An investigation was conducted on the reaction between silica glass and the refractory metals, Mo, V, Nb, Ta, Ti and Zr. The metals were heated to 1650°C under vacuum (5x10⁻⁴m.m. of Hg.) in contact with the silica. The interface was examined metallographically. The formation of compounds was examined by X-ray diffraction technique. A liquid layer was formed by reaction of the metals with silica. This reaction was responsible for bonding between the two phases. Vanadium and tantalum showed the best bonding characteristics. Niobium formed only a fair bond. In the case of molybdenum and titanium little adhesion occurred. Experimental observations and theoretical considerations indicated that in most cases the liquid was a low fusible silicate. The nature of the reaction was found to be essentially oxidation of the metal followed by solution of the oxides in the glass. Vanadium oxides are rapidly dissolved in silica causing extensive corrosion of the metal. The oxides of niobium and tantalum do not dissolve so rapidly. Only molybdenum showed good corrosion resistance under experimental conditions. The oxides found at room temperature were respectively VO₀․₉, Nb₂O₅, Ta₂O₅ and MoO₉. X-Ray data showed that tantalum - silica interface contained other species that could be silicon, silica, sub-oxides, silicides and crystallised silicates. / Applied Science, Faculty of / Materials Engineering, Department of / Graduate

A computational procedure for the evaluation of inelastic responses and ductility demands of three dimensional buildings subjected to multi-component earthquake excitations is presented. The modified substitute structure method is based on elastic modal analysis but is an iterative procedure which involves a fictitious linear structure whose stiffness and damping characteristics are related to the ductility demands. The building is idealized as an assembly of plane frames interconnected by rigid diaphragms. Coupling of individual frames through common columns is taken into account. It is not necessary for all storey masses to lie on a vertical line, so that structures with varying floor dimensions can be modelled. Two reinforced concrete structures of different types, moment resisting frames and coupled wall cores, are tested with the method. The accuracy of the method for predicting ductility demands and lateral deflections is determined by comparison with averaged results obtained from the time step analysis program DRAIN-TABS. The proposed method fills the void between elastic modal analysis which cannot provide information on inelastic behaviour of the structure, and full scale time step analysis which is complex and expensive to use. / Applied Science, Faculty of / Civil Engineering, Department of / Graduate

Background: There is widespread concern about the rise of drug-resistant TB because treatment outcomes of affected patients remain poor and treatment options are limited. After more than a forty-year gap without any breakthrough discovery, several new (bedaquiline and delamanid) and repurposed drugs (linezolid) are increasingly becoming available for use. However, data regarding the efficacy and safety of these drugs in drug-resistant TB patients, with or without HIV infection, from a real-life programmatic setting are lacking. This thesis aims to address that knowledge gap and provide information for management of drug-resistant TB in countries with high disease burden. Methods: A total of 326 drug resistant TB patients were prospectively followed up between January 2008 and April 2018. The efficacy and safety of two new drugs (bedaquiline and delamanid) and one repurposed drug (linezolid) was determined in these patients in three studies. In the first study, 24 months treatment outcomes and adverse event profiles were compared between extensively drug resistant (XDR) TB patients who received programmatic treatment regimens with the backbone of second line injectables and fluoroquinolones (nonbedaquiline-based) and those who received a bedaquiline- and/ or linezolid-based treatment regimen. The second study determined the frequency of system-specific adverse events associated with linezolid. The third study interrogated the safety and effectiveness of a strengthened treatment regimen containing a combination of delamanid and bedaquiline in patients with poor prognostic features compared to bedaquiline-based regimen. Results: In the first study, patients who received a bedaquiline-based treatment regimen had a significantly greater favourable outcome rate (66.2% vs 13.2%; p<0.001) ), more than a fourfold reduction in treatment failure rate (5.9% vs 26%; p<0.001 ) and less than a half of mortality rate compared to patients who received a non-bedaquiline-based regimen. The bedaquiline survival and favourable outcome effect remained significant in HIV-infected patients (p<0.001). The second study showed that linezolid interruption was common in patients receiving a bedaquiline-based treatment regimen, and that system-specific toxicity occurred within predictable time frames. It also showed that anaemia (77.3% versus 7.3%; p<0.001), peripheral neuropathy (63.6% versus 14.6%; p=0.003), and optic neuritis (18.2% versus 9.8%; p=0.34) occurred more frequently in linezolid interrupters than in non-interrupters. The third study showed that the use of delamanid-bedaquiline combination regimen was safe and efficacious in drug resistant TB patients with poor prognosis when compared with outcomes in the less sick patients who received a bedaquiline-based regimen. It also showed no significant difference in culture conversion rate at 6 months (92.5% versus 81.8%; p=0.26) or favourable treatment outcome rate (63.4% versus 67.5%; p=0.66) between the two groups. Although patients who received the combination regimen had more frequent occurrence of QTcF prolongation greater than 60 ms from baseline (p=0.001) and more episodes of QTcF greater than 450 ms during treatment (p=0.001), none of them were symptomatic or had delamanid or bedaquiline withdrawn from their regimen. Conclusion: These data demonstrated that new and repurposed drugs remarkably improved treatment outcomes in patients with drug-resistant TB. Although linezolid, which is an important component of the bedaquiline-based treatment regimen, is often associated with system-specific adverse events, these occurred at predictable time frames thereby guiding physicians to make informed management decisions. Lastly, drug resistant TB patients with poor prognosis may benefit from a regimen containing delamanid and bedaquiline which seems relatively safe from an adverse event perspective. These data, despite some limitations, make a case for a widespread and accelerated roll-out of new and repurposed drugs for the treatment of drug resistant TB.

