The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

This article explores the influence of sadness in ethical decision-making and behavior. In three laboratory studies, we found that an incidental state of sadness reduced individuals’ propensity to engage in morally questionable behavior, including both unethical and selfish acts (Studies 1 to 3). We found this effect to be mediated by the role of sadness in prompting people to pay more attention to the negative consequences of morally questionable acts and perceive those consequences as more problematic (Studies 2 and 3). (...) This effect was consistent using different decision-making contexts and held when rewards to be gained from such behavior were relatively high. Several implications of these findings for business ethics and organizations are discussed. (shrink)

© 2016 Regents of the University of California.The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,062 new measurements from 721 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous (...) tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Among the 117 reviews are many that are new or heavily revised, including those on Pentaquarks and Inflation. The complete Review is published online in a journal and on the website of the Particle Data Group. The printed PDG Book contains the Summary Tables and all review articles but no longer includes the detailed tables from the Particle Listings. A Booklet with the Summary Tables and abbreviated versions of some of the review articles is also available. (shrink)

Previous research has found that funding disparities are driven by applications’ final impact scores and that only a portion of the black/white funding gap can be explained by bibliometrics and topic choice. Using National Institutes of Health R01 applications for council years 2014–2016, we examine assigned reviewers’ preliminary overall impact and criterion scores to evaluate whether racial disparities in impact scores can be explained by application and applicant characteristics. We hypothesize that differences in commensuration—the process of combining criterion scores into (...) overall impact scores—disadvantage black applicants. Using multilevel models and matching on key variables including career stage, gender, and area of science, we find little evidence for racial disparities emerging in the process of combining preliminary criterion scores into preliminary overall impact scores. Instead, preliminary criterion scores fully account for racial disparities—yet do not explain all of the variability—in preliminary overall impact scores. (shrink)

Distributional models of semantics learn word meanings from contextual co‐occurrence patterns across a large sample of natural language. Early models, such as LSA and HAL (Landauer & Dumais, 1997; Lund & Burgess, 1996), counted co‐occurrence events; later models, such as BEAGLE (Jones & Mewhort, 2007), replaced counting co‐occurrences with vector accumulation. All of these models learned from positive information only: Words that occur together within a context become related to each other. A recent class of distributional models, referred to as (...) neural embedding models, are based on a prediction process embedded in the functioning of a neural network: Such models predict words that should surround a target word in a given context (e.g., word2vec; Mikolov, Sutskever, Chen, Corrado, & Dean, 2013). An error signal derived from the prediction is used to update each word's representation via backpropagation. However, another key difference in predictive models is their use of negative information in addition to positive information to develop a semantic representation. The models use negative examples to predict words that should not surround a word in a given context. As before, an error signal derived from the prediction prompts an update of the word's representation, a procedure referred to as negative sampling. Standard uses of word2vec recommend a greater or equal ratio of negative to positive sampling. The use of negative information in developing a representation of semantic information is often thought to be intimately associated with word2vec's prediction process. We assess the role of negative information in developing a semantic representation and show that its power does not reflect the use of a prediction mechanism. Finally, we show how negative information can be efficiently integrated into classic count‐based semantic models using parameter‐free analytical transformations. (shrink)

Nonverbal signals color the meanings of interpersonal relationships. Humans rely on facial, head, postural, and vocal signals to express relational messages along continua. Three of relevance are dominance-submission, composure-nervousness and trust-distrust. Machine learning and new automated analysis tools are making possible a deeper understanding of the dynamics of relational communication. These are explored in the context of group interactions during a game entailing deception. The “messiness” of studying communication under naturalistic conditions creates many measurement and design obstacles that are discussed (...) here. Possibilities for their mitigation are considered. (shrink)

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into (...) two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop. (shrink)

This co-edited volume compares Chinese and Western experiences of engineering, technology, and development. In doing so, it builds a bridge between the East and West and advances a dialogue in the philosophy of engineering. Divided into three parts, the book starts with studies on epistemological and ontological issues, with a special focus on engineering design, creativity, management, feasibility, and sustainability. Part II considers relationships between the history and philosophy of engineering, and includes a general argument for the necessity of dialogue (...) between history and philosophy. It continues with a general introduction to traditional Chinese attitudes toward engineering and technology, and philosophical case studies of the Chinese steel industry, railroads, and cybernetics in the Soviet Union. Part III focuses on engineering, ethics, and society, with chapters on engineering education and practice in China and the West. The book’s analyses of the interactions of science, engineering, ethics, politics, and policy in different societal contexts are of special interest. The volume as a whole marks a new stage in the emergence of the philosophy of engineering as a new regionalization of philosophy. This carefully edited interdisciplinary volume grew out of an international conference on the philosophy of engineering hosted by the University of the Chinese Academy of Sciences in Beijing. It includes 30 contributions by leading philosophers, social scientists, and engineers from Australia, China, Europe, and the United States. (shrink)

