Patients with pulmonary arterial hypertension (PAH) often require parenteral prostanoids to improve symptoms and signs of PAH. Complications of parenteral prostanoids-such as catheter-related infections and intolerable adverse effects-may develop, prompting transition to inhaled prostanoids. We report a prospective, protocol-driven transition from parenteral prostanoids to inhaled prostanoids with monitoring of exercise gas exchange and acute hemodynamics. Three PAH centers recruited patients transitioning from parenteral prostanoids to inhaled trepostinil. Rigid inclusion criteria were used, including parenteral prostanoid dose < 30 ng/kg/min, New York Heart Association functional class (FC) < 3, and pulmonary vascular resistance (PVR) < 6 Wood units. Of the 9 patients meeting initial inclusion criteria, 3 were excluded. In the remaining patients, the parenteral prostanoid was reduced and the inhaled prostanoid was increased over 24-36 hours with continuous hemodynamic monitoring. Exercise capacity and FC were measured at baseline and weeks 1, 4, and 12. All patients were successfully weaned from parenteral prostanoids. An acute PVR decrease was seen with most inhaled prostanoid doses, but PVR varied throughout the transition. Patients tolerated inhaled prostanoids for 9-12 breaths 4 times a day with no treatment-limiting adverse events. At week 12, FC was unchanged, and all patients continued to receive inhaled prostanoids without serious adverse events or additional PAH therapy. In 5 of 6 patients, 6-minute walk distance and peak VO2 were within 10% of baseline. Using a strict transition protocol and rigid patient selection criteria, the parenteral prostanoid to inhaled prostanoid transition appeared safe and well tolerated and did not result in clinical deterioration over 12 weeks. Hemodynamic variability noted acutely during transition in our study did not adversely affect successful transition.

Ce mémoire de doctorat s'inscrit dans le cadre de la conception du diagnostic de la boucle d’air d’un moteur Diesel de l’entreprise PSA Peugeot Citroën. Pour des systèmes complexes, comme les moteurs Diesel, la recherche des tests de cohérence qui permettront de faire le diagnostic n'est pas évidente. La méthode d'Analyse Structurelle est utilisée afin de faciliter cette recherche, car elle permet au concepteur d’un système de diagnostic de disposer d'informations qui l'assistent dans son travail, à savoir la connaissance du potentiel de diagnostic, et la définition exhaustive des possibilités de tests de cohérence. Ce mémoire présente des algorithmes efficaces d’Analyse Structurelle permettant la maîtrise de l'explosion combinatoire des algorithmes actuels. Cet objectif est atteint par une simplification du processus d’analyse : les tests de cohérence renvoyés par les algorithmes développés possèdent de bonnes propriétés de calculabilité d'une part, et offrent un bon potentiel de discrimination des défauts d'autre part. Cette simplification provient de l’intégration de critères de calculabilité et d’un cahier des charges dans les algorithmes actuels. Les algorithmes développés sont intégrés dans un outil logiciel permettant d’analyser les modèles Simulink, et illustrés sur deux cas d’application. Le second cas d’application présenté dans ce mémoire est un modèle interne PSA Peugeot Citroën de boucle d'air du moteur DV6C TED4. Une analyse structurelle permet de construire, des indicateurs discriminant deux défauts d’encrassement, et ainsi, d'augmenter la couverture des diagnostics embarqués et débarqués. / This PHD thesis is a contribution to the design of the diagnosis system of the air path of a PSA Peugeot Citroën Diesel engine. For complex systems, as Diesel engines, searching for the consistency tests which are relevant for diagnosing faults is not obvious. The Structural Analysis method is used in order to make this search easier, for it provides a system's diagnosis designer with information, such as : the diagnosis potential of the system, and the exhaustive definition of consistency tests. This thesis describes efficient structural analysis algorithms, which help manage the complexity of current algorithms. This objective is met thanks to the simplification of the analysis process : the consistency tests returned by the developed algorithms have good properties of computability, and possess good fault isolability potential. This simplification comes from the integration of calculability constraints and of diagnosis requirements into current algorithms. Developed algorithms are integrated into a software allowing to analyze Simulink models, and are illustrated thanks to two application cases. The second application case presented in this thesis is a PSA Peugeot Citroën internal model describing a Diesel engine air path. A structural analysis yields indicators discriminating two types of clogging, and thus allows tto improve the diagnosis coverage of Diesel engines.

