Beat-to-beat ambulatory blood pressure estimation based on random forest

Ambulatory blood pressure is critical in predicting some major cardiovascular events; therefore, cuff-less and noninvasive beat-to-beat ambulatory blood pressure measure-ment is of great significance. Machine-learning methods have shown the potential to derive the relationship between physio-logical signal features and ABP. In this paper, we apply random forest method to systematically explorer the inherent connections between photoplethysmography signal, electrocardiogram signal and ambulatory blood pressure. To archive this goal, 18 features were extracted from PPG and ECG signals. Several models with most significant features as inputs and beat-to-beat ABP as outputs were trained and tested on data from the Multi-Parameter Intelligent Monitoring in Intensive Care II database. Results indicate that compared with the common pulse transit time method, the RF method gives a better performance for one-hour continuous estimation of diastolic blood pressure and systolic blood pressure under both the Association for the Advancement of Medical Instrumentation and British Hyper-tension Society standard

Cuffless ambulatory blood pressure measurement using the photoplethysmogram and the electrocardiogram

Blood pressure (BP), as with other vital signs such as heart rate and respiratory rate, exhibits endogenous oscillations over a period of approximately 24 hours, a phenomenon known as circadian rhythmicity. This rhythm typically reaches a nadir during sleep, however, different BP circadian rhythm phenotypes exist depending on the magnitude and direction of the nocturnal change. Analysis of these phenotypes has been shown to be an independent indicator for the onset of cardiovascular disease, the leading cause of non-communicable mortality and morbidity worldwide. However, currently the established technique for monitoring BP over 24 hours in the general population requires an inflatable cuff wrapped around the upper arm. This procedure is highly disruptive to sleep and daily life, and therefore rarely performed in primary care. Although commercial cuffless BP devices do exist, their accuracy has been questioned, and consequently, the clinical community do not recommend their use. In this thesis, I investigated techniques to measure BP in an ambulatory environment without an inflatable cuff using two signals commonly acquired by wearable sensors: the photoplethysmogram (PPG) and the electrocardiogram (ECG). Given the diverse mechanisms by which the autonomic nervous system regulates BP, I developed methodologies using data from multiple individuals with BP perturbed by various, diverse, mechanisms. To identify surrogate measures of BP derived from the PPG and ECG signals, I designed a clinical study in which significant BP changes were induced through a pharmacological intervention in thirty healthy volunteers. Using data from this study, I established that changes in the pulse arrival time (PAT, the time delay between fiducial points on the ECG and PPG waveforms) and morphological features of the PPG waveform could provide reliable cuffless indicators for changes in BP. Even at rest, however, these signals are confounded by factors such as the pre-ejection period (PEP) and signal measurement noise. Additionally, accurate absolute measurements of BP required calibration using a reference BP device. Subsequently, I conducted a circadian analysis of these surrogate measures of BP using a large cohort of 1,508 patients during the 24-hour period prior to their discharge from an intensive care unit. Through this circadian analysis I suggest that PAT and a subset of features from the PPG waveform exhibit a phenotypically modified circadian rhythm in synchronicity with that of BP. Additionally, I designed a novel ordinal classification algorithm, which utilised circadian features of these signals, in order to identify BP circadian rhythm profiles in a calibration-free manner. This method may provide a cost-effective initial assessment of BP phenotypes in the general population. Notably, estimating absolute BP values using PPG and ECG signals in the ICU resulted in clinically significant mean absolute errors of 9.26 (5.01) mmHg. Finally, I designed a clinical study to extend the work towards cuffless ambulatory BP estimation in a cohort of fifteen healthy volunteers. Hybrid calibration strategies (where model personalisation was handled by user demographics, commonly utilised by commercial cuffless devices) led to clinically significant errors when estimating absolute values of BP, mean absolute error = 9.62 (19.73) mmHg. For the majority of individuals, a more appropriate estimation of BP values was achieved through an individual calibration strategy whereby idiosyncratic models were trained on personalised data, mean absolute error = 5.45 (6.40) mmHg. However, for a handful of individuals, notable estimation errors (>10 mmHg) still persisted using this strategy largely as a result of motion artifacts, inherent intra- and inter-individual variability in PPG features, and inadequate training data. Overall, I suggest that while beat-by-beat measurements of BP can be obtained using PPG and ECG signals, their accuracy is significantly limited in an ambulatory environment. This limitation, combined with the impracticality of individual calibration (due to the low tolerance for ABPM), suggest that cuffless ambulatory blood pressure measurement using the PPG and ECG signals may be infeasible. Nevertheless, macro assessments of cardiovascular health, such as an individual's BP phenotype, may be comparatively more accurately predicted using these signals with the potential to be recorded without calibration. Through further research on the relationship between the circadian rhythms of BP and the PPG and ECG waveforms, it is promising that these signals may be able to assist in detecting deterioration in cardiovascular health in the general population

