Huntington disease: natural history, biomarkers and prospects for therapeutics

Huntington disease (HD) can be seen as a model neurodegenerative disorder, in that it is caused by a single genetic mutation and is amenable to predictive genetic testing, with estimation of years to predicted onset, enabling the entire range of disease natural history to be studied. Structural neuroimaging biomarkers show that progressive regional brain atrophy begins many years before the emergence of diagnosable signs and symptoms of HD, and continues steadily during the symptomatic or 'manifest' period. The continued development of functional, neurochemical and other biomarkers raises hopes that these biomarkers might be useful for future trials of disease-modifying therapeutics to delay the onset and slow the progression of HD. Such advances could herald a new era of personalized preventive therapeutics. We describe the natural history of HD, including the timing of emergence of motor, cognitive and emotional impairments, and the techniques that are used to assess these features. Building on this information, we review recent progress in the development of biomarkers for HD, and potential future roles of these biomarkers in clinical trials

Toward diffusion tensor imaging as a biomarker in neurodegenerative diseases: technical considerations to optimize recordings and data processing

Neuroimaging biomarkers have shown high potential to map the disease processes in the application to neurodegenerative diseases (NDD), e.g., diffusion tensor imaging (DTI). For DTI, the implementation of a standardized scanning and analysis cascade in clinical trials has potential to be further optimized. Over the last few years, various approaches to improve DTI applications to NDD have been developed. The core issue of this review was to address considerations and limitations of DTI in NDD: we discuss suggestions for improvements of DTI applications to NDD. Based on this technical approach, a set of recommendations was proposed for a standardized DTI scan protocol and an analysis cascade of DTI data pre-and postprocessing and statistical analysis. In summary, considering advantages and limitations of the DTI in NDD we suggest improvements for a standardized framework for a DTI-based protocol to be applied to future imaging studies in NDD, towards the goal to proceed to establish DTI as a biomarker in clinical trials in neurodegeneration

Solución rápida y automática de parámetros hipocentrales para eventos sísmicos, mediante el empleo de técnicas de aprendizaje de máquina

La generación de alertas tempranas para sismos es de gran utilidad, en particular para la ciudad de Bogotá-Colombia, dada su importancia social y económica para el país. Con base en la información de la estación sismológica de El Rosal, la cual es una estación de banda ancha y tres componentes, localizada muy cerca de la ciudad, perteneciente al Servicio Geológico Colombiano (SGC) se desarrolló un modelo de regresión basado en máquinas de vectores de soporte (SVM), con un kernel polinomial normalizado, usando como datos de entrada algunas características de la porción inicial de la onda P empleadas en trabajos anteriores tales como la amplitud máxima, los coeficientes de regresión lineal de los mismos, los parámetros de ajuste logarítmico de la envolvente y los valores propios de la relación de las tres componentes del sismograma. El modelo fue entrenado y evaluado aplicando correlación cruzada, permitiendo llevar a cabo el cálculo de la magnitud y la localización de un evento sísmico con una longitud de señal de tan solo cinco segundos. Con el modelo propuesto se logró la determinación de la magnitud local con una precisión de 0.19 unidades de magnitud, la distancia epicentral con una precisión de alrededor de 11 kilómetros, la profundidad hipocentral con una precisión de aproximadamente 40 kilómetros y el azimut de llegada con una precisión de 45°. Las precisiones obtenidas en magnitud y distancia epicentral son mejores que las encontradas en trabajos anteriores, donde se emplean gran número de eventos para la determinación del modelo y en los demás parámetros hipocentrales son del mismo orden. Este trabajo de investigación realiza un aporte considerable en la generación de alertas tempranas para sismos, no solamente para el país sino para cualquier otro lugar donde se deseen implementar los modelos aquí propuestos y es un excelente punto de partida para investigaciones futuras.Abstract. Earthquake early warning alerts generation is very useful, especially for the city of Bogotá-Colombia, given the social and economic importance of this city for the country. Based on the information from the seismological station “El Rosal”, which is a broadband and three components station, located very near the city that belongs to the Servicio Geológico Colombiano (SGC) a Support Vector Machine Regression (SVMR) model was developed, using a Normalized Polynomial Kernel, using as input some characteristics of the initial portion of the P wave used in earlier works such as the maximum amplitude, the linear regression coefficients of such amplitudes, the logarithmic adjustment parameters of the envelope of the waveform and the eigenvalues of the relationship between the three seismogram components of each band. The model was trained and evaluated by applying a cross-correlation strategy, allowing to calculate the magnitude and location of a seismic event with only five seconds of signal. With the proposed model it was possible to estimate local magnitude with an accuracy of 0.19 units of magnitude, epicentral distance with an accuracy of about 11 km, the hipocentral depth with a precision of approximately 40 km and the arrival back-azimut with a precision of 45°. Accuracies obtained in magnitude and epicentral distance are better that those found in earlier works, where a large number of events were used for model determination, and the other hipocentral parameters precisions obtained here are of the same order. This research work makes a considerable contribution in the generation of seismic early warning alerts, not only for the country but for any other place where proposed models here can be applied and is a very good starting point for future research.Doctorad