Les eaux du Golfe du Mexique (GOM) jouent un rôle important dans le systéme climatique global car elles Intluencent les propriétés hydrologiques du Gulf Stream (GS), courant océanique chaud de surface faisant partie Intégrante de la circulation thermohaline (THC). Au cours du dernier cycle climatique, d'énormes écoulements d'eau douce, provenant de la fonte de la calotte Laurentide sur le continent-nord américain, se sont déversées au sein du GOM. moditiant ses caractéristiques hvdrologlques et donc celles du GS. Ces perturbations auraient pu, en altérant la THC, affecter le systéme climatique. La compréhension des transferts entre le continent nord-américain et le GOM au cours du dernier cycle climatique s'avére donc primordiale. En connaissant les principales sources continentales, les facteurs influençant le transport (réalisation de cartes de répartition des minéraux argileux sur le continent nord-américain et dans les sédiments du GOM) et la sédimentation (par modélisation analogique) du matériel terrigéne fin, l'étude des enregistrements sédimentaires (minéralogie des argiles, granulométrie ) et isotopiques ([delta]18O) de deux bassins du nord du GOM (Bassins d'Orca et d'Humphrey) a permis d'appréhender les transferts entre le continent nord-américain et le GOM au cours du dcrnier cycle climatique. La variabilité des apports détritiques du Mississippi et des fleuves du sud-ouest des États-Unis a pu être reliée aux variations paléo-environnementales (fonte de la calotte Laurentide et des glaciers des Montagnes Rocheuses) et paléoclimatiques (modifications des transferts d'humidité depuis le GOM vers le continent) qui affectent le continent nord-américain / The Gulf of Mexico (GOM) is a key area for the global thermohaline circulation (THC) and for the global-climatic system, since its hydrological characteristics (hlgh salinity and temperature) partly control Gulf Stream physical properties. Dunng the last climatic cycle, GOM hydrology was impacted by episodic freshwater inputs via the Mississippi River resulting from intermittent meltmg of the Laurentide Ice Sheet (LIS). The resulting salinity changes affected the THiC. global heat exchange and worldwide climatie conditions. Direct effeets of these freshwater supplies on the GOM paleoceanography have been documented studying the planktonic foraminifera [delta]18O evolution By contras!. terrigenous inputs associated with these meltwater pulses are poorly understood. These detrital fractions are. however. IIkeiv to provide information on the link between continental and marine records during the last climatic cycle. An overview of the main continental detrtital source areas, of the dominant factors controlling clav minerai transport patterns (by drawing clay minerai distribution maps in the US and northem GOM) and of thin terrigenous particle sedimentation in the GOM (by analogical modeIing), lays the groundwork for the use of clay-minerai assembiages for understanding the connection between North America and the GOM. The downcore investigations of sedimentary (clay mineralogy, grain-slze . .) and isotopic ([delta]18O) records ln two minibasins of the GOM (Orca Basin and Basin 4) allow us to explain the fluvial inputs variations, during the last climatic cycle, by paleoenvironmental (ice meltback) and paleocllmatic (atmospheric circulation) fluctuations that affected North America

