bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Public Reason’ and Moral Debate
Authors: Finnis John
Published: October 2011

This chapter provides a close study and critique of Rawls's conception of public reason. ‘Public reason’ can summarily convey four sound elements of classical political thought as found in Aquinas, but as used by Rawls it is confused, arbitrary, and unreasonably restrictive of both discourse and deliberation. A fundamental confusion between the normative and the predictive-descriptive is revealed by its equivocal phrase ‘can reasonably be expected to endorse’. In so far as Political Liberalism rests on A Theory of Justice it suffers from the earlier book's unreasonable assumption of ignorance of value and consequently fallacious fundamental argumentation from what would be chosen or rejected in the ‘Original Position’. The concern to avoid bias and violations of the Golden Rule is sound, as is the principle of reciprocity. But Rawls's application of the principle in relation to unborn persons, like his follower Jeffrey Reiman's more radical application and the doctrine in Roe v Wade, exalts private power over public reason. An endnote lists uses of the phrase from Milton and Hobbes to Rousseau and Jefferson.
Reason, Passions, and Free Speech
Authors: Finnis John
Published: October 2011

This chapter presents a 1967 essay, cited in the US Supreme Court's lasting settlement of obscenity law in 1973, and it explores the applicability of the classic and Humean distinctions between reason and passions to the demarcation of the ‘speech’ protected by constitutional ‘freedom of speech’. It traces the development of obscenity law; the place of reason in Madison's Federalist papers; the idea of aesthetic distance developed by Geoffrey Bullough, Suzanne Langer, and Peter Strawson; and the course of Supreme Court doctrine from 1942 to 1966. The 1973 citation is shown, in the endnote, to have been an empty success.
Intention in Direct Discrimination
Authors: Finnis John
Published: October 2011

The UK Supreme Court's holding about ‘direct’ discrimination in the JFS case (2009) is critiqued in this chapter for its failure to identify and reject the error in the House of Lords' decision in James v Eastleigh (1990). Acting ‘on the grounds of’ X means that X enters into the acting person's or body's deliberation in such a way as to affect that person's selection of means and/or ends. The English judiciary do not see the basic structure of practical reasoning, intending, deciding, and acting whole as it is seen in Aristotle's and Aquinas's demonstration that ends are almost all means and means almost all ends. Ends and means are then both grounds for acting. Side effects, even when ‘intrinsic’, are not. These matters remain relevant under the Equality Act 2010's new definition of ‘direct discrimination’.
Organic Unity, Brain Life, and Our Beginning
Authors: Finnis John
Published: October 2011

This chapter is about a thesis, proposed by Michael Lockwood and some Catholic theologians, that a human life does not begin until the brain has formed and matured to a sufficient degree. The thesis is presented as counterpart to or symmetrical with a thesis about brain death. But the proper criterion is integrated organic functioning, and this precedes ‘brain life’, even if subsequently such integration is a function of the brain. Conception is a radically new beginning, and Lockwood's attempts to obscure this verbally are illuminating. Beneath his arguments is a dualism which is self-refuting.
Brain Death and Peter Singer
Authors: Finnis John
Published: October 2011

This chapter offers a response to a 1998 paper by Peter Singer and it focuses on discussion in 1979 by Grisez and Boyle of the theoretical, factual, and operational definition or criteria of death. That discussion is a model of conceptual (philosophical) clarification, and was mangled in Singer's account of it. But against their factual and operational conclusions linking brain death with loss of integrated organic functioning (the ‘theoretical’ definition of death), the chapter adduces work by Alan Shewmon giving clinical grounds for doubting the necessity or invariable reality of that link. Along the way, dualism of the kind embraced by Jeff McMahan is critiqued, as is Singer's ethic. A last-minute endnote cites Grisez's recent reply to Shewmon.
War and Peace in the Natural Law Tradition
Authors: Finnis John
Published: October 2011

This chapter surveys the history and merits of just war theory: its account of peace and pacific intention in war; its requirements of motive and intention, and relativising of distinctions between grounds for war and intention in going to war; its account of justifying grounds for going to war, and the emergence of a purely defensive justification; its approach to the side effects of going to war; its differing accounts of the moral limits on the conduct of war; its approach to the prospect of defeat, massacre, and unlimited injustice (extremity); its connections with the problem of forcible resistance to political authority; and its attitude to pacifism and ‘non-violent resistance’. Key figures such as Aquinas, Vitoria, Suarez, and Grotius are compared and critiqued, as well as some more recent authorities.
On Hart's Ways: Law as Reason and as Fact
Authors: Finnis John
Published: October 2011

Hart's early philosophical work on deciding and intending, like his later work on self-reference and on intention and his decisively important concept of the internal point of view, opened jurisprudence up to a full recognition that law has its reality not only as fact but also as reasons for action. But as MacCormick showed, Hart's distinction between internal and external points of view was imprecise, and the roots of this failure can be seen in the early work on deliberation, with its Hobbesian, Humean, and Kantian misunderstandings of practical reason which are mirrored in The Concept of Law. The chapter analyses the kinds of reason for compliance that the law offers its subjects, and the extent to which these were and were not noticed in that book. After a brief comment on more recent positivism, the chapter concludes with a close examination of the elements of moral scepticism that Hart sought, with incomplete success, to keep from affecting the results of his legal-philosophical work.
Analogical Reasoning in Law
Authors: Finnis John
Published: October 2011

