Optimal target localization for subthalamic stimulation in patients with Parkinson disease

OBJECTIVE To further determine the causes of variable outcome from deep brain stimulation of the subthalamic nucleus (DBS-STN) in patients with Parkinson disease (PD). METHODS Data were obtained from our cohort of 309 patients with PD who underwent DBS-STN between 1996 and 2009. We examined the relationship between the 1-year motor, cognitive, and psychiatric outcomes and (1) preoperative PD clinical features, (2) MRI measures, (3) surgical procedure, and (4) locations of therapeutic contacts. RESULTS Pre- and postoperative results were obtained in 262 patients with PD. The best motor outcome was obtained when stimulating contacts were located within the STN as compared with the zona incerta (64% vs 49% improvement). Eighteen percent of the patients presented a postoperative cognitive decline, which was found to be principally related to the surgical procedure. Other factors predictive of poor cognitive outcome were perioperative confusion and psychosis. Nineteen patients showed a stimulation-induced hypomania, which was related to both the form of the disease (younger age, shorter disease duration, higher levodopa responsiveness) and the ventral contact location. Postoperative depression was more frequent in patients already showing preoperative depressive and/or residual axial motor symptoms. CONCLUSION In this homogeneous cohort of patients with PD, we showed that (1) the STN is the best target to improve motor symptoms, (2) postoperative cognitive deficit is mainly related to the surgery itself, and (3) stimulation-induced hypomania is related to a combination of both the disease characteristics and a more ventral STN location.

The muscarinic antagonists scopolamine and atropine are competitive antagonists at 5-HT3 receptors

Scopolamine is a high affinity muscarinic antagonist that is used for the prevention of post-operative nausea and vomiting. 5-HT3 receptor antagonists are used for the same purpose and are structurally related to scopolamine. To examine whether 5-HT3 receptors are affected by scopolamine we examined the effects of this drug on the electrophysiological and ligand binding properties of 5-HT3A receptors expressed in Xenopus oocytes and HEK293 cells, respectively. 5-HT3 receptor-responses were reversibly inhibited by scopolamine with an IC50 of 2.09 μM. Competitive antagonism was shown by Schild plot (pA2 = 5.02) and by competition with the 5-HT3 receptor antagonists [3H]granisetron (Ki = 6.76 µM) and G-FL (Ki = 4.90 µM). The related molecule, atropine, similarly inhibited 5-HT evoked responses in oocytes with an IC50 of 1.74 µM, and competed with G-FL with a Ki of 7.94 µM. The reverse experiment revealed that granisetron also competitively bound to muscarinic receptors (Ki = 6.5 µM). In behavioural studies scopolamine is used to block muscarinic receptors and induce a cognitive deficit, and centrally administered concentrations can exceed the IC50 values found here. It is therefore possible that 5-HT3 receptors are also inhibited. Studies that utilise higher concentrations of scopolamine should be mindful of these potential off-target effects.

AUSÊNCIA PATERNA E SUAS REPERCUSSÕES SOBRE O DESENVOLVIMENTO INFANTIL

O presente estudo teve por objetivos a) investigar as repercussões da ausência paterna sobre o desenvolvimento da criança; b) descrever o conteúdo intrapsíquico de crianças com pais presentes e de crianças com pais ausentes no lar. Para tanto foram estudados três casos de crianças em idade escolar que freqüentavam uma instituição não governamental da cidade de Santos e utilizou-se dos instrumentos entrevista semi-estruturada com as mães e Procedimento de Desenho-Estória com Tema com as crianças. A aplicação foi feita nos seguintes termos, pediu-se ao participante que desenhasse uma criança e, em seguida que contasse uma estória sobre o desenho. Após, foi solicitado à criança que desenhasse o pai dessa criança e que contasse uma estória sobre esse mesmo desenho. Optamos também por aplicar o Teste das Matrizes Coloridas de Raven - Escala Especial com as crianças. Embora cada caso tivesse revelado suas peculiaridades, os resultados mostraram indicativos de distúrbios da identidade sexual, desamparo, insegurança, tendências depressivas, além de associação entre a ausência paterna, déficit cognitivo e/ou inibição intelectual. Foi também observado em um dos casos, dificuldades da mãe em permitir que o pai paternasse . Concluiu-se que a ausência paterna foi percebida pela criança não somente como a falta da pessoa do pai no lar, mas sim por sua omissão; somando-se ao fato de que a internalização da figura paterna não pareceu determinada pelo laço biológico, mas sim pela possibilidade de oferecimento à criança de identificação e afeto. Entendeu-se com esse estudo que o desenvolvimento psíquico saudável pode ser facilitado pela introjeção das boas figuras materno/paternas pela criança. Sendo assim, estudos dedicados ao tema da paternidade são tão importantes de serem explorados na atualidade quanto o foram aqueles destinados à maternidade ao longo da história da psicologia do desenvolvimento e da psicanálise. (AU)

