RECOMMENDATIONS FOR MINIMUM TRIAL NUMBERS DURING WALKING GAIT

In a rehabilitation context, athletes may not be able to complete large numbers of trials during testing due to joint edema and pain. The purpose of this research was to determine the minimum number of trials needed to achieve a negligibly fluctuating temporal variance profile during walking gait. The time-series kinematics of the hip, knee and ankle were recorded from 10 participants, completing 11 trials each. The time-series variance of each kinematic variables were calculated for ten trials and used as a reference. Using a two-sample SPM1D {t} (α=0.05), all variance combinations (9, 8, 7, ... 3 of 11 trials) from the same participants were compared to the reference. Results showed a minimum of 7 trials were needed to achieve ’stable‘ kinematic variance during walking gait. This study provides evidence for selecting an appropriate number of walking trials in gait analysis, especially in early-stage rehabilitation for patients with joint pain or edema

RECIDIVISM AND THE DARK SIDE OF ETHNIC CAPITAL

Bachelor'sBACHELOR OF SOCIAL SCIENCES (HONOURS

A computer simulation model of the no-claim discount system.

Although the motor insurance business grew by 15.7% to $482 million in terms of gross premiums in 1994, it has been registering losses since the Emergency Period after World War II. The dismal performance of the motor business has often been attributed to the high incurred lost ratio. Although much research had been conducted and actions taken to try to improve the profitability of the motor business, very little has been done on a unique feature of the motor portfolio -- the No-Claim Discount(NCD) system. In fact, the NCD system could have a considerable impact on the motor business. This report looks into the profitability of the current NCD structure in Singapore as well as the equitability of the premiums charged for the different risk groups. This is done firstly by using a theoretical equilibrium state model approach and secondly, by using a computer simulation model. The first approach is a simplified mathematical analysis of the NCD structure using matrix theory to model the movements within the structure. It is found to be insufficient to fully reflect the real-life situation because of the unrealistic assumptions made. To remove these assumptions would make analysis too complicated and hence, computer simulation is necessary. Using Lotus 123, a model is set up to simulate the claims experience of a motor portfolio. The movements of the policyholders were monitored for fifteen years and an analysis of the profitability and equitability of the NCD structure was done. Under different averages for the number of accidents per policyholder per year, different conclusions as regards the profitability issue are obtained, suggesting that the profitability of the current NCD structure varies from insurer to insurer depending on their respective claims experience. As for the equitability of premiums charged, it is observed that a percentage increase in the average number of accidents results in only a very small increase in the total premiums paid. This implies that the structure is not equitable as the better risks are effectively cross-subsidising the poorer risks. Towards the end of the report, the limitations of this study as well as recommendations for future investigation will be presented.BUSINES

Abnormal synchrony of resting state networks in premanifest and symptomatic Huntington disease: the IMAGE-HD study

Background: Functional neural impairments have been documented in people with symptomatic Huntington disease (symp-HD) and in premanifest gene carriers (pre-HD). This study aimed to characterize synchrony in resting state cerebral networks in both pre-HD and symp-HD populations and to determine its association with disease burden and neurocognitive functions. Methods: We acquired functional magnetic resonance imaging (fMRI) data from pre-HD, symp-HD and healthy control participants. The fMRI data were analyzed using multisubject independent component analysis and dual regression. We compared networks of interest among the groups using a nonparametric permutation method and correcting for multiple comparisons. Results: Our study included 25 people in the pre-HD, 23 in the symp-HD and 18 in the healthy control groups. Compared with the control group, the pre-HD group showed decreased synchrony in the sensorimotor and dorsal attention networks; decreased level of synchrony in the sensorimotor network was associated with poorer motor performance. Compared with the control group, the symp-HD group showed widespread reduction in synchrony in the dorsal attention network, which was associated with poorer cognitive performance. The posterior putamen and superior parietal cortex were functionally disconnected from the frontal executive network in the symp-HD compared with control and pre-HD groups. Furthermore, the left frontoparietal network showed areas of increased synchrony in the symp-HD compared with the pre-HD group. Limitations: We could not directly correct for influence of autonomic changes (e.g., heart rate) and respiration on resting state synchronization. Conclusion: Our findings suggest that aberrant synchrony in the sensorimotor and dorsal attention networks may serve as an early signature of neural change in pre-HD individuals. The altered synchrony in dorsal attention, frontoparietal and corticostriatal networks may contribute to the development of clinical symptoms in people with Huntington disease

Multimodal imaging biomarkers in premanifest and early Huntington's disease: 30-month IMAGE-HD data

