Sandia National Laboratories, located in Albuquerque, New Mexico, was originally a part of Los Alamos Laboratory. In 1949, AT&T agreed to manage Sandia, which they did for the next 44 years. During those Cold War years, Sandia was the prime weapons engineering laboratory for Los Alamos and Lawrence Livermore. As such, it bore prime responsibility for designing and adapting nuclear weapons for the military services' delivery systems, and ensuring the safety and reliability of the stockpile. The Labs' history has been (...) unevenly documented, hindered by the secret nature of its work and the desire of management to maintain a low public profile. There have been three history programs at Sandia: a restricted history published internally in 1963; another history program in the early 1980s that resulted in a history of the Labs' first decade; and the current history program dating from the mid-1990s, which has published a general history and several monographs. This article discusses the challenges and problems inherent in documenting the history of a national weapons laboratory during the last 50 years. (shrink)

The Statesman is Plato's neglected political work, but it is crucial for an understanding of the development of his political thinking. In some respects it continues themes from the Republic, particularly the importance of knowledge as entitlement to rule. But there are also changes: Plato has dropped the ambitious metaphysical synthesis of the Republic, changed his view of the moral psychology of the citizen, and revised his position on the role of law and institutions. In its presentation of the statesman's (...) expertise, the Statesman modifies, as well as defending in original ways, this central theme of the Republic. (shrink)

This paper explores Plato and Aristotle 's responses to the pre-Socratic philosopher Parmenides, who paradoxically said that there is no such thing as non-being, and no such things as change. I argue that Plato’s response would have been good enough to defeat the claim in a debate, thereby remedying the political aspects of the Parmenides problem. However, Aristotle ’s answer is required to answer some additional philosophical and scientific aspects. Plato's Sophist is a very difficult dialogue to understand; seeing it (...) in light of Aristotle 's discussion of the same topic helps to explain the complexities of what his teacher Plato wrote. (shrink)

The respective rejections of contractarian explanations and justifications of political allegiance by hume and hegel are outlined. The difference between these rejections is located in a change in conceptualizations of the relationship between human nature and history and this is illustrated by a discussion of herder. In consequence, Hegel does not reproduce hume's arguments because hume's own rejection, Both historical and philosophical, Of contractarianism was premised on the very principles that hegel rejects in his theoretical rejection of rousseau's theoretical reformulation (...) of the notion. (shrink)

When read as Marsiglio asks us to read it, the Defensor minor looks a great deal less like a change of heart on its author's part than an extension and application of the principles that he had formulated fifteen years earlier in the Defensor pacis. The inconsistency some scholars have detected turns out to be based on a sort of false expectation about Marsiglio's political theory, namely, that it must ultimately advocate a single system of government or form of rule (...) in preference to others. For most other political theorists of the Latin Middle Ages this expectation would be warranted. But just as in so many other instances, Marsiglio frustrates our expectations: his approach is distinctive among his contemporaries for exactly the �generic� quality of its argument. This �generic� feature of his thought did not change with time. The Defensor minor illustrates how the �generic� framework can be applied as required in order to lend polemical support to a given temporal ruler. This means, quite simply, that the Defensor minor does not reflect any great change of heart about or pragmatic renunciation of Marsiglio's �true� republican principles. Certainly, Marsiglio's generic account of politics could be adapted in support of a republican regime, such as existed in many of the medieval Italian cities. (shrink)

Abstract:This article is about how a very specific section of the Rio Grande was transformed through human intervention over the course of the twentieth century. Geographically, I focus on the stretch of river between and around the twin border towns of El Paso, Texas and Ciudad Juárez, Chihuahua. This is an important area of analysis not only because of the historic importance of the urban complex to U.S.-Mexico relations, but also because it is a desert. I analyze two major river (...) engineering projects, one in the 1930s, the other in the 1960s, as well as the transformation of the water itself due to increased toxicity beginning in the 1990s. In sum, the river was straightened, completely relocated, lined in concrete, and poisoned. No other place on the entire international divide underwent such extreme changes. I explain this by arguing that both political forces and environmental conditions combined to produce such totalizing interventions in the riverine ecosystem. I also argue that these processes reversed the age-old meaning of water in the desert. Historically, water in the desert has been associated with life and biodiversity, but over the course of the twentieth century the desert section of the Rio Grande border was converted into a deadened zone. (shrink)

