Objective determination of feature resolution in two sea surface temperature analyses

Considerable effort is presently being devoted to producing high-resolution sea surface temperature (SST) analyses with a goal of spatial grid resolutions as low as 1 km. Because grid resolution is not the same as feature resolution, a method is needed to objectively determine the resolution capability and accuracy of SST analysis products. Ocean model SST fields are used in this study as simulated “true” SST data and subsampled based on actual infrared and microwave satellite data coverage. The subsampled data are used to simulate sampling errors due to missing data. Two different SST analyses are considered and run using both the full and the subsampled model SST fields, with and without additional noise. The results are compared as a function of spatial scales of variability using wavenumber auto- and cross-spectral analysis. The spectral variance at high wavenumbers (smallest wavelengths) is shown to be attenuated relative to the true SST because of smoothing that is inherent to both analysis procedures. Comparisons of the two analyses (both having grid sizes of roughly ) show important differences. One analysis tends to reproduce small-scale features more accurately when the high-resolution data coverage is good but produces more spurious small-scale noise when the high-resolution data coverage is poor. Analysis procedures can thus generate small-scale features with and without data, but the small-scale features in an SST analysis may be just noise when high-resolution data are sparse. Users must therefore be skeptical of high-resolution SST products, especially in regions where high-resolution (~5 km) infrared satellite data are limited because of cloud cover.

Intra-crystalline protein diagenesis (IcPD) in Patella vulgata. Part II: Breakdown and temperature sensitivity

Artificial diagenesis of the intra-crystalline proteins isolated from Patella vulgata was induced by isothermal heating at 140 °C, 110 °C and 80 °C. Protein breakdown was quantified for multiple amino acids, measuring the extent of peptide bond hydrolysis, amino acid racemisation and decomposition. The patterns of diagenesis are complex; therefore the kinetic parameters of the main reactions were estimated by two different methods: 1) a well-established approach based on fitting mathematical expressions to the experimental data, e.g. first-order rate equations for hydrolysis and power-transformed first-order rate equations for racemisation; and 2) an alternative model-free approach, which was developed by estimating a “scaling” factor for the independent variable (time) which produces the best alignment of the experimental data. This method allows the calculation of the relative reaction rates for the different temperatures of isothermal heating. High-temperature data were compared with the extent of degradation detected in sub-fossil Patella specimens of known age, and we evaluated the ability of kinetic experiments to mimic diagenesis at burial temperature. The results highlighted a difference between patterns of degradation at low and high temperature and therefore we recommend caution for the extrapolation of protein breakdown rates to low burial temperatures for geochronological purposes when relying solely on kinetic data.

Aircraft routing with minimal climate impact: the REACT4C climate cost function modelling approach (V1.0)

In addition to CO2, the climate impact of aviation is strongly influenced by non-CO2 emissions, such as nitrogen oxides, influencing ozone and methane, and water vapour, which can lead to the formation of persistent contrails in ice-supersaturated regions. Because these non-CO2 emission effects are characterised by a short lifetime, their climate impact largely depends on emission location and time; that is to say, emissions in certain locations (or times) can lead to a greater climate impact (even on the global average) than the same emission in other locations (or times). Avoiding these climate-sensitive regions might thus be beneficial to climate. Here, we describe a modelling chain for investigating this climate impact mitigation option. This modelling chain forms a multi-step modelling approach, starting with the simulation of the fate of emissions released at a certain location and time (time-region grid points). This is performed with the chemistry–climate model EMAC, extended via the two submodels AIRTRAC (V1.0) and CONTRAIL (V1.0), which describe the contribution of emissions to the composition of the atmosphere and to contrail formation, respectively. The impact of emissions from the large number of time-region grid points is efficiently calculated by applying a Lagrangian scheme. EMAC also includes the calculation of radiative impacts, which are, in a second step, the input to climate metric formulas describing the global climate impact of the emission at each time-region grid point. The result of the modelling chain comprises a four-dimensional data set in space and time, which we call climate cost functions and which describes the global climate impact of an emission at each grid point and each point in time. In a third step, these climate cost functions are used in an air traffic simulator (SAAM) coupled to an emission tool (AEM) to optimise aircraft trajectories for the North Atlantic region. Here, we describe the details of this new modelling approach and show some example results. A number of sensitivity analyses are performed to motivate the settings of individual parameters. A stepwise sanity check of the results of the modelling chain is undertaken to demonstrate the plausibility of the climate cost functions.

