Equipoise is an essential condition to justify a clinical trial. The term, describes a state of uncertainty: the data suggest but do not prove a drug's safety and efficacy The only way to resolve this uncertainty is further study In many cases, a clinical trial seems to be the most efficient way to prove safety and efficacy Equipoise is therefore not an esoteric philosophic construct applied to research ethics. Rather, since it is vital for the justification of clinical trials, it (...) is part of how society regulates medical progress. Where there is equipoise, drug design and development proceeds according to Food and Drug Administration and Health and Human Services regulations. When that equipoise ends, a drug is either not approved or becomes standard care. (shrink)

Epistasis plays an important role in the genetic architecture of common human diseases and can be viewed from two perspectives, biological and statistical, each derived from and leading to different assumptions and research strategies. Biological epistasis is the result of physical interactions among biomolecules within gene regulatory networks and biochemical pathways in an individual such that the effect of a gene on a phenotype is dependent on one or more other genes. In contrast, statistical epistasis is defined as deviation from (...) additivity in a mathematical model summarizing the relationship between multilocus genotypes and phenotypic variation in a population. The goal of this essay is to review definitions and examples of biological and statistical epistasis and to explore the relationship between the two. Specifically, we present and discuss the following two questions in the context of human health and disease. First, when does statistical evidence of epistasis in human populations imply underlying biomolecular interactions in the etiology of disease? Second, when do biomolecular interactions produce patterns of statistical epistasis in human populations?Answers to these two reciprocal questions will provide an important framework for using genetic information to improve our ability to diagnose, prevent and treat common human diseases. We propose that systems biology will provide the necessary information for addressing these questions and that model systems such as bacteria, yeast and digital organisms will be a useful place to start. BioEssays 27:637–646, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Equipoise is an essential condition to justify a clinical trial. The term, describes a state of uncertainty: the data suggest but do not prove a drug's safety and efficacy The only way to resolve this uncertainty is further study In many cases, a clinical trial seems to be the most efficient way to prove safety and efficacy Equipoise is therefore not an esoteric philosophic construct applied to research ethics. Rather, since it is vital for the justification of clinical trials, it (...) is part of how society regulates medical progress. Where there is equipoise, drug design and development proceeds according to Food and Drug Administration and Health and Human Services regulations. When that equipoise ends, a drug is either not approved or becomes standard care. (shrink)

Differences across fields and experience levels are frequently considered in discussions of ethical decision making and ethical behavior. In the present study, doctoral students in the health, biological, and social sciences completed measures of ethical decision making. The effects of field and level of experience with respect to ethical decision making, metacognitive reasoning strategies, social-behavioral responses, and exposure to unethical events were examined. Social and biological scientists performed better than health scientists with respect to ethical decision making. Furthermore, the ethical (...) decision making of health science students decreased as experience increased. Moreover, these effects appeared to be linked to the specific strategies underlying participants' ethical decision making. The implications of these findings for ethical decision making are discussed. (shrink)

In recent years, we have seen a new concern with ethics training for research and development professionals. Although ethics training has become more common, the effectiveness of the training being provided is open to question. In the present effort, a new ethics training course was developed that stresses the importance of the strategies people apply to make sense of ethical problems. The effectiveness of this training was assessed in a sample of 59 doctoral students working in the biological and social (...) sciences using a pre-post design with follow-up and a series of ethical decision-making measures serving as the outcome variable. Results showed not only that this training led to sizable gains in ethical decision making but also that these gains were maintained over time. The implications of these findings for ethics training in the sciences are discussed. (shrink)

Ethical decision making measures are widely applied as the principal dependent variable used in studies of research integrity. However, evidence bearing on the internal and external validity of these measures is not available. In this study, ethical decision making measures were administered to 102 graduate students in the biological, health, and social sciences, along with measures examining exposure to ethical breaches and the severity of punishments recommended. The ethical decision making measure was found to be related to exposure to ethical (...) events and the severity of punishments awarded. The implications of these findings for the application of ethical decision making measures are discussed. (shrink)

