An investigation of chemiluminescent miniaturised analytical systems

This thesis examines the feasibility of using chemiluminescence (CL) for detection in miniaturised analytical systems. The aim of this project was to design a miniaturised device that could potentially be used for the remote sensing of metal ions. The development of miniaturised analytical devices for use with two well known chemiluminescent reactions; namely the tris(2,2'-bipyridyl)ruthenium (II) reaction and the luminol reaction, for the detection and quantification of codeine and cobalt (II) respectively are discussed.Chapter 1 introduces the concept, the manufacture, operating principles and applications of miniaturised analytical systems, while the use of chemiluminescence, its requirements and applications as a sensitive, selective yet simple method of detection are reviewed in chapter 2.Chapter 3 describes the manufacture and development of the robust and practical miniaturised analytical devices used for the analyses described in chapters 4 and 5. Several novel developments are described in this chapter. These included the use of thicker top plates that enable the reservoirs to be contained within the single unit structure. This design was intended to prolong the lifetime of the chip system and increase the available reagent volumes. A microwave furnace for thermal bonding of the two glass plates was also used and the detection of the chemiluminesence produced in the chip system was carried out from underneath the chip base.Chapter 4 details the application of the tris(2,2'-bipyridyl)ruthenium (II) (TBR) for analysis in a miniaturised analytical system. This reaction was selected as a model chemiluminescence reaction for the optimisation of the detection system in order to measure the very low levels of light produced. The incorporation of non-ionic surfactants into the analysis and their effect on the enhancement of the chemiluminescence emission intensity and the modification of electroosmotic flow is discussed.A quantitative analysis of codeine was then successfully performed using this set-up. The points for the codeine concentrations of 5x10⁻⁷ to 1x10⁻⁴ mol 1⁻¹ were plotted to give a linear calibration plot. The equation of the line was y = 6.0136x + 0.0949, R2 = 0.9999, where x was the codeine concentration in mol 1⁻¹ and y was the mean CL emission intensity in mV. A limit of detection for codeine was determined at the 95% confidence limits to be 8.3x10-7 mol 1⁻¹ codeine, with an RSD of 8% (n=5) at the 5x10⁻⁵ mol 1⁻¹ level. The sample throughput time including removal of products and water wash was found to be an average of 2 minutes.The work described in chapter 5 builds on the findings of chapter 4 and examines the use of the luminol reaction in a miniaturised analysis system for the quantification of cobalt (II) ions.A multivariate experimental design programme was carried out as part of the work described in this chapter to simultaneously optimise most of the reagent variables. The application of cationic surfactants to this reaction in the miniaturised analysis system is also discussed, with particular emphasis on the observed enhancement of chemiluminescence emission intensity and lifetime, and the modification of the electroosmotic flow characteristics.A quantitative determination of cobalt nitrate was successfully carried out with a calibration over six orders of magnitude. The equation of the linear portion of the graph (10-10- 10-8 mol 1⁻¹) was found to be y = 64.625x + 735.71 with R2 = 0.999, where x (n=3) was the concentration in mol 1⁻¹ and y was the mean CL emission in mV. The limit of detection for cobalt nitrate at the 95% confidence limits was determined as -4x10⁻¹¹ mol 1⁻¹ which equates to 0.01 ng ml⁻¹ cobalt nitrate.An RSD of 6.9% (n=3) was obtained for the 1x10-8 mol 1⁻¹ standard. The sample run time was approximately 12 minutes, which resulted in an average overall throughput time of 15 minutes.The conclusions and ideas for future work are detailed in chapter 6

Establishing gold standard approaches to rapid tranquillisation: a review and discussion of the evidence on the safety and efficacy of medications currently used

Background: Rapid tranquillisation is used when control of agitation, aggression or excitement is required. Throughout the UK there is no consensus over the choice of drugs to be used as first line treatment. The NICE guideline on the management of violent behaviour involving psychiatric inpatients conducted a systematic examination of the literature relating to the effectiveness and safety of rapid tranquillisation (NICE, 2005). This paper presents the key findings from that review and key guideline recommendations generated, and discusses the implications for practice of more recent research and information. Aims: To examine the evidence on the efficacy and safety of medications used for rapid tranquillisation in inpatient psychiatric settings. Method: Systematic review of current guidelines and phase III randomised, controlled trials of medication used for rapid tranquillisation. Formal consensus methods were used to generate clinically relevant recommendations to support safe and effective prescribing of rapid tranquillisation in the development of a NICE guideline. Findings: There is a lack of high quality clinical trial evidence in the UK and therefore a ‘gold standard’ medication regime for rapid tranquillisation has not been established. Rapid tranquillisation and clinical practice: The NICE guideline produced 35 recommendations on rapid tranquillisation practice for the UK, with the primary aim of calming the service user to enable the use of psychosocial techniques. Conclusions and implications for clinical practice: Further UK specific research is urgently needed that provides the clinician with a hierarchy of options for the clinical practice of rapid tranquillisation

