Inflation expectations and Real Return Bonds

The existence of a market for Real Return Bonds in Canada provides a direct tool with which to measure market expectations of inflation by comparing the yields on these bonds with those on conventional Government of Canada long-term bonds. However, there are other factors besides inflation expectations that may affect the yield differential. After reviewing these factors, the authors note that they can lead to a potentially large bias in the level of inflation expectations. The changes in the differential over time may, nonetheless, be a good indicator of movements in long-run inflation expectations. Based on this measure, expectations of long-run inflation have declined since late 1994.

Genetic biomarkers of chemotherapy response and resistance in lung cancer patients

In advanced lung cancer, careful selection of systemic anticancer therapy (SACT) is of vital importance. Companion biomarkers can optimise treatment selection, such as with the use of EGFR tyrosine kinase inhibitors (EGFR TKi) in patients with EGFRmut+ve adenocarcinoma of the lung. There is increasing interest in mutation detection and monitoring, in circulating cell free tumour DNA (ctDNA). This thesis reports that Next Generation Sequencing (NGS) with software VarScan with Annovar, can detect mutations at a 10-fold lower alternate allele frequency compared to alternative software available through Ion Torrent, but with a greater number of low level ‘false positive’ genetic variants. Droplet digital PCR (ddPCR) is more sensitive than NGS, successfully detecting mutations as low as 0.1% alternate allele frequency. Lung cancer mutations were successfully detected in small, formalin-fixed, paraffin embedded (FFPE) tumour tissue samples, and ctDNA, from lung cancer patients, using the same NGS technique, with a commercially available, targeted 50 gene cancer hotspot panel. Results are compared to a custom 22-gene panel. The kinetics of mutation levels in serial ctDNA samples is reported in a case series. In EGFRmut+ve lung adenocarcinoma patients treated with EGFR TKi, decreases in levels of mutant EGFR in ctDNA were observed. Levels remained undetectable during periods of disease control/stability, and increases in mutant EGFR in ctDNA were seen several weeks before the diagnosis of clinical or radiological disease progression. NGS of ctDNA during disease progression revealed novel genetic mutations that were not detected in the original tumour biopsy, and may inform subsequent treatment options. Similar ctDNA kinetics was seen in advanced SCLC patients treated with SACT. The levelof mutated ctDNA, at diagnosis may be an independent prognostic biomarker, using a cut-off of 44.3% alternate allele frequency. SCLC patients who experienced a greater absolute decrease in mutant ctDNA had a poorer prognosis

New mineralogy of the outer solar system and the high-pressure behaviour of methane

This thesis will introduce the study of methane as a mineral. Along with ammonia and water, methane is one of the main planetary-forming materials in the outer solar system. The topic of `new mineralogy of the outer solar system' is outlined and introduced, and previous studies in the area are discussed. This review identities a lack of highpressure structural knowledge on methane when compared to ammonia and water. The significance of this knowledge for the study of the planets Neptune and Uranus is discussed. The crystal structures of methane above 5.2 GPa were, prior to this thesis, unknown. To tackle this long-standing problem an integrated approach of high-pressure diffraction techniques had to be used. The dominance of hydrogen within the structures of methane necessitated the use of neutron diffraction. The difficulties and limitations of highpressure neutron powder diffraction are presented. It will be shown that the complexity of the subsequent structures required the use of single-crystal x-ray diffraction. Using a combination of x-ray and neutron diffraction the structures of methane phase A (5.2 - 10 GPa) and B (10 - 25 GPa) were solved. The structure of phase A, was shown to conform to an indexing from literature [Nakahata 99] of a rhombohedral unit cell with α ≈ 89.3° and a ≈ 8.6 Å. Powder data were insufficient to determine atomic positions for this phase, and a single-crystal xray diffraction study was undertaken. The process of growing samples for this study is described as well as data collection. As a result of these studies the carbon atoms were located within methane phase A, and the density of the structure confined. The heavy atom structure, of phase A, was refined against neutron powder diffraction data, enabling positions of hydrogen atoms to be found. Preliminary powder diffraction studies of methane phase B found that the structure did not conform to the unit cell described within the literature. The phase was instead assigned to a cubic unit cell with a ≈ 11.73 Å. Similarly to the studies of phase A, a single-crystal x-ray diffraction study was undertaken. This was complicated by the presence of a contaminant within the sample area. This contaminant was shown to have no effect on the structural results. From a single-crystal study the heavy atom structure of phase B was found. The thesis charts the attempt, but ultimate failure, to obtain neutron powder diffraction on this phase. Comparisons of phase B with the higher pressure phase HP (25 GPa +) led to the conclusion that there would still be some disorder within the hydrogen atoms of phase B. Other studies have been carried out on the methane phase diagram. A Raman spectroscopy study, in the literature, on the low-temperature and high-pressure region of the phase diagrams (20 K up to 30 GPa) had suggested the existence of 3 additional phases of methane. A low-temperature, high-pressure neutron diffraction experiment was undertaken to try and characterise these phases. It was found that the phase A structure persisted under all conditions (to 20 K and 5 GPa) throwing the original results into question. During the growth of single-crystals for the above studies on phase A and B, a high-temperature solid-solid phase transition was observed. This transition line was mapped out and the phase resulting from it characterised with high-temperature single-crystal x-ray diffraction.EThOS - Electronic Theses Online ServiceGBUnited Kingdo