The non-medical use of pharmaceuticals such as methylphenidate and modafinil for cognitive enhanc... more The non-medical use of pharmaceuticals such as methylphenidate and modafinil for cognitive enhancement has been explored in college students, medical students and various professions in the US and Europe. We present results of an anonymous online survey of such use among members of the Australian financial services industry. Our hypothesis was that industry sectors would report different preferences for different drugs, reflecting different workplace task demands. The survey was advertised to industry groups, online media articles, and social media outlets between September 2016 and October 2017. Industry sector, hours worked per week, and other demographic and personal health factors were also surveyed. 372 responses were received, of which 140 were valid and complete, and 69 were variously incomplete but usable. Different sectors of the financial services industry reported significantly different rates of use among colleagues. Respondents from different industry sectors also nominated different substances as most prevalent with significantly different frequencies. There was a significant difference in reported hours slept per night between those who reported workplace use and those who did not. A number of side effects were also reported, including headaches and mood swings. This is an important first step in exploring the use of attempts at pharmaceutical cognitive enhancement in competitive professional workplaces with diverse task demands.
We study how markets help spread knowledge about solutions to the standard but computationally ha... more We study how markets help spread knowledge about solutions to the standard but computationally hard problem of maximizing value over indivisible goods subject to a budget constraint. In a first experiment, we f ind that complete markets are fairly ineffective. Still, participants use prices and volumes to improve their choices. In a second experiment, inspired by the notion of oracles in computer science, we show that a reduction to only one carefully chosen asset dramatically improves price quality and knowledge dispersion. Our analysis provides a formalization of Hayek's (1945) conjecture that markets help disseminate knowledge in society.
Niemann-Pick disease type C (NPC) is a rare neurometabolic disorder resulting in impaired intrace... more Niemann-Pick disease type C (NPC) is a rare neurometabolic disorder resulting in impaired intracellular lipid trafficking. The only disease-modifying treatment currently available is miglustat, an iminosugar that inhibits the accumulation of lipid metabolites in neurons and other cells. This longitudinal diffusion tensor imaging (DTI) study examined how the rate of white matter change differed between treated and non-treated adult-onset NPC patient groups. Nine adult-onset NPC patients (seven undergoing treatment with miglustat, two not treated) underwent DTI neuroimaging. Rates of change in white matter structure as indexed by Tract-Based Spatial Statistics (TBSS) of fractional anisotropy were compared between treated and untreated patients. Treated patients were found to have a significantly slower rate of white matter change in the corticospinal tracts, the thalamic radiation and the inferior longitudinal fasciculus. This is further evidence that miglustat treatment may have a pr...
Niemann-Pick Type C disease (NPC), is an autosomal recessive neurovisceral disorder of lipid meta... more Niemann-Pick Type C disease (NPC), is an autosomal recessive neurovisceral disorder of lipid metabolism. One characteristic feature of NPC is a vertical supranuclear gaze palsy particularly affecting saccades. However, horizontal saccades are also impaired and as a consequence a parameter related to horizontal peak saccadic velocity was used as an outcome measure in the clinical trial of miglustat, the first drug approved in several jurisdictions for the treatment of NPC. As NPC-related neuropathology is widespread in the brain we examined a wider range of horizontal saccade parameters and to determine whether these showed treatment-related improvement and, if so, if this was maintained over time. Nine adult NPC patients participated in the study; 8 were treated with miglustat for periods between 33 and 61Â months. Data were available for 2 patients before their treatment commenced and 1 patient was untreated. Tasks included reflexive saccades, antisaccades and self-paced saccades, w...