The effect of nutrition on fertility and its contribution thereby to population dynamics are assessed in three social groups (elite, tradesmen and subsistence) in a marginal, pre-industrial population in northern England. This community was particularly susceptible to fluctuations in the price of grains, which formed their basic foodstuff. The subsistence class, who formed the largest part of the population, had low levels of fertility and small family sizes, but women from all social groups had a characteristic and marked subfecundity in (...) the early part of their reproductive lives. The health and nutrition of the mother during pregnancy was the most important factor in determining fertility and neonatal mortality. Inadequate nutrition had many subtle effects on reproduction which interacted to produce a complex web of events. A population boom occurred during the second half of the 18th century; fertility did not change but there was a marked improvement in infant mortality and it is suggested that the steadily improving nutritional standards of the population, particularly during crucial periods in pregnancy (i.e. the last trimester), probably made the biggest contribution to the improvement in infant mortality and so was probably the major factor in triggering the boom. (shrink)

The author sets forth that, especially in later Platonism, some aspects should be noted different from those which are usually considered as being characteristic of Plato's philosophy : in later Platonism the stress is laid on the fact that the visible world is an image of the invisible as perfect as it could possibly be ; soul is superior to body, but not separated from it ; and in the visible world an element of identity is fundamentally admitted. In Parm. (...) and Soph, motion is introduced into the intelligible world. The main theses of Platonism as a whole are : the existence of a transcendent intelligible world, the existence of an analogy between this intelligible world and ours. It neither can be said that modern philosophy as a whole rejects these theses, nor that Antiquity as a whole accepted them. Aristotle and the schools after him rejected the (first thesis, sceptics denied the second ; Neoplatonism restored them both. During the Middle Ages they were generally accepted ; only Occam denied the principle of analogy. So did Kant, and neopositivism seems to have accepted this heritage, when it holds that metaphysics have no sense. On the other hand, the « existentialism » of the school of Sartre denies that an eternal essence of things would precede their concrete existence ; and by this doctrine the first point of Platonism is denied as well. Against these modern philosophers others do accept the first principles of Platonism, and Plato's own attitude towards the materialistic philosophy of nature of his time authorizes the opinion that, on the point in question, Plato would not change his position if he lived in our days. (shrink)

This article is a longitudinal analysis of the relation between gendered labour divisions and new data processing technologies at the Dutch Central Bureau of Statistics. Following social-constructivist and evolutionary economic approaches, the authors hold that the relation between technology and work organization is a two-way process. This means that technology does not only affect the relations between men and women at work, but that these relations also influence technological choices. The proportional numbers of men and women on the labour market (...) and changing conceptions of which work is deemed appropriate for women have been important factors in the strongly varying extent to which women participated in office work. They have also been important factors in determining the course of technological development. Shortages of women on the labour market have even determined search heuristics for new technological solutions in specific directions. (shrink)

Compared to our understanding of positive prediction error signals occurring due to unexpected reward outcomes, less is known about the neural circuitry in humans that drives negative prediction errors during omission of expected rewards. While classical learning theories such as Rescorla–Wagner or temporal difference learning suggest that both types of prediction errors result from a simple subtraction, there has been recent evidence suggesting that different brain regions provide input to dopamine neurons which contributes to specific components of this prediction error (...) computation. Here, we focus on the brain regions responding to negative prediction error signals, which has been well-established in animal studies to involve a distinct pathway through the lateral habenula. We examine the activity of this pathway in humans, using a conditioned inhibition paradigm with high-resolution functional MRI. First, participants learned to associate a sensory stimulus with reward delivery. Then, reward delivery was omitted whenever this stimulus was presented simultaneously with a different sensory stimulus, the conditioned inhibitor. Both reward presentation and the reward-predictive cue activated midbrain dopamine regions, insula and orbitofrontal cortex. While we found significant activity at an uncorrected threshold for the CI in the habenula, consistent with our predictions, it did not survive correction for multiple comparisons and awaits further replication. Additionally, the pallidum and putamen regions of the basal ganglia showed modulations of activity for the inhibitor that did not survive the corrected threshold. (shrink)

