Nos últimos anos, temos nos deparado com a difusão maciça e a popularização crescente de descrições biológicas para aspectos outrora pensados como mentais, sociais, ou relacionais. Visível em diversas arenas leigas e científicas, esta tendência freqüentemente elege o cérebro como o órgão privilegiado da sua atenção. A cada semana é divulgada uma nova localização cerebral correlacionada os mais variados aspectos comportamentais e ou de personalidade. Acompanhando este movimento, é notável o esforço intelectual e financeiro despendido nos últimos anos no campo da saúde mental, no sentido de fazer avançar pesquisas cujo foco central é a descoberta das bases neurobiológicas dos transtornos mentais. Esta tendência apontaria na direção de uma fusão entre a psiquiatria e a neurologia em uma disciplina única, de teor fisicalista, chamada por alguns de cerebrologia. Dentre os acontecimentos que serviram de alicerce para a legitimação e a popularização desta tendência, o desenvolvimento nas últimas décadas de novas técnicas e tecnologias de visualização médica, como a tomografia por emissão de pósitrons (PET scan) e a ressonância magnética funcional (fMRI), foi fundamental. Elas permitiram a construção de imagens das mais diversas categorias nosográficas construídas no campo psiquiátrico, veiculando tacitamente uma série de pressupostos e promessas. Malgrado o imaginário cultural sustentado por estas tecnologias e todo o esforço despendido nas últimas décadas no sentido de se tentar localizar os marcadores biológicos dos transtornos psiquiátricos, não há, até o presente momento, nenhum resultado conclusivo que autorize o diagnóstico por imagem de nosografias como a esquizofrenia, a depressão, e muito menos o jogo patológico. Apesar de todo o alarde midiático e dos montantes milionários direcionados para pesquisas nesta área, os resultados concretos obtidos até agora não estão livres das mais ferozes controvérsias. Entretanto, ainda que estejamos muito longe da construção de mapas precisos para as perturbações mentais é espantoso o poder de convencimento que as neuro-imagens comportam na atualidade. Os scans são exibidos como verdades visuais, ou fatos acerca das pessoas e do mundo, numa proporção muito superior aos dados que apresentam. Alguns críticos chamam este aspecto de neurorealismo, ou de retórica da auto-evidência. A intenção deste trabalho é problematizar o poder persuasivo que as neuro-imagens detém na contemporaneidade, especialmente quando utilizadas com a finalidade diagnóstica no campo da saúde mental. Se estas imagens transmitem uma ideia de neutralidade, transparência imediata e auto-evidência, este trabalho almeja inseri-las num contexto sócio-histórico, a partir do qual puderam adquirir sentido, familiaridade e valor de verdade. O ponto de partida é o de que elas estão localizadas no cruzamento de dois movimentos históricos distintos: o das ilustrações médicas, em sua relação com a produção de conhecimento objetivo; e o das pesquisas acerca da localização no córtex cerebral de comportamentos complexos e traços de personalidade. Além de estabelecer algumas condições históricas de possibilidade para a emergência de um neo-localizacionismo cerebral, mediado pelas novas tecnologias de imageamento, pretende-se enfatizar algumas descontinuidades com projetos anteriores e marcar a influência do contexto cultural da atualidade para o sucesso e poder persuasivo deste tipo de tecnologia. / Lately, we have seen the popularization and massive difusion of biological descriptions to aspects that we used to consider as social or mentaly based. Notable in scientific and lay environments, this tendency frequently chooses the brain as the privileged organ of its attention. Every week, a new cerebral locality, related to behavioral and personality traces, is publicized. Along with this movement, it is remarkable the intellectual and financial efforts undertaken in the last years in the domaine of mental health, to advance the researchs that aim to discover the neurobiological basis of the mental disorders. This tendency points to the fusion between psychiatry and neurology in only one discipline, phisicalistically based, sometimes called brainology. One of the most important events that served as a base to the legitimation and the popularization of this trend was the development, in the last decades, of the new medical imaging techniques and technologies, like the Positron Emission Tomography (PET scan) and the Functional Magnetical Ressonance Imaging (fMRI). These technologies allowed the image construction of almost every nosografic category made up in the psychiatric domaine, transmitting implicitly many assumptions and promises. Notwithstanding the cultural imaginary sustaned by these technologies and the efforts undertaken to localize the biological markers of psychiatric disorders, there isnt, until the present time, any conclusive result that entitle the imaging diagnostic of nosographies like schizophrenia, depression, and the pathogical gambling. In spite of the mediatic attention and the milionaires amounts destined to researchs in this field, the concret results obtained until now arent free from tough controversies. However, even considering we are very far from the construction of accurate maps for the mental disfunctions, its incredible the power of conviction that neuroimages have nowadays. The scans are exhibited as visuable truths, or facts concerning the people and the world, in a proportion much superior to the data they present. Some critics call such an aspect neurorealism, or rhetoric of auto-evidence. The aim of this work is to question the persuasive power acquired by the neuroimages nowadays, especially when addopted to diagnostic aims in the field of mental health. If these images pass the idea of neutrality, immediate transparence and auto-evidence, this work intends to include them in a social-historical context, through wich they have obtained meaning, familiarity, and the status of truth. The point of depart is their localization in the crossing of two different historical movements: that of the medical illustrations, in its relation to the production of objective knowledge; and that of the researches about the localization, in the brain cortex, of complex behaviours and personality traits. Besides the establishment of some historical conditions of possibylity to the emergence of a cerebral neo-localizationism, this work pretends to stress some diferences in relation to preceding localizationist projects, and to emphasize the influence of the contemporary cultural context to the success e persuasive power of this kind of technologie.