Until the recent introduction of short course regimens, treatment regimens for multidrug resistant TB (MDR-TB) were long and toxic. Consequently, only approximately half of MDRTB patients completed their treatment. TB dosing guidelines have historically been unrefined with little consideration for pharmacokinetic/pharmacodynamic relationships. Large knowledge gaps therefore exist in the understanding of pharmacokinetic/pharmacodynamic relationships for both efficacy and toxicity in MDR-TB. My PhD used clinical pharmacology approaches to improve the understanding of drug exposures, toxicity, and exposure-toxicity relationships during the first 12 weeks of MDR-TB therapy. Aims and methods 1. Using non-compartmental analyses, describe the pharmacokinetics of cycloserine and, using regression modelling, explore the association of covariates with cycloserine exposure. 2. Using validated screening tools, describe the incidence of neuropsychiatric toxicity in MDR-TB patients, and explore associations with cycloserine pharmacokinetics. 3. Using a validated pain-rating scale in a crossover study design, investigate whether the addition of a local anaesthetic reduces kanamycin-related injection pain, and explore effects on kanamycin pharmacokinetics. 4. Using geometric mean ratios, compare the exposures of crushed versus whole formulations of pyrazinamide, moxifloxacin, ethionamide, ethambutol, cycloserine, and isoniazid. Results and conclusions We found no measurable terizidone in plasma supporting the hypothesis that terizidone is hydrolysed pre-systemically to cycloserine. The cycloserine time-concentration profile supports once daily dosing of terizidone. We describe a high incidence of peripheral neuropathy in MDR-TB patients with both cycloserine clearance and high-dose pyridoxine significantly associated with neuropathy on multivariate analysis. The addition of a local anaesthetic reduced the pain experienced by MDR-TB patients in the first 15 minutes post intramuscular administration of kanamycin, which could improve adherence to MDR-TB treatment. We also found the bioavailability of crushed isoniazid to be approximately 42% less than the whole tablet formulation, and therefore recommend that the crushing of isoniazid be avoided. Although some recent treatment advances have improved MDR-TB outcomes, enhancing the understanding of drugs used to treat MDR-TB, which continues to have an unacceptably high mortality and treatment-related morbidity, is a public health priority. This thesis comprises four peer-reviewed publications, all of which made a pragmatic contribution to the fight against MDR-TB.

Thesis (Ph.D.) -- McMaster University, 1999. / Includes bibliographical references (leaves 220-228). Also available via World Wide Web.

The interest in study of resistant starch in the pig nutrition is increasing. This experiment was done to evaluate resistant starch content in maize/corn by using an in vitro method. A total of 27 varieties of corn were used in this trial to determine the evaluation of in vitro resistant starch (RS); in vitro non-resistant starch (NRS); in vitro total starch (TS); dry matter (DM); ash and organic matter (OM). All treatments of corn samples were carried out in triplicates. In vitro determination of RS, NRS and TS were determined directly before the spectrophotometer reading with a wavelength of 510 nm. In vitro RS, NRS and TS ranged from 0.56 – 1.98%, 22.11 – 52.33% and 22.69 – 54.27% respectively; DM, Ash and OM ranged from 85.71 – 95.34%, 1.1 – 1.85% and 98.15 – 98.9% respectively. In RS, 424L and 5660 (P/≤/0.05); in NRS, 652N and MC 4050 (P/≤/0.01; in TS, 652N, MC 4050 and 424L (P/≤/0.01, 0.01 and 0.05 respectively); and in DM, 590 (P/≤/0.05). Results indicated that varieties of corn used may be low in amylose content because the RS values were negligible (≤ 1%) giving MC 5800 and 652N as the lowest RS values suitable for growing pigs. Further work is needed to validate these results. Keywords: In vitro; Resistant starch; Corn samples; Non-resistant starch; Total starch; Spectrophotometer

The synthesis and fire retardancy of several bromoesters of 2,4-pentadienoic acid were investigated. The synthesis of 2,4-pentadienoic acid was accomplished by liquid phase reaction of acrolein and malonic acid in the presence of pyridine. The conversion of the acid to bromoesters was performed by two different procedures. In the first procedure, the corresponding acid chloride was prepared from the acid via reaction with SOCl2 in the presence of powdered (3A°) molecular sieves. The molecular sieves serve as an internal trap for by-product HC1 and inhibit the competing polymerization reaction of the acid chloride. Reaction of the acid chloride with various alcohols provided the unsaturated esters. The final step in the first procedure is total bromination of the unsaturated esters. The second procedure involved bromination of 2,4-pentadienoic acid and followed by reaction of the bromo acid with SOCl₂ to produce the corresponding bromo acid chloride. Reaction of the brominated acid chloride with alcohol provided the corresponding brominated esters. A simple laboratory test was developed to measure and compare the flame retardancy of the bromoesters.

Typescript. / Digitized by Kansas State University Libraries

published_or_final_version / abstract / Mechanical Engineering / Doctoral / Doctor of Philosophy

4 pp.