Development of an Internet-based Disease Management Program for People with Diabetes

Diabetes is a chronic illness that currently has no cure. Quality of life can be improved by the person’s own adherence to treatment and motivation to manage their diabetes. Both of these factors are difficult maintain and access to patient education materials is limited. This study developed an Internet-based disease management program for people with diabetes. This diabetes disease management program followed the PRECEDE health program planning model. Focus groups and key informant interviews people with diabetes were run in order to obtain feedback for this program. Cognitive-behavioral and health behavior change theory were integrated in to the program to increase self-efficacy and treatment adherence

Formalisation Multi-Agents de la Sociologie de l'Action Organisée

The sociology of the organised action (Crozier, Friedberg) is widely used to make diagnostics of organisational context when some structural difficulties are encountered. However, the results of a SOA analysis is essentially informal, no comparisons or generalisation are possible. This work present a formalisation of this theory as: - a meta-model of social organisations, - techniques for an analytic study of an organisation, - simulation, using a model of the actors' bounded rationality, to compute how the actors' behaviours could be regularised.Bien souvent utilisée comme outils d'intégration et d'échange entre les différentes parties de projets scientifiques interdisciplinaires, la simulation numérique est en plein essor dans les sciences sociales, et notamment la simulation multi-agents. En effet, la capacité de calcul de plus en plus puissante des ordinateurs et les méthodes de recherche individu-centrées en sciences sociales (micro-économie ou individualisme méthodologique, pour ne citée que celles-ci) ont suscité un intérêt croissant pour la représentation logicielle de processus interagissant les un avec les autres dans le cadre d'un phénomène qualifié de complexe. Notre thèse se positionne ainsi dans ce contexte, plus particulièrement au niveau des relations causales entre des comportements microscopiques en interaction et un phénomène macroscopique émergeant. Notre travail de recherche s'inscrit dans un projet mené en collaboration avec des sociologues qui vise à rendre compte de phénomènes organisationnels. Plutôt que de s'emparer de cas empiriques et de produire des modèles ad'hoc, nous proposons une démarche innovante consistant à formaliser une théorie sociologique : la Sociologie de l'Action Organisée (SAO) de M. Crozier et E. Friedberg. L'intérêt d'une telle modélisation est de disposer d'un méta-modèle sociologiquement fondé permettant de modéliser de façon formelle différentes organisations relevant de son champ d'expertise. Nous proposons de mettre en œuvre cette formalisation via un laboratoire virtuel, SocLab, permettant d'éditer le modèle d'une organisation puis de mener des expériences et tester nos hypothèses. Du méta-modèle de la SAO à l'outil d'expérimentation SocLab, notre thèse propose une démarche méthodologique pour l'analyse organisationnelle assistée par l'expérimentation virtuelle. Dans la perspective d'analyser la causalité émergente des processus organisationnels, nous avons défini une série d'indicateurs numériques qui servent de base aux interprétations indispensables à la vérification et la validation d'un modèle. Ces indicateurs permettent de caractériser acteurs, relations, et transactions dans les termes de la SAO et de comparer différents modèles, d'une même organisation ou d'organisations différentes. Nous présentons ensuite un modèle d'agent adaptatif à base de règles qui rend compte du comportement stratégique des acteurs dont la rationalité est orientée vers la coopération tel que le postule la SAO. Nous présentons par ailleurs une méthodologie de validation des modèles de rationalité. Enfin nous illustrons notre démarche avec un cas d'étude issu du corpus SAO, que nous modélisons, soumettons à diverses hypothèses, que nous interprétons et (in)validons par la simulation. Outre la démarche de formalisation de la SAO et le développement du laboratoire virtuel SocLab, la thèse présente de nombreuses originalités que ce soit au niveau des concepts développés autour de l'échange et de la coopération, au niveau du modèle d'agent stratégique-coopératif, ou au niveau des outils d'analyse produits ou mis en œuvre. L'intérêt principal réside dans le développement d'une démarche rigoureuse couvrant de nombreux aspects de l'utilisation de l'expérimentation virtuelle en sociologie qui devrait permettre au chercheur, à l'étudiant comme aux consultants en organisation de produire des raisonnements solides sur le /phénomène organisation/

Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201).