False alarm reduction in critical care

High false alarm rates in the ICU decrease quality of care by slowing staff response times while increasing patient delirium through noise pollution. The 2015 PhysioNet/Computing in Cardiology Challenge provides a set of 1250 multi-parameter ICU data segments associated with critical arrhythmia alarms, and challenges the general research community to address the issue of false alarm suppression using all available signals. Each data segment was 5 minutes long (for real time analysis), ending at the time of the alarm. For retrospective analysis, we provided a further 30 seconds of data after the alarm was triggered. A total of 750 data segments were made available for training and 500 were held back for testing. Each alarm was reviewed by expert annotators, at least two of whom agreed that the alarm was either true or false. Challenge participants were invited to submit a complete, working algorithm to distinguish true from false alarms, and received a score based on their program's performance on the hidden test set. This score was based on the percentage of alarms correct, but with a penalty that weights the suppression of true alarms five times more heavily than acceptance of false alarms. We provided three example entries based on well-known, open source signal processing algorithms, to serve as a basis for comparison and as a starting point for participants to develop their own code. A total of 38 teams submitted a total of 215 entries in this year's Challenge. This editorial reviews the background issues for this challenge, the design of the challenge itself, the key achievements, and the follow-up research generated as a result of the Challenge, published in the concurrent special issue of Physiological Measurement. Additionally we make some recommendations for future changes in the field of patient monitoring as a result of the Challenge.National Institutes of Health (U.S.) (Grant R01-GM104987)National Institute of General Medical Sciences (U.S.) (Grant U01-EB-008577)National Institutes of Health (U.S.) (Grant R01-EB-001659

A review of machine learning techniques in photoplethysmography for the non-invasive cuff-less measurement of blood pressure

Hypertension or high blood pressure is a leading cause of death throughout the world and a critical factor for increasing the risk of serious diseases, including cardiovascular diseases such as stroke and heart failure. Blood pressure is a primary vital sign that must be monitored regularly for the early detection, prevention and treatment of cardiovascular diseases. Traditional blood pressure measurement techniques are either invasive or cuff-based, which are impractical, intermittent, and uncomfortable for patients. Over the past few decades, several indirect approaches using photoplethysmogram (PPG) have been investigated, namely, pulse transit time, pulse wave velocity, pulse arrival time and pulse wave analysis, in an effort to utilise PPG for estimating blood pressure. Recent advancements in signal processing techniques, including machine learning and artificial intelligence, have also opened up exciting new horizons for PPG-based cuff less and continuous monitoring of blood pressure. Such a device will have a significant and transformative impact in monitoring patients’ vital signs, especially those at risk of cardiovascular disease. This paper provides a comprehensive review for non-invasive cuff-less blood pressure estimation using the PPG approach along with their challenges and limitations

Cuffless Blood Pressure Estimation

The blood pressure is an important factor in the diagnosis and evaluation of several diseases, such as acute myocardial infarction and stroke. This way, continuous monitorization of this parameter is crucial to a correct health evaluation. The current methods, like the oscillometric method, have some major drawbacks, that can influence the output values or even make the measurements impossible. One example is the high frequency evaluation of the blood pressure, in the standard used methods the process of measuring can take up to 3 minutes, and a waiting time is necessary between consecutive measurements. This dissertation presents two different cuffless solution to solve those problems. One based on physical models of the human body, and the other using machine learning techniques. In the first solution seven models that correlate pulse transit time and blood pressure, deducted by different authors, were tested to evaluate which one performed better. The testes were performed in a custom dataset acquired at Fraunhofer AICOS and in clinical environment, with two different devices (low cost device and medical grade device). The results indicate that pulse transit time can be used to track blood pressure, the developed device/method was evaluated as grade A based in the Standard IEEE 1708-2014. The second solution it’s a proof of concept using a public database and three different machine learning methods (Random Forest, Neural Network and AdaBoost). Two sets of features are calculated from the ECG and PPG signals, one using TSFEL (spectral, frequency and time domain features) and a total of 15 custom features. The proposed method outperforms the methods presented in bibliography with mean absolute error of 3.6 mmHg and 2.0 mmHg to systolic and diastolic blood pressure respectively