This chapter offers a comment on Scott Brewer's major study of legal argument by analogy which resulted, it seems, in some substantial revisions to that study, so that it now brings out the importance of what Charles Sanders Peirce called abduction, that is, insight into a mass of items or data. The exemplary cases from 19th-century American law adduced by Brewer to illustrate analogical reasoning are shown, on inspection, to be concerned with the merits of alternative rules or principles, rather than with some other kind of similarity between (kinds of) situations. Analogy-warranting rules or principles, discovered or arrived at by abduction, make comparison of ‘source’ cases with ‘target’ cases redundant.
Adjudication and Legal Change
Authors: Finnis John
Published: October 2011

This chapter is a comment on Kleinwort Benson v Lincoln (1998) grapples with the question how far adjudication differs from legislation even when the court is overruling long-standing precedents long taken to have established a common law rule, now abrogated. This is considered in the context of the question whether the parties' reliance on the now abrogated rule was a mistake of fact or of law; against legal ‘Realism’, it should be regarded as a mistake of law, not of prediction (fact). The ‘declaratory theory of law’ mocked by Austin does not make a historical but rather a normative claim, about judges' duty to differentiate judicial authority and reasoning from that of legislatures. An endnote considers responses to the case that approach more closely Dworkin's one right answer thesis.
Revolutions and Continuity of Law
Authors: Finnis John
Published: October 2011

This chapter is written in the context of judicial appeals to legal theory in the wake of coups d'état or revolutions in the Commonwealth. It considers whether every illegal or unconstitutional act amounts to a change in the constitution and the identity of the legal order, and whether there can be change in that identity otherwise than by violation of some rule. It looks at the problem of coups d'état both in English statute law and in Kelsen and Ross and finally in Hart and Raz, noting the atemporal character of Hart's rule of recognition. The problem of when rules ‘cease to exist’ in considered in the light of law about the effects of repeal of statutes, and of fundamental ‘principle of continuity’. Consideration of whether the legal system is a set of rules (or other normative standards) of persons and institutions leads into more general reflections on method in jurisprudence, and (drawing on Voegelin) the dependence of legal theory on history to identify its subject matter (the group that has law).
Ethics and Revelation: A Fragment
Authors: Finnis John
Published: October 2011

This chapter offers a brief excerpt from a 2008 essay which also included Chapter 5 in Volume I of this text (on Bernard Williams and truth's values) and Chapter 7 in Volume II (on nations) discusses both natural revelation and the different, historical revelation to Israel completed by Jesus of Nazareth. Ethics precedes faith in two ways: it bears on the love of truth that grounds ‘natural’ revelation, and it hears on the assessment of the reliability of purported bearers of historical revelation (prophets). Part of the historical revelation, moreover, is that its moral teachings are all accessible to reason.
Philosophy and God's Nature: Second Thoughts
Authors: Finnis John
Published: October 2011

This chapter offers a reflection on the treatment in Natural Law and Natural Rights (1980) of the question how the basic human goods and requirements of practical reasonableness are related to, or in Mark Murphy's words ‘detachable from’, the rational affirmability of God's existence and nature. (About that nature, the book was too austere and agnostic.) There is ‘detachability’ just to the extent that (say) physics can be done well without raising and pressing further questions about the origins of physical realities and laws. But rationality norms applicable across the whole field of human questioning require that when those questions are raised, in the appropriate (philosophical) discipline, they be answered by affirming the existence of divine causality in tandem with the natural causalities and intelligibilities known to the diverse human fields of inquiry and scholarly disciplines. Neither natural moral law nor any other intelligible order is safe for non-theists. The affirmation that God is love is not foundational, but dependent.
Secularism and ‘The Culture of Death’
Authors: Finnis John
Published: October 2011

This chapter was written for a conference in the wake of the encyclical Evangelium Vitae (1995), which spoke of ‘the culture of death’, referring to cultures in which the intending of death is legally or socially accepted. The meaning of ‘culture’ is first considered, and then the influence of secularism (considered in the light of Plato's analysis as in Chapter 3 of this volume, and of Owen Chadwick's tracing of the secularization of the European mind to the axiom that miracles do not happen. Topics considered include creative causality and providence, freedom of choice, dignity, Nietzsche, the significance of intention and its denial by many proportionalist theologians, and secularism by default.
2 Martha Gurney and the Anti-Slave Trade Movement, 1788–94
Authors: Whelan Timothy
Published: October 2011

This chapter explores the work of Martha Gurney (1733–1816), a staunch Baptist and the leading woman bookseller and publisher in London in the last quarter of the eighteenth century, during the first decade of the abolitionist movement in England. The chapter examines the fourteen abolitionist pamphlets Gurney published or sold between 1787 and 1794 and their place within the abolitionist movement, with special attention to An Address to the People of Great Britain, on the Propriety of Abstaining from West-India Produce (1791) by William Fox. The Address, the most widely distributed pamphlet of the eighteenth century, created widespread support for a nationwide boycott of sugar from the West Indies. Though Gurney and her pamphleteers were unable to persuade parliament to end the slave trade at that time, they laid the groundwork for the later work of Elizabeth Heyrick and the boycott movement of the 1820s.
4 The Dissenting Voice of Elizabeth Heyrick: An Exploration of the Links Between Gender, Religious Dissent, and Anti-Slavery Radicalism
Authors: Midgley Clare
Published: October 2011

