The feasibility of reversing human aging within a matter of decades has traditionally been dismissed by all professional biogerontologists, on the grounds that not only is aging still poorly understood, but also many of those aspects that we do understand are not reversible by any current or foreseeable therapeutic regimen. This broad consensus has recently been challenged by the publication, by five respected experimentalists in diverse subfields of biogerontology together with three of the present authors, of an article (Ann NY (...) Acad Sci 959, 452–462) whose conclusion was that all the key components of mammalian aging are indeed amenable to substantial reversal (not merely retardation) in mice, with technology that has a reasonable prospect of being developed within about a decade. Translation of that panel of interventions to humans who are already alive, within a few decades thereafter, was deemed potentially feasible (though it was not claimed to be likely). If the prospect of controlling human aging within the foreseeable future cannot be categorically rejected, then it becomes a matter of personal significance to most people presently alive. Consequently, we suggest that serious public debate on this subject is now warranted, and we survey here several of the biological, social and political issues relating to it. BioEssays 24:667–676, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Society has historically not taken a benign view of genetic disease. The laws permitting sterilization of the mentally re tarded~ and those proscribing consanguineous marriages are but two examples. Indeed as far back as the 5th-10th centuries, B.C.E., consanguineous unions were outlawed (Leviticus XVIII, 6). Case law has traditionally tended toward the conservative. It is reactive rather than directive, exerting its influence only after an individual or group has sustained injury and brought suit. In contrast, state legislatures have not been (...) inhibited in enacting statutes. Many of their products can be characterized as hasty, unnecessary, ill-conceived, and based on the heart rather than the head. Moreover the lack of expert consultation sought has also been remarkable. One state legislature, for example, has advocated immunization for sickle cell anemia! Many others have enacted laws for the screening of inborn errors of metabolism, e.g., phenylketon uria, but have poorly defined the lines of responsibility to secure compliance. A spate of specific disease-related bills has emerged in the u.S. Congress, each seeking recognition and appropriations. Sickle cell anemia, hemophilia, Cooley's anemia and Tay-Sachs disease have been among the front-runners for support. Finally, in 1975, Congress has begun to examine an omnibus bill concerning all forms of genetic disease. The bill, termed the National Genetic Diseases Act is, however, still far from being enacted. (shrink)

The feasibility of reversing human aging within a matter of decades has traditionally been dismissed by all professional biogerontologists, on the grounds that not only is aging still poorly understood, but also many of those aspects that we do understand are not reversible by any current or foreseeable therapeutic regimen. This broad consensus has recently been challenged by the publication, by five respected experimentalists in diverse subfields of biogerontology together with three of the present authors, of an article (Ann NY (...) Acad Sci 959, 452–462) whose conclusion was that all the key components of mammalian aging are indeed amenable to substantial reversal (not merely retardation) in mice, with technology that has a reasonable prospect of being developed within about a decade. Translation of that panel of interventions to humans who are already alive, within a few decades thereafter, was deemed potentially feasible (though it was not claimed to be likely). If the prospect of controlling human aging within the foreseeable future cannot be categorically rejected, then it becomes a matter of personal significance to most people presently alive. Consequently, we suggest that serious public debate on this subject is now warranted, and we survey here several of the biological, social and political issues relating to it. BioEssays 24:667–676, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Over recent years, evidence has been accumulating in favour of the free radical theory of aging, first proposed by Harman. Despite this, an understanding of the mechanism by which cells might succumb to the effects of free radicals has proved elusive. This paper proposes such a mechanism, based on a previously unexplored hypothesis for the proliferation of mutant mitochondrial DNA: that mitochondria with reduced respiratory function, due to a mutation or deletion affecting the respiratory chain, suffer less frequent lysosomal degradation, (...) because they inflict free radical damage more slowly on their own membranes. Once such a mutation occurs in a mitochondrion of a non‐dividing cell, therefore, mitochondria carrying it will rapidly populate that cell, thereby destroying the cell's respiratory capability. The accumulation of cells that have undergone this transition results in aging at the organismal level. The consistency of the hypothesis with known facts is discussed, and technically feasible tests are suggested, of both the proposed mechanism and its overall contribution to mammalian aging. (shrink)

