VictorJuiz/thesis huggingface dataset:
A New Conceptualization of Occupational Outcome
Keywords: outcome
occupational health
stakeholders
quality

This thesis presents a new conceptual model of occupational outcome based on the results of input from 5 key stakeholder groups in the field of occupational health including patients, healthcare providers, employers, unions, and insurers. Data from 77 participants who took part in one of either 18 individual interviews or 11 focus groups were qualitatively content analyzed. The goals were to: 1) compare the range of meanings given to the concepts of health, occupational health, and occupational outcome, 2) understand the range of opinions among stakeholders and identify areas of agreement or disagreement and, 3) to develop a framework of occupational outcome incorporating the views of all key stakeholders. Health, occupational health, and occupational outcome were found to have different and complex meanings that extended beyond those in existing research, and that related to the role a variable is hypothesized to have in a larger framework. Stakeholders differed in the depth, breadth, and qualitative nature of the themes discussed. Natural alignments among some stakeholder groups emerged which varied depending on the context, however a specific focus could be identified for each group. No single stakeholder group alone expressed all the themes and the complexity of the relationships among them; the whole could only be understood in terms of the sum of the stakeholder parts. A new model emerges in which occupational outcome is encompassed by the interactions of 3 key factors: Function and Ability, Individual Behaviours, and Environmental Factors. These are embedded within larger models of both occupational health that includes both individual health and workplace health, and of quality which is comprised of the interactions between structure variables, system participant factors, and outcome. The new model and the process undertaken to develop it meet two important needs for occupational health; enhancing understanding and conceptualization of occupational outcome, and enhancing understanding of the perspectives of stakeholders in the occupational healthcare system. The findings have implications for research, and delivery of quality care to patients with occupational disease or injuries. Some next steps include model validation and testing, measurement scale development, clarifying new variables through ongoing stakeholder discussion, and model application.
GLI2 Transcriptional Cascade During Mouse Fetal Lung Development
Keywords: Sonic Hedgehog
Gli2
Foxf1
Lung
Pulmonary
Mouse
Transgenic
Development
Gli3
Shh
Cellular Proliferation
Morphogenesis
Fgf10
Branching Morphogenesis
Embryo
Transgene

The lung is an organ that contains a vast system of airways carefully constructed to achieve maximal surface area in a confined space, requiring guidance from a multitude of developmental factors. The Shh pathway is one such signaling mechanism that is critical to proper lung formation, guiding branching morphogenesis and cellular proliferation through its downstream Gli transcription factors. Additionally, Foxf1 has been shown to be a key developmental factor required for proper lung formation during embryogenesis. Although theorized that the Gli transcription factors are responsible for regulating foxf1 levels, their exact relationship has yet to be revealed. Using five different models for Shh signaling (gli2 null, gli2 over-expressor [hVER-Gli2], gli3 null, Gli3 constitutive repressor [Gli3Δ699] and cyclopamine treated lung explants), I compared and contrasted the role of Gli2 and Gli3 in terms of their effect on cell cycle regulation, and on the expression levels of foxf1 and its potential downstream target genes tbx4, tbx5 and fgf10. I found that ectopic over-expression of gli2 resulted in increased Shh pathway activation, and increased expression of G1/S phase cyclins, which was associated with increased cellular proliferation and lung growth. However, no change in the levels of G1/S phase cyclins due to altered Gli3 signaling was observed. Foxf1 levels positively correlate with the levels of gli2, and appear to be independent of Gli3 activity. The amount of tbx4, tbx5, and fgf10 transcripts were observed to follow the levels of gli2 in the different gli2 mouse models, however, there was no significant change in gli3 null or Gli3Δ699 mice. Finally, by analyzing gene expression at different time points during gestation, I found that while gli2 levels affect foxf1 throughout gestation, the relationship to tbx4, tbx5 and fgf10, occurs only during the latter stages of lung development. I conclude, that Gli2 and not Gli3 appears to be the primary transducer of Shh signaling influencing cyclin regulation, leading to changes in embryonic lung growth. Furthermore, that Gli2 and not Gli3 appears to regulate foxf1 expression levels, and that this may extend downstream to influence tbx4, tbx5 and fgf10 expression.
Point-based Ionizing Radiation Dosimetry Using Radiochromic Materials and a Fibreoptic Readout System
Keywords: radiation dosimetry
radiochromic media
fibre-optic readout