Improving cuff-less continuous blood pressure estimation with linear regression analysis

In this work, the authors investigate the cuff-less estimation of continuous BP through pulse transit time (PTT) and heart rate (HR) using regression techniques, which is intended as a first step towards continuous BP estimation with a low error, according to AAMI guidelines. Hypertension (the 'silent killer') is one of the main risk factors for cardiovascular diseases (CVDs), which are the main cause of death worldwide. Its continuous monitoring can offer a valid tool for patient care, as blood pressure (BP) is a significant indicator of health and, using it together with other parameters, such as heart and breath rates, could strongly improve prevention of CVDs. The novelties introduced in this work are represented by the implementation of pre-processing and by the innovative method for features research and features processing to continuously monitor blood pressure in a non-invasive way. Currently, invasive methods are the only reliable methods for continuous monitoring, while non-invasive techniques measure the values every few minutes. The proposed approach can be considered the first step for the integration of these types of algorithms on wearable devices, in particular on those developed for the SINTEC project

Stress monitoring using wearable sensors:a pilot study and stress-predict dataset

With the recent advancements in the field of wearable technologies, the opportunity to monitor stress continuously using different physiological variables has gained significant interest. The early detection of stress can help improve healthcare and minimizes the negative impact of long-term stress. This paper reports outcomes of a pilot study and associated stress-monitoring dataset, named the “Stress-Predict Dataset”, created by collecting physiological signals from healthy subjects using wrist-worn watches with a photoplethysmogram (PPG) sensor. While wearing these watches, 35 healthy volunteers underwent a series of tasks (i.e., Stroop color test, Trier Social Stress Test and Hyperventilation Provocation Test), along with a rest period in-between each task. They also answered questionnaires designed to induce stress levels compatible with daily life. The changes in the blood volume pulse (BVP) and heart rate were recorded by the watch and were labelled as occurring during stress-inducing tasks or a rest period (no stress). Additionally, respiratory rate was estimated using the BVP signal. Statistical models and personalised adaptive reference ranges were used to determine the utility of the proposed stressors and the extracted variables (heart rate and respiratory rate). The analysis showed that the interview session was the most significant stress stimulus, causing a significant variation in heart rate of 27 (77%) participants and respiratory rate of 28 (80%) participants out of 35. The outcomes of this study contribute to the understanding the role of stressors and their association with physiological response and provide a dataset to help develop new wearable solutions for more reliable, valid, and sensitive physio-logical stress monitoring

