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BACKGROUND: Microbiome dysbiosis has recently been associated with different diseases and disorders. In this context, machine learning (ML) approaches can be useful either to identify new patterns or learn predictive models. However, data to be fed to ML methods can be subject to different sampling, sequencing and preprocessing techniques. Each different choice in the pipeline can lead to a different view (i.e., feature set) of the same individuals, that classical (single-view) ML approaches may fail to simultaneously consider. Moreover, some views may be incomplete, i.e., some individuals may be missing in some views, possibly due to the absence of some measurements or to the fact that some features are not available/applicable for all the individuals. Multi-view learning methods can represent a possible solution to consider multiple feature sets for the same individuals, but most existing multi-view learning methods are limited to binary classification tasks or cannot work with incomplete views. RESULTS: We propose irBoost.SH, an extension of the multi-view boosting algorithm rBoost.SH, based on multi-armed bandits. irBoost.SH solves multi-class classification tasks and can analyze incomplete views. At each iteration, it identifies one winning view using adversarial multi-armed bandits and uses its predictions to update a shared instance weight distribution in a learning process based on boosting. In our experiments, performed on 5 multi-view microbiome datasets, the model learned by irBoost.SH always outperforms the best model learned from a single view, its closest competitor rBoost.SH, and the model learned by a multi-view approach based on feature concatenation, reaching an improvement of 11.8% of the F1-score in the prediction of the Autism Spectrum disorder and of 114% in the prediction of the Colorectal Cancer disease. CONCLUSIONS: The proposed method irBoost.SH exhibited outstanding performances in our experiments, also compared to competitor approaches. The obtained results confirm that irBoost.SH can fruitfully be adopted for the analysis of microbiome data, due to its capability to simultaneously exploit multiple feature sets obtained through different sequencing and preprocessing pipelines.
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Algoritmos , Aprendizaje Automático , Microbiota , HumanosRESUMEN
In this work, we perform a comparative analysis of discrete- and continuous-time estimators of information-theoretic measures quantifying the concept of memory utilization in short-term heart rate variability (HRV). Specifically, considering heartbeat intervals in discrete time we compute the measure of information storage (IS) and decompose it into immediate memory utilization (IMU) and longer memory utilization (MU) terms; considering the timings of heartbeats in continuous time we compute the measure of MU rate (MUR). All measures are computed through model-free approaches based on nearest neighbor entropy estimators applied to the HRV series of a group of 15 healthy subjects measured at rest and during postural stress. We find, moving from rest to stress, statistically significant increases of the IS and the IMU, as well as of the MUR. Our results suggest that both discrete-time and continuous-time approaches can detect the higher predictive capacity of HRV occurring with postural stress, and that such increased memory utilization is due to fast mechanisms likely related to sympathetic activation.
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Memoria a Corto Plazo , Humanos , Frecuencia Cardíaca/fisiología , Entropía , Voluntarios SanosRESUMEN
The human microbiome has become an area of intense research due to its potential impact on human health. However, the analysis and interpretation of this data have proven to be challenging due to its complexity and high dimensionality. Machine learning (ML) algorithms can process vast amounts of data to uncover informative patterns and relationships within the data, even with limited prior knowledge. Therefore, there has been a rapid growth in the development of software specifically designed for the analysis and interpretation of microbiome data using ML techniques. These software incorporate a wide range of ML algorithms for clustering, classification, regression, or feature selection, to identify microbial patterns and relationships within the data and generate predictive models. This rapid development with a constant need for new developments and integration of new features require efforts into compile, catalog and classify these tools to create infrastructures and services with easy, transparent, and trustable standards. Here we review the state-of-the-art for ML tools applied in human microbiome studies, performed as part of the COST Action ML4Microbiome activities. This scoping review focuses on ML based software and framework resources currently available for the analysis of microbiome data in humans. The aim is to support microbiologists and biomedical scientists to go deeper into specialized resources that integrate ML techniques and facilitate future benchmarking to create standards for the analysis of microbiome data. The software resources are organized based on the type of analysis they were developed for and the ML techniques they implement. A description of each software with examples of usage is provided including comments about pitfalls and lacks in the usage of software based on ML methods in relation to microbiome data that need to be considered by developers and users. This review represents an extensive compilation to date, offering valuable insights and guidance for researchers interested in leveraging ML approaches for microbiome analysis.
