Randomized clinical trials provide the best evidence on the effect of treatment studied. There are different types of measures on the treatment effect, depending on the endpoints of the trials. For a given measure, based on the data from clinical trials, various statistical procedures are available for the inference of the treatment effect in terms of this measure. In a cancer clinical trial with a time to an event as the endpoint, hazard ratio is a popular measure for the relative difference between treatment groups. Most current statistical inference procedures for hazard ratio rely on the proportional hazard assumption, which may not be applicable to practice when it does not hold. Nonparametric confidence intervals for the hazard ratio have been proposed based on the asymptotic normality of the kernel estimate for the hazard ratio, but they were found not very satisfactory in the simulation studies. In the first part of this thesis, the empirical likelihood method is used to construct the confidence interval for the time-dependent hazard ratio. The asymptotic distribution of the empirical likelihood ratio is derived and simulation studies are conducted to evaluate the proposed method. It was also argued that the measure of the relative treatment effect based on the hazard ratio may be difficult to understand by clinicians. An alternative measure called probabilistic index was suggested and the C-index was proposed to estimate this index. However, it was pointed out recently that the expected value of the estimate based on the C-index may be far removed from the true index. In the second part of this thesis, assuming a semi-parametric density ratio model, two new estimates based on respectively the conditional likelihood and weighted empirical likelihood are proposed. Associated confidence intervals are also derived based on the bootstrap re-sampling method. The proposed inference procedures are evaluated by Monte-Carlo simulations and applied to the analysis of data from a clinical trial on early breast cancer. After primary analysis including all patients is completed in clinical trials, analysis by subgroups defined based on covariates of patients is often of interest to assess the homogeneity of treatment effects over these subgroups. The treatment-covariate interaction is usually used for this assessment. In the last part of this thesis, a non-parametric measure is used to quantify the interaction between treatments and binary covariates in the presence of censoring. Asymptotic distribution of the interaction estimates are derived and the bootstrap method is applied to construct the confidence intervals. The proposed approaches are also evaluated and compared by Monte-Carlo simulations and applied to a real data set from clinical trial. / Thesis (Ph.D, Mathematics & Statistics) -- Queen's University, 2011-05-21 11:07:52.992

Landfill leachate production is an unavoidable by-product of landfilling solid waste. Mitigation of the adverse environmental impacts of landfill leachate is required at all active and closed landfill sites. Since leachate production continues long after the landfill is closed and no longer generating revenue, management strategies including low-cost passive and naturalized landfill leachate treatment systems are ideal. The past practice of dumping solid waste into unused tracts of land has created many brownfield sites with uncontrolled discharges of leachate to the receiving environment. Belle Park in Kingston, Ontario is an example of such a site that has been reclaimed for recreational use. A seep management strategy, which included the installation of leachate extraction wells, has been implemented at the site. Passive treatment systems, a coastal fringe wetland and a phreatophyte plots, were installed to evaluate their effectiveness in conjunction with the leachate seep management. Modelling estimated that originally, the pumping wells decreased leachate discharge by 60%, and with the newer wells in 2007 the discharge was decreased by 75- 85%. In situ pilot-scale evaluations of treatments systems are required to ensure adequate treatment of the leachate. The Merrick Landfill in North Bay, Ontario currently captures leachate produced on site and is assessing the potential of a hybrid-passive landfill leachate treatment system. This design process started with bench-scale design and assessment of active pretreatment options, followed by an evaluation of passive and semi-passive treatment systems at the bench-scale (treating 2-3 L/day) at both room (24oC) and cold (2oC) ambient temperatures. The design process culminated with a pilot-scale assessment of hybrid-passive treatment systems (treating 2000 L/d). Assessment of flow in passive treatment system is usually conducted with tracer evaluations. Vertical-flow passive treatment systems with intermittent dosing of leachate for passive aeration have both saturated and unsaturated flow regions. This research shows that tracer evaluation of these types of system was insufficient to measure the clogging within the pore spaces. Therefore a time-lagged flux method was created, based on the pilot-scale hybrid passive treatment system at the Merrick Landfill. This analytical solution quantified the changes in saturated hydraulic conductivity in the treatment system cells. / Thesis (Ph.D, Civil Engineering) -- Queen's University, 2011-09-30 15:55:45.73

No description available.

