Doctor of Philosophy

dissertationRecent economic crises have exposed a critical need for appropriate methods to measure, model, and predict financial volatility. Generalized autoregressive conditional heteroskedastic (GARCH) models have been among the most successful and widely studied tools for this task due to their ability to capture the stylized characteristics of financial data. Extending the original univariate GARCH processes to the multivariate framework is important because, in many applications, the primary quantity of interest is the interdependence, or covariance, between different univariate processes. Covariances are used for calculations of hedge ratios, betas of CAPM (Capital Asset Pricing Model), portfolio VaR (Value at Risk) estimates, asset weights in portfolios, and to investigate contagion across financial markets. In Chapter 1 of this dissertation, we briefly review concepts and terminology related to stochastic processes and time series analysis. In Chapter 2, we prove sufficient conditions for existence, uniqueness, and stochastic stability of multivariate GARCH processes. In Chapter 3, we explore the QMLE and VTE methods for estimating multivariate GARCH parameters. We prove sufficient conditions for strong consistency and asymptotic normality of the QMLE and VTE estimators, and we conduct simulation studies to compare the performance of the VTE and QMLE

Validation of a molecular and pathological model for five-year mortality risk in patients with early stage lung adenocarcinoma

Introduction: The aim of this study was to validate a molecular expression signature [cell cycle progression (CCP) score] that identifies patients with a higher risk of cancer-related death after surgical resection of early stage (I-II) lung adenocarcinoma in a large patient cohort and evaluate the effectiveness of combining CCP score and pathological stage for predicting lung cancer mortality. Methods: Formalin-fixed paraffin-embedded surgical tumor samples from 650 patients diagnosed with stage I and II adenocarcinoma who underwent definitive surgical treatment without adjuvant chemotherapy were analyzed for 31 proliferation genes by quantitative real-time polymerase chain reaction. The prognostic discrimination of the expression score was assessed by Cox proportional hazards analysis using 5-year lung cancer-specific death as primary outcome. Results: The CCP score was a significant predictor of lung cancer-specific mortality above clinical covariates [hazard ratio (HR) = 1.46 per interquartile range (95% confidence interval = 1.12–1.90; p = 0.0050)]. The prognostic score, a combination of CCP score and pathological stage, was a more significant indicator of lung cancer mortality risk than pathological stage in the full cohort (HR = 2.01; p = 2.8 × 10−11) and in stage I patients (HR = 1.67; p = 0.00027). Using the 85th percentile of the prognostic score as a threshold, there was a significant difference in lung cancer survival between low-risk and high-risk patient groups (p = 3.8 × 10−7). Conclusions: This study validates the CCP score and the prognostic score as independent predictors of lung cancer death in patients with early stage lung adenocarcinoma treated with surgery alone. Patients with resected stage I lung adenocarcinoma and a high prognostic score may be candidates for adjuvant therapy to reduce cancer-related mortality

Willingness to take multidrug-resistant tuberculosis (MDR-TB) preventive therapy among adult and adolescent household contacts of MDR-TB index cases : an international multisite cross-sectional study