Neurofilaments are one of the major components of the neuronal cytoskeleton and are responsible for maintaining the calibre of axons. They are modified by post‐translational changes that are regulated in complex fashions including by the interaction with neighbouring glial cells. Neurofilament accumulations are seen in several neurological diseases and neurofilament mutations have now been associated with Charcot‐Marie‐Tooth disease, Parkinson's disease and amyotrophic lateral sclerosis. In this review, we discuss the structure, normal function and molecular pathology of neurofilaments. BioEssays 25:346–355, 2003. (...) © 2003 Wiley Periodicals, Inc. (shrink)

BackgroundPregnant people have been overlooked or excluded from clinical research, resulting in a lack of scientific knowledge on medication safety and efficacy during pregnancy. Thus far, both the opportunities to generate evidence-based knowledge beyond clinical trials and the role of pregnant people in changing their status quo have not been discussed. Some scholars have argued that for rare disease patients, for whom, just like pregnant people, a poor evidence base exists regarding treatments, solidarity has played an important role in addressing (...) the evidence gap. This paper explores whether and how the enactment of solidarity among pregnant people can be stimulated to help address the poor evidence base on medications used during pregnancy.MethodWe use the concept of solidarity formulated by Prainsack and Buyx and enrich their concept by providing an account for stimulating the enactment of solidarity. Then we apply this account to the case of pregnant people who use medication.ResultsSolidarity means enacted commitment on the part of an individual to assisting others with whom the person recognizes a similarity in a relevant respect. Although solidarity cannot be imposed, we argue that the empowerment of people is a crucial concept in understanding how solidarity can be stimulated. Empowerment in the context of pregnant people means creating awareness about their status quo, explaining how scientific research can help close the knowledge gap, and how pregnant people can themselves contribute. In particular, how pregnant people can contribute to the collection of health data to strengthen the evidence base for medications used during pregnancy.ConclusionsWe conclude that acting in solidarity can help change the status quo for pregnant people. Furthermore, we argue that the empowerment of pregnant people and other relevant stakeholders is a way to stimulate the enactment of solidarity. The process of empowerment starts by raising awareness about the lack of evidence on medications used during prengnacy and by explaining to pregnant people how they can contribute to changing the way knowledge is being generated by, for example, sharing data on the health effects of medications. (shrink)

This handbook presents a much-needed and comprehensive exploration of the rapidly growing fields of animal welfare and law. In recent years there has been increasing attention paid to our complex, multifaceted relationships with other animals, and in particular, the depth and breadth of various societal uses of animals. This has led to a reconsideration of their moral and social status, which has sometimes challenged the interests of those who use animals. In such a contested domain, sound evidence and reasoning become (...) particularly important. Through firm commitment to such principles, this book explores the biological foundations for the moral consideration of animals, and for evolving conceptualisations of animal welfare. It reviews in detail the welfare concerns associated with numerous forms of animal use. The inclusion of key recent developments such as climate change, pandemics and antimicrobial resistance, ensure this text is among the most current in its field. The ethical implications of the various uses of animals by society are considered, and chapters provide important recommendations for reforms of practice, law or policy. The status of animal law internationally, and in major world regions, is reviewed. Finally, the book considers human behavioural change, and strategies for improving stakeholder communication and education. The handbook is essential reading for students and scholars of animal welfare, animal law and animal ethics everywhere, and for policymakers and other professionals working in the animal welfare sector. (shrink)

