Most lymphocytes of the T cell lineage develop along the CD4/CD8 pathway and express antigen receptors on their surfaces consisting of clonotypic αβ chains associated with invariant CD3‐γδε components and ζ chains, collectively referred to as the T cell antigen receptor complex (TCR). Expression of the TCR complex is dynamically regulated during T cell development, with immature CD4+CD8+ thymocytes expressing only 10% of the number of αβ TCR complexes on their surfaces expressed by mature CD4+ and CD8+ T cells. Recent (...) evidence demonstrates that low surface TCR density on CD4+CD8+ thymocytes results from the limited survival of a single TCR component within the ER, the TCRα chain, which has a half life of only 15 minutes in immature thymocytes, compared to >75 minutes in mature T cells. Instability of TCRα proteins in immature CD4+CD8+ thymocytes represents a novel mechanism by which expression of the multisubunit TCR complex is quantitatively regulated during T cell development. In the current review we discuss our recent findings concerning the assembly, intracellular transport, and expression of αβ TCR complexes in CD4+CD8+ thymocytes and comment on the functional significance of TCRα instability during T cell development. (shrink)

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Despite the frequency of stillbirths, the subsequent implications are overlooked and underappreciated. We present findings from comprehensive, systematic literature reviews, and new analyses of published and unpublished data, to establish the effect of stillbirth on parents, families, health-care providers, and societies worldwide. Data for direct costs of this event are sparse but suggest that a stillbirth needs more resources than a livebirth, both in the perinatal period and in additional surveillance during subsequent pregnancies. Indirect and intangible costs of stillbirth are (...) extensive and are usually met by families alone. This issue is particularly onerous for those with few resources. Negative effects, particularly on parental mental health, might be moderated by empathic attitudes of care providers and tailored interventions. The value of the baby, as well as the associated costs for parents, families, care providers, communities, and society, should be considered to prevent stillbirths and reduce associated morbidity. (shrink)

Collects ten essays on Germain Grisez's writings. Topics include the scriptural basis of Grisez's revision of moral theology, contraception, Grisez's metaphysical work, capital punishment, and the political common good in Aquinas. The book includes a response by Grisez and Joseph Boyle, Jr. to the e.

Intuitively we feel that we ought to (attempt) to save the lives, or ameliorate the suffering, of identifiableIdentifiable individuals where we can (Rulli and Millum, 2016, p. 261). But this comes at a price. It means that there may not be any resources to save the lives of others in similar situations in the future. Or worse, there may not be enough resources left to prevent others from ending up in similar situations in the future. This chapter asks whether this (...) is justifiable or whether we would be better served focusing on public health in the form of preventative medicine. It looks briefly at the supposed difference between benefiting individuals and benefiting populations by considering the difference between interventions aimed at ‘rescue’ and those which are preventative. It then considers the rule of rescueRule of rescue in the health care setting, and looks at some of the reasons stemming from this that we might have for allocating resources to rescue interventions. If these reasons do not provide adequate justification for preferring these types of interventions, then the implication is that our current mode of resource allocation may need to be revised in favour of a more public health-oriented model. (shrink)

In 1960, E. P. Wigner, a joint winner of the 1963 Nobel Prize for Physics, published a paper titled On the Unreasonable Effectiveness of Mathematics in the Natural Sciences [61]. This paper can be construed as an examination and affirmation of Galileo's tenet that “The book of nature is written in the language of mathematics”. To this effect, Wigner presented a large number of examples that demonstrate the effectiveness of mathematics in accurately describing physical phenomena. Wigner viewed these examples as (...) illustrations of what he called the empirical law of epistemology, which asserts that the mathematical formulation of the laws of nature is both appropriate and accurate, and that mathematics is actually the correct language for formulating the laws of nature. At the same time, Wigner pointed out that the reasons for the success of mathematics in the natural sciences are not completely understood; in fact, he went as far as asserting that “… the enormous usefulness of mathematics in the natural sciences is something bordering on the mysterious and there is no rational explanation for it.”. (shrink)

