This is the most stimulating and therefore the most important book elicited by the bicentennial of the American Constitution. At first sight, it appears to be yet another contribution to the ongoing debate among intellectual historians and historians of political theory about the relative influence of Lockean liberalism and so-called "classical republicanism" on the thought and deeds of the American founding generation. Pangle does indeed maintain that Locke, not classical republicanism, was the most powerful influence on America's most thoughtful, articulate, (...) and farsighted statesmen. But his more important claim is that Locke is still "America's philosopher," whose thought even today remains the introduction to philosophy for the Founders' authentic heirs--those public-spirited citizens who wish to take a reasonable pride in America but are perplexed about what, if anything, supports nobility and human dignity in their regime. That is, Pangle does not understand his book to be primarily an exercise in either intellectual history or history of political theory. He argues, rightly I believe, that the most influential present-day historians take for granted the truth of some version of historicism and are thereby prevented either from understanding Locke and the Framers as they understood themselves or from taking seriously the possibility that their understanding of the modern liberal republic may be superior to our own. Thus Pangle aims "to recover for modern liberals and citizens of liberal democracy something of [the] excitement and greatness and challenge" of "the theoretical choices" confronting Locke and the Founders. By suspending the prejudice in favor of historicism, Pangle seeks to show that we are not, simply by virtue of our particular vantage point, beyond the problems with which Locke and the Framers had to wrestle. (shrink)

An increasing number of people seek medical attention for mild cognitive symptoms at older age, worried that they might develop Alzheimer’s disease. Some clinical practice guidelines suggest offering biomarker testing in such cases, using a brain scan or a lumbar puncture, to improve diagnostic certainty about Alzheimer’s disease and enable an earlier diagnosis. Critics, on the other hand, point out that there is no effective Alzheimer treatment available and argue that biomarker tests lack clinical validity. The debate on the ethical (...) desirability of biomarker testing is currently polarized; advocates and opponents tend to focus on their own line of arguments. In this paper, we show how the method of reflective equilibrium can be used to systematically weigh the relevant arguments on both sides of the debate to decide whether to offer Alzheimer biomarker testing. In the tradition of RE, we reflect upon these arguments in light of their coherence with other argumentative elements, including relevant facts, ethical principles, and theories on societal ideals or relevant concepts, such as autonomy. Our stance in the debate therefore rests upon previously set out in-depth arguments and reflects a wide societal perspective. (shrink)

Many philosophers of science and methodologists have argued that the ability to repeat studies and obtain similar results is an essential component of science. A finding is elevated from single observation to scientific evidence when the procedures that were used to obtain it can be reproduced and the finding itself can be replicated. Recent replication attempts show that some high profile results – most notably in psychology, but in many other disciplines as well – cannot be replicated consistently. These replication (...) attempts have generated a considerable amount of controversy, and the issue of whether direct replications have value has, in particular, proven to be contentious. However, much of this discussion has occurred in published commentaries and social media outlets, resulting in a fragmented discourse. To address the need for an integrative summary, we review various types of replication studies and then discuss the most commonly voiced concerns about direct replication. We provide detailed responses to these concerns and consider different statistical ways to evaluate replications. We conclude there are no theoretical or statistical obstacles to making direct replication a routine aspect of psychological science. (shrink)

The Coalition of Immokalee Workers (CIW) has successfully combated modern-day slavery by transforming the ways that over a dozen major brands, including Taco Bell, Subway, and Wal-Mart, manage their supply chains. The CIW’s efforts over more than 20 years have effectively stopped enslavement practices, including abuses such as wage theft and peonage indebtedness. We conducted a field ethnography, interviews, and archival analyses to understand this success. We find that the CIW employs a decentered, egalitarian, and ensemble approach to their multiplicities (...) of alliances by collectively “animating” themselves and their partners through ensemble leadership. This combination of alliances, along with worker-driven monitoring, brings life to the CIW motto “We are all leaders.” Translating this motto into daily practice is how the CIW virtually eradicates enslavement practices in corporate supply chains. (shrink)

