Computerized identification of motor complications in Parkinson's disease

Objective: To investigate whether spirography-based objective measures are able to effectively characterize the severity of unwanted symptom states (Off and dyskinesia) and discriminate them from motor state of healthy elderly subjects. Background: Sixty-five patients with advanced Parkinson’s disease (PD) and 10 healthy elderly (HE) subjects performed repeated assessments of spirography, using a touch screen telemetry device in their home environments. On inclusion, the patients were either treated with levodopa-carbidopa intestinal gel or were candidates for switching to this treatment. On each test occasion, the subjects were asked trace a pre-drawn Archimedes spiral shown on the screen, using an ergonomic pen stylus. The test was repeated three times and was performed using dominant hand. A clinician used a web interface which animated the spiral drawings, allowing him to observe different kinematic features, like accelerations and spatial changes, during the drawing process and to rate different motor impairments. Initially, the motor impairments of drawing speed, irregularity and hesitation were rated on a 0 (normal) to 4 (extremely severe) scales followed by marking the momentary motor state of the patient into 2 categories that is Off and Dyskinesia. A sample of spirals drawn by HE subjects was randomly selected and used in subsequent analysis. Methods: The raw spiral data, consisting of stylus position and timestamp, were processed using time series analysis techniques like discrete wavelet transform, approximate entropy and dynamic time warping in order to extract 13 quantitative measures for representing meaningful motor impairment information. A principal component analysis (PCA) was used to reduce the dimensions of the quantitative measures into 4 principal components (PC). In order to classify the motor states into 3 categories that is Off, HE and dyskinesia, a logistic regression model was used as a classifier to map the 4 PCs to the corresponding clinically assigned motor state categories. A stratified 10-fold cross-validation (also known as rotation estimation) was applied to assess the generalization ability of the logistic regression classifier to future independent data sets. To investigate mean differences of the 4 PCs across the three categories, a one-way ANOVA test followed by Tukey multiple comparisons was used. Results: The agreements between computed and clinician ratings were very good with a weighted area under the receiver operating characteristic curve (AUC) coefficient of 0.91. The mean PC scores were different across the three motor state categories, only at different levels. The first 2 PCs were good at discriminating between the motor states whereas the PC3 was good at discriminating between HE subjects and PD patients. The mean scores of PC4 showed a trend across the three states but without significant differences. The Spearman’s rank correlations between the first 2 PCs and clinically assessed motor impairments were as follows: drawing speed (PC1, 0.34; PC2, 0.83), irregularity (PC1, 0.17; PC2, 0.17), and hesitation (PC1, 0.27; PC2, 0.77). Conclusions: These findings suggest that spirography-based objective measures are valid measures of spatial- and time-dependent deficits and can be used to distinguish drug-related motor dysfunctions between Off and dyskinesia in PD. These measures can be potentially useful during clinical evaluation of individualized drug-related complications such as over- and under-medications thus maximizing the amount of time the patients spend in the On state.

Visualization of spirography-based objective measures in Parkinson's disease

Objective: To investigate whether advanced visualizations of spirography-based objective measures are useful in differentiating drug-related motor dysfunctions between Off and dyskinesia in Parkinson’s disease (PD). Background: During the course of a 3 year longitudinal clinical study, in total 65 patients (43 males and 22 females with mean age of 65) with advanced PD and 10 healthy elderly (HE) subjects (5 males and 5 females with mean age of 61) were assessed. Both patients and HE subjects performed repeated and time-stamped assessments of their objective health indicators using a test battery implemented on a telemetry touch screen handheld computer, in their home environment settings. Among other tasks, the subjects were asked to trace a pre-drawn Archimedes spiral using the dominant hand and repeat the test three times per test occasion. Methods: A web-based framework was developed to enable a visual exploration of relevant spirography-based kinematic features by clinicians so they can in turn evaluate the motor states of the patients i.e. Off and dyskinesia. The system uses different visualization techniques such as time series plots, animation, and interaction and organizes them into different views to aid clinicians in measuring spatial and time-dependent irregularities that could be associated with the motor states. Along with the animation view, the system displays two time series plots for representing drawing speed (blue line) and displacement from ideal trajectory (orange line). The views are coordinated and linked i.e. user interactions in one of the views will be reflected in other views. For instance, when the user points in one of the pixels in the spiral view, the circle size of the underlying pixel increases and a vertical line appears in the time series views to depict the corresponding position. In addition, in order to enable clinicians to observe erratic movements more clearly and thus improve the detection of irregularities, the system displays a color-map which gives an idea of the longevity of the spirography task. Figure 2 shows single randomly selected spirals drawn by a: A) patient who experienced dyskinesias, B) HE subject, and C) patient in Off state. Results: According to a domain expert (DN), the spirals drawn in the Off and dyskinesia motor states are characterized by different spatial and time features. For instance, the spiral shown in Fig. 2A was drawn by a patient who showed symptoms of dyskinesia; the drawing speed was relatively high (cf. blue-colored time series plot and the short timestamp scale in the x axis) and the spatial displacement was high (cf. orange-colored time series plot) associated with smooth deviations as a result of uncontrollable movements. The patient also exhibited low amount of hesitation which could be reflected both in the animation of the spiral as well as time series plots. In contrast, the patient who was in the Off state exhibited different kinematic features, as shown in Fig. 2C. In the case of spirals drawn by a HE subject, there was a great precision during the drawing process as well as unchanging levels of time-dependent features over the test trial, as seen in Fig. 2B. Conclusions: Visualizing spirography-based objective measures enables identification of trends and patterns of drug-related motor dysfunctions at the patient’s individual level. Dynamic access of visualized motor tests may be useful during the evaluation of drug-related complications such as under- and over-medications, providing decision support to clinicians during evaluation of treatment effects as well as improve the quality of life of patients and their caregivers. In future, we plan to evaluate the proposed approach by assessing within- and between-clinician variability in ratings in order to determine its actual usefulness and then use these ratings as target outcomes in supervised machine learning, similarly as it was previously done in the study performed by Memedi et al. (2013).

