The Estrogen Elixir: A History of Hormone Replacement Therapy in America by Elizabeth Siegel Watkins is a thoroughly documented cautionary tale of the information and advice offered to women in the perimenopausal period of their life, and the consequences of exposure to sexual hormones on their health and wellbeing.

The somatic mutation theory (SMT) of cancer has been and remains the prevalent theory attempting to explain how neoplasms arise and progress. This theory proposes that cancer is a clonal, cell‐based disease, and implicitly assumes that quiescence is the default state of cells in multicellular organisms. The SMT has not been rigorously tested, and several lines of evidence raise questions that are not addressed by this theory. Herein, we propose experimental strategies that may validate the SMT. We also call attention (...) to an alternative theory of carcinogenesis, the tissue organization field theory (TOFT), which posits that cancer is a tissue‐based disease and that proliferation is the default state of all cells. Based on epistemological and experimental evidence, we argue that the TOFT compellingly explains carcinogenesis, while placing it within an evolutionarily relevant context.magnified imagemagnified imageAna Soto and Carlos Sonnenschein are at Tufts University School of Medicine, Boston, MA, USA. (shrink)

The somatic mutation theory has been the prevailing paradigm in cancer research for the last 50 years. Its premises are: (1) cancer is derived from a single somatic cell that has accumulated multiple DNA mutations, (2) the default state of cell proliferation in metazoa is quiescence, and (3) cancer is a disease of cell proliferation caused by mutations in genes that control proliferation and the cell cycle. From this compelling simplicity, an increasingly complicated picture has emerged as more than 100 (...) oncogenes and 30 tumor suppressor genes have been identified. To accommodate this complexity, additional ad hoc explanations have been postulated. After a critical review of the data gathered from this perspective, an alternative research program has been proposed. It is based on the tissue organization field theory, the premises of which are that carcinogenesis represents a problem of tissue organization, comparable to organogenesis, and that proliferation is the default state of all cells. The merits of these competing theories are evaluated herein. BioEssays 26:1097–1107, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

For the last 50 years the dominant stance in experimental biology has been reductionism in general, and genetic reductionism in particular. Philosophers were the first to realize that the belief that the Mendelian genes were reduced to DNA molecules was questionable. Soon, experimental data confirmed these misgivings. The optimism of molecular biologists, fueled by early success in tackling relatively simple problems has now been tempered by the difficulties encountered when applying the same simple ideas to complex problems. We analyze three (...) examples taken from experimental data that illustrate the shortcomings of this sort of reductionism. In the first, alterations in the expression of a large number of genes coexist with normal phenotypes at supra-cellular levels of organization; in the second, the supposed intrinsic specificity of hormonal signals is negated; in the third, the notion that cancer is a cellular problem caused by mutated genes is challenged by data gathered both from the reductionist viewpoint and the alternative view proposing that carcinogenesis is development gone awry. As an alternative to reductionism, we propose that the organicist view is a good starting point from which to explore these phenomena. However, new theoretical concepts are needed to grapple with the apparent circular causality of complex biological phenomena. (shrink)

It would be ahistorical to ridicule vitalists. When one reads the writings of one of the leading vitalists like Driesch one is forced to agree with him that many of the basic problems of biology simply cannot be solved by a philosophy as that of Descartes, in which the organism is simply considered a machine…. The logic of the critique of the vitalists was impeccable.At the turn of the new millennium, concomitant with the development of the evo-devo and eco-devo disciplines (...) within developmental biology, critical appraisals of the reductionist stance of the molecular biology revolution became more numerous and noticeable. Several books and papers address the problems posed by this reductionist agenda and suggest... (shrink)

The Estrogen Elixir: A History of Hormone Replacement Therapy in America by Elizabeth Siegel Watkins is a thoroughly documented cautionary tale of the information and advice offered to women in the perimenopausal period of their life, and the consequences of exposure to sexual hormones on their health and wellbeing.

