Dr Claudia Metzler-Baddeley
Reader, NIHR/HCRW Advanced Research Fellow
- metzler-baddeleyc@cardiff.ac.uk
- +44 (0)29 2087 0705
- Cardiff University Brain Research Imaging Centre, Maindy Road, Cardiff, CF24 4HQ
- Available for postgraduate supervision
Overview
Research summary
I am a cognitive neuroscientist who applies quantitative multi-parametric magnetic resonance imaging (MRI) (e.g. multi-shell diffusion-weighted, quantitative magnetization-transfer-weighted, relaxometry MRI) and experimental-cognitive methods to advance our understanding of:
- the brain phenotypes of healthy versus pathological ageing (associated with genetic and lifestyle risk factors of dementia) to identify early disease biomarkers (CARDS),
- the microstructural brain changes underpinning cognitive impairment in neurodegenerative disease such as white matter changes in Huntington's disease and Mild Cognitive Impairment,
- the effects of cognitive/movement training on clinical symptoms and neural plasticity in people with Huntington's disease (HD-DRUM).
I am also using advanced tractography techniques to study the anatomy of white matter pathways such as the cingulum bundle and the fornix.
Cardiff Ageing and Risk of Dementia Study (CARDS):
I am the PI of the Cardiff Ageing and Risk of Dementia Study (CARDS) that was funded by the Alzheimer's Society and BRACE (2014-2018). CARDS recruited over 200 participants (38-71 years of age) to investigate the impact of genetic and lifestyle dementia risk factors on the brain and cognition many years before disease onset. CARDS has discovered interactions between APOE4 carrier status and obesity on limbic grey and white matter microstructure suggestive of tissue damage due to inflammation and hypertension. A UKRI funding application for an 8+ year longitudinal follow-up study of CARDS to identify brain microstructural predictors of cognitive decline is pending.
HD-DRUM - Rhythmic movement training in Huntington's disease:
I study the mechanisms underpinning brain plasticity, including myelin remodelling, and how they can be exploited to the benefit of people with Huntington's disease (HD). With an NIHR/HCRW Advanced Fellowship (2022-2025) I have developed a novel rhythmic drumming training app (HD-DRUM) together with people with HD (HD-Voice), musician Jaime Cantera, and design company Kinneir Dufort. This project is based on our pilot research showing benefits of drumming on cognition and neural pathways in people with HD. As part of the fellowship my research team (Dr Vasilis Ioakeimidis, Lucy Layland, Fionnuala Rogers) and I will study the feasibilty of two-months of HD-DRUM compared with standard care control and effects on the brain and clinical symptoms.
Biography
Undergraduate education
Psychology at Bonn University, Germany
Postgraduate education
D.Phil work on frontal attention deficits at Sussex University
Employment
NIHR/HCRW Advanced Research Fellow (2022-2025)
Reader in Cognitive Neuroscience, Cardiff University (2020-present)
Senior Lecturer, Cardiff University (2016-2020)
Alzheimer’s Society and BRACE Research Fellow (2014-2018)
Research Associate, Cardiff University (2009-2014)
Neuropsychologist at the Research Institute for the Care of Older People (RICE) in Bath (2005-2009)
Lectureship in Psychology at Manchester University and postdoctoral work at the Institute of Psychiatry, King’s College London
Honours and awards
Awards/External Committees
Chartered Psychologist (CPsychol) and Associate Fellow of British Psychological Society (AFBPsS).
