Trois états de vigilance, caractérisés par une activité cérébrale spécifique, sont habituellement décrits chez l'Homme: la veille, le sommeil lent et le sommeil paradoxal. Cependant, certaines situations cliniques comme les parasomnies ou l'inertie de sommeil, ainsi que des travaux expérimentaux récents chez l'animal et chez l'homme, suggèrent la possibilité d'états intermédiaires ou transitionnels. L'étude des micro- éveils apparait pertinente pour appréhender les phénomènes de transition entre états de vigilance. Pour caractériser les micro-éveils chez l'Homme, nous avons enregistré l'activité EEG au cours de micro-éveils "spontanés" ou déclenchés par des stimulations nociceptives, en sommeil lent et en sommeil paradoxal, chez 8 patients épileptiques pharmaco-résistants bénéficiant d'un bilan pré-chirurgical invasif stéréo-électro- encéphalographique. Les puissances spectrales dans différentes bandes de fréquence au cours des micro-éveils ont été comparées à celles déterminées sur le signal précèdant le micro-éveil. Le thalamus (pulvinar médian), le cortex sensorimoteur primaire et plusieurs aires corticales associatives ont été étudiés. Nous avons observé 1) une grande reproductibilité intra et interindividuelle des modifications d'activité EEG associées aux micro-éveils dans le thalamus, et qui correspondent à un état intermédiaire entre la veille et le sommeil. 2) une importante hétérogénéité des modes d'activation corticale au cours des micro-éveils, quand bien même l'activation sous- corticale est stéréotypée. Différents facteurs participent à cette variabilité : le cortex considéré, le stade de sommeil au cours duquel le micro-éveil survient, la nature du stimulus à l'origine du micro-éveil, ou encore des phénomènes homéostatiques. 3) que la composition spectrale du signal au cours des micro-éveils dansle cortex était différente de l'état de veille, ce qui situe les micro-éveils hors du spectre des états de vigilance classiquement différenciés et constitue un argument en faveur du fait que la transition entre le sommeil et la veille au niveau cortical ne se fait pas de façon abrupte et binaire. Ainsi, les micro-éveils apparaissent comme des états d'activation cérébrale régulés au moins en partie localement par des mécanismes impliqués dans la gestion d'une double nécessité théoriquement contradictoire : permettre au dormeur de réagir à des stimulations pertinentes, tout en préservant la continuité du sommeil / Wakefulness, non rapid eye movement (NREM) and rapid eye movement (REM) sleep are characterized by specific brain activities. However, recent experimental findings as well as various clinical conditions (parasomnia, sleep inertia) have revealed the presence of transitional states. Brief intrusions of wakefulness into sleep, namely arousals, appear as relevant phenomena to characterize how brain commutes from sleep to wakefulness. Using intra-cerebral recordings in 8 drug-resistant epileptic patients we analyzed electroencephalographic (EEG) activity during spontaneous or nociceptive-induced arousals in NREM and REM sleep. Wavelet spectral analyses were performed to compare EEG signals during arousals, sleep and wakefulness, simultaneously in the thalamus, and primary, associative or high order cortical areas. We observed that: 1) thalamic activity during arousals is stereotyped and its spectral composition corresponds to a state in-between wakefulness and sleep 2) patterns of cortical activity during arousals are heterogeneous, their manifold spectral composition being related to several factors such as sleep stages, cortical areas, arousal modality ("spontaneous" vs nociceptive-induced) and homeostasis; 3) spectral compositions of EEG signals during arousal and wakefulness differ from each other. Thus, stereotyped arousals at the thalamic level seem to be associated with different patterns of cortical arousals due to various regulation factors. These results suggest that human cortex does not shift from sleep to wake in an abrupt binary way. Arousals may be considered more as different states of the brain than as "short awakenings". This phenomenon may reflect the mechanisms involved in the compromise needed to be found between two main contradictory functional necessities, preserving the continuity of sleep and maintaining the possibility to react