Contemporary liberal thinkers commonly suppose that there is something in principle unjust about the legal prohibition of putatively victimless crimes. Here Robert P. George defends the traditional justification of morals legislation against criticisms advanced by leading liberal theorists. He argues that such legislation can play a legitimate role in maintaining a moral environment conducive to virtue and inhospitable to at least some forms of vice. Among the liberal critics of morals legislation whose views George considers are Ronald Dworkin, Jeremy Waldron, (...) David A.J. Richards, and Joseph Raz. He also considers the influential modern justification for morals legislation offered by Patrick Devlin as an alternative to the traditional approach. George closes with a sketch of a "pluralistic perfectionist" theory of civil liberties and public morality, showing that it is fully compatible with a defense of morals legislation. Making Men Moral will interest legal scholars and political theorists as well as theologians and philosophers focusing on questions of social justice and political morality. (shrink)

Joseph Newhard (2017) argues that a libertarian anarchist society would be at a serious military disadvantage if it extended the nonaggression principle to include potential foreign invaders. He goes so far as to recommend cultivating the ability to launch a nuclear attack on foreign cities. In contrast, I argue that the free society would derive its strength from a total commitment to property rights and the protection of innocent life. Both theory and history suggest that a free society would (...) be capable of defending itself, and indeed that it would probably use other means to avoid military conflict altogether. (shrink)

Natural law theory is enjoying a revival of interest in a variety of scholarly disciplines including law, philosophy, political science, and theology and religious studies. This volume presents twelve original essays by leading natural law theorists and their critics. The contributors discuss natural law theories of morality, law and legal reasoning, politics, and the rule of law. Readers get a clear sense of the wide diversity of viewpoints represented among contemporary theorists, and an opportunity to evaluate the arguments and counterarguments (...) exchanged in the current debates between natural law theorists and their critics. Contributors include Hadley Arkes, Joseph M. Boyle, Jr., John Finnis, Robert P. George, Russell Hittinger, Neil MacCormick, Michael Moore, Jeffrey Stout, Joseph Raz, Jeremy Waldron, Lloyd Weinreb, and Ernest Weinrib. (shrink)

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

Peter Abelard (1079–1142 ce) was the most wide‐ranging philosopher of the twelfth century. He quickly established himself as a leading teacher of logic in and near Paris shortly after 1100. After his affair with Heloise, and his subsequent castration, Abelard became a monk, but he returned to teaching in the Paris schools until 1140, when his work was condemned by a Church Council at Sens. His logical writings were based around discussion of the “Old Logic”: Porphyry's Isagoge, aristotle'S Categories and (...) On Interpretation and boethius'S textbook on topical inference. They comprise a freestanding Dialectica (“Logic”; probably c.1116), a set of commentaries (known as the Logica [Ingredientibus], c. 1119) and a later (c. 1125) commentary on the Isagoge (Logica Nostrorum Petititoni Sociorum or Glossulae). In a work Abelard called his Theologia, issued in three main versions (between 1120 and c.1134), he attempted a logical analysis of trinitarian relations and explored the philosophical problems surrounding God's claims to omnipotence and omniscience. The Collationes (“Debates,” also known as “Dialogue between a Christian, a Philosopher and a Jew”; probably c.1130) present a rational investigation into the nature of the highest good, in which the Christian and the Philosopher (who seems to be modeled on a philosopher of pagan antiquity) are remarkably in agreement. The unfinished Scito teipsum (“Know thyself,” also known as the “Ethics”; c.1138) analyses moral action. (shrink)

