A comparative study of T-cell receptor V beta usage in non-obese diabetic (NOD) and I-E transgenic NOD mice.

The non-obese diabetic (NOD) mouse is a model for the study of insulin-dependent diabetes mellitus (IDDM). Recently transgenic NOD mice have been derived (NOD-E) that express the major histocompatibility complex (MHC) class II I-E molecule. NOD-E do not become diabetic and show negligible pancreatic insulitis. The possibility pertained that NOD-E mice are protected from disease by a process of T-cell deletion or anergy. This paper describes our attempts to discover whether this was so, by comparing NOD and NOD-E mouse T-cell receptor V beta usage. Splenocytes and lymph node cells were therefore tested for their ability to proliferate in response to monoclonal anti-V beta antibodies. We were unable to show any consistent differences between NOD and NOD-E responses to the panel of antibodies used. Previously proposed V beta were shown to be unlikely candidates for deletion or anergy. T cells present at low frequency (V beta 5+) in both NOD and NOD-E mice were shown to be as capable of expansion in response to antigenic stimulation as were more frequently expressed V beta. Our data therefore do not support deletion or anergy as mechanisms which could account for the observed disease protection in NOD-E mice.

Comparative Study of Chemoembolization, Loadable Beads: In vitro Drug Release and Physical Properties of DC Bead and Hepasphere, Loaded with Doxorubicin and Irinotecan

Purpose To characterize in vitro the loadability, physical properties, and release of irinotecan and doxorubicin from two commercially available embolization microspheres. Materials and Methods DC Bead (500-700 μm) and Hepasphere (400-600 μm) microspheres were loaded with either doxorubicin or irinotecan solutions. Drug amount was quantified with spectrophotometry, bead elasticity was measured under compression, and bead size and loading homogeneity were assessed with microscopy image analysis. Drug release was measured over 1-week periods in saline by using a pharmacopeia flow-through method. Results Almost complete drug loading was obtained for both microsphere types and drugs. Doxorubicin-loaded DC Beads maintained their spherical shape throughout the release. In contrast, Hepaspheres showed less homogeneous doxorubicin loading and, after release, some fractured microspheres. Incomplete doxorubicin release was observed in saline over 1 week (27% ± 2 for DC beads and 18% ± 7 for Hepaspheres; P = .013). About 75% of this amount was released within 2.2 hours for both beads. For irinotecan, complete release was obtained for both types of beads, in a sustained manner over 2-3 hours for DC Beads, and in a significantly faster manner as a 7-minute burst for Hepaspheres. Conclusions The two drug-eluting microspheres could be efficiently loaded with both drugs. Incomplete doxorubicin release was attributed to strong drug-bead ionic interactions. Weaker interactions were observed with irinotecan, which led to faster drug release.

Effets des usages différenciés de l'activité physique sur des enfants en classe enfantine : étude pluridisciplinaire et comparative

