Brock Macdonald1, Evi Vakiani2, Rhonda K Yantiss3, Jun Lee4, Robert S Brown Jr5, Samuel H Sigal61Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco, CA, 2Department of Pathology, Memorial Sloan–Kettering Cancer Center, New York, NY, 3Department of Pathology and Laboratory Medicine, New York Weill Cornell Medical College, New York, NY, 4Division of Nephrology, Department of Medicine, Weill Cornell Medical College, New York, NY, 5Division of Gastroenterology, Department of Medicine, Columbia University College of Physicians and Surgeons, New (...) York, NY, 6Division of Gastroenterology and Hepatology, Department of Medicine, New York University, New York, NY, USA: The use of sirolimus as an alternative to calcineurin inhibitors for posttransplant immunosuppression is associated with a variety of inflammatory conditions. In this report, we describe the case of a 34-year-old man who developed abnormal liver tests 6 years after live-donor kidney transplantation and 5 years after initiation of sirolimus-based immunosuppression. Elevated aminotransferase levels persisted after withdrawal of potentially hepatotoxic medications, and serologic evaluation for viral hepatitis, autoimmune disease, and genetic disorders was unrevealing. Liver biopsy revealed prominent hepatocellular injury associated with a mixed inflammatory infiltrate and liver tests normalized within 2 weeks of discontinuation of sirolimus. In this report, we review previous reports of sirolimus hepatotoxicity and propose a unifying hypothesis for the various inflammatory conditions that have been attributed to sirolimus.Keywords: sirolimus, immunosuppression, transplant, inflammatory conditions, hepatotoxicity. (shrink)

End-of-life decision making is fraught with ethical challenges. Withholding or withdrawing life support therapy is widely considered ethical in patients with high treatment burden, poor premorbid status, or significant projected disability even when such treatment is not “futile.” Whether such withdrawal of therapy in the aftermath of attempted suicide is ethical is not well established in the literature. We provide a clinical vignette and propose criteria under which such withdrawal would be ethical. We suggest that it is appropriate to withdraw (...) life support, regardless of the cause of the critical illness or disability, when the following criteria are met: (1) Surrogates request withdrawal of care and the adequacy of surrogates is confirmed, (2) an external reasonability standard is met, (3) passage of time, perhaps 72 hours, to allow certainty regarding the patient's wishes, and (4) psychiatric morbidity should be considered as grounds for withdrawal only in truly treatment-refractory cases. Fundamentally, we believe the question to ask is, “If this were not an attempted suicide, would a request to withdraw care be reasonable?” We believe that under these circumstances, such withdrawal of life support, even in an individual who has attempted suicide, does not constitute physician assistance with suicide and is distinct from physician aid-in-dying in several important respects. (shrink)

End-of-life decision making is fraught with ethical challenges. Withholding or withdrawing life support therapy is widely considered ethical in patients with high treatment burden, poor premorbid status, or significant projected disability even when such treatment is not ?futile.? Whether such withdrawal of therapy in the aftermath of attempted suicide is ethical is not well established in the literature. We provide a clinical vignette and propose criteria under which such withdrawal would be ethical. We suggest that it is appropriate to withdraw (...) life support, regardless of the cause of the critical illness or disability, when the following criteria are met: (1) Surrogates request withdrawal of care and the adequacy of surrogates is confirmed, (2) an external reasonability standard is met, (3) passage of time, perhaps 72 hours, to allow certainty regarding the patient's wishes, and (4) psychiatric morbidity should be considered as grounds for withdrawal only in truly treatment-refractory cases. Fundamentally, we believe the question to ask is, ?If this were not an attempted suicide, would a request to withdraw care be reasonable?? We believe that under these circumstances, such withdrawal of life support, even in an individual who has attempted suicide, does not constitute physician assistance with suicide and is distinct from physician aid-in-dying in several important respects. (shrink)

This volume contains articles covering a broad spectrum of proof theory, with an emphasis on its mathematical aspects. The articles should not only be interesting to specialists of proof theory, but should also be accessible to a diverse audience, including logicians, mathematicians, computer scientists and philosophers. Many of the central topics of proof theory have been included in a self-contained expository of articles, covered in great detail and depth. The chapters are arranged so that the two introductory articles come first; (...) these are then followed by articles from core classical areas of proof theory; the handbook concludes with articles that deal with topics closely related to computer science. (shrink)

We are grateful for the careful reading and insightful responses of the several peer commentaries to our proposed approach to requests to withhold or withdraw life support therapies among patients...