Given the pervasive, debilitating nature of major depressive disorder, a large body of clinical research has evaluated the efficacy of short-term treatments for depression. Researchers have attempted to understand the complex mechanism of therapeutic change by examining treatment response, which is typically defined as the extent of symptom change between the intake and termination sessions. However, this approach fails to recognize that therapy is a non-linear, dynamic longitudinal process. An alternative approach involves analysis of longitudinal repeated measures process and outcome indicators in order to examine change both during treatment as well as following treatment. In order to evaluate dynamic, longitudinal hypotheses, it is necessary to use an appropriate analytical framework. A structural modelling technique termed Latent Difference Score Analysis (LDS) is well suited for this purpose, allowing for evaluation of longitudinal growth within a time series, while also considering multivariate relationships and determinants. / The purpose of this research was to evaluate established theories of depression vulnerability as well as theories of psychotherapy process, both during and following depression treatment. The research described in Chapter 2 examined several theories of the longitudinal relationship between depression and perfectionism during depression treatment, while considering the role of the therapeutic alliance. Longitudinal LDS analyses supported a "personality vulnerability" model of depression, in which perfectionism predicted the subsequent rate of depression change throughout treatment. Results indicate that patients with high levels of perfectionism experience less reduction in their depression scores throughout treatment. Furthermore, the strength of the therapeutic alliance significantly predicted the rate of change in personality vulnerability throughout therapy. The research described in Chapter 3 examined several theories of the longitudinal relationship between depression and stress following treatment termination. Results supported a "stress reactivity" model, in which stressful events led to elevations in the rate of depression change following therapy. Multigroup LDS analysis indicated that stress reactivity only occurred for patients who had been treated with medication, and not for those who had received psychotherapy. / These findings have several implications. First, comprehensive analyses of treatment efficacy can move beyond symptom reduction by examining mechanisms underlying treatment response using an appropriate statistical framework. The first paper demonstrates that an efficient route to symptom reduction involves establishing an adequate therapeutic alliance in order to target personality vulnerability. The second paper demonstrates that importance of evaluating treatment efficacy by considering whether a treatment leads to enduring change. Specifically, results indicate that the enduring effects of psychotherapy (in comparison to medication treatments) following treatment termination involves increased resiliency to stressful life events.

Obesity-related glomerulopathy (ORG) is an emerging epidemic for which an established model, diagnostic guidelines, and dietary treatments are absent. Oxylipins influence inflammation and hemodynamics, yet the renal oxylipin profile or the influence of dietary linoleic acid (LA) and alpha-linolenic acid (ALA) on their formation has yet to be examined. Therefore, obese-prone rats were provided high fat lard/soy diets to induce obesity and subsequently divided among 7 diets with varying LA and ALA levels. The diet-induced obese experimental model developed characteristics of ORG; morphology and histology revealed glomerulomegaly as an early diagnostic marker as it was the first pathological change and indicated further renal damage. Liquid chromatography-tandem mass spectrometry detected 30 oxylipins. Higher dietary ALA resulted in greater n-3 oxylipin levels and resulted in reduced progression of glomerulomegaly and glomerular damage. To conclude, ORG may be diagnosed earlier with glomerulomegaly and treated with dietary oils rich in ALA which alter the oxylipin profile.