Real-time feedback of absorbed dose at a point within a patient can help with radiological quality assurance and innovation. Two radiochromic materials from GafChromic MD-55 and EBT films have been investigated for applicability in real-time in vivo dosimetry of ionizing radiation. Both films were able to produce a real-time measurement of optical density from a small volume, allowing positioning onto a tip of an optical fibre in the future. The increase in optical density was linear with absorbed dose for MD-55, and non-linear for EBT. The non-linearity of EBT is associated with its increased sensitivity to ionizing radiation compared to MD-55, thus reaching optical saturation at a much lower dose. The radiochromic material in EBT film was also shown to polymerize and stabilize faster, decreasing dose rate dependence in real-time measurements in comparison to MD-55. The response of the two media was tested over 75 kVp – 18 MV range of x-ray beams. The optical density measured for EBT was constant within 3% throughout the entire range, while MD-55 exhibited a nearly 40% decrease at low energies. Both materials were also shown to be temperature sensitive, with the change in optical density generally decreasing when the temperature increased from ~22°C to ~37°C. This was accompanied by a shift in the peak absorbance wavelength. It was illustrated that some of this decrease can be corrected for by tracking the peak position and then multiplying the optical density by a correction factor based on the predicted temperature. Overall, the radiochromic material in GafChromic EBT film was found to be a better candidate for in vivo real-time dosimetry than the material in GafChromic MD-55. A novel mathematical model was proposed linking absorbance to physical parameters and processes of the radiochromic materials. The absorbance at every wavelength in the spectrum was represented as a sum of absorbances from multiple absorbers, where absorbance is characterized by its absorption coefficient, initiation constant, and polymerization constant. Preliminary fits of this model to experimental data assuming two absorbers suggested that there is a trade-off between EBT’s greater sensitivity and its dose linearity characteristics. This was confirmed by experimental results.
Graphical Models for Robust Speech Recognition in Adverse Environments
Keywords: Robust Speech Recognition
Graphical Models
Speech Separation
Dynamic Noise Adaptation
Variational Expectation-Maximization (GEM)
Super-human Automatic Speech Recognition (ASR)

Robust speech recognition in acoustic environments that contain multiple speech sources and/or complex non-stationary noise is a difficult problem, but one of great practical interest. The formalism of probabilistic graphical models constitutes a relatively new and very powerful tool for better understanding and extending existing models, learning, and inference algorithms; and a bedrock for the creative, quasi-systematic development of new ones. In this thesis a collection of new graphical models and inference algorithms for robust speech recognition are presented. The problem of speech separation using multiple microphones is first treated. A family of variational algorithms for tractably combining multiple acoustic models of speech with observed sensor likelihoods is presented. The algorithms recover high quality estimates of the speech sources even when there are more sources than microphones, and have improved upon the state-of-the-art in terms of SNR gain by over 10 dB. Next the problem of background compensation in non-stationary acoustic environments is treated. A new dynamic noise adaptation (DNA) algorithm for robust noise compensation is presented, and shown to outperform several existing state-of-the-art front-end denoising systems on the new DNA + Aurora II and Aurora II-M extensions of the Aurora II task. Finally, the problem of speech recognition in speech using a single microphone is treated. The Iroquois system for multi-talker speech separation and recognition is presented. The system won the 2006 Pascal International Speech Separation Challenge, and amazingly, achieved super-human recognition performance on a majority of test cases in the task. The result marks a significant first in automatic speech recognition, and a milestone in computing.
The Ambiguous Greek in Old French and Middle English Literature
Keywords: medieval literature
Middle English
alterity
ancient Greeks
Saracens
Old French
Jews

