Digital spiral analysis for objective assessment of fine motor timing variability in Parkinson's disease

OBJECTIVES: To develop a method for objective assessment of fine motor timing variability in Parkinson’s disease (PD) patients, using digital spiral data gathered by a touch screen device. BACKGROUND: A retrospective analysis was conducted on data from 105 subjects including65 patients with advanced PD (group A), 15 intermediate patients experiencing motor fluctuations (group I), 15 early stage patients (group S), and 10 healthy elderly subjects (HE) were examined. The subjects were asked to perform repeated upper limb motor tasks by tracing a pre-drawn Archimedes spiral as shown on the screen of the device. The spiral tracing test was performed using an ergonomic pen stylus, using dominant hand. The test was repeated three times per test occasion and the subjects were instructed to complete it within 10 seconds. Digital spiral data including stylus position (x-ycoordinates) and timestamps (milliseconds) were collected and used in subsequent analysis. The total number of observations with the test battery were as follows: Swedish group (n=10079), Italian I group (n=822), Italian S group (n = 811), and HE (n=299). METHODS: The raw spiral data were processed with three data processing methods. To quantify motor timing variability during spiral drawing tasks Approximate Entropy (APEN) method was applied on digitized spiral data. APEN is designed to capture the amount of irregularity or complexity in time series. APEN requires determination of two parameters, namely, the window size and similarity measure. In our work and after experimentation, window size was set to 4 and similarity measure to 0.2 (20% of the standard deviation of the time series). The final score obtained by APEN was normalized by total drawing completion time and used in subsequent analysis. The score generated by this method is hence on denoted APEN. In addition, two more methods were applied on digital spiral data and their scores were used in subsequent analysis. The first method was based on Digital Wavelet Transform and Principal Component Analysis and generated a score representing spiral drawing impairment. The score generated by this method is hence on denoted WAV. The second method was based on standard deviation of frequency filtered drawing velocity. The score generated by this method is hence on denoted SDDV. Linear mixed-effects (LME) models were used to evaluate mean differences of the spiral scores of the three methods across the four subject groups. Test-retest reliability of the three scores was assessed after taking mean of the three possible correlations (Spearman’s rank coefficients) between the three test trials. Internal consistency of the methods was assessed by calculating correlations between their scores. RESULTS: When comparing mean spiral scores between the four subject groups, the APEN scores were different between HE subjects and three patient groups (P=0.626 for S group with 9.9% mean value difference, P=0.089 for I group with 30.2%, and P=0.0019 for A group with 44.1%). However, there were no significant differences in mean scores of the other two methods, except for the WAV between the HE and A groups (P<0.001). WAV and SDDV were highly and significantly correlated to each other with a coefficient of 0.69. However, APEN was not correlated to neither WAV nor SDDV with coefficients of 0.11 and 0.12, respectively. Test-retest reliability coefficients of the three scores were as follows: APEN (0.9), WAV(0.83) and SD-DV (0.55). CONCLUSIONS: The results show that the digital spiral analysis-based objective APEN measure is able to significantly differentiate the healthy subjects from patients at advanced level. In contrast to the other two methods (WAV and SDDV) that are designed to quantify dyskinesias (over-medications), this method can be useful for characterizing Off symptoms in PD. The APEN was not correlated to none of the other two methods indicating that it measures a different construct of upper limb motor function in PD patients than WAV and SDDV. The APEN also had a better test-retest reliability indicating that it is more stable and consistent over time than WAV and SDDV.

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.