대규모 인구 모델과 단일 가슴 착용형 장치를 활용한 비침습적 연속 동맥 혈압 모니터링 시스템

학위논문 (박사) -- 서울대학교 대학원 : 공과대학 협동과정 바이오엔지니어링전공, 2021. 2. 김희찬.최근 수십 년 동안 비침습적 연속 혈압 모니터링에 대한 필요성이 점차 대두되면서 맥파 전달 시간, 맥파 도달 시간, 또는 광용적맥파의 파형으로부터 추출된 다양한 특징들을 이용한 혈압 추정 연구들이 전세계적으로 활발하게 진행되었다. 하지만 대부분의 연구들은 국제 혈압 표준을 만족시키지 못하는 매우 적은 수의 피험자들 만을 대상으로 주로 혈압 추정 모델을 개발 및 검증하였기 때문에 성능의 정확도가 적절하게 검증되지 못했다는 한계점이 있었고, 또한 혈압 추정 파라미터 추출을 위한 생체 신호들을 측정하기 위해 대부분 두 개 이상의 모듈을 필요로 하면서 실용성 측면에서 한계점이 있었다. 첫 번째 연구는 대규모 생체신호 데이터베이스들을 분석함으로써 임상적으로 허용 가능한 수준의 정확도가 적절히 검증된 혈압 추정 모델을 개발하는 것을 목적으로 진행되었다. 본 연구에서는 1376명의 수술 중 환자들의 약 250만 심박 주기에 대해 측정된 두 가지 비침습적 생체신호인 심전도와 광용적맥파를 활용한 혈압 추정 방식들을 분석하였다. 맥파 도달 시간, 심박수, 그리고 다양한 광용적맥파 파형 피처들을 포함하는 총 42 종류의 파라미터들을 대상으로 피처 선택 기법들을 적용한 결과, 28개의 피처들이 혈압 추정 파라미터로 결정되었고, 특히 두 가지 광용적맥파 피처들이 기존에 혈압 추정 파라미터로 가장 주요하게 활용되었던 맥파 도달 시간보다 우월한 파라미터들로 분석되었다. 선정된 파라미터들을 활용하여 혈압의 낮은 주파수 성분을 인공신경망으로 모델링하고, 높은 주파수 성분을 순환신경망으로 모델링 한 결과, 수축기 혈압 에러율 0.05 ± 6.92 mmHg와 이완기 혈압 에러율 -0.05 ± 3.99 mmHg 정도의 높은 정확도를 달성하였다. 또 다른 생체신호 데이터베이스에서 추출한 334명의 중환자들을 대상으로 모델을 외부 검증했을 때 유사한 결과를 획득하면서 세 가지 대표적 혈압 측정 장비 기준들을 모두 만족시켰다. 해당 결과를 통해 제안된 혈압 추정 모델이 1000명 이상의 다양한 피험자들을 대상으로 적용 가능함을 확인하였다. 두 번째 연구는 일상 생활 중 장기간 모니터링이 가능한 단일 착용형 혈압 모니터링 시스템을 개발하는 것을 목적으로 진행되었다. 대부분의 기존 혈압 추정 연구들은 혈압 추정 파라미터 추출을 위해 필요한 생체신호들을 측정하기 위해 두 군데 이상의 신체 지점에 두 개 이상의 모듈을 부착하는 등 실용성 측면에서 한계를 나타냈다. 이를 해결하기 위해 본 연구에서는 심전도와 광용적맥파를 동시에 연속적으로 측정하는 단일 가슴 착용형 디바이스를 개발하였고, 개발된 디바이스를 대상으로 총 25명의 건강한 피험자들로부터 데이터를 획득하였다. 손가락에서 측정된 광용적맥파와 가슴에서 측정된 광용적맥파 간 파형의 특성에 유의미한 차이가 있기 때문에 가슴에서 측정된 광용적맥파에서 추출된 피처들을 대응되는 손가락에서 측정된 광용적맥파 피처들로 특성을 변환하는 전달 함수 모델을 개발하였다. 25명으로부터 획득한 데이터에 전달 함수 모델을 적용시킨 후 혈압 추정 모델을 검증한 결과, 수축기 혈압 에러율 0.54 ± 7.47 mmHg와 이완기 혈압 에러율 0.29 ± 4.33 mmHg로 나타나면서 세 가지 혈압 측정 장비 기준들을 모두 만족시켰다. 결론적으로 본 연구에서는 임상적으로 허용 가능한 수준의 정확도로 장기간 일상 생활이 가능한 비침습적 연속 동맥 혈압 모니터링 시스템을 개발하고 다수의 데이터셋을 대상으로 검증함으로써 고혈압 조기 진단 및 예방을 위한 모바일 헬스케어 서비스의 가능성을 확인하였다.As non-invasive continuous blood pressure monitoring (NCBPM) has gained wide attraction in the recent decades, many studies on blood pressure (BP) estimation using pulse transit time (PTT), pulse arrival time (PAT), and characteristics extracted from the morphology of photoplethysmogram (PPG) waveform as indicators of BP have been conducted. However, most of the studies have used small homogeneous subject pools to generate models of BP, which led to inconsistent results in terms of accuracy. Furthermore, the previously proposed modalities to measure BP indicators are questionable in terms of practicality, and lack the potential for being utilized in daily life. The first goal of this thesis is to develop a BP estimation model with clinically valid accuracy using a large pool of heterogeneous subjects undergoing various surgeries. This study presents analyses of BP estimation methods using 2.4 million cardiac cycles of two commonly used non-invasive biosignals, electrocardiogram (ECG) and PPG, from 1376 surgical patients. Feature selection methods were used to determine the best subset of predictors from a total of 42 including PAT, heart rate, and various PPG morphology features. BP estimation models were constructed using linear regression, random forest, artificial neural network (ANN), and recurrent neural network (RNN), and the performances were evaluated. 