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The Role of Serum Lipid Profile and Comorbidities in the Onset and Progression of Multiple Sclerosis

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The Role of Serum Lipid Profile and Comorbidities in the Onset and Progression of Multiple Sclerosis The role of serum lipid profile and comorbidities in the onset and progression of multiple sclerosis By Prudence Tettey BSc (Human Biology); MPhil (Medical Microbiology) A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy (Medical Studies) Menzies Institute for Medical Research December, 2015 Declaration of originality This thesis contains no material which has been accepted for any degree or diploma by the University or any other institution, except by way of background information and duly acknowledged in the thesis, and to the best of my acknowledge and belief, no material previously published or written by another person, except where due acknowledgment is made in the text of the thesis. Signature 8/12/2015 ……………………………….. ……………………………. Prudence Tettey Date II Statement of authority to access This thesis may be available for loan. Copying of any part of this thesis is prohibited for two years from the date this statement was signed; after that time, limited copying is permitted in accordance with the Australian Copyright Act of 1968. Signature 8/12/2015 ……………………………. ………………………………….. Prudence Tettey Date III Statement regarding published work contained in thesis The publishers of the papers contained in this thesis hold the copyright for that content, and access to the material should be sought from the respective journals. The remaining non published content of the thesis may be made available for loan and limited copying and communication in accordance with the Copyright Act 1968. Signature 8/12/2015 ……………………………… …………………………… Prudence Tettey Date IV Statement of Co-authorship This thesis includes papers for which Prudence Tettey (PT) is not sole author. PT took the lead in this research, developing and implementing the analyses, writing manuscript included herein under the supervision of Ingrid van der Mei (IvM), Bruce V Taylor (BVT), and Steve Simpson, Jr. (SSJ). In this process, however, he was assisted by co-authors to varying extent. Following then, the contribution of each co-author is detailed for each respective project. The paper reported in Chapter 2: TETTEY, P., SIMPSON, S., TAYLOR, B. V. & VAN DER MEI, I. Vascular comorbidities in the onset and progression of multiple sclerosis. J Neurol Sci 2014;347:23-33. TETTEY, P. & VAN DER MEI, I. A. 2014. Lipids in multiple sclerosis: adverse lipid profiles, disability and disease progression. Clinical Lipidology, 9, 473-475. Prudence Tettey (PT) undertook the literature review and composed the initial draft with direct assistance from Ingrid van der Mei (IvM). Bruce Vivian Taylor (BVT) and Steve Simpson Jr. (SSJ) provided supervision and were involved in the critical revision of the manuscripts. The paper reported in Chapter 3: TETTEY, P., SIMPSON, S., JR., TAYLOR, B. V. & VAN DER MEI, I. A. 2015. The co- occurrence of multiple sclerosis and type 1 diabetes: shared aetiologic features and clinical implication for MS aetiology. J Neurol Sci, 348, 126-31. TETTEY P, VAN DER MEI I. Frequency of autoimmune comorbidities in MS: the role of interferon-beta therapy. PT undertook the literature review and composed the initial draft with direct assistance from IvM. BVT and SSJ provided supervision and were involved in the critical revision of the manuscripts. V The paper reported in Chapter 4: TETTEY, P., SIMPSON, S., JR., TAYLOR, B., BLIZZARD, L., PONSONBY, A. L., DWYER, T., KOSTNER, K. & VAN DER MEI, I. 2014a. An adverse lipid profile is associated with disability and progression in disability, in people with MS. Mult Scler, 20, 1737-44. PT was involved in the development and implementation of statistical analyses. PT composed the drafts of the manuscript and coordinated revision. This was done under the supervision of IvM, BVT and SSJ. IvM was involved in the development and acquisition of funding for the MS Longitudinal Study from which the data for this analysis was drawn, along with BVT, Anne-Louise Ponsonby (A-LP), Terence Dwyer (TD). IvM was involved in the data collection for the MS Longitudinal Study. IvM was involved in the initial drafting and critical revision of the manuscript along with BVT and SSJ. BVT was involved in the data collection for the MS Longitudinal Study and provided supervision and was involved in the critical revision of the manuscript. SSJ provided guidance and supervision for the statistical analyses undertaken in this study, and was involved in the critical revision of the manuscript. Leigh Blizzard (LB) provided guidance and supervision for all statistical analyses undertaken in this study, and was involved in the initial drafting and critical revision of the manuscript. A-LP was involved in the development and acquisition of funding for the MS Longitudinal Study and contributed to the critical revision of the manuscript. TD was involved in the development and acquisition of funding for the MS Longitudinal