We are grateful for the careful reading and insightful responses of the several peer commentaries to our proposed approach to requests to withhold or withdraw life support therapies among patients...

The best philosophy of science during the last generation has been highly historical; and the best history of science, highly philosophical. No one has better exemplified this intimate relationship between history and philosophy than has Robert E. Butts in his work. Through out his numerous writings, science, its philosophy, and its history have been treated as a seamless web. The result has been a body of work that is sensitive in its conception, ambitious in its scope, and illuminat ing in (...) its execution. Not only has his work opened new paths of inquiry, but his enthusiasm for the discipline, his encouragement of others (particularly students and younger colleagues), and his tireless efforts to build an international community of scholars, have stimulated the growth of HPS throughout Europe and North America. Many of the essays in this volume reflect that influence. Our title, of course, is deliberately ambiguous. The essays herein are by colleagues and former students, all of us wishing to honour an intimate friend. Happy Birthday, Bob! IX INTRODUCTION The essays herein cover a variety of concerns: from Descartes to reduction, from Galileo to gambling, from Freud's psychoanalysis to Kant's thing-in-itself. But under this diversity there is an approach common to them all. Things are largely done with a concern for and a sensitivity to historical matters (including contemporary history, of course). (shrink)

Throughout the Old Testament, the stories, laws, and songs not only teach a way of life that requires individuals to be moral, but they demonstrate how. In biblical studies, character ethics has been one of the fastest-growing areas of interest. Whereas ethics usually studies rules of behavior, character ethics focuses on how people are formed to be moral agents in the world. This book presents the most up-to-date academic work in Old Testament character ethics, covering topics throughout the Torah, the (...) Prophets, and the Writings, in addition to the use of the Bible in the modern world. In addition to Carroll and Lapsley, contributors are Denise M. Ackermann, Cheryl B. Anderson, Samuel E. Balentine, William P. Brown, Walter Brueggemann, Thomas B. Dozeman, Bob Ekblad, Jose Rafael Escobar R., Theodore Hiebert, Kathleen O'Connor, Dennis T. Olson, J. David Pleins, Luis R. Rivera Rodriguez, J. J. M. Roberts, and Daniel L. Smith-Christopher. (shrink)

Samuel R. Buss and Aleksandar Ignjatović. Unprovability of Consistency Statements in Fragments of Bounded Arithmetic.

Partial consistency statements can be expressed as polynomial-size propositional formulas. Frege proof systems have polynomial-size partial self-consistency proofs. Frege proof systems have polynomial-size proofs of partial consistency of extended Frege proof systems if and only if Frege proof systems polynomially simulate extended Frege proof systems. We give a new proof of Reckhow's theorem that any two Frege proof systems p-simulate each other. The proofs depend on polynomial size propositional formulas defining the truth of propositional formulas. These are already known to (...) exist since the Boolean formula value problem is in alternating logarithmic time; this paper presents a proof of this fact based on a construction which is somewhat simpler than the prior proofs of Buss and of Buss-Cook- Gupta-Ramachandran. (shrink)

The four authors present their speculations about the future developments of mathematical logic in the twenty-first century. The areas of recursion theory, proof theory and logic for computer science, model theory, and set theory are discussed independently.

The paper proves refined feasibility properties for the disjunction property of intuitionistic propositional logic. We prove that it is possible to eliminate all cuts from an intuitionistic proof, propositional or first-order, without increasing the Horn closure of the proof. We obtain a polynomial time, interactive, realizability algorithm for propositional intuitionistic proofs. The feasibility of the disjunction property is proved for sequents containing Harrop formulas. Under hardness assumptions for NP and for factoring, it is shown that the intuitionistic propositional calculus does (...) not always have polynomial size proofs and that the classical propositional calculus provides a superpolynomial speedup over the intuitionistic propositional calculus. The disjunction property for intuitionistic propositional logic is proved to be P-hard by a reduction to the circuit value problem. (shrink)

We survey the best known lower bounds on symbols and lines in Frege and extended Frege proofs. We prove that in minimum length sequent calculus proofs, no formula is generated twice or used twice on any single branch of the proof. We prove that the number of distinct subformulas in a minimum length Frege proof is linearly bounded by the number of lines. Depthd Frege proofs ofm lines can be transformed into depthd proofs ofO(m d+1) symbols. We show that renaming (...) Frege proof systems are p-equivalent to extended Frege systems. Some open problems in propositional proof length and in logical flow graphs are discussed. (shrink)