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The rapid development of machine learning (ML) techniques has opened up the data-dense field of microbiome research for novel therapeutic, diagnostic, and prognostic applications targeting a wide range of disorders, which could substantially improve healthcare practices in the era of precision medicine. However, several challenges must be addressed to exploit the benefits of ML in this field fully. In particular, there is a need to establish "gold standard" protocols for conducting ML analysis experiments and improve interactions between microbiome researchers and ML experts. The Machine Learning Techniques in Human Microbiome Studies (ML4Microbiome) COST Action CA18131 is a European network established in 2019 to promote collaboration between discovery-oriented microbiome researchers and data-driven ML experts to optimize and standardize ML approaches for microbiome analysis. This perspective paper presents the key achievements of ML4Microbiome, which include identifying predictive and discriminatory 'omics' features, improving repeatability and comparability, developing automation procedures, and defining priority areas for the novel development of ML methods targeting the microbiome. The insights gained from ML4Microbiome will help to maximize the potential of ML in microbiome research and pave the way for new and improved healthcare practices.
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Anatomical and dynamical connectivity are essential to healthy brain function. However, quantifying variations in connectivity across conditions or between patient populations and appraising their functional significance are highly non-trivial tasks. Here we show that link ranking differences induce specific geometries in a convenient auxiliary space that are often easily recognisable at mere eye inspection. Link ranking can also provide fast and reliable criteria for network reconstruction parameters for which no theoretical guideline has been proposed.
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Enfermedad de Alzheimer , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Cabeza , Humanos , Imagen por Resonancia Magnética , Red Nerviosa/diagnóstico por imagen , Vías Nerviosas/diagnóstico por imagenRESUMEN
In this study, we investigate faecal microbiota composition, in an attempt to evaluate performance of classification algorithms in identifying Inflammatory Bowel Disease (IBD) and its two types: Crohn's disease (CD) and ulcerative colitis (UC). From many investigated algorithms, a random forest (RF) classifier was selected for detailed evaluation in three-class (CD versus UC versus nonIBD) classification task and two binary (nonIBD versus IBD and CD versus UC) classification tasks. We dealt with class imbalance, performed extensive parameter search, dimensionality reduction and two-level classification. In three-class classification, our best model reaches F1 score of 91% in average, which confirms the strong connection of IBD and gastrointestinal microbiome. Among most important features in three-class classification are species Staphylococcus hominis, Porphyromonas endodontalis, Slackia piriformis and genus Bacteroidetes.
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Colitis Ulcerosa , Enfermedad de Crohn , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Actinobacteria , Bacteroidetes , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/microbiología , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/microbiología , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/microbiología , Aprendizaje Automático , Porphyromonas endodontalis , Staphylococcus hominisRESUMEN
Apnea and other breathing-related disorders have been linked to the development of hypertension or impairments of the cardiovascular, cognitive or metabolic systems. The combined assessment of multiple physiological signals acquired during sleep is of fundamental importance for providing additional insights about breathing disorder events and the associated impairments. In this work, we apply information-theoretic measures to describe the joint dynamics of cardiorespiratory physiological processes in a large group of patients reporting repeated episodes of hypopneas, apneas (central, obstructive, mixed) and respiratory effort related arousals (RERAs). We analyze the heart period as the target process and the airflow amplitude as the driver, computing the predictive information, the information storage, the information transfer, the internal information and the cross information, using a fuzzy kernel entropy estimator. The analyses were performed comparing the information measures among segments during, immediately before and after the respiratory event and with control segments. Results highlight a general tendency to decrease of predictive information and information storage of heart period, as well as of cross information and information transfer from respiration to heart period, during the breathing disordered events. The information-theoretic measures also vary according to the breathing disorder, and significant changes of information transfer can be detected during RERAs, suggesting that the latter could represent a risk factor for developing cardiovascular diseases. These findings reflect the impact of different sleep breathing disorders on respiratory sinus arrhythmia, suggesting overall higher complexity of the cardiac dynamics and weaker cardiorespiratory interactions which may have physiological and clinical relevance.
