Intuitionists and classical logicians use in common a large number of the logical axioms, even though they supposedly mean different things by the logical connectives and quantifiers — conquans for short. But Wittgenstein says The meaning of a word is its use in the language. We prove that in a definite sense the intuitionistic axioms do indeed characterize the logical conquans, both for the intuitionist and the classical logician.

The prospect of using genome technologies to modify the human germline has raised profound moral disagreement but also emphasizes the need for wide-ranging discussion and a well-informed policy response. The Hinxton Group brought together scientists, ethicists, policymakers, and journal editors for an international, interdisciplinary meeting on this subject. This consensus statement formulated by the group calls for support of genome editing research and the development of a scientific roadmap for safety and efficacy; recognizes the ethical challenges involved in clinical reproductive (...) applications of genome editing but, importantly, rejects the idea that human reproductive germline modification is necessarily morally unacceptable; and highlights the importance of meaningful engagement in discussions of genome editing and the development of regulation and oversight mechanisms to govern future uses of such technologies. (shrink)

The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

Transoral laser microsurgery applies to the piecemeal removal of malignant tumours of the upper aerodigestive tract using the CO2 laser under the operating microscope. This method of surgery is being increasingly popularised as a single modality treatment of choice in early laryngeal cancers (T1 and T2) and occasionally in the more advanced forms of the disease (T3 and T4), predomi- nantly within the supraglottis. Thomas Kuhn, the American physicist turned philosopher and historian of science, coined the phrase ‘paradigm shift’ in (...) his groundbreaking book The Structure of Scientific Revolutions. He argued that the arrival of the new and often incompatible idea forms the core of a new paradigm, the birth of an entirely new way of thinking. This article discusses whether Steiner and col- leagues truly brought about a paradigm shift in oncological surgery. By rejecting the principle of en block resection and by replacing it with the belief that not only is it oncologically safe to cut through the substance of the tumour but in doing so one can actually achieve better results, Steiner was able to truly revolutionise the man- agement of laryngeal cancer. Even though within this article the repercussions of his insight are limited to the upper aerodigestive tract oncological surgery, his willingness to question other peoples’ dogma makes his contribution truly a genuine paradigm shift. (shrink)

We develop a framework for assessing security market quality, relating five elements of market design to three metrics of market integrity and two metrics of market efficiency. We empirically implement this integrity–efficiency MQ framework by testing a hypothesis that trade-based ramping manipulation at the close raises execution costs on 24 security markets worldwide. Estimating a simultaneous equations model of ramping incidence, spreads, and the probability of deploying real-time surveillance, we show that quoted bid-ask spreads are positively related to the incidence (...) of MTC across seven liquidity deciles. The magnitude is economically significant; improving market integrity by cutting MTC in half reduces spreads 6–11 %. Allowing direct market access in conjunction with RTS, conducting auctions at the close, and developing regulations that require surveillance, all reduce MTC and thereby lower spreads, assuring better market integrity and enhancing market efficiency. Introducing circuit breakers or prohibiting shorts poses integrity–efficiency tradeoffs. (shrink)

Both fairness and efficiency are important considerations in market design and regulation, yet many regulators have neither defined nor measured these concepts. We develop an evidencebased policy framework in which these are both defined and measured using a series of empirical proxies. We then build a systems estimation model to examine the 2003–2011 explosive growth in algorithmic trading on the London Stock Exchange and NYSE Euronext Paris. Our results show that greater AT is associated with increased transactional efficiency and reduced (...) information leakage in top quintile stocks. For less liquid stocks, manipulation at the close declines. We also document the tradeoff between reduced spreads and increased manipulation or information leakage following the introduction of MiFID1. (shrink)

The present volume, a tribute to Harry Dondorp, contains contributions to the symposium held on the occasion of his farewell at the Vrije Universiteit Amsterdam. Written by four eminent scholars in the field of legal history, the contributions are related to his areas of interest: delictual liability, Romano-canonical procedure and comparative law texts. The contributors are Wolfgang Ernst, David Ibbetson, Yves Mausen and Andreas Thier. The introductory words are by Eltjo Schrage, Jan Hallebeek and Hylkje de Jong.

