The effects of ibuprofen and indomethacin on renal function in the presence and absence of frusemide in healthy volunteers on a restricted sodium diet

1. Since salt depletion stimulates the renal prostaglandin system to maintain renal function, the effects of indomethacin and ibuprofen upon renal haemodynamics, electrolyte excretion and renin release were examined in eight healthy male volunteers on a salt restricted diet, before and after frusemide administration. 2. Neither indomethacin (50 mg) nor ibuprofen (400 mg and 800 mg) affected renal blood flow, glomerular filtration rate or electrolyte excretion before frusemide. 3. Renal blood flow and glomerular filtration rate were significantly increased in the first 20 min after frusemide. These changes were significantly attenuated by indomethacin compared with placebo and ibuprofen 400 mg. Frusemide-induced diuresis but not natriuresis was inhibited by all treatments. 4. Both nonsteroidal agents inhibited equally the rise in renin activity seen after frusemide. 5. In this group of healthy volunteers on a salt restricted diet, ibuprofen and indomethacin had no detrimental effects on renal function in the absence of frusemide. The changes in renal haemodynamics due to frusemide were suppressed more by indomethacin than by ibuprofen, probably reflecting the more potent nature of indomethacin as an inhibitor of prostaglandin synthesis.

A comparison of the effects of ibuprofen and indomethacin upon renal haemodynamics and electrolyte excretion in the presence and absence of frusemide

1. This study has compared the effects of ibuprofen and indomethacin upon renal haemodynamics, electrolyte excretion and renin release in the presence and absence of frusemide under sodium replete conditions in eight healthy volunteers. 2. Neither ibuprofen (400 mg and 800 mg) nor indomethacin (50 mg) affected renal blood flow, glomerular filtration rate or electrolyte excretion in the basal state. 3. Frusemide had no effect on renal blood flow, but significantly increased glomerular filtration rate. This latter change was suppressed significantly only by ibuprofen 400 mg. Frusemide-induced diuresis was inhibited by all treatments, while natriuresis following frusemide was inhibited by indomethacin only. 4. Significant increments in plasma renin activity, which were suppressed by all treatments, were observed after frusemide. The degree of inhibition of the renin responses was significantly greater in the presence of indomethacin than with either dose of ibuprofen. 5. In a sodium replete setting in healthy volunteers, indomethacin and ibuprofen had no detrimental effects on basal renal function. In the presence of frusemide, indomethacin had more anti-natriuretic and renin-suppressing effect than ibuprofen. There was no evidence for a dose-related effect of ibuprofen.

Zeros and Os:Silence, Absence and Erasure in an Intercultural O-thello

The performative function of sound and music has received little attention in performance theory and criticism and certainly much less so in studies of intercultural theatre. Such an absence is noteworthy particularly since interculturalism is an appropriative Western theatrical form that absorbs Eastern sources to re-create the targeted Western mise en scene. Consequently, a careful consideration of the employment of sound and music are imperative for sound and music form the vertebrae of Asian traditional performance practices. In acoustemological and ethnomusicological studies, sound and music demarcate cultural boundaries and locate cultures by an auditory (dis)recognition. In the light of this need for a more considered understanding of the performative function of sound and music in intercultural performance, this paper seeks to examine the soundscapes of an intercultural production of Shakespeare’s Othello – Desdemona. Directed by Singaporean Ong Keng Sen, Desdemona was a re-scripting of Shakespeare’s text and a self-conscious performance an identity politics. Staged with a multi-ethnic, multi-national cast, Desdemona employed various Asian performance traditions such as Sanskrit Kutiyattam, Myanmarese puppetry, and Korean p’ansori to create the intercultural spectacle. The spectacle was not only a visual aesthetic but an aural one as well. By examining the soundscapes of fractured silences and eruptive cultural sounds the paper hopes to establish the ways in which Desdemona performs absences and erasures of ‘Asia’ in a simultaneous act of performing an Asian Shakespeare.