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Multiple methods have been developed in an attempt to quantify stimulus-induced neural coordination and to understand internal coordination of neuronal responses by examining the synchronization phenomena in neural discharge patterns. In this work we propose a novel approach to estimate the degree of concomitant firing between two neural units, based on a modified form of mutual information (MI) applied to a two-state representation of the firing activity. The binary profile of each single unit unfolds its discharge activity in time by decomposition into the state of neural quiescence/low activity and state of moderate firing/bursting. Then, the MI computed between the two binary streams is normalized by their minimum entropy and is taken as positive or negative depending on the prevalence of identical or opposite concomitant states. The resulting measure, denoted as Concurrent Firing Index based on MI (CFIMI), relies on a single input parameter and is otherwise assumption-free and symmetric. Exhaustive validation was carried out through controlled experiments in three simulation scenarios, showing that CFIMI is independent on firing rate and recording duration, and is sensitive to correlated and anti-correlated firing patterns. Its ability to detect non-correlated activity was assessed using ad-hoc surrogate data. Moreover, the evaluation of CFIMI on experimental recordings of spiking activity in retinal ganglion cells brought insights into the changes of neural synchrony over time. The proposed measure offers a novel perspective on the estimation of neural synchrony, providing information on the co-occurrence of firing states in the two analyzed trains over longer temporal scales compared to existing measures.
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Modelos Neurológicos , Neuronas , Potenciales de Acción , Simulación por ComputadorRESUMEN
OBJECTIVE: While understanding the interaction patterns among simultaneous recordings of spike trains from multiple neuronal units is a key topic in neuroscience, existing methods either do not consider the inherent point-process nature of spike trains or are based on parametric assumptions. This work presents an information-theoretic framework for the model-free, continuous-time estimation of both undirected (symmetric) and directed (Granger-causal) interactions between spike trains. METHODS: The framework computes the mutual information rate (MIR) and the transfer entropy rate (TER) for two point processes X and Y, showing that the MIR between X and Y can be decomposed as the sum of the TER along the directions X â Y and Y â X. We present theoretical expressions and introduce strategies to estimate efficiently the two measures through nearest neighbor statistics. RESULTS: Using simulations of independent and coupled point processes, we show the accuracy of MIR and TER to assess interactions even for weakly coupled and short realizations, and demonstrate the superiority of continuous-time estimation over the standard discrete-time approach. We also apply the MIR and TER to real-world data, specifically, recordings from in-vitro preparations of spontaneously-growing cultures of cortical neurons. Using this dataset, we demonstrate the ability of MIR and TER to describe how the functional networks between recording units emerge over the course of the maturation of the neuronal cultures. CONCLUSION AND SIGNIFICANCE: the proposed framework provides principled measures to assess undirected and directed spike train interactions with more efficiency and flexibility than previous discrete-time or parametric approaches, opening new perspectives for the analysis of point-process data in neuroscience and many other fields.
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Modelos Neurológicos , Neuronas , Potenciales de Acción , Simulación por Computador , EntropíaRESUMEN
The number of microbiome-related studies has notably increased the availability of data on human microbiome composition and function. These studies provide the essential material to deeply explore host-microbiome associations and their relation to the development and progression of various complex diseases. Improved data-analytical tools are needed to exploit all information from these biological datasets, taking into account the peculiarities of microbiome data, i.e., compositional, heterogeneous and sparse nature of these datasets. The possibility of predicting host-phenotypes based on taxonomy-informed feature selection to establish an association between microbiome and predict disease states is beneficial for personalized medicine. In this regard, machine learning (ML) provides new insights into the development of models that can be used to predict outputs, such as classification and prediction in microbiology, infer host phenotypes to predict diseases and use microbial communities to stratify patients by their characterization of state-specific microbial signatures. Here we review the state-of-the-art ML methods and respective software applied in human microbiome studies, performed as part of the COST Action ML4Microbiome activities. This scoping review focuses on the application of ML in microbiome studies related to association and clinical use for diagnostics, prognostics, and therapeutics. Although the data presented here is more related to the bacterial community, many algorithms could be applied in general, regardless of the feature type. This literature and software review covering this broad topic is aligned with the scoping review methodology. The manual identification of data sources has been complemented with: (1) automated publication search through digital libraries of the three major publishers using natural language processing (NLP) Toolkit, and (2) an automated identification of relevant software repositories on GitHub and ranking of the related research papers relying on learning to rank approach.