Modern scholarship on decision behavior dates from the late 1940s. But that scholarship has been preoccupied with two ideas that are much older. One is the notion of expected utility, first articulated in the scholarly literature by Daniel Bernoulli in 1738. In its simplest form, the expected utility concept applies to monetary gambles. Imagine you are asked to choose between two gifts, either gamble G, which you would then play and get either $9 or nothing, or else a simple, direct (...) payment of $3. As shown in the decision tree in figure 10.1, you receive gamble G's $9 payoff if the toss of a fair die yields one or two pips, but you receive nothing otherwise. (In decision trees, choice points are represented by square nodes, chance points by circular nodes.) The expected value or expectation of a gamble is the sum of its payoffs, each weighted (i.e., multiplied) by its probability. Thus, the expected value of G is EV(G) = (1/3)($9) + (2/3)($0) = $3, the same as the direct payment. So, if you generally make decisions like this one so as to maximize expected value, you would be indifferent between the present options. However, if you are like most people, you are not indifferent. Instead, you are risk‐averse, preferring the guaranteed $3. Why? (shrink)

Foundations of Economic Personalism is a series of three book-length monographs, each closely examining a significant dimension of the Center for Economic Personalism's unique synthesis of Christian personalism and free-economic market theory. In the aftermath of the momentous geo-political and economic changes of the late 1980s, a small group of Christian social ethicists began to converse with free-market economists over the morality of market activity. This interdisciplinary exchange eventually led to the founding of a new academic subdiscipline under the rubric (...) of economic personalism. These scholars attempt to integrate economic theory, history, and methodology with Christian personalism's stress upon human dignity, humane social structures, and social justice. This final volume in the series systematically applies the praxeological and theoretical foundations of the personalist tradition to free-market economic theory. Unlike the previous two, this work defends economic liberty in theologically sensitive terms that reference the personalist tradition, without compromising the disciplinary integrity of either economics or social ethics. (shrink)

Analysis of sites of newly integrated DNA in cellular genomes is important to several fields, but methods for analyzing and visualizing these datasets are still under development. Here, we describe tools for data analysis and visualization that take as input integration site data from our INSPIIRED pipeline. Paired-end sequencing allows inference of the numbers of transduced cells as well as the distributions of integration sites in target genomes. We present interactive heatmaps that allow comparison of distributions of integration sites to (...) genomic features and that support numerous user-defined statistical tests. To summarize integration site data from human gene therapy samples, we developed a reproducible report format that catalogs sample population structure, longitudinal dynamics, and integration frequency near cancer-associated genes. We also introduce a novel summary statistic, the UC50, which provides a single number summarizing possible clonal expansion. Using these tools, we characterize ongoing longitudinal characterization of a patient from the first trial to treat severe combined immunodeficiency-X1, showing successful reconstitution for 15 years accompanied by persistence of a cell clone with an integration site near the cancer-associated gene CCND2. Software is available at https://github.com/BushmanLab/INSPIIRED. (shrink)

BackgroundTurnover intention, an employee’s intention to voluntarily leave their jobs, affects workforce sustainability. However, scarce data are available about turnover intention and its associated factors among psychiatrists in China, especially during the COVID-19 pandemic. The current research was designed to address this gap.MethodsAn anonymous, nationwide online survey was disseminated to psychiatrists in 41 psychiatric hospitals in China. We collected demographic data, job-related information, and participants’ turnover intention in the next 12 months.ResultsIn total, 3,973 psychiatrists completed the survey. The sample was (...) predominantly female and married, and nearly three-fourths had children. More than one-third had a master’s or doctoral degree in addition to their medical degree. The overall level of job satisfaction was moderate. The rate of turnover intention was 22.0% and was comparable in males and females. Psychiatrists who had participated in the frontline work of COVID-19 were more likely to report an intention to leave their current job. Multiple regression analyses suggested that turnover intention was significantly associated with having insomnia, longer working hours, and more working days per week.ConclusionDuring the pandemic period, approximately one-fifth of psychiatrists in China reported turnover intention. Factors associated with turnover intention included high job-related burdens, low job satisfaction, participation in the frontline work against COVID-19, and insomnia. To improve psychiatric workforce sustainability, policymakers and hospital administrators need to be aware of this potential challenge and address the concerns of psychiatrists in China. (shrink)

