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Avaliação da resposta inflamatória e da resposta imune inata na célula apresentadora de antígeno em recém-nascidos de termo sepse tardia / Inflammatory and innate immune response in antigen-presenting cell from term newborn with late onset sepsisAna Carolina Costa Redondo 25 November 2013 (has links)
INTRODUÇÃO: Apesar do contínuo progresso no tratamento e suporte clínico a sepse continua sendo uma das principais causas de morbidade e mortalidade nas unidades de terapia intensiva, com desfechos semelhantes ao longo dos últimos 50 anos. A suscetibilidade à infecção grave no recém-nascido é parcialmente devida à imaturidade do sistema imune inato associado à mínima em exposição antigênica in utero e à ação ineficaz das células T efetoras e das célula B. Embora a ativação do sistema imune inato por padrões de reconhecimento (PRR) como os dos receptores Toll-like (TLR) tenham sua importância amplamente reconhecida nos últimos anos, seu comportamento frente a uma infecção in vivo ainda não foi completamente compreendido. Neste trabalho nós analisamos a expressão dos TLR-2 e TLR-4 em células apresentadoras de antígeno em recém-nascidos com e sem sepse. CAUSUÍSTICA E MÉTODO: Trata-se de um estudo prospectivo realizado no período entre fevereiro de 2011 e janeiro de 2013 onde foram incluídos quarenta e cinco recém-nascidos a termo, sem malformação congênita, admitidos na Unidade de Cuidados Intensivos Neonatal do Instituto da Criança-HCFMUSP e divididos em grupos 1 e 2. O grupo 1 consistiu em 27 recém-nascidos com diagnóstico clínico e laboratorial de sepse tardia enquanto que o grupo 2 foi composto por 18 recém-nascidos sem quadro séptico vigente. As citocinas foram determinadas por teste de CBA em sangue periférico. A expressão e MFI dos TLR-2 e TLR-4 foi determinado por imunofenotipagem em APCs e linfócitos no sangue periférico total através de análise pelo citômetro de fluxo BD FACSDiva. RESULTADOS: Os dados clínicos foram semelhantes entre os grupos 1 e 2, exceto para o estado infeccioso. Microrganismos foram identificados em 37 % no grupo 1 e estes tiveram níveis mais elevados de citocinas pró-inflamatórias (IL-8, IL-6, IL-1beta) e de citocina anti-inflamatória (IL-10). Nas células dendríticas, a expressão de TLR-2 e 4 foi semelhante entre os grupos enquanto que houve menor expressão nos pacientes infectados da molécula co-estimuladora CD86 (p < 0,05) e expressão semelhante de CD1a e CD80 em relação aos RN não infectados. No monócito, o MFI para TLR-2 e a freqüência de expressão do TLR-4 foi maior no grupo 1 (p = 0,01). Apesar da frequência de linfócitos totais ter sido mais baixa no grupo 1 (p = 0,002), não foi observada diferença quanto as suas subpopulações exceto em relação a maior frequência de LT efetor no grupo infectado com menor expressão da molécula CD28. Houve maior frequência de LB ativados no grupo 1 enquanto que a população total e as demais subpopulações foram semelhantes em número, moléculas de ativação e na expressão dos TLR-2 e 4 em ambos os grupos. CONCLUSÃO: Este estudo analisou a resposta imune inata no recém-nascido com e sem sepse. As IL-6, IL-8 e IL-10 foram bons indicadores desta doença. Recém-nascidos sépticos, que dependem quase exclusivamente do sistema imune inato, apresentaram pouca resposta in vivo na ativação de células dendríticas e monócitos propiciando uma resposta imune deficiente e maior susceptibilidade à infecção / INTRODUCTION: Despite continuous progress in the clinical treatment and other supportive care therapies, sepsis remains a leading cause of morbidity and mortality in the intensive care unit with similar outcome throughout the past 50 years. The susceptibility to severe infection is partially due to newborn immature innate immune system associated to minimal in utero antigen exposure and effector T and B cell impaired function. Although the importance of pattern recognition domains such as Toll-like receptors (TLR) in the innate immune system activation has been fully acknowledged within the last few years its behavior in front of an in vivo infection scenario is still not completely understood. Here we analyzed the TLR-2 and TLR-4 expression in antigen-presenting cell in healthy and septic newborns. PATIENTS AND METHODS: This prospective study was conducted during the period from February 2011 until January 2013 at Sao Paulo University, Sao Paulo, Brazil. Forty-five term newborns without congenital malformation were included from the Newborn Intensive