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Applied machine learning in bioinformatics is growing as computer science slowly invades all research spheres. With the arrival of modern next-generation DNA sequencing algorithms, metagenomics is becoming an increasingly interesting research field as it finds countless practical applications exploiting the vast amounts of generated data. This study aims to scope the scientific literature in the field of metagenomic classification in the time interval 2008-2019 and provide an evolutionary timeline of data processing and machine learning in this field. This study follows the scoping review methodology and PRISMA guidelines to identify and process the available literature. Natural Language Processing (NLP) is deployed to ensure efficient and exhaustive search of the literary corpus of three large digital libraries: IEEE, PubMed, and Springer. The search is based on keywords and properties looked up using the digital libraries' search engines. The scoping review results reveal an increasing number of research papers related to metagenomic classification over the past decade. The research is mainly focused on metagenomic classifiers, identifying scope specific metrics for model evaluation, data set sanitization, and dimensionality reduction. Out of all of these subproblems, data preprocessing is the least researched with considerable potential for improvement.
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BACKGROUND: Connected health (CH) technologies have resulted in a paradigm shift, moving health care steadily toward a more patient-centered delivery approach. CH requires a broad range of disciplinary expertise from across the spectrum to work in a cohesive and productive way. Building this interdisciplinary relationship at an earlier stage of career development may nurture and accelerate the CH developments and innovations required for future health care. OBJECTIVE: This study aimed to explore the perceptions of interdisciplinary CH researchers regarding the design and delivery of an interdisciplinary education (IDE) module for disciplines currently engaged in CH research (engineers, computer scientists, health care practitioners, and policy makers). This study also investigated whether this module should be delivered as a taught component of an undergraduate, master's, or doctoral program to facilitate the development of interdisciplinary learning. METHODS: A qualitative, cross-institutional, multistage research approach was adopted, which involved a background study of fundamental concepts, individual interviews with CH researchers in Greece (n=9), and two structured group feedback sessions with CH researchers in Ireland (n=10/16). Thematic analysis was used to identify the themes emerging from the interviews and structured group feedback sessions. RESULTS: A total of two sets of findings emerged from the data. In the first instance, challenges to interdisciplinary work were identified, including communication challenges, divergent awareness of state-of-the-art CH technologies across disciplines, and cultural resistance to interdisciplinarity. The second set of findings were related to the design for interdisciplinarity. In this regard, the need to link research and education with real-world practice emerged as a key design concern. Positioning within the program context was also considered to be important with a need to balance early intervention to embed integration with later repeat interventions that maximize opportunities to share skills and experiences. CONCLUSIONS: The authors raise and address challenges to interdisciplinary program design for CH based on an abductive approach combining interdisciplinary and interprofessional education literature and the collection of qualitative data. This recipe approach for interdisciplinary design offers guidelines for policy makers, educators, and innovators in the CH space. Gaining insight from CH researchers regarding the development of an IDE module has offered the designers a novel insight regarding the curriculum, timing, delivery, and potential challenges that may be encountered.