28 features out of 42 were determined as suitable for BP estimation, in particular two PPG morphology features outperformed PAT, which has been conventionally seen as the best non-invasive indicator of BP. By modelling the low frequency component of BP using ANN and the high frequency component using RNN with the selected predictors, mean errors of 0.05 ± 6.92 mmHg for systolic blood pressure (SBP), and -0.05 ± 3.99 mmHg for diastolic blood pressure (DBP) were achieved. External validation of the model using another biosignal database consisting of 334 intensive care unit patients led to similar results, satisfying three international standards concerning the accuracy of BP monitors. The results indicate that the proposed method can be applied to large number of subjects and various subject phenotypes. The second goal of this thesis is to develop a wearable BP monitoring system, which facilitates NCBPM in daily life. Most previous studies used two or more modules with bulky electrodes to measure biosignals such as ECG and PPG for extracting BP indicators. In this study, a single wireless chest-worn device measuring ECG and PPG simultaneously was developed. Biosignal data from 25 healthy subjects measured by the developed device were acquired, and the BP estimation model developed above was tested on this data after applying a transfer function mapping the chest PPG morphology features to the corresponding finger PPG morphology features. The model yielded mean errors of 0.54 ± 7.47 mmHg for SBP, and 0.29 ± 4.33 mmHg for DBP, again satisfying the three standards for the accuracy of BP monitors. The results indicate that the proposed system can be a stepping stone to the realization of mobile NCBPM in daily life. In conclusion, the clinical validity of the proposed system was checked in three different datasets, and it is a practical solution to NCBPM due to its non-occlusive form as a single wearable device.Abstract i Contents iv List of Tables vii List of Figures viii Chapter 1 General Introduction 1 1.1 Need for Non-invasive Continuous Blood Pressure Monitoring (NCBPM) 2 1.2 Previous Studies for NCBPM 5 1.3 Issues with Previous Studies 9 1.4 Thesis Objectives 12 Chapter 2 Non-invasive Continuous Arterial Blood Pressure Estimation Model in Large Population 14 2.1 Introduction 15 2.1.1 Electrocardiogram (ECG) and Photoplethysmogram (PPG) Features for Blood Pressure (BP) Estimation 15 2.1.2 Description of Surgical Biosignal Databases 16 2.2 Feature Analysis 19 2.2.1 Data Acquisition and Data Pre-processing 19 2.2.2 Feature Extraction 25 2.2.3 Feature Selection 35 2.3 Construction of the BP Estimation Models 44 2.3.1 Frequency Component Separation 44 2.3.2 Modelling Algorithms 47 2.3.3 Summary of Training and Validation 52 2.4 Results and Discussion 54 2.4.1 Feature Analysis 54 2.4.1.1 Pulse Arrival Time versus Pulse Transit Time 54 2.4.1.2 Feature Selection 57 2.4.2 Optimization of the BP Estimation Models 63 2.4.2.1 Frequency Component Separation 63 2.4.2.2 Modelling Algorithms 66 2.4.2.3 Comparison against Different Modelling Settings 68 2.4.3 Performance of the Best-case BP Estimation Model 69 2.4.4 Limitations 75 2.5 Conclusion 78 Chapter 3 Development of the Single Chest-worn Device for Non-invasive Continuous Arterial Blood Pressure Monitoring 80 3.1 Introduction 81 3.2 Development of the Single Chest-worn Device 84 3.2.1 Hardware Development 84 3.2.2 Software Development 90 3.2.3 Clinical Trial 92 3.3 Development of the Transfer Function 95 3.3.1 Finger PPG versus Chest PPG 95 3.3.2 The Concept of the Transfer Function 97 3.3.3 Data Acquisition for Modelling of the Transfer Function 98 3.4 Results and Discussion 100 3.4.1 Construction of the Transfer Function 100 3.4.2 Test of the BP Estimation Model 101 3.4.3 Comparison with the Previous Study using the Single Chest-worn Device 104 3.4.4 Limitations 106 3.5 Conclusion 108 Chapter 4 Thesis Summary and Future Direction 109 4.1 Summary and Contributions 110 4.2 Future Work 113 Bibliography 115 Abstract in Korean 129 Acknowledgement 132Docto

