Baroreflex sensitivity (BRS) is often reduced in elderly populations and patients with chronic cardiovascular diseases leading to a concomitant rise in blood pressure variability (BPV) that is associated with increased cardiovascular related morbidity and mortality. Thus, there is a need to better understand the mechanisms by which BPV causes cardiovascular end-organ damage. Animal studies using sinoaortic denervation (SAD) to increase BPV have demonstrated pathologic changes in the structure of the heart and blood vessels; however, there is a paucity of data investigating changes in functional measures of the heart and smaller, resistance type arteries. Furthermore, the pathogenic mechanisms involved in BPV-induced cardiovascular end-organ damage remain unknown. Baroreceptor denervation results in multiple cardiac stressors, many of which are associated with production of reactive oxygen species. Oxidative stress is known to promote cardiovascular end-organ damage but it is unclear if it plays a role in models of increased BPV. Thus, this study was designed to investigate the functional responses of smaller resistance type arteries and the heart to chronic exposure to enhanced BPV. In addition, the role of oxidative stress on these functional responses in a normotensive rat model of increased BPV was also investigated. Rats were subjected to either SAD surgery or a sham procedure and were observed for six weeks. To determine the role of oxidative stress, SAD rats were either treated with the superoxide dismutase mimetic tempol or left untreated. During the observation period, mean blood pressure remained normotensive, whereas baroreflex sensitivity was reduced and BPV increased two to three fold. Weekly in vivo assessment of vascular function of the long posterior ciliary artery (LPCA) demonstrated a significant reduction in endothelial-dependent dilation starting three weeks after SAD surgery compared to the sham group. Endothelial-independent dilation was not affected by SAD. Structural changes were not evident in the LPCA following SAD. However, structural (wall thickness, wall area, and wall area/lumen area ratio) and functional (strain and distensibility) changes were observed in the aorta. Cardiac structural (hypertrophy) and functional (diastolic dysfunction) effects were also evident following six weeks of increased BPV. Antioxidant treatment with tempol did not have any effect on the SAD-induced increase in BPV or decrease in BRS. Nevertheless, chronic tempol treatment prevented or reduced the cardiovascular end-organ damage (endothelial-dependent vascular dysfunction, decreased aortic distensibility, cardiac and vascular hypertrophy, and cardiac dysfunction) observed in the untreated SAD group. These findings suggest that the pathology observed following SAD is at least partly mediated by oxidative stress. Antioxidant treatment in patients with increased BPV (e.g., hypertension, diabetes, heart failure) may prevent or ameliorate cardiovascular end-organ damage and reduce the overall risk for cardiovascular disease events.

L’objectif de cette thèse est de savoir si au delà d’une préférence linguistique et sociale pour leur langue natale et leurs usagers, les bébés de moins de 6 mois s’impliquent dans les rythmes et opportunités dialogiques des langues. Nous avons choisi d’étudier les comportements communicatifs du bébé âgé de 4-5 mois car cet âge représente une période charnière pour l’intégration de la compétence communicative. D’une part, le « turn-taking » est encore une forme prédominante d’interaction et d’autre part, les bébés de cet âge s’orientent encore principalement vers les partenaires sociaux plutôt qu’exclusivement vers les objets. Cette période est souvent considérée comme celle qui précède l’enculturation ou l’apprentissage culturel. Pourtant, dès 5 mois, le bébé se comporte différemment face à un interlocuteur de langue natale et de langue étrangère et face à un interlocuteur familier et nouveau. Cette thèse comporte 3 études visant à mieux comprendre l’engagement social du nourrisson dans des situations de communication réelle et habituelle et de communication potentielle. La première étude porte sur les différences dans l’organisation du turn-taking vocal entre les contextes français et brésilien. La seconde étude a pour objectif de mettre en lumière les différentes modalités que le bébé peut utiliser lors du turn-taking, au cours des pauses entre les énoncés maternels. Dans la 3ème étude, la seule étude expérimentale, nous avons cherché à savoir si un bébé français aurait des attentes différentes lorsqu’il était face à une interlocutrice parlant le français par rapport à une interlocutrice parlant une langue étrangère (brésilienne en l’occurrence). Dans son ensemble, cette thèse constitue également un plaidoyer pour une approche intégrative de la communication chez les bébés, s’éloignant d’une vision dualiste dans laquelle on sépare le corps de la pensée, le familier du nouveau et l’inné de l’acquis pour aller vers une vision plus holistique de l’humain. / The main objective of this thesis is to find out whether, beyond linguistic and social preferences for their native language and its users, infants younger than 6 months become involved with the rhythms and dialogical opportunities of speech. We chose to study the communicative behavior of infants aged 4 to 5 months because this constitutes a pivotal period for the integration of communicative competence. On the one hand, turn-taking is still a predominant type of organization in social interaction, and on the other hand, infants at this age are still more interested in social partners than in solitary object exploration. Furthermore, this period is usually thought to precede enculturation or the possibility of cultural learning. Yet, by 5 months, infants behave differently with a native language speaker than with a foreign language speaker and with a familiar person than with a stranger. This thesis includes 3 studies aimed at gaining insight into the social engagement of infants in situations of real and potential communication with social partners. The first study focuses on differences in vocal turn-taking organization between Brazilian and French cultural contexts. The second study’s aim is to shed light on the various expressive modalities infants use responsively in both cultural contexts during pauses between maternal utterances. In the third study, which is experimental, we wanted to know whether a French infant would have different expectations when faced with a French-speaking interlocutor compared with an interlocutor speaking a foreign language (Brazilian in this case). Overall, this thesis also makes a case for a more integrative approach to the study of infant communication, away from a dualist vision separating the body from thought, familiarity from novelty and innate from learned behavior and moving towards a more holistic perspective on humans beings.

