Campylobacterjejuni, a Gram-negative enteric pathogen, is the leading cause of bacterial gastroenteritis in the developed world. A C. jejuni strain 8 1-176 transposon library was used to screen for mutants over-producing a calcofluor white (CFW)-reactive polymer implicated in biofilm formation. This identified two lipooligosaccharide (LOS) core mutants: one defective for a two-domain glycosyltransferase (lgtF), and the other defective in a heptosyltransferase (waaF). To determine if other LOS core mutants displayed a similar phenotype, and to explore other biological outcomes of step-wise LOS truncations on C. jejuni stress resistance and pathogenesis, mutant strains defective for GaiT and CstII were also constructed. Silver stain and mass spectrometry analyses confirmed the sequential truncation of sialic acid (ΔcstII), galactose (ΔgalT), two glucoses (ΔlgtF), and heptose II (ΔwaaF). While the ΔlgtF and ΔwaaF mutants exhibited enhanced biofilm formation and ΔlgtF displayed increased sensitivity to complement killing, no effect for these phenotypes and only modest alterations in CFW reactivity were seen with partial outer core truncations. Deletion of LgtF had no effect on mouse colonization in vivo, or on invasion and intracellular survival in epithelial cells in vitro. In contrast, the ΔwaaF mutant exhibited a significant defect in intracellular survival in vitro. Interestingly, the mutants exhibited stepwise increases in susceptibility to the antimicrobial peptide LL-37, with /waaF and ΔlgtF being more susceptible and ΔgalT and ΔstII being more resistant than wild type. In contrast, all of the mutants were highly susceptible to polymyxin B. This is the first report of C. jejuni susceptibility to LL-37 and of LOS affecting polymyxin B resistance. Each of these appears to be independent of overt effects on outer membrane protein expression, membrane stability, or surface hydrophobicity. Together, our data indicate that the length and specific moieties of the LOS play important roles in C. jejuni biology, and suggest a dynamic interplay of the LOS with other stress resistance factors.

Understanding factors limiting population growth is critical for species exhibiting declining populations. Reproductive success has an important effect on population dynamics; however, our ability to accurately estimate productivity is limited. Studies on avian breeding biology have focused on nest survival; however, surviving to fledging does not ensure survival to the end of the breeding season. Furthermore, our understanding of habitat selection by birds based on the nesting cycle may not adequately represent the breeding habitat requirements because habitat use often changes after the young leave the nest. My goal was to examine the postfledging dependence period of two flycatcher species in the central Sierra Nevada: the California state endangered willow flycatcher (Empidonax traillii) and the dusky flycatcher (E. oberholseri). My focus was to estimate fledgling survival and examine factors that influence survival, evaluate postfledging movements and habitat use, and estimate post-breeding home range sizes of postfledging flycatchers. I monitored nests of both flycatcher species, individually color banded nestlings, and observed family groups daily once the young fledged. Flycatcher fledgling survival ranged from 46 percent to 76 percent and varied by year and species. Survival was lowest during the first week of the postfledging dependence period for both species. Fledgling flycatchers moved on average ~45m per day during the dependence period. I detected family groups in the natal meadows from 13 to 33 days. I detected willow flycatchers in riparian shrub vegetation 94 percent of the time, with the remaining detections being along the upland forest edge. Dusky flycatchers were more likely to use upland forest vegetation after leaving the nest, as I detected them in riparian shrub vegetation 70 percent of the time. For both years combined, mean 95 percwnt home range sizes were 1.80 ± 1.44 ha for willow flycatchers and 1.82 ± 1.70 ha for dusky flycatchers. Mean 50 percent core areas were 0.33 ± 0.27 ha for willow flycatchers and 0.38 ± 0.44 ha for dusky flycatchers. My results suggest that using fledgling survival throughout the dependence period to assess reproductive output is more accurate than using nesting data alone. Furthermore, postfledging family groups used a larger area of habitat than what is typically estimated from territory mapping singing males. Future research should continue to stress the importance of gaining knowledge about the postfledging period, especially for species with declining populations.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (p. 131-134).

Thesis (M. Phil.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 91-97).

