Domain wall behaviour in ferromagnetic nanowires with interfacial and geometrical structuring

The magnetic behaviour in nanoscale structures is of great interest for the fundamental understanding of magnetisation processes and also has importance for wide ranging technological applications. This thesis examines mechanisms for the enhanced control of domain walls in these structures via focussed ion beam modifications to magnetic nanowires and through the inclusion of periodic geometrical modifications to the nanowires geometry. A detailed investigation into the effect of focussed ion beam irradiation on the structure of NiFe/Au bilayers was performed through x-ray reflectivity and fluorescence techniques. This analysis revealed the development of interfacial intermixing with low dose irradiation. This is associated with complex changes of the magnetic behaviour including a rapid decrease, followed by a recovery of the saturation magnetisation with low dose irradiation. This behaviour is attributed to changes in the local environment of the atoms at the interface; resulting in modifications to the magnetic moment on Ni and Fe. The development of an induced moment on Au and a change in the spin-orbit interaction is also suggested. Localised control of the magnetic properties in nanowires demonstrates the ability to manipulate domain walls in these structures. Here, irradiated regions provide pinning sites where the width and dose of the irradiated region give control over the pinning potential. The inclusion edge modulation to nanowires geometry provides additional control over their magnetic behaviour. The direct magnetisation reversal field of these structures is explained by an analytical model based on the torque on the spins following the modulated wire geometry. This model is scalable for different modulation parameters and combines with the effect of localised regions of orthogonal anisotropy along the wire; explaining the reversal behaviour over the entire parameter space. Domain wall mediated reversal in modulated wires was also investigated in these structures. The inclusion of modulation shows an improvement in dynamic properties by the suppression of Walker breakdown. This is due to the relationship between geometrical modulations and the periodicity of micromagnetic domain wall structural changes during the Walker breakdown process. The combination of this work shows a route to the optimisation of the dynamic properties whilst minimising the detrimental increase in the de-pinning field from the modulation

Designing brutal multiplayer video games

Non-digital forms of play that allow players to direct brute force directly upon each other, such as martial arts, boxing and full contact team sports,are very popular. However, inter-player brutality has largely been unexplored as a feature of digital gaming. In this paper, we describe the design and study of 2 multi-player games that encourage players to use brute force directly against other players. Balance of Poweris a tug-of-war style game implemented with Xbox Kinect, while Bundleis a playground-inspired chasing game implemented with smartphones. Two groups of five participants(n=10) played both games while being filmed, and were subsequently interviewed. A thematic analysis identified five keycomponents ofthe brutalmultiplayer video gameexperience, which informsa set of sevendesign considerations.This work aims to inspire the design of engaging game experiences based on awareness and enjoyment of our own and others’ physicality

Visual exploration in Parkinson's disease and Parkinson's disease dementia

Parkinson's disease, typically thought of as a movement disorder, is increasingly recognized as causing cognitive impairment and dementia. Eye movement abnormalities are also described, including impairment of rapid eye movements (saccades) and the fixations interspersed between them. Such movements are under the influence of cortical and subcortical networks commonly targeted by the neurodegeneration seen in Parkinson's disease and, as such, may provide a marker for cognitive decline. This study examined the error rates and visual exploration strategies of subjects with Parkinson's disease, with and without cognitive impairment, whilst performing a battery of visuo-cognitive tasks. Error rates were significantly higher in those Parkinson's disease groups with either mild cognitive impairment (P = 0.001) or dementia (P < 0.001), than in cognitively normal subjects with Parkinson's disease. When compared with cognitively normal subjects with Parkinson's disease, exploration strategy, as measured by a number of eye tracking variables, was least efficient in the dementia group but was also affected in those subjects with Parkinson's disease with mild cognitive impairment. When compared with control subjects and cognitively normal subjects with Parkinson's disease, saccade amplitudes were significantly reduced in the groups with mild cognitive impairment or dementia. Fixation duration was longer in all Parkinson's disease groups compared with healthy control subjects but was longest for cognitively impaired Parkinson's disease groups. The strongest predictor of average fixation duration was disease severity. Analysing only data from the most complex task, with the highest error rates, both cognitive impairment and disease severity contributed to a predictive model for fixation duration [F(2,76) = 12.52, P ≤ 0.001], but medication dose did not (r = 0.18, n = 78, P = 0.098, not significant). This study highlights the potential use of exploration strategy measures as a marker of cognitive decline in Parkinson's disease and reveals the efficiency by which fixations and saccades are deployed in the build-up to a cognitive response, rather than merely focusing on the outcome itself. The prolongation of fixation duration, present to a small but significant degree even in cognitively normal subjects with Parkinson's disease, suggests a disease-specific impact on the networks directing visual exploration, although the study also highlights the multi-factorial nature of changes in exploration and the significant impact of cognitive decline on efficiency of visual searc

