Panzootics and the poor: devising a global livestock disease prioritisation framework for poverty alleviation

Panzootics such as highly pathogenic avian influenza and Rift Valley fever have originated from the South, largely among poor communities. On a global level, approximately two-thirds of those individuals living on less than US$2 per day keep livestock. Consequently, there is a need to better target animal health interventions for poverty reduction using an evidence-based approach. Therefore, the paper offers a three-step prioritisation framework using calculations derived from standard poverty measures: the poverty gap and the head count ratio. Data from 265 poor livestock-keeping households in Kenya informed the study. The results demonstrate that, across a spectrum of producers, the dependence upon particular species varies. Furthermore, the same livestock disease has differing impacts on the depth and severity of poverty. Consequently, animal health interventions need to

An item response analysis of the motor and behavioral subscales of the unified Huntington's disease rating scale in huntington disease gene expansion carriers

Although the Unified Huntington's Disease Rating Scale (UHDRS) is widely used in the assessment of Huntington disease (HD), the ability of individual items to discriminate individual differences in motor or behavioral manifestations has not been extensively studied in HD gene expansion carriers without a motor-defined clinical diagnosis (ie, prodromal-HD or prHD). To elucidate the relationship between scores on individual motor and behavioral UHDRS items and total score for each subscale, a nonparametric item response analysis was performed on retrospective data from 2 multicenter longitudinal studies. Motor and behavioral assessments were supplied for 737 prHD individuals with data from 2114 visits (PREDICT-HD) and 686 HD individuals with data from 1482 visits (REGISTRY). Option characteristic curves were generated for UHDRS subscale items in relation to their subscale score. In prHD, overall severity of motor signs was low, and participants had scores of 2 or above on very few items. In HD, motor items that assessed ocular pursuit, saccade initiation, finger tapping, tandem walking, and to a lesser extent, saccade velocity, dysarthria, tongue protrusion, pronation/supination, Luria, bradykinesia, choreas, gait, and balance on the retropulsion test were found to discriminate individual differences across a broad range of motor severity. In prHD, depressed mood, anxiety, and irritable behavior demonstrated good discriminative properties. In HD, depressed mood demonstrated a good relationship with the overall behavioral score. These data suggest that at least some UHDRS items appear to have utility across a broad range of severity, although many items demonstrate problematic features.

Intestinal injury and endotoxemia in children undergoing surgery for congenital heart disease

RATIONALE: Children with congenital heart disease are at risk of gut barrier dysfunction and translocation of gut bacterial antigens into the bloodstream. This may contribute to inflammatory activation and organ dysfunction postoperatively. OBJECTIVES: To investigate the role of intestinal injury and endotoxemia in the pathogenesis of organ dysfunction after surgery for congenital heart disease. METHODS: We analyzed blood levels of intestinal fatty acid binding protein and endotoxin (endotoxin activity assay) alongside global transcriptomic profiling and assays of monocyte endotoxin receptor expression in children undergoing surgery for congenital heart disease. MEASUREMENTS AND MAIN RESULTS: Levels of intestinal fatty acid binding protein and endotoxin were greater in children with duct-dependent cardiac lesions. Endotoxemia was associated with severity of vital organ dysfunction and intensive care stay. We identified activation of pathogen-sensing, antigen-processing, and immune-suppressing pathways at the genomic level postoperatively and down-regulation of pathogen-sensing receptors on circulating immune cells. CONCLUSIONS: Children undergoing surgery for congenital heart disease are at increased risk of intestinal mucosal injury and endotoxemia. Endotoxin activity correlates with a number of outcome variables in this population, and may be used to guide the use of gut-protective strategies.