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Educación/métodos , Estudios Interdisciplinarios/tendencias , Anciano , Europa (Continente) , Femenino , Humanos , Masculino , Investigación CualitativaRESUMEN
BACKGROUND: Wearable sensing and information and communication technologies are key enablers driving the transformation of health care delivery toward a new model of connected health (CH) care. The advances in wearable technologies in the last decade are evidenced in a plethora of original articles, patent documentation, and focused systematic reviews. Although technological innovations continuously respond to emerging challenges and technology availability further supports the evolution of CH solutions, the widespread adoption of wearables remains hindered. OBJECTIVE: This study aimed to scope the scientific literature in the field of pervasive wearable health monitoring in the time interval from January 2010 to February 2019 with respect to four important pillars: technology, safety and security, prescriptive insight, and user-related concerns. The purpose of this study was multifold: identification of (1) trends and milestones that have driven research in wearable technology in the last decade, (2) concerns and barriers from technology and user perspective, and (3) trends in the research literature addressing these issues. METHODS: This study followed the scoping review methodology to identify and process the available literature. As the scope surpasses the possibilities of manual search, we relied on the natural language processing tool kit to ensure an efficient and exhaustive search of the literature corpus in three large digital libraries: Institute of Electrical and Electronics Engineers, PubMed, and Springer. The search was based on the keywords and properties to be found in articles using the search engines of the digital libraries. RESULTS: The annual number of publications in all segments of research on wearable technology shows an increasing trend from 2010 to February 2019. The technology-related topics dominated in the number of contributions, followed by research on information delivery, safety, and security, whereas user-related concerns were the topic least addressed. The literature corpus evidences milestones in sensor technology (miniaturization and placement), communication architectures and fifth generation (5G) cellular network technology, data analytics, and evolution of cloud and edge computing architectures. The research lag in battery technology makes energy efficiency a relevant consideration in the design of both sensors and network architectures with computational offloading. The most addressed user-related concerns were (technology) acceptance and privacy, whereas research gaps indicate that more efforts should be invested into formalizing clear use cases with timely and valuable feedback and prescriptive recommendations. CONCLUSIONS: This study confirms that applications of wearable technology in the CH domain are becoming mature and established as a scientific domain. The current research should bring progress to sustainable delivery of valuable recommendations, enforcement of privacy by design, energy-efficient pervasive sensing, seamless monitoring, and low-latency 5G communications. To complement technology achievements, future work involving all stakeholders providing research evidence on improved care pathways and cost-effectiveness of the CH model is needed.
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Tecnología de Sensores Remotos/métodos , Telemedicina/normas , Dispositivos Electrónicos Vestibles/normas , Humanos , TecnologíaRESUMEN
Using comprehensive analysis of heart rate (HRV) and blood pressure (BPV) short-term variability we estimated the time course of changes of autonomic nervous system remodeling in two stages of doxorubicin-induced cardiomyopathy (DCM). We also investigated the level of gene expression of cardiac ß-1 (ß-1AR) and ß-2 (ß-2AR) adrenoceptors. Experiments were performed in adult male Wistar rats equipped with indwelling catheters for BP recording and blood withdrawal. A 15 mg/kg total cumulative dose of doxorubicin was injected i.p. to rats to induce DCM or saline for control (n=18). Rats were assessed for general toxicity, cardiovascular hemodynamic and echocardiography before treatment (n=6), 35 days (DOX35; n=6) and 70 days (DOX70; n=6) post-treatment. HRV was evaluated by spectral analysis, Poincaré plots, sample and approximate entropy. Expression of ß-1AR and ß-2AR mRNA was evaluated by RT-qPCR. Doxorubicin-treated rats exhibited poor general condition and lower survival than saline-treated rats. In DOX35 rats, there were no echocardiography signs of decompensation, no increase in serum cardiac troponins, but there was an increase of HRV and decrease of HR complexity. In these rats typical microscopic signs of cardiotoxicity were seen along with over-expression of ß-1AR mRNA. 70 days post-treatment echocardiography revealed signs of decompensation and serum cardiac troponin T was increased. At this stage BPV decreased. In conclusion, HRV increase matches transient over-expression of cardiac ß-1AR mRNA in compensate stage of DCM while decompensate stage of DCM is characterized by a decrease of BPV and no changes in ß-1AR and ß-2AR gene expression.
