Placenta is a transient association of the fetal and maternal tissues, that develops during pregnancy, in most viviparous animals. The evolution of placenta ensured the development of the fetus inside the womb of the mother, providing a protected environment for the development of the fetus, and preventing the loss of progeny due to unfavorable environmental conditions. Because it is strategically poised at the maternal and fetal interface, the placenta is ideally suited to carry out alimentary, respiratory and excretory functions for the developing fetus. In addition, it serves as an immunological barrier preventing the rejection of the fetal semi-allograft, by the maternal immune system. Furthermore, the placenta elaborates a variety of protein, polypeptide and steroid hormones. These include growth factors, growth factor receptors, neuropeptides, opioids, progesterone and estrogen, whose secretion is dependent on the gestational age of the placenta and its differentiation status. The human placenta, adapts itself remarkably to cater to the changing requirements of the developing fetus. For instance, during the first trimester of pregnancy, the placenta is an actively dividing, a highly invasive and a rapidly differentiating organ; while near term, it represents a fully differentiated and a non-invasive unit. Furthermore, the placenta of the first trimester and that at term differ in their hormone profiles, extents of apoptosis, expression of several transcription factors, etc. This dramatic change in the phenotype of the human placenta can be considered to be the outcome of an intrinsically programmed pattern of differentiation, which may be referred to as the functional differentiation of the placenta. It may be hypothesized therefore, that this functional differentiation could be brought about by the differential expression of genes in the first trimester and the term placenta. The objectives of the present study were: 1. To gain an insight into this process of " functional differentiation” by investigating the differential expression of genes in the two developmentally distinct stages during gestation, viz. during the first trimester and at term. 2. To understand the functional relevance of the differentially expressed genes. A general introduction of the human placenta, describing the importance of differential expression in modulating placental function, is discussed in chapter 1. The functions of the human placenta along with a brief description of its development and differentiation are also briefly described. A Differential Display RT-PCR-based (DD RT-PCR) approach, using total RNA from the first-trimester and term placental villi, was employed to display the differentially expressed genes in the first trimester and the term placenta. The display so generated was used to identify a few differentially expressed cDNAs. This study was aimed at understanding the functional significance of the transcripts which were identified from the display, rather than just concentrate on documenting the differences in the gene expression patterns in the first trimester and the term placental tissue. A detailed description of the methodology adopted for performing DD-PCR using placental tissue, discussing the advantages and disadvantages of using differential display PCR, is described in chapter2. The use of DD-PCR for studying differential gene expression in the human placenta was validated by the finding that one of the cDNAs that was differentially expressed in the first trimester placental tissue, is a fragment of β-hCG cDNA. It is well documented that the differential expression of the β-subunit of hCG (human chorionic gondatrophin) during the first eight weeks of gestation is the rate limiting step in the synthesis and secretion of the functional hormone, which comprises the α and the β-subunits. Furthermore, the use of the model system viz., the first trimester and term placental tissue, was also validated for carrying out DD-PCR by ensuring that all placental samples used for DD analysis were free of endometrial contamination. A detailed description of optimization and validation of DD-PCR in human placental tissues is given in chapter 2. Cloning and sequencing of yet another cDNA from the first trimester differential display revealed that it is T-Plastin. T-Plastin is a member of a family of proteins that are involved in actin-bundling. Northern blot analysis and immunohistochemical studies using an antibody generated to a peptide corresponding to human T-Plastin, confirmed its differential expression and localization in the first trimester placenta. Considering the fact that several carcinomas show enhanced expression of T-Plastin, we tested the hypothesis that its differential expression is correlated with the proliferative potential of the first-trimester placenta It was observed that the first-trimester tissue expressed high levels of beta-actin as compared to the term placental tissue. This is in agreement with the up-regulation of beta-actin following mitogenic stimulation/proliferation and during neoplastic transformation or transformation-associated invasive behaviour of cells, two characteristic features shared by the early placenta with cancerous