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.

Assessment of PD Speech Anomalies @ Home

Background: Voice processing in real-time is challenging. A drawback of previous work for Hypokinetic Dysarthria (HKD) recognition is the requirement of controlled settings in a laboratory environment. A personal digital assistant (PDA) has been developed for home assessment of PD patients. The PDA offers sound processing capabilities, which allow for developing a module for recognition and quantification HKD. Objective: To compose an algorithm for assessment of PD speech severity in the home environment based on a review synthesis. Methods: A two-tier review methodology is utilized. The first tier focuses on real-time problems in speech detection. In the second tier, acoustics features that are robust to medication changes in Levodopa-responsive patients are investigated for HKD recognition. Keywords such as Hypokinetic Dysarthria , and Speech recognition in real time were used in the search engines. IEEE explorer produced the most useful search hits as compared to Google Scholar, ELIN, EBRARY, PubMed and LIBRIS. Results: Vowel and consonant formants are the most relevant acoustic parameters to reflect PD medication changes. Since relevant speech segments (consonants and vowels) contains minority of speech energy, intelligibility can be improved by amplifying the voice signal using amplitude compression. Pause detection and peak to average power rate calculations for voice segmentation produce rich voice features in real time. Enhancements in voice segmentation can be done by inducing Zero-Crossing rate (ZCR). Consonants have high ZCR whereas vowels have low ZCR. Wavelet transform is found promising for voice analysis since it quantizes non-stationary voice signals over time-series using scale and translation parameters. In this way voice intelligibility in the waveforms can be analyzed in each time frame. Conclusions: This review evaluated HKD recognition algorithms to develop a tool for PD speech home-assessment using modern mobile technology. An algorithm that tackles realtime constraints in HKD recognition based on the review synthesis is proposed. We suggest that speech features may be further processed using wavelet transforms and used with a neural network for detection and quantification of speech anomalies related to PD. Based on this model, patients' speech can be automatically categorized according to UPDRS speech ratings.

Development of an active orthosis prototype for lower limbs

ARAUJO, Márcio V. ; ALSINA, Pablo J. ; MEDEIROS, Adelardo A. D. ; PEREIRA, Jonathan P.P. ; DOMINGOS, Elber C. ; ARAÚJO, Fábio M.U. ; SILVA, Jáder S. . Development of an Active Orthosis Prototype for Lower Limbs. In: INTERNATIONAL CONGRESS OF MECHANICAL ENGINEERING, 20., 2009, Gramado, RS. Proceedings… Gramado, RS: [s. n.], 2009

Application of multivariable control using artificial neural networks in a debutanizer distillation column

LOPES, Jose Soares Batista et al. Application of multivariable control using artificial neural networks in a debutanizer distillation column.In: INTERNATIONAL CONGRESS OF MECHANICAL ENGINEERING - COBEM, 19, 5-9 nov. 2007, Brasilia. Anais... Brasilia, 2007

Cheap assays of malate, glycerol and ethanol in fermenting must and food samples

A preparation, enriched with malate dehydrogenase (MDH), alcohol dehydrogenase (ADH), glycerol -3- P dehydrogenase (GPDH) and glycerol kinase (GK), was obtained from dry baker's yeast. This preparation was used to assay glycerol, ethanol and malate measuring the variations in absorbance (NADH formation) at 340 nm. Good degrees of recoveries were obtained when glycerol was added to red wine and fermenting sugar-cane juice and when L-malate was added to commercial apple juice samples. Good results were also obtained when ethanol was assayed in fermented sugar-cane juice and wine samples, using both the partially purified preparation obtained from dry yeast and a purified commercial alcohol dehydrogenase.

Markers of tumors susceptibility in head and neck cancer

Genetic polymorphisms are associated with a number of enzymes involved in the induction of head and neck carcinomas. It has been suggested that such polymorphisms may be linked to cancer susceptibility. Using a control-case study molecular genetic approach, we have investigated the association between polymorphisms genes (CYPs, GSTs and NAT2 genes) and susceptibility in head and neck cancer.