This dissertation investigates how the Greeks of the Trojan War and Alexander the Great are presented in Old French and Middle English literature. These ancient Greeks are depicted ambiguously: they share some of the characteristics of Jews and Saracens as they are portrayed in medieval literature. The thesis begins with an overview of the frameworks used to define ancient Greek identity. These include the philosophical heritage Greece left to the medieval West; the framework of Jewish identity, encompassing “variable characterization” and the hermeneutics of supersession; and the historical template, seen through the Orosian paradigm of translatio imperii and the Trojan foundation myth. The first chapter examines the Roman de Troie of Benoît de Sainte-Maure. The Greeks of the Trojan War are noble and valorous, but through their gift of the Trojan horse and sack of Troy, they display the treachery associated with post-Incarnation Jews and the cruelty and violence associated with Saracens. Due to the myth that the Trojans founded the Roman people, through their siege of Troy, the Greeks seem like the movers of imperium, the authority to rule, from Troy to Rome, which will eventually become a Christian empire. In the second chapter, I turn to the depiction of Alexander in Thomas of Kent’s Roman de toute chevalerie and the Middle English Wars of Alexander. In the Roman de toute chevalerie, Alexander is ambiguous: he is chivalrous, learned, and even a proto-Christian, though he himself assumes some typical Saracen characteristics. Alexander participates in translatio imperii, holding the right to rule in its Orosian succession and providing a model of empire to Rome. The Wars of Alexander witnesses the changes wrought to Alexander’s depiction in the fourteenth century due to revised views of chivalry, eschatology and crusade. The third chapter investigates the depiction of the Greek Diomede in Chaucer’s Troilus and Criseyde, a depiction informed by classical ideas and Chaucer’s depictions of Jews and Saracens in his other works. Diomede is both treacherous and cruel, seen in his seduction of Criseyde, rather than in battle. The ending of the tale posits a proto-Christian identity for Troilus and the Trojans, and suggests that Diomede participates in the supersession of the Greeks by the Trojans. Greeks function as movers of imperium, and are necessary for the beginnings of Christian empire.
A Passive Mid-infrared Sensor to Measure Real-time Particle Emissivity and Gas Temperature in Coal-fired Boilers and Steelmaking Furnaces
Keywords: spectral particle emissivity
off-gas temperature
combustion diagnostics
mid-infrared emission spectroscopy
pyroelectric detector
optically thick assumption
gas-particle medium
coal-fired boiler
embedded invariance
particle scattering
Basic Oxygen Furnace (BOF)
oxygen lance end-point
steel composition and temperature
first turndown properties
remote sensing
asymptotic approximation of the Radiative Transfer Equation

A novel technique for measuring gas temperature and spectral particle emissivity in high-temperature gas-particle streams is presented. The main application of this optical sensor is to improve the process control of batch unit operations, such as steelmaking furnaces. The spectral emission profile of CO and CO2 and the continuous particle emission in the 3.5 to 5 μm wavelength region was recorded and analyzed in real time with a low-resolution passive sensor. The sensor consisted of light collecting optics, a dispersion element (grating spectrometer) and a 64-pixel pyroelectric array. Wavelength and radiance calibrations were performed. The temperature of the gas-particle medium (Tg+p) followed from the least-squares minimization of the difference between the measured radiance in the 4.56-4.7 μm region –which saturates due to the large CO2 concentrations and path lengths in industrial furnaces– and the corresponding blackbody radiance. Particle emissivity (εp) was calculated at 3.95 μm from an asymptotic approximation of the Radiative Transfer Equation that yields the emerging radiance from a semi-infinite particle cloud. The major source of error in the magnitude of Tg+p and εp could come from particle scattering. Through the method of embedded invariance an expression was developed to estimate the lowering effect of particle size and volume fraction on the saturation of the 4.56-4.7 μm CO2 emission region. An iterative procedure for correcting the values of the gas-particle temperature and particle emissivity was applied to the datasets from the two industrial tests. Results from the measurement campaigns with the infrared sensor prototype at two full-scale furnaces are presented. A proof-of-concept test at a coal-fired boiler for electricity production was followed by more extensive measurements at a Basic Oxygen Furnace (BOF) for steelmaking. The second test provided temperature and particle emissivity profiles for eight heats, which highlighted the simplicity of the technique in obtaining in-situ measurements for modeling studies. Through the analysis of the particle emissivity profile in the BOF and the definition of a new variable –the minimum carbon time– a novel end-point strategy to stop the injection of high-purity oxygen during low-carbon heats in BOF converters was proposed.
Endothelial Injury In Cardiac Transplantation: The Role Of Endothelin Antagonism And Protein Kinases
Keywords: Endothelin-1
Protein Kinase