OBJECTIVES: Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r) provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI) for future use and decreased toxicity. We hypothesized that the level of immune activation (IA) and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification. METHODS: Thirty-four participants with virologic suppression ≥ 48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor) were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8), natural killer (NK) (CD3+CD56+CD16+) cells and cell-associated markers (HLA-DR, CD\u27s 38/69/94/95/158/279). RESULTS: Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL) \u3e50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL \u3e50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023), with an odds ratio of 10.3 (95% CI: 1.92-55.3). Simplification was associated with transient increases in naïve and CD25+ CD4+ T-cells, and had no impact on IA levels. CONCLUSIONS: Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical monitoring. TRIAL REGISTRATION: ClinicalTrials.gov NCT00084019

Complementary Dendritic Cell–activating Function of CD8+ and CD4+ T Cells: Helper Role of CD8+ T Cells in the Development of T Helper Type 1 Responses

Dendritic cells (DCs) activated by CD40L-expressing CD4+ T cells act as mediators of “T helper (Th)” signals for CD8+ T lymphocytes, inducing their cytotoxic function and supporting their long-term activity. Here, we show that the optimal activation of DCs, their ability to produce high levels of bioactive interleukin (IL)-12p70 and to induce Th1-type CD4+ T cells, is supported by the complementary DC-activating signals from both CD4+ and CD8+ T cells. Cord blood– or peripheral blood–isolated naive CD8+ T cells do not express CD40L, but, in contrast to naive CD4+ T cells, they are efficient producers of IFN-γ at the earliest stages of the interaction with DCs. Naive CD8+ T cells cooperate with CD40L-expressing naive CD4+ T cells in the induction of IL-12p70 in DCs, promoting the development of primary Th1-type CD4+ T cell responses. Moreover, the recognition of major histocompatibility complex class I–presented epitopes by antigen-specific CD8+ T cells results in the TNF-α– and IFN-γ–dependent increase in the activation level of DCs and in the induction of type-1 polarized mature DCs capable of producing high levels of IL-12p70 upon a subsequent CD40 ligation. The ability of class I–restricted CD8+ T cells to coactivate and polarize DCs may support the induction of Th1-type responses against class I–presented epitopes of intracellular pathogens and contact allergens, and may have therapeutical implications in cancer and chronic infections

Dendritic Cells Reveal a Broad Range of MHC Class I Epitopes for HIV-1 in Persons with Suppressed Viral Load on Antiretroviral Therapy

Background: HIV-1 remains sequestered during antiretroviral therapy (ART) and can resume high-level replication upon cessation of ART or development of drug resistance. Reactivity of memory CD8+ T lymphocytes to HIV-1 could potentially inhibit this residual viral replication, but is largely muted by ART in relation to suppression of viral antigen burden. Dendritic cells (DC) are important for MHC class I processing and presentation of peptide epitopes to memory CD8+ T cells, and could potentially be targeted to activate memory CD8+ T cells to a broad array of HIV-1 epitopes during ART. Principal Findings: We show for the first time that HIV-1 peptide-loaded, CD40L-matured DC from HIV-1 infected persons on ART induce IFN gamma production by CD8+ T cells specific for a much broader range and magnitude of Gag and Nef epitopes than do peptides without DC. The DC also reveal novel, MHC class I restricted, Gag and Nef epitopes that are able to induce polyfunctional T cells producing various combinations of IFN gamma, interleukin 2, tumor necrosis factor alpha, macrophage inhibitory protein 1 beta and the cytotoxic de-granulation molecule CD107a. Significance: There is an underlying, broad antigenic spectrum of anti-HIV-1, memory CD8+ T cell reactivity in persons on ART that is revealed by DC. This supports the use of DC-based immunotherapy for HIV-1 infection. © 2010 Huang et al

Dysregulation of Chemokine/Chemokine Receptor Axes and NK Cell Tissue Localization during Diseases.

Chemokines are small chemotactic molecules that play key roles in physiological and pathological conditions. Upon signaling via their specific receptors, chemokines regulate tissue mobilization and trafficking of a wide array of immune cells, including natural killer (NK) cells. Current research is focused on analyzing changes in chemokine/chemokine receptor expression during various diseases to interfere with pathological trafficking of cells or to recruit selected cell types to specific tissues. NK cells are a heterogeneous lymphocyte population comprising several subsets endowed with distinct functional properties and mainly representing distinct stages of a linear development process. Because of their different functional potential, the type of subset that accumulates in a tissue drives the final outcome of NK cell-regulated immune response, leading to either protection or pathology. Correspondingly, chemokine receptors, including CXCR4, CXCR3, and CX3CR1, are differentially expressed by NK cell subsets, and their expression levels can be modulated during NK cell activation. At first, this review will summarize the current knowledge on the contribution of chemokines to the localization and generation of NK cell subsets in homeostasis. How an inappropriate chemotactic response can lead to pathology and how chemokine targeting can therapeutically affect tissue recruitment/localization of distinct NK cell subsets will also be discussed