Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves [127]-129).

Thesis (Ph. D.)--Florida State University, 2005. / Advisor: Dr. Ian W. McKeague, Florida State University, College of Arts and Sciences, Dept. of Statistics. Title and description from dissertation home page (viewed June 16, 2005). Document formatted into pages; contains vii, 73 pages. Includes bibliographical references.

Thesis (Ph. D.)--Ohio State University, 2005. / Title from first page of PDF file. Document formatted into pages; contains xi, 108 p.; also includes graphics (some col.) Includes bibliographical references (p. 101-108). Available online via OhioLINK's ETD Center

Background: The main cause of death in HIV patients is tuberculosis (TB). However, few Latin American studies have evaluated the prognosis of patients with coinfection. Aim: To determine the factors associated with survival in patients with HIV-TB coinfection treated at a Peruvian referral hospital. Methods: A retrospective cohort study was performed based on clinical records of patients treated at the Department of Infectious Diseases in the Arzobispo Loayza National Hospital from 2004 to 2012. Survival was assessed using the Kaplan-Meier estimator and Cox Proportional Hazard Model. Results: From 315 patients, 82 died during the follow-up. The mean of follow for each patient was 730 days. The multivariate analysis showed that receiving HAART (HR: 0,31; IC: 0,20-0,50; p < 0,01) and having more weight (HR: 0,96; IC 0,94–0,98; p < 0,01) when the coinfection was diagnosed, were protective factors; while having a pathology different from TB (HR: 1,88; IC: 1,19-2,98; p < 0,01), age in years (HR: 1,76; IC: 1,12-2,74; p ≤ 0,01) and being hospitalized when diagnosed with TB (HR: 1,69; IC 1,02-2,80; p < 0,04) were associated with lower survival. Discussion: Receiving HAART and having more weight when the coinfection is diagnosed were associated with a higher chance of survival. / Revisión por pares

In clinical trials, patients are enrolled into two treatment arms. A researcher may be interested in studying the effectiveness of a new drug or the comparison of two drugs for the treatment of a disease. This survival data is later analysed using the logrank test or the Cox regression model to detect differences in survivor functions. However, the power function of the logrank test depends solely on the number of patients enrolled into the study. Because statisticians will always minimise type I and type II errors, a researcher carrying out a clinical trial must define beforehand, the number of patients to be enrolled into the clinical study. Without proper sample size and power estimation a clinical trial may fail to detect a false hypothesis of the equality of survivor functions. This study presents through simulation, a way of power and sample size estimation for clinical trials that use the logrank test for their data analysis and suggests an easy method to estimate power and sample size in such clinical studies. Findings on power analysis and sample size estimation on logrank test are applied to two real examples: one is the Veterans' Administration Lung Cancer study; and the other is the data from a placebo controlled trial of gamma interferon in chronic granulotomous disease.

La « survie psychique » concerne les sujets qui vivent sous la menace de leur propre disparition et d’un effondrement qui les priverait de tout « a-venir ». Ils doivent faire face à des ruptures dans le continuum qui engagent des « effets de corps » révélant toujoursun corps mal métabolisé psychiquement. Marqué par la discontinuité, l’être puise ici son énergie dans celle du « désêtre», dont l’appréhension passe par ses vicissitudes et celles du lien corps/psyché, mais aussi par les voies de l’originaire et de la sensorialité. Pour s’infiltrer dans les interstices du mort et du vivant, il nous faut donc revenir sur l’émergence du corps sensoriel-érogène, ce corps relationnel qui naît d’une prime de plaisir, en tant qu’elle est la condition de tout mouvement d’investissement, et donc de la vie même. Car lorsque le sentiment d’exister vacille et que la déliaison somato-psychique est à son comble, la retrouvaille d’un « plaisir nécessaire » – sous-entendant celle d’un pictogramme –est de l’ordre du « psychiquement vital ». Dans ce sens, nous parlons d’économie de survie, économie dont l’exploration s’enrichit de la proposition d’un principe de survie/principe d’anéantissement, et trouve ses « limites » dans le flou structural qu’elle sous-tend. A l’écoute des patients qui m’ont incitée à entreprendre cette recherche, cela est d’autant plus saisissant qu’une grande fragilité des assises narcissiques et une problématique prégénitale désorganisatrice (engageant la mobilisation de défenses primitives), cohabitent avec le maintien d’une réflexivité intrapsychique et d’une intelligence souvent remarquable.Pour déjouer ces ruses de la psyché, nous proposons donc la perspective d’un travail aux limites de l’être permettant au temps de retrouver son pouvoir de transformation età la réanimation du corps sensoriel-érogène devant la perte du sentiment continu d’exister de trouver sa source ailleurs que dans une « énergie du désêtre ». / The “psychic survival” concerns subjects who live under the threat of their own disappearance and a breakdown that would deprive them of everything that is “to (be)-come”. They have to face breaches in the continuum which engage “body effects” that always give away a body poorly metabolized psychologically. Marked by discontinuity, the being draws its energy from “unbeing”, while its apprehension goes through its vicissitudes as well as the ones of the bond between body/psyche, but also through the ways of origin and sensoriality. In order to penetrate into the interstices of death and life, we therefore have to return to the emergence of the “sensory-erogenous body”, this relational body that is born out of a pleasure premium which is as such the prerequisite of every move of investment and therefore of life itSelf. For when the “going on being” falters and the psychosomatic unbinding is at its peak, finding a “necessary pleasure” again – meaning the one of a pictogram – is within the range of the “psychologically vital”. In this sense, we talk about the economics of survival, an economy whose exploration is expanded by the proposal of a “principal of survival/principal of annihilation” and which finds its “limits” in the underlying structural vagueness. While listening to patients who have inspired me to conduct this research, it is even more striking to find very fragile narcissistic foundations and disorganising pregenital issues (which engage the mobilization of primitive defence) side-by-side with intrapsychic reflexivity and oftentimes remarkable intelligence. In order to breach the stratagem of the psyche, we therefore propose the perspective of working along the limits of the being, thus allowing the time to find one’s power of transformation and reanimation of the “sensory-erogenous body” facing the loss of the “going on being” by finding its source elsewhere than through the “energy of unbeing”.