Niemann-Pick disease type C (NPC) is a rare neurovisceral disorder resulting in impaired intracel... more Niemann-Pick disease type C (NPC) is a rare neurovisceral disorder resulting in impaired intracellular lipid trafficking. The only disease-modifying treatment available to date is miglustat, an iminosugar inhibiting the accumulation of lipid by-products in neurons. This study explored how changes in cerebellar grey and white matter volumes, and in subcortical volumes, related to patient treatment status and disability and ataxia ratings. Nine adult-onset NPC patients and 17 matched controls underwent T1-weighted MRI. One patient was not receiving miglustat, and pre-treatment data were available for a further patient. Semi-automated cerebellar and subcortical segmentation was undertaken, and the rates of change in putamen, hippocampal, thalamic and caudal volumes, and grey and white matter cerebellar volumes, were compared to rates of change in Iturriaga disability score, Brief Ataxia Rating Scale (BARS), and horizontal saccadic gain. Untreated NPC patients appeared to lose cerebellar grey and white matter, bilateral thalamic volume, and right caudate volume faster than treated patients. Cerebellar grey matter volume loss and volume loss in the left thalamus were significantly correlated with Iturriaga disability scale changes. Change in both cerebellar grey and white matter was correlated with decrease in horizontal saccadic gain, but not with change in BARS. This is the first study to examine longitudinal treatment effects of miglustat on cerebellar and subcortical volumes in patients with adult-onset NPC, and is evidence that miglustat may have a protective effect on cerebellar and subcortical structure and function.
Visual evoked responses to dichoptically presented multifocal stimuli were recorded for 92 eyes. ... more Visual evoked responses to dichoptically presented multifocal stimuli were recorded for 92 eyes. Two stimulus variants were explored: temporally sparse and rapidly contrast reversing. We used hierarchical decomposition (HD) to represent the multifocal responses in terms of a small number of potentially unique component waveforms that are interrelated in a multivariate linear autoregressive (MLAR) relationship. The HD method exploits temporal correlations over a range of delays in the responses to estimate parallel, feedforward and feedback relationships between the HD components. Three HD components having temporal interrelationships constrained (at P < 0.05) to a moving approximately 20 ms window could describe the multifocal responses well (median r2-values up to 90%). HD components were similar for both stimulus types and the component waveforms were temporally correlated, especially the first and third components. The data set was large enough to estimate separate HD components for each multifocal stimulus region. The component waveforms differed somewhat by region but the MLAR relationships were similar. At short delays parallel processing dominated. At longer delays the proportion of response drives that were attributed to feedback and feedforward relationships grew. Overall HD analysis seems to provide an informed summary of multifocal responses and insights into their sources.
Voxel-based analysis has suggested that deep gray matter rather than cortical regions is initiall... more Voxel-based analysis has suggested that deep gray matter rather than cortical regions is initially affected in adult Niemann-Pick type C. We sought to examine a range of deep gray matter structures in adults with NPC and relate these to clinical variables. Ten adult patients with NPC (18-49 years of age) were compared with 27 age- and sex-matched controls, and subcortical structures were automatically segmented from normalized T1-weighted MR images. Absolute volumes (in cubic millimeters) were generated for a range of deep gray matter structures and were compared between groups and correlated with illness variables. Most structures were smaller in patients with NPC compared with controls. The thalamus, hippocampus, and striatum showed the greatest and most significant reductions, and left hippocampal volume correlated with symptom score and cognition. Vertex analysis of the thalamus, hippocampus, and caudate implicated regions involved in memory, executive function, and motor control. Thalamic and hippocampal reductions may underpin the memory and executive deficits seen in adult NPC. Volume losses in other subcortical regions may also be involved in the characteristic range of motor, psychiatric, and cognitive deficits seen in the disease.
Background: Niemann-Pick Type C disease (NPC), is an autosomal recessive neurovisceral disorder o... more Background: Niemann-Pick Type C disease (NPC), is an autosomal recessive neurovisceral disorder of lipid metabolism. One characteristic feature of NPC is a vertical supranuclear gaze palsy particularly affecting saccades. However, horizontal saccades are also impaired and as a consequence a parameter related to horizontal peak saccadic velocity was used as an outcome measure in the clinical trial of miglustat, the first drug approved in several jurisdictions for the treatment of NPC. As NPC-related neuropathology is widespread in the brain we examined a wider range of horizontal saccade parameters and to determine whether these showed treatment-related improvement and, if so, if this was maintained over time.