Utility of the new Movement Disorder Society clinical diagnostic criteria for Parkinson's disease applied retrospectively in a large cohort study of recent onset cases

Objective: To examine the utility of the new Movement Disorder Society (MDS) diagnostic criteria in a large cohort of Parkinson's disease (PD) patients. Methods: Recently diagnosed (&lt;3.5 years) PD cases fulfilling United Kingdom (UK) brain bank criteria in Tracking Parkinson's, a UK multicenter prospective natural history study were assessed by retrospective application of the MDS criteria. Results: In 2000 cases, 1835 (91.7%) met MDS criteria for PD, either clinically established (n = 1261, 63.1%) or clinically probable (n = 574, 28.7%), leaving 165 (8.3%) not fulfilling criteria. Clinically established cases were significantly more likely to have limb rest tremor (89.3%), a good l-dopa response (79.5%), and olfactory loss (71.1%), than clinically probable cases (60.6%, 44.4%, and 34.5% respectively), but differences between probable PD and ‘not PD’ cases were less evident. In cases not fulfilling criteria, the mean MDS UPDRS3 score (25.1, SD 13.2) was significantly higher than in probable PD (22.3, SD 12.7, p = 0.016) but not established PD (22.9, SD 12.0, p = 0.066). The l-dopa equivalent daily dose of 341 mg (SD 261) in non-PD cases was significantly higher than in probable PD (250 mg, SD 214, p &lt; 0.001) and established PD (308 mg, SD 199, p = 0.025). After 30 months' follow-up, 89.5% of clinically established cases at baseline remained as PD (established/probable), and 86.9% of those categorized as clinically probable at baseline remained as PD (established/probable). Cases not fulfilling PD criteria had more severe parkinsonism, in particular relating to postural instability, gait problems, and cognitive impairment. Conclusion: Over 90% of cases clinically diagnosed as early PD fulfilled the MDS criteria for PD. Those not fulfilling criteria may have an atypical parkinsonian disorder or secondary parkinsonism that is not correctly identified by the UK Brain Bank criteria, but possibly by the new criteria

Vascular disease and vascular risk factors in relation to motor features and cognition in early Parkinson's disease

Funded by Parkinson's UK National Institute for Health Research (NIHR) DeNDRoN network NIHR Newcastle Biomedical Research Unit Newcastle University NIHR funded Biomedical Research Centre in CambridgePeer reviewedPublisher PD

Predicting cognitive decline using neuropsychiatric symptoms in prodromal Lewy body dementia: A longitudinal study

Introduction: Neuropsychiatric symptoms (NPS) in Lewy body dementias (LBD) occur frequently and early in disease progression. Such symptoms are associated with worse quality of life, caregiver burden and functional limitations. Limited evidence exists, however, outlining the longitudinal relationship between NPS and cognitive decline in prodromal LBD. Methods: 123 participants were derived from three cohort studies. Patients with mild cognitive impairment (MCI) relating to probable dementia with Lewy bodies (MCI-LB, n = 67) and Parkinson's disease (PD-MCI, n = 56) completed comprehensive cognitive and neuropsychiatric assessment and were followed up longitudinally. Linear regression and mixed effects models assessed the relationship between baseline NPS and cognition at baseline and over time. Results: In MCI-LB, overall NPS burden was associated with declines over time in executive function (p = 0.026) and processing speed (p = 0.028) and baseline aberrant motor behaviour was associated with declines in attention (p < 0.025). Anxiety was significantly associated with poorer visuospatial functioning (p = 0.016) at baseline and poorer attention both at baseline (p = 0.017) and across time points (p = 0.024). In PD-MCI, psychosis was associated with poorer executive functioning at baseline (p = 0.008) and across time points (p = 0.002) but had no association with changes longitudinally. Conclusions: Core neuropsychiatric components of LBD are not strongly associated with cognition in prodromal disease. This may suggest that neuropathological mechanisms underlying NPS may not be the same as those underlying cognitive impairment. Non-core NPS, however, may be more directly associated with cognitive change. Future studies utilising neuroimaging techniques are needed to explore the neuropathological basis of NPS in prodromal LBD

Baseline and longitudinal grey matter changes in newly diagnosed Parkinson\u27s disease: ICICLE-PD study