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. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate

In studying natural history of a disease, incident studies provide the best quality estimates; in contrast, prevalent studies introduce a sampling bias, which, if the onset time of the disease follows a stationary Poisson process, is called length bias. When both types of data are available, combining the samples under the assumption that failure times in incident and prevalent cohorts come from the same distribution function, could improve the estimation process from a revalent sample. We verify this assumption using a Smirnov type of test and construct a likelihood function from a combined sample to parametrically estimate the survival through maximum likelihood approach. Finally, we use Accelerated Failure Time models to compare the effect of covariates on survival in incident, prevalent, and combined populations. Properties of the proposed test and the combined estimator are assessed using simulations, and illustrated with data from the Canadian Study of Health and Aging.

In sub-Saharan Africa, resource-limitation results in scarce availability of HIV prognostic tools such as CD4+ T-Lymphocyte (CD4) count and HIV viral load. To facilitate counselling and clinical decisions in this setting, widely available and inexpensive markers of prognosis are required. Chapter one gives an overview of the epidemiology and pathophysiology of HIV infection (with particular reference to sub-Saharan Africa), and its clinical manifestations. Staging systems for HIV infection and aspects of management in resource-poor environments are briefly discussed. Chapter two describes the epidemiological, pathophysiological and clinical aspects of tuberculosis (TB) in HIV infected patients, the commonest opportunistic infection in sub-Saharan Africa. It further provides HIV and TB prevalence data from the Western Cape, South Africa. In chapter three a study is presented demonstrating the usefulness of the total lymphocyte count (TLC) in combination with the World Health Organisation (WHO) clinical staging system to predict outcome in 831 HIV positive patients. A TLC of 1250/μL was found to be the equivalent of a CD4 count of 200/μL. Patients with early HIV disease (WHO stage 1&2) had low annual rates of progression to AIDS : 3-4% if the TLC was above 1250/μL, 12-14% if the TLC was below 1250/μL. Annual progression to AIDS increased to 25% and 46% in patients with clinical stage 3 and a TLC above or below 1250/μL respectively. Patients with AIDS had 30-55% one-year mortality rates depending on the TLC. Chapter four illustrates that pulmonary tuberculosis (PTB) in HIV infected patients presents with a radiographic spectrum reflecting the degree of HIV induced immune suppression. Chest radiographs and pre-treatment total lymphocyte counts provide prognostic information. Upper zone cavitatory infiltrates typical of reactivation PTB were associated with a preserved CD4 count (mean 389/μL) and predicted a 100% two-year survival. Pleural effusions were associated with a mean CD4 count of 184/μL and predicted 65% two-year survival. Patients with atypical radiographic presentation, including lower and mid-zone infiltrates, hilar and mediastinal adenopathy or interstitial patterns, had low CD4 counts (mean 105/μL) and a 36% survival at two years. Rather than classifying every patient with pleura-pulmonary tuberculosis as WHO stage 3, incorporation of the prognostic value of the chest radiograph into the clinical staging system, such that typical reactivation PTB becomes stage 2, tuberculous pleural effusion stage 3 and atypical PTB stage 4, would enhance the prognostic accuracy of HIV related tuberculosis. Chapter five demonstrates that patients with AIDS could be categorized accord ing to one of three survival patterns, relating to the type of opportunistic illness. One-year survival rates were highest for extra-pulmonary tuberculosis and herpes simplex virus infection (70% ); intermediate for oesophageal candidiasis, cryptococcal meningitis, kaposi sarcoma and pneumocystis carinii pneumonia (45%) ; and poorest for the HIV wasting syndrome, AIDS-dementia complex and performance status 4 (20%). Despite the overall poor prognosis associated with the acquired immunodeficiency syndrome, a substantial proportion of patients survive, even in the absence of anti-retroviral therapy, for a number of years. Chapter six concludes by proposing how the data presented in this thesis could be used in the clinical management of patients with HIV infection in a resource limited environment.

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