The anti-inflammatory properties of intravenous immunoglobulin in a murine model of allergic airway disease ; effects on the development of regulatory T-cells

Les immunoglobulines intraveineuses (IVIg) constituent une préparation polyclonale d’IgG isolée et regroupée à partir du plasma sanguin de multiples donneurs. Initialement utilisé comme traitement de remplacement chez les patients souffrant d’immunodéficience primaire ou secondaire, les IVIg sont maintenant largement utilisées dans le traitement de plusieurs conditions auto-immunes, allergiques ou inflammatoires à une dose élevée, dite immunomodulatrice. Différents mécanismes d’action ont été postulés au fil des années pour expliquer l’effet thérapeutique des IVIg dans les maladies auto-immunes et inflammatoires. Entre autre, un nombre grandissant de données issues de modèles expérimentaux chez l’animal et l’humain suggère que les IVIg induisent l’expansion et augmentent l’action suppressive des cellules T régulatrices (Tregs), par un mécanisme qui demeure encore inconnu. Également, les patients atteints de maladies auto-immunes ou inflammatoires présentent souvent un nombre abaissé de Tregs par rapport aux individus sains. Ainsi, une meilleure compréhension des mécanismes par lesquels les IVIg modulent les cellules T régulatrices est requise afin de permettre un usage plus rationnel de ce produit sanguin en tant qu’alternative thérapeutique dans le traitement des maladies auto-immunes et inflammatoires. Par le biais d’un modèle expérimental d’allergie respiratoire induite par un allergène, nous avons démontré que les IVIg diminuaient significativement l’inflammation au niveau des voies aériennes ce, en association avec une différenciation des Tregs à partir des cellules T non régulatrices du tissu pulmonaire. Nous avons également démontré qu’au sein de notre modèle expérimental, l’effet anti-inflammatoire des IVIg était dépendant des cellules dendritiques CD11c+ (CDs) pulmonaires, puisque cet effet pouvait être complètement reproduit par le transfert adoptif de CDs provenant de souris préalablement traitées par les IVIg. À cet effet, il est déjà établi que les IVIg peuvent moduler l’activation et les propriétés des CDs pour favoriser la tolérance immunitaire et que ces cellules seraient cruciales pour l’induction périphérique des Tregs. C’est pourquoi, nous avons cherché à mieux comprendre comment les IVIg exercent leur effet sur ces cellules. Pour la première fois, nous avons démontré que la fraction d’IgG riche en acide sialique (SA-IVIg) (constituant 2-5% de l’ensemble des IgG des donneurs) interagit avec un récepteur dendritique inhibiteur de type lectine C (DCIR) et active une cascade de signalement intracellulaire initiée par la phosphorylation du motif ITIM qui est responsable des changements observés en faveur de la tolérance immunitaire auprès des cellules dendritiques et des Tregs. L’activité anti-inflammatoire de la composante SA-IVIg a déjà été décrite dans des études antérieures, mais encore une fois le mécanisme par lequel ce traitement modifie la fonction des CDs n’a pas été établi. Nous avons finalement démontré que le récepteur DCIR facilite l’internalisation des molécules d’IgG liées au récepteur et que cette étape est cruciale pour permettre l’induction périphérique des Tregs. En tant que produit sanguin, les IVIg constitue un traitement précieux qui existe en quantité limitée. La caractérisation des mécanismes d’action des IVIg permettra une meilleure utilisation de ce traitement dans un vaste éventail de pathologies auto-immunes et inflammatoires.

Numerical model of solid phase transformations governed by nucleation and growth: microstructure development during isothermal crystallization

A simple numerical model which calculates the kinetics of crystallization involving randomly distributed nucleation and isotropic growth is presented. The model can be applied to different thermal histories and no restrictions are imposed on the time and the temperature dependences of the nucleation and growth rates. We also develop an algorithm which evaluates the corresponding emerging grain-size distribution. The algorithm is easy to implement and particularly flexible, making it possible to simulate several experimental conditions. Its simplicity and minimal computer requirements allow high accuracy for two- and three-dimensional growth simulations. The algorithm is applied to explore the grain morphology development during isothermal treatments for several nucleation regimes. In particular, thermal nucleation, preexisting nuclei, and the combination of both nucleation mechanisms are analyzed. For the first two cases, the universal grain-size distribution is obtained. The high accuracy of the model is stated from its comparison to analytical predictions. Finally, the validity of the Kolmogorov-Johnson-Mehl-Avrami model SSSR, is verified for all the cases studied

Development of curriculum in noise awareness

This paper presents a curriculum in noise awareness developed for use in the second and fourth grades, to teach children about the harmful effects of elevated noise levels.