In spite of the extreme thinness of the avian pulmonary blood-gas barrier (PBGB), it is remarkably strong. To understand the basis of the remarkable strength of the avian PBGB, network of collagen connective tissue that form the lung’s parabronchial fibrous framework and type-IV collagen, a principal component of the basement membrane was investigated in the BGB and in the epithelial-epithelial contacts between the air capillaries in the domestic fowl, Gallus gallus variant domesticus. Techniques of discriminatory staining, selective alkali digestion, vascular casting followed by alkali digestion and immunoelectron microscopy were used. Abundant collagen fibers of the interparabronchial septa, which form part of the tunica adventitia of the interparbronchial vessels, firmly interconnect adjacent parabronchi directly and indirectly (via intraparabronchial vessels). Peripherally, the intraparabronchial artery, with its tunic of collagen fibers, enters and penetrates the exchange tissue mantle. The collagen fibers around the vessel decrease in quantity as it divides into blood capillaries. From the luminal side, the projection of the parabronchial lumen into the exchange tissue mantle as the atria, the infundibulae and the air capillaries, in this order, carry collagen covering which reduces in quantity with each division. The three-dimensional interactions between blood capillaries from the peripheral part and air capillaries from the central lumen allow contact formation between blood capillaries, air capillaries and between air- and blood capillaries. Collagen fiber continuum starting from the interparabronchial septa runs through the exchange tissue by following the three contacts sites and terminates at the parabronchial lumen. At the periphery, the collagen fibers constitute a conspicuous bundle. Within the exchange tissue mantle, the collagen forms diffuse complex interconnections of thin fibers. Towards the parabronchial lumen and within interatrial septa, the thinner collagen fibers of the exchange tissue mantle aggregate to form thick bundles which bind to the connective tissues surrounding the parabronchial muscles. Based on the structural arrangements and function of the smooth muscle, the collagen- and the elastic tissue fibers, and structures like the interparabronchial septa and their associated blood vessels, it was envisaged that: dynamic- tension and compressive forces exist in a parabronchus to form a tensegrity (tension integrity) system. The tensegrity arrangement imparts rigidity to a parabronchus while strengthening the air and the blood capillaries. Mechanical interdependence between parabronchi and between air- and blood capillaries allows efficient transmission and redistribution of tension. The tortuous course of the collagen fiber continuum that follows the three-dimensional intertwining of the gas exchange units- from septa to the lumen- ensures that tension does not travel a straight course and as such, any extrinsic or intrinsic force applied to the structure is transmitted away from the point of origin. Graded exercise intensities and perfusion at different pressures on the integrity of the BGB were used to determine the condition under which the blood-gas barrier in the avian lungs fails. Number of red blood cells and protein concentration in the harvested lung lavage fluid were estimated in the exercised chickens. For histological analysis, numbers of epithelial-epithelial (E-E) breaks and blood-gas barrier (BGB) breaks were counted in each of the four vascular regions of the lung in both the exercised and the perfused lungs. Post exercise blood lactate analysis showed a 4-fold increase between rest and maximal exercise (2.95 m/s) while the numbers of red blood cells and protein concentration increased steadily with increasing exercise intensity, however, the degree of increments appeared to decrease at higher workloads. The two kinds of breaks occurred at all levels of exercise and in the resting birds but at any exercise intensity, there were more E-E breaks than BGB breaks. The numbers of breaks increased with increasing exercise intensity and the difference between the two types of breaks decreased with increasing exercise intensity. In resting birds, there were no breaks in the area of the lung supplied by the cranial branch of the PA. In the exercised birds, differences in number of blood-gas barrier breaks among the four vascular territories only occurred at 0.66 m/s where the lowest and highest counts occurred in the cranial- and caudomedial regions respectively, whereas at all other levels of exercise, the numbers of breaks were comparable. Presence of red blood cells in the lungs of resting birds indicated that failure of the blood-gas barrier might be a common but inconsequential event in the avian lung. A positive linear relationship exists between the perfusion pressure and the numbers of both E-E and blood-gas barrier breaks. At all perfusion pressures, there are more E-E breaks than BGB breaks. The difference between the two types of breaks decreased with increasing pressure. At any perfusion pressure, more breaks occurred in the regions supplied by the accessory- and caudomedial branches of the PA than in the regions supplied by the cranial- and the caudomedial ones. This could be because the pressures in the two blood vessels may be higher since the caudomedial branch is the most direct continuation of the PA while the accessory branch is the narrowest and the first to originate from the PA. Because of the extreme thinness of the blood-gas barrier and unavoidable puncturing of air sac when the thorax is accessed to cannulate the pulmonary vessels, the exact pressure at which the BGB fails could not be ascertained since both types of failure occurred at all perfusion pressures. However, separation of the epithelial-epithelial contacts, caused by distension of the blood capillaries, started appearing at the perfusion pressure of 2.89kPa. This may represent the pressure at which the blood-gas barrier starts to fail.

by Dai Kang Sheng. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1989. / Bibliography: leaves 127-130.