BACKGROUND: Endothelial dysfunction is a principal player in the development of allograft vasculopathy and allograft failure. The hallmark of endothelial dysfunction is impaired nitric oxide bioavailability. Recent evidence implicates endothelin-1 as an integral component of endothelial dysfunction. Immunosuppressive drugs have also been associated with the development of graft vasculopathy. We speculated that endothelin-1 results in endothelial dysfunction by impairing nitric oxide homeostasis and is a player in hypoxia and reperfusion induced vasomotor injury. In addition, we hypothesized that endothelin-1 antagonism with bosentan will limit hypoxia and reperfusion injury and prevent immunosuppressive drug injury. METHODS: We utilized human saphenous vein endothelial cells to evaluate the effects of endothelin-1, hypoxia and reperfusion on endothelial function, protein kinase modulation and cell survival. We also employed a rodent model of chronic drug therapy to assess the effect of cyclosporine and rapamycin treatment on vasomotor function. We investigated the role of nitric oxide augmentation and bosentan in preventing hypoxia and reperfusion injury and in limiting immunosuppressive drug induced vasomotor dysfunction. RESULTS: Elevated endothelin-1 levels resulted in impaired nitric oxide release and endothelial function. The effects of endothelin-1 as well as hypoxia and reperfusion were mediated by altered protein kinase B and protein kinase C activity resulting in endothelial dysfunction. We revealed that endothelin-1 is a key player in hypoxia and reperfusion induced endothelial injury. The immunosuppressive drug cyclosporine induced vasomotor dysfunction while rapamycin preserved vessel homeostasis. Vasomotor dysfunction was characterized by impaired nitric oxide and endothelin-1 homeostasis. Bosentan limited the deleterious effects of endothelin-1, hypoxic injury, reperfusion injury and cyclosporine induced vasomotor impairment. CONCLUSIONS: Our study revealed that endothelin-1 exposure as well as hypoxia and reperfusion results in endothelial dysfunction by altering specific protein kinase C isoform activities and inhibiting protein kinase B. Cyclosporine induced vasomotor dysfunction was mediated by altered nitric oxide and endothelin-1 homeostasis while rapamycin was endothelial protective. Bosentan proved to be an effective therapy at preventing endothelin-1, hypoxia and reperfusion and cyclosporine induced endothelial dysfunction. Protein kinase C modulation as well as bosentan may prove to be NOVEL therapies to prevent endothelial injury during cardiac transplantation.
Retrovirus-mediated Gene Therapy For Farber Disease
Keywords: Gene Therapy
Lysosomal Storage Disease
Farber Disease
Retrovirus

Farber disease is a rare lysosomal storage disease (LSD) caused by a deficiency of acid ceramidase (AC). Patients show a classic triad of symptoms including subcutaneous granulomas, laryngeal involvement and painful swollen joints. The most common and severe form has neurological manifestations and patients typically die by the age of two. Current treatment consists of symptomatic supportive care and allogeneic bone marrow transplantation (BMT). However, BMT has shown limited success. Gene therapy has previously been shown to be a promising treatment strategy for monogenetic diseases and has the potential to treat the underlying cause of the disease. Presented here is the first report of in vivo testing of retrovirus-mediated gene therapy strategies for the treatment of Farber disease. Retroviral vectors were engineered to overexpress AC and a cell surface marker, human CD25. Transduction with these viral vectors corrected the enzymatic defect in Farber patient cells and in vivo administration of the lentiviral vector led to long-term expression of the marking transgene as well as increased AC expression in the liver. To determine the effect of over-expression of AC, human CD34+ cells were transduced and transplanted into NOD/SCID animals. It was found that transgene-expressing cells could reconstitute the host. To address the neurological manifestations of Farber disease, vascular endothelial growth factor (VEGF) was investigated as an agent to transiently open the blood brain barrier for entry of lentivirus. It was found that in addition to increasing the amount of therapeutic virus in the brain, VEGF treatment also increased transduction in other organs. Further, to address the concerns of insertional mutagenesis associated with using integrating vectors, an immunotoxin-based strategy was developed as a safety system to clear transduced cells. It was found that a CD25-targeted immunotoxin could eliminate both transduced hematopoietic cells as well as tumor cells over-expressing CD25. This strategy can be employed following gene therapy should an unwanted proliferative event occur. Together, these studies represent considerable advances towards the development of a cure for Farber disease, demonstrating both therapeutic potential and also containing a built-in safety system.
Asymptotic Optimization of Risk Measures
Keywords: optimization
Value-at-Risk

Value-at-Risk (VaR ) is an industrial standard for monitoring market risk in an investment portfolio. It measures potential osses within a given confidence level. VaR was first used by major financial institutions in the early 1990’s, and widely developed after the release of J.P. Morgan’s Riskmetrics Technical Document in 1996. The efficient calculation, implementation, interpretation and optimization of VaR are a challenge in the practice of risk management when the number of market factors in the portfolio is high. In this thesis, we are concerned with the quadratic analytical estimation of VaR and we present a methodology for an approximation to VaR that is based on the principal components of a sensitivity-adjusted covariance matrix. The result is an explicit expression in terms of portfolio deltas, gammas, and the mean and covariance matrix. It can be viewed as a non-linear extension of the linear model given by the delta-normal-VaR of RiskMetrics, a standard calculation for the risk in the financial sector. We obtain an asymptotic expansion for VaR in the limit when the confidence level approaches 1 and precise estimates of the reminder. We then optimize the approximated VaR with respect to the gradient or delta of the portfolio, a quantity which can be changed by trading the underlying assets (stocks), without entering into any derivative transactions. This analysis provides an optimal trading strategy of the portfolio that minimizes the risk.