Mild cognitive impairment in Parkinson\u27s disease is associated with progression to dementia (Parkinson\u27s disease dementia) in a majority of patients. Determining structural imaging biomarkers associated with prodromal Parkinson\u27s disease dementia may allow for the earlier identification of those at risk, and allow for targeted disease modifying therapies. One hundred and five non-demented subjects with newly diagnosed idiopathic Parkinson\u27s disease and 37 healthy matched controls had serial 3 T structural magnetic resonance imaging scans with clinical and neuropsychological assessments at baseline, which were repeated after 18 months. The Movement Disorder Society Task Force criteria were used to classify the Parkinson\u27s disease subjects into Parkinson\u27s disease with mild cognitive impairment (n = 39) and Parkinson\u27s disease with no cognitive impairment (n = 66). Freesurfer image processing software was used to measure cortical thickness and subcortical volumes at baseline and follow-up. We compared regional percentage change of cortical thinning and subcortical atrophy over 18 months. At baseline, cases with Parkinson\u27s disease with mild cognitive impairment demonstrated widespread cortical thinning relative to controls and atrophy of the nucleus accumbens compared to both controls and subjects with Parkinson\u27s disease with no cognitive impairment. Regional cortical thickness at baseline was correlated with global cognition in the combined Parkinson\u27s disease cohort. Over 18 months, patients with Parkinson\u27s disease with mild cognitive impairment demonstrated more severe cortical thinning in frontal and temporo-parietal cortices, including hippocampal atrophy, relative to those with Parkinson\u27s disease and no cognitive impairment and healthy controls, whereas subjects with Parkinson\u27s disease and no cognitive impairment showed more severe frontal cortical thinning compared to healthy controls. At baseline, Parkinson\u27s disease with no cognitive impairment converters showed bilateral temporal cortex thinning relative to the Parkinson\u27s disease with no cognitive impairment stable subjects. Although loss of both cortical and subcortical volume occurs in non-demented Parkinson\u27s disease, our longitudinal analyses revealed that Parkinson\u27s disease with mild cognitive impairment shows more extensive atrophy and greater percentage of cortical thinning compared to Parkinson\u27s disease with no cognitive impairment. In particular, an extension of cortical thinning in the temporo-parietal regions in addition to frontal atrophy could be a biomarker in therapeutic studies of mild cognitive impairment in Parkinson\u27s disease for progression towards dementia

L-dopa responsiveness in early Parkinson's disease is associated with the rate of motor progression.

BACKGROUND: L-dopa responsiveness in Parkinson's disease (PD) varies, but the clinical correlates and significance of this are ill-defined. METHODS: Patients were assessed before and after their usual morning L-dopa dose, using the MDS Unified PD Rating Scale Part 3 (MDS UPDRS 3), and rated as definite responders (≥24.5% improvement) or limited responders (<24.5%). RESULTS: 1007 cases, mean age 66.1 years (SD 9.1) at diagnosis, were assessed 3.4 (SD 0.9) years after diagnosis. The L-dopa response was definite in 614 cases (61.0%), median reduction in MDS UPDRS 3 scores was 42.0%, (IQR 33.3, 53.1), and was limited in 393 cases (39.0%), median reduction in MDS UPDRS 3 scores 11.5% (IQR 4.3, 18.2). Definite responders were younger (66.3 years at study entry, SD 9.3) than limited responders (69.2 years, SD 8.4, p < 0.001). The MDS UPDRS 3 score at study entry in definite responders (21.0, SD 10.5) was significantly lower than in limited responders (24.7, SD 13.4, p < 0.001). The MDS UPDRS 3 increase over 18 months was less in definite responders at 3.0 (SD 10.4), compared to limited responders (6.4, SD 11.0, p < 0.001). The levodopa equivalent daily dose (LEDD) was not significantly different at study entry (definite responders 317 mg, SD 199, vs limited responders 305 mg, SD 191, p = 0.53). However, LEDD was significantly higher at the time of the L-dopa challenge test in definite responders (541 mg, SD 293) compared to limited responders (485 mg, SD 215, p = 0.01). Responsiveness to L-dopa was unaffected by the challenge test dose (p = 0.54). CONCLUSIONS: The main determinants of variation in the L-dopa response in early PD are age and motor severity. A limited L-dopa response is associated with faster motor progression

Variation in Recent Onset Parkinson's Disease : Implications for Prodromal Detection

The research was funded by Parkinson’s UK and supported by the National Institute for Health Research (NIHR) DeNDRoN network, the NIHR Newcastle Biomedical Research Unit based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, and the NIHR funded Biomedical Research Centre in Cambridge.Peer reviewedPublisher PD

Tracking Parkinson's : Study Design and Baseline Patient Data

Peer reviewedPublisher PD