New insights into ocular blood flow at very high altitudes

Little is known about the ocular and cerebral blood flow during exposure to increasingly hypoxic conditions at high altitudes. There is evidence that an increase in cerebral blood flow resulting from altered autoregulation constitutes a risk factor for acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) by leading to capillary overperfusion and vasogenic cerebral edema. The retina represents the only part of the central nervous system where capillary blood flow is visible and can be measured by noninvasive means. In this study we aimed to gain insights into retinal and choroidal autoregulatory properties during hypoxia and to correlate circulatory changes to symptoms of AMS and clinical signs of HACE. This observational study was performed within the scope of a high-altitude medical research expedition to Mount Muztagh Ata (7,546 m). Twenty seven participants underwent general and ophthalmic examinations up to a maximal height of 6,800 m. Examinations included fundus photography and measurements of retinal and choroidal blood flow, as well as measurement of arterial oxygen saturation and hematocrit. The initial increase in retinal blood velocity was followed by a decrease despite further ascent, whereas choroidal flow increase occurred later, at even higher altitudes. The sum of all adaptational mechanisms resulted in a stable oxygen delivery to the retina and the choroid. Parameters reflecting the retinal circulation and optic disc swelling correlated well with the occurrence of AMS-related symptoms. We demonstrate that sojourns at high altitudes trigger distinct behavior of retinal and choroidal blood flow. Increase in retinal but not in choroidal blood flow correlated with the occurrence of AMS-related symptoms.

Microstructure and Cerebral Blood Flow within White Matter of the Human Brain: A TBSS Analysis.

BACKGROUND White matter (WM) fibers connect different brain regions and are critical for proper brain function. However, little is known about the cerebral blood flow in WM and its relation to WM microstructure. Recent improvements in measuring cerebral blood flow (CBF) by means of arterial spin labeling (ASL) suggest that the signal in white matter may be detected. Its implications for physiology needs to be extensively explored. For this purpose, CBF and its relation to anisotropic diffusion was analyzed across subjects on a voxel-wise basis with tract-based spatial statistics (TBSS) and also across white matter tracts within subjects. METHODS Diffusion tensor imaging and ASL were acquired in 43 healthy subjects (mean age = 26.3 years). RESULTS CBF in WM was observed to correlate positively with fractional anisotropy across subjects in parts of the splenium of corpus callosum, the right posterior thalamic radiation (including the optic radiation), the forceps major, the right inferior fronto-occipital fasciculus, the right inferior longitudinal fasciculus and the right superior longitudinal fasciculus. Furthermore, radial diffusivity correlated negatively with CBF across subjects in similar regions. Moreover, CBF and FA correlated positively across white matter tracts within subjects. CONCLUSION The currently observed findings on a macroscopic level might reflect the metabolic demand of white matter on a microscopic level involving myelination processes or axonal function. However, the exact underlying physiological mechanism of this relationship needs further evaluation.

Application of active heat pulse method with fiber optic temperature sensing for estimation of wetting bulbs and water distribution in drip emitters.

Through the use of the Distributed Fiber Optic Temperature Measurement (DFOT) method, it is possible to measure the temperature in small intervals (on the order of centimeters) for long distances (on the order of kilometers) with a high temporal frequency and great accuracy. The heat pulse method consists of applying a known amount of heat to the soil and monitoring the temperature evolution, which is primarily dependent on the soil moisture content. The use of both methods, which is called the active heat pulse method with fiber optic temperature sensing (AHFO), allows accurate soil moisture content measurements. In order to experimentally study the wetting patterns, i.e. shape, size, and the water distribution, from a drip irrigation emitter, a soil column of 0.5 m of diameter and 0.6 m high was built. Inside the column, a fiber optic cable with a stainless steel sheath was placed forming three concentric helixes of diameters 0.2 m, 0.4 m and 0.6 m, leading to a 148 measurement point network. Before, during, and after the irrigation event, heat pulses were performed supplying electrical power of 20 W/m to the steel. The soil moisture content was measured with a capacitive sensor in one location at depths of 0.1 m, 0.2 m, 0.3 m and 0.4 m during the irrigation. It was also determined by the gravimetric method in several locations and depths before and right after the irrigation. The emitter bulb dimensions and shape evolution was satisfactorily measured during infiltration. Furthermore, some bulb's characteristics difficult to predict (e.g. preferential flow) were detected. The results point out that the AHFO is a useful tool to estimate the wetting pattern of drip irrigation emitters in soil columns and show a high potential for its use in the field.

