Improving NMR Sensitivity: The Synthesis and SABRE Evaluation of Nicotine Isotopologues

This thesis describes the development of a range of isotopically-labelled derivatives of (−)-nicotine, their subsequent hyperpolarisation by SABRE, their characterisation and the evaluation of their performance. Hyperpolarisation is a method of generating significantly enhanced magnetic resonance signals without increased sample size, scan time or prohibitively expensive improvements in equipment. The primary aim of this thesis was to develop a family of (−)-nicotine derivatives as potent SABRE substrates with a view unlocking their future biological applications in areas such as MRI. (−)-Nicotine is an important biological compound of great interest, with potent and well-documented psychoactivity. The relationship between signal enhancement, signal lifetime and a range of dependencies such as temperature, field and substrate choice are examined in detail. Results show that the interdependencies of such conditions are highly complex but follow logical patterns. Kinetic models are developed to more accurately describe the intricacies of the resulting chiral (−)-nicotine-based complexes, and they shed light on significant flaws in existing SABRE exchange models. Collectively, the synthetic 2H-labelling developments and SABRE evaluation involved no less than 23 materials. In addition, our understanding of the role 2H labelling plays in SABRE is secured

On the approximability of the maximum induced matching problem

In this paper we consider the approximability of the maximum induced matching problem (MIM). We give an approximation algorithm with asymptotic performance ratio <i>d</i>-1 for MIM in <i>d</i>-regular graphs, for each <i>d</i>≥3. We also prove that MIM is APX-complete in <i>d</i>-regular graphs, for each <i>d</i>≥3

Routine fixation of humeral shaft fractures is cost-effective:cost-utility analysis of 215 patients at a mean of five years following nonoperative management

Aims: The primary aim was to estimate the cost-effectiveness of routine operative fixation for all patients with humeral shaft fractures. The secondary aim was to estimate the health economic implications of using a Radiographic Union Score for HUmeral fractures (RUSHU) of < 8 to facilitate selective fixation for patients at risk of nonunion. Methods: From 2008 to 2017, 215 patients (mean age 57 yrs (17 to 18), 61% female (n = 130/215)) with a nonoperatively managed humeral diaphyseal fracture were retrospectively identified. Union was achieved in 77% (n = 165/215) after initial nonoperative management, with 23% (n = 50/215) uniting after surgery for nonunion. The EuroQol five-dimension three-level health index (EQ-5D-3L) was obtained via postal survey. Multiple regression was used to determine the independent influence of patient, injury, and management factors upon the EQ-5D-3L. An incremental cost-effectiveness ratio (ICER) of < £20,000 per quality-adjusted life-year (QALY) gained was considered cost-effective. Results: At a mean of 5.4 yrs (1.2 to 11.0), the mean EQ-5D-3L was 0.736 (95% confidence interval (CI) 0.697 to 0.775). Adjusted analysis demonstrated the EQ-5D-3L was inferior among patients who united after nonunion surgery (β = 0.103; p = 0.032). Offering routine fixation to all patients to reduce the rate of nonunion would be associated with increased treatment costs of £1,542/patient, but would confer a potential EQ-5D-3L benefit of 0.120/patient over the study period. The ICER of routine fixation was £12,850/QALY gained. Selective fixation based on a RUSHU < 8 at six weeks post-injury would be associated with reduced treatment costs (£415/patient), and would confer a potential EQ-5D-3L benefit of 0.335 per ‘at-risk patient’. Conclusion: Routine fixation for patients with humeral shaft fractures to reduce the rate of nonunion observed after nonoperative management appears to be a cost-effective intervention at five years post-injury. Selective fixation for patients at risk of nonunion based on their RUSHU may confer even greater cost-effectiveness, given the potential savings and improvement in health-related quality of life. Cite this article: Bone Jt Open 2022;3(7):566–572