BackgroundThe increased risk of developing attention-deficit hyperactivity disorder (ADHD) in extremely preterm infants is well-documented. Better understanding of perinatal risk factors, particularly those that are modifiable, can inform prevention efforts.MethodsWe examined data from the Extremely Low Gestational Age Newborns (ELGAN) Study. Participants were screened for ADHD at age 10 with the Child Symptom Inventory-4 (N = 734) and assessed at age 15 with a structured diagnostic interview (MINI-KID) to evaluate for the diagnosis of ADHD (N = 575). We studied associations (...) of pre-pregnancy maternal body mass index (BMI), pregestational and/or gestational diabetes, maternal smoking during pregnancy (MSDP), and hypertensive disorders of pregnancy (HDP) with 10-year and 15-year ADHD outcomes. Relative risks were calculated using Poisson regression models with robust error variance, adjusted for maternal age, maternal educational status, use of food stamps, public insurance status, marital status at birth, and family history of ADHD. We defined ADHD as a positive screen on the CSI-4 at age 10 and/or meeting DSM-5 criteria at age 15 on the MINI-KID. We evaluated the robustness of the associations to broadening or restricting the definition of ADHD. We limited the analysis to individuals with IQ ≥ 70 to decrease confounding by cognitive functioning. We evaluated interactions between maternal BMI and diabetes status. We assessed for mediation of risk increase by alterations in inflammatory or neurotrophic protein levels in the first week of life.ResultsElevated maternal BMI and maternal diabetes were each associated with a 55–65% increase in risk of ADHD, with evidence of both additive and multiplicative interactions between the two exposures. MSDP and HDP were not associated with the risk of ADHD outcomes. There was some evidence for association of ADHD outcomes with high levels of inflammatory proteins or moderate levels of neurotrophic proteins, but there was no evidence that these mediated the risk associated with maternal BMI or diabetes.ConclusionContrary to previous population-based studies, MSDP and HDP did not predict ADHD outcomes in this extremely preterm cohort, but elevated maternal pre-pregnancy BMI, maternal diabetes, and perinatal inflammatory markers were associated with increased risk of ADHD at age 10 and/or 15, with positive interaction between pre-pregnancy BMI and maternal diabetes. (shrink)

Theories of discourse bring to realism new ideas about how knowledge develops and how representations of reality are influenced. We gain an understanding of the conceptual aspect of social life and the processes by which meaning is produced. This collection reflects the growing interest realist critics have shown towards forms of discourse theory and deconstruction. The diverse range of contributions address such issues as the work of Derrida and deconstruction, discourse theory, Eurocentrism and poststructuralism. What unites all of the contributions (...) is a sense that it is essential to provide a realist alternative to the hitherto dominance of social constructionism, hermeneutics and postmodernism, over many of the issues discussed. By developing a realist perspective the different authors attempt to embed discourse within the structured nature of the reality of the world. Realism can situate language, discourse and ideology within context specific, or 'causally efficacious' circumstances. Realism can help to uncover issues of power, representation, and subjectivity and how discursive and other social practices produce real effects. This can help us understand the manner in which social structures are reproduced through various forms of ideology and discourse. And by knowing this, we can start to address questions concerning human emancipation and how the world is to be transformed. (shrink)

In “Reliabilism Leveled” Jonathan Vogel (2000) provides a strong case against epistemic theories that stress the importance of tracking/sensitivity conditions. A tracking/sensitivity condition is to be understood as some version of the following counterfactual: (T) ~p oÆ ~Bp (T) says that s would not believe p, if p were false. Among other things, tracking is supposed to express the external relation that explains why some justified true beliefs are not knowledge. Champions of the condition include Robert Nozick (1981) and, more (...) recently, Keith DeRose (1995). To my knowledge, the earliest formulation of the counterfactual condition is found in Fred Dretske’s conclusive reasons condition (1971), which says, s would not have had the reason that she does for believing p, if p were false. Vogel contends that any such counterfactual condition on knowledge will render the theory of knowledge too strong. He believes that there is at least some possible reflective knowledge that cannot satisfy the counterfactual--viz., the possible knowledge that one does not believe falsely that p. The alleged impossibility of such reflective knowledge is taken by Vogel to be a decisive objection to the tracking theories advocated by Dretske, Nozick, DeRose1 and others. The criticism finds its roots in Vogel’s earlier work (1987), and recurs in papers by Ernest Sosa (2002, 1996). Sosa suggests that the externalist idea behind tracking is on target, but that Nozick’s counterfactual is a misbegotten regimentation of the idea. In its place Sosa offers his own counterfactual “safety” condition, which he feels properly captures the externalist idea. Sosa’s counterfactual is not the topic of this paper. I mention it only to point out that the criticism that constitutes the subject of my investigation is meant to do a lot of work. In Sosa’s 1 case the criticism is meant to motivate his own counterfactual analysis, and in Vogel’s case the criticism promises to be a silver bullet against a theory that has recently found renewed life in the work of Keith DeRose.. (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)

