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Background and Objective Chronic obstructive pulmonary disease (COPD) requires a multifactorial assessment, evaluating the airflow limitation and symptoms of the patients. The 6-min walk test (6MWT) is commonly used to evaluate the functional exercise capacity in these patients. This study aims to propose a novel predictive model of the major 6MWT outcomes for COPD assessment, without physical performance measurements. Methods Cardiopulmonary and clinical parameters were obtained from fifty COPD patients. These parameters were used as inputs of a Bayesian network (BN), which integrated three multivariate models including the 6-min walking distance (6MWD), the maximum HR (HRmax) after the walking, and the HR decay 3 min after (HRR3). The use of BN allows the assessment of the patients’ status by predicting the 6MWT outcomes, but also inferring disease severity parameters based on actual patient's 6MWT outcomes. Results Firstly, the correlation obtained between the estimated and actual 6MWT measures was strong (R = 0.84, MAPE = 8.10% for HRmax) and moderate (R = 0.58, MAPE = 15.43% for 6MWD and R = 0.58, MAPE = 32.49% for HRR3), improving the classical methods to estimate 6MWD. Secondly, the classification of disease severity showed an accuracy of 78.3% using three severity groups, which increased up to 84.4% for two defined severity groups. Conclusions We propose a powerful two-way assessment tool for COPD patients, capable of predicting 6MWT outcomes without the need for an actual walking exercise. This model-based tool opens the way to implement a continuous monitoring system for COPD patients at home and to provide more personalized care., Peer Reviewed, Postprint (published version)

Objective. Impaired trunk stability is frequent in spinal cord injury (SCI), but there is a lack of quantitative measures for assessing trunk function. Our objectives were to: (a) evaluate trunk muscle activity and movement patterns during a reaching task in SCI patients, (b) compare the impact of cervical (cSCI) and thoracic (tSCI) injuries in trunk function, and (c) investigate the effects of a startling acoustic stimulus (SAS) in these patients. Approach. Electromyographic (EMG) and smartphone accelerometer data were recorded from 15 cSCI patients, nine tSCI patients, and 24 healthy controls, during a reaching task requiring trunk tilting. We calculated the response time (RespT) until pressing a target button, EMG onset latencies and amplitudes, and trunk tilt, lateral deviation, and other movement features from accelerometry. Statistical analysis was applied to analyze the effects of group (cSCI, tSCI, control) and condition (SAS, non-SAS) in each outcome measure. Main results. SCI patients, especially those with cSCI, presented significantly longer RespT and EMG onset latencies than controls. Moreover, in SCI patients, forward trunk tilt was accompanied by significant lateral deviation. RespT and EMG latencies were remarkably shortened by the SAS (the so-called StartReact effect) in tSCI patients and controls, but not in cSCI patients, who also showed higher variability. Significance. The combination of EMG and smartphone accelerometer data can provide quantitative measures for the assessment of trunk function in SCI. Our results show deficits in postural control and compensatory strategies employed by SCI patients, including delayed responses and higher lateral deviations, possibly to improve sitting balance. This is the first study investigating the StartReact responses in trunk muscles in SCI patients and shows that the SAS significantly accelerates RespT in tSCI, but not in cSCI, suggesting an increased cortical control exerted by these patients., Peer Reviewed, Postprint (published version)

© 2021 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting /republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works, Many studies have focused on novel noninvasive techniques to monitor respiratory rate such as bioimpedance. We propose an algorithm to detect respiratory phases using wearable bioimpedance to compute time parameters like respiratory rate, inspiratory and expiratory times, and duty cycle. The proposed algorithm was compared with two other algorithms from literature designed to estimate the respiratory rate using physiological signals like bioimpedance. We acquired bioimpedance and airflow from 50 chronic obstructive pulmonary disease (COPD) patients during an inspiratory loading protocol. We compared performance of the algorithms by computing accuracy and mean average percentage error (MAPE) between the bioimpedance parameters and the reference parameters from airflow. We found similar performance for the three algorithms in terms of accuracy (>0.96) and respiratory time and rate errors (<3.42 %). However, the proposed algorithm showed lower MAPE in duty cycle (10.18 %), inspiratory time (10.65 %) and expiratory time (8.61 %). Furthermore, only the proposed algorithm kept the statistical differences in duty cycle between COPD severity levels that were observed using airflow. Accordingly, we suggest bioimpedance to monitor breathing pattern parameters in home situations.Clinical relevance— This study exhibits the suitability of wearable thoracic bioimpedance to detect respiratory phases and to compute accurate breathing pattern parameters., Peer Reviewed, Postprint (author's final draft)

Intermittent hypoxia (IH) produces autonomic dysfunction that promotes the development of arrhythmia and hypertension in patients with obstructive sleep apnea (OSA). This paper investigated different heart rate variability (HRV) indices in the context of IH using a rat model for OSA. Linear and non-linear HRV parameters were assessed from ultra-short (15-s segments) and short-term (5 min) analyses of heartbeat time-series. Transient changes observed from pre-apnea segments to hypoxia episodes were evaluated, besides the relative and global impact of IH, as a function of its severity. Results showed an overall increase in ultra-short HRV markers as immediate response to hypoxia: standard deviation of normal RR intervals, SDNN = 1.2 ms (IQR: 1.1-2.1) vs 1.4 ms (IQR: 1.2-2.2), p = 0.015; root mean square of the successive differences, RMSSD = 1.7 ms (IQR: 1.5-2.2) vs 1.9 ms (IQR: 1.6-2.4), p = 0.031. The power in the very low frequency (VLF) band also showed a significant increase: 0.09 ms 2 (IQR: 0.05-0.20) vs 0.16 ms 2 (IQR: 0.12-0.23), p = 0.016, probably associated with the potentiation of the carotid body chemo-sensory response to hypoxia. Moreover, a clear link between severity of IH and short-term HRV measures was found in VLF and LF power, besides their progressive increase seen throughout the experiment after each apnea sequence. However, only those markers quantifying fragmentation levels in RR series were significantly affected when the experiment ended, as compared to baseline measures: percentage of inflection points, PIP = 49% (IQR: 45-51) vs 53% (IQR: 47-53), p = 0.031; percentage of short (geq 3 RR intervals) accelerated/decelerated segments, PSS = 75% (IQR: 51-81) vs 87% (IQR: 51-90), p = 0.046. These findings suggest a significant deterioration of cardiac rhythm with a more erratic behavior beyond the normal sinus arrhythmia, that may lead to a future cardiac condition., Peer Reviewed, Postprint (published version)

