In non-inferiority trials, the goal is to show how an experimental treatment is statistically and clinically not inferior to the active control. The three-arm clinical trial usually recommended for non-inferiority trials by the FDA. The three-arm trial consists of a placebo, reference, and an experimental treatment. The three-arm trial shows the superiority of the reference over the placebo and comparison of the reference to an experimental treatment. In this paper, I will assess a non-inferiority trial with Bayesian methods. By employing Bayesian analysis, the parameters are random and assign vague prior distributions. I will compare the models involving different prior distributions to assess the best fit model.

The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non-transport permissive and intact BBB, we also assessed the role of magnetic resonance imaging (MRI) guided focused ultrasound (MRgFUS) disruption of the BBB in enhancing permeation of AuNPs across the intact BBB and tumor BBB in vivo. MRgFUS is a novel technique that can transiently increase BBB permeability thereby allowing delivery of therapeutics into the CNS. We demonstrated enhanced delivery of AuNPs with therapeutic potential into the CNS via MRgFUS. Our study was the first to establish a definitive role for MRgFUS in delivering AuNPs into the CNS. In summary, this thesis describes results from a series of research projects that have contributed to our understanding of the influence of design features on AuNP permeation through the BBB and also the potential role of MRgFUS in AuNP permeation across the BBB.

Complementary electrochemical and spectroscopic techniques were used to characterize the behavior and composition of the passive layer formed at the gold-thiosulfate interface in the presence of copper. Raman studies of three different cationic (calcium, ammonium and sodium) thiosulfate leaching solutions showed that the concentrations of sulfate, thiosulfate, trithionate and tetrathionate remained constant. Initial leaching current densities for the three systems were identical, however, significant differences were noted in the open circuit potentials of these systems. Gold nanorod electrodes were employed as substrates for Surface Enhanced Raman Spectroscopy (SERS) studies of the gold-thiosulfate interface. The composition and behavior of the passive layer at the gold- thiosulfate interface greatly differed from that of the bulk solutions. Higher order polythionate species were not observed, and significant differences were noted in the behavior of species common between the three thiosulfate leaching solutions. Passivation levels determined from SERS indicate that in the presence of copper, the cation associated with thiosulfate may play a key role in the extent of passivation on the gold surface. / Barrick Gold Corp., NSERC

Self-assembled monolayers (SAMs) of organosulfur precursors on gold have been extensively used since they offer a wide range of technological applications such as corrosion inhibition, lubrication, adhesion promotion/inhibition, nanofabrication, chemical and biosensors, catalysis, and molecular electronics. Furthermore, the electronic and optical properties of aromatic SAMs make them a potential candidate for molecular electronics. However, these practical applications are limited by the short-range ordering, low packing density, irreproducibility, and inferior quality of SAMs, which are more critical for aromatic SAMs. Therefore, the discovery of alternative precursors is essential. This thesis reports for the first time, the use of organic sulfenyl chlorides as precursors for the modification of gold surfaces. These precursors may help to overcome some practical limitations of the traditional organosulfur precursors. The modification is done in a non-aqueous medium. Characterization of the modified surfaces is performed by X-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV), polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS), and scanning tunnelling microscopy (STM). Through the use of 4-nitrophenyl sulfenyl chloride, evidence for the formation of well-ordered aromatic SAMs formation on gold is provided. XPS data shows that the modification involves the scission of the S-Cl bond. PM-IRRAS studies further indicate that the adsorbed molecules are nearly vertically oriented on the surface. Both short and long-range well-ordered aromatic SAMs (a 4 x √3 rectangular and √3 x √3 hexagonal unit cells) are obtained from the STM images using two different modification conditions. This molecular density is usually only observed for aliphatic SAMs using the traditional precursors. Along with the main hexagonal lattice, the reversible distinct superstructures including hexagons, partial hexagons, parallelograms, and zigzags resulting from specific arrangements of adsorbed molecules provide submolecular details. This is the first direct experimental example, where the STM has shown its effectiveness to provide physical structure information of standing-up aromatic SAMs at room temperature. This work also provides some insight into a heavily debated issue regarding the origin of the various features and contrasts obtained in STM images of SAMs. The use of 2-nitrophenyl sulfenyl chloride and 2,4-dinitrophenyl sulfenyl chloride for the formation of aromatic SAMs on Au provides some insight regarding the modification extent and the effect of a nitro substituent (at ortho position ) on the quality of nitrophenyl thiolate SAMs on gold. XPS, PM-IRRAS, electrochemistry and STM provide evidence for the formation of less ordered, low density and less stable SAMs that may decompose to sulfur at longer modification times. The efficient deposition of sulfur on gold is observed using a series of substituted methane sulfenyl chlorides (triphenylmethane sulfenyl chloride, trichloromethane sulfenyl chloride and chlorocarbonyl sulfenyl chloride). The XPS, STM and electrochemical data show the formation of high density sulfur phases. These include rhombus, rectangular, and zig-zag sulfur structures. A mechanism is suggested involving the cleavage of the S-Cl bond and the ejection of the molecular backbone. This study also suggests that substituted methane sulfenyl chlorides do not form long-range ordered SAMs.