The neural correlates of rapid eye movements (REMs) in sleep are extraordinarily robust; including REM-locked activation in the retrosplenial cortex, the supplementary eye field and areas overlapping cholinergic basal nucleus. The phenomenology of REMs speaks to the notion that perceptual experience in both sleep and wakefulness is a constructive process – in which we generate predictions of sensory inputs and then test those predictions through actively sampling the sensorium with eye movements. On this view, REMs during sleep may index an (...) internalized active sampling or ‘scanning’ of self-generated visual constructs that are not constrained by visual input. If this view is correct, it renders REMs an ideal probe to study consciousness as “an exclusively internal affair” (Metzinger 2009). In other words, REMs offer a probe of active inference – in the sense of predictive coding – when the brain is isolated from the sensorium in virtue of the natural blockade of sensory input during REM sleep. REMs are temporally precise events that enable powerful inferences based on timeseries analyses. As a natural, task-free probe, [REMs] could be used in non-compliant subjects, including infants and animals. In short, REM constitutes a promising probe to study the ontogenetic and phylogenetic development of consciousness and perhaps its abnormal development in schizophrenia and autism, which have been considered in terms of aberrant predictive coding. (shrink)

In a qualitative study, 22 stroke patients undergoing rehabilitation in three nursing homes were interviewed about constraints on and improvements in their autonomy and about approaches of health professionals regarding autonomy. The data were analysed using grounded theory, with a particular focus on the process of regaining autonomy. An approach by the health professionals that was responsive to changes in the patients’ autonomy was found to be helpful for restoration of their autonomy. Two patterns in health professionals’ approach appeared to (...) be facilitatory: (1) from full support on admission through moderate support and supervision, to reduced supervision at discharge; and (2) from paternalism on admission through partial paternalism (regarding treatment) to shared decision making at discharge. The approach experienced by the patients did not always match their desires regarding their autonomy. Support and supervision were reduced over time, but paternalism was often continued too long. Additionally, the patients experienced a lack of information. Tailoring interventions to patients’ progress in autonomy would stimulate their active participation in rehabilitation and in decision making, and would improve patients’ preparation for autonomous living after discharge. (shrink)

Introduction, by H. J. Cargas.--St. Paul and Teilhard de Chardin, by J. H. Adams.--Teilhard and Dante, by M. Gable.--Tennyson and Teilhard, by E. R. August.--Teilhard, neo-Marxism, existentialism, by M. Barthelemy-Madaule.--Whitman, Teilhard, and Jung, by R. Benoit.--C. G. Jung and Teilhard de Chardin, by N. Braybrooke.--Camus and Teilhard, by P. Rosazza.--Bonhoeffer and Teilhard, by C. M. Hegarty.--Voices of convergence: Teilhard, McLuhan, and Brown, by D. J. Leary.

Alzheimer's disease is characterized by plaques of amyloid-beta peptide, cleaved from amyloid-beta protein precursor . Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AbetaPP mRNA, AbetaPP protein, and Abeta levels in rodents and primates. We also tracked a transcriptional regulator of the AbetaPP gene, specificity protein 1 , and the beta amyloid precursor (...) cleaving enzyme . In mice, AbetaPP and SP1 mRNA and their protein products were elevated late in life; Abeta levels declined in old age. In monkeys, SP1, AbetaPP, and BACE1 mRNA declined in old age, while protein products and Abeta levels rose. Proteolytic processing in both species did not match production of Abeta. In primates, AbetaPP and SP1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products as well as Abeta levels. Comparison of human DNA and mRNA sequences to monkey and mouse counterparts revealed structural features that may explain differences in transcriptional and translational processing. These findings are important for selecting appropriate models for AD and other age-related diseases. (shrink)

Harris levels two main criticisms against our original defence of QALYs (Quality Adjusted Life Years). First, he rejects the assumption implicit in the QALY approach that not all lives are of equal value. Second, he rejects our appeal to Rawls's veil of ignorance test in support of the QALY method. In the present article we defend QALYs against Harris's criticisms. We argue that some of the conclusions Harris draws from our view that resources should be allocated on (...) the basis of potential improvements in quality of life and quantity of life are erroneous, and that others lack the moral implications Harris claims for them. On the other hand, we defend our claim that a rational egoist, behind a veil of ignorance, could consistently choose to allocate life-saving resources in accordance with the QALY method, despite Harris's claim that a rational egoist would allocate randomly if there is no better than a 50% chance of being the recipient. (shrink)