Towards a general theory of extremes for observables of chaotic dynamical systems

In this paper we provide a connection between the geometrical properties of the attractor of a chaotic dynamical system and the distribution of extreme values. We show that the extremes of so-called physical observables are distributed according to the classical generalised Pareto distribution and derive explicit expressions for the scaling and the shape parameter. In particular, we derive that the shape parameter does not depend on the cho- sen observables, but only on the partial dimensions of the invariant measure on the stable, unstable, and neutral manifolds. The shape parameter is negative and is close to zero when high-dimensional systems are considered. This result agrees with what was derived recently using the generalized extreme value approach. Combining the results obtained using such physical observables and the properties of the extremes of distance observables, it is possible to derive estimates of the partial dimensions of the attractor along the stable and the unstable directions of the flow. Moreover, by writing the shape parameter in terms of moments of the extremes of the considered observable and by using linear response theory, we relate the sensitivity to perturbations of the shape parameter to the sensitivity of the moments, of the partial dimensions, and of the Kaplan–Yorke dimension of the attractor. Preliminary numer- ical investigations provide encouraging results on the applicability of the theory presented here. The results presented here do not apply for all combinations of Axiom A systems and observables, but the breakdown seems to be related to very special geometrical configurations.

Tensor regression based on linked multiway parameter analysis

Classical regression methods take vectors as covariates and estimate the corresponding vectors of regression parameters. When addressing regression problems on covariates of more complex form such as multi-dimensional arrays (i.e. tensors), traditional computational models can be severely compromised by ultrahigh dimensionality as well as complex structure. By exploiting the special structure of tensor covariates, the tensor regression model provides a promising solution to reduce the model’s dimensionality to a manageable level, thus leading to efficient estimation. Most of the existing tensor-based methods independently estimate each individual regression problem based on tensor decomposition which allows the simultaneous projections of an input tensor to more than one direction along each mode. As a matter of fact, multi-dimensional data are collected under the same or very similar conditions, so that data share some common latent components but can also have their own independent parameters for each regression task. Therefore, it is beneficial to analyse regression parameters among all the regressions in a linked way. In this paper, we propose a tensor regression model based on Tucker Decomposition, which identifies not only the common components of parameters across all the regression tasks, but also independent factors contributing to each particular regression task simultaneously. Under this paradigm, the number of independent parameters along each mode is constrained by a sparsity-preserving regulariser. Linked multiway parameter analysis and sparsity modeling further reduce the total number of parameters, with lower memory cost than their tensor-based counterparts. The effectiveness of the new method is demonstrated on real data sets.

Climate variability and human impact in South America during the last 2000 years: synthesis and perspectives from pollen records

An improved understanding of present-day climate variability and change relies on high-quality data sets from the past 2 millennia. Global efforts to model regional climate modes are in the process of being validated against, and integrated with, records of past vegetation change. For South America, however, the full potential of vegetation records for evaluating and improving climate models has hitherto not been sufficiently acknowledged due to an absence of information on the spatial and temporal coverage of study sites. This paper therefore serves as a guide to high-quality pollen records that capture environmental variability during the last 2 millennia. We identify 60 vegetation (pollen) records from across South America which satisfy geochronological requirements set out for climate modelling, and we discuss their sensitivity to the spatial signature of climate modes throughout the continent. Diverse patterns of vegetation response to climate change are observed, with more similar patterns of change in the lowlands and varying intensity and direction of responses in the highlands. Pollen records display local-scale responses to climate modes; thus, it is necessary to understand how vegetation–climate interactions might diverge under variable settings. We provide a qualitative translation from pollen metrics to climate variables. Additionally, pollen is an excellent indicator of human impact through time. We discuss evidence for human land use in pollen records and provide an overview considered useful for archaeological hypothesis testing and important in distinguishing natural from anthropogenically driven vegetation change. We stress the need for the palynological community to be more familiar with climate variability patterns to correctly attribute the potential causes of observed vegetation dynamics. This manuscript forms part of the wider LOng-Term multi-proxy climate REconstructions and Dynamics in South America – 2k initiative that provides the ideal framework for the integration of the various palaeoclimatic subdisciplines and palaeo-science, thereby jump-starting and fostering multidisciplinary research into environmental change on centennial and millennial timescales.