CITATION: Suryavanshi, N. et al. 2020. Willingness to Take Multidrug-resistant Tuberculosis (MDR-TB) Preventive Therapy Among Adult and Adolescent Household Contacts of MDR-TB Index Cases: An International Multisite Cross-sectional Study. Clinical Infectious Diseases, 70(3): 436–445. doi:10.1093/cid/ciz254The original publication is available at https://academic.oup.com/cid/Background. Household contacts (HHCs) of individuals with multidrug-resistant tuberculosis (MDR-TB) are at high risk of infection and subsequent disease. There is limited evidence on the willingness of MDR-TB HHCs to take MDR-TB preventive therapy (MDR TPT) to decrease their risk of TB disease. Methods. In this cross-sectional study of HHCs of MDR-TB and rifampicin-resistant tuberculosis (RR-TB) index cases from 16 clinical research sites in 8 countries, enrollees were interviewed to assess willingness to take a hypothetical, newly developed MDR TPT if offered. To identify factors associated with willingness to take MDR TPT, a marginal logistic model was fitted using generalized estimating equations to account for household-level clustering. Results. From 278 MDR-TB/RR-TB index case households, 743 HHCs were enrolled; the median age of HHCs was 33 (interquartile range, 22-49) years, and 62% were women. HHC willingness to take hypothetical MDR TPT was high (79%) and remained high even with the potential for mild side effects (70%). Increased willingness was significantly associated with current employment or schooling (adjusted odds ratio [aOR], 1.83 [95% confidence interval {CI}, 1.07-3.13]), appropriate TB-related knowledge (aOR, 2.22 [95% CI, 1.23-3.99]), confidence in taking MDR TPT (aOR, 7.16 [95% CI, 3.33-15.42]), and being comfortable telling others about taking MDR TPT (aOR, 2.29 [95% CI, 1.29-4.06]). Conclusions. The high percentage of HHCs of MDR-TB/RR-TB index cases willing to take hypothetical MDR TPT provides important evidence for the potential uptake of effective MDR TPT when implemented. Identified HHC-level variables associated with willingness may inform education and counseling efforts to increase HHC confidence in and uptake of MDR TPT.https://academic.oup.com/cid/article/70/3/436/5421246?login=truePublishers versio

Nutritive value and herbage mass of Pueraria phaseoloides (tropical kudzu) in un-utilized open grasslands in north-eastern and central Trinidad and Tobago

Pueraria phaseoloides is an important forage for ruminants in the tropics. However, its nutritive value and availability in areas easily accessed by ruminants and ruminant farmers in Trinidad and Tobago is unknown. This study, therefore, evaluated the effects of harvest date and location on the nutritive value, herbage mass and crude protein yield of P. phaseoloides in un-utilized open grasslands in three locations with high livestock density in Trinidad. Pueraria phaseoloides herbage (whole fraction and leaf) trailing on the upper canopy of open un-utilized grasslands were harvested in the late wet season of 2019 (October - November), early dry (January - February) and early wet (July - August) seasons of 2020 following a stratified random sampling scheme. The crude protein (CP) concentrations of P. phaseoloides leaves (235 g/kg DM) and whole fraction (217 g/kg DM) were highest in Wallerfield during the early wet season. Neutral detergent fibre (NDF), acid detergent fibre (ADF) and lignin were lowest in the early dry season (P < 0.01). Crude protein yield (376–478 kg CP ha−1) and herbage mass (1,742–2,654 kg DM ha−1) were highest during the late wet and early dry season, respectively. In vitro organic matter digestibility (IVOMD) of P. phaseoloides leaf (548–598 g/kg) and whole fraction (549 –580 g/kg) were highest in the late wet season. It was, therefore concluded that open un-utilized grasslands in Trinidad and Tobago produced significant amount of P. phaseoloides herbage year-round to support ruminant livestock production. However, the nutritive value, herbage mass and CP yield of P. phaseoloides herbage were highest during the late wet and early dry seasons

High-throughput glycomic analyses reveal unique oligosaccharide profiles of canine and feline milk samples.

Oligosaccharides are important components of milk, serving as substrates for the intestinal microbiota, acting as antimicrobials that prevent pathogen colonization, and supporting the developing gastrointestinal immune system of neonates. Nutrient composition of canine and feline milk samples has been described previously, but little is known about the oligosaccharide content. Therefore, the objective of this study was to characterize canine and feline milk samples using a high-throughput glycomics approach. 23 dogs (9 Labrador retriever and 14 Labrador retriever x golden retriever crossbreed) and 6 domestic shorthair cats were recruited to the study. Milk samples were collected by manual expression at time points after parturition. Samples were collected across 2 phases per species, differentiated by maternal diet. Following extraction, oligosaccharide content was determined by liquid chromatography-mass spectrometry (LC-MS). In canine milk samples, 3 structures accounted for over 90% of all oligosaccharides detected across two diet groups. These were 3'-sialyllactose, 6'-sialyllactose, and 2'-fucosyllactose. In feline samples, a more diverse range of oligosaccharides was detected, with up to 16 structures present at relative abundance &gt;1% of the total. Difucosyllactose-N-hexaose b, 3'-sialyllactose and lacto-N-neohexaose were all detected at abundances &gt;10% in feline milk samples. Statistically significant differences (p&lt;0.05) in oligosaccharide abundances were observed between collection time points and between diet groups within species. These data explore the oligosaccharide content of canine and feline maternal milk, representing an opportunity to generate a fundamental understanding of the nutritional needs of new-born puppies and kittens