Placing Bruno—both advanced philosopher and magician burned at the stake—in the Hermetic tradition, Yates's acclaimed study gives an overview not only of Renaissance humanism but of its interplay—and conflict—with magic and occult practices. "Among those who have explored the intellectual world of the sixteenth century no one in England can rival Miss Yates. Wherever she looks, she illuminates. Now she has looked on Bruno. This brilliant book takes time to digest, but it is an intellectual adventure to read (...) it. Historians of ideas, of religion, and of science will study it. Some of them, after reading it, will have to think again.... For Miss Yates has put Bruno, for the first time, in his tradition, and has shown what that tradition was."—Hugh Trevor-Roper, _New Statesman_ "A decisive contribution to the understanding of Giordano Bruno, this book will probably remove a great number of misrepresentations that still plague the tormented figure of the Nolan prophet."—Giorgio de Santillana, _American Historical Review_ "Yates's book is an important addition to our knowledge of Giordano Bruno. But it is even more important, I think, as a step toward understanding the unity of the sixteenth century."—J. Bronowski, _New York Review of Books_. (shrink)

This translation of a classic and original work of intellectual history is beautifully done. Rossi’s book Clavis Universalis was first published in Italian in 1960, but Clucas translates the second, revised edition of 1983. The book is about Renaissance and 17th-century encyclopedism, hieroglyphics and cryptography, the techniques of artificial memory, the history of rhetoric, changes in views about logic and method in the scientific revolution, and new ideas about how language and images might reflect or capture reality. Frances Yates’s (...) brilliant The Art of Memory, published in 1966, has so far had much more influence in the English-speaking world. Despite warm citations and many points of contact with Yates’s work, Rossi is less interested in uncovering hidden occult traditions, and more focussed on the way major 17th-century thinkers’ work must be understood against the rich background of schemes for universal grammar and local memory. He shows that scholars working on Bacon, Descartes, and Leibniz miss key references to this intellectual heritage. Half of the book [152] introduces relevant mnemonic, rhetorical, linguistic, medical, and occult writings. Rossi includes illuminating discussions not only of Ramon Lull, Petrus Ramus, Cornelius Agrippa, Giordano Bruno, and all, but also of fascinating minor writers like Guglielmo Gratorolo who systematized advice on medical aids to memory in the mid-16th century, and the wonderful Johannes Spangerbergius, who classified various forms of amnesia in 1570. He then argues that polemic against the arts of memory in both Bacon and Descartes coexisted with intense interest on their part in the supplementing of weak powers of natural memory by various artificial aids and objects outside the boundaries of skull and skin. Rossi tells the strange stories of the great 17th-century encyclopedists and universal language schemers—Alsted, Comenius, Wilkins, Dalgarno—making important connections between Wilkins’s scheme and worries about methods for botanical classification in the early Royal Society. The final chapter is a tour de force on ‘the sources of Leibniz’s universal character’, placing him (as Clucas neatly puts it) ‘at the “end” of a Renaissance intellectual tradition rather than reading him “forwards” as an innovative precursor of modern formal logic’. Historians of science, linguistics, and philosophy have built on many aspects of Rossi’s work since 1983, and Clucas contributes an outstanding introduction which summarizes key strands of recent scholarship. (shrink)

The topic for this volume is a "natural" for the Minnesota Studies. Some of the most important issues concerning both the philosophy and history of science have been in the foreground of discussion for the past few years. Feigl's introductory paper "Beyond Peaceful Coexistence" sets the stage for a confrontation that never quite takes place here. Ernan McMullin's "The History and Philosophy of Science: A Taxonomy" is valuable in helping to sort out the issues by clarifying different types and uses (...) of the history and philosophy of science. Arnold Thackray raises a number of interesting meta-questions concerning the historiographic assumptions that have characterized recent history of science. There are several papers concerned with the issues of hermeticism [[sic]] that have been raised by F. A. Yates' work and a reassessment of philosophical and historical issues raised by the development of relativistic electrodynamics. Altogether this is a fine collection, even though so many different issues are explored that there is little sense of clear focus.--R. J. B. (shrink)

