Studying human exposure to vehicular emissions using computational fluid dynamics and an urban mobility simulator: The effect of sidewalk residence time, vehicular technologies and a traffic-calming device.

A computational system consisting of an urban mobility simulator, validated fluid dynamics and an integral exposure model, is proposed to obtain cyclist and pedestrian exposure to PMx and NOx. Pedestrian activities in the urban anthroposphere include walking and running. The computational experiments take place in a computer-generated urban canyon, subject to emissions from diesel and gasoline Euro 5 and Euro 6 vehicular technologies, in continuous and stop-and-go traffic scenarios, and three wind directions at two speeds. The exposure time in the computational domain of slow and fast pedestrians were obtained. Slow pedestrians had exposure times around 17% more than fast pedestrians due to their higher sidewalk residence time. Runners and cyclists decreased their exposures by 57% and 73% respectively compared with walkers. Two traffic scenarios are implemented: one due the presence of a hump and another without a hump. The presence of the hump, increased exposure and fuel consumption by 60% per heavy duty vehicle, about 44-48% per light duty vehicle and about 54-71% per passenger car. Vehicular technology had a large influence on exposure: Heavy duty-Euro 6 vehicle decreased 86% the exposure to PM2.5 and 66% to NOX with respect to Euro 5. The proposed computational system provides information on how wind velocity influenced the inhomogeneous pollutant distribution in the street-canyon, causing exposure to be dependent on pedestrian route location. Microscale sidewalk areas in the order of meters containing higher concentrations were thus located. The cleanest routes in the urban canyon were identified. When the wind intensity doubled from 2 to 4 m s-1, exposure concentration decreased around 45%. The proposed system provides a computational platform to study urban atmospheric fluids, scenarios such as pedestrian routes, vehicular technologies, traffic velocities, meteorological conditions and urban morphology affecting pollution exposure.

Ocular stability and set-point adaptation.

A fundamental challenge to the brain is how to prevent intrusive movements when quiet is needed. Unwanted limb movements such as tremor impair fine motor control and unwanted eye drifts such as nystagmus impair vision. A stable platform is also necessary to launch accurate movements. Accordingly, nature has designed control systems with agonist (excitation) and antagonist (inhibition) muscle pairs functioning in push-pull, around a steady level of balanced tonic activity, the set-point Sensory information can be organized similarly, as in the vestibulo-ocular reflex, which generates eye movements that compensate for head movements. The semicircular canals, working in coplanar pairs, one in each labyrinth, are reciprocally excited and inhibited as they transduce head rotations. The relative change in activity is relayed to the vestibular nuclei, which operate around a set-point of stable balanced activity. When a pathological imbalance occurs, producing unwanted nystagmus without head movement, an adaptive mechanism restores the proper set-point and eliminates the nystagmus. Here we used 90 min of continuous 7 T magnetic field labyrinthine stimulation (MVS) in normal humans to produce sustained nystagmus simulating vestibular imbalance. We identified multiple time-scale processes towards a new zero set-point showing that MVS is an excellent paradigm to investigate the neurobiology of set-point adaptation.This article is part of the themed issue 'Movement suppression: brain mechanisms for stopping and stillness'.

Ranking current and prospective NO2 pollution mitigation strategies: An environmental and economic modelling investigation in Oxford Street, London.

Air pollution continues to be a problem in the urban environment. A range of different pollutant mitigation strategies that promote dispersion and deposition exist, but there is little evidence with respect to their comparative performance from both an environmental and economic perspective. This paper focuses on examining different NO2 mitigation strategies such as trees, buildings facades coated with photocatalytic paint and solid barriers in Oxford Street in London. The case study findings will support ranking the environmental and economic impacts of these different strategies to improve personal exposure conditions on the footpath and on the road in a real urban street canyon. CFD simulations of airflow and NO2 dispersion in Oxford Street in London were undertaken using the OpenFOAM software platform with the k-ε model, taking into account local prevailing wind conditions. Trees are shown to be the most cost-effective strategy, with a small reduction in NO2 concentrations of up to 0.7% on the road. However, solid barriers with and without the application of photocatalytic paint and an innovative material (20 times more expensive than trees) can improve air quality on the footpaths more substantially, up to 7.4%, yet this has a significant detrimental impact on NO2 concentrations (≤23.8%) on the road. Photocatalytic paint on building surfaces presented a minimal environmental reductions (1.2%) and economic (>100 times more expensive than trees) mitigation strategy. The findings recognised the differences between footpath and road concentrations occurred and that a focused examination of three pollution hotspots can provide more cost effective pollution mitigation. This study considers how a number of pollutant mitigation measures can be applied in a single street canyon and demonstrates the strengths and weaknesses of these strategies from economic and environmental perspectives. Further research is required to extrapolate the findings presented here to different street geometries.