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Antibióticos Antineoplásicos/toxicidad , Cardiomiopatías/inducido químicamente , Doxorrubicina/toxicidad , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 2/genética , Animales , Presión Sanguínea/efectos de los fármacos , Cardiomiopatías/genética , Cardiomiopatías/patología , Cardiomiopatías/fisiopatología , Ecocardiografía , Regulación de la Expresión Génica/efectos de los fármacos , Corazón/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Miocardio/metabolismo , Miocardio/patología , Ratas WistarRESUMEN
BACKGROUND: The advances in extracellular neural recording techniques result in big data volumes that necessitate fast, reliable, and automatic identification of statistically similar units. This study proposes a single framework yielding a compact set of probabilistic descriptors that characterise the firing patterns of a single unit. NEW METHOD: Probabilistic features are estimated from an inter-spike-interval time series, without assumptions about the firing distribution or the stationarity. The first level of proposed firing patterns decomposition divides the inter-spike intervals into bursting, moderate and idle firing modes, yielding a coarse feature set. The second level identifies the successive bursting spikes, or the spiking acceleration/deceleration in the moderate firing mode, yielding a refined feature set. The features are estimated from simulated data and from experimental recordings from the lateral prefrontal cortex in awake, behaving rhesus monkeys. RESULTS: An efficient and stable partitioning of neural units is provided by the ensemble evidence accumulation clustering. The possibility of selecting the number of clusters and choosing among coarse and refined feature sets provides an opportunity to explore and compare different data partitions. CONCLUSIONS: The estimation of features, if applied to a single unit, can serve as a tool for the firing analysis, observing either overall spiking activity or the periods of interest in trial-to-trial recordings. If applied to massively parallel recordings, it additionally serves as an input to the clustering procedure, with the potential to compare the functional properties of various brain structures and to link the types of neural cells to the particular behavioural states.
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Potenciales de Acción , Electrofisiología/métodos , Procesamiento de Señales Asistido por Computador , Algoritmos , Animales , Análisis por Conglomerados , Simulación por Computador , Macaca mulatta , Modelos Neurológicos , Neuronas/fisiología , Corteza Prefrontal/fisiología , Probabilidad , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
Lumbar disc herniation (LDH) is the most common disease among working population requiring surgical intervention. This study aims to predict the return to work after operative treatment of LDH based on the observational study including 153 patients. The classification problem was approached using decision trees (DT), support vector machines (SVM) and multilayer perception (MLP) combined with RELIEF algorithm for feature selection. MLP provided best recall of 0.86 for the class of patients not returning to work, which combined with the selected features enables early identification and personalized targeted interventions towards subjects at risk of prolonged disability. The predictive modeling indicated at the most decisive risk factors in prolongation of work absence: psychosocial factors, mobility of the spine and structural changes of facet joints and professional factors including standing, sitting and microclimate.
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Discectomía/métodos , Desplazamiento del Disco Intervertebral/cirugía , Reinserción al Trabajo , Resultado del Tratamiento , Algoritmos , Árboles de Decisión , Femenino , Humanos , Masculino , Microcirugia/métodos , Modelos Teóricos , Medicina del Trabajo , Serbia , Máquina de Vectores de SoporteRESUMEN
The burden of chronic disease and associated disability present a major threat to financial sustainability of healthcare delivery systems. The need for cost-effective early diagnosis and disease prevention is evident driving the development of personalized home health solutions. The proposed solution presents an easy to use ECG monitoring system. The core hardware component is a biosensor dongle with sensing probes at one end, and micro USB interface at the other end, offering reliable and unobtrusive sensing, preprocessing and storage. An additional component is a smart phone, providing both the biosensor's power supply and an intuitive user application for the real-time data reading. The system usage is simplified, with innovative solutions offering plug and play functionality avoiding additional driver installation. Personalized needs could be met with different sensor combinations enabling adequate monitoring in chronic disease, during physical activity and in the rehabilitation process.