Lipopolysaccharide O antigen status of Yersinia enterocolitica O:8 is essential for virulence and absence of O antigen affects the expression of other Yersinia virulence factors

Lipopolysaccharide (LPS) is the major component of the outer membrane of Gram-negative bacteria. Although much attention has been given to the biological effects of its lipid A portion, a great body of evidence indicates that its O chain polysaccharide (O antigen) portion plays an important role in the bacterium-host interplay. In this work we have studied in-depth the role of the O antigen in Yersinia enterocolitica serotype O:8 pathogenesis. We made a detailed virulence analysis of three mutants having different O antigen phenotypes: (i) LPS with no O antigen (rough mutant); (ii) LPS with one O unit (semirough mutant) and (iii) LPS with random distribution of O antigen chain lengths. We demonstrated that these LPS O antigen mutants were attenuated in virulence regardless of the infection route used. Co-infection experiments revealed that the rough and semirough mutants were severely impaired in their ability to colonize the Peyer's patches and in contrast to the wild-type strain they did not colonize spleen and liver. The mutant with random distribution of O antigen chain lengths, however, survived better but started to be cleared from mouse organs after 8 days. As an explanation to this attenuation we present here evidence that other Yersinia virulence factors depend on the presence of O antigen for their proper function and/or expression. We demonstrated that in the rough mutant: (i) the YadA function but not its expression was altered; (ii) Ail was not expressed and (iii) inv expression was downregulated. On the other hand, expression of flhDC, the flagellar master regulatory operon, was upregulated in this mutant with a concomitant increase in the production of flagellins. Finally, expression of yplA, encoding for the Yersinia phospholipase A, was also upregulated accompanied by an increased flagellar type III secretion system mediated secretion of YplA to culture medium. Together these findings suggest that the absence of O antigen in the outer membrane of Yersinia either directly or indirectly, for example through a cellular or membrane stress, could act as a regulatory signal.

Cathelicidin-like Helminth Defence Molecules (HDMs):Absence of Cytotoxic, Anti-microbial and Anti-protozoan Activities Imply a Specific Adaptation to Immune Modulation

Host defence peptides (HDPs) are expressed throughout the animal and plant kingdoms. They have multifunctional roles in the defence against infectious agents of mammals, possessing both bactericidal and immune-modulatory activities. We have identified a novel family of molecules secreted by helminth parasites (helminth defence molecules; HDMs) that exhibit similar structural and biochemical characteristics to the HDPs. Here, we have analyzed the functional activities of four HDMs derived from Schistosoma mansoni and Fasciola hepatica and compared them to human, mouse, bovine and sheep HDPs. Unlike the mammalian HDPs the helminth-derived HDMs show no antimicrobial activity and are non-cytotoxic to mammalian cells (macrophages and red blood cells). However, both the mammalian- and helminth-derived peptides suppress the activation of macrophages by microbial stimuli and alter the response of B cells to cytokine stimulation. Therefore, we hypothesise that HDMs represent a novel family of HDPs that evolved to regulate the immune responses of their mammalian hosts by retaining potent immune modulatory properties without causing deleterious cytotoxic effects.

The Management of Long-Term Sickness Absence in Large Public Sector Healthcare Organisations: A Realist Evaluation Using Mixed Methods