Pesquisas científicas no campo da engenharia de reabilitação estão proporcionando cada vez mais mecanismos que visam ajudar pessoas portadoras de alguma deficiência física a executar tarefas simples do dia-a-dia. Com isso em mente, esse trabalho tem a finalidade de desenvolver um sistema que utiliza sinais musculares e redes neuro-fuzzy para a caracterização de determinados movimentos de um braço humano, com o objetivo de possibilitar futuramente a integração em sistemas de reabilitação. Ensaios preliminares demonstraram que para a caracterização de movimentos simples realizados por um braço humano, o uso exclusivo de técnicas simples de processamento de sinal é suficiente, como a utilização do valor rms. No entanto, para a caracterização de movimentos complexos é necessário um processamento mais robusto do sinal. Para isso foi desenvolvido um sistema experimental que adquire, através de um eletromiógrafo (EMG) de 8 canais, o sinal mioelétrico com eletrodos de superfície posicionados em lugares estratégicos do braço. O sinal é adquirido utilizando como estímulo um modelo virtual que demonstra ao usuário os movimentos do segmento mão-braço que devem ser executados de forma aleatória. Finalmente, com o uso de uma rede neuro-fuzzy, que possibilita a distinção tanto de movimentos simples como de movimentos compostos, se adaptando a diferentes usuários, os movimentos executados foram caracterizados em 12 movimentos distintos, previamente definidos, com uma taxa de acerto médio de 65%. / The scientific researches in the field of rehabilitation engineering are increasingly providing mechanisms to help people with a disability to perform simple tasks of day-to-day. With that in mind, this work aims to develop an experimental robotic prosthesis in order to implement, in the same, a control system that uses muscle signals and neuro-fuzzy networks for characterization of certain movements of a human arm, in order to enable further integration in rehabilitation systems. Preliminary tests showed that for the characterization of simple movements performed by a human arm, the exclusive use of simple techniques of signal processing is sufficient, as the use of the rms value. However, for the characterization of complex movements is required a more robust signal processing. For this was developed an experimental system that acquires through an electromyography (EMG) of 8 channels, the myoelectric signal with surface electrodes positioned in strategic places of the arm. The acquired signal uses, as a stimulus, a virtual model that demonstrates the hand-arm segment movements to be executed by the user at random. Finally, through a neuro-fuzzy network, which enables the distinction of both simple and compound movements, self-adapting to different users, the movements performed were characterized in 12 distinct movements, previously defined, with an average accuracy of 65%.

