Heterogeneity within MDD has hampered identification of biological markers (e.g., intermediate phenotypes, IPs) that might increase risk for the disorder or reflect closer links to the genes underlying the disease process. The newer characterizations of dimensions of MDD within Research Domain Criteria (RDoC) domains may align well with the goal of defining IPs. We compare a sample of 25 individuals with MDD compared to 29 age and education matched controls in multimodal assessment. The multimodal RDoC assessment included the primary IP (...) biomarker, positron emission tomography (PET) with a selective radiotracer for 5-HT1A ([11C]WAY-100635), as well as event-related functional MRI with a Go/No-go task targeting the Cognitive Control network, neuropsychological assessment of affective perception, negative memory bias and Cognitive Control domains. There was also an exploratory genetic analysis with the serotonin transporter (5-HTTLPR) and monamine oxidase A (MAO-A) genes. In regression analyses, lower 5-HT1A binding potential (BP) in the MDD group was related to diminished engagement of the Cognitive Control network, slowed resolution of interfering cognitive stimuli, one element of Cognitive Control. In contrast, higher/normative levels of 5-HT1A BP in MDD (only) was related to a substantial memory bias toward negative information, but intact resolution of interfering cognitive stimuli and greater engagement of Cognitive Control circuitry. The serotonin transporter risk allele was associated with lower 1a BP and the corresponding imaging and cognitive IPs in MDD. Lowered 5HT 1a BP was present in half of the MDD group relative to the control group. Lowered 5HT 1a BP may represent a subtype including decreased engagement of Cognitive Control network and impaired resolution of interfering cognitive stimuli. Future investigations might link lowered 1a BP to neurobiological pathways and markers, as well as probing subtype-specific treatment targets. (shrink)

Secondary education around the world has been significantly disrupted by covid-19. Students have been forced into new ways of independent learning, often using remote technologies, but without the social nuances and direct teacher interactions of a normal classroom environment. Using data from the School Attitudes Survey—which surveys students regarding the perceived level of difficulty, anxiety level, self-efficacy, enjoyability, subject relevance, and opportunities for creativity with regards to each of their school subjects—this study examines students' responses to this disruption from two (...) very different schools with two very different experiences of the pandemic. This paper reports on the composite attitudinal profiles of students in the senior secondary levels at each school. The findings challenged our expectation that the increased difficulty and anxiety caused by the disruption would reduce perceived opportunities for creativity. Indeed, our analyses showed that the students at both schools demonstrated generally positive attitudes toward their learning and strongly associated opportunities for creativity with other attitudinal constructs including enjoyability, subject relevance, and self-efficacy. These complex associations made by the students appear to have buffered the impacts of the disruption, and they may even have supported creative resilience. (shrink)

A crisis continues to brew within the pharmaceutical research and development (R&D) enterprise: productivity continues declining as costs rise, despite ongoing, often dramatic scientific and technical advances. To reverse this trend, we offer various suggestions for both the expansion and broader adoption of modeling and simulation (M&S) methods. We suggest strategies and scenarios intended to enable new M&S use cases that directly engage R&D knowledge generation and build actionable mechanistic insight, thereby opening the door to enhanced productivity. What M&S requirements (...) must be satisfied to access and open the door, and begin reversing the productivity decline? Can current methods and tools fulfill the requirements, or are new methods necessary? We draw on the relevant, recent literature to provide and explore answers. In so doing, we identify essential, key roles for agent-based and other methods. We assemble a list of requirements necessary for M&S to meet the diverse needs distilled from a collection of research, review, and opinion articles. We argue that to realize its full potential, M&S should be actualized within a larger information technology framework—a dynamic knowledge repository—wherein models of various types execute, evolve, and increase in accuracy over time. We offer some details of the issues that must be addressed for such a repository to accrue the capabilities needed to reverse the productivity decline. (shrink)

This is the first book to offer the best essays, articles, and speeches on ethics and intelligence that demonstrate the complex moral dilemmas in intelligence collection, analysis, and operations. Some are recently declassified and never before published, and all are written by authors whose backgrounds are as varied as their insights, including Robert M. Gates, former Director of the Central Intelligence Agency; John P. Langan, the Joseph Cardinal Bernardin Professor of Catholic Social Thought at the Kennedy Institute of Ethics, (...) Georgetown University; and Loch K. Johnson, Regents Professor of Political Science at the University of Georgia and recipient of the Owens Award for contributions to the understanding of U.S. intelligence activities. Creating the foundation for the study of ethics and intelligence by filling in the gap between warfare and philosophy, this is a valuable collection of literature for building an ethical code that is not dependent on any specific agency, department, or country. (shrink)