Originating from work in operations research the cutting plane refutation systemCP is an extension of resolution, where unsatisfiable propositional logic formulas in conjunctive normal form are recognized by showing the non-existence of boolean solutions to associated families of linear inequalities. Polynomial sizeCP proofs are given for the undirecteds-t connectivity principle. The subsystemsCP q ofCP, forq≥2, are shown to be polynomially equivalent toCP, thus answering problem 19 from the list of open problems of [8]. We present a normal form theorem forCP (...) 2-proofs and thereby for arbitraryCP-proofs. As a corollary, we show that the coefficients and constant terms in arbitrary cutting plane proofs may be exponentially bounded by the number of steps in the proof, at the cost of an at most polynomial increase in the number of steps in the proof. The extensionCPLE +, introduced in [9] and there shown top-simulate Frege systems, is proved to be polynomially equivalent to Frege systems. Lastly, since linear inequalities are related to threshold gates, we introduce a new threshold logic and prove a completeness theorem. (shrink)

Cook and Reckhow defined a propositional formulation of the pigeonhole principle. This paper shows that there are Frege proofs of this propositional pigeonhole principle of polynomial size. This together with a result of Haken gives another proof of Urquhart's theorem that Frege systems have an exponential speedup over resolution. We also discuss connections to provability in theories of bounded arithmetic.

Properties sometimes attributed to the “particle” aspect of a neutron, e.g., mass and magnetic moment, cannot straightforwardly be regarded in the Bohm interpretation of quantum mechanics as localized at the hypothetical position of the particle. This is shown by examining a series of effects in neutron interferometry. A related thought-experiment also provides a variation of a recent demonstration that which-way detectors can appear to behave anomolously in the Bohm theory.

Let T be a first-order theory. A T-normal Kripke structure is one in which every world is a classical model of T. This paper gives a characterization of the intuitionistic theory T of sentences intuitionistically valid in all T-normal Kripke structures and proves the corresponding soundness and completeness theorems. For Peano arithmetic , the theory PA is a proper subtheory of Heyting arithmetic , so HA is complete but not sound for PA-normal Kripke structures.

The bounded arithmetic theory S2 is finitely axiomatized if and only if the polynomial hierarchy provably collapses. If T2i equals S2i + 1 then T2i is equal to S2 and proves that the polynomial time hierarchy collapses to ∑i + 3p, and, in fact, to the Boolean hierarchy over ∑i + 2p and to ∑i + 1p/poly.

Heisenberg'sgendanken experiments in quantum mechanics have given rise to a widespread belief that the indeterminacy relations holding for the variables of a quantal system can be explained quasiclassically in terms of a disturbance suffered by the system in interaction with a quantal measurement, or state preparation, agent. There are a number of criticisms of this doctrine in the literature, which are critically examined in this article and found to be ininconclusive, the chief error being the conflation of this disturbance with (...) the projection postulate. We present a critique of the disturbance theory based on the fact that the required disturbance will in general depend on the interaction time of the system and state-preparer. This point is exploited in the construction of a spin-interaction model which acts as a counterexample to the disturbance doctrine, while remaining faithful to the spirit of Heisenberg'sgedanken experiments. Several consequences of this result are discussed. (shrink)

We refine the constructions of Ferrante-Rackoff and Solovay on iterated definitions in first-order logic and their expressibility with polynomial size formulas. These constructions introduce additional quantifiers; however, we show that these extra quantifiers range over only finite sets and can be eliminated. We prove optimal upper and lower bounds on the quantifier complexity of polynomial size formulas obtained from the iterated definitions. In the quantifier-free case and in the case of purely existential or universal quantifiers, we show that Ω quantifiers (...) are necessary and sufficient. The last lower bounds are obtained with the aid of the Yao-Håstad switching lemma. (shrink)

This paper discusses lower bounds for proof length, especially as measured by number of steps (inferences). We give the first publicly known proof of Gödel's claim that there is superrecursive (in fact. unbounded) proof speedup of (i + 1)st-order arithmetic over ith-order arithmetic, where arithmetic is formalized in Hilbert-style calculi with + and · as function symbols or with the language of PRA. The same results are established for any weakly schematic formalization of higher-order logic: this allows all tautologies as (...) axioms and allows all generalizations of axioms as axioms. Our first proof of Gödel's claim is based on self-referential sentences: we give a second proof that avoids the use of self-reference based loosely on a method of Statman. (shrink)

In his warranted christian belief, Alvin Plantinga launches a forceful attack on apophaticism, the view that God is in some sense or other beyond description. This paper explores his attack before searching for a Plantinga-proof formulation of apophaticism.