A sexualidade nos idosos. Contributo para a avaliação das atitudes face à sexualidade nos idosos e a sua relação com a religião e nível cognitivo

O presente estudo teve como objectivo principal conhecer melhor aspectos relacionados com a sexualidade na 3ª idade. A escala utilizada foi construída por nós, tornando-se num elemento chave para esta pesquisa. A escala de atitudes face à sexualidade no idoso foi relacionada com algumas características sociodemográficas: género, idade, estado civil, escolaridade e religião. Da análise realizada ressaltam evidências de uma atitude conservadora face às questões da sexualidade na 3ª idade. Através de uma amostra de 120 idosos com idades compreendidas entre os 60 e os 97 anos de idade, constatámos que os homens e as mulheres distinguem-se significativamente no que respeita às atitudes face à sexualidade, exibindo os homens uma atitude global mais positiva e liberal (M = 25.82). Os resultados evidenciaram um efeito significativo da variável escolaridade sobre o nível cognitivo, revelando que quanto maior a escolaridade do idoso na nossa amostra, maior é o nível cognitivo. Relativamente ao estado civil, os casados revelaram uma atitude global mais positiva perante a sua sexualidade (M = 31.98) comparativamente aos viúvos (M = 27.26) e aos divorciados (M = 23.67). A religião apenas se mostrou associada com a escala de atitudes face ao cristianismo, evidenciando aqueles que são praticantes, uma atitude mais positiva em relação ao cristianismo. Na nossa amostra, também podémos constatar que quanto maior é o nível cognitivo, mais positiva é a atitude face à sexualidade. Com base nos pontos de corte do MMSE verificou-se que 75% dos idosos da nossa amostra não apresentava qualquer défice cognitivo. Comparados os grupos, sem e com défice cognitivo, constatou-se que o grupo de idosos sem défice cognitivo exibe uma atitude mais positiva face à sexualidade que o grupo com défice cognitivo. Pretendemos que de alguma forma este estudo contribua para dar a conhecer as atitudes dos idosos face à sua sexualidade bem como esperamos que os nossos resultados permitam uma reflexão sobre possíveis estratégias de intervenção no sentido de promover uma sexualidade bem vivida por esta faixa etária. / The present study aimed to better understand the main aspects related to sexuality in the 3rd age. The scale used was built by us, becoming a key element in this research. The scale of attitudes towards sexuality in the elderly was related to sociodemographic characteristics: gender, age, marital status, education and religion. From the analysis point out evidence of a conservative approach in relation to issues of sexuality in the 3rd age. Using a sample of 120 elderly aged 60 and 97 years old, found that men and women differ significantly with regard to attitudes towards sexuality, men showing a more positive overall attitude and liberal (M = 25.82). The results showed a significant effect on the education variable cognitive level, revealing that the higher the education of the elderly in our sample, the higher the cognitive level. With regard to marital status, married people showed a more positive overall attitude towards their sexuality (M = 31.98) compared to widowed (M = 27.26) and divorced (M = 23.67). The only religion was associated with the scale of attitudes to Christianity, showing those who are practitioners, a more positive attitude toward Christianity. In our sample, we can also see that the higher the cognitive level, the more positive attitude towards sexuality. Based on the MMSE cutoffs found that 75% of older people in our sample did not show any cognitive deficit. Comparing the groups with and without cognitive impairment, it was found that the group of elderly people without cognitive impairment display a more positive attitude towards sexuality that the group with cognitive impairment. We intend that somehow this study contributes to publicize the attitudes of the elderly compared to their sexuality and we expect our results allow a discussion on possible intervention strategies to promote a sexuality lived well by this age group.

