25 research outputs found

    J Virol

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    In this placebo-controlled phase II randomized clinical trial, 103 HIV-1 infected patients under c-ART (combined antiretroviral treatment) were randomized 2:1 to receive 3 doses of DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag and gp160) at Week (W)0, W4 and W12 followed by 2 doses of LIPO-5 vaccine containing long peptides from Gag, Pol and Nef at W20 and W24 or placebos. Analytical treatment interruption (ATI) was performed between W36 to W48.At W28, vaccinees experienced an increase in functional CD4(+) T cell responses measured (P\textbackslashtextless0.001 for each cytokine compared to W0) predominantly against Gag and Pol/Env and an increase in HIV-specific CD8(+) T cells producing IL-2 and TNF-α (P=0.001 and 0.013, respectively), predominantly against Pol/Env and Nef. However, analysis of T cell subsets by mass cytometry in a subpopulation showed an increase of W28/W0 ratio for memory CD8(+) T cells co-expressing exhaustion and senescence markers such as PD-1/TIGIT (P=0.004) and CD27/CD57 (P=0.044) in vaccinees compared to placebo. During ATI, all patients experienced viral rebound with a maximum observed HIV RNA level at W42 (median: 4.63 log(10) cp/ml; IQR 4.00-5.09) without any difference between arms. No patient resumed c-ART for CD4 cell count drop. Globally, the vaccine strategy was safe. However, a secondary HIV transmission during ATI was observed.These data show that the prime-boost combination of DNA and LIPO-5 vaccines elicited broad and polyfunctional T cells. The contrast between the quality of immune responses and the lack of potent viral control underscores the need of combined immunomodulatory strategies.IMPORTANCE In this placebo-controlled phase II randomized clinical trial, we evaluated the safety and immunogenicity of a therapeutic prime-boost vaccine strategy using a recombinant DNA vaccine (GTU®-MultiHIV B clade) followed by a boost vaccination by a lipopeptide vaccine (HIV-LIPO-5) in HIV-infected patients while on combined antiretroviral therapy. We show that this prime-boost strategy is well tolerated, consistently with previous studies in HIV-1 infected individuals and healthy volunteers who received each vaccine component individually. Compared to placebo group, vaccines elicited strong and polyfunctional HIV-specific CD4(+) and CD8(+) T cell responses. However, these immune responses presenting some qualitative defects were not able to control viremia following antiretroviral treatment interruption as no difference in HIV viral rebound was observed in vaccine and placebo groups. Several lessons were learned from these results pointing out the urgent need to combine the vaccine strategies with other immune-based interventions

    J Clin Immunol

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    We report a longitudinal analysis of the immune response associated with a fatal case of COVID-19 in Europe. This patient exhibited a rapid evolution towards multiorgan failure. SARS-CoV-2 was detected in multiple nasopharyngeal, blood, and pleural samples, despite antiviral and immunomodulator treatment. Clinical evolution in the blood was marked by an increase (2–3-fold) in differentiated effector T cells expressing exhaustion (PD-1) and senescence (CD57) markers, an expansion of antibody-secreting cells, a 15-fold increase in γδ T cell and proliferating NK-cell populations, and the total disappearance of monocytes, suggesting lung trafficking. In the serum, waves of a pro-inflammatory cytokine storm, Th1 and Th2 activation, and markers of T cell exhaustion, apoptosis, cell cytotoxicity, and endothelial activation were observed until the fatal outcome. This case underscores the need for well-designed studies to investigate complementary approaches to control viral replication, the source of the hyperinflammatory status, and immunomodulation to target the pathophysiological response. The investigation was conducted as part of an overall French clinical cohort assessing patients with COVID-19 and registered in clinicaltrials.gov under the following number: NCT04262921

    Exploring the connections between participation in and benefits from payments for hydrological services programs in Veracruz State, Mexico

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    © 2018 Elsevier B.V. Payments for hydrological services (PHS) programs are expected to confer tangible benefits to households. Impact evaluations of PHS programs, however, find few to no changes in material indicators. One reason for this may be that non-financial motivations and benefits—including environmental or social—influence participation and are important outcomes for households participating in PHS programs. In this paper we test this hypothesis using 56 interviews and 181 surveys from households in Veracruz State, Mexico. Using logistic regression models we find that human, natural, physical and financial capital are important to the decision to participate in PHS, but so are pro-social and pro-environmental motivations. Using counterfactual impact evaluation methods we find few changes in material benefits but do find that PHS participants are more likely to report positive changes in their household and community quality of life over the last five years compared to households not participating in PHS programs. Qualitative information supports these findings. Our results contribute to the evolving theory on PHS that participation is driven by a mix of financial and non-financial motivations and that non-material benefits are an important outcome of these programs

    Evaluation de l'utilisation du portfolio par les internes en médecine générale d'Angers