Assessment of the CMD Mini-Explorer, a new low-frequency multi-coil electromagnetic device, for archaeological investigations

In this article we assess the abilities of a new electromagnetic (EM) system, the CMD Mini-Explorer, for prospecting of archaeological features in Ireland and the UK. The Mini-Explorer is an EM probe which is primarily aimed at the environmental/geological prospecting market for the detection of pipes and geology. It has long been evident from the use of other EM devices that such an instrument might be suitable for shallow soil studies and applicable for archaeological prospecting. Of particular interest for the archaeological surveyor is the fact that the Mini-Explorer simultaneously obtains both quadrature (‘conductivity’) and in-phase (relative to ‘magnetic susceptibility’) data from three depth levels. As the maximum depth range is probably about 1.5 m, a comprehensive analysis of the subsoil within that range is possible. As with all EM devices the measurements require no contact with the ground, thereby negating the problem of high contact resistance that often besets earth resistance data during dry spells. The use of the CMD Mini-Explorer at a number of sites has demonstrated that it has the potential to detect a range of archaeological features and produces high-quality data that are comparable in quality to those obtained from standard earth resistance and magnetometer techniques. In theory the ability to measure two phenomena at three depths suggests that this type of instrument could reduce the number of poor outcomes that are the result of single measurement surveys. The high success rate reported here in the identification of buried archaeology using a multi-depth device that responds to the two most commonly mapped geophysical phenomena has implications for evaluation style surveys. Copyright © 2013 John Wiley & Sons, Ltd.

Do jumps matter for volatility forecasting? Evidence from energy markets

This paper characterizes the dynamics of jumps and analyzes their importance for volatility forecasting. Using high-frequency data on four prominent energy markets, we perform a model-free decomposition of realized variance into its continuous and discontinuous components. We find strong evidence of jumps in energy markets between 2007 and 2012. We then investigate the importance of jumps for volatility forecasting. To this end, we estimate and analyze the predictive ability of several Heterogenous Autoregressive (HAR) models that explicitly capture the dynamics of jumps. Conducting extensive in-sample and out-of-sample analyses, we establish that explicitly modeling jumps does not significantly improve forecast accuracy. Our results are broadly consistent across our four energy markets, forecasting horizons, and loss functions

Implicit equal-weights particle filter

Filter degeneracy is the main obstacle for the implementation of particle filter in non-linear high-dimensional models. A new scheme, the implicit equal-weights particle filter (IEWPF), is introduced. In this scheme samples are drawn implicitly from proposal densities with a different covariance for each particle, such that all particle weights are equal by construction. We test and explore the properties of the new scheme using a 1,000-dimensional simple linear model, and the 1,000-dimensional non-linear Lorenz96 model, and compare the performance of the scheme to a Local Ensemble Kalman Filter. The experiments show that the new scheme can easily be implemented in high-dimensional systems and is never degenerate, with good convergence properties in both systems.

Diel surface temperature range scales with lake size

Ecological and biogeochemical processes in lakes are strongly dependent upon water temperature. Long-term surface warming of many lakes is unequivocal, but little is known about the comparative magnitude of temperature variation at diel timescales, due to a lack of appropriately resolved data. Here we quantify the pattern and magnitude of diel temperature variability of surface waters using high-frequency data from 100 lakes. We show that the near-surface diel temperature range can be substantial in summer relative to long-term change and, for lakes smaller than 3 km2, increases sharply and predictably with decreasing lake area. Most small lakes included in this study experience average summer diel ranges in their near-surface temperatures of between 4 and 7°C. Large diel temperature fluctuations in the majority of lakes undoubtedly influence their structure, function and role in biogeochemical cycles, but the full implications remain largely unexplored.