Elizabeth Heyrick's 1824 pamphlet Immediate, not Gradual Abolition challenged the policy of amelioration and gradual emancipation adopted by the Anti-Slavery Society in Britain at its foundation in 1823, setting in motion debates that led to a fundamental shift in abolitionist policy in both Britain and the US. This chapter traces the religious wellsprings of Heyrick's outspoken radical abolitionism. It explores the roots in the milieu of late eighteenth-century provincial rational dissent, where religious and political radicalism were interlinked. It then examines the ways in which her radicalism was strengthened and sustained through her subsequent involvement in the Society of Friends at a time when Quaker women were asserting spiritual leadership through searing critiques of the increasing ‘worldliness’ of the male leaders of the Society.
The Rules on Interpretation: Misgivings, Misunderstandings, Miscarriage? The ‘Crucible’ Intended by the International Law Commission
Authors: Villiger Mark E.
Published: October 2011

This chapter concentrates on the means of interpretation as codified in Articles 31 and 32 of the 1969 Vienna Convention. It also deals with the misgivings as to rules on interpretation, namely as to whether it is at all possible to establish rules of interpretation and to elicit the ‘correct’ meaning from a treaty term. It further discusses certain misunderstandings, in particular as to the relative structure of the means mentioned in Articles 31 and 32. The chapter finds that Articles 31 and 32 are not only contractually binding, they also enjoy a solid basis in customary international law. Overall, it can be said that these two provisions are among the most important ones of the entire 1969 Vienna Convention. They offer the interpreting agency considerable flexibility to adapt the various means of interpretation to the different types of treaties.
The European Courts and the Law of Treaties: The Continuing Story
Authors: Kuijper Pieter Jan
Published: October 2011

This chapter presents a critical analysis of the case law of the European Court of Justice and of the General Court relating to the application of the international law of treaties. It covers the some forty cases in which the Courts have referred explicitly to the Vienna Convention on the Law of Treaties 1969, and a few more where this happened implicitly, during the period 1998–2010. Inevitably the emphasis falls on the application of the rules of treaty interpretation to the international agreements concluded by the European Union (EU), but also to the founding treaties of the EU itself. The Courts have been confronted with great regularity with questions relating to the law of treaties and thus have become increasingly sophisticated in their use of it. The recent accusation that the Court is adverse to international law seems to be based on a few dramatic cases, not on the steady stream of smaller cases in which the law of treaties plays a role.
The Metamorphosis of Jus Cogens: From an Institution of Treaty Law to the Bedrock of the International Legal Order?
Authors: Zemanek Karl
Published: October 2011

When the Vienna Convention on the Law of Treaties confirmed the existence of peremptory norms of international law (jus cogens) they were conceived, like Roman jus publicum, as absolute law that could not be altered by the will of individual States. Scholars then transformed the concept into the manifestation of public policy (ordre public). They also argued for widening the scope of its application to unilateral legal acts and customary international law. A recent trend in academic theory assigns jus cogens an essential role in the constitutionalization of international law, postulating it either as hierarchically higher order or as embodying the constitutional principles. In view of the rashness of scholars in proclaiming the peremptory character of norms and also of the inexpertness of the European and national courts in applying supposedly peremptory international norms in their decisions, it seems better to keep jus cogens at its original task.
An EroticAristeia
Authors: Brillet‐Dubois Pascale
Published: October 2011

This chapter evaluates the relationship of the Homeric Hymn to Aphrodite to the Iliadic tradition. Taking into consideration the methodological approach of Neoanalysis, it is suggested that the narrative of the Homeric Hymn to Aphrodite interacts with the narrative sequence of the Homeric aristeia. Attention is given throughout to the ways in which the Hymn to Aphrodite defines its own place in relation to the heroic traditions of Homeric epic. A thorough analysis of the Hymn's narrative structure is undertaken.
The SeventhHomeric Hymnto Dionysus
Authors: Jaillard Dominique
Published: October 2011

This chapter examines the epiphanic nature of the narrative of the seventh Homeric Hymn to Dionysus in relation to the other Hymns in the collection, taking into account distinctions of length, and Dionysus' presentation elsewhere in Greek literature (including Euripides' Bacchae) and art. It is argued that the focalization of the seventh Hymn on the epiphany of Dionysus upon the ship of the Tyrsenian pirates is not simply the narration of a divine epiphany; rather one finds in the Hymn the epiphanic structuring of the narrative.
Homeric and Un‐Homeric Hexameter Hymns
Authors: Furley William D.
Published: October 2011

This chapter explores the relationship of the Homeric Hymns to other early hexameter hymns and their possible genesis from theogonic hymns and cult myth. Comparison is made between the Hymns and Hesiod's Theogony and Works and Days, but also to the evidence for an Orphic hymnic theogony contained in the Derveni papyrus and the mock bird theogony in Aristophanes' Birds, among other texts. It is suggested that the Homeric Hymns may have developed as epicized elaborations of theogonic hymns.
Children of Zeus in theHomeric Hymns
Authors: Felson Nancy
Published: October 2011