David Waldron Smithers was, among other things, a physician and a pioneer of cancer radiotherapy and a well-respected figure in British medicine and public health. From the 1940s until his retirement from medical practice in 1973, he was the director of the Radiotherapy Department at the Royal Marsden Hospital and London University Chair of Radiotherapy at the Institute of Cancer Research. Using massive amounts of clinical observations, which he interpreted from an organicist viewpoint, and his impressive synthetic thinking, he proposed (...) a coherent alternative perspective to the somatic mutation theory (SMT) which was then, and still is, the dominant theory of cancer. The purpose of this essay is to acquaint the modern audience with his seminal paper, published in 1962, because it deserves to be recognized as a true classic. In it, he examined the lack of fit between clinical observations and the SMT and proposed the rejection of this reductionist perspective. In addition, he built an organicist alternative in which carcinogenesis is seen as a problem of biological organization. His conceptual contribution to the cancer problem has inspired us and other authors over the last two decades. His essay “Cancer: An Attack on Cytologism,” originally published in The Lancet in 1962, is available as supplementary material in the online version of this article. (shrink)

Why do we remember the past and not the future? What does it mean for time to "flow"? Do we exist in time or does time exist in us? In lyric, accessible prose, Carlo Rovelli invites us to consider questions about the nature of time that continue to puzzle physicists and philosophers alike. For most readers this is unfamiliar terrain. We all experience time, but the more scientists learn about it, the more mysterious it remains. We think of it as (...) uniform and universal, moving steadily from past to future, measured by clocks. Rovelli tears down these assumptions one by one, revealing a strange universe where at the most fundamental level time disappears. He explains how the theory of quantum gravity attempts to understand and give meaning to the resulting extreme landscape of this timeless world. Weaving together ideas from philosophy, science and literature, he suggests that our perception of the flow of time depends on our perspective, better understood starting from the structure of our brain and emotions than from the physical universe. (shrink)

Minding Time: A Philosophical and Theoretical Approach to the Psychology of Time offers an innovative philosophical account of the most fundamental kinds of time representation.

This monograph addresses the question of the increasing irrelevance of philosophy, which has seen scientists as well as philosophers concluding that philosophy is dead and has dissolved into the sciences. It seeks to answer the question of whether or not philosophy can still be fruitful and what kind of philosophy can be such. The author argues that from its very beginning philosophy has focused on knowledge and methods for acquiring knowledge. This view, however, has generally been abandoned in the last (...) century with the belief that, unlike the sciences, philosophy makes no observations or experiments and requires only thought. Thus, in order for philosophy to once again be relevant, it needs to return to its roots and focus on knowledge as well as methods for acquiring knowledge. Accordingly, this book deals with several questions about knowledge that are essential to this view of philosophy, including mathematical knowledge. Coverage examines such issues as the nature of knowledge; plausibility and common sense; knowledge as problem solving; modeling scientific knowledge; mathematical objects, definitions, diagrams; mathematics and reality; and more. This monograph presents a new approach to philosophy, epistemology, and the philosophy of mathematics. It will appeal to graduate students and researchers with interests in the role of knowledge, the analytic method, models of science, and mathematics and reality. (shrink)

Many of the computing systems programmed using Machine Learning are opaque: it is difficult to know why they do what they do or how they work. Explainable Artificial Intelligence aims to develop analytic techniques that render opaque computing systems transparent, but lacks a normative framework with which to evaluate these techniques’ explanatory successes. The aim of the present discussion is to develop such a framework, paying particular attention to different stakeholders’ distinct explanatory requirements. Building on an analysis of “opacity” from (...) philosophy of science, this framework is modeled after accounts of explanation in cognitive science. The framework distinguishes between the explanation-seeking questions that are likely to be asked by different stakeholders, and specifies the general ways in which these questions should be answered so as to allow these stakeholders to perform their roles in the Machine Learning ecosystem. By applying the normative framework to recently developed techniques such as input heatmapping, feature-detector visualization, and diagnostic classification, it is possible to determine whether and to what extent techniques from Explainable Artificial Intelligence can be used to render opaque computing systems transparent and, thus, whether they can be used to solve the Black Box Problem. (shrink)

I am a theoretical physicist, and, following Aristotles' injunction (Aristotle, Physics III, 202b 34), I do consider it my responsibility to discuss the problem of the notion of infinity in the world--in particular, to "inquire whether there is such a thing or not." I will do so here by illustrating some aspects of the notion of infinity in the natural sciences.