Patients with spinal cord injury (SCI) have an increased risk of sleep-disordered breathing (SDB), which can lead to serious comorbidities and impact patients’ recovery and quality of life. However, sleep tests are rarely performed on SCI patients, given their multiple health needs and the cost and complexity of diagnostic equipment. The objective of this study was to use a novel smartphone system as a simple non-invasive tool to monitor SDB in SCI patients. We recorded pulse oximetry, acoustic, and accelerometer data using a smartphone during overnight tests in 19 SCI patients and 19 able-bodied controls. Then, we analyzed these signals with automatic algorithms to detect desaturation, apnea, and hypopnea events and monitor sleep position. The apnea–hypopnea index (AHI) was significantly higher in SCI patients than controls (25 ± 15 vs. 9 ± 7, p < 0.001). We found that 63% of SCI patients had moderate-to-severe SDB (AHI = 15) in contrast to 21% of control subjects. Most SCI patients slept predominantly in supine position, but an increased occurrence of events in supine position was only observed for eight patients. This study highlights the problem of SDB in SCI and provides simple cost-effective sleep monitoring tools to facilitate the detection, understanding, and management of SDB in SCI patients., Peer Reviewed, Postprint (published version)

Poor sleep quality is a risk factor for multiple mental, cardiovascular, and cerebrovascular diseases. Certain sleep positions or excessive position changes can be related to some diseases and poor sleep quality. Nevertheless, sleep position is usually classified into four discrete values: supine, prone, left and right. An increase in sleep position resolution is necessary to better assess sleep position dynamics and to interpret more accurately intermediate sleep positions. This research aims to study the feasibility of smartphones as sleep position monitors by (1) developing algorithms to retrieve the sleep position angle from smartphone accelerometry; (2) monitoring the sleep position angle in patients with obstructive sleep apnea (OSA); (3) comparing the discretized sleep angle versus the four classic sleep positions obtained by the video-validated polysomnography (PSG); and (4) analyzing the presence of positional OSA (pOSA) related to its sleep angle of occurrence. Results from 19 OSA patients reveal that a higher resolution sleep position would help to better diagnose and treat patients with position-dependent diseases such as pOSA. They also show that smartphones are promising mHealth tools for enhanced position monitoring at hospitals and home, as they can provide sleep position with higher resolution than the gold-standard video-validated PSG., Peer Reviewed, Postprint (published version)

Poor sleep quality or disturbed sleep is associated with multiple health conditions. Sleep position affects the severity and occurrence of these complications, and positional therapy is one of the less invasive treatments to deal with them. Sleep positions can be self-reported, which is unreliable, or determined by using specific devices, such as polysomnography, polygraphy or cameras, that can be expensive and difficult to employ at home. The aim of this study is to determine how smartphones could be used to monitor and treat sleep position at home. We divided our research into three tasks: (1) develop an Android smartphone application (‘SleepPos’ app) which monitors angle-based high-resolution sleep position and allows to simultaneously apply positional treatment; (2) test the smartphone application at home coupled with a pulse oximeter; and (3) explore the potential of this tool to detect the positional occurrence of desaturation events. The results show how the ‘SleepPos’ app successfully determined the sleep position and revealed positional patterns of occurrence of desaturation events. The ‘SleepPos’ app also succeeded in applying positional therapy and preventing the subjects from sleeping in the supine sleep position. This study demonstrates how smartphones are capable of reliably monitoring high-resolution sleep position and provide useful clinical information about the positional occurrence of desaturation events., Peer Reviewed, Postprint (published version)

Patients suffering from obstructive sleep apnea (OSA) usually present an increased sympathetic activity caused by the intermittent hypoxia effect on autonomic control. This study evaluated the relationship between sleep stages and the apnea duration, frequency, and type, as well as their impact on HRV markers in different groups of disease severity. The hypnogram and R-R interval signals were extracted in 81 OSA patients from night polysomnographic (PSG) recordings. The apnea-hypopnea index (AHI) defined patient classification as mild-moderate (AHI<=30, n=44) or severe (AHI>30, n=37). The normalized power in VLH, LF, and HF bands of RR series were estimated by a time-frequency approach and averaged in 1-min epochs of normal and apnea segments. The autonomic response and the impact of sleep stages were assessed in both segments to compare patient groups. Deeper sleep stages (particularly S2) concentrated the shorter and mild apnea episodes (from 10 to 40 s) compared to light (SWS) and REM sleep. Longer episodes (>50 s) although less frequent, were of similar incidence in all stages. This pattern was more pronounced for the group of severe patients. Moreover, during apnea segments, LF nu was higher (p=0.044) for the severe group, since V LF nu and HF nu presented the greatest changes when compared to normal segments. The non-REM sleep seems to better differentiate OSA patients groups, particularly through VLF nu and HF nu (p<0.001). A significant difference in both sympathetic and vagal modulation between REM and non-REM sleep was only found within the severe group. These results confirm the importance of considering sleep stages for HRV analysis to further assess OSA disease severity, beyond the traditional and clinically limited AHI values.Clinical relevance—Accounting for sleep stages during HRV analysis could better assess disease severity in OSA patients., Peer Reviewed, Postprint (published version)

This study aims to investigate noninvasive indices of neuromechanical coupling (NMC) and mechanical efficiency (MEff) of parasternal intercostal muscles. Gold standard assessment of diaphragm NMC requires using invasive techniques, limiting the utility of this procedure. Noninvasive NMC indices of parasternal intercostal muscles can be calculated using surface mechanomyography (sMMGpara) and electromyography (sEMGpara). However, the use of sMMGpara as an inspiratory muscle mechanical output measure, and the relationships between sMMGpara, sEMGpara, and simultaneous invasive and noninvasive pressure measurements have not previously been evaluated. sEMGpara, sMMGpara, and both invasive and noninvasive measurements of pressures were recorded in twelve healthy subjects during an inspiratory loading protocol. The ratios of sMMGpara to sEMGpara, which provided muscle-specific noninvasive NMC indices of parasternal intercostal muscles, showed nonsignificant changes with increasing load, since the relationships between sMMGpara and sEMGpara were linear (R2 = 0.85 (0.75–0.9)). The ratios of mouth pressure (Pmo) to sEMGpara and sMMGpara were also proposed as noninvasive indices of parasternal intercostal muscle NMC and MEff, respectively. These indices, similar to the analogous indices calculated using invasive transdiaphragmatic and esophageal pressures, showed nonsignificant changes during threshold loading, since the relationships between Pmo and both sEMGpara (R2 = 0.84 (0.77–0.93)) and sMMGpara (R2 = 0.89 (0.85–0.91)) were linear. The proposed noninvasive NMC and MEff indices of parasternal intercostal muscles may be of potential clinical value, particularly for the regular assessment of patients with disordered respiratory mechanics using noninvasive wearable and wireless devices., Peer Reviewed, Postprint (published version)