This chapter offers a reading of intergenerational conflict in the long Homeric Hymn to Apollo and the twenty‐eighth Hymn to Athena. Detailed attention is given to the relationship of the poem's narratives to the Hesiodic theogony, among other texts. It is argued that both of the Hymns treat the theme of intergenerational conflict, but that Apollo and Athena are ultimately portrayed as allies of Zeus, despite their potential for rebellion.
6 Supplemental Compensation
Authors: Borzu Sabahi
Published: October 2011

In addition to compensation or restitution for material damage, supplemental compensation is necessary to put the victim of an unlawful act fully in the hypothetical position that would exist save for the wrongful act. Supplemental compensation in this book refers to compensation for moral damage (including legal damage), interest, damage caused as a result of currency fluctuations, and arbitration costs. These heads of damages are grouped together as supplemental damages as none of them directly relates to the main material damage done to the investment but may be an integral part of full compensation. This chapter discusses the principles relating to each of these heads of supplemental damage, along with their use in investment treaty arbitration. Punitive damages and the currency of compensation in investment treaty arbitration are also discussed.
7 Limitations on Compensation
Authors: Borzu Sabahi
Published: October 2011

This chapter discusses various principles that may limit the amount of compensation that an investor may recover. Causation is examined, focusing particularly on legal causation. The effects of the investor's actions on compensation through contributory negligence and the obligation to mitigate losses are also discussed. The chapter touches upon a State's counterclaims, particularly the issue of jurisdiction over counterclaims in investment treaty arbitration. The state of necessity defence, in both customary international law and under investment treaties, is examined with its effect on the amount of compensation due; with particular attention to the cases arising from the Argentine financial crisis in 2000–02. Other included principles which affect compensation are the issues of burden of proof and the prohibition of double counting. Finally, the chapter examines the application of equity in awarding compensation.
Governing Like Judges?
Authors: Hiebert Janet L.
Published: October 2011

This chapter expresses a sceptical stance about the extent to which bills of rights can be crafted in such a way as to avoid the damaging consequences of strong judicial review. Research on how bills of rights affect bureaucratic and political behaviour when developing and evaluating legislation in Canada, New Zealand, and the United Kingdom, shows that even ‘weak’ bills of rights lead to cautious executives who refrain from bringing forward legislation that might be considered inconsistent with judicial decisions. In this way, they may be said to ‘govern like judges’ producing legalistic legislation which distorts policy and political judgments regarding human rights concerns. It is as if judges were in the corridors of power at the time legislation is being developed. Moreover, the capacity of parliamentarians to oppose government legislation is reduced if the legislation is thought to be potentially inconsistent with relevant judicial rulings. The chapter therefore believes that weak form systems are unstable and will either revert to parliamentary supremacy of merge into strong court systems. It concludes that, however bills of rights are designed, and allowing for significant differences between Canada, New Zealand, and the UK, the idea of developing robust and effective systems of rights-based parliamentary scrutiny is unrealistic.
Inter-institutional ‘Rights Dialogue’ under the New Zealand Bill of Rights Act
Authors: Geddis Andrew
Published: October 2011

This chapter discusses the extent to which the ‘weak-form’ New Zealand Bill of Rights model promotes a ‘culture of justification’ within public authorities and fosters a ‘dialogue’ between different institutions of government. There is no clear evidence that it has the sort of impact of the legislative process outlined in Chapter 3. Similarly, there is no substantial impact on Parliament's activities as lawmaker through rights ‘vetting’ of proposed legislation by the Attorney-General, commentary by the Human Rights Commission or post-enactment interpretation of legislation, noting that New Zealand has no parliamentary human rights committee. Indeed the New Zealand Parliament seems relaxed about passing government legislation that the Attorney-General deems incompatible with the Bill of Rights. Illustrating these contentions in connection with the Electoral Finance Act 2007, and the Misuse of Drugs (Classification of BZP) Amendment Act 2008, the chapter concludes that New Zealand shows an example of weak-form Bills of Rights which Tushnet sees as reverting to parliamentary supremacy.
Messages from the Front Line: Parliamentarians’ Perspectives on Rights Protection
Authors: Evans Carolyn , Evans Simon
Published: October 2011

Drawing on research relating to the Australian Federal Parliament, this chapter examines the argument that the new statutory bills of rights encourage parliaments to play a more significant role in the protection of rights. It identifies a number of constraints on the capacity of parliamentarians to undertake serious rights-based scrutiny of legislation, such as the lack of time, resources and expertise, the impact of party discipline in small legislatures, and the dominance of the executive. It reports the strong views of parliamentarians that parliaments can and should have a significant role in the protection of human rights and be able to resist the pressure to trust the executive on civil liberties. The chapter argues that empowering political representative is a crucial ingredient in the promotion of the political protection of human rights, and indicates some ways that this objective could be better achieved through the use of electronic technologies in accordance with ideas concerning e-democracy, including direct public input into public policy-making. More speculatively, the chapter suggests that parliamentary representation might be reformed to provide for a more team-based approach that could utilize a broader variety of talents.
Rights and the Citation of Foreign Law
Authors: Waldron Jeremy
Published: October 2011