Multi-Conjugate Adaptive Optics VLT imaging of the distant old open cluster FSR 1415

We employ the recently installed near-infrared Multi-Conjugate Adaptive Optics demonstrator (MAD) to determine the basic properties of a newly identified, old and distant, Galactic open cluster (FSR 1415). The MAD facility remarkably approaches the diffraction limit, reaching a resolution of 0.07 arcsec (in K), that is also uniform in a field of similar to 1.8 arcmin in diameter. The MAD facility provides photometry that is 50 per cent complete at K similar to 19. This corresponds to about 2.5 mag below the cluster main-sequence turn-off. This high-quality data set allows us to derive an accurate heliocentric distance of 8.6 kpc, a metallicity close to solar and an age of similar to 2.5 Gyr. On the other hand, the deepness of the data allows us to reconstruct (completeness-corrected) mass functions (MFs) indicating a relatively massive cluster, with a flat core MF. The Very Large Telescope/MAD capabilities will therefore provide fundamental data for identifying/analysing other faint and distant open clusters in the Galaxy III and IV quadrants.

Characterization of the optical properties of atmospheric aerosols in Amazonia from long-term AERONET monitoring (1993-1995 and 1999-2006)

We present a new climatology of atmospheric aerosols (primarily pyrogenic and biogenic) for the Brazilian tropics on the basis of a high-quality data set of spectral aerosol optical depth and directional sky radiance measurements from Aerosol Robotic Network (AERONET) Cimel Sun-sky radiometers at more than 15 sites distributed across the Amazon basin and adjacent Cerrado region. This network is the only long-term project (with a record including observations from more than 11 years at some locations) ever to have provided ground-based remotely-sensed column aerosol properties for this critical region. Distinctive features of the Amazonian area aerosol are presented by partitioning the region into three aerosol regimes: southern Amazonian forest, Cerrado, and northern Amazonian forest. The monitoring sites generally include measurements from the interval 1999-2006, but some sites have measurement records that date back to the initial days of the AERONET program in 1993. Seasonal time series of aerosol optical depth (AOD), angstrom ngstrom exponent, and columnar-averaged microphysical properties of the aerosol derived from sky radiance inversion techniques (single-scattering albedo, volume size distribution, fine mode fraction of AOD, etc.) are described and contrasted for the defined regions. During the wet season, occurrences of mineral dust penetrating deep into the interior were observed.

Mobile systems for monitoring Parkinson's disease

A challenge for the clinical management of Parkinson's disease (PD) is the large within- and between-patient variability in symptom profiles as well as the emergence of motor complications which represent a significant source of disability in patients. This thesis deals with the development and evaluation of methods and systems for supporting the management of PD by using repeated measures, consisting of subjective assessments of symptoms and objective assessments of motor function through fine motor tests (spirography and tapping), collected by means of a telemetry touch screen device. One aim of the thesis was to develop methods for objective quantification and analysis of the severity of motor impairments being represented in spiral drawings and tapping results. This was accomplished by first quantifying the digitized movement data with time series analysis and then using them in data-driven modelling for automating the process of assessment of symptom severity. The objective measures were then analysed with respect to subjective assessments of motor conditions. Another aim was to develop a method for providing comparable information content as clinical rating scales by combining subjective and objective measures into composite scores, using time series analysis and data-driven methods. The scores represent six symptom dimensions and an overall test score for reflecting the global health condition of the patient. In addition, the thesis presents the development of a web-based system for providing a visual representation of symptoms over time allowing clinicians to remotely monitor the symptom profiles of their patients. The quality of the methods was assessed by reporting different metrics of validity, reliability and sensitivity to treatment interventions and natural PD progression over time. Results from two studies demonstrated that the methods developed for the fine motor tests had good metrics indicating that they are appropriate to quantitatively and objectively assess the severity of motor impairments of PD patients. The fine motor tests captured different symptoms; spiral drawing impairment and tapping accuracy related to dyskinesias (involuntary movements) whereas tapping speed related to bradykinesia (slowness of movements). A longitudinal data analysis indicated that the six symptom dimensions and the overall test score contained important elements of information of the clinical scales and can be used to measure effects of PD treatment interventions and disease progression. A usability evaluation of the web-based system showed that the information presented in the system was comparable to qualitative clinical observations and the system was recognized as a tool that will assist in the management of patients.

