The DNA hypomethylating agents (HMA) azacitidine (AZA) and decitabine (DAC) improve survival and transfusion independence in myelodysplastic syndrome (MDS) and enable a low intensity cytotoxic treatment for aged AML patients unsuitable for intensive chemotherapy, particularly in combination with novel agents. The proposed mechanism of AZA and DAC relies on active DNA replication and therefore patient responses are only observed after multiple cycles of treatment. Although extended dosing may provide the optimal scheduling, the reliance of injectable formulation of the drug limits (...) it to intermittent treatment. Recently, an oral formulation of AZA demonstrated significantly improved patient relapse free survival (RFS) and overall survival (OS) when used as maintenance after chemotherapy for AML. In addition, both DAC and AZA were found to be highly effective to improve survival in elderly patients with AML through combination with other drugs. These recent exciting results have changed the therapeutic paradigm for elderly patients with AML. In light of this, we review current knowledge on HMA mechanism of action, clinical trials exploring dosing and scheduling, and recent HMA combination therapies to enhance efficacy. (shrink)

Department of History and Philosophy of Science. University of Cambridge, Free School Lane, Cambridge CB2 3RH This paper is concerned with the question of whether atomic particles of the same species, i. e. with the same intrinsic state-independent properties of mass, spin, electric charge, etc, violate the Leibnizian Principle of the Identity of Indiscernibles, in the sense that, while there is more than one of them, their state-dependent properties may also all be the same. The answer depends on what (...) exactly the state-dependent properties of atomic particles are taken to be. On the plausible interpretation that these should comprise all monadic and relational properties that can be expressed in terms of physical magnitudes associated with self-adjoint operators that can be defined for the individual particles, then the weakest form of the Principle is shown to be violated for bosons, fermions and higher-order paraparticles, treated in first quantization *Some of the arguments inn this paper appeared in a thesis submited by one of us (S.F.) In partial fulfilment of the requirements for the PhD degree of the University of London, in 1984. entitled 'Identity and ‘Individuality in Classical and Quantum Physics’. (shrink)

Reviewed Works:Andrea Sorbi, Complexity, Logic, and Recursion Theory.Klaus Ambos-Spies, Elvira Mayordomo, Resource-Bounded Measure and Randomness.Marat Arslanov, Degree Structures in Local Degree Theory.Jose L. Balcazar, Ricard Gavalda, Montserrat Hermo, Compressibility of Infinite Binary Sequences.S. Barry Cooper, Beyond Godel's Theorem: The Failure to Capture Information Content.Robert A. Di Paola, Franco Montagna, Progressions of Theories of Bounded Arithmetic.Rodney G. Downey, On Presentations of Algebraic Structures.Sophie Fischer, Lane Hemaspaandra, Leen Torenvliet, Witness-Isomorphic Reductions and Local Search.William Gasarch, Carl H. Smith, A Survey of Inductive (...) Inference with an Emphasis on Queries.Andre Nies, A Uniformity of Degree Structures.Piergiorgio Odifreddi, Short Course on Logic, Algebra, and Topology.Andrea Sorbi, The Enumeration Degrees of the $\sigma^0_2$ Sets.Peter van Emde Boas, The Convenience of Tilings. (shrink)

This chapter contains sections titled: Riding Out of the Cave Discipline and Diet Toughing It Out Surprises Down the Road From Tribulation to Wisdom Notes.

This paper presents a preliminary analysis of the first participatory budgeting experiment in the United States, in Chicago's 49th Ward. There are two avenues of inquiry: First, does participatory budgeting result in different budgetary priorities than standard practices? Second, do projects meet normative social justice outcomes? It is clear that allowing citizens to determine municipal budget projects results in very different outcomes than standard procedures. Importantly, citizens in the 49th Ward consistently choose projects that the research literature classifies as low (...) priority. The results are mixed, however, when it comes to social justice outcomes. While there is no clear pattern in which projects are located only in affluent sections of the ward, there is evidence of geographic clustering. Select areas are awarded projects like community gardens, dog parks, and playgrounds, while others are limited to street resurfacing, sidewalk repairs, bike racks, and bike lanes. Based on our findings, we offer suggestions for future programmatic changes. (shrink)

In the Preface to Rationality, Steven Pinker remarks that “we are smart enough to have … articulated the rules of reason that we so often flout” (p. xiv). Unfortunately, Pinker does not get the rules of reason right in this book. Pinker defends a damagingly irrational conception of reason. But despite this rather drastic failure, there is much of interest in this book, even if at a rather elementary level.