Care Unit at Children\'s Hospital. As group 1, 27 newborns who had clinical and laboratory diagnostic of late onset sepsis were included while 18 newborns were evaluated in a non-septic status and were included at group 2. Cytokines were measured by cytometric bead array in peripheral blood. TLR-2 and TLR-4 expression and MFI were determined by immunophenotyping at peripheral whole blood in APC cells and lymphocytes and analyzed on a BD FACSDiva flow cytometer. RESULTS: Clinical data was similar between septic and non-septic groups except for the infectious status. Group 1 had microorganisms identified in 37 % septic newborns associated with higher levels of pro-inflammatory (IL-8, IL-6, IL-1beta) and anti-inflammatory interleukins (IL-10). When it comes to dendritic cells, the expression of TLR-2 and 4 was similar between groups whereas there was lower expression of co-molecule CD86 (p < 0,05) and similar expression of CD1a and CD80 between infected and non-infected patients. At monocytes, the MFI for TLR-2 and the frequency of TLR-4 expression was higher in infected newborn (p=0,01). There were lower levels of total lymphocytes in infected patients (p=0,002) but no difference was observed in T cells subtypes frequency except for higher levels of effector T cell in infected group with lower expression of CD28 molecule. Group 1 had higher levels of activated B cell whereas total population and the other subsets were similar in number, activation molecules and TLR-2 and 4 expressions in both groups. CONCLUSION: This study investigated the innate immune response in septic and non-septic newborn. Interleukin levels 6, 8 and 10 were good indicators of sepsis. Septic newborns, which count most exclusively with innate immune system, had little in vivo response at dendritic cell and monocyte activation leading to an impaired immune response and increased susceptibility to infection
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Ultrassonografia intraoperatória para avaliação da necessidade de duroplastia no tratamento cirúrgico de doentes com malformação de Chiari tipo I / Intra operative ultrasonography for evaluation of the need of duroplasty in surgery for Chiari I malformationRoger Schmidt Brock 03 April 2017 (has links)
Objetivos: Malformação de Chiari do tipo I (MC-I) é a principal doença malformativa congênita da junção craniovertebral, manifestando-se com ampla variedade de sinais e sintomas neurológicos. A melhor técnica cirúrgica a ser empregada no tratamento dos pacientes com malformação de Chiari do tipo I é ainda controversa. A descompressão das estruturas da fossa craniana posterior com plástica de ampliação dural é considerada procedimento padrão. Embora efetiva e de baixa morbidade, a craniectomia occipital isolada, sem abertura e ampliação dural, implica maior taxa de recidiva dos sintomas. Métodos que selecionam os pacientes quanto a necessidade da duroplastia não foram estabelecidos. O presente trabalho avalia a eficácia da mensuração intraoperatória da velocidade do fluxo do líquido cefalorraquidiano através da ultrassonografia (USG) na seleção da técnica cirúrgica a ser utilizada. Métodos: Foram analisados de forma prospectiva 49 pacientes submetidos à cirurgia para MC-I. A indicação de craniectomia da fossa posterior associada ou não à plástica de ampliação da dura-máter baseou-se na velocidade do fluxo do líquido cefalorraquidiano, mensurada pela ultrassonografia intraoperatória. Dor cervical, cefaleia e qualidade de vida foram avaliadas antes e após o tratamento cirúrgico. Resultados: Dos 49 pacientes incluídos, 36 pacientes (73%) apresentavam fluxo do líquido cefalorraquidiano superior a 3 cm/s e não foram submetidos a duroplastia ampliadora. Nos 13 (27%) pacientes com fluxo inicial inferior a 3 cm/s, indicou-se craniectomia occipital com duroplastia de ampliação. Não houve diferença significativa entre os dois grupos com relação aos parâmetros estudados. Conclusão: A ultrassonografia intraoperatória com avaliação da dinâmica e velocidade do fluxo do líquido cefalorraquidiano da junção craniovertebral auxilia a indicação de duroplastia durante descompressão da fossa craniana posterior em pacientes adultos com MC-I / Objectives: Chiari malformation Type I (CM-I) is the main congenital malformation disease of the craniovertebral junction, and may be responsible for a variety of neurological symptoms. The ideal surgical technique used to treat patients with CM-I is still controversial. Invasive procedures that enters CSF space