A web-based system for visualizing upper limb motor performance of Parkinson’s disease patients

Objective To design, develop and set up a web-based system for enabling graphical visualization of upper limb motor performance (ULMP) of Parkinson’s disease (PD) patients to clinicians. Background Sixty-five patients diagnosed with advanced PD have used a test battery, implemented in a touch-screen handheld computer, in their home environment settings over the course of a 3-year clinical study. The test items consisted of objective measures of ULMP through a set of upper limb motor tests (finger to tapping and spiral drawings). For the tapping tests, patients were asked to perform alternate tapping of two buttons as fast and accurate as possible, first using the right hand and then the left hand. The test duration was 20 seconds. For the spiral drawing test, patients traced a pre-drawn Archimedes spiral using the dominant hand, and the test was repeated 3 times per test occasion. In total, the study database consisted of symptom assessments during 10079 test occasions. Methods Visualization of ULMP The web-based system is used by two neurologists for assessing the performance of PD patients during motor tests collected over the course of the said study. The system employs animations, scatter plots and time series graphs to visualize the ULMP of patients to the neurologists. The performance during spiral tests is depicted by animating the three spiral drawings, allowing the neurologists to observe real-time accelerations or hesitations and sharp changes during the actual drawing process. The tapping performance is visualized by displaying different types of graphs. Information presented included distribution of taps over the two buttons, horizontal tap distance vs. time, vertical tap distance vs. time, and tapping reaction time over the test length. Assessments Different scales are utilized by the neurologists to assess the observed impairments. For the spiral drawing performance, the neurologists rated firstly the ‘impairment’ using a 0 (no impairment) – 10 (extremely severe) scale, secondly three kinematic properties: ‘drawing speed’, ‘irregularity’ and ‘hesitation’ using a 0 (normal) – 4 (extremely severe) scale, and thirdly the probable ‘cause’ for the said impairment using 3 choices including Tremor, Bradykinesia/Rigidity and Dyskinesia. For the tapping performance, a 0 (normal) – 4 (extremely severe) scale is used for first rating four tapping properties: ‘tapping speed’, ‘accuracy’, ‘fatigue’, ‘arrhythmia’, and then the ‘global tapping severity’ (GTS). To achieve a common basis for assessment, initially one neurologist (DN) performed preliminary ratings by browsing through the database to collect and rate at least 20 samples of each GTS level and at least 33 samples of each ‘cause’ category. These preliminary ratings were then observed by the two neurologists (DN and PG) to be used as templates for rating of tests afterwards. In another track, the system randomly selected one test occasion per patient and visualized its items, that is tapping and spiral drawings, to the two neurologists. Statistical methods Inter-rater agreements were assessed using weighted Kappa coefficient. The internal consistency of properties of tapping and spiral drawing tests were assessed using Cronbach’s α test. One-way ANOVA test followed by Tukey multiple comparisons test was used to test if mean scores of properties of tapping and spiral drawing tests were different among GTS and ‘cause’ categories, respectively. Results When rating tapping graphs, inter-rater agreements (Kappa) were as follows: GTS (0.61), ‘tapping speed’ (0.89), ‘accuracy’ (0.66), ‘fatigue’ (0.57) and ‘arrhythmia’ (0.33). The poor inter-rater agreement when assessing “arrhythmia” may be as a result of observation of different things in the graphs, among the two raters. When rating animated spirals, both raters had very good agreement when assessing severity of spiral drawings, that is, ‘impairment’ (0.85) and irregularity (0.72). However, there were poor agreements between the two raters when assessing ‘cause’ (0.38) and time-information properties like ‘drawing speed’ (0.25) and ‘hesitation’ (0.21). Tapping properties, that is ‘tapping speed’, ‘accuracy’, ‘fatigue’ and ‘arrhythmia’ had satisfactory internal consistency with a Cronbach’s α coefficient of 0.77. In general, the trends of mean scores of tapping properties worsened with increasing levels of GTS. The mean scores of the four properties were significantly different to each other, only at different levels. In contrast from tapping properties, kinematic properties of spirals, that is ‘drawing speed’, ‘irregularity’ and ‘hesitation’ had a questionable consistency among them with a coefficient of 0.66. Bradykinetic spirals were associated with more impaired speed (mean = 83.7 % worse, P < 0.001) and hesitation (mean = 77.8% worse, P < 0.001), compared to dyskinetic spirals. Both these ‘cause’ categories had similar mean scores of ‘impairment’ and ‘irregularity’. Conclusions In contrast from current approaches used in clinical setting for the assessment of PD symptoms, this system enables clinicians to animate easily and realistically the ULMP of patients who at the same time are at their homes. Dynamic access of visualized motor tests may also be useful when observing and evaluating therapy-related complications such as under- and over-medications. In future, we foresee to utilize these manual ratings for developing and validating computer methods for automating the process of assessing ULMP of PD patients.

