chief problem is it has difficulty explaining the “realist surface” of moralizing. Quasi-realism is a strategy for explaining the realist surface without abandoning the underlying ideas of expressivism. It aims to explain moral error as well as deal with the so-called Frege-Geach problem. This chapter explains quasi-realism, and evaluates it by comparison with its chief rivals: Aristotelian approaches, Kantian approaches, realist moral naturalism, and fictionalism. (shrink)

Here at last is a coherent, unintimidating introduction to the challenging and fascinating landscape of Western philosophy. Written expressly for "anyone who believes there are big questions out there, but does not know how to approach them," Think provides a sound framework for exploring the most basic themes of philosophy, and for understanding how major philosophers have tackled the questions that have pressed themselves most forcefully on human consciousness. Simon Blackburn, author of the best-selling Oxford Dictionary of Philosophy, begins (...) by making a convincing case for the relevance of philosophy and goes on to give the reader a sense of how the great historical figures such as Plato, Hume, Kant, Descartes, and others have approached its central themes. In a lively and accessible style, Blackburn approaches the nature of human reflection and how we think, or can think, about knowledge, fate, ethics, identity, God, reason, and truth. Each chapter explains a major issue, and gives the reader a self-contained guide through the problems that the philosophers have studied. Because the text approaches these issues from the gound up, the untrained reader will emerge from its pages able to explore other philosophies with greater pleasure and understanding and be able to think--philosophically--for him or herself. Philosophy is often dismissed as a purely academic discipline with no relation to the "real" world non-philosophers are compelled to inhabit. Think dispels this myth and offers a springboard for all those who want to learn how the basic techniques of thinking shape virtually every aspect of our existence. (shrink)

There is a paucity of experimental data addressing how peers influence adolescent risk-taking. Here, we examined peer effects on risky decision-making in adults and adolescents using a virtual social context that enabled experimental control over the peer “interactions”. 40 adolescents (age 11-18) and 28 adults (age 20-38) completed a risk-taking (Wheel of Fortune) task under 4 conditions: in private; while being observed by (fictitious) peers; and after receiving ‘risky’ or ‘safe’ advice from the peers. For high-risk gambles (but not medium-risk (...) or even gambles), adolescents made more risky decisions under peer observation than adults. Adolescents, but not adults, tended to resist ‘safe’ advice for high-risk gambles. Although both groups tended to follow ‘risky’ advice for high-risk gambles, adults did so more than adolescents. These findings highlight the importance of distinguishing between the effects of peer observation and peer advice on risky decision-making. (shrink)

In this clear introduction to ethics Simon Blackburn tackles the major moral questions surrounding birth, death, happiness, desire and freedom, showing us how ...

It is well established that microRNAs (miRNAs) induce mRNA degradation by binding to 3′ untranslated regions (UTRs). The functionality of sites in the coding domain sequence (CDS), on the other hand, remains under discussion. Such sites have limited impact on target mRNA abundance and recent work suggests that miRNAs bind in the CDS to inhibit translation. What then could be the regulatory benefits of translation inhibition through CDS targeting compared to mRNA degradation following 3′ UTR binding? We propose that these (...) domain‐dependent effects serve to diversify the functional repertoire of post‐transcriptional gene expression control. Possible regulatory benefits may include tuning the time‐scale and magnitude of post‐transcriptional regulation, regulating protein abundance depending on or independently of the cellular state, and regulation of the protein abundance of alternative splice variants. Finally, we review emerging evidence that these ideas may generalize to RNA‐binding proteins beyond miRNAs and Argonaute proteins. (shrink)

Should Proverbs be read as prose or poetry? Considering the language craft is of essential significance for a hermeneutical enquiry into the biblical book of Proverbs. Five suppositions to support the presupposition that Proverbs is best read as poetry were considered.

Provides a comprehensive introduction to the major philosophical theories attempting to explain the workings of language.

This volume collects some influential essays in which Simon Blackburn, one of our leading philosophers, explores one of the most profound and fertile of philosophical problems: the way in which our judgments relate to the world. This debate has centered on realism, or the view that what we say is validated by the way things stand in the world, and a variety of oppositions to it. Prominent among the latter are expressive and projective theories, but also a relaxed pluralism (...) that discourages the view that there are substantial issues at stake. The figure of the "quasi-realist" dramatizes the difficulty of conducting these debates. Typically philosophers thinking of themselves as realists will believe that they alone can give a proper or literal account of some of our attachments--to truth, to facts, to the independent world, to knowledge and certainty. The quasi-realist challenge, developed by Blackburn in this volume, is that we can have those attachments without any metaphysic that deserves to be called realism, so that the metaphysical picture that goes with our practices is quite idle. The cases treated here include the theories of value and knowledge, modality, probability, causation, intentionality and rule-following, and explanation. A substantial new introduction has been added, drawing together some of the central themes. The essays articulate a fresh alternative to a primitive realist/anti-realist opposition, and their cumulative effect is to yield a new appreciation of the delicacy of the debate in these central areas. (shrink)

In this note we show that the classical modal technology of Sahlqvist formulas gives quick proofs of the completeness theorems in [8] (D. Gregory, Completeness and decidability results for some propositional modal logics containing “actually” operators, Journal of Philosophical Logic 30(1): 57–78, 2001) and vastly generalizes them. Moreover, as a corollary, interpolation theorems for the logics considered in [8] are obtained. We then compare Gregory's modal language enriched with an “actually” operator with the work of Arthur Prior now known under (...) the name of hybrid logic. This analysis relates the “actually” axioms to standard hybrid axioms, yields the decidability results in [8], and provides a number of complexity results. Finally, we use a bisimulation argument to show that the hybrid language is strictly more expressive than Gregory's language. (shrink)