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)

Conceptual metaphor theory (CMT) has become prominent in metaphor scholarship because of its explanation of the relations between people's metaphoric thoughts and their use of metaphoric discourse. Our aim in this article is to explore the temporal characteristics of how conceptual metaphors shape verbal metaphor use. We argue that cognitive linguistics and psycholinguistics mostly adopt simplistic, and psychologically implausible, views of how conceptual metaphors are activated and then constrain people's comprehension of metaphoric language. But more contemporary ideas on how cognitive (...) processing unfolds over time in human experience provide better models of how conceptual metaphors shape verbal metaphor use. The implications of this newer vision of CMT are discussed, particularly in regard to methods for studying how conceptual metaphors support interpretation of linguistic metaphor. (shrink)

Even though anthropogenic climate change is largely caused by industrialized nations, its burden is distributed unevenly with poor developing countries suffering the most. A common response to livelihood insecurities and destruction is migration. Using Peter Singer's ‘historical principle’, this paper argues that a morally just evaluation requires taking causality between climate change and migration under consideration. The historical principle is employed to emphasize shortcomings in commonly made philosophical arguments to oppose immigration. The article concludes that none of these arguments is (...) able to override the moral responsibility of industrialized countries to compensate for harms that their actions have caused. (shrink)

Garrod, Smith and the contributors of the volume envisage the longue durée poetics of an early modern genre. They interpret its poetics alongside its various epistemic agenda and make a case for the literary status of natural history.

Advances in molecular biological research in the latter half of the twentieth century have made the story of the gene vastly complicated: the more we learn about genes, the less sure we are of what a gene really is. Knowledge about the structure and functioning of genes abounds, but the gene has also become curiously intangible. This collection of essays renews the question: what are genes? Philosophers, historians and working scientists re-evaluate the question in this volume, treating the gene as (...) a focal point of interdisciplinary and international research. It will be of interest to professionals and students in the philosophy and history of science, genetics and molecular biology. (shrink)

Mental causation has been a hotly disputed topic in recent years, with reductive and non-reductive physicalists vying with each other and with dualists over how to accommodate, or else to challenge, two widely accepted metaphysical principles—the principle of the causal closure of the physical domain and the principle of causal non-overdetermination—which together appear to support reductive physicalism, despite the latter’s lack of intuitive appeal. Current debate about these matters appears to have reached something of an impasse, prompting the question of (...) why this should be so. One possibility well worth exploring is that, while this debate makes extensive use of ontological vocabulary—by talking, for instance, of substances, events, states, properties, powers, and relations—relatively little attempt has been made within the debate itself to achieve either clarity or agreement about what, precisely, such terms should be taken to mean. Hence, the debate has become somewhat detached from broader developments in metaphysics and ontology, which have lately been proceeding apace, providing us with an increasingly rich and refined set of ontological categories upon which to draw, as well as a much deeper understanding of how they are related to one another. In preparing this volume, the editors invited leading metaphysicians and philosophers of mind to reflect afresh upon the problem of mental causation in the light of some of these recent developments, with a view to making new headway with one of the most challenging and seemingly intractable issues in contemporary philosophy. (shrink)

Power and authority in terms of the Ten Commandments (TCs) are discussed. The paper reviews the TCs in Christianity, Judaism, and Islam. The treatment and basis for power and authority in each religion are clarified. Implications of power and authority using the perspective of the TCs are provided. The paper suggests that in today's business environment people tend to be selective in identifying only with certain elements of the TCs that fit their interest and that the TCs should be viewed (...) as general moral guidelines. (shrink)

Summary This contribution examines the history of the production of Galileo's 1638 Discorsi. It provides a detailed narrative of Galileo's and his collaborators' attempts to secure a printer for the work. Through analysis of surviving correspondence, manuscripts, and proof copies, I examine in greater detail the working methods of Galileo and his correspondents, particularly in regards to the text's images. This examination serves as a boon to historians of the early modern book, as Galileo's surviving correspondence provides an unusually rich (...) record of his and his collaborators' activities. I show that the volume was produced through a collaborative process in which Galileo's correspondents played a significant role in determining the work's layout, images, and content. The study thus complements the claims of previous scholars, who have argued for the collaborative nature of much of Galileo's intellectual work. It also offers a new perspective on the Discorsi, a text which is often studied for insight into Galileo's process of discovery. (shrink)

As the federal government distributed remdesivir to some of the states COVID-19 hit hardest, policymakers scrambled to develop criteria to allocate the drug to their hospitals. Our state, Michigan, was among those states to receive an initial quantity of the drug from the U.S. government. The disparities in burden of disease in Michigan are striking. Detroit has a death rate more than three times the state average. Our recommendation to the state was that it should prioritize the communities that bear (...) a disproportionate burden of suffering in the allocation of the new potential treatment. This recommendation is justified not only for new drugs with uncertain effects, but also for drugs of certain benefit or vaccines. For states with significant health disparities, such as Michigan, this allocation priority may help to repair them. In fact, any other allocation strategy may make them worse. (shrink)

The essay examines the impact of thought insertion on typical conceptions of self-consciousness. Stephens and Graham have recently argued that thought insertion is compatible with the inseparability thesis, which maintains that with regard to self-consciousness subjectivity is a proper part of introspection--introspection and subjectivity are inseparable. They argue that thought insertion is an error of agency and not an error of subjectivity. The essay contends that even if they are correct in their interpretation that thought insertion is an error of (...) agency rather than subjectivity, which is unlikely, they are incorrect to maintain that it is not also an error of subjectivity. Evidence is put forth to indicate that thought insertion is, at best, a mistake of agency and subjectivity. It is concluded that thought insertion is incompatible with the inseparability thesis, and a new inseparability thesis is thereby postulated. (shrink)