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

A challenge for the clinical management of advanced Parkinson’s disease (PD) patients is the emergence of fluctuations in motor performance, which represents a significant source of disability during activities of daily living of the patients. There is a lack of objective measurement of treatment effects for in-clinic and at-home use that can provide an overview of the treatment response. The objective of this paper was to develop a method for objective quantification of advanced PD motor symptoms related to off episodes and peak dose dyskinesia, using spiral data gathered by a touch screen telemetry device. More specifically, the aim was to objectively characterize motor symptoms (bradykinesia and dyskinesia), to help in automating the process of visual interpretation of movement anomalies in spirals as rated by movement disorder specialists. Digitized upper limb movement data of 65 advanced PD patients and 10 healthy (HE) subjects were recorded as they performed spiral drawing tasks on a touch screen device in their home environment settings. Several spatiotemporal features were extracted from the time series and used as inputs to machine learning methods. The methods were validated against ratings on animated spirals scored by four movement disorder specialists who visually assessed a set of kinematic features and the motor symptom. The ability of the method to discriminate between PD patients and HE subjects and the test-retest reliability of the computed scores were also evaluated. Computed scores correlated well with mean visual ratings of individual kinematic features. The best performing classifier (Multilayer Perceptron) classified the motor symptom (bradykinesia or dyskinesia) with an accuracy of 84% and area under the receiver operating characteristics curve of 0.86 in relation to visual classifications of the raters. In addition, the method provided high discriminating power when distinguishing between PD patients and HE subjects as well as had good test-retest reliability. This study demonstrated the potential of using digital spiral analysis for objective quantification of PD-specific and/or treatment-induced motor symptoms.

Medical treatment and the good death: an ethical analysis of euthanasia, physician assisted suicide, and the right to die

Frequent advances in medical technologies have brought fonh many innovative treatments that allow medical teams to treal many patients with grave illness and serious trauma who would have died only a few years earlier. These changes have given some patients a second chance at life, but for others. these new treatments have merely prolonged their dying. Instead of dying relatively painlessly, these unfortunate patients often suffer from painful tenninal illnesses or exist in a comatose state that robs them of their dignity, since they cannot survive without advanced and often dehumanizing forms of treatment. Due to many of these concerns, euthanasia has become a central issue in medical ethics. Additionally, the debate is impacted by those who believe that patients have the right make choices about the method and timing of their deaths. Euthanasia is defined as a deliberate act by a physician to hasten the death of a patient, whether through active methods such as an injection of morphine, or through the withdrawal of advanced forms of medical care, for reasons of mercy because of a medical condition that they have. This study explores the question of whether euthanasia is an ethical practice and, as determined by ethical theories and professional codes of ethics, whether the physician is allowed to provide the means to give the patient a path to a "good death," rather than one filled with physical and mental suffering. The paper also asks if there is a relevant moral difference between the active and passive forms of euthanasia and seeks to define requirements to ensure fully voluntary decision making through an evaluation of the factors necessary to produce fully informed consent. Additionally, the proper treatments for patients who suffer from painful terminal illnesses, those who exist in persistent vegetative states and infants born with many diverse medical problems are examined. The ultimate conclusions that are reached in the paper are that euthanasia is an ethical practice in certain specific circumstances for patients who have a very low quality of life due to pain, illness or serious mental deficits as a result of irreversible coma, persistent vegetative state or end-stage clinical dementia. This is defended by the fact that the rights of the patient to determine his or her own fate and to autonomously decide the way that he or she dies are paramount to all other factors in decisions of life and death. There are also circumstances where decisions can be made by health care teams in conjunction with the family to hasten the deaths of incompetent patients when continued existence is clearly not in their best interest, as is the case of infants who are born with serious physical anomalies, who are either 'born dying' or have no prospect for a life that is of a reasonable quality. I have rejected the distinction between active and passive methods of euthanasia and have instead chosen to focus on the intentions of the treating physician and the voluntary nature of the patient's request. When applied in equivalent circumstances, active and passive methods of euthanasia produce the same effects, and if the choice to hasten the death of the patient is ethical, then the use of either method can be accepted. The use of active methods of euthanasia and active forms of withdrawal of life support, such as the removal of a respirator are both conscious decisions to end the life of the patient and both bring death within a short period of time. It is false to maintain a distinction that believes that one is active killing. whereas the other form only allows nature to take it's course. Both are conscious choices to hasten the patient's death and should be evaluated as such. Additionally, through an examination of the Hippocratic Oath, and statements made by the American Medical Association and the American College of physicians, it can be shown that the ideals that the medical profession maintains and the respect for the interests of the patient that it holds allows the physician to give aid to patients who wish to choose death as an alternative to continued suffering. The physician is also allowed to and in some circumstances, is morally required, to help dying patients whether through active or passive forms of euthanasia or through assisted suicide. Euthanasia is a difficult topic to think about, but in the end, we should support the choice that respects the patient's autonomous choice or clear best interest and the respect that we have for their dignity and personal worth.