All human civilizations have thought that the world was made of sky above and the Earth below. All except one. For the Greeks, the Earth was a rock floating in space, and under the earth there was no ground, no turtles, nor the gigantic columns of which the Bible speaks. How did the Greeks understand that the Earth is suspended in nothingness? Who understood this and how? It is this unique "scientific revolution" of Anaximander of which the author speaks, which (...) Karl Popper called "one of the most daring ideas, revolutionary and portentous in the entire history of human thought" The concern is with the conflict that was opened, still burning, with the nature of scientific thought, its critical and rebellious character, the force with which it subverts the order of things and our image of the world of scientific knowledge, and the highly effective "error" at the same time --as we teach physics in the twentieth century. Speaking of Anaximander, the author invites us to reflect on what his ideas mean to the scientific revolution opened by Einstein. (shrink)

This article aims to clarify the sharp contrast between the “short path” of Heideggerian ontology and the “long path” adopted by Ricoeur as a representation of the many necessary mediations in the constitution of his philosophical anthropology. Heidegger breaks into contemporary thought with the publication of his treatise “Being and Time” (1927) as a kind of direct settlement in the field of ontology. In contrast, Ricoeur is seen - and sees himself - as a thinker of conceptual mediations in his (...) long itinerary, since adherence to Husserlian phenomenology and subsequent hermeneutic inflection, passing through confrontations with Freudian psychoanalysis, structuralism and analytical philosophy, to the creation of the book “Oneself as Another” (1990). However, the two philosophers built their works on the common horizon of hermeneutics; therefore, are there possible points of convergence between them? And how could we interpret the relevance of this possible interlocution? These questions cannot be answered without a thorough comparative reading. This text does not intend to answer them, but only to suggest elements for further investigations. (shrink)

Introduction -- Youth, a contradictory formation: 1910-18 -- Workers' democracy and factory-councils: 1919-20 -- Passage to maturity: 1921-6 -- Methodological observations on the prison notebooks -- The 'extended' theory of the state -- The party as 'collective intellectual' -- The current relevance and universality of Gramsci.

v. 1. Ensino secundário e médio -- v. 2. Estudos sobre o ensino primário -- Planejamento educacional e contribuições à educação do futuro.

The received view of dynamical explanation is that dynamical cognitive science seeks to provide covering law explanations of cognitive phenomena. By analyzing three prominent examples of dynamicist research, I show that the received view is misleading: some dynamical explanations are mechanistic explanations, and in this way resemble computational and connectionist explanations. Interestingly, these dynamical explanations invoke the mathematical framework of dynamical systems theory to describe mechanisms far more complex and distributed than the ones typically considered by philosophers. Therefore, contemporary dynamicist (...) research reveals the need for a more sophisticated account of mechanistic explanation. (shrink)

Published as a tribute to the memory of Elisha Pazner, this book contains a collection of essays providing a comprehensive view of the design and evaluation of economic mechanisms, written and edited by the major contributors to the field. Amongst the topics included are bargaining theory and the economics of competitive bidding. The surveys are preceded by 'A Perspective', by Leo Hurwicz which contains a systematic account of the development of the literature on mechanism design, and this provides a context (...) for both the surveys and the six published papers authored or co-authored by Elisha Pazner that complete the book and demonstrate Pazner's interest in and contribution to the study of economic mechanisms. Leonid Hurwitcz is the Nobel Prize Winner 2007 for The Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel, along with colleagues Eric Maskin and Roger Myerson, for his work on the effectiveness of markets. (shrink)

Models developed using machine learning are increasingly prevalent in scientific research. At the same time, these models are notoriously opaque. Explainable AI aims to mitigate the impact of opacity by rendering opaque models transparent. More than being just the solution to a problem, however, Explainable AI can also play an invaluable role in scientific exploration. This paper describes how post-hoc analytic techniques from Explainable AI can be used to refine target phenomena in medical science, to identify starting points for future (...) investigations of causal relationships, and to generate possible explanations of target phenomena in cognitive science. In this way, this paper describes how Explainable AI—over and above machine learning itself—contributes to the efficiency and scope of data-driven scientific research. (shrink)

Franz Brentano is not usually associated with mathematics. Generally, only Brentano’s discussion of the continuum and his critique of the mathematical accounts of it is treated in the literature. It is this detailed critique which suggests that Brentano had more than a superficial familiarity with mathematics. Indeed, considering the authors and works quoted in his lectures, Brentano appears well-informed and quite interested in the mathematical research of his time. I specifically address his lectures here as there is much less to (...) be found about mathematics in his published works. Besides Brentano’s own work, it is quite remarkable to see that practically all of his better-known students sooner or later produced a work on the philosophy of mathematics. This also encourages the supposition not just of a common interest in the matter, but of a common theoretical core. All this prompts the question: Can we speak of a Brentanist philosophy of mathematics? (shrink)