This chapter addresses the specific issue of whether or not courts within jurisdictions that involve judicial review of legislation on human-rights grounds should cite foreign law. It argues that, whatever we think of the legitimacy of such powers, if they exist it is preferable that courts should be able to draw on the experience of comparable decisions in other jurisdictions. This enables courts to learn from the deliberations that have taken place elsewhere. It also generates more informed public debate on rights. Further the citation of foreign cases and statutes contributes to the harmonization of human rights law. However, improving the quality of human rights decision making and promoting the global consistency of human rights law should not be confused with the propriety of propriety of the judicial review in question.
8 The Organism as a Semiotic and Cybernetic System
Authors: Auletta Gennaro
Published: October 2011

Here, the concept of sign is introduced as well as those of teleonomic and teleologic mechanisms. The crucial notions of information control and functional equivalence classes are worked out. Chemotaxis is studied as an example of biological cybernetic system. Finally, the notion of biological self is introduced.
17 Memory
Authors: Auletta Gennaro
Published: October 2011

In this chapter, the third fundamental functionality of the brain is examined: Memory. After a short presentation of the nature of memory and of its fundamental features, the chapter introduces the relevant neural mechanisms. This will allow us to deal with the fundamental difference between procedural and declarative memory, which turns out to be connected with two different functions, namely learning and memory. Finally, the problem of the stages of memory consolidation is discussed, starting with the traditional distinction between a short-term and a long-term memory. It shall be seen that it is convenient to establish a dichotomy between active and inactive memory.
Definitions
Authors: Horty John
Published: October 2011

Frege's theory of definition is the subject of this chapter. The chapter focuses on the apparent conflict between two of its central tenets. The first is the requirement of fruitfulness which suggests the idea that definitions should make it possible to prove things that we could not have proved otherwise. However, in interpreting Frege's notion of fruitfulness, the focus has been on a weak, psychological reading. The second tenet of discussion is the requirement of eliminability which proposes the idea that an expression containing defined symbols should share its sense with the expression that results when those symbols have been eliminated.
A simple semantic model
Authors: Horty John
Published: October 2011

This chapter gives a precise semantic framework in which senses can be assigned with definite structures. It aims to examine the robust interpretation of fruitfulness of both defined expressions and “incomplete” expressions in accordance to which the presence of defined and incomplete expressions actually alter the structure of expressible senses. The framework illustrated would be explicitly procedural with the sense of an expression interpreted as a procedure for determining its referent. Given that it is not a standard kind of framework in formal semantics, the chapter begins with a basic definition of the interpretation itself.
Bycatch in South Africa's inshore trawl fishery as determined from observer records
Authors: Attwood Colin G. , Petersen Samantha L. , Kerwath Sven E.
Published: October 2011

Attwood, C. G., Petersen, S. L., and Kerwath, S. E. 2011. Bycatch in South Africa's inshore trawl fishery as determined from observer records. – ICES Journal of Marine Science, 68: 2163–2174. Ship-based observer data were analysed to describe the volume, composition, utilization, and size structure of catches made by South Africa's inshore trawlers. The sampling rate was 3.5% of all trawls, including unsorted and discard samples. In all, 137 nominal species were recorded. Analysis of species composition separated the trawling grounds into seven areas, providing a framework for stratifying the ground for catch estimation and for selection of representative areas for conservation. The target species, Merluccius capensis and Austroglossus pectoralis, made up 58% of the pre-discard catch. Trachurus trachurus, Pterogymnus laniarius, Raja spp., and Chelidonichthys spp. constituted another 23%. Pre-discard catch volumes of the entire fleet were estimated. The average annual pre-discard catch of M. capensis and A. pectoralis was 9653 and 504 t, respectively, closely matching landing statistics. Argyrosomus inodorus, Rhabdosargus globiceps, Argyrozona argyrozona, and Atractoscion aequidens averaged 294, 230, 107, and 83 t annually, respectively, indicating significant overlap with the handline fishery for A. inodorus and A. argyrozona. A comparison of species composition in unsorted and discard samples revealed the species being preferentially retained. Argyrosomus inodorus and A. aequidens were trawled mainly below their size at maturity. Management needs to consider other species when determining catch or effort limits and area restrictions.
Carotenoid Value Addition of Cereal Products by Monoculture and Mixed‐Culture Fermentation of Phaffia rhodozyma and Sporobolomyces roseus
Authors: Ananda Nanjundaswamy , Vadlani Praveen V.
Published: October 2011

Carotenoid value addition of corn whole stillage by red yeast fermentation has yielded astaxanthin‐ and β‐carotene‐enriched distillers dried grains with solubles (DDGS) for animal feed. In this study, commonly used animal feeds (rice bran, wheat bran, milo whole stillage, and soybean products) were subjected to carotenoid value addition. Phaffia rhodozyma and Sporobolomyces roseus monoculture and mixed‐culture submerged fermentation of these substrates supplemented with 5% glycerol were analyzed for astaxanthin, β‐carotene, and residual glycerol. Among all the substrates, full‐fat rice bran and full‐fat soy flour resulted in the highest astaxanthin (80 μg/g by P. rhodozyma) and β‐carotene yields (836 μg/g by S. roseus). P. rhodozyma produced the highest astaxanthin yield on each substrate, whereas depending on the substrate, either the mixed culture or S. roseus monoculture produced the highest β‐carotene yield. Soy hull was a poor substrate for carotenoid value addition. Both yeasts used glycerol as a carbon source for carotenoid production. This study shows that substrates influence the carotenoid yield. However, it is impossible to dissect the effect of specific nutrients on carotenoid production in complex biological substrates. Carotenoid value addition of these substrates provides as much as or more than the required daily dosage of carotenoids in animal feed.
Effects of CYP3A4 inhibition and induction on the pharmacokinetics and pharmacodynamics of tolvaptan, a non‐peptide AVP antagonist in healthy subjects
Authors: Shoaf Susan E. , Bricmont Patricia , Mallikaarjun Suresh
Published: October 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Before these trials were done, the effects of CYP3A4 inhibition and induction on the pharmacokinetics (PK) and pharmacodynamics (PD) of tolvaptan in healthy subjects were unknown. As tolvaptan is a CYP3A4 substrate, knowing the effects of inhibition and induction on CYP3A4‐mediated metabolism was important for dosing recommendations.