tissues. Based on our studies and available information in the literature, it is proposed that T-Plastin expression in the first trimester placenta is a growth-associated phenomenon which is partially responsible for the tumor-like phenotype of the first trimester tissue. Studies carried out with the partial T-Plastin cDNA clone that was isolated from the first trimester differential display, are presented in chapter 3. Sequencing of yet another cDNA clone identified from the term placental differential display, T-18 revealed that it had no homology to any known sequence in the nucleotide or est databases. The sequence corresponding to this clone was submitted to the GenBank and was assigned an accession number- AF089811. The differential expression of T-18 was confirmed by Northern blot analysis and RT-PCR analysis. Attempts were made to isolate the full-length cDNA corresponding to T-18 from a commercially available library from Clontech. However, repeated trials to identify the clone corresponding to T-18 did not yield any positive results. However, a genome database search revealed that T-18 was a portion of a large contig contained in chromosome 15. Analysis of the annotated gene sequences in and around the region in which T-18 is located in chromosome 15, revealed that there are very few ests reported in this contig and quite a few repeat sequences reported. Interestingly, it was observed that 6 kb downstream of the region in which T-18 is located, there was an est that had homology to a Bcl-2 precursor protein (an evolutionarily conserved, anti-apoptotic protein, capable of conferring protection against death-inducing signals) and the death adaptor protein, CRADD {Caspase and RIP adapter with death domain). Further updating of the ests in the database might probably be of help in the identification of the full-length cDNA corresponding to T-18 and confirm as to whether T-18 is a part of the gene/gene cluster that comprises the afore-mentioned est. An account of the identification and cloning of T-18 from the term placenta and the attempts to isolate the full-length cDNA clone corresponding to T-18 from a term placental cDNA library, is described in chapter 4. In the absence of any information on the identity of T-18, a study to understand the functional significance of T-18 expression was carried out. Since it was not possible to carry out studies pertaining to the temporal expression of T-18 throughout gestation on the human placenta for ethical reasons, alternate animal/organ models were employed to study T-18 expression. Rat placenta and rat Corpus Luteum (CL) were chosen as alternate models for studying T-18 expression as these two organs/tissues underwent dynamic changes in their function throughout pregnancy. For instance, it is well known that CL is the primary source of progesterone for maintaining pregnancy in the rat and that the progesterone secreting capacity of the luteal cells peak on day 16 of gestation and decline thereafter. Interestingly, a common feature among all the tissues that were chosen for investigating the regulation of T-18 expression, is the fact that they underwent apoptosis with increase in gestational age. The expression of T-18, in tissues exhibiting increased incidence of apoptosis suggested that T-18 maybe an apoptosis-associated gene. Using an explant culture model it was demonstrated that placental villi when cultured in vitro underwent spontaneous apoptosis and that the levels of T-18 message increased, under these conditions. Furthermore, this spontaneous induction of apoptosis in explant cultures could be blocked when villi were cultured in the presence of superoxide dismutase, a free radical scavenging enzyme. In addition, the expression of T-18 was shown to be modulated following treatment with SOD, or in response to oxidative stress. These studies clearly indicate a role for T-18 in placental apoptosis and moreover, implicate the usefulness of explant culture to examine the molecular mechanisms involved in placental apoptosis. Furthermore, the expression of the anti- and pro-apoptotic genes, bcl-x and bax respectively, were investigated, in an attempt to elucidate the signalling pathway(s) that led to the activation of an important downstream protease, caspase-3, in placental apoptosis. The present study revealed that induction of apoptosis in the placenta in vitro involved a bcl/bax independent, caspase-3 dependant pathway. The validation of an explant culture model for studying placental apoptosis and data pertaining to the role of T-18, bcl-x, bax and CPP32 in placental apoptosis, in response to oxidative stress, are presented in chapter 5. The last section titled general discussion summarizes the work carried out in this study and proposes a model for the apoptotic mechanism(s) that may be operating in placenta In conclusion, the present study has led to the identification of two developmentally-regulated factors, T-Plastin and T-18 in the first trimester and term placenta, respectively. The differential expression of these genes, in addition to several other molecular players, is proposed to be responsible for the overall functional differentiation of the placenta through the course of gestation.