Qualidade de Vida e Atitudes dos Idosos Face à Velhice

A problemática do envelhecimento tem assumido, nos últimos anos, uma crescente importância na consciência coletiva da população, tornando-se cada vez mais importante compreender a população idosa e a sua realidade. Posto isto, foi realizado um estudo quantitativo e correlacional, que teve como objectivo avaliar a qualidade de vida e atitudes face à velhice de idosos, bem como a relação entre estas e as variáveis sociodemográficas e familiares. Foram inquiridos 100 idosos, com mais de 65 anos e sem deficit cognitivo . Para a recolha de dados utilizou-se uma entrevista estruturada, constituída dados sóciodemográficos do idoso, WHOQOL-AGE (Caballero, Miret, Power, Chatterji, Tobiasz-Adamczyk, Koskinen, Leonardi, Olaya, Haro &Ayuso-Mateos, 2013) e o AAQ ( Laidlaw, Power, Schmidt and the WHOQOL-OLD Group, 2007). Dos resultados destacamos os seguintes: A amostra é constituída por 52% de idosos do sexo masculino tendo uma média de idades de 74,7 (DP=6,8). È no fator Perdas Psicossociais e no Desenvolvimento Psicológico que os idosos têm uma melhor atitude face ao envelhecimento. É no item “Tem dinheiro suficiente para satisfazer as suas necessidades?” que os idosos apresentam uma menor qualidade de vida. Não ter doença diagnosticada e ser do sexo masculino permitem ter melhores atitudes face ao envelhecimento. A Qualidade de Vida está relacionada com a idade, com o estado de saúde e com a intensidade de preocupação da família. Constatou-se que os idosos que não estão institucionalizados apresentam uma melhor qualidade de vida e uma melhor atitude face à velhice. Quem não precisa de ajudas técnicas para se movimentar apresenta uma melhor qualidade de vida. Diferenças nas atitudes face ao envelhecimento consoante a residência onde habita são significativas nas mudanças físicas e no desenvolvimento psicológico sendo que os idosos que não vivem em lares têm uma atitude mais positiva em ambos os fatores. / Over the past few years the issue of aging has played a growing importance in the population`s collective consciousness becoming increasingly important to understand the elderly population and this reality. Therefore a quantitative correlational study was performed to assess the quality of life of seniors and their attitudes towards old age, and the relationship between these and the socio-demographic and family factors. 100 seniors with more than 65 years and without cognitive deficit were surveyed. For data collection we used a structured interview consisting of sociodemographic data of the elderly, WHOQOL-AGE (Caballero Miret Power Chatterji Tobiasz-Adamczyk Koskinen Leonardi Olaya Ayuso-Mateos & Haro 2013) and AAQ (Laidlaw Power Schmidt and the WHOQOL-OLD Group 2007). We highlight: The sample is composed of 52% of males with a mean age of 74.7 (SD = 6.8). It is in the factor Psychosocial Losses and Psychological Development that elderly people have a better attitude towards aging. It is in the item "Do you have enough money to meet your needs?" that seniors show less quality of life. Not having illness and being male allows having better attitudes towards aging. Quality of Life is related to age, health condition and the intensity of family concerns. It was observed that the elderly who are not institutionalized have a better quality of life and a better attitude towards old age. Who does not need assistive devices to move around has a better quality of life. Differences in attitudes towards aging, according to residency, are significant in physical changes and psychological development, thus verifying that elderly who do not live in nursing homes have a more positive attitude in both factors.

The Effect of Stress Management Program Using Cognitive Behavior Approach on Mental Health of the Mothers of the Children With Attention Deficit Hyperactivity Disorder

Background: Attention deficit hyperactivity disorder is one of the most common psychiatric disorders in children. Objectives: The study aimed to evaluate the effectiveness of stress management program using cognitive behavior approach on mental health of the mothers of the children with attention deficit hyperactivity disorder. Patients and Methods: In this interventional study, 90 mothers of the children with attention deficit hyperactivity disorder were randomly allocated into three intervention, placebo, and control groups. The general health questionnaire was used to measure mental health. Besides, stress was assessed through the depression-anxiety-stress scale. The two instruments were completed at baseline, immediately after, and one month after the intervention by the mothers. Afterwards, within group comparisons were made using one-sample repeated measurement ANOVA. One-way ANOVA was used for inter group comparisons. Mothers in the placebo group only participated in meetings to talk and express feelings without receiving any interventions. Results: At the baseline, no significant difference was found among the three groups regarding the means of stress, anxiety, depression, and mental health. However, a significant difference was observed in the mean score of stress immediately after the intervention (P = 0.033). The results also showed a significant difference among the three groups regarding the mean score of mental health (P < 0.001). One month after the intervention, the mean difference of mental health score remained significant only in the intervention group (P < 0.001). Conclusions: The study findings confirmed the effectiveness of stress management program utilizing cognitive behavior approach in mental health of the mothers of the children with attention deficit hyperactivity disorder.