This book celebrates the work of Patricia Werhane, an iconic figure in business ethics. This festschrift is a collection of articles that build on Werhane’s contributions to business ethics in such areas as Employee Rights, the Legacy of Adam Smith, Moral Imagination, Women in Business, the development of the field of business ethics, and her contributions to such fields as Health Care, Education, Teaching, and Philosophy. All papers are new contributions to the management literature written by well-known business ethicists, such (...) as Norman Bowie, Richard De George, Ronald Duska, Edwin Hartman, Michael Hoffman, Mollie Painter-Morland, Mark Schwartz, Andrew Wicks, and others. The volume is comprised of articles that reflect on Werhane’s work as well as build on it as a way to advance further research. At the end of the festschrift, Pat Werhane provides responses to each chapter. The first chapter of the book also includes the overview of Patricia Werhane’s work and her academic career. The book is written to appeal to management scholars and graduate students interested in the areas of Business Ethics, Modern Capitalism, and Human Rights. Patricia Werhane is one of the most distinguished figures in the field of business ethics. She was a founder of the field, she is one of its leading scholars, and she has had a profound impact on the world of business practice. Among her many accomplishments, Pat is known for her original work on moral imagination, she is an acclaimed authority on employee rights in the workplace, and she is one of the leading scholars on Adam Smith. Having been active in Academia for over 50 years, Werhane is a prolific author of over a hundred articles and book chapters, and the author or editor of twenty-seven books, including Adam Smith and his Legacy for Modern Capitalism, Moral Imagination and Management Decision-Making, and co-authored books Organization Ethics in Health Care, Alleviating Poverty Through Profitable Partnerships, Obstacles to Ethical Decision-Making, Corporate Responsibility: The American Experience, and Research Approaches to Business Ethics and Corporate Responsibility. (shrink)

Peter Abelard (1079–1142 ce) was the most wide‐ranging philosopher of the twelfth century. He quickly established himself as a leading teacher of logic in and near Paris shortly after 1100. After his affair with Heloise, and his subsequent castration, Abelard became a monk, but he returned to teaching in the Paris schools until 1140, when his work was condemned by a Church Council at Sens. His logical writings were based around discussion of the “Old Logic”: Porphyry's Isagoge, aristotle'S Categories and (...) On Interpretation and boethius'S textbook on topical inference. They comprise a freestanding Dialectica (“Logic”; probably c.1116), a set of commentaries (known as the Logica [Ingredientibus], c. 1119) and a later (c. 1125) commentary on the Isagoge (Logica Nostrorum Petititoni Sociorum or Glossulae). In a work Abelard called his Theologia, issued in three main versions (between 1120 and c.1134), he attempted a logical analysis of trinitarian relations and explored the philosophical problems surrounding God's claims to omnipotence and omniscience. The Collationes (“Debates,” also known as “Dialogue between a Christian, a Philosopher and a Jew”; probably c.1130) present a rational investigation into the nature of the highest good, in which the Christian and the Philosopher (who seems to be modeled on a philosopher of pagan antiquity) are remarkably in agreement. The unfinished Scito teipsum (“Know thyself,” also known as the “Ethics”; c.1138) analyses moral action. (shrink)

A rupture has occurred–something is no longer quite as it was. Our current environmental crisis, climate catastrophe,has left us floundering without words for after three decades of popular ecological writing and decades more of scientificstudies nothing has yet been done to avert our path from its terminal arc. It is a weird occurrence for our words seeminsufficient, our categories incapacitated, and our understanding too flawed to comprehend it. Yet, it is a disasterwhich has already occurred–it is a disaster which we (...) live in the midst of and yet still lack the language with which tospeak. The greatest danger of such an epoch, according to Blanchot, is that, out of convenience, we use an outdatedand unsuitable language to attempt reconciliation. Rather than attempting to apply logical and nomical systems andconcepts to a catastrophe, which is catastrophic precisely because it obsolesces such ways of thinking, a new mode ofthought, of language, is required if climate catastrophe is to be properly understood and addressed. Utilizing the textsof Roland Barthes, Karen Barad, Maurice Blanchot and Timothy Morton, as well as the weird fiction of H.P.Lovecraft, I intend to demonstrate not only the pitfalls of our current agrilogistical approach to climate catastrophe,but also a potential eco-deconstructive alternative that would allow significant change to occur. (shrink)