Growth and exchange rate volatility: a panel data analysis

The aim of this article is to assess the role of real effective exchange rate volatility on long-run economic growth for a set of 82 advanced and emerging economies using a panel data set ranging from 1970 to 2009. With an accurate measure for exchange rate volatility, the results for the two-step system GMM panel growth models show that a more (less) volatile RER has significant negative (positive) impact on economic growth and the results are robust for different model specifications. In addition to that, exchange rate stability seems to be more important to foster long-run economic growth than exchange rate misalignment

Optimisation of environmental gas cleaning routes for solid wastes cogeneration systems - Part I - Analysis of waste incineration steam cycle

Research of advanced technologies for energy generation contemplates a series of alternatives that are introduced both in the investigation of new energy sources and in the improvement and/or development of new components and systems. Even though significant reductions are observed in the amount of emissions, the proposed alternatives require the use of exhaust gases cleaning systems. The results of environmental analyses based on two configurations proposed for urban waste incineration are presented in this paper; the annexation of integer (Boolean) variables to the environomic model makes it possible to define the best gas cleaning routes based on exergetic cost minimisation criteria. In this first part, the results for steam cogeneration system analysis associated with the incineration of municipal solid wastes (MSW) is presented. (c) 2007 Elsevier Ltd. All rights reserved.

Determination of Population Size of Glass-like Carbon Sampling Used in Weibull Analysis

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

Determining the Optimum Processing Parameters of Glass-like Carbon Using Weibull Analysis of its Fracture Behaviour

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

Predictors of first-year survival in patients with advanced COPD treated using long-term oxygen therapy

Little evidence-based guidance is available to aid clinicians in determining short-term prognoses in very severe COPD patients. Therefore, the present study was designed to provide a prospective assessment (1) of the mortality rates and (2) whether the baseline measurements may be determinants of 1-year mortality in hypoxemic COPD patients receiving long-term oxygen therapy (LTOT).Seventy-eight clinically stable patients with advanced COPD treated using LTOT were enrolled in a prospective cohort study. Outcome variable: first-year mortality. Baseline measurements: categorical variables: age (<60 or >= 60 years); gender; body mass index (<20 or >= 20 kg/m(2)); fat-free mass (FFM) index (<16 [men] and <15kg/m(2) [women]; baseline dyspnea index (BDI) (<= 3 or >3); and corticosteroid use. Continuous variables: smoking history; lung function; FFM; fat mass; hemoglobin; hematocrit; arterial blood gases; forearm muscle strength; St. George's Respiratory Questionnaire (SGRQ); and comorbidity score. By the end of 1-year of follow-up, 12 patients (15.4%) had died. Kaplan-Meier curves showed that BDI <= 3 was the only variable associated with higher mortality. Cox proportional hazards analysis revealed that tower PaO2 and SPO2, higher PaCO2 and SGRQ scores were associated with reduced survival. In the multivariate analysis, BDI remained predictive of mortality (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.31-0.81), as did PaO2 (HR, 0.49; 95% CI, 0.26-0.95). These data suggest that readily available parameters as dyspnea intensity and hypoxemia severity may be useful in predicting first-year survival rates in advanced COPD patients receiving LTOT (C) 2007 Elsevier Ltd. All rights reserved.

