http://bura.brunel.ac.uk/handle/2438/143 2013-05-18T22:11:21Z 2013-05-18T22:11:21Z Alshehri, Areej http://bura.brunel.ac.uk/handle/2438/7433 2013-05-10T14:26:41Z 2013-01-01T00:00:00Z

Title: The role of homeobox gene in leukaemia Authors: Alshehri, Areej Abstract: Homeobox genes are known to be active during development and they are turned off after the early stages of developmental life. The HLXB9/MNX1 gene is a homeobox gene localized on human chromosome 7 and is involved in the development of pancreas and the nervous system. However, some leukaemia research groups have reported an over-expression of HLXB9 in leukaemia patients who carry the t(7;12) and in the GDM-1 cell line that carries the t(6;7). The mechanisms of leukaemogenesis in t(7;12) patients are still unclear. The t(7;12) is one of the recurrent cytogenetic abnormalities that is associated with infant acute myeloid leukaemia (AML) patients and has been linked to poor prognosis. The aim of this study was (i) to determine the involvement of HLXB9 in cell lines known to express this gene at the transcript level and (ii) to investigate the position on HLXB9 in AML patients with abnormalities of chromosome 7. This aim was achieved through a series of experiments involving the use of both conventional and molecular cytogenetics. In the first place, the chromosomal abnormalities in leukaemia and lymphoma cell lines (GDM-1, K562 and Pfeiffer) have been analysed using G-banding and Multiplex FISH (M-FISH) techniques. Furthermore, FISH using whole chromosome painting technique was performed on 7 AML patients to investigate chromosome 7 rearrangements. Thirdly, the involvement of the homeobox gene HLXB9 has been investigated in the acute myeloid leukaemia (AML) derived cell line GDM-1 and in 4 AML patients. Fluorescence in situ hybridization (FISH) analysis was carried out using a specific probe for the HLXB9 gene on the AML patients in single and dual colour FISH in combination with an additional probe distal to HLXB9 on the GDM-1 cell line. FISH analysis showed no involvement of the HLXB9 gene in any rearrangement or breaks at chromosomal level on the AML cell line (GDM-1) and AML patients. Nevertheless, a breakpoint either proximal or distal to HLXB9 has been identified. In particular, the breakpoint in the GDM-1 cell line has been confirmed on between the two probes used. This thesis poses the basis for further studies to investigate the mechanisms of oncogenesis in leukaemias with over-expression of HLXB9 in relation to possible breakage of chromosome 7 in the vicinity of the gene Description: This thesis was submitted for the degree of Master of Philosophy and was awarded by Brunel University

2013-01-01T00:00:00Z Ashworth-Beaumont, Jim http://bura.brunel.ac.uk/handle/2438/7376 2013-04-25T09:41:14Z 2012-01-01T00:00:00Z

Title: The effect of anodal transcranial direct current stimulation on spatial motor skill learning in healthy and spinal cord injured humans Authors: Ashworth-Beaumont, Jim Abstract: Anodal transcranial direct current stimulation (tDCS) is an intervention which is thought to enhance motor learning in healthy and stroke-injured states, when applied adjunctively during skill learning. We set out to investigate whether anodal tDCS might enhance functional rehabilitation from incomplete tetraplegic SCI. To address current limitations in the measurement of task-dependent skill, a novel integrated skill training and measurement task, the Motor Skill Rehabilitation Task (MSRT) was designed and developed. Measures of performance from this task delivered the functional measure of spatial motor skill learning, Task Productivity Rate (TPR). TPR was analysed and validated as a univariate dependent outcome, which is of potential importance to the future development of clinical measures measuring goal-directed motor skills. The MSRT was included alongside conventional behavioural measures in a repeated-measures RCT pilot study, the first to investigate the effect of anodal tDCS on rehabilitation of motor skill from chronic spinal cord injury. Adjunctive application of anodal tDCS had a statistically significant benefit upon retention of skill in the incomplete spinal cord injured population, but only when the independent factor of sensory acuity was included in the analysis. Differences between the development of task-dependent skill and generic dexterity over time suggested that spatial skill development was subject to an interaction of short-term and lasting effects. A larger study in healthy persons further investigated these phenomena, also applying Transcranial Magnetic Stimulation (TMS)–evoked measurements to investigate intervention-dependent effects upon the excitability of projections between the primary motor cortex and muscles involved in the prehension task. The findings revealed that active tDCS did not enhance skill learning at 7 days beyond the training period, but did significantly alter the development of motor skill following a period of learning and subsequent skill consolidation which was associated with underlying perturbation of motor control strategy. Significant and divergent patterns of cortical plasticity were evoked in projections to muscles necessary for reaching and grasping. The main findings of this thesis do not support anodal tDCS as an effective adjunctive means of enhancing spatial motor skill in rehabilitation from incomplete tetraplegic SCI. If applied in patient populations, the clinical benefits of anodal tDCS may be contingent both on the nature of the sensorimotor deficit affecting upper limb function and the spatial demands of the behavioural task. The findings of this project serve to inform further research in relation to the effect of anodal tDCS on the brain and behavioural outcomes, the potential for efficacy in target patient groups and the sensitivity of outcome measures to spatial and temporal dimensions of practical motor skills. Description: This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.