I began my review of volume 6 of the new critical edition by saying that from the three volumes published we could see how the editors planned to deal with almost all the problems that they faced. I shall not be tempted into any rash statement of this kind again; for it is clear that every volume brings its own special problems with it. The present volume contains the manuscript that Hegel wrote for a course on “Realphilosophie” which he probably (...) gave for the first time at Jena in the Winter Semester of 1805/6, and again in Summer 1806. This manuscript was first utilized by K. Michelet, who inserted copious quotations from the “Naturphilosophie” into the Zusätze for his edition of the Encyclopedia “Philosophy of Nature”. Michelet already knew fairly accurately what the provenance and date of the manuscript were. Modern studies have only made the dating a little more precise and altogether more secure. The whole manuscript was finally published by J. Hoffmeister in 1931. It has been known to us for the last forty-five years as Jenenser Realphilosophie II. (shrink)

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into (...) two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop. (shrink)

Alzheimer's disease is characterized by amyloid-beta peptide -loaded plaques in the brain. Abeta is a cleavage fragment of amyloid-beta protein precursor and over production of APP may lead to amyloidogenesis. The regulatory region of the APP gene contains consensus sites recognized by the transcription factor, specificity protein 1 , which has been shown to be required for the regulation of APP and Abeta. To understand the role of SP1 in APP biogenesis, herein we have characterized the relative distribution and localization (...) of SP1, APP, and Abeta in various brain regions of rodent and primate models using immunohistochemistry. We observed that overall distribution and cellular localization of SP1, APP, and Abeta are similar and neuronal in origin. Their distribution is abundant in various layers of neocortex, but restricted to the Purkinje cell layer of the cerebellum, and the pyramidal cell layer of hippocampus. These findings suggest that overproduction of Abeta in vivo may be associated with transcriptional pathways involving SP1 and the APP gene. (shrink)

Harris argues that if QALYs are used only 50% of the population will be eligible for survival, whereas if random methods of allocation are used 100% will be eligible. We argue that this involves an equivocation in the use of "eligible", and provides no support for the random method. There is no advantage in having a 100% chance of being "eligible" for survival behind a veil of ignorance if you still only have a 50% chance of survival once the (...) veil is lifted. A 100% chance of a 50% chance is still only a 50% chance. We also argue that Harris provides no plausible way of dealing with the criticism that his random method of allocation may result in the squandering of resources. (shrink)

Only 27 percent of Americans in a 1995 Harris poll said they had read or heard “quite a lot” about genetic tests. Nonetheless, 68 percent said they would be either “very likely” or “somewhat likely” to undergo genetic testing even for diseases “for which there is presently no cure or treatment.” Perhaps most astonishing, 56 percent found it either “very” or “somewhat acceptable” to develop a government computerized DNA bank with samples taken from all newborns, and their names attached (...) to the samples. This does not necessarily mean the public is unconcerned about genetic privacy. More likely it means that the public is still uninformed about the risks associated with genetic testing, and has not thought at all about the risks involved in storing identifiable DNA samples.A central question presented by genetic screening and testing is whether the genetic information so obtained is different in kind from other medical information, and, if so, whether this means that it should receive special legal protection. (shrink)

Broad, C. D. Leibniz's predicate-in-notion principle and some of its alleged consequences.--Couturat, L. On Leibniz's metaphysics.--Friedrich, C. J. Philosophical reflections of Leibniz on law, politics, and the state.--Curley, E. M. The root of contingency. Furth, M. Monadology.--Hacking, I. Individual substance.--Hintikka, J. Leibniz on plenitude, relations, and the "reign of law."--Ishiguro, H. Leibniz's theory of the ideality of relations.--Kneale, M. Leibniz and Spinoza on activity.--Koyré, A. Leibniz and Newton.--Lovejoy, A. O. Plenitude and sufficient reason in Leibniz and Spinoza.--Mates, B. Leibniz on (...) possible worlds.--Russell, B. Recent work on the philosophy of Leibniz.--Wilson, M. D. On Leibniz's explication of "necessary truth.". (shrink)

I respond to Selinger and Mix (Selinger, E. and Mix, J. 2004. On interactional expertise: Pragmatic and ontological considerations. Phenomenology and the Cognitive Sciences 3: 145–163), concentrating on their charges that Collins (Collins, H. M. 2004a. Interactional expertise as a third form of knowledge. Phenomenology and the Cognitive Sciences 3: 125–143) underrates the importance of interactional expertise as an expertise sui generis and that the paper fails to analyse the idea of embodiment sufficiently holistically, misleading treating the ‘body’ as no (...) more than the linear sum of its parts. (shrink)