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In designated nutrient-sensitive areas, phosphorus must be removed from sewage before it is discharged to the receiving water body. Phosphorus-rich sludge is generated, which is usually digested anaerobically prior to disposal. This research investigated the effect of phosphorus enrichment on metal and phosphorus fractionation in anaerobically digested sludge. The use of two complementary sequential chemical extraction procedures to measure phosphorus and metal fractionation, was a key focus of the research. The fractionation procedures were tested by sequentially extracting inorganic compounds (phosphates, sulphides and carbonates) which showed that the operationally defined metal and phosphorus fractions were not always representative of precise metal phases. Species were tentatively assigned to metal and phosphorus fractions using model compound results. Laboratory-scale batch anaerobic digestion experiments were performed, in which model compounds were used to simulate conditions of soluble and insoluble phosphorus enrichment. Soluble phosphorus at concentrations of 500 mg/l or greater was found to retard volatile solids removal and methane production in the laboratory digesters. Soluble phosphorus enrichment facilitated precipitation of calcium, magnesium and manganese but increased trace metal solubility, particularly that of chromium. Enrichment of digesters with Na2HP04 and MgCb caused struvite to precipitate in digesters containing 1000 mg/l of additional phosphorus. FeP04 enrichment of digested sludge showed that ferric iron was reduced to ferrous iron, releasing soluble phosphorus into the digester. Most of the phosphorus was reprecipitated as ferrous phosphate, causing co-precipitation of magnesium, manganese and cobalt. By contrast, A1P04 added to the digesters was stable in the sludge. Full-scale CPR sludge digestion (Fe2(S04)3 dosing) caused soluble phosphorus in the digester to decrease below 0.05 mg/l. Phosphorus remained associated with iron in the sludge fraction but soluble calcium and magnesium concentrations in the full-scale digester increased as a result of CPR sludge digestion. Comparison of laboratory and full-scale results showed that the fate of iron-precipitated phosphorus in digested sludge was primarily dependent pn the molar ratio of Fe:P in the sludge. Full-scale BPR sludge digestion showed high concentrations of soluble phosphorus in the digester and some struvite precipitation, although phosphorus was precipitated primarily as calcium phosphate, as was found to occur in the laboratory digesters simulating BPR sludge digestion.

Apical periodontitis, an acute or chronic inflamination around the apex of the tooth, is caused by bacteria in the root canal. In Sweden the dentists devote around 10X of their total time to treating this disease. The treatment usually requires 3 to 5 sessions. The treatment may fail in up to 25X of the cases. In the present study various treatment regimens were evaluated. One hundred and forty singlerooted teeth with apical periodontitis were treated. The importance of mechanical instrumentation, irrigating solutions and antibacterial dressings in eliminating bacteria from the infected root canals was studied using bacteriological techniques. The healing of the apical periodontitis after treatment was followed for 2 to 5 years on recall radiographs. Bacteria were found in all 140 root canals at the beginning of the treatment. Most of these bacteria were anaerobes and they represented a restricted group of bacteria compared to the bacteria present at other sites in the oral cavity. Mechanical instrumentation with files and reamers in combination with saline irrigation reduced the number of bacterial cells in the root canal 100- to 1000-fold during one treatment session. Bacteria could be eliminated from about half the number of root canals if this treatment was performed at 4 sessions. Mechanical instrumentation and irrigation with 0.5X or 5X sodium hypochlorite solutions or with the 5X solution in combination with 15X EDTA solution wa3 more efficient and the bacteria were eliminated from about half the treated canals after one treatment session. The bacteria which persisted in the root canal after this treatment usually increased in number during the interval up to the next session and reached levels which were often as high as in the initial sample at the previous session. All bacteria persistent in the root canals after the previous treatment regimens were with 2 exceptions eliminated by dressing the root canals for 1 to 2 months with calcium hydroxide paste. Thirty-four out of 35 root canals treated at the first session with mechanical instrumentation, irrigation with sodium hypochlorite solution and dressed with calcium hydroxide paste were free of bacteria at the second session. Calcium hydroxide paste was superior to camphorated phenol and camphorated paramonochlorophenol as dressing. Healing of 79 out of the 140 treated teeth was followed for 2 to 5 years. The majority of the lesions healed completely or decreased in size in such a way that they could be expected to heal. There was no or only an insignificant decrease in the size of the lesions in 5 cases. In 2 of these cases bacteria were demonstrated in the periapical tissues and in a third case dentin chips. Periapical lesions may thus fail to heal in a few cases due to an establishment of bacteria outside the root canal, and in that site the bacteria are inaccessible to conventional endodontic treatment. The present study showed that treatment of the majority of infected non-vital teeth can be completed in only 2 sessions, if mechanical instrumentation, sodium hypochlorite irrigation and calcium hydroxide dressing are combined. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1986, härtill 5 uppsatser.</p> / digitalisering@umu

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No description available.