and are associated with dural repair, are considered the gold standard. Although effective and less morbidity, isolated bone decompression without dural opening, implies greater recurrence of symptoms. Objective parameters to select patients, who need or not to have a duroplasty performed, have not been established. Our study evaluates the efficacy of intra-operative CSF flow measurement through the use of ultrasonography (USG) as a determining parameter in the selection of these patients. Methods: We analyzed prospectively 49 posterior fossa surgeries for patients with CM-I. Patients underwent decompressive surgery with or without opening of the dura mater after conducting USG intra-operatively with measured flow rate, being adopted 3cm/s flow rate as a determining value. The quality of life before and after surgery and the improvement of neck pain and headache were the parameters evaluated. Results: Of the 49 patients enrolled, 36 patients (73%) had adequate CSF flow above 3 cm / s and have not undergone duroplasty. In 13 (27%) patients with initial flow < 3 cm / s an opening in dura mater was performed together with duroplasty. There was no significant difference between the two groups regarding the parameters studied. Conclusion: Intraoperative ultrasound with measurement of CSF flow, having a flow of 3 cm / s as cut-off, allows the proper selection of patients with CM-I that can have a less invasive surgery with bone decompression without duroplasty
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Molekulare Analyse eines Homöobox-Gen-Promotors in der Gehirnanlage von Wirbeltierembryonen / Molecular analysis of a homeobox gene promotor in the prospective forebrain of vertebratesSpieler, Derek 07 April 2005 (has links)
No description available.
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Littoralisation de la Façade Nord-Méditerranéenne : Analyse Spatiale et Prospective dans le contexte du Changement ClimatiqueSophie, Liziard 11 December 2013 (has links) (PDF)
Sur les littoraux de l'Arc Latin, les pressions anthropiques croissantes et les changements climatiques soulèvent de nombreuses interrogations quant à leur devenir. Cette thèse développe des méthodes et connaissances prospectives soutenant l'anticipation requise, en termes de prévention et d'adaptation, dans une perspective de durabilité territoriale. Deux axes de recherche sont explorés : une prospective des dynamiques spatiales de littoralisation de l'Arc Latin et une évaluation de l'adaptabilité des territoires littoraux au changement climatique. Ils renvoient à une problématique méthodologique commune, qui est celle de l'évaluation des potentialités d'évolution des territoires littoraux. Interrogeant le rôle des configurations spatiales dans l'évolution des territoires, la posture générale est celle de la prospective spatiale, qui consiste à analyser le devenir des systèmes spatiaux à partir de leur fonctionnement passé et actuel et des propriétés du changement spatial. Des méthodes quantitatives d'analyse spatiale sont combinées avec des méthodes qualitatives pour intégrer les dynamiques spatio-temporelles et la complexité de l'évolution des territoires. Les résultats de l'analyse des trajectoires de peuplement de l'Arc Latin fournissent une vision d'ensemble et spatialement différenciée de la littoralisation et de ses évolutions potentielles. L'adaptabilité des territoires au changement climatique est analysée par des simulations sur des espaces théoriques et par un diagnostic finalisé appliqué à la montée du niveau de la mer en Camargue. Prendre en compte les configurations spatiales permet d'identifier des mesures d'adaptation en adéquation avec les territoires.
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Oral Health Related Quality of Life Outcomes of Orthodontics in ChildrenAgou, Shoroog 13 April 2010 (has links)
Contemporary conceptual models of health emphasize the importance of patient-based outcomes and recognize the complexity involved in their assessment. Various health conditions, personal, social, and environmental factors, are all thought to contribute to individual’s quality of life. However, the impact of orthodontic treatment on Oral Health-related Quality of Life (OH-QOL) outcomes in children has not yet been systematically studied. Hence, this research was planned to assess the effect orthodontic treatment has on pediatric OH-QOL outcomes. Further, the important moderational role of children’s psychological assets on OH-QOL reports is explored.