Molecular Dynamics Simulations of Couette flow

The first steps towards developing a continuum-molecular coupled simulations techniques are presented, for the purpose of computing macroscopic systems of confined fluids. The idea is to compute the interface wall-fluid by Molecular Dynamics simulations, where Lennard-Jones potential (and others) have been employed for the molecular interactions, so the usual non slip boundary condition is not specified. Instead, a shear rate can be imposed at the wall, which allows to obtain the properties of the wall material by means of an iterative method. The remaining fluid region will be computed by a spectral hp method. We present MD simulations of a Couette flow, and the results of the developed boundary conditions from the wall fluid interaction.

Pulsatile blood flow interaction with arterial walls of aorta : autoregulation and impedance pressure boundary condition and its biomedical applications

Para las decisiones urgentes sobre intervenciones quirúrgicas en el sistema cardiovascular se necesitan simulaciones computacionales con resultados fiables y que consuman un tiempo de cálculo razonable. Durante años los investigadores han trabajado en diversos métodos numéricos de cálculo que resulten atractivos para los cirujanos. Estos métodos, precisos pero costosos desde el punto de vista del coste computacional, crean un desajuste entre la oferta de los ingenieros que realizan las simulaciones y los médicos que operan en el quirófano. Por otra parte, los métodos de cálculo más simplificados reducen el tiempo de cálculo pero pueden proporcionar resultados no realistas. El objetivo de esta tesis es combinar los conceptos de autorregulación e impedancia del sistema circulatorio, la interacción flujo sanguíneo-pared arterial y modelos geométricos idealizados tridimensionales de las arterias pero sin pérdida de realismo, con objeto de proponer una metodología de simulación que proporcione resultados correctos y completos, con tiempos de cálculo moderados. En las simulaciones numéricas, las condiciones de contorno basadas en historias de presión presentan inconvenientes por ser difícil conocerlas con detalle, y porque los resultados son muy sensibles ante pequeñas variaciones de dichas historias. La metodología propuesta se basa en los conceptos de autorregulación, para imponer la demanda de flujo aguas abajo del modelo en el ciclo cardiaco, y la impedancia, para representar el efecto que ejerce el flujo en el resto del sistema circulatorio sobre las arterias modeladas. De este modo las historias de presión en el contorno son resultados del cálculo, que se obtienen de manera iterativa. El método propuesto se aplica en una geometría idealizada del arco aórtico sin patologías y en otra geometría correspondiente a una disección Stanford de tipo A, considerando la interacción del flujo pulsátil con las paredes arteriales. El efecto de los tejidos circundantes también se incorpora en los modelos. También se hacen aplicaciones considerando la interacción en una geometría especifica de un paciente anciano que proviene de una tomografía computarizada. Finalmente se analiza una disección Stanford tipo B con tres modelos que incluyen la fenestración del saco. Clinicians demand fast and reliable numerical results of cardiovascular biomechanic simulations for their urgent pre-surgery decissions. Researchers during many years have work on different numerical methods in order to attract the clinicians' confidence to their colorful contours. Though precise but expensive and time-consuming methodologies create a gap between numerical biomechanics and hospital personnel. On the other hand, simulation simplifications with the aim of reduction in computational time may cause in production of unrealistic outcomes. The main objective of the current investigation is to combine ideas such as autoregulation, impedance, fluid-solid interaction and idealized geometries in order to propose a computationally cheap methodology without excessive or unrealistic simplifications. The pressure boundary conditions are critical and polemic in numerical simulations of cardiovascular system, in which a specific arterial site is of interest and the rest of the netwrok is neglected but represented by a boundary condition. The proposed methodology is a pressure boundary condition which takes advantage of numerical simplicity of application of an imposed pressure boundary condition on outlets, while it includes more sophisticated concepts such as autoregulation and impedance to gain more realistic results. Incorporation of autoregulation and impedance converts the pressure boundary conditions to an active and dynamic boundary conditions, receiving feedback from the results during the numerical calculations and comparing them with the physiological requirements. On the other hand, the impedance boundary condition defines the shapes of the pressure history curves applied at outlets. The applications of the proposed method are seen on idealized geometry of the healthy arotic arch as well as idealized Stanford type A dissection, considering the interaction of the arterial walls with the pulsatile blood flow. The effect of surrounding tissues is incorporated and studied in the models. The simulations continue with FSI analysis of a patient-specific CT scanned geometry of an old individual. Finally, inspiring of the statistic results of mortality rates in Stanford type B dissection, three models of fenestrated dissection sac is studied and discussed. Applying the developed boundary condition, an alternative hypothesis is proposed by the author with respect to the decrease in mortality rates in patients with fenestrations.