2012-01-01T00:00:00Z Takian, A Petrakaki, D Cornford, T Sheikh, A Barber, N http://bura.brunel.ac.uk/handle/2438/7365 2013-04-22T13:30:50Z 2012-01-01T00:00:00Z

Title: Methodological reflections on the evaluation of the implementation and adoption of national electronic health record systems Authors: Takian, A; Petrakaki, D; Cornford, T; Sheikh, A; Barber, N Abstract: Introduction/purpose of presentation: Far-reaching policy commitments to information technology-centered transformations of healthcare systems have now been made in many countries. There is as yet little empirical evidence to justify such decisions, hence the need for rigorous independent evaluation of current implementation efforts. Such evaluations however pose a number of important challenges. This presentation has been designed as a part of a Panel based on our experience of evaluating the National Health Service’s (NHS) implementation of electronic health records (EHR) systems in hospitals throughout England. We discuss the methodological challenges encountered in planning and undertaking an evaluation of a program of this scale and reflect on why and how we adapted our evaluation approach—both conceptually and methodologically—in response to these challenges. Study design/population studied: Critical reflections on a multi-disciplinary and multi-facet independent evaluation of a national program to implement electronic health record systems into 12 ‘early wave’ NHS hospitals in England. Findings: Our initial plan was to employ a mixed methods longitudinal ‘before-during-after’ study design. We however found this unsustainable in the light of fluxes in policy, contractual issues and over-optimistic schedules for EHR deployments. More importantly, this research design failed adequately to address the core of multi-faceted evolving EHRs as understood by key stakeholders and as worked out in their distinct work settings. Thus conventional outcomes-centric evaluations may not easily scale-up when evaluating transformational programs and may indeed prove misleading. New assumptions concerning the implementation process of EHR need to be developed that recognize the constantly changing milieu of policy, product, projects and professions that are inherent to such national implementations. The approaches we subsequently developed substitute the positivist view that EHR initiatives are self-evident and self-contained interventions, which are amenable to traditional quantitative evaluations, to one that focuses on how they are understood by various stakeholders and made to work in specific contexts. These assumptions recast the role of evaluation towards an approach that explores and interprets processes of socio-technical change that surround EHR implementation and adoption as seen by multiple stakeholders. Conclusions and policy implications: There is likely to be an increase in politically-driven national programs of reform of healthcare based on information and communication technologies. Programs on such a scale are inherently complex with extended temporalities and extensive and dynamic sets of stakeholders. They are, in short, different and pose new evaluation challenges that previously formulated evaluation methods for health information systems cannot easily address. This calls for methodological innovation amongst research teams and their supporting bodies. We argue that evaluation of such system-wide transformation programs are likely to demand both breadth and depth of experience within a multidisciplinary research team, constant questioning of what is and what can be evaluated and how, and a particular way of working that emphasizes continuous dialogue and reflexivity. Making this transition is essential to enable evaluations that can usefully inform policy-making. Health policy experts urgently need to reassess the evaluation strategies they employ as they come to address national policies for system-wide transformation based on new electronic health infrastructures. Description: Copyright @ 2012, International Journal of Integrated Care (IJIC). This work is licensed under a (http://creativecommons.org/licenses/by/3.0) Creative Commons Attribution 3.0 Unported License.

2012-01-01T00:00:00Z Wakhisi, Anthony Simiyu http://bura.brunel.ac.uk/handle/2438/7355 2013-04-23T13:58:27Z 2013-01-01T00:00:00Z

Title: A social marketing perspective of young people’s sexual health Authors: Wakhisi, Anthony Simiyu Abstract: BACGROUND:Unintended pregnancy and sexually transmitted infections among young people are priority public health issues in the UK. Social marketing is the preferred Government approach to intervention despite limited evidence on efficacy. There is need to understand its applicability and effectiveness in addressing the specified sexual health issues.METHODS:Three studies were carried out, of which the first was a systematic review of 12 studies assessing the effectiveness of social marketing in reducing unintended teenage pregnancies. The second and third were consumer research applications examining factors associated with Long Acting Reversible Contraceptive (LARC) use and Chlamydia screening respectively. The second study involved analysing five ONS Contraception survey datasets while the third involved analysing Havering PCT Chlamydia screening records and qualitative data from 28 participants. Data were analysed using Stata.10 and Framework statistical packages and maps drawn using MapInfo.10.5. RESULTS:The systematic review showed that nine studies achieved significant effects on at least one of the specified outcomes (reduced pregnancy rates and related behaviour changes). The second study showed that the NICE guidelines published in 2005 successfully addressed the disparity in LARC uptake previously experienced by women aged below 20. The third study identified females and non-white participants as more likely to take Chlamydia tests. Motivating factors for testing included convenient access to kits and fear of infertility, while barriers included ignorance and fear of results. CONCLUSIONS:Social marketing appears to be effective in reducing unintended teenage pregnancies but evidence is limited to particular outcomes and context. Consumer research provides vital intelligence about target populations necessary for designing effective interventions and addressing inequalities. However to assess its influence on outcomes, studies that feature all social marketing components are required. Overall there is need for more studies that specifically utilize social marketing principles to enable more robust evaluations. Description: This thesis was submitted for the degree of Doctor of Philosophy and was awarded by Brunel University

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