Tornado outbreaks have significant human impact, so it is imperative forecasts of these phenomena are accurate. As a synoptic setup lays the foundation for a forecast, synoptic-scale aspects of Storm Prediction Center (SPC) outbreak forecasts of varying accuracy were assessed. The percentages of the number of tornado outbreaks within SPC 10% tornado probability polygons were calculated. False alarm events were separately considered. The outbreaks were separated into quartiles using a point-in-polygon algorithm. Statistical composite fields were created to represent the synoptic conditions of these groups and facilitate comparison. Overall, temperature advection had the greatest differences between the groups. Additionally, there were significant differences in the jet streak strengths and amounts of vertical wind shear. The events forecasted with low accuracy consisted of the weakest synoptic-scale setups. These results suggest it is possible that events with weak synoptic setups should be regarded as areas of concern by tornado outbreak forecasters.

The purpose of this research is to simulate warm-season mesoscale convective systems (MCSs) using the Weather Research and Forecasting Model (WRF) to determine whether modeled atmospheric variables are capable of discriminating between derecho formation and intensity. Fifty total events are selected with half being derecho-producing MCSs and half being non-derecho producing MCSs. WRF is used to model each event with a high-resolution domain centered over the Midwest using the North American Regional Reanalysis (NARR) dataset as initial and boundary conditions. Atmospheric conditions downstream of the MCS damage path are compared to thresholds established by previous research to determine if the model accurately simulates the expected environment. The goal of the research is to gain insight into how well a high-resolution model can simulate the environment that is expected. It is anticipated that the model will be able to distinguish between environments associated with a derecho-producing MCS and a non-derecho MCS.

Sepsis is an uncontrolled response to infection. Severe sepsis is associated with organ dysfunction, and has mortality rate of 30-50%. Identification of severity of sepsis and prediction on mortality is crucial in making clinical decisions. Recently, cell-free DNA (cfDNA) in blood was found to have high discriminative power in predicting ICU mortality in patients with severe sepsis. In an analysis of 80 severely septic patients, the mean cfDNA level in survivors (1.16±0.13μg/ml) was similar to that of healthy volunteers (0.93±0.76μg/ml), while that of non-survivors (4.65±0.48μg/ml) was notably higher. Therefore, rapid quantification of cfDNA concentration in blood will enable physicians to quickly predict mortality of sepsis and decide on treatment. Current methods for quantification of cfDNA involve multiple steps including centrifugation, DNA-extraction from plasma, and its quantification either through spectroscopic methods or quantitative PCR. The whole process is time consuming, thus is not suitable for immediate bedside assessment. To solve the problems, a microfluidic device is designed and fabricated in this thesis, which is potential for cfDNA quantification directly using blood in 5 minutes. The goal is to use this device for distinguishing survivors or healthy donors from non-survivors in patients with severe sepsis. The two-layer device consists of a sample channel (top) and an accumulation channel (bottom) that intersect each other. The accumulation channel is preloaded with 1% agarose gel, and the blood containing cfDNA and intercalating fluorescent dye is loaded in the sample channel. Fluorescently labeled DNA is able to be trapped and concentrated at the intersection using a DC electric field, and fluorescent intensity of the accumulated DNA is representative of its concentration in the blood. The simulated electric field in the sample channel reveals that both the magnitude and the gradient of electric field reach their maximum values at the intersection. Force analysis shows that DNA was driven into the gel by the dominate electrophoretic force, while red blood cells moved away from the gel due to a strong dielectrophoretic force. In this thesis, 4 types of samples have been used to characterize the performance of the device. It showed that DNA was efficiently accumulated at the intersection, and the fluorescent intensity could be measured using a fluorescent microscope. Samples from healthy donors were able to be distinguished from that of severely septic patients in 5 minutes. However, better resolution was needed for differentiating various cfDNA concentrations in patient samples. The discussion on the effect of applied voltage showed that 9V is an optimized setting compared with 3V and 15V. In addition, it has been proved that the fluorescent reagent could be immobilized in the device and the sample preparation could be absolutely eliminated. In summary, the device proposed in this thesis is capable of distinguishing severely septic patients from healthy donors using clinical plasma in 5 minutes, and is potential to be applied in clinical blood samples. It has low cost, and is ready to be developed into a fully functioned system. This tool can be a valuable addition to the ICU to rapidly assess the severity of sepsis for informed decision making. / Thesis / Master of Applied Science (MASc)