Characterization of mineral contents on androgen deficient and chronic ethanol consuming rats by biochemistry and non-destructive techniques

Ethanol can compromise the body mineral composition and affect bone, and when associated to hypogonadism is considered an important risk factor for osteoporosis in man. The aim of this study was to investigate the effect of androgen deficient and chronic ethanol consuming on mineral contents by biochemistry and non-destructive techniques. Wistar rat (n=54) were divided in orchiectomy (ORQ) or SHAM-operated and subdivided by diet. They were daily fed with a Lieber DeCarli diet model for 8 weeks long. The controls groups were free-diet and pair-fed. Ca and P were analyzed by biochemistry test in the blood and by nX-ray fluorescence and FT-Raman on the femur area. Serum analysis revealed hypocalcaemia and hypeiphosphataemia in ethanol groups more than pair-fed and free-diet. In similarity, spectroscopy indicated a decrease in bone Ca content in ORQ groups, mainly for ethanol groups. Phosphorus content and Ca/P molar ratio, otherwise, doesn't diverge in all 6 groups. Ethanol consumption impaired Ca and P homeostasis in ORQ rat more than SHAM. The relationships among ethanol consume and androgen deficit support the hypothesis that ethanol affects the mineral-regulating hormones and may mediate some effects on bone. These findings demonstrate that ethanol seemed to interfere with the normal compensatory response to these Ca and P levels and is more significant M androgen deficiency rats.

Obstrução intestinal congênita em cão por aderência de alça em osso púbico

Atendeu-se uma cadela, sem raça definida, com aproximadamente cinco meses de idade, apresentando anamnese com queixa de apatia e hiporexia associadas a vômitos e emagrecimento progressivo com início incerto. Ao exame físico era evidente distensão abdominal com dilatação intestinal e aumento de peristaltismo. O animal apresentava-se emaciado e subdesenvolvido, com acentuado grau de desidratação, pulso filiforme e nível de consciência reduzido. Minutos após o início do atendimento a cadela foi a óbito. À necropsia, pôde-se observar um segmento do intestino delgado atravessando o púbis e com lúmen reduzido. Tal apresentação se faz relevante por se tratar de um caso nunca antes descrito na literatura veterinária.

Study of the effects of exposure to ionizing irradiation on the materials used for dental restoration

A quantitative study was made about the effects caused by ionizing irradiation on materials used for dental restoration (amalgams, compound resins and compomere), aiming to alleviate in bearers of head and neck cancer, the possible harmful effects of radiotherapy perceived when the repaired teething is within the radiation field. Research also encourages further studies for new alternative materials to be used in dental repair of patients submitted to radiotherapy for head and neck cancer. Test samples were submitted to a gamma radiation beam coming from a cobalt-therapy source and analyzed according to the X-ray fluorescence technique, comparing the chemical composition of the samples before and after irradiation. Radiation detectors such as an ionization chamber and a Geiger-Muller were used to measure the rate of residual dose. Gamma spectrometry with Nal detectors was also performed on the same samples. Results showed that there was no significant change in the chemical composition and that at post-irradiation, samples did not exhibit radiation emission, that is to say they had not become radioactive.

INFLUENCE of THE EVAPORATOR POSITION IN STATIC DOMESTIC REFRIGERATORS

The temperature and velocity distributions of the air inside the cabinet of domestic refrigerators affect the quality of food products. If the consumer knows the location of warm and cold zones in the refrigerator, the products can be placed in the right zone. In addition, the knowledge of the thickness of thermal and hydrodynamic boundary layers near the evaporator and the other walls is also important. If the product is too close to the evaporator wall, freezing can occur, and if it is too close to warm walls, the products can be deteriorated. The aim of the present work is to develop a steady state computational fluid dynamics (CFD) model for domestic refrigerators working on natural convection regime. The Finite Volume Methodology is chosen as numerical procedure for discretizing the governing equations. The SIMPLE-Semi-Implicit Method for Pressure-Linked Equations algorithm applied to a staggered mesh was used for solving the pressure-velocity coupling problem. The Power-Law scheme is employed as interpolation function for the convective-diffusive terms, and the TDMA-Tri-Diagonal Matrix Algorithm is used to solve the systems of algebraic equations. The model is applied to a commercial static refrigerator, where the cabinet is considered an empty three-dimensional rectangular cavity with one drawer at the bottom of the cabinet, but without shelves. In order to analyze the velocity and temperature fields of the air flow inside the cabinet the evaporator temperature, Te, was varied from -20 degrees C to 0 degrees C, and nine different evaporator positions are evaluated for evaporator temperature of -15 degrees C. The cooling capacity of the evaporator for the steady state regime is also computed for each case. One can conclude that the vertical positioning of the evaporator inside the cabinet plays an important role on the temperature distribution inside the cabinet.