Relationships between Oak powdery mildew incidence and severity and commensal fungi

Oak (Quercus robur) powdery mildew is a common and damaging fungal disease. In a local survey at Reading, UK, oak powdery mildew was common on trees of all height classes but was most common on trees of 3-9m. A variety of other fungal species were commonly found growing in association with oak powdery mildew colonies. The abundance of such fungi was estimated through stratified sample surveys for 2.5 years. The taxa most commonly associated with oak powdery mildew were Acremonium sp., Trichoderma sp., Ampelomyces/Phoma sp. and Leptosphaerulina australis. Nearly 90% of mildew colonies were associated with L. australis, which is not generally considered as a mycoparasite or antagonist, in contrast with the other three fungi. Abundance varied between June and October surveys. Acremonium sp. abundance was greater in summer samplings whereas L. australis and Trichoderma sp. abundances were greater in autumn samplings. Ampelomyces/Phoma sp. was never observed in the absence of powdery mildew. Relationships between the mildew-associated fungi and oak powdery mildew appeared curved and differed significantly between sampling years. L. australis was positively correlated with the other three associated fungi studied when powdery mildew was also present. The variety and high population densities of the mildew associated fungi suggest that they may be important in determining the final density of oak mildew and the damage caused by it.

Osteopontin involvement in granuloma formation and in the severity of Paracoccidioides brasiliensis infection

The participation of osteopontin (OPN) in Paracoccidioides brasiliensis infected mice, its association to granulomatogenesis, severity of infection, pattern of lesions, nitric oxide (NO) levels and fungal load were evaluated in this investigation. Immunohistochemistry analysis showed marked OPN staining in extracellular matrix and in macrophages and multinucleated giant cells at the center of lesions, suggesting a possible role of OPN in the distribution of these cells within the granulomas. At 15 days post-infection with a virulent P. brasiliensis isolate, OPN(+) cells were more numerous and intensely immunostained in the loose granulomas of susceptible mice than in those of resistant mice. In addition, high fungal loads and low NO levels were observed in susceptible mice. At 120 days after infection, resistant mice had increased total OPN levels (ELISA) and OPN positivity in compact granulomas, higher NO levels and lower fungal loads than susceptible mice. Residual lesions associated with low OPN levels, high NO and control of fungal dissemination were observed in both mouse strains at 120 days post-infection with the slightly virulent fungal isolate. Therefore, OPN could be associated with higher severity of the disease in an early phase of infection and with a degree of control of the progressive infection.

Association of Human T Lymphotropic Virus 1 Amplification of Periodontitis Severity with Altered Cytokine Expression in Response to a Standard Periodontopathogen Infection

Background. Periodontal diseases (PDs) are infectious diseases in which periodontopathogens trigger chronic inflammatory and immune responses that lead to tissue destruction. Recently, viruses have been implicated in the pathogenesis of PDs. Individuals infected with human T lymphotropic virus 1 (HTLV-1) present with abnormal oral health and a marked increased prevalence of periodontal disease. Methods. In this study, we investigated the patterns of periodontopathogen infection and local inflammatory immune markers in HTLV-1-seropositive individuals with chronic periodontitis (CP/HTLV-1 group) compared with HTLV-1 -seronegative individuals with chronic periodontitis (CP group) and periodontally healthy, HTLV-1 -seronegative individuals (control group). Results. Patients in the CP/HTLV-1 group had significantly higher values of bleeding on probing, mean probing depth, and attachment loss than patients in the CP group. The expression of tumor necrosis factor a and interleukin (IL) 4 was found to be similar in the CP and CP/HTLV-1 groups, whereas IL-12 and IL-17 levels trended toward a higher expression in the CP/HTLV-1 group. A significant increase was seen in the levels of IL-1 beta and interferon gamma in the CP/HTLV-1 group compared with the CP group, whereas expression of the regulatory T cell marker FOXp3 and IL-10 was significantly decreased in the lesions from the CP/HTLV-1 group. Interestingly, similar frequency and/or load of periodontopathogens (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Aggregatibacter actinomycetemcomitans) and frequency of viruses (herpes simplex virus 1, human cytomegalovirus, and Epstein-Barr virus) characteristically associated with PDs were found in the CP/HTLV and CP groups. Conclusions. HTLV-1 may play a critical role in the pathogenesis of periodontal disease through the deregulation of the local cytokine network, resulting in an exacerbated response against a standard periodontopathogen infection.