A sustainable global program to reduce mercury use in artisanal and small-scale gold mining (ASGM) will require the demonstration of credible, continuous progress to secure political support and financing, and ultimately achieve success. Focused progress measurement has been lacking to date for ASGM at the global level. This research analyses information on appropriate options to measure mercury reduction progress in ASGM. Research methods included a case study of Mongolia, supplemented with information analyzed from semi-structured interviews related to ASGM and other applicable evaluation approaches. The study concludes by proposing the development of a framework approach for measuring progress and by offering guiding principles and recommendations. Recommendations for the framework approach include: on-going and enhanced support to an information database; simplified evaluation metrics for the ASGM Partnership; tracking the level of political commitment of national governments as an indicator of progress; and promoting common reporting metrics across global programming.

No description available.

The use of microorganisms notably bacteria in mineral processing industry is presently one of the leading emerging pre-treatment techniques being employed for the processing of double refractory gold ores and concentrates. Currently numerous studies are in progress to further improve upon the efficiency of the bacterial process and to investigate the potential of other microorganisms. In this study, microbial pre-treatment of double refractory gold ore (sample A) and concentrate (sample B) was investigated using a white-rot fungus, Tramestes versicolor (ATTC 20869). Pulp density, temperature, pH and retention times were the process variables considered. Preliminary studies investigated the amenability of selected pure sulfide sulfur minerals, various types of coal and ore sample A to fungal degradation. Various pre-treatment scenarios were also studied to optimize gold extraction. These were single stage, a two-step and two stage processes involving the well known chemolithotrophic bacteria Acidithiobacillus thiooxidans (ATTC 15494), Acidithiobacillus ferrooxidans (ATTC 19859) and Leptospirillum ferrooxidans (ATTC 53992), the bacterium, Streptomyces setonii (ATTC 39116) and the white-rot fungus, Tramestes versicolor. Preliminary results for sample A indicated that T. versicolor did not degrade sulfides significantly at its optimum growth conditions (pH range of 4.5 – 5.0) and carbonaceous matter was not degraded but rather passivated as preg-robbing decreased significantly. Lignite was inert to passivation by T. versicolor unlike bituminous coal and to lower extent anthracite. Stimulated alkaline conditions (pH range of 9.5 – 10.5) recorded the overall best sulfur oxidation. Results of both the single stage and two-step processes confirmed that carbonaceous matter was passivated by T. versicolor; as preg-robbing decreased significantly from 18.1% to ≤ 1.0%. Gold extraction by cyanidation of the pre-treated sample A was 82.5% for the two-step as against 80.5 % for the single stage and 15.0% for the untreated sample. Application of the two-step and single stage process conditions to sample B resulted in 93.3% and 89.9% gold extraction respectively as against untreated concentrate of 30.5%. For the various two stage pre-treatment processes investigated, the abiotic - S. setonii process recorded the best gold extraction of 81.5% for sample A. S. Setonii degraded carbonaceous matter unlike T. versicolor which passivated it. However, it takes only 3 - 7 days for T. versicolor to effect passivation and eliminate preg-robbing while 14 - 56 days is required for S. setonii to degrade carbonaceous matter significantly. The result of the novel microbial pre-treatment process indicated that sulfide sulfur was degraded under alkaline conditions and carbonaceous matter passivated by T. versicolor at its optimum growth conditions. This led to a significant improvement in gold extraction from the double refractory gold ore and concentrate investigated. / Thesis (Master, Mining Engineering) -- Queen's University, 2008-09-22 16:42:01.272