The late Joseph Grange is perhaps the most sharply focused and elegantly lucid of the group of North American philosophers to build new aesthetic metaphysical visions from the legacies of process philosophy and pragmatism. His peers include, among others, George Allan,1 Roger Ames,2 Chung-ying Cheng,3 Robert Corrington,4 Frederick Ferre,5 Warren Frisina,6 David L. Hall,7 Judith Jones,8 Elizabeth Kraus,9 Hugh P. McDonald,10 Steve Odin,11 Sandra Rosenthal,12 Robert Smid,13 David Weissman,14 and myself, along with our many students and colleagues. This group (...) has widely variant systems, yet what unites us is an emphasis on the aesthetic and a lack of the fear to enter deeply into metaphysics when relevant.. (shrink)

ABSTRACT‘Not in Heaven’: Coherence and Complexity in Biblical Narrative. Edited by J. P. Rosenblatt and J. C. Sitterson Jr.Towards a Grammar of Biblical Poetics: Tales of the Prophets. By Herbert Chanan Brichto.The Historical Jesus: The Life of a Mediterranean Jewish Peasant. By John Dominic Crossan.Jesus and the Oral Gospel Tradition. Edited by Henry Wansbrough.The Rhetoric of Righteousness in Romans 3.21‐26. By Douglas A. Campbell.Paul and the Rhetoric of Reconciliation: An Exegetical Investigation of rhe Language and Composition of I Corinthians. By (...) Margaret M. Mitchell.Divine Disclosure: An Introduction to Jewish Apocalyptic. By D. S. Russell.Judaism. By Hans Küng.Jewish History and Thought: An Introduction. By Menahem Mansoor.Studies in the Jewish Background to Christianity. By Daniel R. Schwartz.Der verborgene und offenbare Gott: Hauptthemen der ffühen jüdischen Mystik. By Peter Schäfer.The Foundations of Mysticism: Origins to the Fifth Century. By Bernard McGinn.The Eucharistic Prayer of Addai and Mari. By A. Gelston.Thomas Becket in the Medieval Latin Preaching Tradition: An Inventory of Sermons about St Thomas Becket c.1170‐c.1400. By Phyllis B. Roberts.Einsiclit und Bekehrung: Ausgangspunkt der Fundamental theologie bei Bernard Lunergan. By Grzegorz Dobroczynski.The Liberation of Consciousness: Bemurd Lonergan's Theological Foundations in Dialogue with the Theological Aesthetics of Hans Urs von Balthasar. By Hilary A. Mooney.Systematic Theology, Volume I. By Wolfhart Pannenberg.Revelation: From Metaphor to Analogy. By Richard Swinburne.Sociology and Liturgy: Re‐presentations of the Holy. By Kieran Flanagan.Communication Theory for Christian Witness. By Charles H. Kraft.Contemporary Literary Theory: A Christian Appraisal. Edited by Clarence Walhout and Leland Ryken.Eucharistic Poetry: The Search for Presence in the Writings of John Donne, Gerard Manley Hopkins, Dylan Thomas and Geoffrey Hill. By Eleanor J. McNees.La Vie religieuse: Un chemin d'humanitk. By Paul Lebeau.Venantius Fortunatus: A Latin Poet in Merovingian Gaul. By Judith George.The Rise of Magic in Early Medieval Europe. By Valerie I. J. Flint.The Later Crusades: From Lyons to Alcazar, 1274‐1580. By Norman Housley.Beneath the Cross: Catholics and Huguenots in Sixteenth‐Century Paris. By Barbara B. Diefendorf.Gentlemen and Jesuits: Quests for Glory and Adventure in the Early Days of New France. By Elizabeth Jones.Education in New France. By Roger Magnuson.Early American Methodism. By Russell E. Richey.Cheap Bibles: Nineteenth‐Century Publishing and the British and Foreign Bible Society. By Leslie Howsam.Hopkins: A Literary Biography. By Norman White.The Old Palace: A History of the Oxford University Catholic Chaplaincy. By Walter Drumm.Peace Movements: International Protest and World Politics since 1945. By April Carter.The Christian Church in the Cold War. By Owen Chadwick.Spirit of Africa: The Healing Ministry of Archbishop Milingo of Zambia. By Gerrie Ter Haar.Aristotle's ‘Physics’: A Collection of Essays. Edited by Lindsay Judson.Oxford Studies in Ancient Philosophy: Supplementary Volume, 1991. Edited by Henry Blumenthal and Howard Robinson.Substance and Predication in Aristotle. By Frank A. Lewis.The Perfection of the Universe according to Aquinas: A Theological Cosmology. By Oliva Blanchette.The Thought of Thomas Aquinas. By Brian Davies.Kant's Philosophy of Religion Reconsidered. Edited by Philip J. Rossi and Michael Wreen.Marx's Theory of History: The Contemporary Debate. Edited by Paul Wetherly.The Cambridge Companion to Marx. Edited by R. Terrell Carver.Essentialism: A Wittgensteinian Critique. By Garth L. Hallett.The Realistic Spirit: Wittgenstein, Philosophy and the Mind. By Cora Diamond.From Existence to God: A Contemporary Philosophical Argument. By Barry Miller.Will and World: A Study in Metaphysics. By N. M. L. Nathan.Being A Philosopher: The History of a Practice. By David Hamlyn. (shrink)