WHAT THIS STUDY ADDS

• This paper describes the changes in tolvaptan PK and PD following inhibition or induction of CYP3A4 and explores the mechanisms behind the disparity seen between tolvaptan PK and effects on urine output. It also discusses the concentrations at which tolvaptan produces its maximal response on urine output and the timing of the onset and offset of this response.

AIMS In vitro studies indicated CYP3A4 alone was responsible for tolvaptan metabolism. To determine the effect of a CYP3A4 inhibitor (ketoconazole) and a CYP3A4 inducer (rifampicin) on tolvaptan pharmacokinetics (PK) and pharmacodynamics (PD), two clinical trials were performed.

METHODS For CYP3A4 inhibition, a double‐blind, randomized (5:1), placebo‐controlled trial was conducted in 24 healthy subjects given either a single 30 mg dose of tolvaptan (n= 19) or matching placebo (n= 5) on day 1 with a 72 h washout followed by a 3 day regimen of 200 mg ketoconazole, once daily with 30 mg tolvaptan or placebo also given on day 5. For CYP3A4 induction, 14 healthy subjects were given a single dose of 240 mg tolvaptan with 48 h washout followed by a 7 day regimen of 600 mg rifampicin, once daily, with 240 mg tolvaptan also given on the seventh day.

RESULTS When co‐administered with ketoconazole, mean Cmax and AUC(0,∞) of tolvaptan were increased 3.48‐ and 5.40‐fold, respectively. Twenty‐four hour urine volume increased from 5.9 to 7.7 l. Erythromycin breath testing showed no difference following a single dose of tolvaptan. With rifampicin, tolvaptan mean Cmax and AUC were reduced to 0.13‐ and 0.17‐fold of tolvaptan administered alone. Twenty‐four hour urine volume decreased from 12.3 to 8.8 l.

CONCLUSIONS Tolvaptan is a sensitive CYP3A4 substrate with no inhibitory activity. Due to the saturable nature of tolvaptan's effect on urine excretion rate, changes in the pharmacokinetic profile of tolvaptan do not produce proportional changes in urine output.
Ceftazidime dosage regimen in intensive care unit patients: from a population pharmacokinetic approach to clinical practice via Monte Carlo simulations
Authors: Georges Bernard , Conil Jean‐Marie , Ruiz Stéphanie , Seguin Thierry , Cougot Pierre , Fourcade Olivier , Houin Georges , Saivin Sylvie
Published: October 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

The large variability in drug pharmacokinetic disposition has already been described in ICU patients leading to important variations in drugs concentrations.

The usual recommended dosage of ceftazidime is not adapted for all ICU situations and ceftazidime should be monitored closely. New recommendations have to be given for some specific cases.

WHAT THIS STUDY ADDS

Our results propose individual therapeutic drug monitoring taking into account:

• For the patient: the reason of admission in the ICU, the mechanical ventilation status and the creatinine clearance calculated by the modified diet in enal disease (MDRD).

• For the antibiotics: the lung distribution, the minimal inhibitory concentration (MIC) of the strain to eradicate and the potential toxicity.

AIM To predict the ceftazidime dosage regimen as a function of the glomerular filtration rate expressed by the modification of the diet in renal disease (MDRD), reason for admission and mechanical ventilation in intensive care unit (ICU) patients to treat Pseudomonas aeruginosa pneumonia.

METHOD A published and qualified population pharmacokinetic model was used to perform Monte Carlo simulations of ceftazidime concentrations. The serum target of 40–100 mg l−1 was defined based on the minimal inhibitory concentration (MIC), the European break point (EBP), the pulmonary drug diffusion and toxicity. The recommended dosage regimens were based on the maximum percentile of the patients with simulated steady state concentrations reaching the target.

RESULTS Steady‐state was reached at 72 h whatever the MDRD. The simulations of serum concentrations generated higher percentiles of the population reaching the target after continuous administration. We recommend a 4 g continuous dose after the usual 2 g loading dose for patients with MDRD from 10 to 30 ml min−1, 6 g for MDRD between 40 and 80 ml min−1, 8 g for MDRD from 90 to 110 ml min−1, 10 g for MDRD from 120 to 190 ml min−1 and 12 g day−1 for patients with MDRD higher than 200 ml min−1.