Analysis of Hyporheic Flow Induced by a Bar in a Gravel Stream: an Experimental Study

Thesis (Master, Civil Engineering) -- Queen's University, 2016-06-01 00:03:02.939

Single-cell ELISA and flow cytometry as methods for highlighting potential neuronal and astrocytic toxicant specificity

The timeline imposed by recent worldwide chemical legislation is not amenable to conventional in vivo toxicity testing, requiring the development of rapid, economical in vitro screening strategies which have acceptable predictive capacities. When acquiring regulatory neurotoxicity data, distinction on whether a toxic agent affects neurons and/or astrocytes is essential. This study evaluated neurofilament (NF) and glial fibrillary acidic protein (GFAP) directed single-cell (S-C) ELISA and flow cytometry as methods for distinguishing cell-specific cytoskeletal responses, using the established human NT2 neuronal/astrocytic (NT2.N/A) co-culture model and a range of neurotoxic (acrylamide, atropine, caffeine, chloroquine, nicotine) and non-neurotoxic (chloramphenicol, rifampicin, verapamil) test chemicals. NF and GFAP directed flow cytometry was able to identify several of the test chemicals as being specifically neurotoxic (chloroquine, nicotine) or astrocytoxic (atropine, chloramphenicol) via quantification of cell death in the NT2.N/A model at cytotoxic concentrations using the resazurin cytotoxicity assay. Those neurotoxicants with low associated cytotoxicity are the most significant in terms of potential hazard to the human nervous system. The NF and GFAP directed S-C ELISA data predominantly demonstrated the known neurotoxicants only to affect the neuronal and/or astrocytic cytoskeleton in the NT2.N/A cell model at concentrations below those affecting cell viability. This report concluded that NF and GFAP directed S-C ELISA and flow cytometric methods may prove to be valuable additions to an in vitro screening strategy for differentiating cytotoxicity from specific neuronal and/or astrocytic toxicity. Further work using the NT2.N/A model and a broader array of toxicants is appropriate in order to confirm the applicability of these methods.

Autonomic dysfunction and systemic oxidative stress associated with glaucomatous optic neuropathy

There were four principal sections to the work: 1. Investigation of ocular and systemic vascular risk factors in POAG. The principal findings of this work were: a). Glaucoma patients exhibit an anticipatory reaction to the physical stress, similar to subjects at risk for cardiovascular diseases; a blunted BP response and a reduction in ONH blood flow in response to cold provocation was also recorded. b). Silent myocardial ischaemic episodes occurred during peaks in systemic BP and HR. c). Independent of a positive history for cardiovascular diseases, patients suffering from POAG demonstrate a blunt circadian rhythm of the ANS. 2. Assessment of the relationship between vascular and systemic vascular risk factors in GON. The principal findings of this work were: a). POAG patients demonstrate a high sympathetic tonus over a 24-h period. b). POAG patients with lower OBF demonstrate both 24-h systemic BP and HRV abnormalities. c). OBF alterations observed in some glaucoma patients could be either primary or secondary to systemic haemodynamic disturbances and not a consequence of ONH damage. 3. Assessment of the level of systemic anti-oxidant defence in POAG patients. The principal finding of this work was: Patients suffering from POAG demonstrated significantly lower GSH and t-GSH levels than normal controls. 4. Investigation of the effect of treatment with latanoprost 0.005% on visual function and OBF. The findings of this work were: a). Treatment with latanoprost 0.005% resulted in a significant decrease in IOP and increase in OPP. VF damage progression has also been stopped. b). Treatment with latanoprost 0.005% resulted in a significant increase in the OBF parameters measured at the ONH and peripapillary retina levels. Finally, the importance of a clear protocol for managing new POAG cases is highlighted and a clinical conduit is proposed.

Topographic, haemodynamic and psychophysical investigation of glaucomatous optic neuropathy