© 2021 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting /republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works, Obstructive sleep apnea (OSA) is a sleep disorder in which repetitive upper airway obstructive events occur during sleep. These events can induce hypoxia, which is a risk factor for multiple cardiovascular and cerebrovascular diseases. Chronic obstructive pulmonary disease (COPD) is a disorder which induces a persistent inflammation of the lungs. This condition produces hypoventilation, affecting the blood oxygenation, and leads to an increased risk of developing lung cancer and heart disease. In this study, we evaluated how COPD affects the severity and characteristics of OSA in a multivariate demographic database including polysomnographic signals. Results showed SpO2 subtle variations, such as more non-recovered desaturations and increased time below a 90% SpO2 level, which, in the long term, could worsen the risk to suffer cardiovascular and cerebrovascular diseases., Peer Reviewed, Postprint (author's final draft)

© 2021 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting /republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works, Fixed sample entropy (fSampEn) is a promising technique for the analysis of respiratory electromyographic (EMG) signals. Its use has shown outperformance of amplitude-based estimators such as the root mean square (RMS) in the evaluation of respiratory EMG signals with cardiac noise and a high correlation with respiratory signals, allowing changes in respiratory muscle activity to be tracked. However, the relationship between the fSampEn response to a given muscle activation has not been investigated. The aim of this study was to analyze the nature of the fSampEn measurements that are produced as the EMG activity increases linearly. Simulated EMG signals were generated and increased linearly. The effect of the parameters r and the size of the moving window N of the fSampEn were evaluated and compared with those obtained using the RMS. The RMS showed a linear trend throughout the study. A non-linear, sigmoidal-like behavior was found when analyzing the EMG signals using the fSampEn. The lower the values of r, the higher the non-linearity observed in the fSampEn results. Greater moving windows reduced the variation produced by too small values of r., Peer Reviewed, Postprint (author's final draft)

© 2020 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting /republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works, Chronic Obstructive Pulmonary Disease (COPD) is one of the most common chronic conditions. The current assessment of COPD requires a maximal maneuver during a spirometry test to quantify airflow limitations of patients. Other less invasive measurements such as thoracic bioimpedance and myographic signals have been studied as an alternative to classical methods as they provide information about respiration. Particularly, strong correlations have been shown between thoracic bioimpedance and respiratory volume. The main objective of this study is to investigate bioimpedance and its combination with myographic parameters in COPD patients to assess the applicability in respiratory disease monitoring. We measured bioimpedance, surface electromyography and surface mechanomyography in forty-three COPD patients during an incremental inspiratory threshold loading protocol. We introduced two novel features that can be used to assess COPD condition derived from the variation of bioimpedance and the electrical and mechanical activity during each respiratory cycle. These features demonstrate significant differences between mild and severe patients, indicating a lower inspiratory contribution of the inspiratory muscles to global respiratory ventilation in the severest COPD patients. In conclusion, the combination of bioimpedance and myographic signals provides useful indices to noninvasively assess the breathing of COPD patients., Peer Reviewed, Postprint (updated version)

Surface electromyography (sEMG) can be used for the evaluation of respiratory muscle activity. Recording sEMG involves the use of surface electrodes in a bipolar configuration. However, electrocardiographic (ECG) interference and electrode orientation represent considerable drawbacks to bipolar acquisition. As an alternative, concentric ring electrodes (CREs) can be used for sEMG acquisition and offer great potential for the evaluation of respiratory muscle activity due to their enhanced spatial resolution and simple placement protocol, which does not depend on muscle fiber orientation. The aim of this work was to analyze the performance of CREs during respiratory sEMG acquisitions. Respiratory muscle sEMG was applied to the diaphragm and sternocleidomastoid muscles using a bipolar and a CRE configuration. Thirty-two subjects underwent four inspiratory load spontaneous breathing tests which was repeated after interchanging the electrode positions. We calculated parameters such as (1) spectral power and (2) median frequency during inspiration, and power ratios of inspiratory sEMG without ECG in relation to (3) basal sEMG without ECG (Rins/noise), (4) basal sEMG with ECG (Rins/cardio) and (5) expiratory sEMG without ECG (Rins/exp). Spectral power, Rins/noise and Rins/cardio increased with the inspiratory load. Significantly higher values (p <; 0.05) of Rins/cardio and significantly higher median frequencies were obtained for CREs. Rins/noise and Rins/exp were higher for the bipolar configuration only in diaphragm sEMG recordings, whereas no significant differences were found in the sternocleidomastoid recordings. Our results suggest that the evaluation of respiratory muscle activity by means of sEMG can benefit from the remarkably reduced influence of cardiac activity, the enhanced detection of the shift in frequency content and the axial isotropy of CREs which facilitates its placement., Peer Reviewed, Postprint (author's final draft)

Trunk stability is essential to maintain upright posture and support functional movements. In this study, we aimed to characterize the muscle activity and movement patterns of trunk flexion during an arm reaching task in sitting healthy subjects and investigate whether trunk stability is affected by a startling acoustic stimulus (SAS). For these purposes, we calculated the electromyographic (EMG) onset latencies and amplitude parameters in 8 trunk, neck, and shoulder muscles, and the tilt angle and movement features from smartphone accelerometer signals recorded during trunk bending in 33 healthy volunteers. Two-way repeated measures ANOVAs were applied to examine the effects of SAS and target distance (15 cm vs 30 cm). We found that SAS markedly reduced the response time and EMG onset latencies of all muscles, without changing neither movement duration nor muscle recruitment pattern. Longer durations, higher tilt angles, and higher EMG amplitudes were observed at 30 cm compared to 15 cm. The accelerometer signals had a higher frequency content in SAS trials, suggesting reduced movement control. The proposed measures have helped to establish the trunk flexion pattern in arm reaching in healthy subjects, which could be useful for future objective assessment of trunk stability in patients with neurological affections., Peer Reviewed, Postprint (published version)