It is commonly held that early career experiences influence ethical behavior. One way early career experiences might operate is to influence the decisions people make when presented with problems that raise ethical concerns. To test this proposition, 102 first-year doctoral students were asked to complete a series of measures examining ethical decision making along with a series of measures examining environmental experiences and climate perceptions. Factoring of the environmental measure yielded five dimensions: professional leadership, poor coping, lack of rewards, limited (...) competitive pressure, and poor career direction. Factoring of the climate inventory yielded four dimensions: equity, interpersonal conflict, occupational engagement, and work commitment. When these dimensions were used to predict performance on the ethical decision-making task, it was found that the environmental dimensions were better predictors than the climate dimensions. The implications of these findings for research on ethical conduct are discussed. (shrink)

Pleiotropy, in which one mutation causes multiple phenotypes, has traditionally been seen as a deviation from the conventional observation in which one gene affects one phenotype. Epistasis, or gene–gene interaction, has also been treated as an exception to the Mendelian one gene–one phenotype paradigm. This simplified perspective belies the pervasive complexity of biology and hinders progress toward a deeper understanding of biological systems. We assert that epistasis and pleiotropy are not isolated occurrences, but ubiquitous and inherent properties of biomolecular networks. (...) These phenomena should not be treated as exceptions, but rather as fundamental components of genetic analyses. A systems level understanding of epistasis and pleiotropy is, therefore, critical to furthering our understanding of human genetics and its contribution to common human disease. Finally, graph theory offers an intuitive and powerful set of tools with which to study the network bases of these important genetic phenomena. (shrink)

During the 1970s and 1980s, political psychologists at the State University of New York at Stony Brook focused political scientists’ attention on online processing. Borrowing from the new field of social cognition in psychology, they argued that voters’ evaluations of candidates are the products of a summing up of reactions to happenings during a campaign. Voters might not remember the specific events later on, but their running tallies of reactions over the duration of the campaign would ensure that they take (...) the forgotten information into account when entering the voting booth. Later, these same scholars yet again borrowed from (a very changed) psychology, and argued that many people, especially the most politically sophisticated, try to confirm their current political evaluations—for example, by seeking out confirmatory evidence and dismissing evidence that challenges their attitudes. We ask whether online processing and motivated reasoning have the same or different implications for democratic governance, and whether the two empirical perspectives can be reconciled. (shrink)

During the 1970s and 1980s, political psychologists at the State University of New York at Stony Brook focused political scientists’ attention on online processing. Borrowing from the new field of social cognition in psychology, they argued that voters’ evaluations of candidates are the products of a summing up of reactions to happenings during a campaign. Voters might not remember the specific events later on, but their running tallies of reactions over the duration of the campaign would ensure that they take (...) the forgotten information into account when entering the voting booth. Later, these same scholars yet again borrowed from (a very changed) psychology, and argued that many people, especially the most politically sophisticated, try to confirm their current political evaluations—for example, by seeking out confirmatory evidence and dismissing evidence that challenges their attitudes. We ask whether online processing and motivated reasoning have the same or different implications for democratic governance, and whether the two empirical perspectives can be reconciled. (shrink)

The Romans commanded the largest and most complex empire the world had ever seen, or would see until modern times. The challenges, however, were not just political, economic and military: Rome was also the hub of a vast information network, drawing in worldwide expertise and refashioning it for its own purposes. This fascinating collection of essays considers the dialogue between technical literature and imperial society, drawing on, developing and critiquing a range of modern cultural theories. How was knowledge shaped into (...) textual forms, and how did those forms encode relationships between emperor and subjects, theory and practice, Roman and Greek, centre and periphery? Ordering Knowledge in the Roman Empire will be required reading for those concerned with the intellectual and cultural history of the Roman Empire, and its lasting legacy in the medieval world and beyond. (shrink)

Developing cells acquire mature fates in part by selective (i.e. qualitatively different) expression of a few cell‐specific genes. However, all cells share the same basic repertoire of molecular and subcellular building blocks. Therefore, cells must also specialize according to quantitative differences in cell‐specific distributions of those common molecular resources. Here we propose the novel hypothesis that evolutionarily‐conserved transcription factors called scaling factors (SFs) regulate quantitative differences among mature cell types. SFs: (1) are induced during late stages of cell maturation; (2) (...) are dedicated to specific subcellular domains; and, thus, (3) allow cells to emphasize specific subcellular features. We identify candidate SFs and discuss one in detail: MIST1 (BHLHA15, vertebrates)/DIMM (CG8667, Drosophila); professional secretory cells use this SF to scale up regulated secretion. Because cells use SFs to develop their mature properties and also to adapt them to ever‐changing environmental conditions, SF aberrations likely contribute to diseases of adult onset. (shrink)

Uses an ongoing legal controversy to explore the controversial subject of religious liberty and education.