Spermatogenesis is a complex process of male germ cell development in which the diploid spermatogonia undergo series of mitotic divisions and differentiation steps culminating into the preleptotene spermatocytes which then enter into the meiotic prophase following a single replication cycle. This phase is characterized by meiotic recombination and is followed by reduction division resulting in haploid round spermatids. These cells then undergo extensive morphological and nuclear changes to form a unique cell, spermatozoa. This entire germ cell differentiation process occurs in a unique environment present inside the seminiferous tubules which is created by the Sertoli cells, the somatic cells in the tubules by forming junctions with each other thus providing unique milieu to the developing germ cells. Within the tubule, the germ cells are also arranged in an orderly manner called stages of spermatogenesis indicating a complex mechanism of germ cell differentiation. This complex differentiation process is a consequence of developmentally and precisely regulated differential gene expression (Eddy, 2002). Unraveling the molecular mechanisms involved in the male germ cell development is an uphill task due to the complexity of the cyto-architecture existing in the tubules and further complicated by unavailability of established germ cell lines and lack of cell culture systems that facilitate the germ cell differentiation in vitro. Comparative gene expression analysis of spermatogenesis in nematodes, flies and rodents revealed highly conserved transcriptomes and have provided some insights into its regulation (Schlecht and Primig, 2003). However, these data fail to represent the genetic and biological complexity of human spermatogenesis. In the present study, an attempt has been made to identify the genes that are differentially expressed in human tetraploid and haploid germ cells and to investigate the mechanism of regulation of the genes expressed in the post-meiotic germ cells. To identify the cell type specific genes, expression profiling of the human tetraploid and haploid germ cells was carried out using cDNA microarray. These cells were purified by centrifugal elutriation (Meistrich et al., 1981; Shetty et al., 1996) from the human testicular tissues obtained from the patients undergoing orchidectomy as treatment for prostate cancer. Purity of the enriched population of the germ cells was ascertained by DNA flow cytometry and by RT-PCR analysis using the known cell-specific markers and ruling out contamination of the somatic cells such as the Sertoli cells and the Leydig cells. Microarray experiments were carried out with the RNA isolated from each cell type and labeling the cDNA with Cy3/Cy5-dUTP and hybridizing to the human 19K array chip (University Health Network, Toronto, Canada) containing 19,200 ESTs. Two independent hybridizations were carried out using the germ cells isolated from two individuals and the microarray data were analyzed using Avadis 3.1 software (Strand Life Sciences, India). Analysis of the microarray data following normalization revealed that 723 transcripts showed higher expression in the meiotic cells whereas 459 transcripts showed higher expression in the post-meiotic germ cells. Microarray data were validated further by RT-PCR analysis of some of the differentially regulated genes. The DAVID analysis (Database for Annotation, Visualization and Integrated Discovery; http://david.abcc.ncifcrf.gov/) of these genes revealed that many genes associated with diverse functions and pathways appeared to be differentially expressed in both cell types. It is known that many biological systems exhibit distinct temporal gene expression profiles during different processes related to cell cycle, stress response and differentiation. Similarly, there are sets of genes, which respond to specific stimuli, appear to be synchronized in their expression. Such ‘synexpressed’ genes have been shown to be regulated by common transcription regulatory processes and have similar upstream transcription factor binding sites (Niehrs and Pollet, 1999). And therefore, having identified genes that appeared to be differentially expressed in the haploid and the tetraploid germ cells, attempt was made to analyze transcription factor binding sites in the promoter of those genes. In silico promoter analysis of several genes showing higher post-meiotic expression was carried out in order to identify the common regulatory motifs. Analysis of the annotated promoters (available from Eukaryotic Promoter Database; http://www.epd.isb-sib.ch/) of about forty genes highly expressed in the post-meiotic