Failure time data analysis, or survival analysis, is involved in various research fields, such as medicine and public health. One basic assumption in standard survival analysis is that every individual in the study population will eventually experience the event of interest. However, this assumption is usually violated in practice, for example when the variable of interest is the time to relapse of a curable disease resulting in the existence of long-term survivors. Also, presence of unobservable risk factors in the group of susceptible individuals may introduce heterogeneity to the population, which is not properly addressed in standard survival models. Moreover, the individuals in the population may be grouped in clusters, where there are associations among observations from a cluster. There are methodologies in the literature to address each of these problems, but there is yet no natural and satisfactory way to accommodate the coexistence of a non-susceptible group and the heterogeneity in the susceptible group under a univariate setting. Also, various kinds of associations among survival data with a cure are not properly accommodated. To address the above-mentioned problems, a class of models is introduced to model univariate and multivariate data with long-term survivors. A semiparametric cure model for univariate failure time data with long-term survivors is introduced. It accommodates a proportion of non-susceptible individuals and the heterogeneity in the susceptible group using a compound- Poisson distributed random effect term, which is commonly called a frailty. It is a frailty-Cox model which does not place any parametric assumption on the baseline hazard function. An estimation method using multiple imputation is proposed for right-censored data, and the method is naturally extended to accommodate interval-censored data. The univariate cure model is extended to a multivariate setting by introducing correlations among the compound- Poisson frailties for individuals from the same cluster. This multivariate cure model is similar to a shared frailty model where the degree of association among each pair of observations in a cluster is the same. The model is further extended to accommodate repeated measurements from a single individual leading to serially correlated observations. Similar estimation methods using multiple imputation are developed for the multivariate models. The univariate model is applied to a breast cancer data and the multivariate models are applied to the hypobaric decompression sickness data from National Aeronautics and Space Administration, although the methodologies are applicable to a wide range of data sets. / published_or_final_version / Statistics and Actuarial Science / Master / Master of Philosophy

I examined habitat selection of middens within insect-damaged forest and compared home range and survival for Mt. Graham red squirrels (Tamiasciurus hudsonicus grahamensis) in insect-damaged and healthy forest. Squirrels used habitat in areas with < 69% tree mortality. Basal area, canopy cover, and log volume were greater at middens than random locations. Within midden sites, only greater basal area of live trees distinguished occupied sites from unoccupied sites. Surface temperature at occupied middens tended to be cooler than unoccupied middens. Squirrels living in insect-damaged forest had larger home ranges than in healthy forest. Squirrel body mass and reproductive condition did not differ between forest types, suggesting that insectdamaged forest provided adequate resources. However, squirrels inhabiting insectdamaged forest experienced lower survivorship and 50% fewer potential reproductive events than squirrels in healthy forest, implicating presence of an ecological trap. Preservation of remaining healthy forest is a priority for management of this endangered species.

published_or_final_version / abstract / toc / Statistics and Actuarial Science / Master / Master of Philosophy

The first study was designed to determine the occurrence of bacteria in dishcloths used in restaurants and bars. Coliforms were isolated from 89% of dishcloths and 70% of tabletops. Escherichia coli was isolated from 54% of dishcloths and 20% of tabletops. The numbers of heterotrophic bacteria (HPC) and coliforms were higher in bars than in restaurants. The levels of HPC found in dishcloths were 25-fold and coliforms were 60-to 120-fold lower than the levels found in dishcloths in previous home studies. The most commonly isolated genera from dishcloths in restaurants and bars differed from those in homes. The numbers of HPC on restaurant tabletops were 45-fold greater after cleaning than prior to cleaning. The mandatory use of sanitizers in restaurants and bars may therefore have reduced contamination levels and caused a shift in the microbial populations present in food service establishments. The second study was designed to determine the recovery efficiency and the survival of two respiratory viruses on produce and was compared to the survival of the enteric poliovirus 1. Adenovirus was recovered with an efficiency of 56%, 32% and 35% from lettuce, strawberries and raspberries, respectively. Coronavirus was recovered from lettuce with an efficiency of 19.6%, but could not be recovered from strawberries. Poliovirus was recovered from lettuce with an efficiency of 76.6% and 0.06% from strawberries. The survival of the viruses was observed for up to eight days. Adenovirus survived the longest on raspberries, with a log₁₀ reduction of 0.61, followed by 1.68- and 1.75-log₁₀ reductions on strawberries and lettuce, respectively. Coronavirus declined by 0.41-log₁₀ after two days and >1.34 log₁₀ by day 4 on lettuce. The enteric poliovirus 1 survived longer on produce, decreasing by only 0.37-log₁₀ on lettuce and 1.30-log₁₀ on strawberries. A microbial risk assessment was performed to assess the risk of infection from ingesting 1, 10, and 100 particles of adenovirus on lettuce. The estimated risk of infection by ingesting these numbers were 1:2000, 1:200, and 1:20, respectively and increased in a proportional way as the number of servings was increased from one to ten and 365 servings of lettuce.

Introduction: This study evaluated long-term outcomes of young survivors of colorectal cancer including survival, development of acute illnesses, and childbirth. Methods: Persons aged 20-44 diagnosed with colorectal cancer and surviving at least five years were identified using the Ontario Cancer Registry and compared to randomly selected controls. Outcomes included death, admission to hospital for acute illness, and childbirth in women, determined by linkage to provincial administrative data. Results: There were 917 cancer survivors in this study. Survivors were more likely to die (HR 8.2, 95%CI [5.8, 11.6]), and require admission to hospital for acute illness (rate ratio 3.4, 95%CI [2.9, 4.1]) than controls. There was no difference in admissions for childbirth in women (HR 0.6, 95%CI [0.3, 1.4]). Conclusions: Five-year survivors of colorectal cancer remain at high risk of long-term death and illness. Aggressive surveillance for recurrent malignant disease is necessary to mitigate risk of death.