Chronic obstructive pulmonary disease (COPD) patients exhibit impaired autonomic control which can be assessed by heart rate variability analysis. The study aims to evaluate the cardiac autonomic responses of COPD patients after completing a conventional six-minute walk test (6MWT). Fifty COPD patients were included in the study, for which an ECG signal (lead II) was acquired by a wearable device, before, during, and after the test. We used the heart rate (HR) time-series to assess the heart rate dynamic during recovery. The heart rate recovery (HRR) marker was evaluated every 5 s after the 6MWT and showed different dynamic trends among severity groups. We compared the HRR among patient groups classified according to the GOLD standard. Significantly larger normalized HRR values (nHRR) were found in mild COPD patients (n=23, GOLD={1,2}; nHRR1=14.8±7.5 %, nHRR2=18.6±8.1 %) compared to those with more disease severity (n=23, GOLD={3,4}; nHRR1=9.3±5.8 %, p=0.002; and nHRR2= 13.7±6.7 %, p=0.041). The largest differences were observed around the first 30 s of the recovery phase (nHRR=10.8±6.6 % vs. nHRR=5.6±4 % p=0.001). Our results showed a slower recovery for the severest patients, suggesting that cardiac parameters like the ones we propose here, may provide valuable information for a better characterization of COPD severity., Peer Reviewed, Postprint (published version)

Chronic obstructive pulmonary disease (COPD) patients exhibit depressed heart rate variability (HRV), while comorbidities may worsen the patients’ prognosis. We investigated whether HRV analyis, clinical markers of disease severity and respiratory function, may explain the presence of cardiac-related comorbidities. Several HRV indices were evaluated in 46 COPD patients before a 6-minute walk test (6MWT). Maximum heart rate (HRmax) and walked distance (Dist) were measured during the test, while heart rate recovery (HRR) was estimated immediately afterwards. All these features and the patient characteristics were used to identify cardiac-related comorbidities (COPDco, n=11). A logistic regression lassifier with regularization was used for modeling and feature selection, while model assessment was performed by leave-oneout cross-validation. Only 4 features were needed to accurately identify comorbidities with overall performance metrics AUC=84%, sensitivity=73% specificity=83%. The feature subset included the ratio given by the forced expiratory volume and the forced vital capacity ((FEV1/FVC), the normalized HRR at minute 3, the Borg-scale of exertional dyspnea and the normalized LF power. These features could provide relevant nformation for early identification of cardiac comorbidities in COPD patients., Peer Reviewed, Postprint (published version)

Background: Home hospitalization is widely accepted as a cost-effective alternative to conventional hospitalization for selected patients. A recent analysis of the home hospitalization and early discharge (HH/ED) program at Hospital Clínic de Barcelona over a 10-year period demonstrated high levels of acceptance by patients and professionals, as well as health value-based generation at the provider and health-system levels. However, health risk assessment was identified as an unmet need with the potential to enhance clinical decision making. Objective: The objective of this study is to generate and assess predictive models of mortality and in-hospital admission at entry and at HH/ED discharge. Methods: Predictive modeling of mortality and in-hospital admission was done in 2 different scenarios: at entry into the HH/ED program and at discharge, from January 2009 to December 2015. Multisource predictive variables, including standard clinical data, patients’ functional features, and population health risk assessment, were considered. Results: We studied 1925 HH/ED patients by applying a random forest classifier, as it showed the best performance. Average results of the area under the receiver operating characteristic curve (AUROC; sensitivity/specificity) for the prediction of mortality were 0.88 (0.81/0.76) and 0.89 (0.81/0.81) at entry and at home hospitalization discharge, respectively; the AUROC (sensitivity/specificity) values for in-hospital admission were 0.71 (0.67/0.64) and 0.70 (0.71/0.61) at entry and at home hospitalization discharge, respectively. Conclusions: The results showed potential for feeding clinical decision support systems aimed at supporting health professionals for inclusion of candidates into the HH/ED program, and have the capacity to guide transitions toward community-based care at HH discharge., Peer Reviewed, Postprint (published version)

Respiratory sounds yield pertinent information about respiratory function in both health and disease. Normal lung sound intensity is a characteristic that correlates well with airflow and it can therefore be used to quantify the airflow changes and limitations imposed by respiratory diseases. The dual aims of this study are firstly to establish whether previously reported asymmetries in normal lung sound intensity are affected by varying the inspiratory threshold load or the airflow of respiration, and secondly to investigate whether fixed sample entropy can be used as a valid measure of lung sound intensity. Respiratory sounds were acquired from twelve healthy individuals using four contact microphones on the posterior skin surface during an inspiratory threshold loading protocol and a varying airflow protocol. The spatial distribution of the normal lung sounds intensity was examined. During the protocols explored here the normal lung sound intensity in the left and right lungs in healthy populations was found to be similar, with asymmetries of less than 3 dB. This agrees with values reported in other studies. The fixed sample entropy of the respiratory sound signal was also calculated and compared with the gold standard root mean square representation of lung sound intensity showing good agreement., Postprint (author's final draft)

Obstructive sleep apnea (OSA) is a sleep disorder in which repetitive upper airway obstructive events occur during sleep. These events can induce hypoxia, which is a risk factor for multiple cardiovascular and cerebrovascular diseases. OSA is also known to be position-dependent in some patients, which is referred to as positional OSA (pOSA). Screening for pOSA is necessary in order to design more personalized and effective treatment strategies. In this article, we propose analyzing accelerometry signals, recorded with a smartphone, to detect and monitor OSA at home. Our objectives were to: (1) develop an algorithm for detecting thoracic movement associated with disordered breathing events; (2) compare the performance of smartphones as OSA monitoring tools with a type 3 portable sleep monitor; and (3) explore the feasibility of using smartphone accelerometry to retrieve reliable patient sleep position data and assess pOSA. Accelerometry signals were collected through simultaneous overnight acquisition using both devices with 13 subjects. The smartphone tool showed a high degree of concordance compared to the portable device and succeeded in estimating the apnea-hypopnea index (AHI) and classifying the severity level in most subjects. To assess the agreement between the two systems, an event-by-event comparison was performed, which found a sensitivity of 90% and a positive predictive value of 80%. It was also possible to identify pOSA by determining the ratio of events occurring in a specific position versus the time spent in that position during the night. These novel results suggest that smartphones are promising mHealth tools for OSA and pOSA monitoring at home., Peer Reviewed, Postprint (published version)