Zygon®, Volume 57, Issue 2, Page 514-516, June 2022.

Written by epidemiologists, ethicists and legal scholars, this book provides an in-depth account of the moral problems that often confront epidemiologists, including both theoretical and practical issues. The first edition has sold almost three thousand copies since it was published in 1996. This edition is fully revised and includes three new chapters: Ethical Issues in Public Health Practice, Ethical Issues in Genetic Epidemiology, and Ethical Issues in International Health Research and Epidemiology. These chapters collectively address important developments of the past (...) decade. Three chapters from the first edition have also been reorganized: Ethicall Optimized Study Deisgns in Epidemiology, Ethical Issues in Epidemiologic Research with Children, and The Ethics of Epidemiologic Research with Older Populations. Instead of standing alone, these chapters have been integrated into chapters on informed consent, confidentiality and privacy protection, and community-based intervention studies. (shrink)

What are the forces shaping the future of international green politics? This book provides an objective account of the basis of green arguments and their social and political implications. It offers a clear overview of the most pressing environmental threats.

Although Darwin insisted that human intelligence could be fully explained by the theory of evolution, the codiscoverer of natural selection, Alfred Russel Wallace, claimed that abstract intelligence was of no use to ancestral humans and could only be explained by intelligent design. Wallace’s apparent paradox can be dissolved with two hypotheses about human cognition. One is that intelligence is an adaptation to a knowledge-using, socially interdependent lifestyle, the “cognitive niche.” This embraces the ability to overcome the evolutionary fixed defenses of (...) plants and animals by applications of reasoning, including weapons, traps, coordinated driving of game, and detoxification of plants. Such reasoning exploits intuitive theories about different aspects of the world, such as objects, forces, paths, places, states, substances, and other people’s beliefs and desires. The theory explains many zoologically unusual traits in Homo sapiens, including our complex toolkit, wide range of habitats and diets, extended childhoods and long lives, hypersociality, complex mating, division into cultures, and language (which multiplies the benefit of knowledge because know-how is useful not only for its practical benefits but as a trade good with others, enhancing the evolution.. (shrink)

A work of and about comparative philosophy that stresses the importance of language in intercultural endeavors.

Past research has found that skin colouration, particularly facial redness, influences the perceived health and emotional state of target individuals. In the current work, we explore several extensions of this past research. In Experiment 1, we manipulated facial redness incrementally on neutral and angry faces and had participants rate each face for anger and health. Different red effects emerged, as perceived anger increased in a linear manner as facial redness increased. Health ratings instead showed a curvilinear trend, as both extreme (...) paleness and redness were rated as less healthy than moderate levels of red. Experiment 2 replicated and extended these findings by manipulating the masculinity of both angry and neutral faces that varied in redness. The results found the effect of red on perceived anger and health was moderated by masculine face structure. Collectively, these results show that facial redness has context dependent effects that vary based on facial expression, appearance, and differentially impact ratings of emotional states and health. (shrink)

We discuss three varieties of affective dynamics ( affective instability, emotional inertia, and emotional differentiation). In each case, we suggest how these affective dynamics should be operationalized and measured in daily life using time-intensive methods, like ecological momentary assessment or ambulatory assessment, and recommend time-sensitive analyses that take into account not only the variability but also the temporal dependency of reports. Studies that explore how these affective dynamics are associated with psychological disorders and symptoms are reviewed, and we emphasize that (...) these affective processes are within a nexus of other components of emotion regulation. (shrink)

v. 1. A doctrine of divine illumination -- v. 2. God at the core of cognition.

In the not too distant past, it was common to treat Hume's skeptical doubts regarding the justification of our beliefs in causal connections—understood as necessary connections between objects or events—as having appeared per conceptionem immaculatam in his post-Cartesian mind. Thanks to recent efforts by scholars in early modern philosophy, however, we are now more informed about the roots of Hume's conclusions in Cartesian thought itself, especially the influence of Malebranche and his arguments for occasionalism. And by the research of historians (...) of Medieval philosophy we are reminded that many aspects of seventeenth-century occasionalism, in turn, have their ancestry in Latin and Arabic thought of the Middle Ages. In this paper I offer a small contribution to the overall project of illuminating the precedents in Medieval philosophy for the theses and arguments in Malebranche that so clearly influenced the most important and influential philosophical analysis of causation ever. There is a tradition here, where the goal is to undermine claims to discover real causal relations or powers in nature. I will concentrate on one particular aspect or tool of that tradition: the negative argument that we can never perceive a sufficiently necessary connection between any two natural objects or events. (shrink)