germ cells using TFSEARCH program (http://www.cbrc.jp/ research/db/TFSEARCH.html) confirmed that many genes had common transcription factor binding sites. Interestingly, almost all of the analyzed genes harbored SRY (Sex determining Region in Y)/SOX (SRY-box containing) binding motifs. In addition, the promoters of genes such as Protamine 1 and 2, Transition protein 1 and 2, A kinase (PRKA) anchor protein 4 that are known to be expressed post-meiotically, also harbor SRY binding sites suggesting that SRY may be one of the key regulators of the post-meiotic gene expression. SRY is a HMG-box containing member of Sox-family of architectural transcription factors. SRY is encoded by the Y chromosome and was first discovered as the testis-determining factor in mammals (Koopman et al., 1991). SRY HMG-box is eighty amino acids conserved motif that binds to the minor groove of the DNA in a sequence-dependent manner resulting in its bending and thus regulating the gene expression. The RT-PCR analysis of the human haploid and tetraploid germ cells showed very high expression of SRY in the post-meiotic cells further suggesting key role of SRY in the post-meiotic gene regulation. Role of SRY in the post-meiotic gene expression was investigated by determining the effect of SRY on human Protamine 1 (PRM1) promoter, a gene known to be exclusively expressed in the round spermatids and as indicated above, harbors many SRY binding sites in its promoter. SRY cDNA was cloned into the mammalian expression vector, pcDNA3.1 and the PRM1 promoter was cloned into the promoter-less pGL3 Basic vector upstream of the Luciferase reporter gene. Co-transfection of both constructs led to up-regulation of PRM1 promoter activity in both HeLa cells and LNCaP cells in a dose-dependent manner clearly demonstrating the role of SRY in PRM1 gene expression. Sequential deletion of the SRY binding sites in the PRM1 promoter led to the identification of the critical SRY binding motif important for SRY-mediated upregulation of PRM1 gene expression. This was confirmed by demonstrating in vitro binding of SRY to its critical binding site in the PRM1 promoter by gel shift assay using the nuclear extract of the HeLa cells transfected with FLAG-tagged SRY. The human SRY is an atypical transcription factor that binds DNA through its HMG, but unlike the mouse Sry and other Sox proteins, lacks the trans-activation domain and therefore requires other factors for its actions. Recently, the glutamine-rich, zinc-finger containing transactivator, Specificity protein 1 (Sp1) has been identified as one such interacting partner (Wissmuller et al., 2006). RT-PCR analysis showed that human SP1 is highly expressed in the haploid germ cells and could up-regulate PRM1 expression which harbors two SP1 binding sites in its promoter. When co-transfected, SRY and SP1 up-regulated PRM1 promoter in co-operative manner suggesting that SP1 may act in coordination with SRY in regulating PRM1. All these data taken together clearly signifies a critical role of SRY in post-meiotic germ cell gene expression. Recent reports suggest that SRY is also expressed in the adult human brain and prostate. However, its role in these tissues is not clearly understood. The Y chromosome has been shown to be frequently lost in prostate cancer and has also been shown to suppress the tumorigenicity of the PC-3 prostate cancer cells suggesting that the Y chromosome encoded genes may be involved in tumor suppression. SRY can physically interact with the androgen receptor (AR) and thereby interfere in its downstream signaling (Yuan et al., 2001). Since the prostate tumors show initial androgen-dependency, it was interesting to look at the role of SRY in the prostate cancer. To decipher the effect of SRY on the androgen-responsive LNCaP cells, stable clones of LNCaP expressing human SRY were generated. These clones showed significant decrease in growth in response to 5α-dihydrotestosterone (DHT) compared to the vector transfected or the parental LNCaP cells. In the soft agar colony formation assay, the SRY expressing LNCaP formed smaller colonies as compared to the controls in presence of DHT. Preliminary experiments in male athymic nude mice demonstrated that one of the SRY expressing clones showed reduced tumor growth compared to control cells suggesting that SRY may play a role in prostate cancer progression by decreasing the sensitivity to DHT. To summarize, the present study has identified several genes differentially expressed in the human haploid and tetraploid germ cells and further showed that SRY may be one of the key regulators of the post-meiotic gene expression.