Marseilleviridae est une famille de virus géants isolés initialement à partir de prélèvements environnementaux, dont Marseillevirus est le membre fondateur. La présence des marseillevirus chez l’Homme a été démontrée dans quelques études. Les objectifs sont de mieux documenter la présence des marseillevirus chez l’Homme, de modéliser l’infection par Marseillevirus chez la souris, et enfin, de décrire les génomes des marseillevirus. Nous rapportons un cas d’infection par Marseillevirus chez une patiente atteinte d’un cancer des ganglions, soulevant la question d’un éventuel lien entre Marseillevirus et cancer, à l’instar de l’association existant entre d’autres virus et les cancers. L’infection des souris par Marseillevirus montre que celui-ci persiste un mois au niveau des «amygdales», confirmant le portage pharyngé chronique observé chez un deuxième patient. Enfin, nous identifions deux nouveaux groupes au sein de la famille, soulignant l’importante diversité génétique de la famille. / Marseilleviridae is a new family of giant viruses primarily isolated from environmental samples and whose Marseillevirus is the founding member. The presence of marseilleviruses in humans has been demonstrated in few studies. The aims are to better document the presence of marseilleviruses in humans, to develop a model of infection of mice with Marseillevirus, and to describe the genomes of marseilleviruses. We report a first caes of infection by Marseillevirus in apatient with a lymph nodes cancer, raising the question of a potential link between Marseillevirus and cancer, as the well established association between some viruses and cancers. The infection of miceshows that Marseillevirus persist one month in the “tonsils”, confirming the chronic pharyngeal carriage reported in a second patient. Finally, we identify two new subgroups in the family, highlighting the considerable genetic diversity of the family.

Chez les humains et les animaux, l’exposition répétée à une séquence de stimulus conduit à la création de représentations mentales isomorphes aux régularités statistiques de cette séquence. Cette thèse étudie la dynamique avec laquelle les unités et sous-unités sont extraites, s’influencent et s’organisent lors de l’apprentissage séquentiel chez l’humain et le primate non-humain (babouin Papio papio). Nos résultats montrent que lors de l’apprentissage d’une séquence régulière ABC, la sous-unité finale BC est apprise plus rapidement que la sous-unité initiale AB chez les humains comme les primates non- humains. Avec une séquence plus longue ABCD, cet effet ne s’étend pas au-delà des deux termes précédents celui à prédire lors des 2000 essais d’apprentissage. Une seconde étude montre que les humains sont capables d’utiliser la prédictibilité des éléments à différents niveaux de complexité, alors que les singes sont limités aux dépendances locales. Enfin notre dernière étude montre que les humains comme les singes ne bénéficient pas d’un contexte d’homogénéité de longueurs des unités par rapport à un contexte d’hétérogénéité de longueurs des unités. Ensemble, ces études montrent des continuités et discontinuités entre les primates humains et non-humains dans l’extraction, l’influence et l’organisation des unités de différents niveaux. Elles donnent des informations d’une finesse nécessaires pour contraindre les différents modèles computationnels qui ont été proposés pour décrire l’apprentissage de régularités. / In humans and animals, the repeated exposure to a sequence of stimulus creates mental representations which have the same statistical regularities as that sequence. This thesis investigates the dynamics, influence and organization of units and sub-units during sequence learning, in humans and non-human primates (Guinea baboons, Papio papio).Our results show an advantage of the final sub- unit BC over the initial sub-unit AB during learning of sequences with the form ABC in both humans and baboons. We interpret this effect as resulting from the richer contextual information AB predicting C compared to the single term A predicting B. This effect is limited to the 2 previous terms before the one term to be predicted, across 2000 learning trials. A second finding shows that in learning sequences of 3 units (i.e. ABC, DEF, HGI), humans are able to use the predictability of elements at both local (within units) and global (within sequence) levels, whereas monkeys are limited to local dependencies. A third section investigates the extraction of regularities in homogeneous (i.e., units of the same length) and heterogeneous contexts (units of different lengths). Results in humans and monkeys showed no advantage for either of these contexts.Considered together, our studies show continuities and discontinuities between human and non-human primates in the extraction, influence and organization of units of different levels. This fine-grained level of information is necessary to constrain the computational models proposed to describe the mechanisms underlying regularity extraction.