Given the possibilities of synthetic biology, weapons of mass destruction and global climate change, humans may achieve the capacity globally to alter life. This crisis calls for an ethics that furnishes effective motives to take global action necessary for survival. We propose a research program for understanding why ethical principles change across time and culture. We also propose provisional motives and methods for reaching global consensus on engineering field ethics. Current interdisciplinary research in ethics, psychology, neuroscience and evolutionary theory grounds (...) these proposals. Experimental ethics, the application of scientific principles to ethical studies, provides a model for developing policies to advance solutions. A growing literature proposes evolutionary explanations for moral development. Connecting these approaches necessitates an experimental or scientific ethics that deliberately examines theories of morality for reliability. To illustrate how such an approach works, we cover three areas. The first section analyzes cross-cultural ethical systems in light of evolutionary theory. While such research is in its early stages, its assumptions entail consequences for engineering education. The second section discusses Howard University and University of Puerto Rico/Mayagüez (UPRM) courses that bring ethicists together with scientists and engineers to unite ethical theory and practice. We include a syllabus for engineering and STEM (Science, Technology, Engineering and Mathematics) ethics courses and a checklist model for translating educational theory and practice into community action. The model is based on aviation, medicine and engineering practice. The third and concluding section illustrates Howard University and UPRM efforts to translate engineering educational theory into community action. Multidisciplinary teams of engineering students and instructors take their expertise from the classroom to global communities to examine further the ethicality of prospective technologies and the decision-making processes that lead to them. (shrink)

Aims. Currently, methylphenidate (MPH, trade name Ritalin) is the most widely prescribed medication for attention deficit/hyperactivity disorder (ADHD). We examined the ability of repeated MPH administration to produce a sensitized appetitive eagerness type response in laboratory rats, as indexed by 50-kHz ultrasonic vocalizations (50-kHz USVs). We also examined the ability of MPH to reduce play behavior in rats which may be partially implicated in the clinical efficacy of MPH in ADHD. Design. 56 adolescent rats received injections of either 5.0 mg/kg (...) MPH, or vehicle each day for 8 consecutive days, and a week later received a challenge injection of either MPH or vehicle. Measurements. Both play behavior (pins) and 50-kHz USVs were recorded after each drug or vehicle administration. Results. MPH challenge produced a substantial 73% reduction in play behavior during the initial treatment phase, and during the last test (1 week post drug), 50-kHz USVs were elevated approximately threefold only in animals with previous MPH experience. Conclusions. These data suggest that MPH treatment may lead to psychostimulant sensitization in young animals, perhaps by increasing future drug-seeking tendencies due to an elevated eagerness for positive incentives. Further, we hypothesize that MPH may be reducing ADHD symptoms, in part, by blocking playful tendencies, whose neuro-maturational and psychological functions remain to be adequately characterized. (shrink)

Any attempt to justify war in the fashion of just war theories risks underestimating its morally problematic nature. This becomes clear if we ask how the individual soldier or citizen is supposed to use just war theory in his own thinking. Michael Walzer's recent book, Just and Unjust Wars, illustrates the problem nicely. Walzer's view is that whether a state is justified in going to war is not a matter for the citizen to judge, and with regard to the way (...) the war is conducted the individual soldier can have only minimal moral responsibility for what is done. Walzer's position is criticized in detail and the conclusion drawn that such an understanding of just war theory undermines the theory's significance as a moral outlook on war. It is also argued that a more pertinent version of just war theory must have strong implications for social change. (shrink)