Thesis (MSc. (Human Physiology, Faculty of Health Sciences))--University of Pretoria, 2008. / Summary in English. Includes bibliographical references.

No abstract available. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Durban, 2005.

No description available.

The thesis deals with car cabin environment and thermal comfort inside. A car cabin heat load model was developed in Dymola/Modelica to investigate influence of ambient environmental parameters. The model was validated on the data set of eight test cases measured in a climatic chamber and in a real traffic. The main objective of the thesis was to develop a human thermal comfort model suitable for non-homogenous environments and for a car cabin environment especially. The Coupled model of human physiology and thermal comfort was developed in Dymola/Modelica. The model allows predicting an overall human thermal comfort from local boundary conditions representing ambient and personal factors. The model was validated by 16 test cases taken from experiments in literature. Moreover three test cases were created in Theseus-FE to consider an asymmetrical heat load from Sun rays inside a car cabin. Prediction of the Coupled model was compared with Fiala model and experimental data. The Coupled model predicted mean skin temperature for moderate activities in neutral and warm environment well. In cold environment a predicted core temperature was very affected by ambient temperature and during high activity exercises, the predicted mean skin temperature was too high.

Les modèles actuels de prédiction de la sensation thermique et du confort thermique ainsi que les solutions visant à améliorer l’état de bien-être thermique des occupants d’un bâtiment sont insuffisants. Ils ne prennent pas assez en compte les différences interindividuelles de jugement thermosensoriel. Pourtant, ces différences, souvent associées à la sensibilité thermique de chaque individu, existent mais restent inexpliquées sur le plan physiologique. Ces travaux de thèse, qui se sont déroulés en deux étapes, ont pour objectif d'identifier les causes physiologiques potentielles des différences interindividuelles du ressenti thermique, à travers des expérimentations multiparamétriques basées sur des mesurées cutanées. Toutes les mesures ont été réalisées après 30 minutes d’acclimatation en environnement thermique contrôlé. La première étape, exploratoire, a permis d’analyser à la fois l’activité neurosensorielle, les propriétés thermo-vasculaires et les propriétés du film hydrolipidique cutané de deux groupes présentant des sensibilités au froid distinctes (selon leur sensation thermique déclarée). Ainsi, les expérimentations ont montré qu’il était plus pertinent d’analyser davantage les propriétés cutanées thermiques et hydriques (reliées aux mécanismes de thermorégulation) plutôt que l’activité neurosensorielle des volontaires pour caractériser les différences interindividuelles de jugement thermosensoriel. Elles ont également mis en évidence la nécessité de contrôler les facteurs non thermiques des environnements et de sélectionner rigoureusement les sujets. La deuxième étape s’est focalisée sur l’analyse des propriétés thermo-vasculaires et des propriétés du film hydrolipidique de deux groupes de sensibilité au froid. Pour cela, 13 femmes ont été confrontées à 6 environnements de températures modérées comprises entre 17°C et 30°C (avec 2 transitions chaudes et 2 transitions froides) et les groupes ont été construits à partir du degré de frilosité déclaré par les sujets. Des différences sur les paramètres cutanées ont alors pu être relevées entre les deux groupes. Le résultat le plus significatif est que les individus dits « frileux » présentent une activité microcirculatoire plus intense sur les joues avec une vasoconstriction plus forte au froid et une vasodilatation plus forte au chaud que l’autre groupe « non sensible au froid » (p=0,002 d’après le test de l’ANCOVA pour l’effet des groupes). De plus, il a été montré que l’approche multiparamétrique (introduction de variables non thermiques comme variables prédictives) ainsi que la prise en compte des sensibilités thermiques individuelles améliorent la prédiction du confort thermique surtout pour le groupe « frileux » (+ 6,4 %). / Current models for predicting thermal sensation and thermal comfort as well as the solutions to improve the state of thermal well-being of the occupants of a building are insufficient. They do not sufficiently take into account interindividual differences of thermosensory judgment. However, these differences, often associated with thermal