Member of Scientific Advisory Board, BRACE Alzheimer's charity
Member of UKRI BBSRC Ageing Across the Lifecourse Working Group
Member of editorial board for Scientific Reports (NPG)
Professional memberships
Society for Neuroscience (SfN)
Cognitive Neuroscience Society (CNS)
Organisation of Human Brain Mapping (OHBM)
International Society for Magnetic Resonance in Medicine (ISMRM)
Publications
2022
- Metzler-Baddeley, C., Busse, M. E., Drew, C. J., Pallmann, P., Jones, D. K. and Rosser, A. 2022. HD-DRUM – a novel computerised drumming training for movement and cognitive abilities in people with Huntington’s disease – app development and protocol of a randomised controlled feasibility study. Presented at: EHDN 2022 Plenary Meeting, Bologna, Italy, 16-18 September 2022, Vol. 93. Vol. S1. pp. A100-A101., (10.1136/jnnp-2022-ehdn.267)
- Casella, C. et al. 2022. Mutation-related magnetization-transfer, not axon density, drives white matter differences in premanifest Huntington's disease: Evidence from in vivo ultra-strong gradient MRI. Human Brain Mapping 43(11), pp. 3439-3460. (10.1002/hbm.25859)
- Coad, B., Ghomroudi, P. A., Sims, R., Aggleton, J., Vann, S. D. and Metzler-Baddeley, C. 2022. Apolipoprotein ε4 modifies obesity-related atrophy in the hippocampal formation of cognitively healthy adults. Neurobiology of Aging 113, pp. 39-54. (10.1016/j.neurobiolaging.2022.02.004)
- Lipp, I., Mole, J. P., Subramanian, L., Linden, D. E. J. and Metzler-Baddeley, C. 2022. Investigating the Anatomy and Microstructure of the Dentato-rubro-thalamic and Subthalamo-ponto-cerebellar Tracts in Parkinson's Disease. Frontiers in Neurology 13, article number: 793693. (10.3389/fneur.2022.793693)
- Clarke, H., Messaritaki, E., Dimitriadis, S. and Metzler-Baddeley, C. 2022. Dementia risk factors modify hubs but leave other connectivity measures unchanged in asymptomatic individuals: a graph theoretical analysis. Brain Connectivity 12(1), pp. 26-40. (10.1089/brain.2020.0935)
2021
- Casella, C. et al. 2021. Mutation-related apparent myelin, not axon density, drives white matter differences in premanifest Huntington's disease: evidence from in vivo ultra-strong gradient MRI. [Online]. bioRxiv. (10.1101/2021.11.29.469517) Available at: https://doi.org/10.1101/2021.11.29.469517
- Coad, B. M., Ghomroudi, P. A., Sims, R., Aggleton, J. P., Vann, S. D. and Metzler-Baddeley, C. 2021. Apolipoprotein ε4 modifies obesity-related atrophy in the hippocampal formation of cognitively healthy adults. [Online]. bioRxiv. Available at: https://doi.org/10.1101/2021.11.12.468385
- Casella, C. et al. 2021. Multi-compartment analysis of the complex gradient-echo signal quantifies myelin breakdown in premanifest Huntington's disease. NeuroImage: Clinical 30, article number: 102658. (10.1016/j.nicl.2021.102658)
2020
- Mole, J. P., Fasano, F., Evans, J., Sims, R., Hamilton, D. A., Kidd, E. and Metzler-Baddeley, C. 2020. Genetic risk of dementia modifies obesity effects on white matter myelin in cognitively healthy adults.. Neurobiology of Aging 94, pp. 298-310. (10.1016/j.neurobiolaging.2020.06.014)
- Casella, C. et al. 2020. Drumming motor sequence training induces apparent myelin remodelling in Huntington’s disease: a longitudinal diffusion MRI and quantitative magnetization transfer study. Journal of Huntington's Disease 9(3), pp. 303-320. (10.3233/JHD-200424)
- Casella, C., Rosser, A., Lipp, I., Jones, D. and Metzler-Baddeley, C. 2020. A critical review of white matter changes in Huntington’s disease. Movement Disorders 35(8), pp. 1302-1311. (10.1002/mds.28109)
- Revie, L., Hamilton, C., Ciafone, J., Donaghy, P. C., Thomas, A. and Metzler-Baddeley, C. 2020. Visuo-perceptual and decision-making contributions to visual hallucinations in mild cognitive impairment in Lewy body disease: insights from a drift diffusion analysis. Brain Sciences 10(8), article number: 540. (10.3390/brainsci10080540)