Accounts of the religious debates sparked by the theory of evolution tend, almost inevitably, to focus on the late nineteenth century. Darwinism is treated as a symbol of the scientific naturalism that so traumatized Victorian thought. Modern accounts have shown, however, that religious thinkers were in the end able to take on board an evolutionism purged of its most materialistic tendencies. We tend to assume that in Britain, at least, the arguments had largely died down by the end of the (...) nineteenth century. Led by Aubrey Moore, the Anglican Church made its accommodation, and Moore's contribution of an essay to the volume Lux mundi, edited by Charles Gore in 1889, symbolized the ability of even the conservative Anglo-Catholic wing of the Church to move in the direction of modernization. In America, of course, the compromise broke down with the rise of Fundamentalism in the early twentieth century, but most British commentators saw the ‘Scopes trial’ of 1925 as a strange transatlantic phenomenon that was unlikely to have a parallel in their own country. (shrink)

An engaging and accessible introduction to mathematical proof incorporating ideas from real analysis A mathematical proof is an inferential argument for a mathematical statement. Since the time of the ancient Greek mathematicians, the proof has been a cornerstone of the science of mathematics. The goal of this book is to help students learn to follow and understand the function and structure of mathematical proof and to produce proofs of their own. An Introduction to Proof through Real Analysis is based on (...) course material developed and refined over thirty years by Professor Daniel J. Madden and was designed to function as a complete text for both first proofs and first analysis courses. Written in an engaging and accessible narrative style, this book systematically covers the basic techniques of proof writing, beginning with real numbers and progressing to logic, set theory, topology, and continuity. The book proceeds from natural numbers to rational numbers in a familiar way, and justifies the need for a rigorous definition of real numbers. The mathematical climax of the story it tells is the Intermediate Value Theorem, which justifies the notion that the real numbers are sufficient for solving all geometric problems. • Concentrates solely on designing proofs by placing instruction on proof writing on top of discussions of specific mathematical subjects • Departs from traditional guides to proofs by incorporating elements of both real analysis and algebraic representation • Written in an engaging narrative style to tell the story of proof and its meaning, function, and construction • Uses a particular mathematical idea as the focus of each type of proof presented • Developed from material that has been class-tested and fine-tuned over thirty years in university introductory courses An Introduction to Proof through Real Analysis is the ideal introductory text to proofs for second and third-year undergraduate mathematics students, especially those who have completed a calculus sequence, students learning real analysis for the first time, and those learning proofs for the first time. Daniel J. Madden, PhD, is an Associate Professor of Mathematics at The University of Arizona, Tucson, Arizona, USA. He has taught a junior level course introducing students to the idea of a rigorous proof based on real analysis almost every semester since 1990. Dr. Madden is the winner of the 2015 Southwest Section of the Mathematical Association of America Distinguished Teacher Award. Jason A. Aubrey, PhD, is Assistant Professor of Mathematics and Director, Mathematics Center of the University of Arizona. (shrink)

This volume makes a bold and successful attempt to trace the historical roots of memory-art from the Greek era to the Middle Ages where the Art's role was central to all other arts—literary, architectural, etc. Yates concentrates on the Renaissance period with a detailed study of the memory theater of Giulio Camillo, the continuation of Lullism as an Art of Memory, the influence of Giordano Bruno and Peter Ramus. Several chapters are devoted to the Theatre Memory system of Robert (...) Fludd and the reconstruction of the Globe Theatre. A final chapter indicates that although the gradual birth of a new way of thinking—the scientific method of Bacon, Kepler, et alio—would seem to quiet forever mnemonic arts, this latter art played no small influence on the more scientific thinkers, especially Leibniz and his "dissertation on the art of combining." The book is supplemented with numerous plates and charts of antiquity which illustrate the forgotten art of memory.—J. J. R. (shrink)