Effects of acetazolamide on infantile nystagmus syndrome waveforms: comparisons to contact lenses and convergence in a well-studied subject.

AIM: To determine if acetazolamide, an effective treatment for certain inherited channelopathies, has therapeutic effects on infantile nystagmus syndrome (INS) in a well-studied subject, compare them to other therapies in the same subject and to tenotomy and reattachment (T&R) in other subjects. METHODS: Eye-movement data were taken using a high-speed digital video recording system. Nystagmus waveforms were analyzed by applying an eXpanded Nystagmus Acuity Function (NAFX) at different gaze angles and determining the Longest Foveation Domain (LFD). RESULTS: Acetazolamide improved foveation by both a 59.7% increase in the peak value of the NAFX function (from 0.395 to 0.580) and a 70% broadening of the NAFX vs Gaze Angle curve (the LFD increased from 20° to 34°). The resulting U-shaped improvement in the percent NAFX vs Gaze Angle curve, varied from ~60% near the NAFX peak to over 1000% laterally. The therapeutic improvements in NAFX from acetazolamide (similar to T&R) were intermediate between those of soft contact lenses and convergence, the latter was best; for LFD improvements, acetazolamide and contact lenses were equivalent and less effective than convergence. Computer simulations suggested that damping the central oscillation driving INS was insufficient to produce the foveation improvements and increased NAFX values. CONCLUSION: Acetazolamide resulted in improved-foveation INS waveforms over a broadened range of gaze angles, probably acting at more than one site. This raises the question of whether hereditary INS involves an inherited channelopathy, and whether other agents with known effects on ion channels should be investigated as therapy for this condition.

Evaluation of optic neuropathy in multiple sclerosis using low-contrast visual evoked potentials.

BACKGROUND: Contrast acuity (identification of low-contrast letters on a white background) is frequently reduced in patients with demyelinating optic neuropathy associated with multiple sclerosis (MS), even when high-contrast (Snellen) visual acuity is normal. Since visual evoked potentials (VEPs) induced with high-contrast pattern-reversal stimuli are typically increased in latency in demyelinating optic neuropathy, we asked if VEPs induced with low-contrast stimuli would be more prolonged and thus helpful in identifying demyelinating optic neuropathy in MS. METHODS: We studied 15 patients with clinically definite MS and 15 age-matched normal controls. All subjects underwent a neuro-ophthalmologic assessment, including measurement of high-contrast visual acuity and low-contrast acuities with 25%, 10%, 5%, 2.5%, and 1.25% contrast Sloan charts. In patients with MS, peripapillary retinal nerve fiber layer (RNFL) thickness was determined using optical coherence tomography. Monocular VEPs were induced using pattern-reversal checkerboard stimuli with 100% and 10% contrast between checks, at 5 spatial frequencies (8-130 minutes of arc). RESULTS: VEP latencies were significantly increased in response to low- compared with high-contrast stimuli in both groups. VEP latencies were significantly greater in patients with MS than controls for both high- and low-contrast stimuli. VEP latencies correlated with high- and low-contrast visual acuities and RNFL thickness. VEPs were less likely to be induced with low- than with high-contrast stimuli in eyes with severe residual visual loss. CONCLUSIONS: Visual evoked potentials obtained in patients with multiple sclerosis using low-contrast stimuli are increased in latency or absent when compared with those obtained using high-contrast stimuli and, thus, may prove to be helpful in identifying demyelinating optic neuropathy.

Using fast eye movements to study fatigue in multiple sclerosis.