Functional magnetic resonance brain imaging of executive cognitive performance in young first-episode schizophrenia patients and age-matched long-term cannabis users

Converging evidence from epidemiological, clinical and neuropsychological research suggests a link between cannabis use and increased risk of psychosis. Long-term cannabis use has also been related to deficit-like “negative” symptoms and cognitive impairment that resemble some of the clinical and cognitive features of schizophrenia. The current functional brain imaging study investigated the impact of a history of heavy cannabis use on impaired executive function in first-episode schizophrenia patients. Whilst performing the Tower of London task in a magnetic resonance imaging scanner, event-related blood oxygenation level-dependent (BOLD) brain activation was compared between four age and gender-matched groups: 12 first-episode schizophrenia patients; 17 long-term cannabis users; seven cannabis using first-episode schizophrenia patients; and 17 healthy control subjects. BOLD activation was assessed as a function of increasing task difficulty within and between groups as well as the main effects of cannabis use and the diagnosis of schizophrenia. Cannabis users and non-drug using first-episode schizophrenia patients exhibited equivalently reduced dorsolateral prefrontal activation in response to task difficulty. A trend towards additional prefrontal and left superior parietal cortical activation deficits was observed in cannabis-using first-episode schizophrenia patients while a history of cannabis use accounted for increased activation in the visual cortex. Cannabis users and schizophrenia patients fail to adequately activate the dorsolateral prefrontal cortex, thus pointing to a common working memory impairment which is particularly evident in cannabis-using first-episode schizophrenia patients. A history of heavy cannabis use, on the other hand, accounted for increased primary visual processing, suggesting compensatory imagery processing of the task.

Reduced motor facilitation during action observation in schizophrenia : a mirror neuron deficit?

Impairments in social cognitive functioning are well documented in schizophrenia, however the neural basis of these deficits is unclear. A recent explanatory model of social cognition centers upon the activity of mirror neurons, which are cortical brain cells that become active during both the performance and observation of behavior. Here, we test for the first time whether mirror neuron functioning is reduced in schizophrenia. Fifteen individuals with schizophrenia or schizoaffective disorder and fifteen healthy controls completed a transcranial magnetic stimulation (TMS) experiment designed to assess mirror neuron activation. While patients demonstrated no abnormalities in cortical excitability, motor facilitation during action observation, putatively reflecting mirror neuron activity, was reduced in schizophrenia. Dysfunction within the mirror neuron system may contribute to the pathophysiology of schizophrenia.

Extract of Ginkgo biloba leaves reverses yohimbine-induced spatial working memory deficit in rats

Extract of Ginkgo biloba is used to alleviate age-related decline in cognitive function, which may be associated with the loss of catecholamines in the prefrontal cortex. The purpose of this study was to verify whether alpha-2 adrenergic activity is involved in the facilitative effects of extract of Ginkgo biloba on prefrontal cognitive function. Male Wistar rats were trained to reach criterion in the delayed alternation task (0, 25, and 50-s delay intervals). A pilot study found that 3 or 4 mg/kg of yohimbine (intraperitoneal) reduced the choice accuracy of the delayed alternation task in a dose and delay-dependent manner, without influencing motor ability or perseverative behaviour. Acute oral pre-treatment with doses of 50, 100, or 200 mg/kg (but not 25 mg/kg) of extract of Ginkgo biloba prevented the reduction in choice accuracy induced by 4 mg/kg yohimbine. These data suggest that the prefrontal cognition-enhancing effects of extract of Ginkgo biloba are related to its actions on alpha-2-adrenoceptors.

Donepezil attenuates hippocampal neuronal damage and cognitive deficits after global cerebral ischemia in gerbils.