abstract: Magnetic Resonance Imaging using spiral trajectories has many advantages in speed, efficiency in data-acquistion and robustness to motion and flow related artifacts. The increase in sampling speed, however, requires high performance of the gradient system. Hardware inaccuracies from system delays and eddy currents can cause spatial and temporal distortions in the encoding gradient waveforms. This causes sampling discrepancies between the actual and the ideal k-space trajectory. Reconstruction assuming an ideal trajectory can result in shading and blurring artifacts in spiral images. Current methods to estimate such hardware errors require many modifications to the pulse sequence, phantom measurements or specialized hardware. This work presents a new method to estimate time-varying system delays for spiral-based trajectories. It requires a minor modification of a conventional stack-of-spirals sequence and analyzes data collected on three orthogonal cylinders. The method is fast, robust to off-resonance effects, requires no phantom measurements or specialized hardware and estimate variable system delays for the three gradient channels over the data-sampling period. The initial results are presented for acquired phantom and in-vivo data, which show a substantial reduction in the artifacts and improvement in the image quality. / Dissertation/Thesis / M.S. Bioengineering 2013

Submitted by Isaac Francisco de Souza Dias (isaac.souzadias@ufpe.br) on 2016-01-25T18:22:30Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação_Ramon_Bezerra_Souza_versão_final.pdf: 3177211 bytes, checksum: 017ba69bf52dcd924ae27162d811437a (MD5) / Made available in DSpace on 2016-01-25T18:22:30Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação_Ramon_Bezerra_Souza_versão_final.pdf: 3177211 bytes, checksum: 017ba69bf52dcd924ae27162d811437a (MD5) Previous issue date: 2014-08-29 / CAPES / O Brasil apresenta um amplo potencial eólico a ser explorado, atualmente, observa-se a grande expansão desta fonte de geração, principalmente no nordeste do Brasil, onde os ventos apresentam uma importante característica de complementaridade em relação às vazões do rio São Francisco. Porém, devido à incerteza associada à potência disponível, o aprimoramento das ferramentas de previsão de curto prazo representa um fator determinante para a operação do sistema, contribuindo para facilitar a comercialização de energia elétrica, o controle dos parques eólicos e fornecer uma estimativa futura para determinada localidade. Este trabalho é uma contribuição aos modelos de previsão de velocidades médias horárias dos ventos, para o horizonte de previsão de uma a quatro horas, utilizando as Redes Neurais Artificiais, sistemas Neuro-Fuzzy e o Reservoir Computing como métodos de inteligência artificial e as variáveis velocidade média do vento, umidade do ar, radiação solar e temperatura como entradas dos modelos de previsão. Os resultados obtidos para as previsões com alguns modelos propostos, revelaram ganhos da ordem de 50 % quando comparados com o modelo de referência, ratificando a eficiência dos modelos desenvolvidos. / Brazil has a large wind potential to be exploited, currently, there is a great expansion of this source of generation, primarily in northeastern Brazil, where winds have an important feature of complementarity with the flows San Francisco River. However, due to the uncertainty associated with the available power, the improvement in short-term forecasting tools is a key factor for system operation, helping to facilitate the sale of electricity, control of wind farms and provide an estimate for future Local determined. This work is a contribution to the average speeds hourly forecast models of the winds, to the forecasting horizon of one to four hours, using the Artificial Neural Networks, Neuro-Fuzzy systems and Reservoir Computing as methods of artificial intelligence and speed variables average wind, humidity, solar radiation and temperature as inputs for forecasting models. The results obtained for predictions with some proposed models, showed gains of about 50% compared to the reference model, confirming the efficiency of the developed models.

This research aims at finding a foundation for assessment of capabilities and applying the concept in a human resource selection. The research identifies a common ground for assessing individuals’ applied capability in a given job based on literature review of various disciplines in engineering, human sciences and economics. A set of criteria is found to be common and appropriate to be used as the basis of this assessment. Applied Capability is then described in this research as the impact of the person in fulfilling job requirements and also their level of usage from their resources with regards to the identified criteria. In other words how their available resources (abilities, skills, value sets, personal attributes and previous performance records) can be used in completing a job. Translation of the person’s resources and task requirements using the proposed criteria is done through a novel algorithm and two prevalent statistical inference techniques (OLS regression and Fuzzy) are used to estimate quantitative levels of impact and utilisation. A survey on post graduate students is conducted to estimate their applied capabilities in a given job. Moreover, expert academics are surveyed on their views on key applied capability assessment criteria, and how different levels of match between job requirement and person’s resources in those criteria might affect the impact levels. The results from both surveys were mathematically modelled and the predictive ability of the conceptual and mathematical developments were compared and further contrasted with the observed data. The models were tested for robustness using experimental data and the results for both estimation methods in both surveys are close to one another with the regression models being closer to observations. It is believed that this research has provided sound conceptual and mathematical platforms which can satisfactorily predict individuals’ applied capability in a given job. This research has contributed to the current knowledge and practice by a) providing a comparison of capability definitions and uses in different disciplines, b) defining criteria for applied capability assessment, c) developing an algorithm to capture applied capabilities, d) quantification of an existing parallel model and finally e) estimating impact and utilisation indices using mathematical methods.