The animal welfare legislation that is discussed in this Dissertation is just a sample of the available legislation from the chosen foreign jurisdictions and South Africa. The chosen foreign jurisdictions were chosen as a lens to gain a needed perspective on South African animal welfare legislation. The legislation chosen for discussion falls within particular categories that are discussed fully in the later chapters.i Despite the fact that the animal rights and animal welfare movements are recorded to date back as far as 500B.C, the majority of jurisdictions throughout the world still consider animals to be property that can be bought, traded, hunted and after they are killed, their remains kept as trophies or souvenirs. Within these jurisdictions (which includes South Africa and the other four chosen foreign jurisdictions – Kenya, India, Switzerland and the United States of America) there is a demonstrated lack of proper enforcement of the animal welfare/animal anti-cruelty legislation, regulations and industry rules, which is made worse by the actions of uncaring, abusive and/or ignorant people. South Africa is no better or worse to the four chosen jurisdictions in that it has similar anti-cruelty/animal welfare legislation. The lack of proper enforcement of this animal welfare legislation in South Africa should be of great concern as many studies have indicated that there is a link between animal abuse/cruelty and ‘human’ abuse. The same studies also indicate that animal abusers are at a greater risk of becoming violent criminals or of committing a violent crime. For example, the Federal Bureau of Investigation has noted that most serial killers in the USA had a history of torturing, abusing and killing animals before they moved on to torturing, abusing and/or killing humans in their adult life. Needed changes to the animal welfare legislation and how people view animals should be made in South Africa to ensure that welfare of animals is protected. For example, the Government could educate people about animal welfare in order to overcome any ignorance that may be the cause of animal pain and abuse, as well as strengthening existing animal welfare legislation. The eradication of ignorance, as well as a necessary change in the current animal welfare legislation, will help to create a real change in how people view and treat i Chapter 5 and 6. [iii] animals. People will come to realise that animals exist in their own right and that they were not created to serve or to be exploited by man.

Heart transplantation (HTx) is now an established therapy for end-stage cardiac failure not responding to medical treatment. Recent decades have seen improved outcome following HTx due to more effective and targeted immunosuppressive therapy. However, acute and chronic rejection remains a major cause of morbidity and mortality. At the same time, immunosuppressive strategies are associated with significant side effects, including development of tumours. Hence, the induction of immunologic tolerance to alloantigen is considered the “holy grail” of transplant research. T regulatory cells (Tregs) are a subset of T cells that appear to suppresscytotoxic cell and initiate tolerance to foreign tissues. The Tregs suppresscytotoxic cells through specific cytokine pathways and cell-cell contact. In-vivo T reg migration has been a matter of debate in recent years. Treg trafficking is governed by chemokines, which are small secreted proteins, acting via their distinct trans-membrane serpentine receptors. Experimental work has demonstrated an involvement of distinct chemokine pathways in Tregs migration and localization following cardiac transplantation; however, there is paucity of data in humans. I investigated the effects of chemokines on Tregs in heart transplant recipients through a series of observational studies. My study demonstrated that acute rejection following heart transplantation is associated with a significant elevation of peripheral blood Th1 chemokine levels. I hereby further show that peripheral blood Treg counts in stable heart transplant recipients are not affected by immunosuppression but are significantly lower in patients taking statins. I have demonstrated via in-vitro chemotaxis assays a specific pattern of chemotactic response for Tregs and the effector T cells. Using double immunofluorescence staining and immunostaining, I show for the first time that Tregs may migrate to the allograft under the influence of CCL17.

The present study contributes an apparatus and research paradigm useful in generating human performances sensitive to concurrent schedules of reinforcement. Five participants produced performances observed to be under temporal and ratio control of concurrent fixed interval-fixed ratio schedules. Two aspects of interaction between FI and FR schedules were distinguishable in the data. First, interaction between two schedules was observed in that changes in the value of one schedule affected behavior reinforced on another schedule. Second, switching from one pattern to the other functioned as an operant unit, showing stability during schedule maintenance conditions and sensitivity to extinction. These effects are discussed in the context of current views on behavior under concurrent schedules of reinforcement, and some implications for the conceptualization, measurement, analysis, and treatment of complex behavior are presented.