Development and experimental identification of a biomechanical model of the trunk for functional electrical stimulation control in paraplegia

Objectives. Theoretic modeling and experimental studies suggest that functional electrical stimulation (FES) can improve trunk balance in spinal cord injured subjects. This can have a positive impact on daily life, increasing the volume of bimanual workspace, improving sitting posture, and wheelchair propulsion. A closed loop controller for the stimulation is desirable, as it can potentially decrease muscle fatigue and offer better rejection to disturbances. This paper proposes a biomechanical model of the human trunk, and a procedure for its identification, to be used for the future development of FES controllers. The advantage over previous models resides in the simplicity of the solution proposed, which makes it possible to identify the model just before a stimulation session ( taking into account the variability of the muscle response to the FES). Materials and Methods. The structure of the model is based on previous research on FES and muscle physiology. Some details could not be inferred from previous studies, and were determined from experimental data. Experiments with a paraplegic volunteer were conducted in order to measure the moments exerted by the trunk-passive tissues and artificially stimulated muscles. Data for model identification and validation also were collected. Results. Using the proposed structure and identification procedure, the model could adequately reproduce the moments exerted during the experiments. The study reveals that the stimulated trunk extensors can exert maximal moment when the trunk is in the upright position. In contrast, previous studies show that able-bodied subjects can exert maximal trunk extension when flexed forward. Conclusions. The proposed model and identification procedure are a successful first step toward the development of a model-based controller for trunk FES. The model also gives information on the trunk in unique conditions, normally not observable in able-bodied subjects (ie, subject only to extensor muscles contraction).

A hypoplastic model of skeletal muscle development displaying reduced foetal myoblast cell numbers, increased oxidative myofibres and improved specific tension capacity

The major component of skeletal muscle is the myofibre. Genetic intervention inducing over-enlargement of myofibres beyond a certain threshold through acellular growth causes a reduction in the specific tension generating capacity of the muscle. However the physiological parameters of a genetic model that harbours reduced skeletal muscle mass have yet to be analysed. Genetic deletion of Meox2 in mice leads to reduced limb muscle size and causes some patterning defects. The loss of Meox2 is not embryonically lethal and a small percentage of animals survive to adulthood making it an excellent model with which to investigate how skeletal muscle responds to reductions in mass. In this study we have performed a detailed analysis of both late foetal and adult muscle development in the absence of Meox2. In the adult, we show that the loss of Meox2 results in smaller limb muscles that harbour reduced numbers of myofibres. However, these fibres are enlarged. These myofibres display a molecular and metabolic fibre type switch towards a more oxidative phenotype that is induced through abnormalities in foetal fibre formation. In spite of these changes, the muscle from Meox2 mutant mice is able to generate increased levels of specific tension compared to that of the wild type.

The UK Department of National Heritage: a model for the development and integration of leisure policy in the new Europe?

Leisure is in the vanguard of a social and cultural revolution which is replacing the former East/West political bipolarity with a globalised economic system in which the new Europe has a central rôle. Within this revolution, leisure, including recreation, culture and tourism, is constructed as the epitome of successful capitalist development; the very legitimisation of the global transmogrification from a production to a consumption orientation. While acting as a direct encouragement to the political transformation in many eastern European states, it is uncertain how the issue of leisure policy is being handled, given its centrality to the new economic order. This paper therefore examines the experience of western Europe, considering in particular the degree to which the newly-created Department of National Heritage in the UK provides a potential model for leisure development and policy integration in the new Europe. Despite an official rhetoric of support and promotion of leisure activities, reflecting the growing economic significance of tourism and the positive relationship between leisure provision and regional economic development, the paper establishes that in the place of the traditional rôle of the state in promoting leisure interests, the introduction of the Department has signified a shift to the use of leisure to promote the Government's interests, particularly in regenerating citizen rights claims towards the market. While an institution such as the Department of National Heritage may have relevance to emerging states as a element in the maintenance of political hegemony, therefore, it is questionable how far it can be viewed as a promoter or protector of leisure as a signifier of a newly-won political, economic and cultural freedom throughout Europe.

The persistence of distance: a gravity model of European cross-border real estate development flows

Purpose – This paper aims to investigate the scale and drivers of cross-border real estate development in Western Europe and Central and Eastern Europe. Design/methodology/approach – Placing cross-border real estate development within the framework of foreign direct investment (FDI), conceptual complexities in characterizing the notional real estate developer are emphasized. Drawing upon a transaction database, this paper proxies cross-border real estate development flows with asset sales by developers. Findings – Much higher levels of market penetration by international real estate developers are found in the less mature markets of Central and Eastern Europe. Analysis suggests a complex range of determinants with physical distance remaining a consistent barrier to cross-border development flows. Originality/value – This analysis adds significant value in terms of understanding cross-border real estate development flows. In this study, a detailed examination of the issues based on a rigorous empirical analysis through gravity modelling is offered. The gravity framework is one of the most confirmed empirical regularities in international economics and commonly applied to trade, FDI, migration, foreign portfolio investment inter alia. This paper assesses the extent to which it provides useful insights into the pattern of cross-border real estate development flows.