The ketogenic diet is commonly used to control epilepsy, especially in cases when medications cannot. The diet typically consists of high fat, low carb, and adequate protein and produces a metabolite called acetoacetate. Seizure activity is characterized by glutamate excitotoxicity and therefore glutamate regulation is a point of research for control of these disorders. Acetoacetate is heavily implicated as the primary molecule responsible for decreasing glutamate in the synapse; it is believed that acetoacetate interferes with the transport of glutamate into the synaptic vesicles. The effects on synaptic transmission at glutamatergic synapses was studied in relation to the ketogenic diet in Drosophila larvae for this thesis. Various measures of synaptic transmission were conducted. Acetoacetate decreased neurotransmission at the synapse. It was also found that acetoacetate has direct effects on the postsynaptic membrane, which indicates a novel role for the metabolite.

Global climate change is projected to impact multiple levels of biodiversity by imposing strong selection pressures on existing populations, triggering shifts in species distributions, and reorganizing entire communities. The Lower Guineo-Congolian region in central Africa, a reservoir for amphibian diversity, is predicted to be severely affected by future climate change through rising temperatures and greater variability in rainfall. Geospatial modelling can be used to assess how environmental variation shapes patterns of biological variation – from the genomic to the community level – and use these associations to predict patterns of biological change across space and time. The overall goal of this dissertation is to examine potential impacts of climate change on amphibian diversity in central Africa. Geospatial modeling is used to: 1) map the distribution of the amphibian fungal pathogen, Batrachochytrium dendrobatidis (Bd) in a biodiversity hotspot in Cameroon under current and future climate; 2) assess phenotypic and adaptive genomic variation in a widespread frog species, Phrynobatrachus auritus, in order to predict areas where populations may best adapt under climate change; 3) determine how amphibian community composition may shift with climate change and which areas may experience greatest loss of functional groups. Findings show that most Bd samples belong to a globally hypervirulent lineage. However, areas of highest predicted environmental suitability for Bd are predicted to shrink under warming temperatures. Within P. auritus, most phenotypic and genomic turnover occurred across known ecological gradients and are heavily influenced by seasonal precipitation. Current amphibian beta diversity is greatest throughout the Cameroonian highlands and forest-savanna ecotones flanking the central Congolian lowland forests. Greatest shifts in community composition under climate change are predicted to occur in coastal Cameroon and its eastern border whereas the greatest predicted loss of functional richness was in central Gabon. Overall, this dissertation shows that areas of elevated environmentally-associated phenotypic, genomic, and community turnover are associated with key ecological gradients. Regions predicted to experience high genomic mismatch, large shifts in community composition, and high loss of functional richness resulting from climate change may warrant conservation attention.