“Public health legal preparedness” is a term born in the ferment, beginning in the late 1990s, that has led to unprecedented recognition of the essential role law plays in public health and, even more recently, in protecting the public from terrorism and other potentially catastrophic health threats.The initial articulation of public health has not kept pace with rapid evolution in the concept and in practical development of public health preparedness itself. This poses the risk that legal preparedness may fall behind (...) construction of general readiness in the public health system—and may, in fact, undercut achievement of comprehensive public health preparedness for massive threats to health in both the United States and world-wide. Inadvertent results might include both negative health impacts and infringement on individual rights. (shrink)

We offer a systematic examination of propensity interpretations of fitness, which emphasizes the role that fitness plays in evolutionary theory and takes seriously the probabilistic character of evolutionary change. We distinguish questions of the probabilistic character of fitness from the particular interpretations of probability which could be incorporated. The roles of selection and drift in evolutionary models support the view that fitness must be understood within a probabilistic framework, and the specific character of organism/environment interactions supports the conclusion that fitness (...) must be understood as a propensity rather than as a limiting frequency. (shrink)

Signaling by the Epidermal Growth Factor Receptor (EGFR) and related ErbB family receptor tyrosine kinases can be deregulated in human malignancies as the result of mutations in the genes that encode these receptors. The recent identification of EGFR mutations that correlate with sensitivity and resistance to EGFR tyrosine kinase inhibitors in lung and colon tumors has renewed interest in such activating mutations. Here we review current models for ligand stimulation of receptor dimerization and for activation of receptor signaling by receptor (...) dimerization. In the context of these models, we discuss ErbB receptor mutations that affect ligand binding and those that cause constitutive receptor phosphorylation and signaling as a result of constitutive receptor dimerization. We discuss mutations in the cytoplasmic regions that affect enzymatic activity, substrate specificity and coupling to effectors and downstream signaling pathways. Finally, we discuss how emergent mechanisms of ErbB receptor mutational activation could impact the search for clinically relevant ErbB receptor mutations. BioEssays 29:558–565, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Chisholm’s Epistemology Roderick M. Chisholm, a luminary of 20th century philosophy, is best known for his contributions in epistemology and metaphysics. His groundbreaking theory of knowledge opened the door to the late 20th and early 21st century work on the analysis of knowledge, skepticism, foundationalism, internalism, the ethics of beliefs, and evidentialism, to name just … Continue reading Roderick M. Chisholm: Epistemology →.

Early exposure to stressful life events is associated with greater risk of chronic diseases and mental health problems, including anxiety. However, there is significant variation in how individuals respond to environmental adversity, perhaps due to individual differences in processing and regulating emotional information. Differences in cognitive control – processes necessary for implementing goal directed behavior – have been linked to both stress exposure and anxiety, but the directionality of these links is unclear. The present study investigated the longitudinal pathway of (...) environmental stress exposure during early adolescence on later adolescent anxiety, and the possible mediating mechanism of cognitive control. Participants were 674 Mexican-origin adolescents (mean age = 10.8 years, 50% male) enrolled in the California Families Project, an ongoing longitudinal study of Mexican-origin families. In the current analysis, we examined self-reports of environmental stressors at age 14 (Time 1), cognitive control at age 16 (Time 2), and anxiety at age 18 (Time 3). Structural equation modeling revealed that environmental stressors (Time 1) had both direct and indirect effects on later anxiety (Time 3) through their effects on cognitive control (Time 2), even when accounting for prior levels of anxiety (Time 2). Cognitive control accounted for 18% of the association between environmental stressors and adolescent anxiety: an increase in stressors decreased cognitive control (β = −0.20, p p = 0.004). These findings deepen our understanding of the mechanisms underlying the development of anxiety and highlight the importance of cognitive control as a potential protective factor. (shrink)