CONCLUSION Our study demonstrated that in ICU patients for a given MDRD, steady‐state takes longer to reach in polytrauma patients than in patients with medical or post surgery reasons for admission. Continuous infusion ensures that a higher percentage of patients reaches the target than the same dose given by discontinuous administration and this only depends on MDRD.
Association of vitamin D and antimicrobial peptide production during late‐phase allergic responses in the lung
Authors: Liu M. C. , Xiao H.‐Q. , Brown A. J. , Ritter C. S. , Schroeder J.
Published: October 2011

Background

Vitamin D may play important roles in regulating immune responses and in defence against infectious diseases by effects on both innate and adaptive immune responses. Little is known regarding activation of vitamin D within airway tissues and its relationship to inflammation and antimicrobial responses.

Objective

The objective of this study was to investigate the activation of vitamin D within the airways and to define relationships between vitamin D metabolites and measures of inflammatory and antimicrobial responses assessed by bronchoalveolar lavage (BAL) during late‐phase responses following allergen challenge of allergic subjects.

Methods

Segmental allergen challenge was performed with saline and allergen in 16 adult allergic subjects. BAL was performed in both saline and allergen‐challenged sites 20–24 h. after challenge. Following extraction from BAL fluids, levels of 25‐hydroxy‐vitamin D (25(OH)D) and 1,25‐dihydroxy‐vitamin D (1,25(OH)2D) were assayed by specific radioimmunoassays. The cleavage product of cathelicidin, LL‐37, was assayed by ELISA. Cellular constituents and albumin were measured.

Results

Levels of vitamin D metabolites were increased in concentrated BAL fluids after allergen compared to saline challenge. Levels of 1,25(OH)2D increased from largely undetectable to 2.5 pm (median; range: 1–29.5; P = 0.005) while 25(OH)D increased from 3.2 (0.8–6.2) to 6.2 (1.5–184.9) nm (P = 0.0006). Levels of LL‐37 increased from 2.1 (1.4–4.1) to 14.5 (2.2–106.7) ng/mL BAL (P = 0.0005). Levels of LL‐37, 1,25(OH)2D, and 25(OH)D following allergen challenge were correlated with each other (P < 0.0001), cellular changes, and levels of albumin (P < 0.001).

Conclusions and Clinical Relevance

Levels of vitamin D metabolites, particularly 1,25(OH)2D, were low within the airways and increased after allergen challenge. The increases correlated with the magnitude of inflammation and increases in cathelicidin. Normalization to albumin suggested plasma exudation as a mechanism for the increases. The findings support a role for vitamin D in allergic and innate immune responses in the lung.
Activation of a prophage‐encoded tyrosine kinase by a heterologous infecting phage results in a self‐inflicted abortive infection
Authors: Friedman David I. , Mozola Cara C. , Beeri Karen , Ko Ching‐Chung , Reynolds Jared L.
Published: October 2011

Bacteria in their struggle for survival have evolved or acquired defences against attacking phage. However, phage often contribute to this defence through mechanisms in which a prophage protects the bacterial population from attack by another, often unrelated, phage. The 933W prophage, which carries Shiga toxin genes that enhance pathogenicity of enterohaemorrhagic Escherichia coli strain O157:H7, also carries the stk gene encoding a eukaryotic‐like tyrosine kinase that excludes (aborts) infection by phage HK97. This exclusion requires the kinase activity of Stk. Little, if any, protein tyrosine phosphorylation can be detected in a 933W lysogen prior to infection with HK97, while extensive Stk‐mediated tyrosine phosphorylation is evident following infection. This includes autophosphorylation that stabilizes Stk protein from degradation. Although increased levels of Stk are found following HK97 infection, these higher levels are not necessary or sufficient for exclusion or protein phosphorylation. An HK97 open reading frame, orf41, is necessary for exclusion and Stk kinase activity. We hypothesize that interaction with gp41 stimulates Stk kinase activity. Exclusion of HK97 appears to be specific since other phages tested, λ, φ80, H‐19B, λ‐P22dis and T4rII, were not excluded. Infection of the 933W lysogen with a non‐excluded phage fails to induce Stk‐determined phosphorylation.
Expression of the Aeluropus littoralis AlSAP gene in rice confers broad tolerance to abiotic stresses through maintenance of photosynthesis
Authors: BEN SAAD RANIA , FABRE DENIS , MIEULET DELPHINE , MEYNARD DONALDO , DINGKUHN MICHAEL , AL‐DOSS ABDULLAH , GUIDERDONI EMMANUEL , HASSAIRI AFIF
Published: October 2011

The expression of AlSAP, in rice cv. Nipponbare, enhances plant tolerance to cold, drought and salt stresses. AlSAP lines showed 100% survival rate and set seeds while control plants did not recover from the cold treatment. Under a severe drought stress treatment (fraction of transpirable soil water down to 0.1), AlSAP lines exhibited enhanced Transpiration Efficiency (TE) and maintained a high A (Assimilation rate) value (22 µmol·m−2 s−1) while these values dramatically decreased (A = 4 µmol·m−2 s−1) in control plants which were subsequently unable to recover from the stress. Of noteworthy is that AlSAP rice plants yielded a similar and a 60% seed set under control and stress conditions respectively, with regard to wild‐type (WT) plants grown under control conditions. This indicates that AlSAP expression imposes no yield penalty and allows seed production even following a severe drought stress at the vegetative stage. Furthermore, AlSAP rice was shown to accumulate transcripts of a pilot set of eight stress‐related genes at a significantly higher level than WT plants, both under control and stressed conditions. The results suggest that AlSAP expression generates stress tolerance in plants through maintenance of the photosynthetic apparatus integrity and by stimulating an endogenous adaptive potential which is not effectively accomplished in WT plants.
Arabidopsis growth under prolonged high temperature and water deficit: independent or interactive effects?
Authors: VILE DENIS , PERVENT MARJORIE , BELLUAU MICHAËL , VASSEUR FRANÇOIS , BRESSON JUSTINE , MULLER BERTRAND , GRANIER CHRISTINE , SIMONNEAU THIERRY
Published: October 2011