Objectives: To quantify the use of do-not-resuscitate orders in a tertiary-care children’s hospital and to characterise the circumstances in which such orders are written.Design: Retrospective study conducted in a 500-bed children’s hospital in Taiwan.Patients: The course of 101 patients who died between January 2002 and December 2005 was reviewed. The following data were collected: age at death, gender, disease and its status, place of death and survival. There were 59 males and 42 females with a median age of 103 months (...) . 50 children had leukaemias, and 51 had malignancies other than leukaemia. The t test and the χ2 test were applied as appropriate.Results: The study found that 44% of patient deaths occurred in the paediatric oncology ward; 29% of patient deaths occurred in the intensive care unit; and 28% of patients died in their home or at another hospital. Other findings included the following: 46 of 101 patients died after attempted cardiopulmonary resuscitation and 55 died with a DNR order in effect. The mean age at death was 9.8 years in both groups with or without DNR orders.Conclusions: From the study of patient deaths in this tertiary-care children’s hospital, it was concluded that an explicit DNR order is now the rule rather than the exception, with more DNR orders being written for patients who have been ill longer, who have solid tumours, who are not in remission and who are in the ward. (shrink)

© 2015, Springer-Verlag Berlin Heidelberg.Genetic studies have identified single nucleotide polymorphisms associated with the risk of prostate cancer. It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score and aggressiveness. Statistical analyses were used to compare the frequency (...) of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 was significantly and inversely associated with aggressive and high-grade disease in European men. Similar associations with aggressive and high-grade disease were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness. (shrink)

As studies continue to accumulate on leader humility, it has become clear that humility in a leader is largely beneficial to his or her followers. While the majority of the empirical research on this topic has demonstrated the positive effects of leader humility, this study challenges that consensus by arguing that a leader’s humble behavior can have contradictory outcomes in followers’ voice behavior. Drawing on attachment theory, we develop a model which takes into account the ways in which leader humility (...) influences the seemingly contradictory voice behavior of followers, i.e., inducing challenging voice, and defensive voice depending on the followers’ sense of security as reflected by feeling trusted and self-efficacy for voice. The results of this empirical study confirm that leader humility influences followers’ voice in a contradictory way through their sense of security. (shrink)

_Practical Bioethics_ offers a mix of theory and readings, presented in a format that is succinct and approachable. Each chapter begins and ends with a case study, illustrating the core issues at play and emphasizing the practical nature of the dilemmas arising in medicine. Primary source texts are provided to flesh out the issues, and each of these is carefully edited and presented with interwoven explanatory comments to assist student readers. Throughout, J.K. Miles shows the importance of health-care ethics to (...) us all, whether we be medical providers, patients, or both. (shrink)

For two thousand years the Mencius was revered as one of the foundational texts of the Confucian canon, which formed the basis of traditional Chinese education. Today it commands considerable attention in current debates on "Asian values" raging in classrooms and boardrooms in both East Asia and the West. This volume, which represents the work of fifteen respected scholars of early Chinese thought and culture, is an especially timely effort to bring the Mencius under fresh scrutiny. Making use of recently (...) excavated manuscripts, the contributors approach the Mencius from novel perspectives, challenge established interpretations, and confront anew issues that continue to attract and divide students of this classic text. The famous Mencian doctrine of the "goodness" of human nature forms one main focus. Questions of context and interpretation bring into sharp relief key hermeneutical issues that surround the text. Does the Mencius present a coherent and systematically developed ethical teaching? Or should it be read as a composite work, comprising different layers of material that reflect different emphases and conflicting doctrines? Traversing contested territories and exploring new avenues of understanding, the essays presented here do not aim at settling debates; on the contrary, they afford ample opportunities for further discussion on the background, interpretation, and continued relevance of this classic of Confucian philosophy. Contributors: Roger T. Ames, Irene Bloom, A. Taeko Brooks, E. Bruce Brooks, Alan K. L. Chan, Kim-Chong Chong, Antonio S. Cua, Robert Eno, Jiuan Heng, Donald J. Munro, Ning Chen, David Nivison, Kwong-Loi Shun, Sor-Hoon Tan. (shrink)