A comparative study of what the most influential writers of Ancient Greece and China thought it meant to have knowledge and whether they distinguished knowledge from other forms of wisdom. It surveys selected works of poetry, history and philosophy from the period of roughly the eighth through to the second century BCE, including Homer's "Odyssey", the ancient Chinese "Classic of Poetry", Thucydides' "History of the Peloponnesian War", Sima Qian's "Records of the Historian", Plato's "Symposium", and Laozi's "Dao de Jing and (...) the writings of Zhuangzi". The intention, through such juxtaposition, is to introduce the foundational texts of each tradition which continue to influence the majority of the world's population. (shrink)

Gauge theories are theories that are invariant under a characteristic group of "gauge" transformations. General relativity is invariant under transformations of the diffeomorphism group. This has prompted many philosophers and physicists to treat general relativity as a gauge theory, and diffeomorphisms as gauge transformations. I argue that this approach is misguided.

Simple finite axiomatizations are given for versions of the modal logics K and K4 with non-contingency (or contingency) as the sole modal primitive. This answers two questions of I. L. Humberstone.

"First Published in 1990, Routledge is an imprint of Taylor & Francis, an informa company.".

What can the art of living after Foucault contribute to ethics in relation to the mediation of human existence by technology? To develop the relation between technical mediation and ethics, firstly the theme of technical mediation is elaborated in line with Foucault’s notion of ethical problematization. Every view of what technology does to us at the same time expresses an ethical concern about technology. The contemporary conception of technical mediation tends towards the acknowledgement of ongoing hybridization, not ultimately good or (...) bad but ambivalent, which means for us the challenge of taking care of ourselves as hybrid beings. Secondly, the work of Foucault provides elements for imagining this care for our hybrid selves, notably his notions of freedom as a practice and of the care of the self. A conclusions about technical mediation and ethics is that whereas the approaches of the delegation of morality to technology by Latour and mediated morality by Verbeek see technical mediation of behavior and moral outlook as an answer in ethics, this should rather be considered the problem that ethics is about. (shrink)

The spring, summer, and fall 2006 editions of Critical Inquiry hosted a heated exchange between Ernesto Laclau and Slavoj Žižek regarding the proper definition of the Lacanian Real. Žižek claims "the Real is the inexorable abstract spectral logic of capital that determines what goes on in social reality". In response, Laclau states that Žižek's "spectral logic of capital" is a gross distortion of Lacanian theory: "The Real is not a specifiable object endowed with laws of movement on its own but, (...) on the contrary, something that only exists and shows itself through its disruptive effects within the Symbolic". Laclau's formulation of the Real, however, forecloses the possibility of... (shrink)

Kaci Hickox was a nurse who worked with persons who were infected with Ebola in West Africa. When she returned to the United States, the governors of New Jersey and Maine intervened to confine her to inpatient quarantine despite the fact that she was asymptomatic and had no serological evidence of infection. She defied the quarantine which resulted in enormous public attention and discussion of quarantine and public fear. This article summarizes the case discussing the history of the case, the (...) government actions, and the final legal rulings. (shrink)

Is it true that an ethics of care offers something distinct from other approaches to ethical problems in nursing, especially principlism? In this article an attempt is made to clarify an ethics of care and then to argue that there need be no substantial difference between principlism and an ethics of care when the latter is considered in the context of nursing. The article begins by considering the question of how one could in fact differentiate moral theories. As is explained, (...) this cannot be done merely in light of the moral judgements they defend, nor their ontological commitments (e.g. their view of the nature of persons). Following these methodological beginnings, care-based ethics is described and critically discussed. It is shown that ontological commitments embraced within care ethics do not themselves show that care ethics is distinct from other approaches. The idea of ‘psychological care’ is also discussed, which stems from the work of Margaret Little. Her claim that the ‘gestalts’ of justice and care cannot be combined is rejected in favour of an approach that does just that and which has been developed by Joan Tronto. It is then claimed that the moral commitments of principlism are certainly not incompatible with those of an ethics of care in the nursing context. A challenge to the idea that principlism and ethics of care might be compatible is anticipated in the work of Eva Feder Kittay. This challenge is responded to and it is concluded that care considered as a moral orientation and the moral values embedded in principlism are best combined in the nursing context. Care provides a moral orientation over which the obligations referred to in principlism can be laid. (shrink)