Approaches to clinical ethics dilemmas that rely on basic principles or rules are difficult to apply because of vagueness and conflict among basic values. In response, casuistry rejects the use of basic values, and specification produces a large set of specified rules that are presumably easily applicable. Balancing is a method employed to weigh the relative importance of different and conflicting values in application. We argue against casuistry and specification, claiming that balancing is superior partly because it most clearly exhibits (...) the reasoning behind moral decision-making. Hence, balancing may be most effective in teaching bioethics to medical professionals. (shrink)

This book is a comprehensive introduction to the many ethical and legal issues that arise in the practice of nursing. Ethical analysis is supplemented with the rigorous discussion of precedents from the American legal system as well as the requirements of professional codes operating at the national and state levels. Topics include informed consent, end-of-life treatment, impaired decisional capacity, privacy and confidentiality, and much more.

In Socrates among Strangers, Joseph P. Lawrence reclaims the enigmatic sage from those who have seen him either as a prophet of science, seeking the security of knowledge, or as a wily actor who shed light on the dangerous world of politics while maintaining a prudent distance from it. The Socrates Lawrence seeks is the imprudent one, the man who knew how to die. The institutionalization of philosophy in the modern world has come at the cost of its most (...) vital concern: the achievement of life wisdom. Those who have ceased to grow (those who think they know) close their ears to the wisdom of strangers—and Socrates, who stood face to face with death, is the archetypal stranger. His avowal of ignorance, Lawrence suggests, is more needed than ever in an age defined by technical mastery and expert knowledge. (shrink)

Researchers designing a clinical trial may be aware of disputed evidence of serious risks from previous studies. These researchers must decide whether and how to describe these risks in their model informed consent document. They have an ethical obligation to provide fully informed consent, but does this obligation include notice of controversial evidence? With ACCORD as an example, we describe a framework and criteria that make clear the conditions requiring inclusion of important controversial risks. The ACCORD model consent document did (...) not include notice of prior trials with excess death. We develop and explain a new standard labeled risk in equipoise. We argue that our approach provides an optimal level of integrity to protect the informational needs of the reasonable volunteers who agree to participate in clinical trials. We suggest language to be used in a model consent document and the informed consent discussion when such controversial evidence exists. (shrink)

The controversy over the equivalence of continuous sedation until death (CSD) and physician-assisted suicide/euthanasia (PAS/E) provides an opportunity to focus on a significant extended use of CSD. This extension, suggested by the equivalence of PAS/E and CSD, is designed to promote additional patient autonomy at the end-of-life. Samuel LiPuma, in his article, “Continuous Sedation Until Death as Physician-Assisted Suicide/Euthanasia: A Conceptual Analysis” claims equivalence between CSD and death; his paper is seminal in the equivalency debate. Critics contend that sedation follows (...) proportionality protocols for which LiPuma’s thesis does not adequately account. Furthermore, sedation may not eliminate consciousness, and as such LiPuma’s contention that CSD is equivalent to neocortical death is suspect. We not only defend the equivalence thesis, but also expand it to include additional moral considerations. First, we explain the equivalence thesis. This is followed by a defense of the thesis against five criticisms. The third section critiques the current use of CSD. Finally, we offer two proposals that, if adopted, would broaden the use of PAS/E and CSD and thereby expand options at the end-of-life. (shrink)