Introduction: This study evaluated long-term outcomes of young survivors of colorectal cancer including survival, development of acute illnesses, and childbirth. Methods: Persons aged 20-44 diagnosed with colorectal cancer and surviving at least five years were identified using the Ontario Cancer Registry and compared to randomly selected controls. Outcomes included death, admission to hospital for acute illness, and childbirth in women, determined by linkage to provincial administrative data. Results: There were 917 cancer survivors in this study. Survivors were more likely to die (HR 8.2, 95%CI [5.8, 11.6]), and require admission to hospital for acute illness (rate ratio 3.4, 95%CI [2.9, 4.1]) than controls. There was no difference in admissions for childbirth in women (HR 0.6, 95%CI [0.3, 1.4]). Conclusions: Five-year survivors of colorectal cancer remain at high risk of long-term death and illness. Aggressive surveillance for recurrent malignant disease is necessary to mitigate risk of death.

Background: Inflammatory breast cancer (IBC) is a rare form of breast cancer associated with a poor prognosis. This study describes the incidence, survival, and management of IBC in the province of Ontario. Methods: We conducted a retrospective, population-based, cohort study using data systems held at the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario. Using the Ontario Cancer Registry (OCR), we identified all primary, pathologically confirmed cases of breast cancer. IBC cases were identified using the unique histology code ‘85303’. OCR records were linked to Statistics Canada data, Canadian Institutes of Health Information (CIHI) records of surgical procedures, and cancer centre records detailing radiotherapy and chemotherapy administration. We calculated age-adjusted incidence rates of IBC for cases diagnosed between 1984 and 2005. Using the Kaplan Meier product-limit method and log-rank statistics we compared overall survival for IBC and non-IBC, and assessed temporal and regional variations in IBC survival. We described the management of IBC for patients diagnosed between 1984 and 2004, and assessed variations over time and across cancer centres. Results: Age-adjusted incidence rates of IBC increased from 0.57/105 women-years in 1984-1987 to 1.15/105 women-years in 2003-2005 (p<0.0001). 10-year survival was 21.5% for IBC compared to 61.7% for non-IBC (p<0.0001). For IBC, 10-year survival increased from 12.0% (95% CI: 8.3–16.3) for those diagnosed between 1984-1994 to 24.0% (95% CI: 20.1–28.2) for those diagnosed between 1995-2005. The utilization of combined mastectomy and postoperative radiotherapy increased from 28.9% in 1984-1994 to 46.1% in 1995-2004 (p<0.0001). We observed no statistically significant difference in the utilization of chemotherapy over time. Differences in the utilization of combined mastectomy and postoperative radiotherapy were observed across cancer centres (29.8% at centre C vs. 54.7% at centre A, p<0.0001). We also observed wide variations in the estimates of survival across cancer centres. Discussion: Rates of IBC have increased over time in Ontario and we observed an improvement in the long-term survival. Management has shifted over time towards increased use of mastectomy and postoperative radiotherapy. Additional prognostic information is needed to determine how variations in practice may be related to variations in outcome. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2009-09-24 16:15:10.068

No description available.

No description available.

This study was conducted to test the hypothesis that dietary supplementation with L-arginine during early pregnancy will ameliorate embryonic loss in pigs. Gilts were bred at the second estrus, and housed individually in pens and fed twice daily 1 kg of a corn- and soybean meal-based diet supplemented with 0.0%, 0.4%, or 0.8% L-arginine (w/w) between d 0 and 25 of gestation (Experiment 1) or between d 14 and 25 of gestation (Experiments 2 and 3). At d 25 (Experiment 1 and 2) or d 60 (Experiment 3) of gestation, gilts were hysterectomized to obtain uteri and conceptuses. Total RNA and protein were extracted from the frozen tissues. Quantitative RT-PCR, western blotting, and microarray analyses were performed to determine the changes of gene expression at mRNA and protein levels. Dietary supplementation with 0.8% L-arginine between d 0 and 25 of gestation decreased uterine weight, total number of fetuses, number of corpora lutea (CL), total fetal weight, total volume of allantoic and amniotic fluids, concentrations of progesterone in maternal plasma and allantoic fluid, compared to the control group. However, dietary supplementation with 0.4% or 0.8% L-arginine between d 14 and 25 of gestation increased total volume of amniotic fluid, total amounts of arginine in allantoic and amniotic fluids, total amounts of fructose and most amino acids in amniotic fluid, placental growth, and the number of viable fetuses per litter by 2. Dietary supplementation with 0.4% or 0.8% L-arginine between d 14 and 25 of gestation increased the total number of fetuses and number of live fetuses, rate of embryonic survival, and volumes of allantoic and amniotic fluids in gilts with 15 to 18 CL on d 60 of gestation compared with the control group. The abundance of placental protein and expression of mRNA related to the genes for arginine transport and metabolism, including cationic amino acid transporter 1, endothelial nitric oxide synthase (NOS3), phosphorylated-NOS3, ornithine decarboxylase, and guanosine triphosphate cyclohydrolase-I was increased by dietary supplementation with 0.8% L-arginine between d 0 and 25 of gestation. The abundance of total and phosphorylated mechanistic target of rapamycin was also enhanced by dietary 0.8% L-arginine supplementation between d 0 and 25 of gestation. Microarray analysis revealed that supplementation with 0.8% arginine between d 14 and 25 of gestation affected placental expression of 575 genes. Findings from the current study not only advance basic knowledge of mammalian reproductive biology, but also have important implications for developing practical means to enhance fertility in female pigs.