Gliomas are diffuse and invasive brain tumors with the nefarious ability to evade even seemingly draconian treatment measures. Here we introduce a simple mathematical model for drug delivery of chemotherapeutic agents to treat such a tumor. The model predicts that heterogeneity in drug delivery related to variability in vascular density throughout the brain results in an apparent tumor reduction based on imaging studies despite continual spread beyond the resolution of the imaging modality. We discuss a clinical example for which the (...) model-predicted scenario is relevant. The analysis and results suggest an explanation for the clinical problem of the long-standing confounding observation of shrinkage of the lesion in certain areas of the brain with continued growth in other areas. (shrink)

In numerous texts Leibniz claimed that while metaphysical necessity is inconsistent with free choice, moral necessity is not. A question naturally arises concerning what Leibniz took moral necessity to be. In a series of recent articles Michael Murray has argued that the concept of moral necessity Leibniz utilized is one developed and deployed by a group of 17th century Spanish Jesuits. This chapter argues that Leibniz's commitment to certain deep metaphysical principles suggests otherwise.

Background: The factors influencing parents’ willingness to enroll their children in biobanks are poorly understood. This study sought to assess parents’ willingness to enroll their children, and their perceived benefits, concerns, and information needs under different consent and data-sharing scenarios, and to identify factors associated with willingness. Methods: This large, experimental survey of patients at the 11 eMERGE Network sites used a disproportionate stratified sampling scheme to enrich the sample with historically underrepresented groups. Participants were randomized to receive one of (...) three consent and data-sharing scenarios. Results: In total, 90,000 surveys were mailed and 13,000 individuals responded (15.8% response rate). 5737 respondents were parents of minor children. Overall, 55% (95% confidence interval 50–59%) of parents were willing to enroll their youngest minor child in a hypothetical biobank; willingness did not differ between consent and data-sharing scenarios. Lower educational attainment, higher religiosity, lower trust, worries about privacy, and attitudes about benefits, concerns, and information needs were independently associated with less willingness to allow their child to participate. Of parents who were willing to participate themselves, 25% were not willing to allow their child to participate. Being willing to participate but not willing to allow one’s child to participate was independently associated with multiple factors, including race, lower educational attainment, lower annual household income, public health care insurance, and higher religiosity. Conclusions: Fifty-five percent of parents were willing to allow their youngest minor child to participate in a hypothetical biobank. Building trust, protecting privacy, and addressing attitudes may increase enrollment and diversity in pediatric biobanks. (shrink)

This book is a collection of secondary essays on America's most important philosophic thinkers—statesmen, judges, writers, educators, and activists—from the colonial period to the present. Each essay is a comprehensive introduction to the thought of a noted American on the fundamental meaning of the American regime.

We propose a model mechanism for the initiation and spatial positioning of teeth primordia in the alligator, Alligator mississippiensis. Detailed embryological studies by Westergaard and Ferguson have shown that jaw growth plays a crucial role in the developmental patterning of the tooth initiation process. Based on biological data we develop a dynamic patterning mechanism, which crucially includes domain growth. The mechanism can reproduce the spatial pattern development of the first seven teeth primordia in each half jaw of A. mississippiensis. The (...) results for the precise spatio-temporal sequence compare well with experiment. Simulation of the model also predicts that certain transplantations can alter the spatial sequence of teeth primordia initiation. (shrink)

Attribution theorists assume that character information informs judgments of blame. But there is disagreement over why. One camp holds that character information is a fundamental determinant of blame. Another camp holds that character information merely provides evidence about the mental states and processes that determine responsibility. We argue for a two-channel view, where character simultaneously has fundamental and evidential effects on blame. In two large factorial studies (n = 495), participants rate whether someone is blameworthy when he makes a mistake (...) (burns a cake or misses a bus stop). Although mental state inferences predict blame judgments, character information does not. Using mediation analyses, we find that character information influences responsibility via two channels (Studies 3–4; n = 447), which are sensitive to different kinds of information (Study 5; n = 149). On the one hand, forgetfulness increases judgments of responsibility, because mental lapses manifest an objectionable character flaw. On the other hand, forgetfulness decreases judgments of state control, which in turn decreases responsibility judgments. These two channels cancel out, which is why we find no aggregate effect of forgetfulness on responsibility. Our results challenge several fundamental assumptions about the role of character information in moral judgment, including that good character typically mitigates blame. (shrink)

1. HUME’S ARGUMENT, FLEW CORRECTLY EXPLAINS, IS NOT THAT MIRACLES CANNOT HAPPEN, BUT THAT THERE MUST BE A CONFLICT IN THE EVIDENCE TO SHOW THAT THEY DO. 2. (I) FLEW FURTHER APPEALS TO THE INHERENT WEAKNESS OF HISTORICAL AS OPPOSED TO SCIENTIFIC EVIDENCE. BUT ONE’S ASSESSMENT OF THE EVIDENCE MUST DEPEND ON WHETHER THE CONCEPT IS POSSIBLE. (II) FLEW CLAIMS THAT HUME CAN BE TAKEN TO MEAN THAT WHAT IS ALLOWED TO BE A LOGICAL POSSIBILITY SHOULD YET BE DISMISSED AS (...) IMPOSSIBLE IN FACT. BUT THIS DISTINCTION CANNOT BE APPLIED IN ADVANCE OF AN OCCURRENCE, WITHOUT BEGGING THE QUESTION AS TO WHETHER IT IS INDEED POSSIBLE OR NOT. 3. PACE HUME AND FLEW, ENTERTAINING THE CONCEPT IS NOT INCOHERENT. FOR (I) THE RELEVANT "LAW OF NATURE" CAN BE THOUGHT OF AS POTENTIALLY APPLICABLE, THOUGH NOT IN FACT SO; (II) ONE MAY CONCEIVE OF AN "UNCAUSED" EVENT, ONCE ONE SUPPOSES THAT IN MOST OTHER CASES THE UNIVERSE IS UNIFORM. THUS IT COULD BE RATIONAL TO JUDGE THAT A MIRACLE HAD OCCURRED, SINCE THIS WOULD NOT CAL. (shrink)

Vijf Nederlandse filosofen geven elk vanuit een andere filosofische achtergrond weer wat hun mensbeeld is.

Hawthorne and Magidor's criticisms of the model of presupposition and assertion that I have used and defended are all based on a rejection of some transparency or introspection of assumptions about speaker presupposition. This response to those criticisms aims first to clarify, and then to defend, the required transparency assumptions. It is argued, first, that if the assumptions are properly understood, some prima facie problems for them do not apply, second, that rejecting the assumptions has intuitively implausible consequences, and third, (...) that the 'margin of error' argument against the principle of positive introspection has a false premiss. The paper concludes with a response to a criticism of what Hawthorne and Magidor call 'the uniformity principle' that is used in the model to explain some pragmatic phenomena. (shrink)