Reaching and grasping (R&G) is a skilled voluntary movement which is critical for animals. In this work, we aim to identify muscle synergy patterns from R&G movements in rats and show how these patterns can be used to characterize such movements and investigate their consistency and repeatability. For that purpose, we analyzed the electromyographic (EMG) activity of five forelimb muscles recorded while the animals were engaged in R&G tasks. Our dataset included 200 R&G attempts from three different rats. Non-negative matrix factorization was used to decompose EMG signals and extract muscle synergies. We compared all pairs of attempts and created cross-validated models to study intra- and inter-subject variability. We found that three synergies were enough to accurately reconstruct the EMG envelopes. These muscle synergies and their corresponding activation coefficients were very similar for all the attempts in the database, providing a general pattern to describe the movement. Results suggested that the movement strategy adopted by an individual in its different attempts was highly repetitive, but also resembled the strategies adopted by the other animals. Inter-subject variability was not much higher than intra-subject variability. This study is a proof-of-concept, but the proposed approaches can help to establish whether there is a stereotyped pattern of neuromuscular activity in R&G movement in healthy rats, and the changes that occur in animal models of acute neurological injuries. Research on muscle synergies could elucidate motor control mechanisms, and lead to quantitative tools for evaluating upper limb motor impairment after an injury, Peer Reviewed, Postprint (published version)

ung sound (LS) signals are often contaminated by impulsive artifacts that complicate the estimation of lung sound intensity (LSI) using conventional amplitude estimators. Fixed sample entropy (fSampEn) has proven to be robust to cardiac artifacts in myographic respiratory signals. Similarly, fSampEn is expected to be robust to artifacts in LS signals, thus providing accurate LSI estimates. However, the choice of fSampEn parameters depends on the application and fSampEn has not previously been applied to LS signals. This study aimed to perform an evaluation of the performance of the most relevant fSampEn parameters on LS signals, and to propose optimal fSampEn parameters for LSI estimation. Different combinations of fSampEn parameters were analyzed in LS signals recorded in a heterogeneous population of healthy subjects and chronic obstructive pulmonary disease patients during loaded breathing. The performance of fSampEn was assessed by means of its cross-covariance with flow signals, and optimal fSampEn parameters for LSI estimation were proposed., Postprint (author's final draft)

© 2020 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting /republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works, Neural respiratory drive as measured by the electromyography allows the study of the imbalance between the load on respiratory muscles and its capacity. Surface respiratory electromyography (sEMG) is a non-invasive tool used for indirectly assessment of NRD. It also provides a way to evaluate the level and pattern of respiratory muscle activation. The prevalence of electrocardiographic activity (ECG) in respiratory sEMG signals hinders its proper evaluation. Moreover, the occurrence of abnormal heartbeats or cardiac arrhythmias in respiratory sEMG measures can make even more challenging the NRD estimation. Respiratory sEMG can be evaluated using the fixed sample entropy (fSampEn), a technique which is less affected by cardiac artefacts. The aim of this work was to investigate the performance of the fSampEn, the root mean square (RMS) and the average rectified value (ARV) on respiratory sEMG signals with supraventricular arrhythmias (SVA) for NRD estimation. fSampEn, ARV and RMS parameters increased as the inspiratory load increased during the test. fSampEn was less influenced by ECG with SVAs for the NRD estimation showing a greater response to respiratory sEMG, reflected with a higher percentage increase with increasing load (228 % total increase, compared to 142 % and 135 % for ARV and RMS, respectively)., Peer Reviewed, Postprint (author's final draft)

this work, we evaluated a non-linear approach to estimate morphological variations in ECG depolarization, in the context of intermittent hypoxia (IH). Obstructive apnea sequences were provoked for 15 minutes in anesthetized Sprague-Dawley rats, alternating with equal periods of normal breathing, in a recurrent obstructive sleep apnea (OSA) model. Each apnea episode lasted 15 s, while the frequency used for each sequence was randomly selected. Average heartbeats obtained before the start and at the end of each episode, were delineated to extract only the QRS wave. Then, the segmented QRS waves were non-linearly aligned using the dynamic time warping (DWT) algorithm. Morphological QRS changes in both the amplitude and temporal domains were estimated from this alignment procedure. The hypoxic and basal segments were analyzed using ECG (lead I) recordings acquired during the experiment. To assess the effects of IH over time, the changes relative to the basal QRS wave were determined, in the intervals prior to each successive events until the end of the experiment. The results showed a progressive increase in the amplitude and time-domain morphological markers of the QRS wave along the experiment, which were strongly correlated with the changes in traditional QRS markers (r ˜ 0.9). Significant changes were found between pre-apnea and hypoxic measures only for the time-domain analysis (p<; 0.001), probably due to the short duration of the simulated apnea episodes. Clinical relevance Increased variability in ECG depolarization morphology during recurrent hypoxic episodes would be closely related to the expression of cardiovascular dysfunction in OSA patients., Peer Reviewed, Postprint (author's final draft)

© 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting /republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works, Cardiovascular diseases are one of the most common causes of death in elderly patients. The etiology of cardiomyopathies is difficult to discern clinically. The objective of this study was to classify cardiomyopathy patients using coupling analysis, through their cardiovascular behavior and the baroreflex response. A total of thirty-eight cardiomyopathy patients (CMP) classified as ischemic (ICM, 25 patients) and dilated (DCM, 13 patients) were analyzed. Thirty elderly control subjects (CON) were used as reference. Their electrocardiographic (ECG) and blood pressure (BP) signals were studied. To characterize the cardiovascular activity, the following temporal series were extracted: beat-to-beat intervals (from the ECG signal), and end- systolic and diastolic blood pressure amplitudes (from the BP signal). Non-linear characterization techniques like high resolution joint symbolic dynamics, segmented Poincaré plot analysis, normalized shorttime partial directed coherence, and dual sequence method were used to characterize these times series. The best indices were used to build support vector machine models for classification. The optimal model for ICM versus DCM patients achieved 84.2% accuracy, 76.9% sensitivity, and 88% specificity. When CMP patients and CON subjects were compared, the best model achieved 95.5% accuracy, 97.3% sensitivity, and 93.3% specificity. These results suggest a disfunction in the baroreflex mechanism in cardiomyopathies patients, Peer Reviewed, Postprint (author's final draft)