OBJECTIVE: To investigate whether internuclear ophthalmoparesis (INO) due to demyelination of the medial longitudinal fasciculus (MLF) provides a model for studying the poorly understood symptom of fatigue in multiple sclerosis (MS). We asked whether repetitive horizontal saccades increased eye movement disconjugacy in patients with MS with INO, but not in healthy subjects. METHODS: We compared conjugacy of horizontal saccades in 9 patients with INO (4 bilateral, total 13) and 8 controls during minute 1 and minute 10 of a fatigue test; we measured the ratio of abducting/adducting peak velocity (versional disconjugacy index [VDI]). RESULTS: VDI values were greater in patients than controls. During the fatigue test, controls showed no changes of VDI, but patients did (p < 0.005) for 10/13 INOs, with increased ratios in 5 cases and a decrease in the other 5. CONCLUSION: Fatigue-induced worsening of conjugacy was observed in milder internuclear ophthalmoparesis (INO), and may reflect deteriorated fidelity of saccadic pulse transmission along demyelinated medial longitudinal fasciculus. Improved conjugacy was observed in the more severe INOs, and may be due to adaptive mechanisms, such as recruitment of vergence to aid gaze shifts. INO may provide an accessible, reductionist model to study how decreased neural transmission influences fatigue in multiple sclerosis, how the brain adapts to it, and whether drugs may prove therapeutic.

Evidence for three-dimensional cortical control of gaze from epileptic patients.

Electrophysiological studies in primates indicate that the eye fields of the cerebral hemispheres control gaze in three-dimensional space, and contain neurons that encode both conjugate (versive) and vergence eye movements. Two patients with epilepsy who exhibited disconjugate contraversive horizontal eye movements are described, one during electrical stimulation of the frontal eye fields and the other during focal seizures. We postulate that these eye movements resulted from combined contralateral version and vergence, and suggest that human cortical eye fields also govern visual search in a three-dimensional world, shifting the point of fixation between targets lying in different directions and at different depths.

Dynamic properties of eye movements in mitochondrial chronic progressive external ophthalmoplegia.

AIMS: To relate dynamic properties of eye movements to visual disability in a patient with chronic progressive external ophthalmoplegia (CPEO) due to mitochondrial DNA deletion. METHODS: Visual function was evaluated by neuro-ophthalmological examination and visual function index (VF-14). Eye movements were measured using the magnetic search coil technique. RESULTS: The patient denied diplopia or oscillopsia at rest or during locomotion. His range of eye movements was limited to <12 degrees horizontally, and <19 degrees vertically with smaller movements of the left eye. All classes of movements were impaired, but the eyes accelerated to over 1000 degrees /s/s at the onset of saccades and in response to brisk head rotations. CONCLUSIONS: Diplopia and oscillopsia were suppressed, probably due to visual system adaptation during the slow disease progression. We postulate that relative sparing of pale global extraocular fibres accounted for preserved acceleration of saccades and vestibular eye movements.

Applying saccade models to account for oscillations.

Saccadic oscillations are unwanted back-to-back saccades occurring one upon the other that produce a high-frequency oscillation of the eyes (usually 15-30 Hz). These may occur transiently in normal subjects, for example, around the orthogonal axis of a purely horizontal or vertical saccade, during combined saccade-vergence gaze shifts or during blinks. Some subjects may produce saccadic oscillations at will, usually with convergence. Pathological, involuntary saccadic oscillations such as flutter and opsoclonus are prominent in certain diseases. Our recent mathematical model of the premotor circuit for generating saccades includes brainstem burst neurons in the paramedian pontine reticular formation (PPRF), which show the physiological phenomenon of post-inhibitory rebound (PIR). This model makes saccadic oscillations because of the positive feedback among excitatory and inhibitory burst neurons. Here we review our recent findings and hypotheses and show how they may be reproduced using our lumped model of the saccadic premotor circuitry by reducing the inhibitory efficacy of omnipause neurons.

Impulsive head rotation resets oculopalatal tremor: examination of a model.

We have described a neuromimetic model of the interaction between the inferior olive (IO) and the cerebellum that accounts for symptomatic oculopalatal tremor (OPT), a disorder characterized by oscillations of the eyes (nystagmus), palate and other branchial muscles. OPT develops months after some brainstem strokes, in association with hypertrophic degeneration of the inferior olivary nucleus (IO). We hypothesized that OPT requires both (1) a pulsatile oscillator created by tighter electrotonic coupling between cells in the IO, and (2) a learned response from the cerebellar cortex that combines with the IO pulses to generate the quasi-pendular oscillations. Since the vestibular nuclei project to both IO and vestibulocerebellum, one prediction of the model is that rapid head rotations could interrupt the oscillator, effectively resetting the timing of the ocular nystagmus. The ocular oscillations in OPT vary in amplitude and phase, making it difficult to determine by Fourier analysis whether head perturbations phase-shift the nystagmus. We applied complex wavelet analysis to data from four patients with OPT and checked whether vestibular stimuli induced a change in phase of the nystagmus. First we calculated a threshold for the spontaneous rate of change of phase of OPT by comparing many segments of nystagmus waveform with their time-shifted versions, bootstrapping these arrays, and computing 95% prediction intervals for each patient. Then we compared the rate of change of phase due to each head perturbation with the threshold for that patient. To minimize the effects of the head perturbation itself on the wavelet analysis, we measured effects in a plane orthogonal to the head rotation, e.g., effects of horizontal head rotations on the torsional component of OPT. In all four patients, the rate of change of phase shift increased sharply at the time of the head perturbation, and in three the change was judged to be statistically significant. Thus, the experimental tests supported the prediction of our model for OPT.