- Yhnell, E. et al. 2020. A randomised feasibility study of computerised cognitive training as a therapeutic intervention for people with Huntington's disease (CogTrainHD). Pilot and Feasibility Studies 6, article number: 88. (10.1186/s40814-020-00623-z)
- Coad, B., Craig, E., Louch, R., Aggleton, J., Vann, S. and Metzler-Baddeley, C. 2020. Precommissural and postcommissural fornix microstructure in healthy aging and cognition. Brain and Neuroscience Advances 4, pp. 1-12. (10.1177/2398212819899316)
- Revie, L., Bayer, A., Teufel, C. and Metzler-Baddeley, C. 2020. A review of the perceptual and attentional-executive characteristics of dementia with Lewy bodies relative to Alzheimer's and Parkinson's disease. PsyArXiv
- Mole, J. P., Fasano, F., Evans, J., Sims, R., Kidd, E., Aggleton, J. and Metzler-Baddeley, C. 2020. APOE-e4-related differences in left thalamic microstructure in cognitively healthy adults. Scientific Reports 10, article number: 19787. (10.1038/s41598-020-75992-9)
2019
- Bourbon Teles, J., Bells, S., Jones, D. K., Coulthard, E., Rosser, A. and Metzler-Baddeley, C. 2019. Myelin breakdown in human Huntington's disease: multi-modal evidence from diffusion MRI and quantitative magnetization transfer. Neuroscience 403, pp. 79-92. (10.1016/j.neuroscience.2017.05.042)
- Metzler-Baddeley, C. et al. 2019. Sex-specific effects of central adiposity and inflammatory markers on limbic microstructure. NeuroImage 189, pp. 793-803. (10.1016/j.neuroimage.2019.02.007)
- Metzler-Baddeley, C. et al. 2019. Fornix white matter glia damage causes hippocampal gray matter damage during age-dependent limbic decline. Scientific Reports 9, article number: 1060. (10.1038/s41598-018-37658-5)
- Hartopp, N., Wright, P., Ray, N., Evans, T., Metzler-Baddeley, C., Aggleton, J. and O'Sullivan, M. 2019. A key role for subiculum-fornix connectivity in recollection in older age. Frontiers in Systems Neuroscience 12, article number: 70. (10.3389/fnsys.2018.00070)
2018
- Furby, H., Yhnell, E., Mazzaschi, F., Mole, J., Busse, M., Rosser, A. E. and Metzler-Baddeley, C. 2018. Using 3T MRI to explore myelin break-down in pre-symptomatic huntington’s disease. Journal of Neurology, Neurosurgery and Psychiatry 89(S1), pp. A37-A38., article number: E06. (10.1136/jnnp-2018-EHDN.100)
- Bubb, E., Metzler-Baddeley, C. and Aggleton, J. 2018. The cingulum bundle: anatomy, function, and dysfunction. Neuroscience and Biobehavioral Reviews 92, pp. 104-127. (10.1016/j.neubiorev.2018.05.008)
- Yhnell, E. et al. 2018. Exploring computerised cognitive training as a therapeutic intervention for people with Huntington's disease (CogTrainHD): protocol for a randomised feasibility study. Pilot and Feasibility Studies 4, article number: 45. (10.1186/s40814-018-0237-0)
- Caeyenberghs, K. et al. 2018. Evidence for training-dependent structural neuroplasticity in brain-injured patients: A critical review. Neurorehabilitation and Neural Repair 32(2), pp. 99-114. (10.1177/1545968317753076)
2017
- Gan, C. L., O'Sullivan, M. J., Metzler-Baddeley, C. and Halpin, S. 2017. Association of imaging abnormalities of the subcallosal septal area with Alzheimer's disease and mild cognitive impairment. Clinical Radiology 72(11), pp. 915-922. (10.1016/j.crad.2017.04.021)
- Metzler-Baddeley, C., Foley, S., De Santis, S., Charron, C., Hampshire, A., Caeyenberghs, K. and Jones, D. 2017. Dynamics of white matter plasticity underlying working memory training: Multi-modal evidence from diffusion MRI and relaxometry. Journal of Cognitive Neuroscience 29(9), pp. 1509-1520. (10.1162/jocn_a_01127)
2016