Study and contributed to the critical revision of the manuscript. VI Karam Kostner (KK) was involved in the data collection for the MS Longitudinal Study and contributed to the critical revision of the manuscript. The paper reported in Chapter 5: TETTEY, P., SIMPSON, S., JR., TAYLOR, B., BLIZZARD, L., PONSONBY, A. L., DWYER, T., KOSTNER, K. & VAN DER MEI, I. 2014. Adverse lipid profile is not associated with relapse risk in MS: results from an observational cohort study. J Neurol Sci, 340, 230-2. PT was involved in the development and implementation of statistical analyses. PT composed the drafts of the manuscript and coordinated revision. This was done under the supervision of IvM, BVT and SSJ. IvM was involved in the development and acquisition of funding for the MS Longitudinal Study from which the data for this analysis was drawn, along with BVT, A-LP and TD. IvM was involved in the data collection for the MS Longitudinal Study. IvM was involved in the initial drafting and critical revision of the manuscript along with BVT and SSJ. BVT was involved in the data collection for the MS Longitudinal Study and provided supervision and was involved in the critical revision of the manuscript. SSJ provided guidance and supervision for the statistical analyses undertaken in this study, and was involved in the critical revision of the manuscript. LB provided guidance and supervision for all statistical analyses undertaken in this study, and was involved in the initial drafting and critical revision of the manuscript. A-LP was involved in the development and acquisition of funding for the MS Longitudinal Study and contributed to the critical revision of the manuscript. VII TD was involved in the development and acquisition of funding for the MS Longitudinal Study and contributed to the critical revision of the manuscript. KK was involved in the data collection for the MS Longitudinal Study and contributed to the critical revision of the manuscript. The paper reported in Chapter 6: TETTEY, P., SIMPSON, S., JR., TAYLOR, B., BLIZZARD, L., PONSONBY, A. L., DWYER, T., LUCAS, RM & VAN DER MEI, I. An adverse lipid profile and increased body mass index significantly predicts clinical course after a first demyelinating event. PT was involved in the development and implementation of statistical analyses. PT composed the drafts of the manuscript and coordinated revision. This was done under the supervision of IvM, BVT and SSJ. IvM was involved in the development and acquisition of funding for the MS Longitudinal Study from which the data for this analysis was drawn, along with BVT, A-LP and TD. IvM was involved in the data collection for the MS Longitudinal Study. IvM was involved in the initial drafting and critical revision of the manuscript along with BVT and SSJ. BVT was involved in the data collection for the MS Longitudinal Study and provided supervision and was involved in the critical revision of the manuscript. SSJ provided guidance and supervision for the statistical analyses undertaken in this study, and was involved in the critical revision of the manuscript. LB provided guidance and supervision for all statistical analyses undertaken in this study, and was involved in the initial drafting and critical revision of the manuscript. A-LP was involved in the development and acquisition of funding for the MS Longitudinal Study and contributed to the critical revision of the manuscript. VIII TD was involved in the development and acquisition of funding for the MS Longitudinal Study and contributed to the critical revision of the manuscript. KK was involved in the data collection for the MS Longitudinal Study and contributed to the critical revision of the manuscript. LMR was involved in the development and acquisition of funding for the MS Longitudinal Study and contributed to the critical revision of the manuscript. The paper reported in Chapter 7: TETTEY, P., SIEJKA D., SIMPSON, S., JR., TAYLOR, B., BLIZZARD, L., PONSONBY, A. L., DWYER, T., & VAN DER MEI, I. Frequency of comorbidities and their association with clinical disability and relapse in multiple sclerosis. Neuroepidemiology 2016;46:106- 113. PT was involved in the development and implementation of statistical analyses. PT composed the drafts of the manuscript and coordinated revision. This was done under the supervision of IvM, BVT and SSJ. Dylan Siejka (DS) was involved in analyses, initial drafting and critical revision of the manuscript. IvM was involved in the development and acquisition of funding for the MS Longitudinal Study from which the data for this analysis was drawn, along with BVT, A-LP and TD. IvM was involved in the data collection for the MS Longitudinal Study. IvM was involved in the initial drafting and critical revision of the manuscript along with BVT and SSJ. BVT was involved in the data collection for the MS Longitudinal Study and provided supervision and was involved in the critical revision of the manuscript. IX SSJ provided guidance and supervision for the statistical analyses undertaken in this study, and was involved in the critical revision of the manuscript.
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