La thèse traite de projets de classes enfantines avec de l'activité physique, projets pilotes ayant entre autres le but d'évaluer les effets d'un apport d'activité physique auprès d'enfants de 4 à 6 ans. Le projet de recherche saisit l'opportunité de pouvoir observer les effets de l'AP sur de jeunes enfants (n=86, classes AP=40, classes contrôles=46) et ceci par trois regards distincts : une quantification de l'activité physique, l'influence de cette dernière sur certaines composantes cognitives (créativité, intelligence et concentration) des jeunes enfants et, enfin, l'influence de l'activité physique au niveau psychosocial (microsystèmes familial et scolaire). La méthodologie mélange des méthodes qualitatives (entretiens, observations) et quantitatives (accéléromètres (GT1M), tests de créativité (Krampen, 1996), d'intelligence (Cattell, Weiss & Osterland, 1997), de concentration (Krampen, 2007)). Les principaux résultats démontrent que ce type de projet permet d'augmenter l'AP durant le temps scolaire et les résultats sont plus contrastés en extrascolaire. Un temps supérieur consacré à l'AP ne démontre aucune diminution des capacités cognitives dans cette tranche d'âge-là. L'analyse du microsystème familial nous informe sur le fait que les parents qui ont placé leurs enfants dans ce type de classes sont eux-mêmes plus actifs que la moyenne de la population suisse (Lamprecht, Fischer, & Stamm, 2008a). Enfin, un apport d'AP ne permet pas d'augmenter le nombre de feedbacks tournés vers l'autonomie et le style contrôlant est même renforcé. Nos résultats sont discutés sur la base des études de Kriemler et al. (2010) qui démontrent toute la difficulté d'une intervention scolaire pour modifier les comportements familiaux en extrascolaire. La fonction exécutive (Tomporowski et al., 2008) offre un regard neurophysiologique éclairant les effets de l'AP sur les différentes capacités étudiées. Enfin, il semble que la pression générée par la mise en place de projets liés à un apport d'AP en école enfantine va dans le sens d'une augmentation d'un style contrôlant (Tessier, 2006). Ce choix d'approcher les observations selon plusieurs angles d'étude est audacieux car il se situe en situation écologique mais il représente en même temps le seul moyen d'observer les effets en tenant davantage compte de la complexité des conduites des interactions entre différents facteurs. - The aim of the study is to evaluate the effect of physical activity (PA) in kindergartens with children aged from 4 to 6 years old. The project seizes the opportunity to observe the effects of PA on young children (n=86, classes AP=40, control classes=46) with three different axes: a quantification of PA, the influence of PA on cognitive functions (creativity, intelligence and concentration), and the influence on the family and the climate in the class. The methodology is based on a mix of qualitative (interviews, observations) and quantitative (accelerometer (GT1M), creativity test (Krampen, 1996), intelligence test (Cattell, Weiss & Osterland, 1997), concentration test (Krampen, 2007)) methods. The main results show that PA during the schooltime increased and the results outside of the school present more contrasts. More time spent for PA doesn't influence negatively the evolution of the cognitive functions at this age. The parents, who have interest for this kind of kindergartens for their children move significantly more than the Swiss population (Lamprecht, et al., 2008a). More PA during the lessons doesn't increase the feedbacks given with autonomy and more control is even observed. The results show the difficulty of changing the behaviors of a family linked to PA outside of the school (Kriemler et al., 2010). The discussion of the results of the cognitive functions is based on the executive function, which seems to be linked to PA (Tomporowski et al., 2008). Finally, it seems that the pressure occurred by those projects with PA tend to foster a climate with more control (Tessier, 2006). The choice of structuring the thesis with three different axes represents a risk because it is established in ecological conditions, but it also allows to observe the effects of PA taking into consideration the interactions between the different factors.

Sources of comparative advantage in polluting industries

We study the determinants of comparative advantage in polluting industries. We combine data on environmental policy at the country level with data on pollution intensity at the industry level to show that countries with laxer environmental regulation have a comparative advantage in polluting industries. Further, we address the potential problem of reverse causality. We propose an instrument for environmental regulation based on meteorological determinants of pollution dispersion identified by the atmospheric pollution literature. We find that the effect of environmental regulation on the pattern of trade is causal and comparable in magnitude to the effect of physical and human capital.

A Comparative Study of Transvaginal Tape, Transobturator Tape Outside-in, and Transvaginal Tape-obturator Inside-out Surgical Procedures in the Treatment of Stress Urinary Incontinence

The aim of this work was to use the Urinary Distress Inventory (UDI-6) and Incontinence Impact Quality of Life (IIQ-7) questionnaires to compare 3 surgical techniques for stress urinary incontinence: the transvaginal tape (TVT) (105 women), the transobturator tape outside-in (TOT) (43 women), and the transvaginal tape-obturator inside-out (TVT-O) (54 women). There were no significant differences in frequent urination, urine leakage related to the feeling of urgency, urine leakage related to physical activity, or small amounts of urine leakage. TVT-operated women had a lower percentage of micturition difficulties compared with TOT women. TVT-O-operated women described slight discomfort in the genital area compared with the TVT technique, but this difference was not significant when compared with the TOT technique. When utilizing the UDI-6 and IIQ-7 scoring modifications before and after surgery, no difference among these 3 techniques is apparent.