Purpose The success of measures to reduce long-term sickness absence (LTSA) in public sector organisations is contingent on organisational context. This realist evaluation investigates how interventions interact with context to influence successful management of LTSA. Methods Multi-method case study in three Health and Social Care Trusts in Northern Ireland comprising realist literature review, semi-structured interviews (61 participants), Process-Mapping and feedback meetings (59 participants), observation of training, analysis of documents. Results Important activities included early intervention; workplace-based occupational rehabilitation; robust sickness absence policies with clear trigger points for action. Used appropriately, in a context of good interpersonal and interdepartmental communication and shared goals, these are able to increase the motivation of staff to return to work. Line managers are encouraged to take a proactive approach when senior managers provide support and accountability. Hindering factors: delayed intervention; inconsistent implementation of policy and procedure; lack of resources; organisational complexity; stakeholders misunderstanding each other’s goals and motives. Conclusions Different mechanisms have the potential to encourage common motivations for earlier return from LTSA, such as employees feeling that they have the support of their line manager to return to work and having the confidence to do so. Line managers’ proactively engage when they have confidence in the support of seniors and in their own ability to address LTSA. Fostering these motivations calls for a thoughtful, diagnostic process, taking into account the contextual factors (and whether they can be modified) and considering how a given intervention can be used to trigger the appropriate mechanisms.

Measuring beta diversity for presence-absence data

1. Little consensus has been reached as to general features of spatial variation in beta diversity, a fundamental component of species diversity. This could reflect a genuine lack of simple gradients in beta diversity, or a lack of agreement as to just what constitutes beta diversity. Unfortunately, a large number of approaches have been applied to the investigation of variation in beta diversity, which potentially makes comparisons of the findings difficult.

2. We review 24 measures of beta diversity for presence/absence data (the most frequent form of data to which such measures are applied) that have been employed in the literature, express many of them for the first time in common terms, and compare some of their basic properties.

3. Four groups of measures are distinguished, with a fundamental distinction arising between 'broad sense' measures incorporating differences in composition attributable to species richness gradients, and 'narrow sense' measures that focus on compositional differences independent of such gradients. On a number of occasions on which the former have been employed in the literature the latter may have been more appropriate, and there are many situations in which consideration of both kinds of measures would be valuable.

4. We particularly recommend (i) considering beta diversity measures in terms of matching/mismatching components (usually denoted a , b and c) and thereby identifying the contribution of different sources of variation in species composition, and (ii) the use of ternary plots to express the relationship between the values of these measures and of the components, and as a way of understanding patterns in beta diversity.

Chronic PEGylated obestatin treatment prevents the onset of high fat diet-induced hypertension and endothelial dysfunction in the absence of metabolic actions

Background: Obestatin is a gastrointestinal peptide with established metabolic actions and emerging vascular effects which involve activation of NO signalling. The aim of this study was to investigate effects of a recently-characterised stable analogue, PEGylated obestatin (PEG-OB), in the setting of diet-induced obesity which is associated with both metabolic and vascular dysfunction. Methods: Male Sprague Dawley rats (6 weeks; n=8) were maintained on standard (SD) or high fat (HF) diet (60% fat) for 8 weeks with once-daily injection of either PEG-OB (50nmol/kg/day) or saline from 2 weeks. Results: HF feeding for 8 weeks resulted in marked body weight gain which was not affected by chronic PEG-OB treatment (HF saline, 175.0±12.2; HF PEG-OB, 190.4±6.4g; P=NS). Similarly, blood glucose, as indicated by HbA1c (HF saline, 6.30±0.15; HF PEG-OB, 6.13±0.36%; P=NS) and insulin tolerance (HF saline, 105.2±52.5; HF PEG-OB, 90.3±45.4mmol/L.min; P=NS), were unaltered by PEG-OB. Despite the apparent lack of metabolic effects, chronic PEG-OB treatment markedly attenuated development of HF-induced hypertension (HF saline, 146.5±4.9mmHg; HF PEG-OB, 123.0±9.7mmHg; P<0.01), assessed by tail-cuff plethysmography. Furthermore, organ bath pharmacology in isolated aortic rings, indicated that HF diet-induced endothelial dysfunction was completely prevented by PEG-OB (acetylcholine, EC50: SD saline, 335±113; HF saline, 758±164; HF PEG-OB, 277±85nmol/L; P<0.05). However, contraction to phenylephrine and relaxation to the NO donor, sodium nitroprusside, were unaltered between groups. Conclusions: PEG-OB exerts beneficial effects on hypertension and endothelial function in diabetes independently of metabolic actions suggesting that obestatin signalling may represent a novel therapeutic target to reduce the risk of associated cardiovascular complications.