The electrical activity of the diaphragm measured by surface electromyography (sEMGdi) provides indirect information on neural respiratory drive. Moreover, it allows evaluating the ventilatory pattern from the onset and offset (ntoff) estimation of the neural inspiratory time. sEMGdi amplitude variation was quantified using the fixed sample entropy (fSampEn), a less sensitive method to the interference from cardiac activity. The detection of the ntoff is controversial, since it is located in an intermediate point between the maximum value and the cessation of sEMGdi inspiratory activity, evaluated by the fSampEn. In this work ntoff detection has been analyzed using thresholds between 40% and 100 % of the fSampEn peak. Furthermore, fSampEn was evaluated analyzing the r parameter from 0.05 to 0.6, using a m equal to 1 and a sliding window size equal to 250 ms. The ntoff has been compared to the offset time (toff) obtained from the airflow during a controlled respiratory protocol varying the fractional inspiratory time from 0.54 to 0.18 whilst the respiratory rate was constant at 16 bpm. Results show that the optimal threshold values were between 66.0 % to 77.0 % of the fSampEn peak value. r values between 0.25 to 0.50 were found suitable to be used with the fSampEn., Postprint (author's final draft)

© 2020 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting /republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works, Home hospitalization (HH) is presented as a healthcare alternative capable of providing high standards of care when patients no longer need hospital facilities. Although HH seems to lower healthcare costs by shortening hospital stays and improving patient's quality of life, the lack of continuous observation at home may lead to complications in some patients. Since blood tests have been proven to provide relevant prognosis information in many diseases, this paper analyzes the impact of different sampling methods on the prediction of HH outcomes. After a first exploratory analysis, some variables extracted from routine blood tests performed at the moment of HH admission, such as hemoglobin, lymphocytes or creatinine, were found to unmask statistically significant differences between patients undergoing successful and unsucessful HH stays. Then, predictive models were built with these data, in order to identify unsuccessful cases eventually needing hospital facilities. However, since these hospital admissions during HH programs are rare, their identification through conventional machine-learning approaches is challenging. Thus, several sampling strategies designed to face class imbalance were herein overviewed and compared. Among the analyzed approaches, over-sampling strategies, such as ROSE (Random Over-Sampling Examples) and conventional random over-sampling, showed the best performances. Nevertheless, further improvements should be proposed in the future so as to better identify those patients not benefiting from HH, Peer Reviewed, Postprint (author's final draft)

© 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting /republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works, Bioimpedance is known for its linear relation with volume during normal breathing. For that reason, bioimpedance can be used as a noninvasive and comfortable technique for measuring respiration. The goal of this study is to analyze the temporal behavior of bioimpedance measured in four different electrode configurations during inspiratory loaded breathing. We measured four bioimpedance channels and airflow simultaneously in 10 healthy subjects while incremental inspiratory loads were imposed. Inspiratory loading threshold protocols are associated with breathing pattern changes and were used in respiratory mechanics studies. Consequently, this respiratory protocol allowed us to induce breathing pattern changes and evaluate the temporal relationship of bioimpedance with volume. We estimated the temporal delay between bioimpedance and volume respiratory cycles to evaluate the differences in their temporal behavior. The delays were computed as the lag which maximize the cross-correlation of the signals cycle by cycle. Six of the ten subjects showed delays in at least two different inspiratory loads. The delays were dependent on electrode configuration, hence the appearance of the delays between bioimpedance and volume were conditioned to the location and geometry of the electrode configuration. In conclusion, the delays between these signals could provide information about breathing pattern when breathing conditions change., Peer Reviewed, Postprint (author's final draft)

Bioimpedance is an unobtrusive noninvasive technique to measure respiration and has a linear relation with volume during normal breathing. The objective of this paper was to assess this linear relation during inspiratory loading protocol and determine the best electrode configuration for bioimpedance measurement. The inspiratory load is a way to estimate inspiratory muscle function and has been widely used in studies of respiratory mechanics. Therefore, this protocol permitted us to evaluate bioimpedance performance under breathing pattern changes. We measured four electrode configurations of bioimpedance and airflow simultaneously in ten healthy subjects using a wearable device and a standard wired laboratory acquisition system, respectively. The subjects were asked to perform an incremental inspiratory threshold loading protocol during the measurements. The load values were selected to increase progressively until the 60% of the subject's maximal inspiratory pressure. The linear relation of the signals was assessed by Pearson correlation (r) and the waveform agreement by the mean absolute percentage error (MAPE), both computed cycle by cycle. The results showed a median greater than 0.965 in r coefficients and lower than 11 % in the MAPE values for the entire population in all loads and configurations. Thus, a strong linear relation was found during all loaded breathing and configurations. However, one out of the four electrode configurations showed robust results in terms of agreement with volume during the highest load. In conclusion, bioimpedance measurement using a wearable device is a noninvasive and a comfortable alternative to classical methods for monitoring respiratory diseases in normal and restrictive breathing., Postprint (published version)

© 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works., Obstructive sleep apnea (OSA) is a common disorder with a low diagnosis ratio, leaving many patients undiagnosed and untreated. In the last decades, accelerometry has been found to be a feasible solution to obtain respiratory activity and a potential tool to monitor OSA. On the other hand, many smartphone-based systems have already been developed to propose solutions for OSA monitoring and treatment. The objective of this work was to develop an automatic event detector based on smartphone accelerometry and pulse oximetry, and to assess its ability to detect thoracic movements. It was validated with a commercial OSA monitoring system at home. Results of this preliminary pilot study showed that the proposed event detector for accelerometry signals is a feasible tool to detect abnormal respiratory events, such as apneas and hypopneas, and has potential to be included in smartphone-based systems for OSA assessment., Postprint (published version)

© 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works., © 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works., EMG signals reflect the neuromuscular activation patterns related to the execution of a certain movement or task. In this work, we focus on reaching and grasping (R&G) movements in rats. Our objective is to develop an automatic algorithm to detect the onsets and offsets of muscle activity and use it to study muscle latencies in R&G maneuvers. We had a dataset of intramuscular EMG signals containing 51 R&G attempts from 2 different animals. Simultaneous video recordings were used for segmentation and comparison. We developed an automatic onset/offset detector based on the ratio of local maxima of Teager-Kaiser Energy (TKE). Then, we applied it to compute muscle latencies and other features related to the muscle activation pattern during R&G cycles. The automatic onsets that we found were consistent with visual inspection and video labels. Despite the variability between attempts and animals, the two rats shared a sequential pattern of muscle activations. Statistical tests confirmed the differences between the latencies of the studied muscles during R&G tasks. This work provides an automatic tool to detect EMG onsets and offsets and conducts a preliminary characterization of muscle activation during R&G movements in rats. This kind of approaches and data processing algorithms can facilitate the studies on upper limb motor control and motor impairment after spinal cord injury or stroke., Postprint (published version)