In a context of pervasive digitalization of the social world, both before and during the COVID-19 pandemic, the field of education has undergone major changes with the development of digital practices and settings. However, the physical presence of the subjects and the body remain something primordial and irreplaceable in traditional educational processes. Thus, it is often assumed that virtuality is opposed to the corporeal reality of the subjects involved in teaching, learning and studying. In this paper we aim to critically (...) challenge this assumption by addressing the phenomenon of virtuality in a more original sense: as a fundamental dimension of corporeality itself. Drawing on Merleau-Ponty’s phenomenological insights, we argue that the experience of the virtual is inherently embodied and fully real. We understand corporeality and virtuality as entangled and multidimensional phenomena. At the same time, this leads us to rethink the digital as only one possible medium in which virtuality can appear as inherent to embodied experience. We develop our phenomenological approach in three instances. First, we question and bracket two common assumptions about corporeality. From our critical perspective, assumptions about a disembodied digitality and a devirtualized corporeality represent extremes within which educational discourses currently move. Second, we address the inherent virtuality of embodied experience. We outline the heuristic concept of the virtual body to describe corporeality and virtuality as entangled and multidimensional phenomena that encompass extension, intercorporeality and intermediality. Finally, we make some remarks on the relationships of corporeality and virtuality considering the challenges of digital education. (shrink)

In the last few decades there has been a revival of interest in diagrams in mathematics. But the revival, at least at its origin, has been motivated by adherence to the view that the method of mathematics is the axiomatic method, and specifically by the attempt to fit diagrams into the axiomatic method, translating particular diagrams into statements and inference rules of a formal system. This approach does not deal with diagrams qua diagrams, and is incapable of accounting for the (...) role diagrams play as means of discovery and understanding. Alternatively, this paper purports to show that the view that the method of mathematics is the analytic method is capable of dealing with diagrams qua diagrams, and of accounting for such role. (shrink)

Bayesian reverse-engineering is a research strategy for developing three-level explanations of behavior and cognition. Starting from a computational-level analysis of behavior and cognition as optimal probabilistic inference, Bayesian reverse-engineers apply numerous tweaks and heuristics to formulate testable hypotheses at the algorithmic and implementational levels. In so doing, they exploit recent technological advances in Bayesian artificial intelligence, machine learning, and statistics, but also consider established principles from cognitive psychology and neuroscience. Although these tweaks and heuristics are highly pragmatic in character and (...) are often deployed unsystematically, Bayesian reverse-engineering avoids several important worries that have been raised about the explanatory credentials of Bayesian cognitive science: the worry that the lower levels of analysis are being ignored altogether; the challenge that the mathematical models being developed are unfalsifiable; and the charge that the terms ‘optimal’ and ‘rational’ have lost their customary normative force. But while Bayesian reverse-engineering is therefore a viable and productive research strategy, it is also no fool-proof recipe for explanatory success. (shrink)

The philosophy of mathematics of the last few decades is commonly distinguished into mainstream and maverick, to which a ‘third way’ has been recently added, the philosophy of mathematical practice. In this paper the limitations of these trends in the philosophy of mathematics are pointed out, and it is argued that they are due to the fact that all of them are based on a top-down approach, that is, an approach which explains the nature of mathematics in terms of some (...) general unproven assumption. As an alternative, a bottom-up approach is proposed, which explains the nature of mathematics in terms of the activity of real individuals and interactions between them. This involves distinguishing between mathematics as a discipline and the mathematics embodied in organisms as a result of biological evolution, which however, while being distinguished, are not opposed. Moreover, it requires a view of mathematical proof, mathematical definition and mathematical objects which is alternative to the top-down approach. (shrink)

The philosophical conception of mechanistic explanation is grounded on a limited number of canonical examples. These examples provide an overly narrow view of contemporary scientific practice, because they do not reflect the extent to which the heuristic strategies and descriptive practices that contribute to mechanistic explanation have evolved beyond the well-known methods of decomposition, localization, and pictorial representation. Recent examples from evolutionary robotics and network approaches to biology and neuroscience demonstrate the increasingly important role played by computer simulations and mathematical (...) representations in the epistemic practices of mechanism discovery and mechanism description. These examples also indicate that the scope of mechanistic explanation must be re-examined: With new and increasingly powerful methods of discovery and description comes the possibility of describing mechanisms far more complex than traditionally assumed. (shrink)