- Christiansen, K., Metzler-Baddeley, C., Parker, G., Muhlert, N., Jones, D. K., Aggleton, J. P. and Vann, S. D. 2016. Topographic separation of fornical fibers associated with the anterior and posterior hippocampus in the human brain: an MRI-diffusion study. Brain and Behavior 7(1) (10.1002/brb3.604)
- Rok, B., Metzler-Baddeley, C., Arfan, I. M., Jones, D. and O'Sullivan, M. 2016. Global efficiency of structural networks mediates cognitive control in Mild Cognitive Impairment. Frontiers in Aging Neuroscience 8, article number: 292. (10.3389/fnagi.2016.00292)
- Mole, J. P., Subramanian, L., Bracht, T., Morris, H., Metzler-Baddeley, C. and Linden, D. E. J. 2016. Increased fractional anisotropy in the motor tracts of Parkinson's disease suggests compensatory neuroplasticity or selective neurodegeneration. European Radiology 26(10), pp. 3327-3335. (10.1007/s00330-015-4178-1)
- Metzler-Baddeley, C., Caeyenberghs, K., Foley, S. and Jones, D. K. 2016. Longitudinal data on cortical thickness before and after working memory training. Data in Brief 7, pp. 1143-1147. (10.1016/j.dib.2016.03.090)
- Christiansen, K., Aggleton, J. P., Parker, G. D., O'Sullivan, M. J., Vann, S. D. and Metzler-Baddeley, C. 2016. The status of the precommissural and postcommissural fornix in normal ageing and mild cognitive impairment: An MRI tractography study. NeuroImage 130, pp. 35-47. (10.1016/j.neuroimage.2015.12.055)
- Metzler-Baddeley, C., Caeyenberghs, K., Foley, S. and Jones, D. K. 2016. Task complexity and location specific changes of cortical thickness in executive and salience networks after working memory training. NeuroImage 130, pp. 48-62. (10.1016/j.neuroimage.2016.01.007)
- Caeyenberghs, K., Metzler-Baddeley, C., Foley, S. and Jones, D. K. 2016. Dynamics of the human structural connectome underlying working memory training. Journal of Neuroscience 36(14), pp. 4056-4066. (10.1523/JNEUROSCI.1973-15.2016)
2015
- Kehoe, E. G. et al. 2015. Fornix white matter is correlated with resting state functional connectivity of the thalamus and hippocampus in healthy aging but not in mild cognitive impairment- a preliminary study. Frontiers in Aging Neuroscience 7, article number: 10. (10.3389/fnagi.2015.00010)
- Ray, N. J. et al. 2015. Cholinergic basal forebrain structure influences the reconfiguration of white matter connections to support residual memory in mild cognitive impairment. Journal of Neuroscience 35(2), pp. 739-747. (10.1523/JNEUROSCI.3617-14.2015)
- Gomez, P. A., Sperl, J. I., Sprenger, T., Metzler-Baddeley, C., Jones, D. K. and Saemann, P. 2015. Joint reconstruction of multi-contrast MRI for Multiple Sclerosis lesion segmentation. Bildverarbeitung fuer die Medizin 2015, pp. 155-160. (10.1007/978-3-662-46224-9_28)
2014
- Berlot, R., Metzler-Baddeley, C., Jones, D. K. and O'Sullivan, M. J. 2014. CSF contamination contributes to apparent microstructural alterations in mild cognitive impairment. NeuroImage 92, pp. 27-35. (10.1016/j.neuroimage.2014.01.031)
- Metzler-Baddeley, C., Cantera, J., Coulthard, E., Rosser, A. E., Jones, D. K. and Baddeley, R. J. 2014. Improved executive function and callosal white matter microstructure after rhythmn exercise in Huntington's disease. Journal of Huntington's Disease 3(3), pp. 273-283. (10.3233/JHD-140113)
2013
- Metzler-Baddeley, C., Baddeley, R. J., Jones, D. K., Aggleton, J. P. and O'Sullivan, M. 2013. Individual differences in fornix microstructure and body mass index. PLoS ONE 8(3), article number: e59849. (10.1371/journal.pone.0059849)
2012
- Metzler-Baddeley, C., Jones, D. K., Steventon, J., Westacott, L., Aggleton, J. P. and O'Sullivan, M. 2012. Cingulum microstructure predicts cognitive control in older age and mild cognitive impairment. Journal of Neuroscience 32(49), pp. 17612-17619. (10.1523/JNEUROSCI.3299-12.2012)