The non-medical use of pharmaceuticals such as methylphenidate and modafinil for cognitive enhanc... more The non-medical use of pharmaceuticals such as methylphenidate and modafinil for cognitive enhancement has been explored in college students, medical students and various professions in the US and Europe. We present results of an anonymous online survey of such use among members of the Australian financial services industry. Our hypothesis was that industry sectors would report different preferences for different drugs, reflecting different workplace task demands. The survey was advertised to industry groups, online media articles, and social media outlets between September 2016 and October 2017. Industry sector, hours worked per week, and other demographic and personal health factors were also surveyed. 372 responses were received, of which 140 were valid and complete, and 69 were variously incomplete but usable. Different sectors of the financial services industry reported significantly different rates of use among colleagues. Respondents from different industry sectors also nominated different substances as most prevalent with significantly different frequencies. There was a significant difference in reported hours slept per night between those who reported workplace use and those who did not. A number of side effects were also reported, including headaches and mood swings. This is an important first step in exploring the use of attempts at pharmaceutical cognitive enhancement in competitive professional workplaces with diverse task demands.
We study how markets help spread knowledge about solutions to the standard but computationally ha... more We study how markets help spread knowledge about solutions to the standard but computationally hard problem of maximizing value over indivisible goods subject to a budget constraint. In a first experiment, we f ind that complete markets are fairly ineffective. Still, participants use prices and volumes to improve their choices. In a second experiment, inspired by the notion of oracles in computer science, we show that a reduction to only one carefully chosen asset dramatically improves price quality and knowledge dispersion. Our analysis provides a formalization of Hayek's (1945) conjecture that markets help disseminate knowledge in society.
Niemann-Pick disease type C (NPC) is a rare neurometabolic disorder resulting in impaired intrace... more Niemann-Pick disease type C (NPC) is a rare neurometabolic disorder resulting in impaired intracellular lipid trafficking. The only disease-modifying treatment currently available is miglustat, an iminosugar that inhibits the accumulation of lipid metabolites in neurons and other cells. This longitudinal diffusion tensor imaging (DTI) study examined how the rate of white matter change differed between treated and non-treated adult-onset NPC patient groups. Nine adult-onset NPC patients (seven undergoing treatment with miglustat, two not treated) underwent DTI neuroimaging. Rates of change in white matter structure as indexed by Tract-Based Spatial Statistics (TBSS) of fractional anisotropy were compared between treated and untreated patients. Treated patients were found to have a significantly slower rate of white matter change in the corticospinal tracts, the thalamic radiation and the inferior longitudinal fasciculus. This is further evidence that miglustat treatment may have a pr...
Niemann-Pick Type C disease (NPC), is an autosomal recessive neurovisceral disorder of lipid meta... more Niemann-Pick Type C disease (NPC), is an autosomal recessive neurovisceral disorder of lipid metabolism. One characteristic feature of NPC is a vertical supranuclear gaze palsy particularly affecting saccades. However, horizontal saccades are also impaired and as a consequence a parameter related to horizontal peak saccadic velocity was used as an outcome measure in the clinical trial of miglustat, the first drug approved in several jurisdictions for the treatment of NPC. As NPC-related neuropathology is widespread in the brain we examined a wider range of horizontal saccade parameters and to determine whether these showed treatment-related improvement and, if so, if this was maintained over time. Nine adult NPC patients participated in the study; 8 were treated with miglustat for periods between 33 and 61Â months. Data were available for 2 patients before their treatment commenced and 1 patient was untreated. Tasks included reflexive saccades, antisaccades and self-paced saccades, w...