L'addiction aux drogues est une pathologie psychiatrique chronique qui représente un problème de santé publique majeur. Malgré des avancées importantes permettant de mieux comprendre les modifications cérébrales induites par les drogues d'abus, les thérapies restent encore limitées. Ainsi, l'étude des processus cérébraux qui sous-tendent les risques de rechute à long terme semble être centrale à l'élaboration de nouvelles stratégies thérapeutiques. Une partie de cette thèse vise à déterminer les modifications cérébrales induites à long terme lors du sevrage, suite à une prise chronique de cocaïne. Notre première étude a révélé une réduction de la densité vasculaire cérébrale lors du sevrage précoce, exclusivement localisée dans le cortex cingulaire. Dans la seconde étude, nous avons mis en évidence des modifications du métabolisme cérébral et étudié leur évolution lors du sevrage. Après un mois de sevrage, période où l'on trouve le phénomène d'incubation du « craving », nous avons mis en évidence une réduction du métabolisme cortical et striatal alors que l'amygdale se voit hyperactivée témoignant d'une dérégulation des fonctions cérébrales. Enfin, nous avons caractérisé le mécanisme sous-jacent à l'effet « anti-craving » de l'environnement enrichi (EE). Nous avons émis l'hypothèse que l'EE agirait comme une récompense alternative pour diminuer la recherche de cocaïne, ainsi nous avons testé les effets de l'exposition au sucrose et à l'exercice physique sur le comportement de recherche de drogue. Nous avons montré que l'accès à une récompense alternative pendant le sevrage ne permet pas de réduire la recherche de cocaïne suggérant que l’EE n'agit pas exclusivement comme une récompense alternative. / Drugs addiction is a chronic brain disorder representing a major public health problem. Although important advances allowed a better understanding of the cerebral modifications induced by chronic exposure to drugs, the therapies still nowadays limited. Therefore the investigation of cerebral processes that underlie the persistent risks of relapse, seem to be crucial to offer new therapeutic strategies. A part of this thesis aims at investigating the cerebral modifications induced in a long term during the withdrawal, due to a chronic voluntary intake of cocaine. In our first study we found a reduction of the density of cerebral vessels during the early withdrawal selectively localized in the cingular cortex. In our second study we found that cocaine intake leads to modifications of cerebral metabolism that evolve during the withdrawal. After one month of withdrawal, at a time when the phenomenon of incubation of craving is found, we found a decrease in cortical and striatal metabolism and a hyperactivation of the amygdala which demonstrates a persistent disregulation of brain functioning. Finally, in our third study, we tried to dissect the mechanism underlying the anti-craving effect of the enriched environment (EE). We hypothesized that the EE acts as an alternative reward to decrease the cocaine seeking behavior. Thus we tested the effects of exposure to sucrose or the physical exercise on relapse to cocaine. We demonstrated that the access to an alternative reward during the withdrawal does not allow reducing cocaine seeking which suggests that the EE does not act exclusively as an alternative reward.