- Metzler-Baddeley, C., Hunt, S., Jones, D. K., Leemans, A., Aggleton, J. P. and O'Sullivan, M. 2012. Temporal association tracts and the breakdown of episodic memory in mild cognitive impairment. Neurology 79(23), pp. 2233-2240. (10.1212/WNL.0b013e31827689e8)
- Metzler-Baddeley, C., O'Sullivan, M., Bells, S., Pasternak, O. and Jones, D. K. 2012. How and how not to correct for CSF-contamination in diffusion MRI. Neuroimage 59(2), pp. 1394-1403. (10.1016/j.neuroimage.2011.08.043)
2011
- Metzler-Baddeley, C., Jones, D. K., Belaroussi, B., Aggleton, J. P. and O'Sullivan, M. 2011. Frontotemporal connections in episodic memory and aging: A diffusion MRI tractography study. The Journal of Neuroscience 31(37), pp. 13236-13245. (10.1523/JNEUROSCI.2317-11.2011)
- Metzler-Baddeley, C., Jones, D. K., Aggleton, J. P. and O'Sullivan, M. 2011. The fornix in ageing and memory decline: a diffusion MRI tractography study. Journal of Neurology 258(S1), pp. 18-18. (10.1007/s00415-011-6026-9)
2010
- Laffan, A. J., Metzler-Baddeley, C., Walker, I. and Jones, R. W. 2010. Making errorless learning more active: Self-generation in an error free learning context is superior to standard errorless learning of face-name associations in people with Alzheimer's disease. Neuropsychological Rehabilitation 20(2), pp. 197-211. (10.1080/09602010903202432)
- Metzler-Baddeley, C. and Jones, R. W. 2010. Brief Communication: Cognitive Rehabilitation of Executive Functioning in a Case of Craniopharyngioma. Applied Neuropsychology 17(4), pp. 299-304. (10.1080/09084282.2010.523394)
- Metzler-Baddeley, C., Baddeley, R. J., Lovell, P. G., Laffan, A. and Jones, R. W. 2010. Visual impairments in dementia with Lewy bodies and posterior cortical atrophy.. Neuropsychology 24(1), pp. 35-48. (10.1037/a0016834)
2009
- Metzler-Baddeley, C. and Baddeley, R. J. 2009. Does adaptive training work?. Applied Cognitive Psychology 23(2), pp. 254-266. (10.1002/acp.1454)
- Metzler-Baddeley, C., Baddeley, R. J., Lovell, P. G. and Jones, R. W. 2009. Visual impairment in posterior cortical atrophy and dementia with lewy bodies [Abstract]. Alzheimer's and Dementia 5(4), pp. P458. (10.1016/j.jalz.2009.04.862)
2008
- Metzler-Baddeley, C., Salter, A. and Jones, R. W. 2008. The significance of dyslexia screening for the assessment of dementia in older people. International Journal of Geriatric Psychiatry 23(7), pp. 766-768. (10.1002/gps.1957)
2007
- Metzler-Baddeley, C. 2007. A Review of Cognitive Impairments in Dementia with Lewy Bodies Relative to Alzheimer's Disease and Parkinson's Disease with Dementia. Cortex 43(5), pp. 583-600. (10.1016/S0010-9452(08)70489-1)
2005
- Metzler-Baddeley, C. and Snowden, J. S. 2005. Brief Report: Errorless versus Errorful Learning as a Memory Rehabilitation Approach in Alzheimer's Disease. Journal of Clinical and Experimental Neuropsychology 27(8), pp. 1070-1079. (10.1080/13803390490919164)
2001
- Metzler-Baddeley, C. 2001. Effects of left frontal lesions on the selection of context-appropriate meanings. Neuropsychology 15(3), pp. 315-328. (10.1037/0894-4105.15.3.315)
- Metzler-Baddeley, C. 2001. Location negative priming may be abolished in older age. Zeitschrift für Gerontopsychologie & -psychiatrie 14(4), pp. 187-202. (10.1024//1011-6877.14.4.187)
2000
- Metzler-Baddeley, C. and Parkin, A. J. 2000. Reversed negative priming following frontal lobe lesions. Neuropsychologia 38(4), pp. 363-379. (10.1016/S0028-3932(99)00097-4)
1996
- Parkin, A. J., Bindschaedler, C., Harsent, L. and Metzler-Baddeley, C. 1996. Pathological false alarm rates following damage to the left frontal cortex. Brain and Cognition 32(1), pp. 14-27. (10.1006/brcg.1996.0055)
Teaching
I lecture on the BSc Psychology Year 1 modules Introduction to Psychology (PS1016), the Year 3 module Memory Processes and Disorders (PS3208), and MSc Topics in Psychology (PST720).
