Heterogeneity in families with ATTRV30M amyloidosis: a historical and longitudinal Portuguese case study impact for genetic counselling.

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is an inherited disease, where the study of family history holds importance. This study evaluates the changes of age-of-onset (AOO) and other age-related clinical factors within and among families affected by ATTRv amyloidosis. METHODS: We analysed information from 934 trees, focusing on family, parents, probands and siblings relationships. We focused on 1494 female and 1712 male symptomatic ATTRV30M patients. Results are presented alongside a comparison of current with historical records. Clinical and genealogical indicators identify major changes. RESULTS: Overall, analysis of familial data shows the existence of families with both early and late patients (1/6). It identifies long familial follow-up times since patient families tend to be diagnosed over several years. Finally, results show a large difference between parent-child and proband-patient relationships (20-30 years). CONCLUSIONS: This study reveals that there has been a shift in patient profile, with a recent increase in male elderly cases, especially regarding probands. It shows that symptomatic patients exhibit less variability towards siblings, when compared to other family members, namely the transmitting ancestors' age of onset. This can influence genetic counselling guidelines.

Clinical model for Hereditary Transthyretin Amyloidosis age of onset prediction.

Introduction: Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is a rare neurological hereditary disease clinically characterized as severe, progressive, and life-threatening while the age of onset represents the moment in time when the first symptoms are felt. In this study, we present and discuss our results on the study, development, and evaluation of an approach that allows for time-to-event prediction of the age of onset, while focusing on genealogical feature construction. Materials and methods: This research was triggered by the need to answer the medical problem of when will an asymptomatic ATTRv patient show symptoms of the disease. To do so, we defined and studied the impact of 77 features (ranging from demographic and genealogical to familial disease history) we studied and compared a pool of prediction algorithms, namely, linear regression (LR), elastic net (EN), lasso (LA), ridge (RI), support vector machines (SV), decision tree (DT), random forest (RF), and XGboost (XG), both in a classification as well as a regression setting; we assembled a baseline (BL) which corresponds to the current medical knowledge of the disease; we studied the problem of predicting the age of onset of ATTRv patients; we assessed the viability of predicting age of onset on short term horizons, with a classification framing, on localized sets of patients (currently symptomatic and asymptomatic carriers, with and without genealogical information); and we compared the results with an out-of-bag evaluation set and assembled in a different time-frame than the original data in order to account for data leakage. Results: Currently, we observe that our approach outperforms the BL model, which follows a set of clinical heuristics and represents current medical practice. Overall, our results show the supremacy of SV and XG for both the prediction tasks although impacted by data characteristics, namely, the existence of missing values, complex data, and small-sized available inputs. Discussion: With this study, we defined a predictive model approach capable to be well-understood by medical professionals, compared with the current practice, namely, the baseline approach (BL), and successfully showed the improvement achieved to the current medical knowledge.

The robustness of Random Forest and Support Vector Machine Algorithms to a Faulty Heart Sound Segmentation.

Cardiac auscultation is the key exam to screen cardiac diseases both in developed and developing countries. A heart sound auscultation procedure can detect the presence of murmurs and point to a diagnosis, thus it is an important first-line assessment and also cost-effective tool. The design automatic recommendation systems based on heart sound auscultation can play an important role in boosting the accuracy and the pervasiveness of screening tools. One such as step, consists in detecting the fundamental heart sound states, a process known as segmentation. A faulty segmentation or a wrong estimation of the heart rate might result in an incapability of heart sound classifiers to detect abnormal waves, such as murmurs. In the process of understanding the impact of a faulty segmentation, several common heart sound segmentation errors are studied in detail, namely those where the heart rate is badly estimated and those where S1/S2 and Systolic/Diastolic states are swapped in comparison with the ground truth state sequence. From the tested algorithms, support vector machine (SVMs) and random forest (RFs) shown to be more sensitive to a wrong estimation of the heart rate (an expected drop of 6% and 8% on the overall performance, respectively) than to a swap in the state sequence of events (an expected drop of 1.9% and 4.6%, respectively).

The CirCor DigiScope Dataset: From Murmur Detection to Murmur Classification.

Cardiac auscultation is one of the most cost-effective techniques used to detect and identify many heart conditions. Computer-assisted decision systems based on auscultation can support physicians in their decisions. Unfortunately, the application of such systems in clinical trials is still minimal since most of them only aim to detect the presence of extra or abnormal waves in the phonocardiogram signal, i.e., only a binary ground truth variable (normal vs abnormal) is provided. This is mainly due to the lack of large publicly available datasets, where a more detailed description of such abnormal waves (e.g., cardiac murmurs) exists. To pave the way to more effective research on healthcare recommendation systems based on auscultation, our team has prepared the currently largest pediatric heart sound dataset. A total of 5282 recordings have been collected from the four main auscultation locations of 1568 patients, in the process, 215780 heart sounds have been manually annotated. Furthermore, and for the first time, each cardiac murmur has been manually annotated by an expert annotator according to its timing, shape, pitch, grading, and quality. In addition, the auscultation locations where the murmur is present were identified as well as the auscultation location where the murmur is detected more intensively. Such detailed description for a relatively large number of heart sounds may pave the way for new machine learning algorithms with a real-world application for the detection and analysis of murmur waves for diagnostic purposes.