Obstructive Sleep Apnea severity is commonly determined after a sleep polysomnographic study by the Apnea-Hypopnea Index (AHI). This index does not contain information about the duration of events, and weights apneas and hypopneas alike. Significant differences in disease severity have been reported in patients with the same AHI. The aim of this work was to study the effect of obstructive event type and duration on the subsequent oxygen desaturation (SaO 2 ) by mixed-effects models. These models allow continuous and categorical independent variables and can model within-subject variability through random effects. The desaturation depth dSaO 2 , desaturation duration dtSaO 2 and desaturation area dSaO 2 A were analyzed in the 2022 apneas and hypopneas of eight severe patients. A mixed-effects model was defined to account for the influence of event duration (AD), event type, and their interaction on SaO 2 parameters. A two-step backward model reduction process was applied for random and fixed effects optimization. The optimum model obtained for dtSaO 2 suggests an almost subject-independent proportion increase with AD, which did not significantly change in apneas as compared to hypopneas. The optimum model for dSaO 2 reveals a significantly higher increase as a function of AD in apneas than hypopneas. Dependence of on event type and duration was different in every subject, and a subject-specific model could be obtained. The optimum model for SaO 2 A combines the effects of the other two. In conclusion, the proposed mixed-effects models for SaO 2 parameters allow to study the effect of respiratory event duration and type, and to include repeated events within each subject. This simple model can be easily extended to include the contribution of other important factors such as patient severity, sleep stage, sleeping position, or the presence of arousals., Postprint (published version)

Fixed sample entropy (fSampEn) has been successfully applied to myographic signals for inspiratory muscle activity estimation, attenuating interference from cardiac activity. However, several values have been suggested for fSampEn parameters depending on the application, and there is no consensus standard for optimum values. This study aimed to perform a thorough evaluation of the performance of the most relevant fSampEn parameters in myographic respiratory signals, and to propose, for the first time, a set of optimal general fSampEn parameters for a proper estimation of inspiratory muscle activity. Different combinations of fSampEn parameters were used to calculate fSampEn in both non-invasive and the gold standard invasive myographic respiratory signals. All signals were recorded in a heterogeneous population of healthy subjects and chronic obstructive pulmonary disease patients during loaded breathing, thus allowing the performance of fSampEn to be evaluated for a variety of inspiratory muscle activation levels. The performance of fSampEn was assessed by means of the cross-covariance of fSampEn time-series and both mouth and transdiaphragmatic pressures generated by inspiratory muscles. A set of optimal general fSampEn parameters was proposed, allowing fSampEn of different subjects to be compared and contributing to improving the assessment of inspiratory muscle activity in health and disease, Peer Reviewed, Postprint (published version)

© 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting /republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works, In this paper, a non-linear HRV analysis was performed to assess fragmentation signatures observed in heartbeat time series after intermittent hypoxia (IH). Three markers quantifying short-term fragmentation levels, PIP, IALS and PSS, were evaluated on R-R interval series obtained in a rat model of recurrent apnea. Through airway obstructions, apnea episodes were periodically simulated in six anesthetized Sprague-Dawley rats. The number of apnea events per hour (AHI index) was varied during the first half of the experiment while apnea episodes lasted 15 s. For the second part, apnea episodes lasted 5, 10 or 15 s, but the AHI index was fixed. Recurrent apnea was repeated for 15-min time intervals in all cases, alternating with basal periods of the same duration. The fragmentation markers were evaluated in segments of 5 minutes, selected at the beginning and end of the experiment. The impact of the heart and breathing rates (HR and BR, respectively) on the parameter estimates was also investigated. The results obtained show a significant increase (from 5 to 10%, p <; 0.05) in fragmentation measures of heartbeat time series after IH, indicating a clear deterioration of the initial conditions. Moreover, there was a strong linear relationship (r > 0.9) between these markers and BR, as well as with the ratio given by HR/BR. Although fragmentation may be impacted by IH, we found that it is highly dependent on HR and BR values and thus, they should be considered during its calculation or used to normalize the fragmentation estimates, Peer Reviewed, Postprint (published version)

Obstructive sleep apnea (OSA) is a prevalent disease, but most patients remain undiagnosed and untreated. Here we propose analyzing smartphone audio signals for screening OSA patients at home. Our objectives were to: (1) develop an algorithm for detecting silence events and classifying them into apneas or hypopneas; (2) evaluate the performance of this system; and (3) compare the information provided with a type 3 portable sleep monitor, based mainly on nasal airflow. Overnight signals were acquired simultaneously by both systems in 13 subjects (3 healthy subjects and 10 OSA patients). The sample entropy of audio signals was used to identify apnea/hypopnea events. The apnea-hypopnea indices predicted by the two systems presented a very high degree of concordance and the smartphone correctly detected and stratified all the OSA patients. An event-by-event comparison demonstrated good agreement between silence events and apnea/hypopnea events in the reference system (Sensitivity = 76%, Positive Predictive Value = 82%). Most apneas were detected (89%), but not so many hypopneas (61%). We observed that many hypopneas were accompanied by snoring, so there was no sound reduction. The apnea/hypopnea classification accuracy was 70%, but most discrepancies resulted from the inability of the nasal cannula of the reference device to record oral breathing. We provided a spectral characterization of oral and nasal breathing to correct this effect, and the classification accuracy increased to 82%. This novel knowledge from acoustic signals may be of great interest for clinical practice to develop new non-invasive techniques for screening and monitoring OSA patients at home, Peer Reviewed, Postprint (published version)