One of the primary missions of the National Weather Service (NWS) is to use a network of more than 150 NEXRAD radar installations to monitor weather for threats to life and property. Large hail produced by severe thunderstorms is a major focus of this mission. An algorithm known as the Maximum Estimated Size of Hail (MESH) algorithm is in operational use to diagnose the presence and size of hail. This study aims to use dual-Doppler observations as well as the MESH algorithm to test the idea that storms that rotate produce larger hail. Previous studies have used polarimetric radar products to detect the presence of large hail and dual-Doppler methods have been used to study embryonic hail, but no research has tested the theory of hail and rotating storms with observational evidence. A set of 59 case studies was gathered; each included a hail report submitted by a trained weather spotter or NWS employee and complete radar observations through the depth of a storm from two radars. The radar observations were resampled to a three-dimensional Cartesian grid and a dual-Doppler analysis was run on each case study. A strong correlation (stronger even than the MESH algorithm) was found between measured vorticity and hail size, lending credence to the idea that rotating storms do indeed have a higher ceiling for hail production. However, no correlation was found between MESH error and rotation. Further research will be required to evaluate whether or not this relationship can be used to augment the MESH algorithm so as to improve its skill. / Master of Science

Traditional animal models of severe asthma do not recapitulate defining asthma characteristics, including persistent airway hyper-responsiveness, and chronic neutrophilic inflammation. This is problematic because moderating airway hyper-responsiveness decreases asthma frequency and severity, making it a paramount pharmacological goal in asthma research. Employing a spontaneous equine asthma model (equine pasture asthma, EPA), we first confirmed reversible airway obstruction in eight diseased horses during asthma exacerbations in response to ß2renergic agonist stimulation. Next, non-specific airway hyper-responsiveness was confirmed using methacholine bronchoprovocation to identify the provocative concentration causing a 40% increase in baseline lung resistance (PC40RL)- a threshold similarly employed in evaluating human asthmatics unable to mount forced expiration. The PC40RL of ten EPA horses was consistently <1mg/ml of methacholine, which is a cutoff that has been used to diagnose severe human asthma. Like non-asthmatic humans, ten control horses did not respond to methacholine doses up to 16 mg/ml. Finally, persistence of AHR was documented during absence of seasonal aeroallergen triggers in five horses that were evaluated between 3 and 31 months following the initial methacholine bronchoprovocation. This unique ability of EPA horses to model AHR attributes that are not addressed by other animal models points to the suitability of EPA horses to decipher the mechanistic basis of airway hyper-responsiveness. Building on knowledge that 2renergic receptor (AR) signaling is required to develop the asthma phenotype in a murine model, differentially expressed genes from serial lung biopsies of two EPA affected and two controls were filtered to identify genes that interact with the 2-AR. Hyperpolarization Activated Cyclic Nucleotide-Gated Potassium Channel 4 (HCN4) was prioritized because of its interactions with the 2-AR. Relative to control horses, HCN4 was constitutively expressed in airway smooth muscle of EPA horses during remission and increased during seasonal disease exacerbation. Agonism of airway contraction by HCN4 was proven using the specific HCN4 antagonist, ivabradine, which caused dose dependent decreases in carbachol induced contractile responses in both EPA and control bronchi in vitro. These findings highlight utility of EPA as a model of severe asthma and HCN4 as a mediator of airway contraction that warrants further investigation in severe human asthma.