Shortages of new therapeutics to treat coronavirus disease (COVID-19) have forced clinicians, public health officials, and health systems to grapple with difficult questions about how to fairly allocate potentially life-saving treatments when there are not enough for all patients in need (1). Shortages have occurred with remdesivir, tocilizumab, monoclonal antibodies, and the oral antiviral Paxlovid (2) -/- Ensuring equitable allocation is especially important in light of the disproportionate burden experienced during the COVID-19 pandemic by disadvantaged groups, including Black, Hispanic/Latino and (...) Indigenous communities, individuals with certain disabilities, and low-income persons. However, many health systems have resorted to first-come, first-served approaches to allocation, which tend to disadvantage individuals with barriers in access to care (3). There is mounting evidence of racial, ethnic, and socioeconomic disparities in access to medications for COVID-19 (4, 5). -/- One potential method to promote equitable allocation is to use a weighted lottery, which is an allocation strategy that gives all eligible patients a chance to receive the scarce treatment while also allowing the assignment of higher or lower chances according to other ethical considerations (6). We sought to assess the feasibility of implementing a weighted lottery to allocate scarce COVID-19 medications in a large U.S. health system and to determine whether the weighted lottery promotes equitable allocation. (shrink)

Member States of the United Nations proposed Seventeen Sustainable Development Goals (SDGs) in 2015, emphasizing the well-being of people, planet, prosperity, peace, and partnership. Countries are expected to work diligently to achieve these goals by the year 2030. The paths chosen to achieve the SDGs depend on each country’s specific needs, challenges, and opportunities. This contribution conducts a bibliometric study of selected SDG research related to hunger and climate change among countries of the North Asia Pacific region. A review of (...) literature related to the seventeen SDGs is provided to update the current research in SDGs as a background for the regional bibliometric search. The academic published literature related to this work were collected and text mined to create a research database for trend analysis. In this research, the natural language model KeyBERT and a text mining algorithm for normalized term frequency were used to extract key terminologies for bibliometric analysis. The study provides an overview of the seventeen SDGs in the literature review and then focuses on SDG 2 (zero hunger) and SDG 13 (climate action) publication trends. These two SDGs are in close alignment with sustainable food systems and agricultural development. The conclusion indicates that greater cooperation (SDG 17) is critical to improving the quality of life within the region and in building an ethical framework that restricts external exploitation of resources that benefit newly developed economies over developing economies. (shrink)

Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

That the palliatae of Plautus and Terence, besides purporting to depict Greek life, were in general adaptations of Greek plays has always been known. Statements in the prologues of the Latin plays and by other ancient authors left no room for doubt about this, while allowing the possibility of some exceptions. The question of the relationship of the Latin plays to their Greek models was first seriously addressed in the nineteenth century, mainly by German scholars, under the stimulus of Romantic (...) criticism which attached paramount importance to originality in art. Since then the question has been constantly debated, often with acrimony, and to this day very different answers to it continue to be given. Yet the question is obviously important, both for those who would measure the artistic achievement of the Latin dramatists and for those who would use the plays to document aspects of Greek or Roman life. It is not disputed that Plautus' plays contain many Roman allusions and Latin puns which cannot have been derived from any Greek model and must be attributed to the Roman adapter. What is disputed is whether this overt Romanization is merely a superficial veneer overlaid on fundamentally Greek structures or whether Plautus made more radical changes to the structure as well as the spirit of his models. (shrink)

This paper focuses on invasive therapeutic procedures, defined as procedures requiring the introduction of hands, instruments, or devices into the body via incisions or punctures of the skin or mucous membranes performed with the intent of changing the natural history of a human disease or condition for the better. Ethical and methodological concerns have been expressed about studies designed to evaluate the effects of invasive therapeutic procedures. Can such studies meet the same standards demanded of those, for example, evaluating pharmaceutical (...) agents? This paper describes a research project aimed at examining the interplay and sometimes apparent conflict between ethical standards for human research and standards for methodological rigor in trials of invasive procedures. The paper discusses how the authors plan to develop a set of consensus standards that, if met, would result in substantial and much-needed improvements in the methodological and ethical quality of such trials. (shrink)