Background The discovery of potential disease-modifying therapies in a neurodegenerative condition like Huntington's disease depends on the availability of sensitive biomarkers that reflect decline across disease stages and that are functionally and clinically relevant. Aims To quantify macrostructural and microstructural changes in participants with premanifest and symptomatic Huntington's disease over 30 months, and to establish their functional and clinical relevance. Method Multimodal magnetic resonance imaging study measuring changes in macrostructural (volume) and microstructural (diffusivity) measures in 40 patients with premanifest Huntington's disease, 36 patients with symptomatic Huntington's disease and 36 healthy control participants over three testing sessions spanning 30 months. Results Relative to controls, there was greater longitudinal atrophy in participants with symptomatic Huntington's disease in whole brain, grey matter, caudate and putamen, as well as increased caudate fractional anisotropy; caudate volume loss was the only measure to differ between premanifest Huntington's disease and control groups. Changes in caudate volume and fractional anisotropy correlated with each other and neurocognitive decline; caudate volume loss also correlated with clinical and disease severity. Conclusions Caudate neurodegeneration, especially atrophy, may be the most suitable candidate surrogate biomarker for consideration in the development of upcoming clinical trials

Multi-modal neuroimaging in premanifest and early Huntington's disease: 18 Month longitudinal data from the IMAGE-HD study

IMAGE-HD is an Australian based multi-modal longitudinal magnetic resonance imaging (MRI) study in premanifest and early symptomatic Huntington’s disease (pre-HD and symp-HD, respectively). In this investigation we sought to determine the sensitivity of imaging methods to detect macrostructural (volume) and microstructural (diffusivity) longitudinal change in HD. We used a 3T MRI scanner to acquire T(1) and diffusion weighted images at baseline and 18 months in 31 pre-HD, 31 symp-HD and 29 controls. Volume was measured across the whole brain, and volume and diffusion measures were ascertained for caudate and putamen. We observed a range of significant volumetric and, for the first time, diffusion changes over 18 months in both pre-HD and symp-HD, relative to controls, detectable at the brain-wide level (volume change in grey and white matter) and in caudate and putamen (volume and diffusivity change). Importantly, longitudinal volume change in the caudate was the only measure that discriminated between groups across all stages of disease: far from diagnosis (>15 years), close to diagnosis (<15 years) and after diagnosis. Of the two diffusion metrics (mean diffusivity, MD; fractional anisotropy, FA), only longitudinal FA change was sensitive to group differences, but only after diagnosis. These findings further confirm caudate atrophy as one of the most sensitive and early biomarkers of neurodegeneration in HD. They also highlight that different tissue properties have varying schedules in their ability to discriminate between groups along disease progression and may therefore inform biomarker selection for future therapeutic interventions

Longitudinal change in white matter microstructure in Huntington's disease: The IMAGE-HD study

Objective: To quantify 18-month changes in white matter microstructure in premanifest (pre-HD) and symptomatic Huntington's disease (symp-HD). To investigate baseline clinical, cognitive and motor symptoms that are predictive of white matter microstructural change over 18 months. Method: Diffusion tensor imaging (DTI) data were analyzed for 28 pre-HD, 25 symp-HD, and 27 controls scanned at baseline and after 18 months. Unbiased tract-based spatial statistics (TBSS) methods were used to identify longitudinal changes in fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) of white matter. Stepwise linear regression models were used to identify baseline clinical, cognitive, and motor measures that are predictive of longitudinal diffusion changes. Results: Symp-HD compared to controls showed 18-month reductions in FA in the corpus callosum and cingulum white matter. Symp-HD compared to pre-HD showed increased RD in the corpus callosum and striatal projection pathways. FA in the body, genu, and splenium of the corpus callosum was significantly associated with a baseline clinical motor measure (Unified Huntington's Disease Rating Scale: total motor scores: UHDRS–TMS) across both HD groups. This measure was also the only independent predictor of longitudinal decline in FA in all parts of the corpus callosum across both HD groups. Conclusions: We provide direct evidence of longitudinal decline in white matter microstructure in symp-HD. Although pre-HD did not show longitudinal change, clinical symptoms and motor function predicted white matter microstructural changes for all gene positive subjects. These findings suggest that loss of axonal integrity is an early hallmark of neurodegenerative changes which are clinically relevant

Medial frontal hyperactivity to sad faces in generalized social anxiety disorder and modulation by oxytocin

Generalized social anxiety disorder (GSAD) is associated with heightened limbic and prefrontal activation to negative social cues conveying threat (e.g. fearful faces), but less is known about brain response to negative non-threatening social stimuli. The neuropeptide oxytocin (Oxt) has been shown to attenuate (and normalize) fear-related brain activation and reactivity to emotionally negative cues. Here, we examined the effects of intranasal Oxt on cortical activation to non-threatening sad faces in patients with GSAD and matched controls (Con). In a double-blind placebo-controlled within-subjects design, the cortical activation to sad and happy (vs. neutral) faces was examined using functional magnetic resonance imaging following acute intranasal administration of 24 IU Oxt and placebo. Relative to the Con group, GSAD patients exhibited heightened activity to sad faces in the medial prefrontal cortex (mPFC/BA 10) extending into anterior cingulate cortex (ACC/BA 32). Oxt significantly reduced this heightened activation in the mPFC/ACC regions to levels similar to that of controls. These findings suggest that GSAD is associated with cortical hyperactivity to non-threatening negative but not positive social cues and that Oxt attenuates this exaggerated cortical activity. The modulation of cortical activity by Oxt highlights a broader mechanistic role of this neuropeptide in modulating socially negative cues in GSAD