Hardpans, or cemented layers, form from precipitation and subsequent cementation of secondary minerals in mine tailings and can act as both physical and chemical barriers. During precipitation, metals in the tailings are sequestered, making hardpan a potentially viable method of natural attenuation. At Montague Gold Mines, Nova Scotia, tailings are partially cemented by the iron (Fe) arsenate mineral scorodite (FeAsO4•2H2O). Scorodite is known as a phase that can effectively limit aqueous arsenic (As) concentrations due to its relatively low solubility (<1 ppm, pH 5) and high As content (~30 wt.%). However, scorodite will not lower As concentrations from waters to below the Canadian drinking water guideline (0.010 ppm). To identify current field conditions influencing scorodite precipitation and dissolution and to better understand the mineralogical and chemical relationship between hardpan and tailings, coexisting waters and solids were sampled to provide information on tailings-water interactions. Hardpan cement compositions were found to include Fe arsenate and Fe oxyhydroxide in addition to scorodite. End-member pore water chemistry was identified based on pH and dissolved concentration extremes (e.g. pH 3.78, As(aq) 35.8 ppm) compared to most other samples (avg. pH 6.41, As(aq) 2.07 ppm). These end-member characteristics coincide with the most extensive and dispersed areas of hardpan. Nearly all hardpan is associated with historical arsenopyrite-bearing concentrate which provides a source of acidity and dissolved As+5 and Fe+3 for scorodite precipitation. A proposed model of progressive arsenopyrite oxidation suggests localized As cycling involving scorodite is occurring but is dependent on sulfide persistence. Therefore, permanent As sequestration is not expected. Remediation efforts would have to consider the possibility of scorodite dissolution after complete sulfide consumption or as a consequence of applying certain technologies, such as a cover. Conversely, if scorodite stability were maintained, the hardpan could be considered as a component in remediating the tailings at Montague. / Thesis (Master, Geological Sciences & Geological Engineering) -- Queen's University, 2008-12-22 09:36:08.157

The Alto Chicama district, Central Andean Cordillera Occidental, La Libertad, northern Perú, hosts the 14 M oz, Miocene Lagunas Norte high-sulphidation epithermal Au-(Ag) deposit (Latitude 7° 56ʹ30ʺ S; Longitude 78°14ʹ50ʺ W), in addition to several important, epithermal and mesothermal precious ± base-metal vein systems and porphyry Cu-Au-(Mo) deposits and prospects. The district is underlain by lower Oligocene-to-Middle Miocene, subaerial, Calipuy Supergroup volcanic rocks, unconformably overlying Upper Jurassic – Lower Cretaceous marine sedimentary strata affected by late Eocene-early Oligocene thin-skinned fold and thrust deformation. Mineralization at Lagunas Norte is largely hosted by intensely-folded Valanginian Chimú Formation quartz arenite, but extends into overlying, weakly-deformed, Lower Miocene dacitic volcaniclastic deposits. Fold- and thrust-related deformation at the deposit, and subsequent magmatic and hydrothermal activity, were localized along a long-lived, crustal-scale cross-strike discontinuity. Hydrothermal activity at Lagunas Norte was associated with local extension within an overall regional compressive regime. Ore formation occurred during the terminal stages of andesitic-to-dacitic magmatism in the deposit area, immediately following the sector collapse of an adjacent volcanic centre, and during eruption of late-stage peripheral dacitic domes. Intense advanced-argillic alteration occurred in at least two major pulses over a ~ 0.9 m.y. period, implying repeated magma influx in a shallow subjacent chamber. The ensuing Au-(Ag)-pyrite-enargite deposition resulted from mixing of magmatic vapour with oxidized groundwaters, a process stimulated by the contiguous incision of a steep-walled valley-pediment. The local volcanic rocks record a transition from “normal arc” to higher-pressure “adakitic” magmatism, initiated during ore deposition at Lagunas Norte, but exhibited by the entire Calipuy arc in northern Perú, and interpreted to reflect the destabilization of plagioclase and stabilization of garnet in inferred lower-crustal magmas. The progressive depletion of 18O and D in meteoric water recorded in late Oligocene-to-Late Miocene hypogene and supergene minerals is in permissive agreement with major uplift from ~ 1000 m to over 3000 m a.s.l. during hydrothermal activity. Hydrothermal activity and related ore deposition at Lagunas Norte unambiguously predated, by at least 2 m.y., the impingement of the aseismic Nazca Ridge at the Perú Trench and the ensuing flattening of the subducting slab / Thesis (Ph.D, Geological Sciences & Geological Engineering) -- Queen's University, 2012-04-05 11:09:14.751

No description available.