Loss of optic nerve head (ONH) axons in primary open angle glaucoma (POAG) has been attributed to both mechanical and vascular factors. Confocal scanning laser ophthalmoscopy (cSLO) provides a promising tool for the topographic follow-up of the ONH in glaucoma, while scanning laser Doppler flowmetry (SLDF) facilitates the rapid non-invasive assessment of retinal capillary blood flow. The purposes of these investigations were to optimise the techniques and explore their potential to classify and monitor disease. Preliminary investigations explored the reproducibility and validity of cSLO and SLDF and showed that: For cSLO: In a model eye, measurements are accurate over a range of axial lengths. For best reproducibility, seven images per visit are required, with a contour line located on Elschnig's scleral ring and transferred automatically between images. For SLDF: Three perfusion images are required for optimum reproducibility. Physiological changes induced by gas perturbation can be measured. Cross-sectional comparison of groups of normal subjects and early POAG patients showed that: cSLO parameters differentiate the early POAG group. Blood volume measured by SLDF showed group differences in superior nasal retina only. Longitudinal investigation of ONH topography, haemodynamic and visual field indices in normal subjects and POAG patients showed that: cSLO detects topographical change over time more frequently in the POAG group. Important parameters include: C:D area ratio, cup and rim area, mean depth in contour, volumes above and below reference and surface. Factor analysis identified "cup" and "rim" factors that can be used to detect change over time in individual patients. Blood flow changes were most apparent in the inferior nasal peripapillary retina of the POAG group. Perimetry is of clinical value for the identification of glaucoma but is less sensitive than cSLO for monitoring glaucomatous change.

Regional variation in peripapillary retinal blood flow in primary open angle glaucoma:a follow-up study

Purpose: To investigate whether regional long-term changes in peripapillary retinal flow, measured by scanning laser Doppler flowmetry (SLDF), occur in patients with primary open angle glaucoma (POAG). Methods: 31 healthy volunteers (mean age: 65 8.3 years) and 33 POAG patients (mean age: 71.2 7.6 years) were followed up every 4 months for 16 months. Using SLDF, three images of the superior and inferior optic nerve head were obtained for each subject. A 1010-pixel frame was used to measure blood flow, volume and velocity in the four quadrants of the peripapillary retina. Central 24-2 visual field testing was carried out at each visit. Repeated measures analysis of covariance was used to assess change over time between the normal and POAG groups for the SLDF parameters. Univariate linear regression analysis for mean deviation and glaucoma change probability (GCP) analysis were used to identify visual field progression. Results: Blood volume, flow and velocity measured in the inferior nasal quadrant of the peripapillary retina decreased significantly over time for the POAG group compared to the normal group (p=0.0073, 0.0097, 0.0095 respectively). Overall, 2 glaucoma patients showed a significantly deteriorating MD slope, while 7 patients showed visual field progression with GPA. All of the patients progressing with GPA, showed change in the superior hemifield and, of those, 14% showed change in the inferior hemifield. Conclusion: Glaucoma patients showed a decrease in blood flow, volume and velocity in the inferior nasal peripapillary retina. A regional variation in microvascular retinal capillary blood flow may provide insight into the pathogenesis of glaucomatous optic neuropathy. Keywords: 331 blood supply • 554 retina • 624 visual fields

Field data, numerical simulations and probability analyses to assess lava flow hazards at Mount Etna

Improving lava flow hazard assessment is one of the most important and challenging fields of volcanology, and has an immediate and practical impact on society. Here, we present a methodology for the quantitative assessment of lava flow hazards based on a combination of field data, numerical simulations and probability analyses. With the extensive data available on historic eruptions of Mt. Etna, going back over 2000 years, it has been possible to construct two hazard maps, one for flank and the other for summit eruptions, allowing a quantitative analysis of the most likely future courses of lava flows. The effective use of hazard maps of Etna may help in minimizing the damage from volcanic eruptions through correct land use in densely urbanized area with a population of almost one million people. Although this study was conducted on Mt. Etna, the approach used is designed to be applicable to other volcanic areas.

ANALYSIS OF HYPORHEIC FLOW INDUCED BY A BAR IN A GRAVEL STREAM: AN EXPERIMENTAL STUDY

Pipelines are one of the safest means to transport crude oil, but are not spill-free. This is of concern in North America, due to the large volumes of crude oil shipped by Canadian producers and the lengthy network of pipelines. Each pipeline crosses many rivers, supporting a wide variety of human activities, and rich aquatic life. However, there is a knowledge gap on the risks of contamination of river beds due to oil spills. This thesis addresses this knowledge gap by focussing on mechanisms that transport water (and contaminants) from the free surface flow to the bed sediments, and vice-versa. The work focuses on gravel rivers, in which bed sediments are sufficiently permeable that pressure gradients caused by the interactions of flow with topographic elements (gravel bars), or changes in direction induce exchanges of water between the free surface flow and the bed, known as hyporheic flows. The objectives of the thesis are: to present a new method to visualize and quantify hyporheic flows in laboratory experiments; to conduct a novel series of experiments on hyporheic flow induced by a gravel bar under different free surface flows. The new method to quantify hyporheic flows rests on injections of a solution of dye and water. The method yielded accurate flow lines, and reasonable estimates of the hyporheic flow velocities. The present series of experiments was carried out in a 11 m long, 0.39 m wide, and 0.41 m deep tilting flume. The gravel had a mean particle size of 7.7 mm. Different free surface flows were imposed by changing the flume slope and flow depth. Measured hyporheic flows were turbulent. Smaller free surface flow depths resulted in stronger hyporheic flows (higher velocities, and deeper dye penetration into the sediment). A significant finding is that different free surface flows (different velocities, Reynolds number, etc.) produce similar hyporheic flows as long as the downstream hydraulic gradients are similar. This suggests, that for a specified bar geometry, the characteristics of the hyporheic flows depend on the downstream hydraulic gradients, and not or only minimally on the internal dynamics of the free surface flow.