Feasibility of oncoplastic techniques in the surgical management of locally advanced breast cancer

Background: Locally advanced breast cancer (LABC) is still common in developing countries. The association between neoadjuvant chemotherapy (NC) and oncoplastic surgery (OS) might provide an oncological treatment with satisfactory aesthetic results.Purpose: The goal was to demonstrate if oncoplastic surgical techniques can be utilized to treat LABC which was submitted to neoadjuvant chemotherapy.Methods: This prospective clinical trial included breast cancer patients, clinical stage III, who underwent established NC regimen. All patients underwent preoperative planning to control the tumor size and to define the surgical technique. A detailed analysis of the pathological specimen was performed.Results: 50 patients were assessed and surgically treated. Tumor size ranged from 3.0 to 14.0 cm (median 6.5 cm). Pathologic response was rated as stable, progressive, partial response, and complete response in 10%, 8%, 80% and 2% of the cases, respectively. Seventeen (34%) patients were submitted to OS. No patient had positive margins. Skin involvement was presented in 36% of pathologic specimen.Conclusions: Oncoplastic surgical techniques for selected patients decrease the rates of radical surgery despite large tumors. (www.clinicaltrials.gov, NCT00820690). (C) 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Electrophoretic analysis of the protein in the midgut of stingless bees (Apidae; Meliponinae) with a comparison of necrophagous and feeding pollen workers

SDS electrophoresis of midgut proteins from two Trigonini species with different feeding habits shows many similarities and the absence of unique protein in the necrophagous stingless bee Trigona hypogea, suggesting that biochemical adaptation to necrophagy, in this bee, occurs more in the qualitative than in quantitative level. Workers of different ages display some variations in the midgut protein pattern, suggesting that it is important to know the age in studies regarding to bee digestion.

Analysis of tectonic-controlled fluvial morphology and sedimentary processes of the western Amazon Basin: an approach using satellite images and digital elevation model

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Evaluation of the influences of solution path length and additives concentrations on the solar photo-Fenton degradation of 4-chlorophenol using multivariate analysis

This study reports the photodegradation of 4-chlorophenol (4-CP) in aqueous solution by the photo-Fenton process using solar irradiation. The influence of solution path length, and Fe(NO3)(3) and H2O2 concentrations on the degradation of 4-CP is evaluated by response surface methodology. The degradation process was monitored by the removal of total organic carbon (TOC) and the release of chloride ion. The results showed a very important role of iron concentration either for TOC removal or dechlorination. on the other hand, a negative effect of increasing solution path length on mineralization was observed, which can be compensated by increasing the iron concentration. This permits an adjustment of the iron concentration according to the irradiation exposure area and path length (depth of a tank reactor). Under optimum conditions of 1.5 mM Fe(NO3)(3), 20.0 mM H2O2 and 4.5 cm solution path length, 17 min irradiation under solar light were sufficient to reduce a 72 mg C L-1 solution of 4-CP by 91 (c) 2006 Elsevier B.V. All rights reserved.

Multivariate analysis of photo-Fenton degradation of the herbicides tebuthiuron, diuron and 2,4-D

The degradation of herbicides in aqueous solution by photo-Fenton process using ferrioxalate complex (FeOx) as source of Fe2+ was evaluated under blacklight irradiation. The commercial products of the herbicides tebuthiuron, diuron and 2,4-D were used. The multivariate analysis, more precisely, the response surface methodology was applied to evaluate the role of FeOx and hydrogen peroxide concentrations as variables in the degradation process, and in particular, to define the concentration ranges that result in the most efficient degradation of the herbicides. The degradation process was evaluated by the determination of the remaining total organic carbon content (TOC), by monitoring the decrease of the concentrations of the original compounds using HPLC and by the chloride ion release in the case of diuron and 2,4-D. Under optimized conditions, 20min were sufficient to mineralize 93% of TOC from 2,4-D and 90% of diuron, including oxalate. Complete dechlorination of these compounds was achieved after 10 min reaction. It was found that the most recalcitrant herbicide is tebuthiuron, while diuron shows the highest degradability. However, under optimized conditions the initial concentration of tebuthiuron was reduced to less than 15%, while diuron and 2,4-D were reduced to around 2% after only 1 min reaction. Furthermore, it was observed that the ferrioxalate complex plays a more important role than H2O2 in the photodegradation of these herbicides in the ranges of concentrations investigated. (C) 2004 Elsevier Ltd. All rights reserved.