Neural correlates of multisensory integration of ecologically valid audiovisual events

Oligosaccharides are important components of milk, serving as substrates for the intestinal microbiota, acting as antimicrobials that prevent pathogen colonization, and supporting the developing gastrointestinal immune system of neonates. Nutrient composition of canine and feline milk samples has been described previously, but little is known about the oligosaccharide content. Therefore, the objective of this study was to characterize canine and feline milk samples using a high-throughput glycomics approach. 23 dogs (9 Labrador retriever and 14 Labrador retriever x golden retriever crossbreed) and 6 domestic shorthair cats were recruited to the study. Milk samples were collected by manual expression at time points after parturition. Samples were collected across 2 phases per species, differentiated by maternal diet. Following extraction, oligosaccharide content was determined by liquid chromatography-mass spectrometry (LC-MS). In canine milk samples, 3 structures accounted for over 90% of all oligosaccharides detected across two diet groups. These were 3'-sialyllactose, 6'-sialyllactose, and 2'-fucosyllactose. In feline samples, a more diverse range of oligosaccharides was detected, with up to 16 structures present at relative abundance >1% of the total. Difucosyllactose-N-hexaose b, 3'-sialyllactose and lacto-N-neohexaose were all detected at abundances >10% in feline milk samples. Statistically significant differences (p<0.05) in oligosaccharide abundances were observed between collection time points and between diet groups within species. These data explore the oligosaccharide content of canine and feline maternal milk, representing an opportunity to generate a fundamental understanding of the nutritional needs of new-born puppies and kittens

Prediction of distant recurrence in resected stage I and II lung adenocarcinoma

Objectives Optimal procedures for adjuvant treatment and post-surgical surveillance of resected non-small-cell lung cancer remain under discussion. Pathological features are the main determinant of follow-up therapy but have limited ability to identify patients at risk of recurrence. Increasingly, molecular markers are incorporated into clinical decision-making, including measures of tumor growth. The CCP score is a quantitative, molecular measure of proliferation derived from the RNA expression of 31 cell cycle genes and a component of the molecular prognostic score (mPS). The mPS score is a linear combination of CCP score and pathological stage. CCP score and mPS are independent predictors of survival in resected lung adenocarcinoma. Materials and methods CCP scores were determined by RT-qPCR for 318 patients diagnosed with stage IâII lung adenocarcinoma. Association of mPS and CCP score with distant recurrence and lung-cancer specific survival was assessed in Cox proportional hazards regression models adjusted for age, gender, tumor size, pathological stage and pleural invasion. Distant recurrence-free survival and lung-cancer specific survival by mPS risk group were calculated by Kaplan-Meier survival analysis. Results CCP scores were obtained for 205 stage I and 84 stage II patients. CCP score and mPS were independent markers of distant recurrence (CCP: HR 1.62, 95%CI 1.15-2.29, pÂ&nbsp;=Â&nbsp;0.0055; mPS: HR 2.22, 95%CI 1.11-4.44, pÂ&nbsp;=Â&nbsp;0.023). Patients with low mPS tumors were at significantly reduced risk of distant recurrence (log-rank pÂ&nbsp;=Â&nbsp;4.2Â&nbsp;ÃÂ&nbsp;10â5). Among stage I patients, stratification by mPS identified a patient group with increased risk of distant recurrence (36%, 95%CI 28â46%, log-rank pÂ&nbsp;=Â&nbsp;0.0011) Conclusions The molecular prognostic score stratifies early-stage, resected lung cancer patients for risk of distant recurrence and could be useful to inform treatment and surveillance decisions