Analysis of friction factor reduction in turbulent water flow using a superhydrophobic coating

This study provides experimental and theoretical evidence that the coating of the inner surface of copper pipes with superhydrophobic (SH) materials induces a Cassie state flow regime on the flow of water. This results in an increase in the fluid's dimensionless velocity distribution coefficient, a, which gives rise to an increase in the apparent Reynolds number, which may approach the "plug flow state". Experimental evidence from the SH coating of a classic unsteady-state flow system resulted in a significant decrease in the friction factor and associated energy loss. The friction factor decrease can be attributed to an increase in the apparent Reynolds number. The study demonstrates that the Cassie effects imposed by SH coating can be quantitatively shown to decrease the frictional resistance to flow in commercial pipes.

A two-fluid model for tissue growth within a dynamic flow environment

We study the growth of a tissue construct in a perfusion bioreactor, focussing on its response to the mechanical environment. The bioreactor system is modelled as a two-dimensional channel containing a tissue construct through which a flow of culture medium is driven. We employ a multiphase formulation of the type presented by G. Lemon, J. King, H. Byrne, O. Jensen and K. Shakesheff in their study (Multiphase modelling of tissue growth using the theory of mixtures. J. Math. Biol. 52(2), 2006, 571–594) restricted to two interacting fluid phases, representing a cell population (and attendant extracellular matrix) and a culture medium, and employ the simplifying limit of large interphase viscous drag after S. Franks in her study (Mathematical Modelling of Tumour Growth and Stability. Ph.D. Thesis, University of Nottingham, UK, 2002) and S. Franks and J. King in their study Interactions between a uniformly proliferating tumour and its surrounding: Uniform material properties. Math. Med. Biol. 20, 2003, 47–89). The novel aspects of this study are: (i) the investigation of the effect of an imposed flow on the growth of the tissue construct, and (ii) the inclusion of a chanotransduction mechanism regulating the response of the cells to the local mechanical environment. Specifically, we consider the response of the cells to their local density and the culture medium pressure. As such, this study forms the first step towards a general multiphase formulation that incorporates the effect of mechanotransduction on the growth and morphology of a tissue construct. The model is analysed using analytic and numerical techniques, the results of which illustrate the potential use of the model to predict the dominant regulatory stimuli in a cell population.

Effects of flow regulation in the life-cycles of a mediterranean cyprinid species, the Iberian chub (Squalius carolitertii Doadrio, 1987)

Streamflow is considered a driver of inter and intra‐specific life‐history differences among freshwater fish. Therefore, dams and related flow regulation, can have deleterious impacts on their life‐cycles. The main objective of this study is to assess the effects of flow regulation on the growth and reproduction of a non‐migratory fish species. During one year, samples were collected from two populations of Iberian chub, inhabiting rivers with non‐regulated and regulated flow regimes. Flow regulation for water derivation promoted changes in chub’s condition, duration of gonad maturation and spawning, fecundity and oocyte size. However, this non‐migratory species was less responsive to streamflow regulation than a migratory species analysed. Findings from this study are important to understand changes imposed by regulated rivers on fish and can be used as guidelines for flow requirements implementations; RESUMO: O caudal é um dos fatores responsáveis pelo funcionamento dos ciclos de vida das espécies piscícolas dulciaquícolas. As barragens, e a regularização de caudal associada, podem ter impactes nos ciclos de vida destas espécies. O objetivo deste estudo prende‐se com a avaliação dos efeitos da regularização de caudal no crescimento e reprodução de uma espécie piscícola não‐migradora. A análise de amostras recolhidas em populações de escalo do Norte provenientes de dois rios de caudal regularizado e não regularizado, identificaram impactes significativos a nível da condição corporal, da maturação das gónadas e desova, da fecundidade e da dimensão dos oócitos. Esta espécie não‐migradora parece ser menos responsiva à artificialização do caudal que uma espécie migradora previamente analisada. Estes resultados permitem compreender as alterações impostas pela regularização do caudal e podem ser usados em programas de reabilitação fluvial.