A modified rat model of neonatal anoxia: Development and evaluation by pulseoximetry, arterial gasometry and Fos immunoreactivity

Neonatal anoxia is a worldwide clinical problem that has serious and lasting consequences. The diversity of models does not allow complete reproducibility, so a standardized model is needed. In this study, we developed a rat model of neonatal anoxia that utilizes a semi-hermetic system suitable for oxygen deprivation. The validity of this model was confirmed using pulse oximetry, arterial gasometry, observation of skin color and behavior and analysis of Fos immunoreactivity in brain regions that function in respiratory control. For these experiments, 87 male albino neonate rats (Rattus norvegicus, lineage Wistar) aged approximate 30 postnatal hours were divided into anoxia and control groups. The pups were kept in an euthanasia polycarbonate chamber at 36 +/- 1 degrees C, with continuous 100% nitrogen gas flow at 3 L/min and 101.7 kPa for 25 min. The peripheral arterial oxygen saturation of the anoxia group decreased 75% from its initial value. Decreased pH and partial pressure of oxygen and increased partial pressure of carbon dioxide were observed in this group, indicating metabolic acidosis, hypoxia and hypercapnia. respectively. Analysis of neuronal activation showed Fos immunoreactivity in the solitary tract nucleus, the lateral reticular nucleus and the area postrema, confirming that those conditions activated areas related to respiratory control in the nervous system. Therefore, the proposed model of neonatal anoxia allows standardization and precise control of the anoxic condition, which should be of great value in indentifying both the mechanisms underlying neonatal anoxia and novel therapeutic strategies to combat or prevent this widespread public health problem. (C) 2011 Elsevier B.V. All rights reserved.

City-to-surf - a peer-to-peer model of on-line professional development: a collaborative mentoring model

This project explores the potential of electronic communications to support peer-to-peer interaction between separate whole-school communities as a means of providing both authentic, situated, professional development for teachers, concurrent with the development of enhanced student learning outcomes, and the intentional sharing of school 'culture'.  The intense use of telecommunications by both teacher and students in a 'many-to-many' manner provides rich opportunities for teachers to rethink their pedagogy, reconceptualise their classroom culture, and for students to see teachers as learners 'in situ'.  An extensive trial between two schools some 120km apart has demonstrated the basic functionality of the model.  This paper discusses the origins of the project, findings from the trial, and the nature of the changes to be made to the model to enhance its effects.

From personal reflection to social positioning: the development of a transformational model of a professional education in midwifery

A transformational model of professional identity formation, anchored and globalized in workplace conversations, is advanced. Whilst the need to theorize the aims and methods of clinical education has been served by the techno-rational platform of 'reflective practice', this platform does not provide an adequate psychological tool to explore the dynamics of social episodes in professional learning and this led us to positioning theory. Positioning theory is one such appropriate tool in which individuals metaphorically locate themselves within discursive action in everyday conversations to do with personal positioning, institutional practices and societal rhetoric. This paper develops the case for researching social episodes in clinical education through professional conversations where midwifery students, in practice settings, are encouraged to account for their moment-by-moment interactions with their preceptors/midwives and university mentors. It is our belief that the reflection elaborated by positioning theory should be considered as the new epistemology for professional education where professional conversations are key to transformative learning processes for persons and institutions.

Development and application of model of resource utilization, costs, and outcomes for stroke (MORUCOS): an Australian economic model for stroke.

Objectives: To outline the development, structure, data assumptions, and application of an Australian economic model for stroke (Model of Resource Utilization, Costs, and Outcomes for Stroke [MORUCOS]). Methods: The model has a linked spreadsheet format with four modules to describe the disease burden and treatment pathways, estimate prevalence-based and incidence-based costs, and derive life expectancy and quality of life consequences. The model uses patient-level, community-based, stroke cohort data and macro-level simulations. An interventions module allows options for change to be consistently evaluated by modifying aspects of the other modules. To date, model validation has included sensitivity testing, face validity, and peer review. Further validation of technical and predictive accuracy is needed. The generic pathway model was assessed by comparison with a stroke subtypes (ischemic, hemorrhagic, or undetermined) approach and used to determine the relative cost-effectiveness of four interventions. Results: The generic pathway model produced lower costs compared with a subtypes version (total average first-year costs/case AUD$15,117 versus AUD$17,786, respectively). Optimal evidence-based uptake of anticoagulation therapy for primary and secondary stroke prevention and intravenous thrombolytic therapy within 3 hours of stroke were more cost-effective than current practice (base year, 1997). Conclusions: MORUCOS is transparent and flexible in describing Australian stroke care and can effectively be used to systematically evaluate a range of different interventions. Adjusting results to account for stroke subtypes, as they influence cost estimates, could enhance the generic model.

Development of a model of the antecedents and consequences of an inclusivie team climate

Exclusion due to the tendency of people to form subgroups based on perceived interpersonal similarities and dissimilarities still prevents many individuals and teams from reaching their full potential. Using research from the social psychology and organisational behaviour literature we examine the relationship between perceived dissimilarity, subgroup formation and team climate and individual team member's responses to the team and propose a model of the antecedents and consequences of individual team members propensity to perceive dissimilarity and an inclusive team climate.