Automatic spiral analysis for objective assessment of motor symptoms in Parkinson's disease

Objective: To develop a method for objective quantification of PD motor symptoms related to Off episodes and peak dose dyskinesias, using spiral data gathered by using a touch screen telemetry device. The aim was to objectively characterize predominant motor phenotypes (bradykinesia and dyskinesia), to help in automating the process of visual interpretation of movement anomalies in spirals as rated by movement disorder specialists. Background: A retrospective analysis was conducted on recordings from 65 patients with advanced idiopathic PD from nine different clinics in Sweden, recruited from January 2006 until August 2010. In addition to the patient group, 10 healthy elderly subjects were recruited. Upper limb movement data were collected using a touch screen telemetry device from home environments of the subjects. Measurements with the device were performed four times per day during week-long test periods. On each test occasion, the subjects were asked to trace pre-drawn Archimedean spirals, using the dominant hand. The pre-drawn spiral was shown on the screen of the device. The spiral test was repeated three times per test occasion and they were instructed to complete it within 10 seconds. The device had a sampling rate of 10Hz and measured both position and time-stamps (in milliseconds) of the pen tip. Methods: Four independent raters (FB, DH, AJ and DN) used a web interface that animated the spiral drawings and allowed them to observe different kinematic features during the drawing process and to rate task performance. Initially, a number of kinematic features were assessed including ‘impairment’, ‘speed’, ‘irregularity’ and ‘hesitation’ followed by marking the predominant motor phenotype on a 3-category scale: tremor, bradykinesia and/or choreatic dyskinesia. There were only 2 test occasions for which all the four raters either classified them as tremor or could not identify the motor phenotype. Therefore, the two main motor phenotype categories were bradykinesia and dyskinesia. ‘Impairment’ was rated on a scale from 0 (no impairment) to 10 (extremely severe) whereas ‘speed’, ‘irregularity’ and ‘hesitation’ were rated on a scale from 0 (normal) to 4 (extremely severe). The proposed data-driven method consisted of the following steps. Initially, 28 spatiotemporal features were extracted from the time series signals before being presented to a Multilayer Perceptron (MLP) classifier. The features were based on different kinematic quantities of spirals including radius, angle, speed and velocity with the aim of measuring the severity of involuntary symptoms and discriminate between PD-specific (bradykinesia) and/or treatment-induced symptoms (dyskinesia). A Principal Component Analysis was applied on the features to reduce their dimensions where 4 relevant principal components (PCs) were retained and used as inputs to the MLP classifier. Finally, the MLP classifier mapped these components to the corresponding visually assessed motor phenotype scores for automating the process of scoring the bradykinesia and dyskinesia in PD patients whilst they draw spirals using the touch screen device. For motor phenotype (bradykinesia vs. dyskinesia) classification, the stratified 10-fold cross validation technique was employed. Results: There were good agreements between the four raters when rating the individual kinematic features with intra-class correlation coefficient (ICC) of 0.88 for ‘impairment’, 0.74 for ‘speed’, 0.70 for ‘irregularity’, and moderate agreements when rating ‘hesitation’ with an ICC of 0.49. When assessing the two main motor phenotype categories (bradykinesia or dyskinesia) in animated spirals the agreements between the four raters ranged from fair to moderate. There were good correlations between mean ratings of the four raters on individual kinematic features and computed scores. The MLP classifier classified the motor phenotype that is bradykinesia or dyskinesia with an accuracy of 85% in relation to visual classifications of the four movement disorder specialists. The test-retest reliability of the four PCs across the three spiral test trials was good with Cronbach’s Alpha coefficients of 0.80, 0.82, 0.54 and 0.49, respectively. These results indicate that the computed scores are stable and consistent over time. Significant differences were found between the two groups (patients and healthy elderly subjects) in all the PCs, except for the PC3. Conclusions: The proposed method automatically assessed the severity of unwanted symptoms and could reasonably well discriminate between PD-specific and/or treatment-induced motor symptoms, in relation to visual assessments of movement disorder specialists. The objective assessments could provide a time-effect summary score that could be useful for improving decision-making during symptom evaluation of individualized treatment when the goal is to maximize functional On time for patients while minimizing their Off episodes and troublesome dyskinesias.