Ocean circulation is a fundamental component of the Earth's climate system. The Atlantic thermohaline circulation, driven by deep convection at high latitudes, has a central role in regulating European climate through its transport and redistribution of heat. Either directly or indirectly, Mediterranean Water (MW) provides the high salinities found in the Nordic Seas which are required to precondition for deep convection. The precise mechanisms and pathways remain undetermined and yet are fundamental to understanding the effect that any change in the Mediterranean Outflow may have on circulation and ultimately on climate. This thesis investigates the transport of MW in the North Atlantic Ocean using hydrographic and model data. The primary objective is to quantify how much MW flows northwards and how much flows westwards from its source in the Gulf of Cadiz. Two boxes (Med Boxes) were constructed using hydrographic sections in the eastern North Atlantic enclosing the Strait of Gibraltar and Mediterranean Outflow. Inverse methods were used to determine the velocity field from which volume transports and salt fluxes were calculated. The main northward flow of MW across 41°N occurs east of 12°W, at depths of 500 to 1500 m, and transports 50 to 75% of the MW. An advective westward pathway across 20°W transports MW at similar depths into the ocean interior between 35°N and 40°N. Insignificant salt fluxes across the southern section (24°N) at MW depths confirm that no MW crosses the southern Med Box boundary. The net overturning circulation of the Med Box, with inflowing surface waters and outflowing intermediate waters, is attributed both to the exchange at the Strait of Gibraltar and also to water mass transformation associated with entrainment of North Atlantic Water into the Mediterranean Outflow. The magnitude of the circulation provides an estimate of this entrainment of 1.6 ± 0.6 Sv, within the Med Box boundaries. For comparison with these observational estimates, the model used is OCCAM, a level model from the Ocean Circulation and Climate Advance Modelling Project. The primary reason for choosing this model is that experiments have been undertaken with the Strait of Gibraltar both open and closed, enabling a new approach to the investigation of MW transport. MW is identified using the salinity difference between the two model experiments. Although the model circulation (in the open-Strait run) has a similar net overturning to the hydrography, different MW transport pathways are observed. A weak and variable northward pathway along the Iberian Peninsula and a strong southwestward flow from the Gulf of Cadiz result in a higher proportion of MW flowing westwards (61%) than northwards (39%). Seasonal variability is observed, with maximum westward flow in Autumn (70%) and minimum in Spring (50%). There is no evidence in the model that the northward boundary current provides a direct route for Mediterranean salt to reach the Nordic Seas.

Numerical simulation of the January and July global climate with the OSU two-level atmospheric general circulation model has generated time series of the global distribution of selected climatic variables. Analyses of these data for the kinetic energy and available potential energy based on 31-day time mean statistics have been made in the form of the zonal mean and the transient and stationary eddies. The generation and dissipation rates of the various forms of energy in this model are also computed, and the energy cycle for January and July is presented in comparison with the corresponding results from observation and from other models. / Graduation date: 1980

The thesis examines the applicability of a two-dimensional flow acceleration model to describe a terrain-induced flow perturbation as measured at Yaquina Head on the central Oregon coast. The geometry of Yaquina Head together with the upstream wind values were used in estimating hilltop winds. These estimates compare well with the observed wind values. A second method to estimate the hilltop winds was attempted by developing a mean ratio of Yaquina Head winds to the upstream Yaquina South Jetty winds. This ratio was taken from one winter's data and used to estimate the next winter hilltop winds. The same upstream wind values were used with this method as were used with the geometric model. Statistical evaluation in the form of regression analysis was performed to determine the ability of the geometric and statistical models to estimate the hilltop wind on Yaquina Head. It was found that both models did reasonably well but that neither model was appreciably better than the other. / Graduation date: 1979

Graduation date: 1984

Thesis (M.S.)--Oregon Graduate Center, 1981.