Simultaneous prediction of symptom severity and cause in data from a test battery for Parkinson patients, using machine learning methods

The main purpose of this thesis project is to prediction of symptom severity and cause in data from test battery of the Parkinson’s disease patient, which is based on data mining. The collection of the data is from test battery on a hand in computer. We use the Chi-Square method and check which variables are important and which are not important. Then we apply different data mining techniques on our normalize data and check which technique or method gives good results.The implementation of this thesis is in WEKA. We normalize our data and then apply different methods on this data. The methods which we used are Naïve Bayes, CART and KNN. We draw the Bland Altman and Spearman’s Correlation for checking the final results and prediction of data. The Bland Altman tells how the percentage of our confident level in this data is correct and Spearman’s Correlation tells us our relationship is strong. On the basis of results and analysis we see all three methods give nearly same results. But if we see our CART (J48 Decision Tree) it gives good result of under predicted and over predicted values that’s lies between -2 to +2. The correlation between the Actual and Predicted values is 0,794in CART. Cause gives the better percentage classification result then disability because it can use two classes.

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.

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 and objective assessment of alternating tapping performance in Parkinson’s disease

This paper presents the development and evaluation of a method for enabling quantitative and automatic scoring of alternating tapping performance of patients with Parkinson’s disease (PD). Ten healthy elderly subjects and 95 patients in different clinical stages of PD have utilized a touch-pad handheld computer to perform alternate tapping tests in their home environments. First, a neurologist used a web-based system to visually assess impairments in four tapping dimensions (‘speed’, ‘accuracy’, ‘fatigue’ and ‘arrhythmia’) and a global tapping severity (GTS). Second, tapping signals were processed with time series analysis and statistical methods to derive 24 quantitative parameters. Third, principal component analysis was used to reduce the dimensions of these parameters and to obtain scores for the four dimensions. Finally, a logistic regression classifier was trained using a 10-fold stratified cross-validation to map the reduced parameters to the corresponding visually assessed GTS scores. Results showed that the computed scores correlated well to visually assessed scores and were significantly different across Unified Parkinson’s Disease Rating Scale scores of upper limb motor performance. In addition, they had good internal consistency, had good ability to discriminate between healthy elderly and patients in different disease stages, had good sensitivity to treatment interventions and could reflect the natural disease progression over time. In conclusion, the automatic method can be useful to objectively assess the tapping performance of PD patients and can be included in telemedicine tools for remote monitoring of tapping.

First-principle data-driven models for assessment of motor disorders in Parkinson’s disease