sensitivity of each person, exist but remain unexplained physiologically. This work, divided into two stages, is intended to identify the potential physiological causes of interindividual differences of thermal feeling through multiparametric experiments based on skin measurements. All measurements were performed after 30 minutes of acclimatization in controlled environment. The exploratory phase allowed to analyze both neurosensory activity, thermo-vascular properties and properties of the skin hydrolipidic film of two groups with different cold sensitivities (depending on their declared thermal sensation). For example, experiments have shown that it was more appropriate to analyse thermal and hydric skin properties (related to thermoregulation mechanisms) rather than neurosensory activity of volunteers to characterize interindividual differences of thermosensory judgment. They have also highlighted the need to control the non-thermal factors of environments and rigorously select subjects. The second step focused on the analysis of thermo-vascular properties and properties of the hydrolipidic film of two groups of different cold sensitivity. Thirteen women have faced in 6 environments of moderate temperatures between 17 ° C and 30 ° C (with 2 warm transitions and 2 cold transitions). Groups were built according to their degree of cold sensitivity. Differences in skin parameters have been found between the two groups. The most significant result is that cold-sensitive individuals have a more intense microcirculatory activity on cheeks with a stronger vasoconstriction in cold environments and a stronger vasodilation in warm environement than the non cold-sensitive group (p = 0. 002 according to ANCOVA test for groups effect). In addition, it has been shown that the multi-parametric approach (introduction of non-thermal parameters as predictors) as well as taking into account individual thermal sensitivities improve the prediction of thermal comfort especially for the cold-sensitive group (+ 6.4%).

La thérapie par compression médicale est reconnue comme une composante essentielle dans le traitement des pathologies veineuses et demeure incontournable dans la prise en charge des affections veineuses aux différents stades de la pathologie (jambes lourdes, œdèmes, ulcères). Si le bénéfice est reconnu par les patients eux-mêmes ainsi que par les médecins, il n’existe à l’heure actuelle que peu d’éléments permettant de quantifier ce bénéfice. Dans ce contexte, l’objectif de ces travaux de thèse est d’apporter des éléments de compréhension et d’objectiver les effets bénéfiques des bas médicaux de compression (BMC) aux niveaux physiologique, neurophysiologique et comportemental. Trois axes de recherche ont été dégagés. Le premier axe de recherche est l’étude de l’effet de la compression sur l’activité microcirculatoire cutanée dans les membres inférieurs en utilisant le dispositif Hématron, dispositif ambulatoire exclusif d’évaluation de l’activité microcirculatoire cutanée. Les résultats ont montré une amélioration de l’activité microcirculatoire pour différentes classes de BMC et pour différentes positions. Ces résultats tendraient à mettre en cause l’hypothèse, largement admise, que les BMC améliorent le retour veineux principalement en diminuant la section des veines (superficielles voire profondes). La deuxième piste de recherche concerne l’objectivation de l’amélioration de la qualité de vie liée au port des BMC, généralement exprimée subjectivement par les personnes atteintes de pathologie veineuse. Les résultats préliminaires montrent que l’analyse de la variabilité cardiaque permet de mettre en évidence une relation entre le paramètre indicateur de l’activité de la balance sympatho-vagale et le port de la compression médicale au cours d’une journée. Compte tenu de la grande dispersion des résultats, cette étude serait à poursuivre sur une population plus large pour aboutir à des conclusions fiables. Le dernier axe de recherche est lié à l’impact du port des BMC sur le comportement du sujet et plus précisément sur sa déambulation. Les patients déclarent une fatigue physique dans les membres inférieurs moins intense en fin de journée grâce à la compression médicale. Notre hypothèse est que le port des BMC impacterait directement la dynamique de la déambulation. Pour évaluer la cinétique de la marche, nous avons conçu, développé et validé une instrumentation intégrant des capteurs accéléromètres. Des tests préliminaires ont permis de dégager des paramètres pertinents caractéristiques de la déambulation. La prochaine étape sera de conduire une