Spirituality and religion in outpatients with schizophrenia: A multi-site comparative study of Switzerland, Canada, and the United States

Objective: To assess the importance of spirituality and religious coping among outpatients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder living in three countries. Method: A total of 276 outpatients (92 from Geneva, Switzerland, 121 from Trois-Rivières, Canada, and 63 from Durham, North Carolina), aged 18-65, were administered a semi-structured interview on the role of spirituality and religiousness in their lives and to cope with their illness. Results: Religion is important for outpatients in each of the three country sites, and religious involvement is higher than in the general population. Religion was helpful (i.e., provided a positive sense of self and positive coping with the illness) among 87% of the participants and harmful (a source of despair and suffering) among 13%. Helpful religion was associated with better social, clinical and psychological status. The opposite was observed for the harmful aspects of religion. In addition, religion sometimes conflicted with psychiatric treatment. Conclusions: These results indicate that outpatients with schizophrenia or schizoaffective disorder often use spirituality and religion to cope with their illness, basically positively, yet sometimes negatively. These results underscore the importance of clinicians taking into account the spiritual and religious lives of patients with schizophrenia.

Entretiens phénoménologiques et entretiens focalisés sur l'activité : analyse comparative, similitudes et variations.

Cet article présente une analyse comparative des résultats de deux formes d'entretiens : en 2005, des entretiens phénoménologiques, en 2006 des entretiens centrés sur l'activité. Deux problématiques sont abordées : la perception de la santé au travail et les pratiques de contraception. Nous présentons les premiers résultats de cette analyse comparative : ils montrent que l'adaptation des entretiens centrés sur l'activité au domaine de la santé présente un grand intérêt au niveau des apports de contenus. Le retour du sujet sur le discours concernant son activité concrète facilite la réflexivité et conduit à des transformations personnelles. Des difficultés concernant la position du chercheur et l'adéquation de la technique à la Psychologie de la Santé sont discutées. Cette première exploration ne détermine pas encore ce qui est dû à la différence des techniques. Nos travaux comparatifs vont se poursuivre en vue d'explorer des alternatives méthodologiques applicables en Psychologie de la Santé.

Analysis of susceptibility to human immunodeficiency virus 1 (HIV-1) by comparative genetics