For two thousand years the Mencius was revered as one of the foundational texts of the Confucian canon, which formed the basis of traditional Chinese education. Today it commands considerable attention in current debates on "Asian values" raging in classrooms and boardrooms in both East Asia and the West. This volume, which represents the work of fifteen respected scholars of early Chinese thought and culture, is an especially timely effort to bring the Mencius under fresh scrutiny. Making use of recently (...) excavated manuscripts, the contributors approach the Mencius from novel perspectives, challenge established interpretations, and confront anew issues that continue to attract and divide students of this classic text. The famous Mencian doctrine of the "goodness" of human nature forms one main focus. Questions of context and interpretation bring into sharp relief key hermeneutical issues that surround the text. Does the Mencius present a coherent and systematically developed ethical teaching? Or should it be read as a composite work, comprising different layers of material that reflect different emphases and conflicting doctrines? Traversing contested territories and exploring new avenues of understanding, the essays presented here do not aim at settling debates; on the contrary, they afford ample opportunities for further discussion on the background, interpretation, and continued relevance of this classic of Confucian philosophy. Contributors: Roger T. Ames, Irene Bloom, A. Taeko Brooks, E. Bruce Brooks, Alan K. L. Chan, Kim-Chong Chong, Antonio S. Cua, Robert Eno, Jiuan Heng, Donald J. Munro, Ning Chen, David Nivison, Kwong-Loi Shun, Sor-Hoon Tan. (shrink)

This new edition of Law and Medical Ethics continues to chart the ever-widening field that the topics cover. The interplay between the health caring professions and the public during the period intervening since the last edition has, perhaps, been mainly dominated by wide-ranging changes in the administration of the National Health Service and of the professions themselves but these have been paralleled by important developments in medical jurisprudence.

Originally published in 1926, this book attempts to state 'what has been believed with regard to God's incapacity for suffering'. Mozley charts the development of the doctrine from the Apostolic Fathers through the Reformation to the modern influence of metaphysical philosophy and concludes with six questions intended to prompt further theological discussion on this point. This book will be of value to anyone with an interest in the history of Christian theology.

Recently, new developments took place in the Dutch debate on the legislation of euthanasia. After a brief account of that debate, the article discusses a new government proposal for legislation in this field, which was submitted to the Dutch parliament in November 1991. This proposal relates not only to euthanasia but also to some other medical decisions concerning the end of life. The author concludes that, for several reasons, it is unsatisfactory.

The advent of personal genomics companies offering direct translation of scientific data into personal health information, calls into question traditional policies to refuse disclosure of such scientific data to research participants. This seems especially true for population biobanks, as they collect not only genotype information but also associated phenotype information, and thus may be in a unique position to translate their scientific findings into personal health information for their participants. Disclosure of such information seems mandated by the expectations raised by (...) biobanks and their participants' rights to know health information, to know clinical research results, to life and health and particularly their right to benefit. Refusals to disclose such information can be grounded in the lack of analytical validity and/or clinical utility of most findings, the need to avoid the therapeutic misconception, the complexity and costs involved in translation and disclosure and the disproportionate burden resulting from the obligation to respect participants' right not to know before any disclosure can be made. Currently, any demands by participants in population biobanks for full disclosure of all pertinent personal health information potentially resulting from the biobank's scientific findings are unlikely to be granted by a Dutch court under Dutch and international law. As the law stands now, a population biobank is neither a doctor nor a personal genomics company. However, in view of the rapid scientific, medical, technological, commercial and social developments, population biobanks must prepare to take more care of their participants' legitimate interest in receiving as much validated personal health information as reasonably possible, in a timely fashion, by developing appropriate translation and disclosure mechanisms. This paper examines whether population biobank participants have the right, under Dutch civil law and international law, to full disclosure, i.e. to all information generated by the biobank that is pertinent to their present and future health. It pioneers the format of a hypothetical court case to elucidate the legal and policy arguments" for and against full disclosure. (shrink)

Replication protein A (RPA) is the main eukaryotic single‐stranded DNA (ssDNA) binding protein, having essential roles in all DNA metabolic reactions involving ssDNA. RPA binds ssDNA with high affinity, thereby preventing the formation of secondary structures and protecting ssDNA from the action of nucleases, and directly interacts with other DNA processing proteins. Here, we discuss recent results supporting the idea that one function of RPA is to prevent annealing between short repeats that can lead to chromosome rearrangements by microhomology‐mediated end (...) joining or the formation of hairpin structures that are substrates for structure‐selective nucleases. We suggest that replication fork catastrophe caused by depletion of RPA could result from cleavage of secondary structures by nucleases, and that failure to cleave hairpin structures formed at DNA ends could lead to gene amplification. These studies highlight the important role RPA plays in maintaining genome integrity. (shrink)