Understanding migratory connectivity is essential for assessing the drivers behind population dynamics and for implementing effective management in migratory species. Genetic markers provide a means to describe migratory connectivity, as well as incorporate population genetic analyses, however genetic markers can be uninformative for species with weak genetic structure. In this study, we evaluate range-wide population genetic structure and migratory connectivity in the prothonotary warbler, Protonotaria citrea, a wetland-dependent neotropical migratory songbird, using high-resolution genetic markers. We reveal regional genetic structure between sampling sites in the Mississippi River Valley and the Atlantic Seaboard with overall weak genetic differentiation among populations (FST = 0.0051). By ranking loci by FST and using subsets of the most differentiated genetic markers (200 – 3000), we identify a maximum assignment accuracy (89.7% to site, 94.3% to region) using 600 single nucleotide polymorphisms. We assign samples from unknown origin nonbreeding sites to a breeding region, illustrating weak migratory connectivity between prothonotary warbler breeding and nonbreeding grounds. Our results highlight the importance of using high-resolution markers in studies of migratory connectivity with species exhibiting weak genetic structure. Using similar techniques, studies may begin to describe population genetic structure that was previously undocumented, allowing us to infer the migratory patterns of an increasing number of species.

Isovaleric Acid (IVA) is a 5-carbon branched chain fatty acid present in fermented foods and produced by the fermentation of leucine by colonic bacteria. IVA activates G-protein coupled receptors such as FFAR2, FFAR3, and OR51E1 known to be expressed on enteric neurons and enteroendocrine cells. We previously reported that the shorter, straight chain fatty acids acetate, propionate and butyrate, differentially affect colonic propulsion; however, the effect of branched chain fatty acids on gastrointestinal motility is unknown. We hypothesize that IVA relaxes smooth muscle in a cAMP/PKA dependent manner by direct action on smooth muscle cells. IVA will also decrease peristalsis and encourage retention of luminal contents. This thesis investigates the effect of IVA on smooth muscle tension and peristaltic activity in isolated colon and individual smooth muscle cells. Colon segments from C57BL/6J mice were placed in a longitudinal orientation in organ baths in Krebs buffer and fastened to force transducers. Segments were contracted with 10 μM acetylcholine (ACh) and the effects of IVA at several concentrations were measured in the absence and presence of Nitric Oxide Synthase inhibitor L-N-nitroarginine (L-NNA), neuronal action potential inhibitor tetrodotoxin (TTX), and adenylate cyclase inhibitor SQ22536. To study individual live cells, mouse smooth muscle was isolated from colon, suspended in smooth muscle buffer, and after contraction with ACh were relaxed with micromolar concentrations of IVA. For peristalsis studies, whole colonic segments isolated from C57BL/6J were catheterized and placed horizontally in organ baths with circulating Krebs buffer. The colon was clamped on the anal end, and a solution (5 μL per mm of colon length) of either Krebs buffer or 50 mM IVA was delivered from the oral end to the lumen. Video of the peristalsis was then analyzed for diameter, changes in diameter, velocity of diameter changes along the length of the colon, normalized to the anatomical changes in the proximal region. IVA in concentrations of 10 mM to 50 mM relaxed the ACh-induced contraction in a sigmoidal fashion. In separate studies, L-NNA nor TTX affected the ability of IVA to inhibit relaxation. SQ22536 inhibited IVA induced relaxation in longitudinal colon compared to vehicle control. In isolated cells, SQ22536 and PKA inhibitor H-89 inhibited IVA-induced relaxation. In peristalsis studies, 50 mM IVA in Krebs buffer changed the character of the peristaltic action by increasing proximal diameter, inhibiting contractions in the proximal end of the colon, and decreasing overall velocity of peristaltic contractions in the proximal region. The data indicate that the branched chain fatty acid IVA causes a concentration-dependent relaxation of colonic smooth muscle that is direct to the smooth muscle and independent of neuronal activity. This relaxation is cAMP/PKA dependent. In addition to the direct relaxation of smooth muscle, intraluminal IVA decreased overall colonic propulsive activity and encouraged retention of the luminal contents. We conclude that the ingestion and production of branched chain fatty acids could affect overall GI motility and is an area for study in dietary and therapeutic control of bowel activity.