campagne d’expérimentation destinée à objectiver la fatigue comportementale en fin d’après-midi mesurée avec ou sans compression médicale portée au cours de la journée. / Medical compression therapy is recognized as an essential component in the treatment of venous diseases and is indispensable in the treatment of venous diseases at different stages of the disease (heavy legs, edema and ulcers). Although the benefit is recognized by the patients themselves and by physicians, there is at present little evidence to quantify this benefit. Against this background, the aim of this thesis is to provide more understanding and objectify the benefits of compression stockings (MCS) on in terms of physiology, neurophysiology and gait dynamics. Three areas of research were identified and studied. The first line of research is the study of the effect of compression on skin microcirculatory activity in the lower limbs using the Hematron ambulatory device. The results showed an improvement in skin blood flow activity for different classes of MCS and at different positions. These results would tend to challenge the widely accepted assumption that MCS improve venous return primarily by decreasing the cross-sectional area of (superficial or deep) veins. The second line of research involves the objectification of the improvement in the quality of life resulting from the wearing of MCS, usually this is expressed subjectively by people with venous disease. Preliminary results show that the analysis of heart rate variability highlights a relationship between the indicators of sympathovagal balance activity and the use of medical compression during the day. Given the wide dispersion in the results, this study should be carried out on a larger population to draw more reliable conclusions. The last line of research relates to the impact of MCS on the behavior and, in particular, the gait of the subject. Patients report that physical fatigue in the lower limbs is less prevalent at the end of the day with compression therapy. Our hypothesis is that the wearing of MCS has a direct impact on gait. To evaluate the kinetics of walking, we have designed, developed and validated an instrumentation involving accelerometers sensors. Preliminary tests have yielded relevant parameters characteristic of gait dynamics. The next step is to conduct an experimental campaign to objectify behavioral fatigue, with or without the wearing of medical compression, at the end of the afternoon.

Les maladies chroniques impliquant le système respiratoire nécessitent un suivi sur la durée. L’activité physique et les paramètres cardiovasculaires sont essentiels pour ces pathologies. Nous nous sommes intéressés en particulier à la BPCO et à l’apnée obstructive du sommeil. La BPCO est caractérisée par un cercle vicieux d’inactivité : une gêne respiratoire entraîne une diminution de l’activité, qui elle-même augmente la gêne respiratoire par désentraînement. Le monitoring de l’activité, en lien avec la SpO2 est donc essentiel pour cette pathologie. Les désaturations nocturnes sont un paramètre cardinal de l’apnée du sommeil. Un actimètre permet d’évaluer la qualité du sommeil, complétant ainsi le suivi de cette pathologie. De plus, l’activité diurne est un indicateur de l’asthénie provoquée par le syndrome. Le but de ce travail a donc été la mise au point d’un actimètre communicant, capable de mesurer l’activité diurne, d’évaluer le temps de sommeil et de s’interfacer avec un oxymètre de pouls pour synchroniser la collecte de données. À partir des données récoltées durant 26 jours d’enRégistrements, nous avons mis au point et évalué un algorithme permettant de mesurer le temps passé assis, debout et allongé. Cet algorithme a été conçu pour être embarqué dans un microcontrôleur, ayant des ressources de calcul limitées. Nous avons également proposé un algorithme de détection des pas, dont le fonctionnement a été validé sur plus de 5 heures de marche, sur 22 patients différents, contre un comptage manuel. Nous avons enfin proposé une méthode de détection des transitions assis-debout pour l’instrumentation du test de levers de chaise de 3 minutes. Lors de l’analyse nocturne, nous avons mis au point un algorithme de détection du temps de sommeil, testé sur 25 nuits. Nous avons également proposé une méthode d’analyse de l’onde de pouls permettant d’extraire le rapport LF/HF de la variabilité cardiaque, permettant de détecter le sommeil paradoxal. Nous avons montré le résultat de l’agrégation des différentes données acquises par le système formé de l’actimètre et de l’oxymètre lors d’une nuit d’examen, comme