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Since the Fukushima Daiichi nuclear accident, there have been ongoing efforts to enhance the modelling capabilities for severe accidents in nuclear power plants. The primary severe accident analysis code used in Canada for its CANDU reactors is MAAP-CANDU (adapted from MAAP-LWR). In order to meet the new requirements that have evolved since Fukushima, upgrades to MAAP-CANDU have been made most recently by the Canadian nuclear industry. While the newest version (i.e. MAAP5-CANDU) offers several important improvements primarily in core nodalization and core collapse modelling, it still lacks mechanistic models for many key thermo-mechanical deformation phenomena that may significantly impact accident progression and event timings. It is also a general consensus that having alternative analysis tools is beneficial in improving our confidence in the simulation results, especially given the complex nature of severe accident phenomena in CANDU and the limited experimental support. This thesis seeks a novel approach to CANDU severe accident modelling by combining the best-estimate thermal-hydraulic code RELAP5, the severe accident models in SCDAP, and several CANDU-specific mechanistic deformation models developed by the author. This work mainly consists of two parts. The first part is focused on the assessment of natural circulation heat sinks following crash-cooldown in the early-phase of a Station Blackout (SBO) accident where fuel channel deformation can be precluded. The effectiveness of steam generator heat removal after crash-cooldown and that of the several water make-up options were demonstrated through the simulation of several SBO scenarios with/without crash-cooldown, sensitivity studies, as well as benchmarking against station and experimental measurements. In the second part, several mechanistic severe accident models were developed to enhance the simulation fidelity beyond the initial steam generator heat sink phase to the moderator boil-off and core disassembly phases. This includes models for predicting the pressure tube ballooning and sagging phenomena during the fuel channel heat-up phase and models for the sagging and disassembly of fuel channel assemblies during the core disassembly phase. After benchmarking against relevant channel deformation experiments, the models were successfully integrated into the RELAP/SCDAPSIM/MOD3.6 code as part of the SCDAP subroutines. The advantage of utilizing a code such as SCDAP is that generic models for fission product release and hydrogen generations, which are well benchmarked, can be directly applied to CANDU simulations. With the modified MOD3.6 code the early-phase SBO simulations were extended to include the later stages of SBO until the calandria vessel dryout. The current modelling approach replaced the simple threshold-type models commonly seen in the integrated severe accident codes such as MAAP-CANDU with more mechanistic models thereby providing a more robust treatment of the core degradation process during severe accident in CANDU. / Thesis / Doctor of Philosophy (PhD)

In part ONE of this thesis, including the most up to date information on SARS virology, disease transmission, pathogenesis and laboratory diagnosis will be summarized and presented, including the results of many studies in which I have participated (these references will be underlined as they appear in text). This of course summarizes knowledge that is now known in 2006 but was largely unknown during the initial outbreak. In part TWO, six original clinical studies performed at PWH will be presented: study (1) describes the clinical manifestations and severity of SARS, and its potential to cause major hospital outbreaks; (2) demonstrates the importance of epidemiological linkage in diagnosing SARS; (3) reports the clinical outcomes of a stepwise treatment protocol, which includes the use of corticosteroid therapy as an immunomodulant; (4) demonstrates that corticosteroid therapy can retard viral clearance, and should be used judiciously; (5) demonstrates that a more robust humoral response is associated with severe SARS, thus indicating that passive immunity treatment strategies seem only suitable either during early illness or as prophylaxis; and (6) shows that SARS has few early discriminating laboratory features compared to other causes of community-acquired pneumonia, thus a high index of suspicion is needed to recognize this infection in the absence of worldwide transmission. A thorough review of the relevant published material will be included in the discussion section of each study. / Severe Acute Respiratory Syndrome (SARS) is an emerging infectious disease caused by a novel coronavirus. It caused a global outbreak in 2003, resulting in more than 8000 infections, 700 deaths, and major social and economic disruption. In the initial phase of the SARS outbreak, the medical profession had no knowledge regarding the responsible pathogen, nor the clinical manifestations of SARS and the course of illness. There was no reliable diagnostic tool and no known effective therapy. But for the first time in medical history, we witnessed the rapid accumulation of knowledge on a disease as it evolved, which in turn assisted its management and control. / Since conducting randomized-controlled trials during the 2003 crisis was almost impossible, most of the presented studies are either descriptive or case-controlled in design. However, these studies have laid foundations for recent and future research into the clinical diagnosis and management of SARS. Moreover, the construction of the SARS clinical database has contributed to the work of other investigators, which has resulted in over thirty-six publications. It is my hope that these research endeavors can contribute to the understanding of this emerging, deadly disease. / Lee Lai Shun, Nelson. / "April 2006." / Source: Dissertation Abstracts International, Volume: 69-01, Section: B, page: 0205. / Thesis (M.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 264-292). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.