Decreased cerebral blood flow causes cognitive impairments and neuronal injury in vascular dementia. In the present study, we reported that donepezil, a cholinesterase inhibitor, improved transient global cerebral ischemia-induced spatial memory impairment in gerbils. Treatment with 5mg/kg of donepezil for 21 consecutive days following a 10-min period of ischemia significantly inhibited delayed neuronal death in the hippocampal CA1 region. In Morris water maze test, memory impairment was significantly improved by donepezil treatment. Western blot analysis showed that donepezil treatment prevented reductions in p-CaMKII and p-CREB protein levels in the hippocampus. These results suggest that donepezil attenuates the memory deficit induced by transient global cerebral ischemia and this neuroprotection may be associated with the phosphorylation of CaMKII and CERB in the hippocampus.

Cognitive maturation in preterm and term born adolescents

Background: Adolescence is a critical period of brain structural reorganisation and maturation of cognitive abilities. This relatively late developmental reorganisation may be altered in individuals who were born preterm.

Methods: We carried out longitudinal neuropsychological testing in 94 very preterm individuals (VPT; before 33 weeks' gestation) and 44 term born individuals at mean ages of 15.3 years ( adolescence) and 19.5 years (young adulthood).

Results: Full scale, verbal and performance IQ and phonological verbal fluency were significantly lower in the VPT group than the term group at both ages. Repeated measures ANOVA showed only one group by time point interaction for semantic verbal fluency (F= 10.25; df = 107; p = 0.002). Paired- sample t tests showed that semantic verbal fluency increased significantly in the term group over adolescence (t = -5.10; df = 42; p < 0.001), but did not increase in the VPT group (t = 0.141; df = 69; p = 0.889). For verbal IQ, there was a significant interaction between time point and sex (F = 4.48; df = 1; p = 0.036) with paired- sample t tests showing that verbal IQ decreased in males between adolescence and adulthood (t = 3.35; df = 71; p = 0.001), but did not change significantly in females (t = 0.20; df = 52; p = 0.845).

Conclusion: Decrements of intellectual functioning in VPT individuals persist into adulthood. Additionally, there is a deficit in the adolescent maturation of semantic verbal fluency in individuals born VPT.

The Development of TASTER, a Cognitive Training Game Using Human-Centered Design, Tailored for Children with Global and Specific Cognitive Impairments

Children with Prader-Willi syndrome often exhibit challenging behavior in response to changes to routine. This phenomenon has been linked to a deficit in task switching ability which has been observed in children with the syndrome. TASTER is a cognitive training game which is being designed with input from a group of children with Prader- Willi syndrome, which aims to train task switching ability and thus reduce associated challenging behavior.

The efficacy of cognitive retraining of attentional deficits for a client who has schizophrenia

The purpose of this study was to assess the efficacy of the Process Specific Approach to cognitive rehabilitation for a client with schizophrenia who has attentional deficits. The study was a single case experimental design which followed a variation of the multiple baseline approach. Prior to training of the attentional deficit, multiple baseline assessments were completed. These included an ov:erview of the sUbject's information processing ability, random measures of attention and a genera.l level of functioning in living, learning and working environments. During the re-training, attention tests were administered at the completion of each attention component. A general functional evaluation through interviews and a measure of information processing ability were. completed after the re-training was concluded. The results of the study demonstrate a significant i'mprovement in attention and memory measures. Qualitative data indicate si·gni.ficant others observed improvements in performance in r livi'ng, learning and working environments. The results suggest this approach to cognitive rehabilitation was effective with this subject and further research to establish generalizability is recommended.

Working memory in Alzheimer’s disease and mild cognitive impairment (MCI) : assessment and intervention