Over the past decade, ethical leadership has increasingly become one of the most popular topics in the areas of leadership and business ethics. As a result, there now exists a substantial body of empirical research addressing ethical leadership issues, but the findings reported by this body of research are highly fragmented. The topic has advanced to the stage where a review and synthesis of existing literature can provide great value and help move the scholarly conversation forward. The primary purposes of (...) this article are to review empirical findings from the ethical leadership literature utilizing a framework consisting of the antecedents, mediators, moderators and outcomes of ethical leadership, and suggest a set of interesting research opportunities, thereby facilitating future investigation. We base our synthesis on a review of 62 empirical studies on ethical leadership that were published between 2005 and mid-2015. (shrink)

As concerns over the negative social and environmental impacts of industrial agriculture become more widespread, efforts to define and regulate sustainable agriculture have proliferated in the US. Whereas the USDA spearheaded previous efforts, today such efforts have largely shifted to Tripartite Standards Regimes (TSRs). Using a case study of the Leonardo Academy’s initiative to develop a US sustainable agriculture standard, this paper examines the standards-development process and efforts by agribusiness to influence the process. Specifically, we analyze how politics operate in (...) seemingly “depoliticized” TSRs, and how agribusiness and the USDA use “framing practices” and procedural complaints to influence the standard-development process. We contend that although governance mechanisms are a potentially powerful tool for advocates of alternative agrifood, their efficacy may be constrained by science-based requirements, an agribusiness countermovement, and a captured state. (shrink)

Dr. theol. Ulrich H.J. Körtner ist Professor für Systematische Theologie an der Evangelisch-Theologischen Fakultät der Universität Wien.

He-Yin Zhen (1886–1920) was a female theorist who played a central role in the birth of Chinese feminism. Editor of a prominent feminist-anarchist journal in the early twentieth century and exponent of a particularly incisive analysis of China and the world. Unlike her contemporaries, He-Yin Zhen was concerned less with China’s fate as a nation and more with the relationship among patriarchy, imperialism, capitalism, and gender subjugation as global and transhistorical problems. Her bold writings were considered radical and dangerous in (...) her lifetime and gradually have been erased from the historical record. This volume, the first translation and study of He-Yin’s work in English or Chinese, is also a critical reconstruction of early twentieth-century Chinese feminist thought in a transnational context. The book repositions He-Yin Zhen as central to the development of feminism in China, juxtaposing her writing with fresh translations of works by two of her better-known male interlocutors. -/- The editors begin with a detailed portrait of He-Yin Zhen’s life and an analysis of her thought in comparative terms. They then present annotated translations of six of her major essays, as well as two foundational tracts by her male contemporaries, Jin Tianhe (1873–1947) and Liang Qichao (1873–1929), to which He-Yin’s work responds and with which it engages. Jin Tianhe, a poet and educator, and Liang Qichao, a philosopher and journalist, understood feminism as a paternalistic cause that “enlightened” male intellectuals like themselves should defend. Zhen counters with an alternative conception of feminism that draws upon anarchism and other radical trends in thought. Ahead of her time within the context of both modernizing China and global feminism, He-Yin Zhen complicates traditional accounts of women and modern history, offering original perspectives on sex, gender, labor, and power that continue to be relevant to feminist theorists in China, Europe, and America. (shrink)

Deep brain stimulation of the subthalamic nucleus is a clinically effective tool for treating medically refractory Parkinson’s disease, but its neural mechanisms remain debated. Previous work has demonstrated that STN DBS results in evoked potentials in the primary motor cortex, suggesting that modulation of cortical physiology may be involved in its therapeutic effects. Due to technical challenges presented by high-amplitude DBS artifacts, these EPs are often measured in response to low-frequency stimulation, which is generally ineffective at PD symptom management. This (...) study aims to characterize STN-to-cortex EPs seen during clinically relevant high-frequency STN DBS for PD. Intraoperatively, we applied STN DBS to 6 PD patients while recording electrocorticography from an electrode strip over the ipsilateral central sulcus. Using recently published techniques, we removed large stimulation artifacts to enable quantification of STN-to-cortex EPs. Two cortical EPs were observed – one synchronized with DBS onset and persisting during ongoing stimulation, and one immediately following DBS offset, here termed the “start” and the “end” EPs respectively. The start EP is, to our knowledge, the first long-latency cortical EP reported during ongoing high-frequency DBS. The start and end EPs differ in magnitude and latency, and the end, but not the start, EP magnitude has a significant relationship to ongoing high gamma power during the EP. These contrasts may suggest mechanistic or circuit differences in EP production during the two time periods. This represents a potential framework for relating DBS clinical efficacy to the effects of a variety of stimulation parameters on EPs. (shrink)