Staphylococcus argenteus transmission among healthy Royal Marines: a molecular epidemiology case-study

Objectives: During a prospective study of S. aureus carriage in Royal Marines recruits, six S. argenteus strains were identified in four recruits. As S. argenteus sepsis leads to mortality similar to S. aureus, we determined the potential for within same troop transmission, to evaluate future outbreak risk. Methods: We used whole-genome sequencing to characterise S. argenteus and investigate phylogenetic relationships between isolates. Results: S. argenteus strains (t5078, ST2250) were detected in 4/40 recruits in the same troop (training cohort) in weeks 1, 6 or 15 of training. No mec, tsst or LukPV genes were detected. We identified differences of 1-17 core SNPs between S. argenteus from different recruits. In two recruits, two S. argenteus strains were isolated; these could be distinguished by 2 and 15 core SNPs. Conclusions: The identification of S. argenteus within a single troop from the total recruit population suggests a common source for transmission, though high number of SNPs were identified, both within-host and within-cluster. The high number of SNPs between some isolates may indicate a common source of diverse isolates or a high level of S. argenteus mutation in carriage. S. argenteus is newly recognised species; and understanding of the frequency of genetic changes during transmission and transition from asymptomatic carriage to disease is required

Patients’ Preference and Experiences of Forced Medication and Seclusion

This study examined patients’ preferences for coercive methods and the extent to which patients’ choices were determined by previous experience, demographic, clinical and intervention-setting variables. Before discharge from closed psychiatric units, 161 adult patients completed a questionnaire. The association between patients’ preferences and the underlying variables was analyzed using logistic regression. We found that patients’ preferences were mainly defined by earlier experiences: patients without coercive experiences or who had had experienced seclusion and forced medication, favoured forced medication. Those who had been secluded preferred seclusion in future emergencies, but only if they approved its duration. This suggests that seclusion, if it does not last too long, does not have to be abandoned from psychiatric practices. In an emergency, however, most patients prefer to be medicated. Our findings show that patients’ preferences cannot guide the establishment of international uniform methods for managing violent behaviour. Therefore patients’ individual choices should be considered

An integrative review exploring decision-making factors influencing mental health nurses in the use of restraint

Introduction: While mechanical and manual restraint as an institutional method of control within mental health settings may be perceived to seem necessary at times, there is emergent literature highlighting the potential counter-therapeutic impact of this practice for patients as well as staff. Nurses are the professional group who are most likely to use mechanical and manual restraint methods within mental health settings. In-depth insights to understand what factors influence nurses’ decision-making related to restraint use are therefore warranted. Aim: To explore what influences mental health nurses’ decision-making in the use of restraint. Method: An integrative review using Cooper’s framework was undertaken. Results: Eight emerging themes were identified: ‘safety for all’, ‘restraint as a necessary intervention’, ‘restraint as a last resort’, ‘role conflict’, ‘maintaining control’, ‘staff composition’, ‘knowledge and perception of patient behaviours’, and ‘psychological impact’. These themes highlight how mental health nurses’ decision-making is influenced by ethical and safety responsibilities, as well as, interpersonal and staff-related factors. Conclusion: Research to further understand the experience and actualization of ‘last resort’ in the use of restraint and to provide strategies to prevent restraint use in mental health settings are needed

Introduction. Art, articulation and incarnation: mystical theology and seeing the invisible

The introduction presents an overview of critical debates in relation to mysticism and medieval aesthetics, before offering a short case study of medieval and modern representation of the mystery of the Incarnation intended to highlight the key themes and tension address over the volume as a whole. An examination of the 'Incarnation Initials' of Insular Gospel Books and Gerald of Wales's discussion of the Gospels of Kildare highlights the importance of craft, materiality and the transcendent to these medieval works of art. Padraic Colum's mid-twentieth-century poem responds to the Book of Kells with a meditation on the practice of its creator. Finally, the paradox of worldly art being able both to facilitate and to hinder access to the divine is addressed in relation to some Middle English lyrics

Nakedness and anthropology in Julian of Norwich and Maurice Merleau Ponty: conversation partners or dangerous liaisons

This essay explores the extent to which Julian of Norwich and Maurice Merleau-Ponty can usefully be treated as dialogue partners. Examining the use that each makes of the image of ‘nakedness’, it focuses on the relationship between transcendence and immanence in Julian's Revelations and Merleau-Ponty's The Visible and the Invisible. It is argued that although there are tantalising family resemblances one risks losing that which makes each author so compelling if the differences between them on this issue are not acknowledged