Despite the central importance of conditional discriminations to the derivation of equivalence relations, there is little research relating the dynamics of conditional discrimination learning to the derivation of equivalence relations. Prior research has shown that conditional discriminations with simple sample and comparison stimuli are acquired faster than conditional discriminations with complex sample and comparison stimuli. This study attempted to replicate these earlier results and extend them by attempting to relate conditional discrimination learning to equivalence relations. Each of four adult humans learned four, four-choice conditional discriminations (simple-simple, simple-complex, complex-simple, and complex-complex) and were tested to see if equivalence relations had developed. The results confirm earlier findings showing acquisition to be facilitated with simple stimuli and retarded with complex stimuli. There was no difference in outcomes on equivalence tests, however. The results are in implicit agreement with Sidman's theory of stimulus equivalence.

Multiple Sclerosis (MS) is a lifelong progressive neurologic disease of the central nervous system (CNS) that interrupts the flow of information within the brain and between the brain and the body, resulting in a variety of symptoms across the visual, sensory, motor, and autonomic functions. The concept of psychological resilience is emerging in clinical research, including research on MS, as a productive way to view the outcomes and experiences of living with a chronic disease and identify potential protective factors. The purpose of this dissertation was to examine the protective and predictive quality of psychological resilience in various domains of motor functioning. A sample of 130 patients underwent neuropsychological testing along with neurological examination at two distinct time points (baseline and 3-year follow-up). As part of each evaluation, patients were administered various tasks of motor functioning: the two-minute walk test (2MWT; a measure of gait endurance and stamina), timed 25-foot walk (T25FW; a measure of gait speed), nine-hole peg test (NHPT; a measure of upper extremity speed and coordination), grooved pegboard (G-Pegs; a measure of fine motor speed and dexterity), grip strength (Grip; a measure of upper body strength), and finger tapping test (FTT; a measure of simple motor speed), which served as this study’s outcomes. Psychological resilience, the primary predictor of interest, was operationalized as the self-reported ability of adapting well in the face of substantial adversity and significant sources of stress and was estimated using a validated self-report measure the Connor-Davidson Resilience Scale, 10 item version (CD-RISC-10). Additional predictors included mood, fatigue, demographic variables, disease variables, and magnetic resonance imaging (MRI) estimates. In contrast to our hypothesis, psychological resilience and functional outcomes were not correlated. Psychological resilience did not predict change in motor functioning over time and did not serve as a moderator between disease burden and motor functioning. As such, the present study does not provide support for psychological resilience as a protective factor for the motor system in MS or for resilience in predicting differential decline in motor functioning.

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In his book The Crucified God; Jürgen Moltmann argues that the Church’s identity and relevance are intimately tied to what Christian theology has to say about God’s response in Christ – in referring to the meaning of the suffering and crucified Christ for the suffering of humankind and the created order. However the problem of human suffering cannot be approached without becoming aware of how God, in his revelation, becomes involved in a Trinitarian way. The intention is to search for answers to the problem in Jürgen Moltmann’s understanding of the Holy Trinity in its relation to human suffering. The crucified God, in Christ and Christ in God, meets us in our moments and situations of despair and God-forsakenness. When we cry out – Where is God? – and whilst crying out to the unreachable God in our lack of capacity, He reaches down in Trinitarian involvement in our world and in our history. The Trinitarian God reaches down to us in his gracious love, and plants His cross alongside our crosses of pain and destruction. God does that in His unexplainable kindness in our world order of the globalization of extreme evil and total exploitation of everything in God’s created world. The Triune God makes our suffering His suffering, and in His unending love He becomes the crucified God – for us victims and perpetrators. / Dissertation (MA)--University of Pretoria, 2018. / Dogmatics and Christian Ethics / MA / Unrestricted