Parkinson’s disease (PD) is an increasing neurological disorder in an aging society. The motor and non-motor symptoms of PD advance with the disease progression and occur in varying frequency and duration. In order to affirm the full extent of a patient’s condition, repeated assessments are necessary to adjust medical prescription. In clinical studies, symptoms are assessed using the unified Parkinson’s disease rating scale (UPDRS). On one hand, the subjective rating using UPDRS relies on clinical expertise. On the other hand, it requires the physical presence of patients in clinics which implies high logistical costs. Another limitation of clinical assessment is that the observation in hospital may not accurately represent a patient’s situation at home. For such reasons, the practical frequency of tracking PD symptoms may under-represent the true time scale of PD fluctuations and may result in an overall inaccurate assessment. Current technologies for at-home PD treatment are based on data-driven approaches for which the interpretation and reproduction of results are problematic.  The overall objective of this thesis is to develop and evaluate unobtrusive computer methods for enabling remote monitoring of patients with PD. It investigates first-principle data-driven model based novel signal and image processing techniques for extraction of clinically useful information from audio recordings of speech (in texts read aloud) and video recordings of gait and finger-tapping motor examinations. The aim is to map between PD symptoms severities estimated using novel computer methods and the clinical ratings based on UPDRS part-III (motor examination). A web-based test battery system consisting of self-assessment of symptoms and motor function tests was previously constructed for a touch screen mobile device. A comprehensive speech framework has been developed for this device to analyze text-dependent running speech by: (1) extracting novel signal features that are able to represent PD deficits in each individual component of the speech system, (2) mapping between clinical ratings and feature estimates of speech symptom severity, and (3) classifying between UPDRS part-III severity levels using speech features and statistical machine learning tools. A novel speech processing method called cepstral separation difference showed stronger ability to classify between speech symptom severities as compared to existing features of PD speech. In the case of finger tapping, the recorded videos of rapid finger tapping examination were processed using a novel computer-vision (CV) algorithm that extracts symptom information from video-based tapping signals using motion analysis of the index-finger which incorporates a face detection module for signal calibration. This algorithm was able to discriminate between UPDRS part III severity levels of finger tapping with high classification rates. Further analysis was performed on novel CV based gait features constructed using a standard human model to discriminate between a healthy gait and a Parkinsonian gait. The findings of this study suggest that the symptom severity levels in PD can be discriminated with high accuracies by involving a combination of first-principle (features) and data-driven (classification) approaches. The processing of audio and video recordings on one hand allows remote monitoring of speech, gait and finger-tapping examinations by the clinical staff. On the other hand, the first-principles approach eases the understanding of symptom estimates for clinicians. We have demonstrated that the selected features of speech, gait and finger tapping were able to discriminate between symptom severity levels, as well as, between healthy controls and PD patients with high classification rates. The findings support suitability of these methods to be used as decision support tools in the context of PD assessment.

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.

Muscular Dystrophy in Dogs: Does the Crossing of Breeds Influence Disease Phenotype?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Graft versus host disease in a rat small bowel transplant model after T-cell depleted donor specific bone marrow infusion

Baixas doses de irradiação associadas à infusão de células da medula óssea não previnem a ocorrência da reação do enxerto versus hospedeiro após o transplante intestinal. OBJETIVO: Neste estudo foi avaliado a potencial vantagem em estender o regime imunossupressor associado a infusão de células de medula óssea do doador depletadas de células T na prevenção da reação do enxerto versus hospedeiro após o transplante intestinal. MÉTODOS: Transplante heterotópico de intestino delgado foi realizado em ratos Lewis como receptores e da como doadores, distribuídos em cinco grupos de acordo com a duração da imunossupressão, irradiação e do uso de medula óssea normal ou depletada: G1 (n=6), sem irradiação e G2 (n=9), G3 (n=4), G4 (n=5) e G5 (n=6) foram irradiados com 250 rd. Grupos1, 2, 4 e G3 e 5 foram infundidos com 100 x 10(6) células da medula normal e depletada respectivamente. Animais no G1,2,3 foram imunossuprimidos com 1mg/kg/FK506/ IM por cinco dias e G4 e cinco por 15 dias. Anticorpos monoclonais contra células CD3 e colunas magnéticas foram utilizadas para a depleção da medula óssea. Os animais foram examinados para a presença de rejeição, reação do enxerto versus hospedeiro, chimerismo e biópsias intestinais e da pele. RESULTADOS: Rejeição mínima foi observada em todos os grupos; entretanto, a reação do enxerto versus hospedeiro somente nos animais irradiados. Extensão da imunossupressão alterou a gravidade da reação nos animais dos G4 e 5. Rejeição foi a causa mortis no G1 e a reação do enxerto versus hospedeiro nos Grupos 2,3,4 e 5, não controlada com a infusão de medula óssea depletada. O chimerismo total e de células T do doador foi estatisticamente maior nos grupos irradiados em comparação ao G1. CONCLUSÃO: A extensão do regime de imunossupressão associado a baixas doses de irradiação diminui a gravidade da reação do enxerto versus hospedeiro, não abolida pelo uso de medula óssea depletada.