A Confederacy of Dunces (Confederacy) by John Kennedy Toole portrays an interplay between competing definitions of humanism. The one school of humanism—called by some the Modernist Paradigm—saw the Italian Renaissance as the origin of nineteenth- and twentieth-century modernist views that celebrated science, technology, and individual human freedom. The other school, led by Paul Oskar Kristeller, sought to historicize humanism by establishing that Renaissance writers and thinkers were generally conservative and preserved the philosophical ideas of the medieval era. Kristeller was (...) the President of the Renaissance Society of America and was at the height of his influence at Columbia University during the late 1950s, when Toole studied for his Master’s degree there. The main character in Confederacy, Ignatius J. Reilly, presents a parody of Kristeller’s position, which he uses to critique modern society. Ignatius also plays the part of a child of the planetary god Saturn, both by acting out the ancient astrological tradition of associating Saturn with misfortune and disorder and by being a parody of the Renaissance concept of the Genius as a Child of Saturn begun by the Renaissance philosopher whom Kristeller studied most, Marsilio Ficino. Ignatius’s worldview is an antithesis of the Modernist Paradigm. Confederacy is critical of both Modernist humanism with its attendant materialism and its antithesis—Ignatius’s dysfunctional version of Kristeller’s Renaissance philosophy. When the community expels Ignatius as a scapegoat, Toole appears to gesture toward a dialectical synthesis of the two concepts of humanism in the novel’s happy ending. (shrink)

A Confederacy of Dunces (Confederacy) by John Kennedy Toole portrays an interplay between competing definitions of humanism. The one school of humanism—called by some the Modernist Paradigm—saw the Italian Renaissance as the origin of nineteenth- and twentieth-century modernist views that celebrated science, technology, and individual human freedom. The other school, led by Paul Oskar Kristeller, sought to historicize humanism by establishing that Renaissance writers and thinkers were generally conservative and preserved the philosophical ideas of the medieval era. Kristeller was (...) the President of the Renaissance Society of America and was at the height of his influence at Columbia University during the late 1950s, when Toole studied for his Master’s degree there. The main character in Confederacy, Ignatius J. Reilly, presents a parody of Kristeller’s position, which he uses to critique modern society. Ignatius also plays the part of a child of the planetary god Saturn, both by acting out the ancient astrological tradition of associating Saturn with misfortune and disorder and by being a parody of the Renaissance concept of the Genius as a Child of Saturn begun by the Renaissance philosopher whom Kristeller studied most, Marsilio Ficino. Ignatius’s worldview is an antithesis of the Modernist Paradigm. Confederacy is critical of both Modernist humanism with its attendant materialism and its antithesis—Ignatius’s dysfunctional version of Kristeller’s Renaissance philosophy. When the community expels Ignatius as a scapegoat, Toole appears to gesture toward a dialectical synthesis of the two concepts of humanism in the novel’s happy ending. (shrink)

The Confidentiality Advisory Group is a specialised body that advises the Health Research Authority and the Secretary of State for Health on requests for access to confidential information, in the absence of informed consent from its owners. Its primary role is to oversee the safe use of such information and to counsel the governing bodies mentioned above as to whether such use is appropriate or inappropriate. Researchers who seek access to England or Wales-based confidential data, for medical purposes that are (...) in the interest of the public, are typically required to submit an application to this body. However, it is not always clear to researchers whether requests for access to patient data fit within the remit of the CAG or a Trust’s local information governance team. This commentary will, therefore, explore the role of the CAG and reflect on how best to support researchers with this question. (shrink)

The Eton Latin Grammar, For Use in the Higher Forms. By Francis Hay Rawlins, M.A., and William Ralph Inge. London: Murray, 1888. 6s.The Revised Latin Primer. By Benjamin Hall Kennedy, D.D. Longmans, 1888. 2s. 6d.The New Latin Primer. Edited by J. P. Postgate, M.A., and C. H. Vince, M.A. Cassell, 1888. 2s. 6d.The Shorter Latin Primer, by Dr. Kennedy. Longmans, 1888. 1s.

In A General View of Positivism French philosopher Auguste Comte gives an overview of his social philosophy known as Positivism. Comte, credited with coining the term 'sociology' and one of the first to argue for it as a science, is concerned with reform, progress and the problem of social order in society. In this English edition of the work, published in 1865, he addresses the practical problems of implementing his philosophy or doctrine, as he also refers to Positivism, into society. (...) He believes that society evolves through a series of stages that are ruled by social laws and culminate in a superior form of social life. During this reorganisation of society, which will find its greatest supporters among women and the working class, a 'new moral power' will emerge. Under the motto 'love, order and progress' Comte wishes humanism to replace organised religion as the object of spiritual worship. (shrink)

In the two related works in this volume, Bentham offers a detailed critique of William Blackstone's Commentaries on the Laws of England. He provides important refelctions on the nature of law, and more particularly on the nature of customary and statute law, and on judicial interpretation.