In cancer research the efficacy of a new treatment is often assessed by means of a clinical trial. In such trials the outcome measure of interest is usually time to death from entry into the study. The time to intermediate events may also be of interest, for example time to the spread of the disease to other organs (metastases). Thus, cancer clinical trials can be seen to generate multi-state data, in which patients may be in anyone of a finite number of states at a particular time. The classical analysis of data from cancer clinical trials uses a survival regression model. This type of model allows for the fact that patients in the trial will have been observed for different lengths of time and for some patients the time to the event of interest will not be observed (censored). The regression structure means that a measure of treatment effect can be obtained after allowing for other important factors. Clinical trials are not conducted in isolation, but are part of an on-going learning process. In order to assess the current weight of evidence for the use of a particular treatment a Bayesian approach is necessary. Such an approach allows for the formal inclusion of prior information, either in the form of clinical expertise or the results from previous studies, into the statistical analysis. An initial Bayesian analysis, for a single non-recurrent event, can be performed using non-temporal models that consider the occurrence of events up to a specific time from entry into the study. Although these models are conceptually simple, they do not explicitly allow for censoring or covariates. In order to address both of these deficiencies a Bayesian fully parametric multiplicative intensity regression model is developed. The extra complexity of this model means that approximate integration techniques are required. Asymptotic Laplace approximations and the more computer intensive Gauss-Hermite quadrature are shown to perform well and yield virtually identical results. By adopting counting process notation the multiplicative intensity model is extended to the multi-state scenario quite easily. These models are used in the analysis of a cancer clinical trial to assess the efficacy of neutron therapy compared to standard photon therapy for patients with cancer of the pelvic region. In this trial there is prior information both in the form of clinical prior beliefs and results from previous studies. The usefulness of multi-state models is also demonstrated in the analysis of a pilot quality of life study. Bayesian multi-state models are shown to provide a coherent framework for the analysis of clinical studies, both interventionist and observational, yielding clinically meaningful summaries about the current state of knowledge concerning the disease/treatment process.

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

Campylobacterjejuni, a Gram-negative enteric pathogen, is the leading cause of bacterial gastroenteritis in the developed world. A C. jejuni strain 8 1-176 transposon library was used to screen for mutants over-producing a calcofluor white (CFW)-reactive polymer implicated in biofilm formation. This identified two lipooligosaccharide (LOS) core mutants: one defective for a two-domain glycosyltransferase (lgtF), and the other defective in a heptosyltransferase (waaF). To determine if other LOS core mutants displayed a similar phenotype, and to explore other biological outcomes of step-wise LOS truncations on C. jejuni stress resistance and pathogenesis, mutant strains defective for GaiT and CstII were also constructed. Silver stain and mass spectrometry analyses confirmed the sequential truncation of sialic acid (ΔcstII), galactose (ΔgalT), two glucoses (ΔlgtF), and heptose II (ΔwaaF). While the ΔlgtF and ΔwaaF mutants exhibited enhanced biofilm formation and ΔlgtF displayed increased sensitivity to complement killing, no effect for these phenotypes and only modest alterations in CFW reactivity were seen with partial outer core truncations. Deletion of LgtF had no effect on mouse colonization in vivo, or on invasion and intracellular survival in epithelial cells in vitro. In contrast, the ΔwaaF mutant exhibited a significant defect in intracellular survival in vitro. Interestingly, the mutants exhibited stepwise increases in susceptibility to the antimicrobial peptide LL-37, with /waaF and ΔlgtF being more susceptible and ΔgalT and ΔstII being more resistant than wild type. In contrast, all of the mutants were highly susceptible to polymyxin B. This is the first report of C. jejuni susceptibility to LL-37 and of LOS affecting polymyxin B resistance. Each of these appears to be independent of overt effects on outer membrane protein expression, membrane stability, or surface hydrophobicity. Together, our data indicate that the length and specific moieties of the LOS play important roles in C. jejuni biology, and suggest a dynamic interplay of the LOS with other stress resistance factors.

Diabetes Care Program of Nova Scotia (DCPNS) Registry data were used to examine factors associated with survival for clinically confirmed diabetes mellitus (DM) cases. Type 1 (N=2,043) and type 2 (N=47,974) cases were followed from first Diabetes Centre visit until death/study end. Kaplan Meier curves and Cox proportional hazard models were used to explore differences in survival by sex, district health authority of care, and comorbidity status (hypertension and/or dyslipidemia). Median lifespan for type 1 cases was 12 years shorter than for type 2 cases. Hazard rate ratios for those with dyslipidemia, hypertension, or both compared to those with neither comorbidity were 1.63, 2.57, and 7.52 for type 1 cases and 0.95, 1.15, and 1.00 for type 2 cases. Disease progression and the relationship between comorbidity status and survival differed markedly for the type 1 and type 2 DM populations underscoring the need to examine these populations separately.

No description available.

Thesis (M.S.)--Georgia State University, 2008. / Title from file title page. Xu Zhang, committee chair; Yichuan Zhao, Jiawei Liu, Yu-Sheng Hsu, committee members. Electronic text (51 p.) : digital, PDF file. Description based on contents viewed July 15, 2008. Includes bibliographical references (p. 50-51).