Self-cutting and prospective repetition of self-harm: studies of emergency department presentations in Ireland

Background Self-harm places an individual at increased risk of future self-harm and suicide, and indicates distress and maladaptive coping. Those who present to hospital with self-cutting form a significant minority of self-harm patients who are at increased risk of prospective repetition of self-harm and suicide compared with those presenting with intentional overdose. In addition to increased risk, there is emerging evidence of demographic, psychological, clinical, and social differences between those presenting with self-cutting and those presenting with overdose. Aim and Key Objectives The aim of the current doctoral work was to examine in detail the association between presenting with self-cutting and risk of prospective repetition. The objectives were: to identify evidence-based risk factors for repetition of self-harm among those presenting to emergency departments with self-harm; to compare demographic and presentation characteristics and prospective repetition across presentations of self-cutting only, self-cutting plus intentional overdose, and intentional overdose only; to compare prospective repetition and other characteristics within self-cutting presentations based on the type of treatment received; to compare self-cutting and intentional overdose patients on psychological risk and protective factors for repetition; and to examine the lived experience of engaging in repeated overdose and self-cutting. Methods The current doctoral work used a mixed-methods approach and is comprised of one systematic review and four empirical studies. The empirical studies were two registry-based prospective studies of Irish hospital presentations of self-harm, one prospective structured interview study, and one qualitative study using Interpretative Phenomenological Analysis. Results The systematic review identified several consistent and emerging risk factors for repetition of self-harm, compared to which self-cutting had a medium-sized effect. The registry studies demonstrated that the involvement of self-cutting, particularly less medically severe selfcutting, confers an increased risk of 1-month and 12-month repetition among Irish index selfharm presentations. The structured psychological study detected higher hopelessness and lower non-reactivity to inner experience among those presenting with self-cutting, and higher depression among those who repeated self-harm. Repeaters had lower baseline levels of protective psychological factors than non-repeaters and continued to have higher depression and hopelessness at follow-up. Finally, the qualitative study indicated that self-harm is a purposeful action taken in response to an overwhelming situation and is evaluated afterwards in terms of personal and social effects. Chosen method of self-harm seemed to be influenced by the desired outcome of the self-harm act, capability, accessibility and previous experience. Conclusion Despite limitations in terms of recruitment rates, the work presented in this thesis is innovative in examining the issue of the association between self-cutting and repetition from multiple perspectives. No one factor can reliably predict all repetition but self-cutting represents one consistent and easily detected risk factor for repetition. Those who present with self-cutting exhibit significant differences on demographic, clinical, and psychological variables compared with those presenting with intentional overdose, and seem to exhibit a more vulnerable profile. However, those who present with self-cutting do not form a discrete or homogenous group, and self-harm methods and levels of suicidal intent are liable to fluctuate over time.

Catalyst and substrate effects in enantioselective C–H insertion reactions of α-diazosulfones

This thesis describes a systematic investigation of the mechanistic and synthetic aspects of intramolecular reactions of a series of α-diazo-β-oxo sulfone derivatives using copper and, to a lesser extent, rhodium catalysts. The key reaction pathways explored were C–H insertion and cyclopropanation, with hydride transfer competing in certain instances. Significantly, up to 98% ee has been achieved in the C–H insertion processes using copper-NaBARF-bisoxazoline catalysts, with the presence of the additive NaBARF critical to the efficiency of the transformations. This novel synthetic methodology provides access to a diverse range of enantioenriched heterocyclic compounds including thiopyrans, sulfolanes, β- and γ-lactams, in addition to carbocycles such as fused cyclopropanes. The synthesis of the α-diazosulfones required for subsequent investigations is initially described. Of the twenty seven diazo sulfones described, nineteen are novel and are fully characterised in this work. The discussion is subsequently focused on a study of the copper and rhodium catalysed reactions of the α-diazosulfones with Chapter Four concentrated on highly enantioselective C–H insertion to form thiopyrans and sufolanes, Chapter Five focused on C–H insertion to form fused sulfolanes, Chapter Six focused on C–H insertion in sulfonyl α-diazoamides where both lactam formation and / or thiopyran / sulfolane formation can result from competing C–H insertion pathways, while Chapter Seven focuses on cyclopropanation to yield fused cyclopropane derviatives. One of the key outcomes of this work is an insight into the steric and / or electronic factors on both the substrate and the catalyst which control regio-, diastereo- and enantioselectivity patterns in these synthetically powerful transformations. Full experimental details for the synthesis and spectral characterisation of the compounds are included at the end of each Chapter, with details of chiral stationary phase HPLC analysis and assignment of absolute stereochemistry included in the appendix.

Constraint-force-based approach of modelling compliant mechanisms: principle and application

Numerous works have been conducted on modelling basic compliant elements such as wire beams, and closed-form analytical models of most basic compliant elements have been well developed. However, the modelling of complex compliant mechanisms is still a challenging work. This paper proposes a constraint-force-based (CFB) modelling approach to model compliant mechanisms with a particular emphasis on modelling complex compliant mechanisms. The proposed CFB modelling approach can be regarded as an improved free-body- diagram (FBD) based modelling approach, and can be extended to a development of the screw-theory-based design approach. A compliant mechanism can be decomposed into rigid stages and compliant modules. A compliant module can offer elastic forces due to its deformation. Such elastic forces are regarded as variable constraint forces in the CFB modelling approach. Additionally, the CFB modelling approach defines external forces applied on a compliant mechanism as constant constraint forces. If a compliant mechanism is at static equilibrium, all the rigid stages are also at static equilibrium under the influence of the variable and constant constraint forces. Therefore, the constraint force equilibrium equations for all the rigid stages can be obtained, and the analytical model of the compliant mechanism can be derived based on the constraint force equilibrium equations. The CFB modelling approach can model a compliant mechanism linearly and nonlinearly, can obtain displacements of any points of the rigid stages, and allows external forces to be exerted on any positions of the rigid stages. Compared with the FBD based modelling approach, the CFB modelling approach does not need to identify the possible deformed configuration of a complex compliant mechanism to obtain the geometric compatibility conditions and the force equilibrium equations. Additionally, the mathematical expressions in the CFB approach have an easily understood physical meaning. Using the CFB modelling approach, the variable constraint forces of three compliant modules, a wire beam, a four-beam compliant module and an eight-beam compliant module, have been derived in this paper. Based on these variable constraint forces, the linear and non-linear models of a decoupled XYZ compliant parallel mechanism are derived, and verified by FEA simulations and experimental tests.