Cuffless bood pressure estimation

L'hypertension est une maladie qui affecte plus d'un milliard de personnes dans le monde. Il s'agit d'une des principales causes de décès; le suivi et la gestion de cette maladie sont donc cruciaux. La technologie de mesure de la pression artérielle la plus répandue, utilisant le brassard pressurisé, ne permet cependant pas un suivi en continu de la pression, ce qui limite l'étendue de son utilisation. Ces obstacles pourraient être surmontés par la mesure indirecte de la pression par l'entremise de l'électrocardiographie ou de la photopléthysmographie, qui se prêtent à la création d'appareils portables, confortables et peu coûteux. Ce travail de recherche, réalisé en collaboration avec le département d'ingénierie biomédicale de l'université de Lund, en Suède, porte principalement sur la base de données publique Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) Waveform Datasetde PhysioNet, largement utilisée dans la littérature portant sur le développement et la validation d'algorithmes d'estimation de la pression artérielle sans brassard pressurisé. Puisque ces données proviennent d'unités de soins intensifs et ont été recueillies dans des conditions non contrôlées, plusieurs chercheurs ont avancé que les modèles d'estimation de la pression artérielle se basant sur ces données ne sont pas valides pour la population générale. Pour la première fois dans la littérature, cette hypothèse est ici mise à l'épreuve en comparant les données de MIMIC à un ensemble de données de référence plus représentatif de la population générale et recueilli selon une procédure expérimentale bien définie. Des tests statistiques révèlent une différence significative entre les ensembles de données, ainsi qu'une réponse différente aux changements de pression artérielle, et ce, pour la majorité des caractéristiques extraites du photopléthysmogramme. De plus, les répercussions de ces différences sont démontrées à l'aide d'un test pratique d'estimation de la pression artérielle par apprentissage machine. En effet, un modèle entraîné sur l'un des ensembles de données perd en grande partie sa capacité prédictive lorsque validé sur l'autre ensemble, par rapport à sa performance en validation croisée sur l'ensemble d'entraînement. Ces résultats constituent les contributions principales de ce travail et ont été soumis sous forme d'article à la revue Physiological Measurement. Un volet additionnel de la recherche portant sur l'analyse du pouls par décomposition (pulse de composition analysis ou PDA) est présenté dans un deuxième temps. La PDA est une technique permettant de séparer l'onde du pouls en une composante excitative et ses réflexions, utilisée pour extraire des caractéristiques du signal dans le contexte de l'estimation de la pression artérielle. Les résultats obtenus démontrent que l'estimation de la position temporelle des réflexions à partir de points de référence de la dérivée seconde du signal donne d'aussi bons résultats que leur détermination par la méthode traditionnelle d'approximation successive, tout en étant beaucoup plus rapide. Une méthode récursive rapide de PDA est également étudiée, mais démontrée comme inadéquate dans un contexte de comparaison intersujet.Hypertension affects more than one billion people worldwide. As one of the leading causes of death, tracking and management of the condition is critical, but is impeded by the current cuff-based blood pressure monitoring technology. Continuous and more ubiquitous blood pressure monitoring may be achieved through simpler, cheaper and less invasive cuff-less devices, performing an indirect measure through electrocardiography or photoplethysmography. Produced in collaboration with the department of biomedical engineering of Lund Universityin Sweden, this work focuses on public data that has been widely used in the literature to develop and validate cuffless blood pressure estimation algorithms: The Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) Waveform Dataset from PhysioNet. Because it is sourced from intensive care units and collected in absence of controlled conditions, it has many times been hypothesized that blood pressure estimation models based on its data may not generalize to the normal population. This work tests that hypothesis for the first time by comparing the MIMIC dataset to another reference dataset more representative of the general population and obtained under controlled experimental conditions. Through statistical testing, a majority of photoplethysmogram based features extracted from MIMIC are shown to differ significantly from the reference dataset and to respond differently to blood pressure changes. In addition, the practical impact of those differences is tested through the training and cross validating of machine learning models on both datasets, demonstrating an acute loss of predictive powers of models facing data from outside the dataset used in the training phase. As the main contribution of this work, these findings have been submitted as a journal paper to Physiological Measurement. Additional original research is also presented in relation to pulse decomposition analysis (PDA), a technique used to separate the pulse wave from its reflections, in the context of blood pressure estimation. The results obtained through this work show that when using the timing of reflections as part of blood pressure predictors, estimating those timings from fiducial points in the second derivative works as well as using the traditional and computationally costly successive approximation PDA method, while being many times faster. An alternative fast recursive PDA algorithm is also presented and shown to perform inadequately in an inter-subject comparison context