Why do patients with PSP fall? Evidence for abnormal otolith responses.

BACKGROUND: Patients with progressive supranuclear palsy (PSP) fall frequently, beginning early in the course of their disease. Abnormal vestibulospinal reflexes are suspected, but the angular vestibulo-ocular reflex, which is mediated by the labyrinthine semicircular canals, survives late into the course of the disease. OBJECTIVE: To test the hypothesis that otolithic-mediated reflexes are abnormal in PSP. METHODS: We tested otolith-ocular reflexes (the translational vestibulo-ocular reflex [tVOR]) during combined rotation-translation in nine patients with PSP and nine age-matched control subjects; subjects viewed far and near targets. We also tested click-induced otolith-spinal reflexes (vestibular-evoked myogenic potentials [VEMPs]) in 10 patients with PSP and 30 age-matched controls. RESULTS: All patients with PSP had small tVOR responses during near viewing that were, on average, only 12% of those of control subjects (p = 0.001). Patients with PSP also showed a reduction of the amplitude of VEMPs compared to control subjects (median [range]: 54.3 [16.8 to 214] vs 149 [11.6 to 466], p = 0.001). CONCLUSIONS: Taken together, these results indicate that abnormal otolith-mediated reflexes may be at least partly responsible for frequent falls in progressive supranuclear palsy, and deserve further study.

Chronic ataxic neuropathy mimicking dorsal midbrain syndrome.

We describe the clinical course, with special attention to the disturbance of eye movements, of a 29-year-old man with chronic ataxic neuropathy with ophthalmoplegia, IgM paraprotein, cold agglutinins and anti-GD1b disialosyl antibodies (CANOMAD). Using the magnetic search coil technique, we documented convergence during upward saccades and other features suggestive of dorsal midbrain syndrome. Thus, in common with Miller Fisher syndrome, CANOMAD may present with clinical findings implicating involvement of the central nervous system, which contains ganglioside antigens to anti-GD1b antibodies.

Tenotomy does not affect saccadic velocities: support for the "small-signal" gain hypothesis.

We investigated the effects of four-muscle tenotomy on saccadic characteristics in infantile nystagmus syndrome (INS) and acquired pendular nystagmus (APN). Eye movements of 10 subjects with INS and one with APN were recorded using infrared reflection, magnetic search coil, or high-speed digital video. The expanded nystagmus acuity function (NAFX) quantified tenotomy-induced foveation changes in the INS. Saccadic characteristics and peak-to-peak nystagmus amplitudes were measured. Novel statistical tests were performed on the saccadic data. Six out of the 10 INS subjects showed no changes in saccadic duration, peak velocity, acceleration, or trajectory. In the other four, the differences were less than in peak-to-peak amplitudes (from 14.6% to 39.5%) and NAFX (from 22.2% to 162.4%). The APN subject also showed no changes despite a 50% decrease in peak-to-peak amplitude and a 34% increase in NAFX. The "small-signal" changes (peak-to-peak nystagmus amplitude and NAFX) were found to far exceed any "large-signal" changes (saccadic). Tenotomy successfully reduced INS and APN, enabling higher visual acuity without adversely affecting saccadic characteristics. These findings support the peripheral, small-signal gain reduction (via proprioceptive tension control) hypothesis. Current linear plant models, limited to normal steady-state muscle tension levels, cannot explain the effects of the tenotomy.

Evaluating large saccades in patients with brain-stem or cerebellar disorders.