Following completion of a preliminary study to confirm the psychometric properties of the Child Perception Questionnaire (CPQl1-14), the current two-phase study was undertaken. This consisted of a cross-sectional study examining the relationship among Self-Esteem (SE), malocclusion, and OH-QOL, and a longitudinal study examining the influence of orthodontics and children’s Psychological Wellbeing (PWB) on OH-QOL reports.
This PhD dissertation is presented in the “Publishable Style”. The journals which hold the copyrights for the papers published from this thesis have given permission for the reproduction of the text and figures for this dissertation.
The preliminary data confirmed that the CPQ11-14 is sensitive to change when used with children receiving orthodontic treatment. Our cross-sectional findings indicated that the impact of malocclusion on OH-QOL is substantial in children with low SE and identified SE as a salient determinant of OH-QOL in children seeking orthodontic treatment. Longitudinal data, on the other hand, detected significant improvement of OH-QOL outcomes after orthodontic treatment. As postulated, these improvements were most evident for the social and emotional domains of OH-QOL. However, covariate analysis emphasized the important role psychological factors play in moderating OH-QOL reports, as children with better PWB were more likely to report better OH-QOL regardless of their orthodontic treatment status.
These results substantiate the validity of contemporary models of patient-based outcomes linking biological, personal, social, and environmental factors. Researchers and clinicians are encouraged to adopt this forward thinking approach when dealing with children with oro-facial conditions. Further studies with larger samples and longer follow-ups would be of value to expand on these findings.
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Utilisation des médecines complémentaires par les enfants atteints d'arthrite juvénile idiopathique et d'incapacités physiquesToupin April, Karine 03 1900 (has links)
Contexte : Les enfants atteints de maladies chroniques utilisent souvent des médecines complémentaires. Plusieurs études traitent de l’utilisation de ces traitements et des facteurs qui y sont associés chez les enfants atteints d’arthrite juvénile mais aucune étude n’est longitudinale. De plus, aucune n’a documenté l’utilisation de ces traitements chez les enfants ayant des incapacités physiques en attente de services publics de réadaptation.
Objectifs : Les objectifs de cette étude étaient de déterminer la fréquence d’utilisation des médecines complémentaires chez les enfants atteints d’arthrite juvénile et d’incapacités physiques, d’évaluer leur efficacité telle que perçue par les parents et d’explorer les facteurs associés à leur utilisation.
Méthodes : Une cohorte d’enfants atteints d’arthrite juvénile idiopathique (n=182, âge moyen : 10,2 ans) qui fréquentent des cliniques d’arthrite et une cohorte d’enfants ayant des incapacités physiques en attente de services de réadaptation publics (n=224, âge moyen : 2,6 ans) ont été suivis durant une période d’un an. L’utilisation des médecines complémentaires et la perception de leur efficacité d’après les parents ont été évaluées à l’aide de statistiques descriptives à chaque trois mois pour la cohorte d’enfants atteints d’arthrite et au début de l’étude pour la cohorte d’enfants ayant des incapacités physiques. Les facteurs associés à l’utilisation de ces traitements ont été explorés par des analyses de type GEE (« Generalized estimating equations ») et des régressions polytomique et logistique.
Résultats : L’utilisation antérieure de ces médecines était de 51,1% pour les enfants atteints d’arthrite et de 15% pour les enfants ayant des incapacités physiques. Les médecines complémentaires étaient considérées comme étant efficaces dans 72% des cas par les parents d’enfants atteints d’arthrite et dans 83% des cas par les parents d’enfants ayant des incapacités physiques. Les facteurs associés à l’utilisation des médecines complémentaires chez les enfants atteints d’arthrite étaient l’utilisation antérieure des médecines complémentaires par les parents et la perception des parents que les médicaments prescrits ne sont pas utiles pour leur enfant. Chez les enfants ayant des incapacités physiques, les facteurs associés à l’utilisation des médecines complémentaires étaient l’origine culturelle canadienne, un niveau de scolarité plus élevé que le diplôme d’études secondaires et une moins bonne qualité de vie reliée à la santé. Finalement, l’utilisation des médecines complémentaires semblait associée à de moins bons résultats chez les enfants atteints d’arthrite.