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    Contexte :Le portfolio est un outil d'évaluation reconnu du parcours des internes en médecine générale. Articulé autour des activités d'apprentissage, d'enseignement et d'évaluation, il permet l'acquisition d'une démarche réflexive et une évaluation formative. Il implique également la mise en oeuvre du feedback pédagogique par le biais du tutorat et l'analyse des Récits de Situation Complexe Authentique (RSCA).Objectifs :Les internes qui ont validé leur troisième année de Diplôme d'Etudes Spécialisées (DES) de médecine générale à la faculté d'Angers en 2010 constituent la première promotion angevine à avoir utilisé le portfolio dès le début de leur formation. Cette étude réalise un premier état des lieux afin d'optimiser l'utilisation future de cet outil.Méthode :Un questionnaire d'évaluation, dont les items ont été ciblés par un focus group, a été soumis à tous les internes angevins inscrits en 3ème année de DES de médecine générale pour l'année universitaire 2009-2010.Résultats :La majorité reconnaît l'intérêt du portfolio dans l'analyse des pratiques professionnelles. Le nouveau rôle actif de l'apprenant est bien intégré mais reste dépendant de la qualité de la relation avec le tuteur. Le frein principal à la constitution du portfolio est le manque de temps. La crainte de s'exposer à travers les RSCA est également évoquée.Conclusion :Une utilisation optimale du portfolio nécessite une présentation claire en début de DES puis l'investissement réciproque de la part de l'interne et du tuteur tout au long du cursus. Le processus d'intégration de cet outil doit être accéléré en première année pour éviter une surcharge de travail en fin de DES.National audienc

    A new environmental governance

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    At present, there is no unified theoretical framework to deal with environmental governance issues. Consequently, there is a diversity of interpretations of the concept at the public-political arena both nationally and internationally. Recent Latin American efforts have given a step forward conceptualizing environmental governance from the South and systematizing experiences to illustrate a diverse contemporaneous reality. At a regional scale, within the last decades, discursive turns in national policies such as the introduction of the sustainable development concept have triggered an increase in studies and applications of environmental governance (e.g., forest’s governance, climate change, marine coastal zones) including the use of the ecosystem services concept. The instrumentation of public actions in relation to environmental governance derives from the states. However, if analyzed with a beyond-the-States view, governance can be understood as a process involving the participation of governmental and non-governmental actors reaching decisions, for mutual benefits, through negotiation processes. However, there is not, still, within the countries of the region, inclusive and participative governance oriented toward the sustainable use of natural resources. Although there are many challenges, in this chapter we discuss two of them: (1) to build an analytical framework to understand the environmental governance modes currently available in Latin America and (2) to generate a new sociopolitical interdisciplinary framework involving both natural and sociopolitical systems as a contribution to a new analytical framework for environmental governance. In other words, new environmental governance for Latin America.Fil: Delgado, Luisa E.. Universidad de Chile; ChileFil: Zorondo Rodriguez, Francisco. Universidad de Santiago de Chile; ChileFil: Bachmann Vargas, Pamela. University of Agriculture Wageningen; Países BajosFil: Soto, Carmiña. Universidad Nacional de Asunción; ParaguayFil: Avila Foucat, Veronique S.. Universidad Nacional Autónoma de México; MéxicoFil: Gutierrez, Ricardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Política y Gobierno; ArgentinaFil: Muñoz Barriga, Andrea. Pontificia Universidad Católica del Ecuador; EcuadorFil: Ferreiro, Oscar E.. Universidad Nacional de Asunción; Paragua

    Decentralizing Payments for Hydrological Services Programs in Veracruz, Mexico: Challenges and Implications for Long-term Sustainability

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    © 2018, © 2018 Taylor & Francis. In this policy review, we analyze two payments for hydrological services matching programs operating in the Antigua water basin in the state of Veracruz, Mexico. Mexico’s Matching Program was created to transition from the national payments for hydrological services program to programs that would be financed by local governments, local water users and the private sector. Based on the analysis of organizational documents and key informant interviews with institutional actors, we describe the distinctive origins and organizational structures of these two programs, and how these differences have led to unique challenges for each program. We conclude that payments for ecosystem services programs that incorporate community-level organization and extensive technical assistance, along with expanded direct payments from ecosystem service users, have the greatest potential for achieving long-term sustainability

    Household’s Allocation of Payment for Ecosystem Services in “La Antigua” Watershed, Veracruz, México

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    Payment for ecosystem services (PES) is an environmental policy looking to improve ecosystem conservation and well-being. Assets have been used to evaluate socioeconomic outcomes of the program; however, the allocation of PES at a household level and its explaining variables have not been addressed. Thus, the aim of this article is to study the allocation of PES in nondurable and durable goods and the determinants of this household decision. Results from the La Antigua watershed located in Mexico indicate that the PES program is primarily used in durable goods, mainly on health, house infrastructure, agricultural inputs, and reforestation. Econometric models show that this allocation to one or several assets depends on the average age of the household head, on participation in a community organization, and on the average income. In contrast, government transfers are not significant. Based on this, policy recommendations are made related to the program’s socioeconomic outcomes and alignment with other conditional cash transfer
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