outils à disposition du praticien. L’actimètre mis au point dans le cadre de ces travaux et les méthodes d’analyse du signal associées sont adaptés au suivi non invasif de pathologies respiratoires. Ils peuvent également être intégrés à un système de télémédecine via une passerelle informatique pour un suivi de long terme. / Chronic diseases affecting the respiratory system require a long-term monitoring. Physical activity and cardiovascular parameters are essential in those pathologies. We focused on two of those diseases : COPD and obstructive sleep apnea. COPD is characterized by a downward cycle of inactivity : a respiratory impairment leads to a reduction of activity, whose in turn worsen the respiratory impairment by a conditioning loss. As a consequence, activity monitoring and SpO2 are essential for the monitoring of this pathology. Nocturnal oxygen desaturation are a main feature of sleep apnea. An actimeter allows for sleep quality evaluation, and is a logical choice for a complementary measure of this disease. Moreover, diurnal activity is an indicator of the degree of physical weakness that can occur as a consequence of sleep apnea. The main goal of the work has been the developement of a connected actimeter, able to monitor diurnal activity, estimate the duration of sleep and collect data from a pulse oximeter to synchronise the data. From 26 days of accelerometric measures, we designed and validated an algorithm that compute the time spend sitting, standing and lying. This algorithm has been designed to be embedded in a microcontroler with limited computing power. We also proposed a step detection algorithm validated on 5 hours of walking, on 22 different patients, against a visual count. Finally, we designed a method to detect the sitting-standing change of posture to monitor the 3-minutes chair stand test. On the nocturnal aspect, we designed an algorithm used to estimate the sleep duration during a night. It as been tested on 25 nights. We also proposed a pulse wave analysis method to extract the LF/HF ratio of cardiac variability, to detect REM sleep. We showed the result of the aggregation of the different parameters collected by the system composed of the actimeter and the oximeter during a monitored night, as a tool to the healthcare professional. The actimeter design in the context of this work and the associated signal processing methods are appropriate to the monitoring of respiratory pathologies with a light equipment. They also can be integrated into a telemedecine system through a gateway computer, allowing for a long-term monitoring.

Head stabilisation during gait related tasks is thought to be fundamental to whole body stability, but this has received little attention in the older population. There is a need to examine any age related changes in neuromechanical mechanisms underpinning head stabilisation that may challenge the control of head stability, and consequently whole body stability. The present Thesis examined the mechanisms contributing to head stabilisation, and whole body stability during two gait tasks, steady state gait and gait initiation in young and older females, with the overall aim of contributing to negating fall risk. Four studies were designed to examine a) head position and walking speed on gait stability during steady state gait; b) neuromechanical mechanisms underpinning head stabilisation during gait initiation; c) head position on whole body stability during gait initiation; and d) head stabilisation during gait initiation at different speeds. Results showed that a) gait stability, was unaffected by head position and different walking speeds during steady state gait, b) decreased head stability in older individuals during gait initiation can be attributed to a deterioration of the neuromechanical mechanisms relating to head stability, c) free head movement during gait initiation does not affect head stabilisation or whole body stability but it does affect gait parameters, while d) initiating gait at faster than comfortable speeds compromises head stabilisation and reduces whole body stability in older individuals. Collectively, these results demonstrate that older individuals adopt an increased head flexion position when walking, while impaired head stability can be attributed to deterioration of the function of their neuromechanical mechanisms compared to their younger counterparts during gait tasks at comfortable speeds. These findings provide an understanding of the effect head stabilisation can have on older adults’ gait and on their fall risk during gait and gait initiation.