Intuitive prosthetic control is limited by the inability to easily convey intention and perceive physical requirements of the task. Rather than providing haptic feedback and allowing users to consciously control every component of manipulation, relegating some aspects of control to the device may simplify operation. This study focuses on the development and testing of a control scheme able to identify object stiffness and regulate impedance. The system includes an algorithm to detect the apparent stiffness of an object, a proportional nonlinear EMG control algorithm for interpreting a user’s desired grasp aperture, and an antagonistically acting impedance controller. Performance of a testbed prosthetic simulation used to controllably extrude pastes of different properties from a compliant tube was compared to that of the non-dominant human hand. The paste volume extrusion error and response time to perform the task were recorded for comparison. Statistical analysis using (GEE) and (TOST) suggests the prosthetic controller and human hand performed similarly along these metrics. Performance differences in the trials were more strongly correlated to tube type and repetition block. The results suggest that the developed controller allows users to perform a controlled squeezing task at a level comparable to the human hand with minimal training. It also suggests that a priori stiffness estimation acquired through quick palpations may be sufficient for effective control during simple manipulation. The lack of a learning curve suggests that the development of systems that automatically control aspects of mechanical interaction may offer users more advanced control capabilities with low cognitive load.

Breast cancer is one of the leading causes of morbidity and mortality among women. A diagnosis of cancer is a stressful event that requires an individual to adapt to new stressors. The purpose of this qualitative study was to better understand the perceptions of mana'olana/hope and living with breast cancer among Native Hawaiian women. The conceptual framework of this phenomenological study was positive psychology. Data collection included in-depth interviews with 5 Native Hawaiian women who had been diagnosed with breast cancer. Data coding and analysis resulted in identification of 8 themes. The themes included: (a) mana'olana /hope is the essence of my being, (b) family strengthens me and gave me mana'olana/hope, (c) my relationship with God and Jesus promoted mana'olana/hope in me, (d) my religious affiliation promoted mana'olana/hope in me, (e) the cancer support group promoted mana'olana/hope in me, (f) the cancer treatment team promoted mana'olana/hope in me, (g) treatment options; Allopathic, Osteopathic, Naturopathic, Alternative medicine, and herbal remedies promoted mana'olana/hope in me, and (h) nature's beauty and the arts promoted mana'olana/hope in me. Results may be used by health psychologists, cancer treatment practitioners, and the field of biobehavioral oncology to support and improve the well-being and health outcomes of women diagnosed with breast cancer.

Objective: From a patient-centered perspective, this study sought to explore cancer patient experiences using integrative health techniques, while undergoing or after having completed conventional cancer therapy. Methods: Recruitment and data collection both occurred within the Supportive Care Medicine Department of a comprehensive cancer center in the southeastern United States. The primary collection method was semi-structured interviews, of which 13 were conducted. Results: Patients using integrative therapies experienced a variety of physical and mental/emotional benefits from their chosen therapy, such as management of lymphedema and nerve damage, increased mobility, and improved self-confidence. Conclusion: Integrative therapies can provide many benefits to patients in mitigating treatment side effects and other cancer related symptoms. CAM practitioners themselves played an important role in post-treatment cancer support; both by acting as a health educator and by administrating the therapy itself.

<p>Alongside the complementary and alternative medicine movements, a new concept is emerging: integrative medicine. Though more and more authors have begun to use this term, they use it to refer to widely varying concepts of health care. This study begins with a theoretical look at integration and continues with an examination of current integrative efforts. These general discussions are followed by the presentation of the situation in Sweden, and at the Vidarklinik in particular. Finally the study turns to an empirical study investigating the communication between the Vidarklinik and the outside biomedical system. The research suggests a much more comprehensive picture of integrative medicine than those put forward by most authors and finds that to create and maintain an integrative system, all the levels of health care must be actively engaged in the system and the entire spectrum of care must be coordinated for the patient. Attempts at integration are found in diverse local efforts, which are all limited by lack of cooperation between different levels of health care. The study of communication at the Vidarklinik in Sweden illustrates that communication is crucial between all levels of health care in order for even relatively localised efforts in integration, and further that various factors limit whom various individuals and groups can communicate with, while in-person dialogue mitigates some of these factors.</p>