High temperature (HT) and water deficit (WD) are frequent environmental constraints restricting plant growth and productivity. These stresses often occur simultaneously in the field, but little is known about their combined impacts on plant growth, development and physiology. We evaluated the responses of 10 Arabidopsis thaliana natural accessions to prolonged elevated air temperature (30 °C) and soil WD applied separately or in combination. Plant growth was significantly reduced under both stresses and their combination was even more detrimental to plant performance. The effects of the two stresses were globally additive, but some traits responded specifically to one but not the other stress. Root allocation increased in response to WD, while reproductive allocation, hyponasty and specific leaf area increased under HT. All the traits that varied in response to combined stresses also responded to at least one of them. Tolerance to WD was higher in small‐sized accessions under control temperature and HT and in accessions with high biomass allocation to root under control conditions. Accessions that originate from sites with higher temperature have less stomatal density and allocate less biomass to the roots when cultivated under HT. Independence and interaction between stresses as well as the relationships between traits and stress responses are discussed.
Transient gibberellin application promotes Arabidopsis thaliana hypocotyl cell elongation without maintaining transverse orientation of microtubules on the outer tangential wall of epidermal cells
Authors: Sauret‐Güeto Susanna , Calder Grant , Harberd Nicholas P.
Published: October 2011

The phytohormone gibberellin (GA) promotes plant growth by stimulating cellular expansion. Whilst it is known that GA acts by opposing the growth‐repressing effects of DELLA proteins, it is not known how these events promote cellular expansion. Here we present a time‐lapse analysis of the effects of a single pulse of GA on the growth of Arabidopsis hypocotyls. Our analyses permit kinetic resolution of the transient growth effects of GA on expanding cells. We show that pulsed application of GA to the relatively slowly growing cells of the unexpanded light‐grown Arabidopsis hypocotyl results in a transient burst of anisotropic cellular growth. This burst, and the subsequent restoration of initial cellular elongation rates, occurred respectively following the degradation and subsequent reappearance of a GFP‐tagged DELLA (GFP‐RGA). In addition, we used a GFP‐tagged α‐tubulin 6 (GFP‐TUA6) to visualise the behaviour of microtubules (MTs) on the outer tangential wall (OTW) of epidermal cells. In contrast to some current hypotheses concerning the effect of GA on MTs, we show that the GA‐induced boost of hypocotyl cell elongation rate is not dependent upon the maintenance of transverse orientation of the OTW MTs. This confirms that transverse alignment of outer face MTs is not necessary to maintain rapid elongation rates of light‐grown hypocotyls. Together with future studies on MT dynamics in other faces of epidermal cells and in cells deeper within the hypocotyl, our observations advance understanding of the mechanisms by which GA promotes plant cell and organ growth.
Race‐specific type 1 diabetes risk of HLA‐DR7 haplotypes
Authors: Noble J. A. , Johnson J. , Lane J. A. , Valdes A. M.
Published: October 2011

The aim of this study was to test the hypothesis that closely related human leukocyte antigen (HLA) haplotypes containing the DRB1*07:01 gene [‘DR7’ (DRB1*07:01‐DQA1*02:01‐DQB1*02:01g or DRB1*07:01‐DQA1*03:01‐DQB1*02:01g) haplotypes] derived from European and African populations differ in their genetic susceptibility for type 1 diabetes (T1D) depending on the DQ‐α molecule present. A combined total of 98 African American T1D patients from the Type 1 Diabetes Genetics Consortium and from Children's Hospital and Research Center Oakland were genotyped for the HLA class II loci DRB1, DQA1, and DQB1. DNA samples extracted from newborn blood spot cards from African Americans born in California (n = 947) were used as a population‐based control group. Among African American cases, the European‐derived DRB1*07:01‐DQA1*02:01‐DQB1*02:01g haplotype was protective for T1D risk (odds ratio (OR) = 0.34; 95% confidence interval (CI) 0.14–0.78; P < 0.011), but the African‐derived DRB1*07:01‐DQA1*03:01‐DQB1*02:01g haplotype increased T1D risk (OR = 3.96; 95% CI 1.94–8.08; P < 5.5E‐05). The effect of DRB1*07:01‐DQB1*02:01g on T1D susceptibility depends on the DQA1 allele. DRB1*07:01‐DQA1*02:01‐DQB1*02:01g is protective for T1D; however, the presence of DQA1*03:01 on the DRB1*07:01‐DQB1*02:01g haplotype not only renders the DR7 haplotype not protective but also creates a haplotype with significant T1D risk. These data underscore the importance of assessing genetic effects within ethnic context.