Summary [résumé français voir ci-dessous] From the beginning of the 20th century the world population has been confronted with the human immune deficiency virus 1 (HIV-1). This virus has the particularity to mutate fast, and could thus evade and adapt to the human host. Our closest evolutionary related organisms, the non-human primates, are less susceptible to HIV-1. In a broader sense, primates are differentially susceptible to various retrovirus. Species specificity may be due to genetic differences among primates. In the present study we applied evolutionary and comparative genetic techniques to characterize the evolutionary pattern of host cellular determinants of HIV-1 pathogenesis. The study of the evolution of genes coding for proteins participating to the restriction or pathogenesis of HIV-1 may help understanding the genetic basis of modern human susceptibility to infection. To perform comparative genetics analysis, we constituted a collection of primate DNA and RNA to allow generation of de novo sequence of gene orthologs. More recently, release to the public domain of two new primate complete genomes (bornean orang-utan and common marmoset) in addition of the three previously available genomes (human, chimpanzee and Rhesus monkey) help scaling up the evolutionary and comparative genome analysis. Sequence analysis used phylogenetic and statistical methods for detecting molecular adaptation. We identified different selective pressures acting on host proteins involved in HIV-1 pathogenesis. Proteins with HIV-1 restriction properties in non-human primates were under strong positive selection, in particular in regions of interaction with viral proteins. These regions carried key residues for the antiviral activity. Proteins of the innate immunity presented an evolutionary pattern of conservation (purifying selection) but with signals of relaxed constrain if we compared them to the average profile of purifying selection of the primate genomes. Large scale analysis resulted in patterns of evolutionary pressures according to molecular function, biological process and cellular distribution. The data generated by various analyses served to guide the ancestral reconstruction of TRIM5a a potent antiviral host factor. The resurrected TRIM5a from the common ancestor of Old world monkeys was effective against HIV-1 and the recent resurrected hominoid variants were more effective against other retrovirus. Thus, as the result of trade-offs in the ability to restrict different retrovirus, human might have been exposed to HIV-1 at a time when TRIM5a lacked the appropriate specific restriction activity. The application of evolutionary and comparative genetic tools should be considered for the systematical assessment of host proteins relevant in viral pathogenesis, and to guide biological and functional studies. Résumé La population mondiale est confrontée depuis le début du vingtième siècle au virus de l'immunodéficience humaine 1 (VIH-1). Ce virus a un taux de mutation particulièrement élevé, il peut donc s'évader et s'adapter très efficacement à son hôte. Les organismes évolutivement le plus proches de l'homme les primates nonhumains sont moins susceptibles au VIH-1. De façon générale, les primates répondent différemment aux rétrovirus. Cette spécificité entre espèces doit résider dans les différences génétiques entre primates. Dans cette étude nous avons appliqué des techniques d'évolution et de génétique comparative pour caractériser le modèle évolutif des déterminants cellulaires impliqués dans la pathogenèse du VIH- 1. L'étude de l'évolution des gènes, codant pour des protéines impliquées dans la restriction ou la pathogenèse du VIH-1, aidera à la compréhension des bases génétiques ayant récemment rendu l'homme susceptible. Pour les analyses de génétique comparative, nous avons constitué une collection d'ADN et d'ARN de primates dans le but d'obtenir des nouvelles séquences de gènes orthologues. Récemment deux nouveaux génomes complets ont été publiés (l'orang-outan du Bornéo et Marmoset commun) en plus des trois génomes déjà disponibles (humain, chimpanzé, macaque rhésus). Ceci a permis d'améliorer considérablement l'étendue de l'analyse. Pour détecter l'adaptation moléculaire nous avons analysé les séquences à l'aide de méthodes phylogénétiques et statistiques. Nous avons identifié différentes pressions de sélection agissant sur les protéines impliquées dans la pathogenèse du VIH-1. Des protéines avec des propriétés de restriction du VIH-1 dans les primates non-humains présentent un taux particulièrement haut de remplacement d'acides aminés (sélection positive). En particulier dans les régions d'interaction avec les protéines virales. Ces régions incluent des acides aminés clé pour l'activité de restriction. Les protéines appartenant à l'immunité inné présentent un modèle d'évolution de conservation (sélection purifiante) mais avec des traces de "relaxation" comparé au profil général de sélection purifiante du génome des primates. Une analyse à grande échelle a permis de classifier les modèles de pression évolutive selon leur fonction moléculaire, processus biologique et distribution cellulaire. Les données générées par les différentes analyses ont permis la reconstruction ancestrale de TRIM5a, un puissant facteur antiretroviral. Le TRIM5a ressuscité, correspondant à l'ancêtre commun entre les grands singes et les groupe des catarrhiniens, est efficace contre le VIH-1 moderne. Les TRIM5a ressuscités plus récents, correspondant aux ancêtres des grands singes, sont plus efficaces contre d'autres rétrovirus. Ainsi, trouver un compromis dans la capacité de restreindre différents rétrovirus, l'homme aurait été exposé au VIH-1 à une période où TRIM5a manquait d'activité de restriction spécifique contre celui-ci. L'application de techniques d'évolution et de génétique comparative devraient être considérées pour l'évaluation systématique de protéines impliquées dans la pathogenèse virale, ainsi que pour guider des études biologiques et fonctionnelles

Comparative resilience of clinical perimetric tests to induced levels of intraocular straylight.

PURPOSE: To investigate the effect of intraocular straylight (IOS) induced by white opacity filters (WOF) on threshold measurements for stimuli employed in three perimeters: standard automated perimetry (SAP), pulsar perimetry (PP) and the Moorfields motion displacement test (MDT).¦METHODS: Four healthy young (24-28 years old) observers were tested six times with each perimeter, each time with one of five different WOFs and once without, inducing various levels of IOS (from 10% to 200%). An increase in IOS was measured with a straylight meter. The change in sensitivity from baseline was normalized, allowing comparison of standardized (z) scores (change divided by the SD of normative values) for each instrument.¦RESULTS: SAP and PP thresholds were significantly affected (P < 0.001) by moderate to large increases in IOS (50%-200%). The drop in motion displacement (MD) from baseline with WOF 5, was approximately 5 dB, in both SAP and PP which represents a clinically significant loss; in contrast the change in MD with MDT was on average 1 minute of arc, which is not likely to indicate a clinically significant loss.¦CONCLUSIONS: The Moorfields MDT is more robust to the effects of additional straylight in comparison with SAP or PP.