Research topics and related papers
HD-DRUM: cognitive and motor training, brain plasticity, Huntington's disease
CARDS: Healthy and pathological ageing/ risk factors of dementia
Neurodegenerative diseases (Alzheimer's disease, Lewy body disease, Huntington's disease)
Neuroglia models of ageing and neurodegeneration
Anatomy of limbic white matter pathways
Funding
Metzler-Baddeley, C (PI) (2022-2025) Development and feasibility randomised controlled pilot study of HD-DRUM – a novel motor sequence training app for people with Huntington’s disease. National Institute for Health Research (NIHR)/ Health Care and Research Wales (HCRW) Advanced Research Fellowship. £917,217.
Duckers, J et al (CoA) (2019) Cystic Fibrosis - Memory assessment and MRI screening. Health & Care Research Wales. £19,200.
Rosser, A, Busse, M & Metzler-Baddeley (2016) Exploring cognitive training as a non-pharmaceutical intervention for people with Huntington's disease. Jaque and Gloria Gossweiler Foundation. £94,714.
Metzler-Baddeley C (PI) (2014) How do individual differences in midlife adiposity and APOE genotype as risk factors for dementia affect brain structure and cognition? A cross-sectional MRI study. Alzheimer’s Society and BRACE Fellowship. £305,161.
Metzler-Baddeley, C (PI), Jones, DK, Rosser AE. (2014) Effects of a novel intervention on white matter microstructure and cognition in Huntington’s disease. NISCHR and Welcome Trust ISSF project grant. £69,769.
Research group
CUBRIC
Cognitive Neuroscience
Imaging Science
Research collaborators
- Professor Derek Jones (Cardiff)
- Professor David Linden (Cardiff)
- Professor Anne Rosser (Cardiff)
- Professor John Aggleton (Cardiff)
- Dr Seralynne Vann (Cardiff)
- Professor Monica Busse (Cardiff)
- Dr John Evans (Cardiff)
- Dr Rebecca Sims (Cardiff)
- Dr Emma Kidd (Cardiff)
- Fabrizio Fasano (Siemens)
- Dr Elizabeth Coulthard (Bristol)
- Dr Roland J Baddeley (Bristol)
- Professor Karen Caeyenberghs (Deakin University, Australia)
- Professor Michael O'Sullivan (University of Queensland, Australia)
- Professor Fernando Maestu (University of Madrid, Spain)
- Dr Michael Funke (University of Texas, USA)
- Professor Derek Hamilton (University of New Mexico, USA)
Media
- What does CUBRIC mean to you? https://youtu.be/1OB2krtm434
- Good evening Wales, BBC Radio Wales (11/12/2018)
- ITV Wales (23/04/18).
- BBC Wales http://www.bbc.co.uk/news/uk-wales-36286847,
- Guardian - https://www.theguardian.com/science/2016/aug/04/brains-of-overweight-people-look-ten-years-older-than-those-of-lean-peers (4/08/16)
- Panorama programme “Living with Dementia – Chris’ story broadcasted on BBC One (2/06/16).
- Pint of Science Event Cardiff on brain plasticity (11/05/18)
- BBC documentation on Terry Pratchett Living with Alzheimer’s, broadcast February 2009 https://www.bbc.co.uk/programmes/b00hhgsb
- BBC Radio 4 Memory Experience.
Supervision
Post-doctoral research associate: Vasilis Ioakeimidis (funded by NIHR/HCRW Advanced Fellowship)
Current PhD students research brain plasticity in ageing: Lucy Layland (School of Psychology Open PhD studentship 2022-2025), Fionnuala Rogers (School of Psychology Open PhD studentship 2021-2024)
Previous PhD students: Chiara Casella, Lauren Revie, Jilu Mole, Kat Christiansen
Past projects
Chiara Casella - Moving beyond the tensor - Advanced characterisation of white matter microstructure in Huntington's disease using translational imaging, PhD Thesis, Cardiff University 2021. Haydn Ellis Prize for best PhD thesis 2021.
Lauren Review - Visual perception and attention and their neurochemical and microstructural brain correlates in healthy and pathological ageing, PhD Thesis, Cardiff University 2021.
Jilu P Mole - The white matter microstructure of the basal ganglia circuitry and its changes in Parkinson's disease, PhD Thesis, Cardiff University 2018.
Kat Christiansen - An integrated analysis of the extended hippocampal system across species. PhD Thesis, Cardiff University 2017.