Clinicians conventionally test saccades at the bedside by noting the accuracy, initiation time, and speed of large movements, with the patient's head stationary. Partly for methodological reasons, laboratory analysis of saccades has mainly focused on movements of 20 degrees or less. By measuring the velocity waveform of large saccades, it is possible to examine more closely the way in which brain stem and cerebellum guide the eye to the target. Large saccades made by healthy humans show a positively skewed velocity profile. Slow saccades made by patients with brain-stem disorders show a prolonged plateau of low velocity. Some patients with cerebellar disorders may show increased acceleration and deceleration of saccades. Each of these velocity waveforms can be modeled by changing the parameters that describe medium-lead burst neuron firing. In certain other brain-stem and cerebellar disorders, transient decelerations or premature terminations of saccades occur; such velocity waveforms cannot be modeled solely by changing the parameters that describe burst neuron firing. Instead, it is necessary to postulate dysfunction of the mechanism that normally inhibits pontine omnipause neurons, thereby permitting burst neurons to discharge until the saccade is completed. Analysis of large, abnormal saccades calls for application of novel techniques to identify the beginning and end of the saccadic pulse command.

Neuro-ophthalmology of late-onset Tay-Sachs disease (LOTS).

BACKGROUND: Late-onset Tay-Sachs disease (LOTS) is an adult-onset, autosomal recessive, progressive variant of GM2 gangliosidosis, characterized by involvement of the cerebellum and anterior horn cells. OBJECTIVE: To determine the range of visual and ocular motor abnormalities in LOTS, as a prelude to evaluating the effectiveness of novel therapies. METHODS: Fourteen patients with biochemically confirmed LOTS (8 men; age range 24 to 53 years; disease duration 5 to 30 years) and 10 age-matched control subjects were studied. Snellen visual acuity, contrast sensitivity, color vision, stereopsis, and visual fields were measured, and optic fundi were photographed. Horizontal and vertical eye movements (search coil) were recorded, and saccades, pursuit, vestibulo-ocular reflex (VOR), vergence, and optokinetic (OK) responses were measured. RESULTS: All patients showed normal visual functions and optic fundi. The main eye movement abnormality concerned saccades, which were "multistep," consisting of a series of small saccades and larger movements that showed transient decelerations. Larger saccades ended earlier and more abruptly (greater peak deceleration) in LOTS patients than in control subjects; these changes can be attributed to premature termination of the saccadic pulse. Smooth-pursuit and slow-phase OK gains were reduced, but VOR, vergence, and gaze holding were normal. CONCLUSIONS: Patients with late-onset Tay-Sachs disease (LOTS) show characteristic abnormalities of saccades but normal afferent visual systems. Hypometria, transient decelerations, and premature termination of saccades suggest disruption of a "latch circuit" that normally inhibits pontine omnipause neurons, permitting burst neurons to discharge until the eye movement is completed. These measurable abnormalities of saccades provide a means to evaluate the effects of novel treatments for LOTS.

Abnormalities of optokinetic nystagmus in progressive supranuclear palsy.

OBJECTIVES: To measure vertical and horizontal responses to optokinetic (OK) stimulation and investigate directional abnormalities of quick phases in progressive supranuclear palsy (PSP). METHODS: Saccades and OK nystagmus were studied in six PSP patients, five with Parkinson's disease (PD), and 10 controls. The OK stimulus subtended 72 degrees horizontally, 60 degrees vertically, consisted of black and white stripes, and moved at 10-50 degrees /s. RESULTS: All PSP patients showed slowed voluntary vertical saccades and nystagmus quick phases compared with PD or controls. Small, paired, horizontal saccadic intrusions (SWJ) were more frequent and larger in PSP during fixation. Vertical saccades were transiently faster at the time of SWJ and horizontal saccades in PSP. During vertical OK nystagmus, small quick phases were often combined with horizontal SWJ in all subjects; in PSP the vector was closer to horizontal. Vertical OK slow phase gain was reduced in PSP but, in most PD patients, was similar to normals. The average position of gaze shifted in the direction of vertical OK stimulus in PSP patients with preserved slow phase responses but impaired quick phases. CONCLUSIONS: Vertical OK responses in PSP show impaired slow phase responses, and quick phases that are slowed and combined with SWJ to produce an oblique vector. SWJ facilitate vertical saccades and quick phases in PSP, but it is unclear whether this is an adaptive process or a result of the disease. A large OK stimulus is useful to induce responses that can be quantitatively analysed in patients with limited voluntary range of vertical gaze.