Comparison of AGNES (absence of gradients and Nernstian equilibrium stripping) and SSCP (scanned stripping chronopotentiometry) for trace metal speciation analysis

The free metal ion concentrations obtained by SSCP (stripping chronopotentiometry at scanned deposition potential) and by AGNES (absence of gradients and Nernstian equilibrium stripping) techniques have been compared and the usefulness of the combination of both techniques in the same electrochemical cell for trace metal speciation analysis is assessed. The free metal ion concentrations and the stability constants obtained for lead(II) and cadmium(II) complexation by pyridinedicarboxylic acid, by 40 nm radius carboxylated latex nanospheres and by a humic acid extracted from an ombrotrophic peat bog were determined. Whenever possible, the free metal ion concentrations were compared with the theoretical predictions of the code MEDUSA and with the free metal ion concentrations estimated from ion selective electrodes (ISE). SSCP values were in agreement with the ones obtained by AGNES, and both of them agreed reasonably with the ISE values and the theoretical predictions. For the lead(II)-humic acid, it was not possible to obtain the stability constants by SSCP due to the heterogeneity effect. However, using AGNES it is possible to obtain, for these heterogeneous systems, the free bulk metal concentration, which allows us to retrieve the stability constant at bulk conditions.

Mon élève a le cancer--comment intervenir? perceptions d'enseignantes du primaire ayant accueilli un élève traité pour un cancer sur les services offerts et souhaités

Cette recherche aborde un phénomène encore peu documenté soit l'expérience d'enseignantes ayant accueilli un élève traité pour un cancer. Les études démontrent que l'école est peu préparée pour répondre aux besoins de ces élèves et offrir un soutien adéquat quant aux difficultés scolaires qu'ils risquent de présenter : fatigue, problème de mémoire, difficultés de concentration et d'apprentissage, etc. Résultant d'entrevues auprès de dix enseignantes, notre analyse qualitative a permis de dégager les services offerts et souhaités pour soutenir efficacement un élève traité pour un cancer dans son cheminement scolaire. En fonction de la situation et des difficultés de l'élève, les enseignantes disent avoir soutenu l'élève sur le plan affectif et social. Plusieurs proposent des moyens pour améliorer l'organisation de la classe. Enfin, notre discussion présente des pistes d'actions pour pallier l'absence de formation, accroître la concertation entre les milieux scolaires, communautaires et hospitaliers et favoriser l'inclusion scolaire de ces élèves.

Aims of education and well-being as absence of disorder

This thesis offers an original account of what personal well-being can be. Any account of education, it is believed, has to do with and aims at personal well-being. I approach this view on well-being not in a positive but in a negative way. I put forward some items that in certain circumstances can be taken by and called sources or forms of disorder. In the absence of such forms or sources of disorder, I assume that a certain order, prudential or moral, takes place and that constitutes the well-being of the person. The concept of ‘absence of disorder’ is introduced and argued as an educationally appropriate view of personal well-being which is the central educational aim. Therefore, ‘absence of disorder’ is positioned as the central aim of education. This concept is illuminated, for practical reasoning, by a list of seven possible forms of disorder: Comparison, Corruption, Dependency, Division, Fear, Self-disintegration and Violence. As a view of personal well-being, ‘absence of disorder’ is initially rooted in informed desire satisfaction, via the introduction of the concept of entropy. Prudentially, the agent’s informed desire is satisfied by living a life with low build up of entropy or disorder. But, in a second move such a base is also provided by the Levinasinian concept of ‘disinterest’ as a root for ‘what is to be a human’. Such ‘disinterest’ is related to the concepts of love and of ‘action for its own sake’. It is at this final approach that an attempt is made towards the approximation of the ethical and the prudential aspects of social practices. Even if only to some extent successful, the argument is directed to the following conclusion: an education aiming at ‘absence of disorder’ may promote prudential well-being and give us some confidence in simultaneously favouring moral education.