Conclusion: Une proportion non-négligeable des enfants participant à la présente étude ont utilisé des médecines complémentaires. Leur utilisation était plus fréquente chez les enfants atteints d’arthrite juvénile idiopathique, surtout chez ceux dont les parents avaient déjà utilisé les médecines complémentaires par le passé et chez ceux qui trouvaient la médication peu efficace. Chez les enfants ayant des incapacités physiques, l’utilisation des médecines complémentaires était associée à des facteurs socio-démographiques et à des besoins plus élevés en matière de santé. Les médecines complémentaires étaient considérées comme étant efficaces dans les deux cohortes mais leur utilisation était associée à de faibles résultats chez les enfants atteints d’arthrite. Ces résultats démontrent l’importance d’évaluer l’utilisation des médecines complémentaires afin de mieux renseigner les parents et de les aider à prendre les meilleures décisions possibles concernant le traitement de leur enfant. / Background: Children with chronic diseases often use complementary and alternative health care (CAHC). Several studies described the use of these treatments and the factors associated with it. However, no longitudinal studies were conducted to determine the use of these treatments over time. Furthermore, no study has evaluated CAHC use in children who were waiting for public rehabilitation services.
Objective: The aim was to determine the frequency of CAHC use in children with juvenile idiopathic arthritis (JIA) and children with various physical disabilities (PD), to evaluate its effectiveness from the parents’ points of view and to explore the factors associated with their utilization.
Methods: A cohort of children with JIA (n=182, mean age: 10.2 years) who attended arthritis clinics and a cohort of children with physical disabilities (n=224, mean age: 2.6 years) waiting for public rehabilitation services were followed for one year. We evaluated the use of CAHC and its effectiveness from the parents’ points of view at three month intervals for children with JIA and at the beginning of the study for children with PD, using descriptive statistics. We explored factors associated with their utilization, using GEE (“Generalized estimating equations »), polytomous and logistic regression.
Results : Previous use of CAHC was 51.1% for children with JIA and 15% for children with PD. CAHC was considered beneficial in 72% of the cases by parents of children with JIA and in 83% of the cases by parents of children with PD. Factors associated with higher use of CAHC in children with JIA were previous use of CAHC by parents and lower perceived helpfulness of prescribed medications (p<0.05). In children with PD, factors associated with higher use of CAHC were Canadian cultural background, mother’s level of education higher than high school and lower health-related quality of life. Finally, in children with JIA, CAHC use was associated with worse outcomes.
Conclusions: Many children in our study used CAHC. Its use was more common in children with JIA, particularly among those whose parents used it previously and found medications to be less helpful. For children with PD, use of CAHC was associated with socio-demographic factors as well as higher children’s health needs. CAHC were perceived to be beneficial in both cohorts but its use was associated with worse outcomes for children with JIA. This underlines the importance for health professionals to evaluate CAHC use in order to better inform parents, which may help them make the best decisions regarding their child’s treatment.
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Stratégie d'internationalisation d'une Petite Economie Mature Ouverte (PEMO) : le cas du Luxembourg : déterminants, défis et leviersHostert, Marc 18 October 2013 (has links) (PDF)
L'attractivité des territoires vis-à-vis des investissements directs étrangers constitue, avec l'ouverture accrue des espaces économiques et politiques, un élément clé de l'intensification des flux d'échanges et d'investissements.Pour tous les pays et, plus particulièrement, pour ceux ne disposant pas d'un marché national important, l'établissement d'un diagnostic d'attractivité et la détermination d'axes prioritaires de développement constituent une démarche fondamentale applicable particulièrement à l'exemple du Luxembourg, une économie considérée comme une petite économie mature ouverte (PEMO).A travers cette recherche, on s'attachera à appliquer et à adapter un modèle d'analyse des fondements de l'attractivité, puis un modèle de détermination des orientations économiques et institutionnelles à privilégier.Cette recherche conduit à définir une démarche prospective structurée, appliquée à la PEMO considérée :- en partant de l'établissement d'une liste de déterminants de compétitivité et d'attractivité ayant potentiellement trait à une PEMO en général, validée ensuite pour le cas concret du Luxembourg par un panel de décideurs ;- en permettant l'établissement d'un diagnostic d'attractivité portant sur la situation actuelle de la PEMO considérée ;- pour déboucher sur la détermination d'activités prioritaires et de profilsd'investisseurs directs étrangers à privilégier, dans un " espace de référence " géo - sectoriel reconsidéré.Cette recherche devrait permettre d'identifier les secteurs d'investissement les plus attractifs pour les entreprises étrangères dans une PEMO comme le Luxembourg.