L’objectif principal de cette thèse est d’examiner et d’intervenir auprès des déficits de la mémoire de travail (MdeT) à l’intérieur de deux populations cliniques : la maladie d’Alzheimer (MA) et le trouble cognitif léger (TCL). La thèse se compose de trois articles empiriques. Le but de la première expérimentation était d’examiner les déficits de MdeT dans le vieillissement normal, le TCL et la MA à l’aide de deux versions de l’empan complexe : l’empan de phrases et l’empan arithmétique. De plus, l’effet de «l’oubli» (forgetting) a été mesuré en manipulant la longueur de l’intervalle de rétention. Les résultats aux tâches d’empan complexe indiquent que la MdeT est déficitaire chez les individus atteints de TCL et encore plus chez les gens ayant la MA. Les données recueillies supportent également le rôle de l’oubli à l’intérieur de la MdeT. L’augmentation de l’intervalle de rétention exacerbait le déficit dans la MA et permettait de prédire un pronostic négatif dans le TCL. L’objectif de la deuxième étude était d’examiner la faisabilité d’un programme d’entraînement cognitif à l’ordinateur pour la composante de contrôle attentionnel à l’intérieur de la MdeT. Cette étude a été réalisée auprès de personnes âgées saines et de personnes âgées avec TCL. Les données de cette expérimentation ont révélé des effets positifs de l’entraînement pour les deux groupes de personnes. Toutefois, l’absence d’un groupe contrôle a limité l’interprétation des résultats. Sur la base de ces données, la troisième expérimentation visait à implémenter une étude randomisée à double-insu avec groupe contrôle d’un entraînement du contrôle attentionnel chez des personnes TCL avec atteinte exécutive. Ce protocole impliquait un paradigme de double-tâche composé d’une tâche de détection visuelle et d’une tâche de jugement alpha-arithmétique. Alors que le groupe contrôle pratiquait simplement la double-tâche sur six périodes d’une heure chacune, le groupe expérimental recevait un entraînement de type priorité variable dans lequel les participants devaient gérer leur contrôle attentionnel en variant la proportion de ressources attentionnelles allouée à chaque tâche. Les résultats montrent un effet significatif de l’intervention sur une des deux tâches impliquées (précision à la tâche de détection visuelle) ainsi qu’une tendance au transfert à une autre tâche d’attention divisée, mais peu d’effets de généralisation à d’autres tâches d’attention. En résumé, les données originales rapportées dans la présente thèse démontrent un déficit de la MdeT dans les maladies neurodégénératives liées à l’âge, avec un gradient entre le TCL et la MA. Elles suggèrent également une préservation de la plasticité des capacités attentionnelles chez les personnes à risque de développer une démence.

Age-related eye disease and cognitive function

Objectif: Évaluer la relation entre la fonction cognitive chez les personnes âgées atteintes de dégénérescence maculaire reliée à l’âge (DMLA), de glaucome ou de dystrophie cornéenne de Fuchs et les comparer avec les personnes âgées n’ayant pas de maladie oculaire. Devis: Étude transversale de population hospitalière. Participants: 420 participants (113 avec la DMLA, 66 avec la dystrophie cornéenne de Fuchs, 130 avec le glaucome et 111 témoins). Méthodes: Nous avons recruté les patients à partir de la clinique d’ophtalmologie de l’Hôpital Maisonneuve-Rosemont (Montréal, Canada) de septembre 2009 à septembre 2013. Les patients atteints de la DMLA ou de la maladie de Fuchs ont une acuité visuelle inférieure à 20/40 dans les deux yeux, tandis que les patients avec du glaucome ont un champ visuel dans le pire œil inférieur ou égal à -4dB. Les patients contrôles, qui ont été recrutés à partir des mêmes cliniques, ont une acuité visuelle et un champ visuel normaux. Nous avons colligé des données concernant la fonction cognitive à partir du test Mini-Mental State Exam (MMSE)-version aveugle. Pour mesurer la fonction visuelle, nous avons mesuré l’acuité visuelle, la sensibilité au contraste et le champ visuel. Nous avons également révisé le dossier médical. Pour les analyses statistiques, nous avons utilisé la régression linéaire. Critère de jugement principal: MMSE-version aveugle. Résultats: Les trois maladies oculaires ont été associées à une limitation de la cognition. Le score de MMSE-version aveugle se situe de 0.7 à 0.8 unités plus basses par rapport au groupe contrôle. Comparativement aux contrôles, les patients avec maladies oculaires ont eu un score moyen diminué (P < 0.05). Le niveau d’éducation élevé est associé à une meilleure cognition (P < 0.001). Conclusions: Nos résultats suggèrent que les maladies oculaires sont associées à une diminution de la fonction cognitive chez les personnes âgées. De futures études sont nécessaires pour évaluer l’impact des maladies oculaires sur le déclin cognitif chez cette population pour pouvoir envisager des interventions ciblées qui pourraient les aider à maintenir leur indépendance le plus longtemps possible.