In today’s rapidly changing world of work, where dramatic, unpredictable and complex change is redefining the way in which organisations are to be managed, a realisation has emerged that the intra- and interpersonal communication techniques of people are fundamental in organisational success. This study argues that Neuro Linguistic Programming (NLP) consists of the necessary techniques to impact on an organisation, while its communication model and leadership behaviour adds to achieving organisational success. Previous research in NLP has been done mostly in disciplines such as psychology and linguistics, but a call is made to apply NLP in an organisational context. Little empirical evidence exists with regards to the benefits of NLP techniques while even fewer evidence is available in a South African context. In this study NLP’s relationship with Emotional Intelligence, the development of leadership, the corporate world and several communication theories are explored so as to understand the value it can contribute in a time where the concept of organisational success is being re-defined. An integrated framework of organisational success, incorporating NLP, Emotional Intelligence and intrapersonal communication, is introduced that serves as an additional guideline to measure the elements of organisational success in organisations, leaders or communication models. This framework also leads to the conclusion that organisations, leaders and communication models making use of NLP are better off than those not making use of it. The benefits of NLP include motivating employees, managing conflict and self-motivation, managing emotional states, communicating effectively, building trust, increasing productivity, improving customer care, strategic planning, setting goals as well as aligning visions and better flexibility. This study establishes that intelligent leadership, the application of NLP techniques to the intra- and interpersonal communication behaviour and management approaches of leaders, can be correlated with organisational success. This is done by means of a case study on the Solidarity Movement, a large non-profit organisation in South-Africa, where five strategic leaders are analysed who are believed to be using and have implemented NLP in the organisation. The result is that evidence is found to support the notion that NLP improves the intra- and interpersonal behaviour of leaders and in turn contributes to organisational success by applying NLP in their communication and leadership behaviour. NLP is often presented as a magic toolkit for the self-improvement of individuals and have since recently relied more on presuppositions than either qualitative or quantitative research. This study adds to the credibility of NLP as an increasingly important instrument for communication management as a discipline. / Dissertation (MCom)--University of Pretoria, 2014. / gm2014 / Communication Management / Unrestricted

De par sa localisation anatomique, ses connexions anatomiques et fonctionnelles, l’hippocampe est une structure impliquée dans la mémoire (encodage et stockage de l’information) et dans la régulation des émotions. La prolifération des cellules au niveau du gyrus denté, les nouvelles connexions synaptiques et la modulation de l’efficacité des synapses déjà existantes par la Long Term Potentiantion (LTP) et la Long Term Depression (LTD) participent aux fonctions mnésiques. Le rétro-feedback négatif qu’exerce l’hippocampe sur l’axe hypothalamo-hypophyso-surrénalien permet une régulation de la réaction à un stress auquel est soumis l’organisme. La dépression est en outre considérée comme étant un état de stress pour l’organisme.La prolifération de progéniteurs neuronaux, la plasticité neuronale, sont des caractéristiques essentielles du fonctionnement de l’hippocampe. L’effet des traitements antidépresseurs, aussi bien médicamenteux que l’électro-convulsivo-thérapie (ECT) soulignent l’importance de cette caractéristique.Concernant plus particulièrement une forme de dépression dite endogène, la mélancolie, de nombreux facteurs génétiques sont retrouvés comme étant des facteurs de vulnérabilité. Des évènements traumatiques, particulièrement dans l’enfance, sont à l’origine de l’expression de cette vulnérabilité.Des troubles de la mémoire sont retrouvés de manière inconstante en lien avec la dépression. Le caractère répétitif de la dépression, qui est une maladie récurrente, pourrait expliquer que ces troubles mnésiques ne soient retrouvés qu’après plusieurs épisodes dépressifs, il s’agirait d’un caractère cumulatif, quantitatif. Ou bien, les spécificités liées à la mélancolie seraient à l’origine d’une plus grande neuro-toxicité de cette forme de dépression et expliqueraient que les troubles de la mémoire soient liés à ce type d’épisode, de manière cette fois qualitative.Voulant étudier le poids respectif de ces deux hypothèses, l’une impliquant d’étudier des sujets ayant des temps de vie passés en dépression variables et donc des âges variables, et la fonction testée étant la mémoire qui est altérée avec le vieillissement, nous avons tout d’abord étudié l’impact de l’âge. L’âge n’est pas un facteur indépendant pouvant expliquer une moins bonne récupération de la fonction mnésique après un épisode dépressif majeur lorsque sont pris en compte le niveau de performance mnésique de base et les symptômes persistants.L’étude du poids de l’hypothèse qualitative et quantitative a montré que le temps de vie passé en dépression est corrélé à la performance en mémoire déclarative différée et à la taille de l’hippocampe droit, le score de mélancolie ne l’est pas. En revanche temps de vie passé en dépression et score de mélancolie sont corrélés.La dépression apparaît donc être toxique par un mécanisme cumulatif de chaque épisode qui représente un état de stress pour l’organisme avec une hyper activation de l’axe hypothalamo-hypophyso-surrénalien et une sécrétion accrue de cortisol. Mais du fait des facteurs de vulnérabilité génétique, qui sont liés au type endogène de dépression, et à la théorie de l’embrasement, des évènements de stress de moins en moins importants précédant un épisode dépressif majeur, ce pourrait être les mêmes sujets qui sont à la fois soumis à des épisodes dépressifs à caractéristique mélancolique et à un trouble dépressif multi-récurrent. Il s’agit cependant d’une corrélation statistique entre temps