Niemann-Pick disease type C (NPC) is a rare neurovisceral disorder resulting in impaired intracel... more Niemann-Pick disease type C (NPC) is a rare neurovisceral disorder resulting in impaired intracellular lipid trafficking. The only disease-modifying treatment available to date is miglustat, an iminosugar inhibiting the accumulation of lipid by-products in neurons. This study explored how changes in cerebellar grey and white matter volumes, and in subcortical volumes, related to patient treatment status and disability and ataxia ratings. Nine adult-onset NPC patients and 17 matched controls underwent T1-weighted MRI. One patient was not receiving miglustat, and pre-treatment data were available for a further patient. Semi-automated cerebellar and subcortical segmentation was undertaken, and the rates of change in putamen, hippocampal, thalamic and caudal volumes, and grey and white matter cerebellar volumes, were compared to rates of change in Iturriaga disability score, Brief Ataxia Rating Scale (BARS), and horizontal saccadic gain. Untreated NPC patients appeared to lose cerebellar grey and white matter, bilateral thalamic volume, and right caudate volume faster than treated patients. Cerebellar grey matter volume loss and volume loss in the left thalamus were significantly correlated with Iturriaga disability scale changes. Change in both cerebellar grey and white matter was correlated with decrease in horizontal saccadic gain, but not with change in BARS. This is the first study to examine longitudinal treatment effects of miglustat on cerebellar and subcortical volumes in patients with adult-onset NPC, and is evidence that miglustat may have a protective effect on cerebellar and subcortical structure and function.
Visual evoked responses to dichoptically presented multifocal stimuli were recorded for 92 eyes. ... more Visual evoked responses to dichoptically presented multifocal stimuli were recorded for 92 eyes. Two stimulus variants were explored: temporally sparse and rapidly contrast reversing. We used hierarchical decomposition (HD) to represent the multifocal responses in terms of a small number of potentially unique component waveforms that are interrelated in a multivariate linear autoregressive (MLAR) relationship. The HD method exploits temporal correlations over a range of delays in the responses to estimate parallel, feedforward and feedback relationships between the HD components. Three HD components having temporal interrelationships constrained (at P < 0.05) to a moving approximately 20 ms window could describe the multifocal responses well (median r2-values up to 90%). HD components were similar for both stimulus types and the component waveforms were temporally correlated, especially the first and third components. The data set was large enough to estimate separate HD components for each multifocal stimulus region. The component waveforms differed somewhat by region but the MLAR relationships were similar. At short delays parallel processing dominated. At longer delays the proportion of response drives that were attributed to feedback and feedforward relationships grew. Overall HD analysis seems to provide an informed summary of multifocal responses and insights into their sources.
Voxel-based analysis has suggested that deep gray matter rather than cortical regions is initiall... more Voxel-based analysis has suggested that deep gray matter rather than cortical regions is initially affected in adult Niemann-Pick type C. We sought to examine a range of deep gray matter structures in adults with NPC and relate these to clinical variables. Ten adult patients with NPC (18-49 years of age) were compared with 27 age- and sex-matched controls, and subcortical structures were automatically segmented from normalized T1-weighted MR images. Absolute volumes (in cubic millimeters) were generated for a range of deep gray matter structures and were compared between groups and correlated with illness variables. Most structures were smaller in patients with NPC compared with controls. The thalamus, hippocampus, and striatum showed the greatest and most significant reductions, and left hippocampal volume correlated with symptom score and cognition. Vertex analysis of the thalamus, hippocampus, and caudate implicated regions involved in memory, executive function, and motor control. Thalamic and hippocampal reductions may underpin the memory and executive deficits seen in adult NPC. Volume losses in other subcortical regions may also be involved in the characteristic range of motor, psychiatric, and cognitive deficits seen in the disease.
Background: Niemann-Pick Type C disease (NPC), is an autosomal recessive neurovisceral disorder o... more Background: Niemann-Pick Type C disease (NPC), is an autosomal recessive neurovisceral disorder of lipid metabolism. One characteristic feature of NPC is a vertical supranuclear gaze palsy particularly affecting saccades. However, horizontal saccades are also impaired and as a consequence a parameter related to horizontal peak saccadic velocity was used as an outcome measure in the clinical trial of miglustat, the first drug approved in several jurisdictions for the treatment of NPC. As NPC-related neuropathology is widespread in the brain we examined a wider range of horizontal saccade parameters and to determine whether these showed treatment-related improvement and, if so, if this was maintained over time.
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