Smart grids are rolling out internationally, with the United States nearing completion of a significant USD4-plus-billion federal program funded under the American Recovery and Reinvestment Act. The emergence of smart grids is widespread across developed countries. Multiple approaches to analyzing the benefits of smart grids have emerged. The goals of this white paper are to review these approaches and analyze examples of each to highlight their differences, advantages, and disadvantages. This work was conducted under the auspices of a joint U.S.-China (...) research effort, the Climate Change Working Group Implementation Plan, Smart Grid. We present comparative benefits assessments of smart grid demonstrations in the U.S. and China along with a BA of a pilot project in Europe. In the U.S., we assess projects at two sites: the University of California, Irvine campus, which consists of two distinct demonstrations: Southern California Edison’s Irvine Smart Grid Demonstration Project and the UCI campus itself; and the Navy Yard area in Philadelphia, which has been repurposed as a mixed commercial-industrial, and possibly residential, development. In China, we cover several smart-grid aspects of the Sino-Singapore Tianjin Eco-city and the Shenzhen Bay Technology and Ecology City. In Europe, we look at a BA of a pilot smart grid project in the Malagrotta area west of Rome, Italy, contributed by the Joint Research Centre of the European Commission. The Irvine sub-project BAs use the U.S. Department of Energy Smart Grid Computational Tool, which is built on methods developed by the Electric Power Research Institute. The TEC sub-project BAs apply Smart Grid Multi-Criteria Analysis developed by the State Grid Corporation of China based on the analytic hierarchy process with fuzzy logic. The B-TEC and TNY sub-project BAs are evaluated using new approaches developed by those project teams. JRC has adopted an approach similar to EPRI’s but tailored to the Malagrotta distribution grid. (shrink)

To what extent should scientists, doctors and the community be constrained in their decision-making by a duty to posterity? How should we as a community balance our desire to benefit the present generation against the need not to irretrievably harm our successors? These questions are discussed with particular reference to genetic research and treatment that may have great potential for people suffering from genetic disease but may cause inherited changes in future generations, either deliberately or inadvertently. We conclude that the (...) community should take account of the interests of its successors but this should not immobilise us in the decisions we make for the present. (shrink)

The idea that deep brain stimulation (DBS) induces changes to personality, identity, agency, authenticity, autonomy and self (PIAAAS) is so deeply entrenched within neuroethics discourses that it has become an unchallenged narrative. In this article, we critically assess evidence about putative effects of DBS on PIAAAS. We conducted a literature review of more than 1535 articles to investigate the prevalence of scientific evidence regarding these potential DBS-induced changes. While we observed an increase in the number of publications in theoretical neuroethics (...) that mention putative DBS-induced changes to patients’ postoperative PIAAAS, we found a critical lack of primary empirical studies corroborating these claims. Our findings strongly suggest that the theoretical neuroethics debate on putative effects of DBS relies on very limited empirical evidence and is, instead, reliant on unsubstantiated speculative assumptions probablyin lieuof robust evidence. As such, this may reflect the likelihood of a speculative neuroethics bubble that may need to be deflated. Nevertheless, despite the low number of first-hand primary studies and large number of marginal and single case reports, potential postoperative DBS changes experienced by patients remain a critical ethical concern. We recommend further empirical research in order to enhance theoretical neuroethics work in the area. In particular, we call for the development of better instruments capable of capturing potential postoperative variations of PIAAAS. (shrink)

In a framework describing manifestly covariant relativistic evolution using a scalar time τ, consistency demands that τ-dependent fields be used. In recent work by the authors, general features of a classical parametrized theory of gravitation, paralleling general relativity where possible, were outlined. The existence of a preferred “time” coordinate τ changes the theory significantly. In particular, the Hamiltonian constraint for τ is removed From the Euler-Lagrange equations. Instead of the 5-dimensional stress-energy tensor, a tensor comprised of 4-momentum density mid flux (...) density only serves as the source. Building on that foundation, in this paper we develop a linear approximate theory of parametrized gravitation in the spirit of the flat spacetime approach to general relativity. Using a modified form of Kraichnan's flat spacetime derivation of general relativity, we extend the linear theory to a family of nonlinear theories in which the flat metric and the gravitational field coalesce into a single effective curved metric. (shrink)