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Oral Health Related Quality of Life Outcomes of Orthodontics in ChildrenAgou, Shoroog 13 April 2010 (has links)
Contemporary conceptual models of health emphasize the importance of patient-based outcomes and recognize the complexity involved in their assessment. Various health conditions, personal, social, and environmental factors, are all thought to contribute to individual’s quality of life. However, the impact of orthodontic treatment on Oral Health-related Quality of Life (OH-QOL) outcomes in children has not yet been systematically studied. Hence, this research was planned to assess the effect orthodontic treatment has on pediatric OH-QOL outcomes. Further, the important moderational role of children’s psychological assets on OH-QOL reports is explored.
Following completion of a preliminary study to confirm the psychometric properties of the Child Perception Questionnaire (CPQl1-14), the current two-phase study was undertaken. This consisted of a cross-sectional study examining the relationship among Self-Esteem (SE), malocclusion, and OH-QOL, and a longitudinal study examining the influence of orthodontics and children’s Psychological Wellbeing (PWB) on OH-QOL reports.
This PhD dissertation is presented in the “Publishable Style”. The journals which hold the copyrights for the papers published from this thesis have given permission for the reproduction of the text and figures for this dissertation.
The preliminary data confirmed that the CPQ11-14 is sensitive to change when used with children receiving orthodontic treatment. Our cross-sectional findings indicated that the impact of malocclusion on OH-QOL is substantial in children with low SE and identified SE as a salient determinant of OH-QOL in children seeking orthodontic treatment. Longitudinal data, on the other hand, detected significant improvement of OH-QOL outcomes after orthodontic treatment. As postulated, these improvements were most evident for the social and emotional domains of OH-QOL. However, covariate analysis emphasized the important role psychological factors play in moderating OH-QOL reports, as children with better PWB were more likely to report better OH-QOL regardless of their orthodontic treatment status.
These results substantiate the validity of contemporary models of patient-based outcomes linking biological, personal, social, and environmental factors. Researchers and clinicians are encouraged to adopt this forward thinking approach when dealing with children with oro-facial conditions. Further studies with larger samples and longer follow-ups would be of value to expand on these findings.
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Construction, diffusion et effectivité des standards transnationaux en matière de responsabilité sociale des entreprisesStamm, Christoph B. 08 1900 (has links)
No description available.
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Estimate and prospective studies on Peruvian environmental legal system after Río + 20 / Estimativas y prospectivas sobre el sistema jurídico ambiental peruano post-Río + 20Foy Valencia, Pierre Claudio 10 April 2018 (has links)
This article is intended to explain core ideas resulting from processes of which Peruvian environmental legal system is derived; it is morean overview rather than a system characterization, as well as a perspective or sampling foresight representing Río +20 process meaning. In that sense, it examines the modern environmental regulations rising context and provides a brief retrospective of Peruvian environmental legal system development and prospective studies within the frame of green economy paradigms and the environmental governance, presenting only three prospective references aschallenges and trends on: Climate and Energy Law, a new legal Framework for a Green Economy and Sustainable Enterprise, and finally, stressing emphatically on mega-cities, Conurbation and Land use Planning issues given little attention usually law renders to this matters. / El ensayo pretende explicar las ideas fuerza de los procesos quedan origen al sistema jurídico ambiental peruano, una reseña antes que una caracterización del sistema, así como una perspectiva o prospectiva muestral a resultas de lo que representa el proceso denominado Río + 20. En ese sentido, da cuenta del contexto en que surge la normativa ambiental nacional moderna, igualmente ofrece una breve retrospectiva del desarrollo del sistema jurídico ambiental peruano y las prospectivas en el marco de los paradigmas de la economía verde y la gobernanza ambiental, mostrando solo tres referentes proyectivos a modo de desafíos y tendencias sobre el derecho climático y derecho energético, el imperativo de un nuevo marco legal parauna economía verde y empresa sostenible; y un gran énfasis al tema de las megaciudades, conurbación y ordenamiento territorial, con énfasis, debido a la poca atención que le suele brindar el derecho.
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