Tragic allusions to contemporary events are not, as a rule, taken on trust, but the Eumenides of Aeschylus provides three notable exceptions. The view that the Athenian-Argive alliance of 462 B.C. is reflected in Eum. 287–91, 667–73, anc^ 762–74 has won wide acceptance, although no systematic theory of the relation between the drama and the historical context has yet been advanced. If demonstration in detail has been wanting, the view seems to be supported by three general considerations. In the first (...) place, the emphasis put on the dramatic declaration of friendship exceeds the requirements of the plot: the acquittal of Orestes rather than his gesture of gratitude to Athens is the natural climax of this part of the drama, 1–777, and yet the gesture has been considered important enough to be heralded twice before it is actually made in 762–74. Secondly, Orestes' declaration is not limited in duration but binding on his successors in perpetuity; it seems, therefore, to have been deliberately formulated in order to react upon historical fact. Thirdly, in instituting the Council of the Areopagus and dwelling upon the importance of its constitutional function , Aeschylus seems to have gone out of his way to pass judgement of some sort on the recent reforms of Ephialtes and Pericles; the theory that he has also appreciated their foreign policy on the tragic stage is thus relieved of some of the obvious practical objections and made inherently more plausible. (shrink)

Tragic allusions to contemporary events are not, as a rule, taken on trust, but the Eumenides of Aeschylus provides three notable exceptions. The view that the Athenian-Argive alliance of 462 B.C. is reflected in Eum. 287–91, 667–73, anc^ 762–74 has won wide acceptance, although no systematic theory of the relation between the drama and the historical context has yet been advanced. If demonstration in detail has been wanting, the view seems to be supported by three general considerations. In the first (...) place, the emphasis put on the dramatic declaration of friendship exceeds the requirements of the plot: the acquittal of Orestes rather than his gesture of gratitude to Athens is the natural climax of this part of the drama, 1–777, and yet the gesture has been considered important enough to be heralded twice before it is actually made in 762–74. Secondly, Orestes' declaration is not limited in duration but binding on his successors in perpetuity; it seems, therefore, to have been deliberately formulated in order to react upon historical fact. Thirdly, in instituting the Council of the Areopagus and dwelling upon the importance of its constitutional function, Aeschylus seems to have gone out of his way to pass judgement of some sort on the recent reforms of Ephialtes and Pericles; the theory that he has also appreciated their foreign policy on the tragic stage is thus relieved of some of the obvious practical objections and made inherently more plausible. (shrink)

My object in this paper is to suggest a few reflections on some themes in Bentham's work which others as well as I have noted, without perhaps developing them as fully as might with advantage be done. There will be nothing like full development in the limited compass of what is said here, but what is said may at least indicate possible directions for further exploration. The greater part of the paper will be concerned with the notion of natural authority; (...) but I want to begin by taking a broader, though no doubt rather superficial, view of the role in Bentham's thinking of the concepts of ‘nature’ and ‘the natural’. (shrink)

The object of this article is to examine, with the work of Jeremy Bentham as the principal example, one strand in the complex pattern of European social theory during the second half of the eighteenth century. This was of course the period not only of the American and French revolutions, but of the culmination of the movements of thought constituting what we know as the Enlightenment. Like all great historical episodes, the Enlightenment was both the fulfilment of long-established processes and (...) the inauguration of new processes of which the fulfilment lay in the future. Thus the seminal ideas of seventeenth-century rationalism realized and perhaps exhausted their potentialities in the eighteenth-century Enlightenment. The ideas with which this article is concerned, however—conveniently grouped and labelled as the ideas of utilitarianism—only began to achieve systematic development in these later decades of the eighteenth century. Within that period—during the first half and more of Bentham's long life—attempts to apply those ideas to the solution of social problems met largely with failure and frustration. Yet unrealized potentialities remained, the realization of which was reserved for a time when the world of the philosophes no longer existed. The movements for social and political reform which have played so large a part in modern history since the French Revolution may be judged in widely differing ways; but whatever the verdict, these movements surely cannot be understood without due consideration of that part of their origins which lies in eighteenth-century utilitarianism. (shrink)

This guide is intended to be a comprehensive survey of Dewey's work. It consists of ten essays by Dewey scholars surveying an area of Dewey's work. Each essay is followed by a checklist of articles and books. The topics include divisions such as Dewey's Psychology, Philosophy and Philosophic Method, Logic and Theory of Knowledge, Ethics, etc. Contributors include Schneider, Hahn, Kennedy, Rucker, Leys, among others. Despite the enormous amount of work that must have gone into producing this volume, its (...) value is questionable. One reason for this is that Dewey's thought does not lend itself into such convenient divisions--it is difficult to think of a standard "topic" that isn't intertwined with some other. The novice may be bewildered by the rapid surveys and checklists. And scholars of Dewey and American philosophy may detect other groupings which they consider more illuminating. Although one can appreciate the desire not to reproduce the type of bibliography prepared by M. H. Thomas, a complete annotated bibliography would have been a much more helpful guide than the present one. Nevertheless the present guide does help the novice and the scholar to see important connections among the more than thousand items that make up the Dewey corpus.--R. J. B. (shrink)

One of the earliest and best-known of Bentham's works, the Introduction to the Principles of Morals and Legislation sets out a profound and innovative philosophical argument. This definitive edition includes both the late H. L. A. Hart's classic essay on the work and a new introduction by F. Rosen.