On absence: society’s return to barbarians

The problem of social exclusion is dealt here through the lens of a particularly radical social theory, that of autopoietic society by Niklas Luhmann. Here, exclusion is included in society, no longer as an issue for care, integration and therapy, but as a mechanism to show the importance of the visibility of exclusion. The inclusion of exclusion in autopoiesis is a far-reaching step that demands a revisiting of the concept of autopoietic society. This article proposes a radicalization of the concept on the basis of an acknowledgment of the impossibility of communication with the excluded. This acknowledgement conditions society from within. It is built upon the Luhmannian description of Barbarism as the included exclusion, and is further conceptualized as its excess, as a 'space of absence'. Within autopoiesis, absence is described as an aporetic rather than a paradoxical structure, a memento vanitas that irritates the system from within, constantly reminding it of its limitations.

La gigantomachie de Lousanna-Vidy suivie de considérations sur la transmission du motif de l'anguipède

Considérations méthodologiques Nous avons limité aux précisions indispensables à la compréhension de notre propos les considérations sur la gigantomachie en général. Nous renvoyons aux études signalées plus haut (supra, p. 7, n. 2), principalement pour ce qui concerne les géants avant leur transformation en anguipèdes à partir de l'époque hellénistique. Notre recherche de parallèles reposera sur quelques oeuvres d'art encore existantes : les sculptures décorant les plus importantes d'entre elles feront dès lors figure d'archétype, même si, bien sûr, rien ne permet d'exclure qu'il en ait existé de plus significatives. Parmi les nombreux monuments aujourd'hui disparus, respectivement parmi ceux qui seraient encore à découvrir, il s'en trouvait sans doute qui auraient été susceptibles de servir de modèle pour les sculptures ornant le fanum de Lousonna, duquel bien peu de restes nous sont parvenus. A l'exception de quelques renvois ponctuels, notre démarche s'est appuyée exclusivement sur du matériel et des informations déjà publiés. Pour la reconstitution des bas-reliefs de Lousonna, nous nous sommes inspiré généralement de sculptures hellénistiques et romaines dont l'ornementation présentait des similitudes avec les fragments à notre disposition ; la plupart des parallèles sont mentionnés dans le Lexicon Iconographicum Mythologiae Classicae. L'examen des volumes du Corpus Signorum Imperii Romani et de quelques autres recueils nous a permis de faire des propositions pour les cas restés en suspens. A une exception près, l'échantillonnage aéré formé à partir d'ensembles sculptés qui devaient avoir les mêmes caractéristiques que le matériel que nous tenterons d'identifier : ils comportaient des monstres anguipèdes avec les jambes se terminant par la tête du serpent, remontant au plus tard à la fin de la période romaine et produits dans un atelier gréco-romain. Afin de recréer avec le plus de vraisemblance possible l'environnement du fanum de Lousonna, nous avons recherché des édifices de caractéristiques semblables dans les catalogues de temples gallo-romains dressés par P. D. HORNE et A. C. KING (1980), respectivement I. FAUDUET et P. ARCELIN (1993). Tant l'absence presque complète de restes architecturaux susceptibles d'être rapportés à l'édifice religieux que la nature somme toute modeste du vicus lémanique nous ont fait opter pour une variante minimaliste, se limitant finalement à la structure supportant la gigantomachie devant un temple sans aucune décoration. Pour tenter de préciser les modalités de la transmission du thème des géants, nous envisagerons trois cheminements possibles : la tradition orale, la transmission littéraire et, enfin, la représentation iconographique, qu'il s'agisse de monuments, d'objets mobiliers ou même des quelques rares illustrations de textes antiques. Sauf indication contraire, les textes anciens sont cités dans les traductions