This paper traces the development of parental rights to accept or to refuse treatment for a defective newborn infant in the United Kingdom and in the United States of America; its main purpose is to explore the common trends from which an acceptable policy may be derived. It is probable that the British law on parental decision-making in respect of infants suffering from Down's syndrome is to be found in the civil case of In Re B rather than in the (...) criminal case of R v Arthur. United States court decisions are strongly influenced by constitutional law and reflect the right to personal privacy. The position on each side of the Atlantic seems very similar but this similarity includes a sense of uncertainty as to legal responsibility. There is a case for agreed guidelines and a suggested format is offered for consideration. (shrink)

Mason and McCall Smith's classic textbook discusses the relationship of medical practice and ethics with the operation of the law. The subjects covered include natural and assisted reproduction, the impact of modern genetics on medicine, medical confidentiality, consent to medical treatment, the use of resources and problems surrounding death in the new medical era. It is of significance to anyone with an interest in the ethical and legal practice of medicine.

This article revisits long-standing questions about consent, membership and emigration in Locke’s thought. Commentators such as A John Simmons have argued that Locke opens political membership to both express consenters and some kind of tacit consenters, and not just to the former, as some have suggested. Simmons’s reading seems to render Locke more sensible in that it does not exclude large numbers of people from membership or burden the few members with all the civic duties, and also in that it (...) allows at least tacit-consenting members the right to relocate, while this right is denied to express-consenting members. Against this reading, the article shows, by resolving seemingly conflicting claims in the text, that people become members only by express consent. It also responds to the criticism that the express-consent-only reading would limit membership to a few and so would render Locke’s account implausible from a practical point of view. The article then addresses the purported restriction Locke imposes on express consenters’ right to emigrate, arguing that the restriction concerns the change of membership and not the right to relocate. (shrink)

Recent scholarship on technology-induced ‘conceptual disruption’ has spotlighted the notion of a conceptual gap. Conceptual gaps have also been discussed in scholarship on epistemic injustice, yet up until now these bodies of work have remained disconnected. This article shows that ‘gaps’ of interest to both bodies of literature are closely related, and argues that a joint examination of conceptual disruption and epistemic injustice is fruitful for both fields. I argue that hermeneutical marginalization—a skewed division of hermeneutical resources, which serves to (...) diminish the experiences of marginalized folk—does not only transpire because of conceptual gaps, but also because of two other kinds of conceptual disruption: conceptual overlaps and conceptual misalignments. Hence, there are multiple kinds of conceptual disruption that can be usefully studied through the normative lens of epistemic injustice. Technology can play different roles vis-a-vis epistemic injustices, both as a causal trigger of conceptual disruption, but also as a mediator of hermeneutical resources. Its role is normatively significant, in particular because socially disruptive technologies can have different epistemic implications for different groups: they may amplify the epistemic resources of some groups, while diminishing those of others. (shrink)

The literature on collective action largely ignores the constraints that moral principle places on action-prompting intentions. Here I suggest that neither individualism nor holism can account for the generality of intentional contents demanded by universalizability principles, respect for persons, or proactive altruism. Utilitarian and communitarian ethics are criticized for nominalism with respect to social intentions. The failure of individualism and holism as grounds for moral theory is confirmed by comparing Tuomela's reductivist analysis of we-intentions with Gilbert's analysis of social facts. (...) Tuomela's account founders over intentions to cooperate, and Gilbert's cannot accommodate legitimate authority, vicarious agency, or group structure. (shrink)

With a previous paper (Niu & Wang, 1995), a general, hypothetical outline of the mechanism of carcinogenesis was proposed. With reference to the fact of starvation-induced hypermutation in micro-organisms, we propose that the hypoxia commonly seen in the cells at the centre of solid tumours might also result in hypermutation, and then p53-dependent programmed cell death. Like the apparently adaptive mutations in micro-organisms, only those genes (e.g. p53) that enable the cells to escape from apoptosis may be selected.

Division of labour is a marked feature of multicellular organisms. Margulis proposed that the ancestors of metazoans had only one microtubule organizing center (MTOC), so they could not move and divide simultaneously. Selection for simultaneous movement and cell division had driven the division of labour between cells. However, no evidence or explanation for this assumption was provided. Why could the unicellular ancetors not have multiple MTOCs? The gain and loss of three possible strategies are discussed. It was found that the (...) advantage of one or two MTOC per cell is environment-dependent. Unicellular organisms with only one MTOC per cell are favored only in resource-limited environments without strong predatory pressure. If division of labour occurring in a bicellular organism just makes simultaneous movement and cell division possible, the possibility of its fixation by natural selection is very low because a somatic cell performing the function of an MTOC is obviously wasting resources. Evolutionary biologists should search for other selective forces for division of labour in cells. (shrink)