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tert-Alkyl-substituted phosphines are commonly used as ligands in metal catalysis due to their sterically bulky, electron-rich nature. Methods to synthesise them by P-C bond formation are inefficient and operationally complex, requiring highly reactive organometallic reagents and chlorophosphines (Chapter 1). Despite advances in varying other groups on phosphorus to improve catalytic performance, the diversity of tert-alkyl groups remains low. Here, this challenge is addressed by taking an umpolung 'P−/C+' approach to the problem. Initial efforts using a silylphosphine were complicated by the observation of protodesilylation to give toxic, pyrophoric phosphine gas PH3, but this species was itself alkylated to give air-stable di-tert-alkylphosphonium salts (Chapter 2). To avoid direct handling of PH3, a two-chamber protocol for in situ generation of the gas from zinc phosphide was developed. The resulting phosphonium salts were found to be competent surrogates for free secondary phosphines (by in situ deprotonation), and were used in typical functionalisation reactions as well as the synthesis of a library of ligands based on the known JohnPhos biaryl backbone. Stereoelectronic properties of these ligands were measured and the variation in tert-alkyl group was shown to have a significant impact. A further use for the two-chamber reactor was found in the synthesis of CagePhos (Chapter 3), a uniquely sterically bulky, electron-poor and air-stable secondary phosphine which is currently underexplored in catalysis. The operational ease and safety of the two-chamber reactor provided significant quantities of CagePhos in a convenient solid form. An exploration of the incorporation of the CagePhos moiety into novel electron-poor aryl CagePhos ligands was conducted, and CagePhos was also tert-alkylated to give a completely new class of sterically bulky yet electron-poor tertiary phosphines (isolated as their air-stable phosphonium salts).

Patients with rapid eye movement sleep behaviour disorder (RBD) have a high long-term risk of developing Parkinson’s disease or a related synucleinopathy. Their individual trajectories are enormously varied, however, causing considerable prognostic uncertainty. This thesis examined aspects of the clinical and neuroimaging phenotype of RBD patients which might shed light on the underlying neurodegenerative process and thereby contribute to future risk stratification. We found that across a range of clinical prodromal features, RBD patients were at least as impaired as those with established Parkinson’s and that neuropsychiatric disorders were particularly prominent in RBD patients. Genetic, environmental and demographic factors differed between PD and RBD groups. In a multi-centre longitudinal analysis, the outcomes of simple in-clinic tests were shown to substantially affect the risk of phenoconversion. Using ioflupane SPECT, we found that 43% of RBD patients already had evidence of dopaminergic deficit, and that this declines by an estimated 7% per year. Neuromelaninsensitive and susceptibility weighted MRI of the substantia nigra revealed signal changes in RBD patients consistent with early neurodegeneration. A combination of these novel MRI markers accurately distinguished PD patients from controls, suggesting an ability to capture the hallmark pathological process. We found that apathy was common and under-recognised in RBD patients and dissociable from other neuropsychiatric features. SPECT neuroimaging data revealed that apathy was correlated with serotonin levels in the dorsal raphe nucleus, but not with dopaminergic availability. We used an eye-tracking paradigm to show that reward sensitivity is blunted in RBD patients, but that this relates to dopaminergic decline rather than clinical apathy. Overall, our data indicate that RBD patients have extensive evidence of underlying neurodegeneration, which manifests as a clinical phenotype with unique characteristics, suggesting that RBD may represent the prodromal phase of a particular synucleinopathy subtype. Multimodal assessment with in-clinic measures, neuroimaging and biometric data has the potential to facilitate risk stratification on an individual basis and will be important in selecting high-risk RBD patients for neuroprotective clinical trials.

This dissertation explores the lived experience of problematic anger in young men. Qualitative phenomenological research was conducted using semi-structured interviews with a sample of six male participants between the ages of 20-25 years. The accounts were analysed using Interpretative Phenomenological Analysis (IPA) and three main themes were identified. Theme one explores how anger initially stirs within the participants, impacting their sense of agency and their bodily feelings and sensations. Theme two illuminates how anger impacts the participant’s changing self-concept, a loss of awareness and control, and the issue of responsibility for actions taken. Theme three highlights how the participants attempt to regain control of themselves and return to a state of calm and composure. The study seeks to contribute to the paucity of research into the lived-experience of anger in young men. Findings suggest that anger is an intensely dynamic experience that unfolds with an increasing impact on young men’s ability to retain control over their sense of self as experienced in time, space, in their bodies and inter-relationally. The study recommends that continued research be undertaken into anger through the lens of these four areas, often referred to as the ‘existentials’.

This thesis investigates the prospects of measuring anomalous triple gauge boson couplings in the ATLAS detector at the Large Hadron Collider (LHC). The most general(V ZZ, V = Z, g) vertex is parametrised by four couplings, fV = Z,gi=4,5 , all of which are zero in the Standard Model. Non-zero couplings would manifest themselves as an excess of events in ZZ diboson channels, and, if observed, would be a direct probe of new physics beyond the Standard Model. A set of criteria are outlined to select events recorded by ATLAS in two such channels, ZZ to llll(l = e, mu) and ZZ to llnunu. With 1 fb-1 of integrated luminosity at a centre of mass energy of sqrt(s) = 7 TeV, ATLAS can expect to observe 10+/-1 events in the ZZ to llllchannel, with 0.5+0.9-0.2 background events. In the ZZ to llnunu channel, 6.2+/-0.7 signal events are expected, with a background of 1.9+2.0-0.2 events. The expected sensitivity of ATLAS to non-zero anomalous couplings is calculated by performing extended, unbinned maximum-likelihood fits to the Z boson transverse momentum spectrum. For 1 fb-1 of integrated luminosity at sqrt(s) = 7 TeV, ATLAS has the potential to place constraints on the coupling parameters of |fZi | < 0.06 and |fig | < 0.07 at the 95% confidence level. These limits assume a form factor with a cutoff of Lambda_FF = 1.2 TeV. As a prelude to ZZ observation, criteria are defined to select Z to ll(l = e, mu) events in the first 315 nb-1 of ATLAS pp collision data at sqrt(s) = 7 TeV. In total 57 events are observed in the electron channel, with 109 in the muon channel, leading to cross-section measurements of sigma (Z to ee) = 0.70+/-0.09 (stat)+/-0.10 (syst)+/-0.08 (lumi) pband sigma(Z to mumu) = 0.90+/-0.09 (stat) +/-0.07 (syst) +/-0.10 (lumi) pb, both of which are consistent with the Standard Model predictions. In addition, this thesis presents a summary of developments made to the Data Acquisition (DAQ) system of the ATLAS Semiconductor Tracker (SCT). These include the construction of a test system, involving a scaled-down version of the entire SCT readout chain. The test system was subsequently used to develop a number of new DAQ features, including a hardware-based event simulator and monitoring framework.