de vie passé en dépression et atteinte de l’hippocampe, les mécanismes biologiques de causalité expliquant ce constat ne sont pas connus. Seule une partie de la population pourrait être exposée à une vulnérabilité génétique et à un grand nombre d’épisodes dépressifs, ou bien les épisodes dépressifs pourraient prendre une caractéristique mélancolique après un certain nombre de récurrence. Des recherches dans ce domaine sont à développer. / Through its cerebral localization, its anatomical and functional connectivity, the hippocampus is involved in memory (coding and storing) and in emotion regulation. Cell proliferation in the dentate gyrus, new synaptic connections and the modulation of the efficiency of existing synaptic connections by the Long Term Potentiation and Long Term Depression, participate in memory function. Negative retro feedback that the hippocampus has on the hypothalamic-pituitary-adrenal axis allows a regulation of the reaction of the organism to stress it undergoes. Depression can in fact be considered as a state of stress for the organism.Neuron progenitor proliferation and neuronal plasticity are essential characteristics of the hippocampus ‘functioning. The effect of antidepressant therapeutics, medicinal ones as well as electro convulsive therapy, underlies the importance of this characteristic.Concerning more precisely an endogenous subtype of depression, melancholia, numerous genetic factors have been found as being vulnerability factors. Traumatic events, especially during childhood, are at the origin of the expression of this vulnerability.Memory impairments are found inconstantly in relation to depression. The repetitive character of depression, which is pathology with a high rate of recurrence, could explain that these impairments are only found after several depressive episodes. This is a cumulative or quantitative hypothesis. Or, specificities linked to melancholia could make this subtype more neurotoxic and could explain that memory impairments would be linked to melancholia. This is a qualitative hypothesis.Willing to explore the influence of each of these hypotheses, but one of them requiring studying subjects with different lifetimes being depressed and different ages, we first studied the impact of age on memory impairment. Age is not an independent factor explaining worse memory recovery after a depressive episode once remaining symptoms and memory at baseline are controlled for.Studying the respective influence of the quantitative hypothesis and the qualitative hypothesis we found that the lifetime being depressed is correlated to delayed verbal memory impairment and size of the right hippocampus, whereas the score at scale of melancholia is not. However, lifetime being depressed and the rate of melancholia are correlated.Depression appears to be neurotoxic through a cumulative mechanism, each depressive episode being a stress for the organism with a hyper activation of the hypothalamic-pituitary-adrenal axis and a hyper secretion of cortisol. But taking into account the genetic vulnerability factors, which are linked to endogenous subtype of depression, and the kindling hypothesis with smaller and smaller stressful life events preceding a depressive episode, it could be the same subjects that both have depressive episodes with melancholic characteristics and depression with a high rate of recurrence. This is only a statistic correlation between lifetime being depressed and hippocampal atrophy, biological mechanisms explaining causality for this correlation are not yet known. Only a part of the subjects could be exposed to genetic vulnerability and high recurrence of the depressive episodes or depressive episodes could become melancholic after several recurrences. Further research on this topic is needed. Moreover, looking at the high cost of depression and the high influence of life conditions during childhood, maternal care and traumas, special attention must be payed to them.

La dégénérescence des photorécepteurs dans la pathologie de la dégénérescence maculaire liée à l'âge (DMLA) est associée à une infiltration et accumulation des phagocytes mononuclées (PM). Nous avons montré précédemment que les souris déficientes pour Cx3cr1 développent une accumulation des PM sous-rétiniens avec l'âge et avec le stress, qui est associée une dégénérescence des photorécepteurs. Dans le cerveau, la déficience de Cx3cr1 dans les PM induit une augmentation de la mort des neurones via IL-1β. La raison de l'augmentation de la sécrétion d'IL-1β par les PM déficients en Cx3cr1 reste inconnue. Nous montrons que les PM déficients en Cx3cr1 surexpriment le récepteur P2RX7 qui stimule la maturation et la sécrétion d'IL-1β. L'inhibition de P2RX7 et d'Il-1β diminuent la mort des photorécepteurs dans un modèle de cocultures de monocytes/rétine et avec le modèle d'illumination in vivo. Nos résultats suggèrent que l'inhibition de P2RX7 ou d'Il-1β peut diminuer l'inflammation sous-rétinienne qui est associée à la mort des photorécepteurs dans la pathologie de la DMLA, où il n'existe aucun traitement à l'heure actuelle pour la forme atrophique. / Photoreceptor degeneration in age-related macular degeneration (AMD) is associated with an infiltration and chronic accumulation of mononuclear phagocytes (MPs). We have previously shown that Cx3cr1 -deficient mice develop age- and stress- related subretinal accumulation of MPs, which is associated with photoreceptor degeneration. Cx3cr1 -deficient MPs have been shown to increase neuronal apoptosis through IL-1β in neuroinflammation of the brain. The reason for increased IL-1 β secretion from Cx3cr1 -deficient MPs, and whether IL-1β is responsible for increased photoreceptor apoptosis in Cx3cr1 -deficient mice, has not been elucidated. Here we show that Cx3cr1 -deficient MPs express increased surface P2X7 receptor (P2RX7), which stimulates IL-1β maturation and secretion. P2RX7 and IL-1_β inhibition efficiently blunted Cx3cr1 -MP-dependent photoreceptor apoptosis in a monocyte/retina coculture system and in light induced subretinal inflammation of Cx3cr1 -deficient mice in vivo. Our results provide an explanation for increased CX3CR1-dependent IL-1β secretion and suggest that IL-1β or P2RX7 inhibition can help inhibit the inflammation-associated photoreceptor cell loss in late AMD, including geographic atrophy, for which no efficient treatment currently exists.