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Electrocardiografía Ambulatoria/instrumentación , Teléfono Inteligente , Electrocardiografía Ambulatoria/métodos , Humanos , Aplicaciones Móviles , Telemedicina/instrumentación , Dispositivos Electrónicos VestiblesRESUMEN
This study seeks to characterize the neuronal mechanisms underlying voluntary decisions to check/verify. In order to describe and potentially decode decisions from brain signals we analyzed intracortical recordings from monkey prefrontal regions obtained during a cognitive task requiring self-initiated as well as cue-instructed decisions. Using local field potentials (LFP) and single units, we analyzed power spectral density, oscillatory modes, power profiles in time, single unit firing rate, and spike-phase relationships in the ß band. Our results point toward specific but variable activation patterns of oscillations in ß band from separate recordings, with task-dependent frequency preference and amplitude modulation of power. The results suggest relationships between particular LFP oscillations and functions engaged at specific time in the task.
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Toma de Decisiones , Potenciales de Acción , Animales , Encéfalo , Haplorrinos , NeuronasRESUMEN
In this paper a copula approach is applied as a tool for assessing the measure of statistical dependence of parallel cardiovascular time series. Families of Archimedean copulas (Clayton, Frank and Gumbel) are applied to pulse interval, systolic and diastolic blood pressure recorded from male Wistar rats at baseline conditions, and to their isodistributional surrogates with the same marginal, but randomized joint distribution functions. The influence of time offset of the parallel time series is explored. The amount of data required for a stable working point is discussed.
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Determinación de la Presión Sanguínea/métodos , Análisis Multivariante , Pulso Arterial/métodos , Procesamiento de Señales Asistido por Computador , Animales , Presión Sanguínea/fisiología , Electrocardiografía , Masculino , Ratas , Ratas WistarRESUMEN
BACKGROUND/AIM: The lack of effective therapy for advanced stages of melanoma emphasizes the importance of preventive measures and screenings of population at risk. Identifying individuals at high risk should allow targeted screenings and follow-up involving those who would benefit most. The aim of this study was to identify most significant factors for melanoma prediction in our population and to create prognostic models for identification and differentiation of individuals at risk. METHODS: This case-control study included 697 participants (341 patients and 356 controls) that underwent extensive interview and skin examination in order to check risk factors for melanoma. Pairwise univariate statistical comparison was used for the coarse selection of the most significant risk factors. These factors were fed into logistic regression (LR) and alternating decision trees (ADT) prognostic models that were assessed for their usefulness in identification of patients at risk to develop melanoma. Validation of the LR model was done by Hosmer and Lemeshow test, whereas the ADT was validated by 10-fold cross-validation. The achieved sensitivity, specificity, accuracy and AUC for both models were calculated. The melanoma risk score (MRS) based on the outcome of the LR model was presented. RESULTS: The LR model showed that the following risk factors were associated with melanoma: sunbeds (OR = 4.018; 95% CI 1.724-9.366 for those that sometimes used sunbeds), solar damage of the skin (OR = 8.274; 95% CI 2.661-25.730 for those with severe solar damage), hair color (OR = 3.222; 95% CI 1.984-5.231 for light brown/blond hair), the number of common naevi (over 100 naevi had OR = 3.57; 95% CI 1.427-8.931), the number of dysplastic naevi (from 1 to 10 dysplastic naevi OR was 2.672; 95% CI 1.572-4.540; for more than 10 naevi OR was 6.487; 95%; CI 1.993-21.119), Fitzpatricks phototype and the presence of congenital naevi. Red hair, phototype I and large congenital naevi were only present in melanoma patients and thus were strongly associated with melanoma. The percentage of correctly classified subjects in the LR model was 74.9%, sensitivity 71%, specificity 78.7% and AUC 0.805. For the ADT percentage of correctly classified instances was 71.9%, sensitivity 71.9%, specificity 79.4% and AUC 0.808. CONCLUSION: Application of different models for risk assessment and prediction of melanoma should provide efficient and standardized tool in the hands of clinicians. The presented models offer effective discrimination of individuals at high risk, transparent decision making and real-time implementation suitable for clinical practice. A continuous melanoma database growth would provide for further adjustments and enhancements in model accuracy as well as offering a possibility for successful application of more advanced data mining algorithms.