The current debate on “free agency” seems to highlight the romantic aspects of free agent and considers it a genuine response to changing economic conditions (e.g., high-unemployment rate, importance of knowledge in the labor market, the eclipse of organizational loyalty, and self pride). Little attention, if any, has been given to the religious root of the free agency concept and its persistent existence across history. In this paper, the current discourse on free agency and the conditions that have led to (...) its emergence are briefly discussed. The paper focuses on the theological perspectives of Judaism, Christianity, and Islam on the concept. Implications for management and business organizations are provided. (shrink)

The generation of evidence is integral to the work of public health and health service providers. Traditionally, ethics has been addressed differently in research projects, compared with other forms of evidence generation, such as quality improvement, program evaluation, and surveillance, with review of non-research activities falling outside the purview of the research ethics board. However, the boundaries between research and these other evaluative activities are not distinct. Efforts to delineate a boundary – whether on grounds of primary purpose, temporality, underlying (...) legal authority, departure from usual practice, or direct benefits to participants – have been unsatisfactory. (shrink)

The dominant approach to the study of dynamic preference is to generate preference change by manipulating aspects of decision-problem presentation (problem description, task procedure, contextual options). The predisposing approach instead manipulates the decision maker’s mental state while holding problem presentation constant. Three illustrative studies are outlined here. The first modified preferences for ambitious consumption by manipulating subjects’ consumption energy. The second modified preferences for immediate consumption by manipulating subjects’ hedonic resources. The third modified preferences for consumption itself by manipulating subjects’ (...) desire proneness. Whereas framing is thought to affect perception, predisposing apparently can affect tastes and so involves a special kind of preference dynamism. (shrink)

Lankford’s (2013) essential empirical argument, which is based on evidence such as psychological autopsies, is that suicide attacks are caused by suicidality. By operationalizing this causal claim in a hypothetical experiment, I show the claim to be provable, and I contend that its truth is supported by Lankford’s data. However, I question the success of his follow-on arguments about beauty and goodness.

The meaning of an experimental result depends on the experiment's conceptual backdrop, particularly its null hypothesis. This observation provides the basis for a functional interpretation of belief in the base rate fallacy. On this interpretation, if the base rate fallacy is to be labelled a “myth,” then it should be recognized that this label is not necessarily a disparaging one.

Lankford’s (2013) essential empirical argument, which is based on evidence such as psychological autopsies, is that suicide attacks are caused by suicidality. By operationalizing this causal claim in a hypothetical experiment, I show the claim to be provable, and I contend that its truth is supported by Lankford’s data. However, I question the success of his follow-on arguments about beauty and goodness.

One of the more draining aspects of being a clinical ethicist is dealing with the emotions of patients, family members, as well as healthcare providers. Generally, by the time a clinical ethicist is called into a case, stress levels are running high, patience is low, and interpersonal communication is strained. Management of this emotional burden of clinical ethics is an underexamined aspect of the profession and academic literature. The emotional nature of doing clinical ethics consultation may be better addressed by (...) utilizing concepts and tools from clinical psychology. Management of countertransference, the natural emotional reaction by the therapist toward the patient, is a widely discussed topic in the psychotherapeutic literature. This concept can be adapted to the clinical ethics encounter by broadening it beyond the patient-therapist relationship to refer to the ethics consultant's emotional response toward the patient, the family, or other members the healthcare team. Further, it may aid the consultant because a recognition of the source and nature of these reactions can help maintain ‘critical distance’ and minimize bias in the same way that a psychologist maintains neutrality in psychotherapy. This paper will offer suggestions on how to manage these emotional responses and their burden in the clinical ethics encounter, drawing upon techniques and strategies recommended in the psychotherapeutic literature. Using these techniques may improve consultation outcomes and reduce the emotional burden on the clinical ethicist. (shrink)

In this article, we address the problem of how technoscience knowledge and practices are translated when they are relocated during the highly organized, international encounters between cultures, often called “development.” We examine efforts to build a “model” Australian dairy and instantiate Australian dairy practices in East Timor following East Timor’s recent emergence as a nation-state. Through this ethnography of development’s construction of a heterogeneous sociotechnical assemblage, we show how knowledge and power inform the practices that enable Western models of production (...) and exchange to be reassembled in postcolonial spaces. In aiming to conduct a symmetrical anthropology of development based in the actor-network approach, we follow development’s actors and actants as well as its epistemic divisions—nature and culture, human and nonhuman, us and them—into East Timor, arguing that the politics and agency of technology transfer is distributed among discourse, epistemology, and human and nonhuman actors. (shrink)

Organizational integrity is a key concept with and through which a company can assume its responsibility for ethical and societal issues. It is a basic premise for sustainable corporate success, as ethical risks ultimately become economic risks for a company. Recent research shows the potential of integrity‐based governance models to reduce corporate risks and to improve business performance. However, companies are not yet able to assess nor evaluate their level of organizational integrity in a sound and systematic way. We aim (...) to develop a theoretical model as a basis for the measurement of organizational integrity by conceptualizing the construct and sizing the theoretical model's scope. We suggest that the theoretical model follows a holistic approach and involves three types of dimensions: prerequisite dimensions, independent dimensions, and dependent dimensions. The organizational integrity triad—consisting of active commitments to self‐imposed norms and principles, their transparent institutionalization into corporate processes and structures, and their implementation into action—plays a key role in this context. (shrink)