En ventilation assistée, l’inadéquation entre l’activité des muscles respiratoires du patient et l’assistance délivrée par le ventilateur se traduit par la survenue d’une dysharmonie patient-ventilateur potentiellement associée avec la survenue d’asynchronies patient-ventilateur et d’une dyspnée. Minimiser cette dysharmonie est un objectif majeur de la ventilation assistée. Le Neuro Asservissement de la Ventilation Assistée (NAVA) et la Ventilation Assistée Proportionnelle (PAV) sont deux nouveaux modes qui pourraient améliorer l’harmonie patient-ventilateur. Nous avons montré que, de façon similaire, le NAVA et la PAV diminuent le nombre d’asynchronie patient-ventilateur, préviennent la surdistension pulmonaire, restaurent la variabilité cycle à cycle du comportement ventilatoire et améliorent l’équilibre charge-capacité et le couplage neuromécanique. De plus, l’utilisation du mode NAVA en ventilation non invasive pourrait également permettre d’améliorer la synchronisation patient-ventilateur. Nous avons également montré aux cours de différents travaux sur la dyspnée en ventilation mécanique que celle ci était fréquente mais néanmoins difficile à identifier, en particulier chez les patients non communicants. L’EMG de surface des muscles inspiratoires extra-diaphragmatiques pourrait constituer un outil simple et objectif pouvant permettre au clinicien de diagnostiquer une dyspnée en ventilation mécanique et optimiser les réglages du ventilateur dans le but de minimiser la dysharmonie patient-ventilateur. Ces données permettent de progresser vers une meilleure connaissance de la dysharmonie patient- ventilateur. L’impact clinique de l’utilisation des modes proportionnels et d’une détection précoce de la dyspnée doit maintenant être évalué par des essais cliniques. / Ventilatory support must be tailored to the load capacity balance of the respiratory system to avoid patient-ventilator dysharmony as it may lead to patient-ventilator asynchronies and dyspnea. Minimizing this dysharmony is crucial. Neurally Ventilatory Assist Ventilation (NAVA) and Proportional Assist Ventilation (PAV) modes may improve patient-ventilator interaction. We showed in this work that PAV and NAVA both prevents overdistension, restores breath by breath variability of the breathing pattern and improves neuromechanical coupling and patient- ventilator asynchrony in fairly similar ways compared to pressure support ventilation. In addition the use of NAVA with non-invasive ventilation may also improve patient-ventilator interaction. We also demonstrated that dyspnea is a frequent issue in mechanically ventilated ICU patients and it can be difficult to assess when the patient is unable to report it. Surface electromyograms of extradiaphragmatic inspiratory muscles provides a simple, reliable and non-invasive indicator of respiratory muscle loading/unloading in mechanically ventilated patients. Because this EMG activity is strongly correlated to the intensity of dyspnea, it could be used as a surrogate of respiratory sensations in mechanically ventilated patients, and might, therefore, provide a monitoring tool in patients in whom detection and quantification of dyspnea is complex if not impossible. These data provide a better understanding of patient-ventilator dysharmony. Further studies are needed to evaluate the possible clinical benefits of NAVA and PAV on clinical outcomes and the impact of an early detection of dyspnea in mechanical ventilation.