Do we really need a segmentation step in heart sound classification algorithms?

Cardiac auscultation is the key screening procedure to detect and identify cardiovascular diseases (CVDs). One of many steps to automatically detect CVDs using auscultation, concerns the detection and delimitation of the heart sound boundaries, a process known as segmentation. Whether to include or not a segmentation step in the signal classification pipeline is nowadays a topic of discussion. Up to our knowledge, the outcome of a segmentation algorithm has been used almost exclusively to align the different signal segments according to the heartbeat. In this paper, the need for a heartbeat alignment step is tested and evaluated over different machine learning algorithms, including deep learning solutions. From the different classifiers tested, Gate Recurrent Unit (GRU) Network and Convolutional Neural Network (CNN) algorithms are shown to be the most robust. Namely, these algorithms can detect the presence of heart murmurs even without a heartbeat alignment step. Furthermore, Support Vector Machine (SVM) and Random Forest (RF) algorithms require an explicit segmentation step to effectively detect heart sounds and murmurs, the overall performance is expected drop approximately 5% on both cases.

Classifying Heart Sounds Using Images of Motifs, MFCC and Temporal Features.

Cardiovascular disease is the leading cause of death in the world, and its early detection is a key to improving long-term health outcomes. The auscultation of the heart is still an important method in the medical process because it is very simple and cheap. To detect possible heart anomalies at an early stage, an automatic method enabling cardiac health low-cost screening for the general population would be highly valuable. By analyzing the phonocardiogram signals, it is possible to perform cardiac diagnosis and find possible anomalies at an early-term. Therefore, the development of intelligent and automated analysis tools of the phonocardiogram is very relevant. In this work, we use simultaneously collected electrocardiograms and phonocardiograms from the Physionet Challenge database with the main objective of determining whether a phonocardiogram corresponds to a "normal" or "abnormal" physiological state. Our main contribution is the methodological combination of time domain features and frequency domain features of phonocardiogram signals to improve cardiac disease automatic classification. This novel approach is developed using both features. First, the phonocardiogram signals are segmented with an algorithm based on a logistic regression hidden semi-Markov model, which uses electrocardiogram signals as a reference. Then, two groups of features from the time and frequency domain are extracted from the phonocardiogram segments. One group is based on motifs and the other on Mel-frequency cepstral coefficients. After that, we combine these features into a two-dimensional time-frequency heat map representation. Lastly, a binary classifier is applied to both groups of features to learn a model that discriminates between normal and abnormal phonocardiogram signals. In the experiments, three classification algorithms are used: Support Vector Machines, Convolutional Neural Network, and Random Forest. The best results are achieved when both time and Mel-frequency cepstral coefficients features are considered using a Support Vector Machines with a radial kernel.

Aplicación de software estadísticos y modelos matemáticos para la evaluación de la velocidad de corrosión en el acero / Application of statistical software and mathematical models for the evaluation of the corrosion rate in steel

RESUMEN La corrosión es un fenómeno que se presenta día a día, no solo en los procesos industriales sino en la propia naturale- za. Debido a que la corrosión tiene graves consecuencias, desde hace mucho tiempo, es considerada un problema de gran magnitud alrededor del mundo. En este trabajo, se aplican métodos estadísticos para el análisis de resultados experimentales. La aplicación del diseño de experimentos de bloques al azar permitió evaluar el comportamiento de la velocidad de corrosión del acero, a partir de software estadís- ticos y modelos matemáticos, teniendo en cuenta la influencia de la variable bloque: tiempo de exposición en la cámara de niebla salina neutra y el comportamiento del grado de oxidación. Se evidenció, que los factores tienen un efecto estadísticamente significativo en la velocidad de Corrosión, al nivel de confianza de 95,0%. El diseño de experimento garantiza minimizar la cantidad de recursos, la posibilidad del estudio de las variaciones de los factores durante el proceso y la selección de una estrategia sobre las decisiones a tomar en el futuro, con vistas a reducir la intensidad del fenómeno.

SUMMARY Corrosion is a phenomenon that occurs every day, not only in industrial processes but also in nature itself. Because corrosion has serious consequences, it has long been considered a problem of great magnitude around the world. Statistical methods are applied in this work for the analysis of experimental results. The application of the randomized block experimental are applied design allowed the evaluation of the behavior of the steel corrosion rate from statistical software and mathematical models, taking into account the influence of the block variable: exposure time in the neutral salt fog chamber and the behavior of the degree of oxidation. It was evidenced that the factors have a statistically significant effect on the corrosion rate at the confidence level of 95.0%. The design of the experiment guarantees to minimize the amount of resources, the possibility of studying the variations of the factors during the process and the selection of a strategy on the decisions to be made in the future, in order to reduce the intensity of the phenomenon.