We study the long-standing open problem of giving$\forall {\rm{\Sigma }}_1^b$separations for fragments of bounded arithmetic in the relativized setting. Rather than considering the usual fragments defined by the amount of induction they allow, we study Jeřábek’s theories for approximate counting and their subtheories. We show that the$\forall {\rm{\Sigma }}_1^b$Herbrandized ordering principle is unprovable in a fragment of bounded arithmetic that includes the injective weak pigeonhole principle for polynomial time functions, and also in a fragment that includes the surjective weak pigeonhole (...) principle for FPNPfunctions. We further give new propositional translations, in terms of random resolution refutations, for the consequences of$T_2^1$augmented with the surjective weak pigeonhole principle for polynomial time functions. (shrink)

We review the dynamical approach to spacetime theories---in particular, its origins in the development of special relativity, its opposition to the contemporary `geometrical' approach, and the manner in which it plays out in general relativity. In addition, we demonstrate that the approach is compatible with the `angle bracket school'.

This paper investigates what the source of time-asymmetry is in thermodynamics, and comments on the question whether a time-symmetric formulation of the Second Law is possible.

Thought experiments have a long and illustrious history. But in spite of their acknowledged importance, there has until recently been remarkably little said about them. How do they work? Why do they work? What are the different ways in which they work? And above all: How is it possible that just by thinking we can learn something new about the world? This paper surveys some of the recent approaches, including my own , and discusses their various prospects. Chief among the (...) alternatives is John Norton′s “argument” view. The paper ends by drawing attention to some of the outstanding problems in thought experiments. These are some of the issues that will likely be the focus of attention and research in the future. (shrink)

A culture in crisis -- The rise of the living will -- Empirical and ethical problems with living wills -- Living wills don't make decisions : human beings do -- The barbaric life of the ICU -- Life after the ICU -- Reform : the current state of the art -- Healing the intensive care unit.

The world food economy has undergone a basic transformation during the seventies. Not only did the world have surplus stocks and excess production capacity at the beginning of the decade, but it also appeared that both would be around for a long time to come. Suddenly in 1972 and 1973, they disappeared and the whole world was trying to make it from one harvest to the next. During the mid-seventies global food insecurity was greater than at any time since the (...) war-torn years immediately following World War II. (shrink)

In this paper we argue that the moral value of an agent is determined solely by their dispositions to act intentionally and freely. We then put this conclusion to work. It resolves a putative moral paradox first posed by Saul Smilansky, and it undermines a prominent line of argument for a variety of Trinitarian theology. Finally, we derive our conclusion about the moral worth of agents not only from our initial series of thought experiments, but also from Abrahamic theism itself. (...) This means that Smilansky’s paradox can only possibly be rehabilitated by an atheist, and that the aforementioned line of argumentation for the Trinity is radically self-undermining, since it relies upon the denial of a corollary of Abrahamic theism. (shrink)

The quantum theory of de Broglie and Bohm solves the measurement problem, but the hypothetical corpuscles play no role in the argument. The solution finds a more natural home in the Everett interpretation.

It is argued that Minkowski space-time cannot serve as the deep structure within a ``constructive'' version of the special theory of relativity, contrary to widespread opinion in the philosophical community.

The action-reaction principle (AR) is examined in three contexts: (1) the inertial-gravitational interaction between a particle and space-time geometry, (2) protective observation of an extended wave function of a single particle, and (3) the causal-stochastic or Bohm interpretation of quantum mechanics. A new criterion of reality is formulated using the AR principle. This criterion implies that the wave function of a single particle is real and justifies in the Bohm interpretation the dual ontology of the particle and its associated wave (...) function. But it is concluded that the Bohm theory is not dynamically complete because the particle and its associated wave function do not satisfy the AR principle. (shrink)

Abstract The historical evolution of the principle of relativity from Galileo to Einstein is briefly traced, and purported difficulties with Einstein's formulation of the principle are examined and dismissed. This formulation is then compared to a precise version formulated recently in the geometrical language of spacetime theories. We claim that the recent version is both logically puzzling and fails to capture a crucial physical insight contained in the earlier formulations. The implications of this claim for the modern treatment of general (...) dynamical symmetries are discussed. (shrink)