Tunnelling

Tunnelling has become a fragmented process, excessively influenced by lawyers'notions of confrontational contractual bases. This prevents the pooling of skills, essential to the achievement of the promoters' objectives. Tunnelling: Management by Design seeks the reversal of this trend. After a brief historical treatment of selected developments, t

Thyroid Immune Related Adverse Events Following Immune Checkpoint Inhibitor Treatment

The efficacy of immune checkpoint inhibitor (ICI) treatment rivals traditional anti-tumor therapies and in most cases results in significantly less drug related toxicity. However, ICI-use can result in a myriad of immune and inflammatory side effects termed immune related adverse events (irAEs). Thyroid irAEs are the most common endocrine toxicity related to ICI-treatment. In affected patients, permanent thyroid dysfunction can result, necessitating lifelong thyroid hormone replacement and long-term clinical follow-up is required. Prior to this candidature, clinical descriptions of thyroid irAEs were predominately based on small, heterogeneous patient cohorts and little was known about the underlying pathogenesis responsible for their development. This thesis produced a detailed phenotypic report of 1246 patients with melanoma undergoing ICI-treatment. We clearly showed that prevalence of thyroid irAEs was substantially higher than previously reported, and that most patients developed subclinical disease only. We demonstrated that overt thyrotoxicosis had distinct clinical features from other thyroid irAE presentations and was uniquely associated with improvements in survival. We prospectively measured anti-thyroid antibody levels and showed they were highly specific for identifying patients likely to experience a thyroid irAE. Our antibody work was complemented by preclinical studies including development of an animal model to test for autoantibodies against novel thyroid antigens, a genetic study to test for an association with FLT3 gene polymorphism and immunophenotyping peripheral blood to identify key immune cell populations involved in the pathogenesis of thyroid irAEs. In totality, the work in this thesis significantly advances understanding of thyroid irAEs and the mechanisms underpinning their development

Preparative and spectroscopic studies of some phosphorus (V) chloride and bromide derivatives

Further preparative and Raman spectroscopic investigations of products derived from reactions of phosphorus (III) halides, boron trihalides and halogens have been made. A new compound of empirical formula P2BCl13 has been formulated as [equations] and may be considered as the parent of a series involving the [equations] cations. The structural implications of the proposed single halide anions and the relationship of the compounds to metastable PCl5 (Phase III) is discussed; changes which occur on heating have been monitored by Raman and magic angle rotation NMR spectroscopy. A further compound analogous to P2Cl9Br has been reported. The compounds MePCl4, Me2PCl3 and Me3PCl2 were prepared and 31Raman and P magic angle rotation NMR measurements support ionicformulations containing single halide ions. Complexes of these withLewis acids were made and the characteristic shifts associated withthe presence of single halide ions in the Raman spectra of the phosphonium cations were observed. Mixed chlorobromo cations ofthese methylphosphoranes were prepared and their Raman spectrapartially assigned. Conventional matrix isolation as well as low temperature sublimation experiments were performed on the vapours above PCl5, PBr5 and MePCl4. Monomeric species were observed for both PCI5 and MePCl4 but decomposition occurred with PBr5. In these studies Raman spectra were monitored from 15K to ambient temperatures and the conversion of covalent to ionic species was observed.<p

4,5,6,7-Tetra­bromo-1,1,3-trimethyl-3-(2,3,4,5-tetra­bromo­phen­yl)indane

The title compound (OctaInd), C18H12Br8, is a commercial brominated flame retardant (BFR). In the mol­ecule, the five-membered ring has a slight envelope conformation, with a deviation of 0.317 (9) Å for the flap C atom from four essentially planar C atoms. The dihedral angle between the two benzene rings is 74.00 (16) Å