Previous research has shown that emotionally-valenced words are given higher judgements of learning (JOLs) than are neutral words. The current study examined potential explanations for this emotional salience effect on JOLs. Experiment 1 replicated the basic emotionality/JOL effect. In Experiments 2A and 2B, we used pre-study JOLs and assessed memory beliefs qualitatively, finding that, on average, participants believed that positive and negative words were more memorable than neutral words. Experiment 3 utilised a lexical decision task, resulting in lower reaction times (...) (RTs) for positive words than for neutral words, but equivalent RTs for negative and neutral words, suggesting that processing fluency may partially account for higher JOLs for positive words, but not for negative words. Finally, we conducted a series of moderation analyses in Experiment 4 which assessed the relative contributions of fluency and beliefs to JOLs by measuring both factors in the same participants, showing that RTs made no significant contribution to JOLs for either positive or negative words. Our findings suggest that although positive words may be more fluently processed than neutral words, memory beliefs are the primary factor underlying higher JOLs for both positive and negative words. (shrink)

A new field of gene expression regulation research is emerging that has previously been overlooked. This new area is concerned with distinguishing the expression of a single gene from the averaged expression of many gene copies within the cell population. This paper reviews research focused on individual genes in inducible gene expression systems. The main experimental strategy is to measure the gene expression level of a single cell containing a single reporter gene molecule. In contrast to the commonly held belief, (...) gene induction is found to be stochastic under certain conditions. The possible mechanisms and implications are discussed. (shrink)

The new science of genomics endeavors to chart the genomes of individuals around the world, with the dual goals of understanding the role genetic factors play in human health and solving problems of disease and disability. From the perspective of indigenous peoples and developing countries, the promises and perils of genomic science appear against a backdrop of global health disparity and political vulnerability. These conditions pose a dilemma for many communities when attempting to decide about participating in genomic research or (...) any other biomedical research. Genomic research offers the possibility of improved technologies for managing the acute and chronic diseases that plague their members. Yet, the history of particularly biomedical research among people in indigenous and developing nations offers salient examples of unethical practice, misuse of data, and failed promises. This dilemma creates risks for communities who decide either to participate or not to participate in genomic science research. Some argue that the history of poor scientific practice justifies refusal to join genomic research projects. Others argue that disease poses such great threats to the well-being of people in indigenous communities and developing nations that not participating in genomic research risks irrevocable harm. Thus, some communities particularly among indigenous peoples have declined to participate as subjects in genomic research. At the same time, some communities have begun developing new guidelines, procedures, and practices for engaging with the scientific community that offer opportunities to bridge the gap between genomic science and indigenous and/or developing communities. Four new approaches warrant special attention and further support: consulting with local communities; negotiating the complexities of consent; training members of local communities in science and health care; and training scientists to work with indigenous communities. Implicit is a new definition of “rigorous scientific research,” one that includes both community development and scientific progress as legitimate objectives of genomic research. Innovative translational research is needed to develop practical, mutually acceptable methods for crossing the divide between genomic researchers and indigenous communities. This may mean the difference between success and failure in genomic science, and in improving health for all peoples. (shrink)

The new science of genomics endeavors to chart the genomes of individuals around the world, with the dual goals of understanding the role genetic factors play in human health and solving problems of disease and disability. From the perspective of indigenous peoples and developing countries, the promises and perils of genomic science appear against a backdrop of global health disparity and political vulnerability. These conditions pose a dilemma for many communities when attempting to decide about participating in genomic research or (...) any other biomedical research. Genomic research offers the possibility of improved technologies for managing the acute and chronic diseases that plague their members. Yet, the history of biomedical research among people in indigenous and developing nations offers salient examples of unethical practice, misuse of data and failed promises. This dilemma creates risks for communities who decide either to participate or not to participate in genomic science research. (shrink)