des Belles-Lettres, des Sources chrétiennes ou de la Loeb Classical Library dont la liste figure à la page 161. La version française des textes dont aucune traduction n'était disponible est généralement due à François Mottas (traduction F.M.). Nous ne reportons les dates de naissance des auteurs ou des artistes mentionnés que lorsqu'elles sont utiles à la compréhension de notre exposé. En plus du rôle qu'ont pu jouer les oeuvres d'art disparues au cours des deux derniers millénaires, divers facteurs ont dû assurer la constitution et la mise au point d'un imaginaire de plus en plus élaboré des gigantomachies. La mémoire a certes sa part dans l'inspiration des artistes qui réalisèrent les sculptures de la cité lémanique; mais si un mythe ou le récit d'un événement peuvent s'être transmis de bouche à oreille au cours des siècles, certaines ressemblances dans l'attitude des personnages sont trop frappantes, même en tenant compte de ces gestes qu'il n'existe qu'une seule façon de représenter: il n'est dès lors pas possible d'imaginer que la transmission des détails des scènes se serait pratiquée uniquement par voie orale. Si le voyage touristique; tel que nous l'entendons de nos jours, n'a pas existé, les personnes susceptibles d'avoir ramené des informations de leurs déplacements à travers l'Empire sont plus nombreuses qu'on ne le croirait au premier abord. Fonctionnaires allant prendre leur charge ou en mission dans une contrée voisine; soldats, parmi lesquels des mercenaires gaulois; pèlerins ayant visité de grands sanctuaires, comme celui d'Esculape à Pergame, emplacement de la gigantomachie la plus impressionnante, ou d'autres lieux de culte; jeunes fortunés ayant étudié à Athènes; commerçants accompagnés par des muletiers ou des portefaix acheminant leurs marchandises; membres de corporations ou artisans exerçant des métiers itinérants; esclaves, dont l'exportation devait représenter une source de revenus intéressante pour les commerçants romains; en dernier lieu, sans parler des artistes eux-mêmes, ces arpenteurs-géomètres chargés de toutes sortes de relevés qui accompagnaient les empereurs lors de leurs déplacements (infra, p. 36). Il faudra cependant rester prudent quant à l'affirmation d'une connaissance visuelle directe que les sculpteurs de Lousonna auraient eue des réalisations antiques avec lesquelles nous mettrons la gigantomachie en parallèle. Même si elle n'a toujours pas pu être prouvée, la circulation de cahiers de modèles semble bel et bien assurée: dans un atelier, les maîtres ont forcément passé leurs croquis à leurs successeurs et ceci s'est peut-être répété pour plusieurs générations d'artisans. Sans parler des monnaies, d'autres moyens de transmission peuvent encore être mentionnés : éventuelles éditions illustrées de textes antiques, motifs gravés sur des gemmes ou représentés sur des récipients décorés... Une observation s'impose ici : la plupart des monuments que nous utiliserons pour notre reconstitution existaient encore lors de l'érection de notre gigantomachie. Une fois les bas-reliefs de Lousonna reconstitués, restait donc à combler l'absence de toute étude sur la survie de la gigantomachie à travers les âges et à préciser l'emploi qui en serait fait à la Renaissance. Divers recueils d'ouvrages consacrés à la mythologie et remontant à cette période nous ont permis de décrire les modalités de la reprise du récit de la guerre des géants; en l'absence de toute synthèse sur ceux-ci dans la peinture de la Renaissance, c'est en partant de l'examen des nombreux travaux consacrés au Palazzo del Te à Mantoue que nous avons pu établir un lien entre les représentations de géants peintes durant la première moitié du 16ème siècle, au cours duquel la gigantomachie était redevenue un sujet d'actualité. Le monument de la bourgade lémanique comporte encore neuf personnages et constitue, avec celui d'Yzeures-sur-Creuse, l'exemplaire le plus complet découvert dans la partie occidentale de l'Empire romain : il méritait bien d'être à l'origine d'une telle démarche.