Continuous adventitious sounds (CAS) are commonly observed in obstructive pulmonary diseases and are of great clinical interest. However, their evaluation is generally subjective. We have previously developed an automatic CAS segmentation and classification algorithm for CAS recorded on the chest surface. The aim of this study is to establish whether these pulmonary CAS can be identified in a similar way using a tracheal microphone. Respiratory sounds were originally recorded from 25 participants using five contact microphones, four on the chest and one on the trachea, during three progressive respiratory maneuvers. In this work CAS component detection was performed on the tracheal channel using our automatic algorithm based on the Hilbert spectrum. The tracheal CAS detected were then compared to the previously analyzed pulmonary CAS. The sensitivity of CAS identification was lower at the tracheal microphone, with CAS that appeared simultaneously in all four pulmonary recordings more likely to be identified in the tracheal recordings. These observations could be due to the CAS being obscured by the lower SNR present in the tracheal recordings or not being transmitted through the airways to the trachea. Further work to optimize the algorithm for the tracheal recordings will be conducted in the future., Postprint (published version)

Using wearable devices in clinical routines could reduce healthcare costs and improve the quality of assessment in patients with chronic respiratory diseases. The purpose of this study is to evaluate the capability of a Shimmer3 wearable device device to extract reliable cardiorespiratory parameters from surface diaphragm electromyography (EMGdi). Twenty healthy volunteers underwent an incremental load respiratory test whilst EMGdi was recorded with a Shimmer3 wearable device (EMGdiW). Simultaneously, a second EMGdi (EMGdiL), the inspiratory mouth pressure (Pmouth) and the lead-I electrocardiogram (ECG) were recorded via a standard wired laboratory acquisition system. Different cardiorespiratory parameters have been extracted from both EMGdiW and EMGdiL signals.: heart rate, respiratory rate, respiratory muscle activity and mean frequency of EMGdi signals. Alongside these, similar parameters were also extracted from reference signals (Pmouth and ECG). High correlations were found between the data extracted from the EMGdiW and the reference signal data: heart rate (R = 0.947), respiratory rate (R = 0.940), respiratory muscle activity (R = 0.877), and mean frequency (R = 0.895). Moreover, similar increments in EMGdiW and EMGdiL activity were observed when Pmouth was raised, enabling the study of respiratory muscle activation. In summary, the Shimmer3 device is a promising and cost-effective solution for ambulatory monitoring of respiratory muscle function in chronic respiratory diseases., Postprint (author's final draft)

© 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting /republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works, Hypoxia induced by obstructive sleep apnea (OSA) leads to the deregulation of the autonomic nervous system (ANS), resulting in an abnormally increased sympathetic activity. Since ANS modulation varies throughout the night, notably for each sleep stage, the hypno-gram and heart rate signals of 81 OSA patients were collected during a polysomnography. They were classified as mild-moderate (n=44) or severe (n=37) based on their apnea-hypopnea index (AHI). Spectral heart rate variability (HRV) series were extracted by a time-frequency approach. These series were then averaged for each sleep stage, in order to compare the sympathetic modulation of mild-moderate and severe patients at the following phases: rapid eye movement (REM), S1, S2 and SWS (slow wave sleep). According to normalized power at the low-frequency band (LF nu ) values, severe OSA seems to be associated with an increased sympathetic modulation at non-REM sleep. Moreover, a decreased autonomic variability throughout the night may be related to a reduced adaptability of the cardiovascular system, characterizing a more advanced stage of the disease. These results provide further evidence for the role of autonomic alterations induced by hypoxia, suggesting the use of HRV analysis, together with AHI, for the study of OSA severity, Peer Reviewed, Postprint (author's final draft)

Diaphragm neuromechanical coupling (NMC), which reflects the efficiency of conversion of neural activation to transdiaphragmatic pressure (Pdi), is increasingly recognized to be a useful clinical index of diaphragm function and respiratory mechanics in neuromuscular weakness and cardiorespiratory disease. However, the current gold standard assessment of diaphragm NMC requires invasive measurements of Pdi and crural diaphragm electromyography (oesEMGdi), which complicates the measurement of diaphragm NMC in clinical practice. This is the first study to compare invasive measurements of diaphragm NMC (iNMC) using the relationship between Pdi and oesEMGdi, with noninvasive assessment of NMC (nNMC) using surface mechanomyography (sMMGlic) and electromyography (sEMGlic) of lower chest wall inspiratory muscles. Both invasive and noninvasive measurements were recorded in twelve healthy adult subjects during an inspiratory threshold loading protocol. A linear relationship between noninvasive sMMGlic and sEMGlic measurements was found, resulting in little change in nNMC with increasing inspiratory load. By contrast, a curvilinear relationship between invasive Pdi and oesEMGdi measurements was observed, such that there was a progressive increase in iNMC with increasing inspiratory threshold load. Progressive recruitment of lower ribcage muscles, serving to enhance the mechanical advantage of the diaphragm, may explain the more linear relationship between sMMGlic and sEMGlic (both representing lower intercostal plus costal diaphragm activity) than between Pdi and crural oesEMGdi. Noninvasive indices of NMC derived from sEMGlic and sMMGlic may prove to be useful indices of lower chest wall inspiratory muscle NMC, particularly in settings that do not have access to invasive measures of diaphragm function., Peer Reviewed, Postprint (published version)

Bioimpedance has been widely studied as alternative to respiratory monitoring methods because of its linear relationship with respiratory volume during normal breathing. However, other body tissues and fluids contribute to the bioimpedance measurement. The objective of this study is to investigate the relevance of chest movement in thoracic bioimpedance contributions to evaluate the applicability of bioimpedance for respiratory monitoring. We measured airflow, bioimpedance at four electrode configurations and thoracic accelerometer data in 10 healthy subjects during inspiratory loading. This protocol permitted us to study the contributions during different levels of inspiratory muscle activity. We used chest movement and volume signals to characterize the bioimpedance signal using linear mixed-effect models and neural networks for each subject and level of muscle activity. The performance was evaluated using the Mean Average Percentage Errors for each respiratory cycle. The lowest errors corresponded to the combination of chest movement and volume for both linear models and neural networks. Particularly, neural networks presented lower errors (median below 4.29%). At high levels of muscle activity, the differences in model performance indicated an increased contribution of chest movement to the bioimpedance signal. Accordingly, chest movement contributed substantially to bioimpedance measurement and more notably at high muscle activity levels., Peer Reviewed, Postprint (published version)

Cardiovascular diseases are one of the most common causes of death; however, the early detection of patients at high risk of sudden cardiac death (SCD) remains an issue. The aim of this study was to analyze the cardio-vascular couplings based on heart rate variability (HRV) and blood pressure variability (BPV) analyses in order to introduce new indices for noninvasive risk stratification in idiopathic dilated cardiomyopathy patients (IDC). High-resolution electrocardiogram (ECG) and continuous noninvasive blood pressure (BP) signals were recorded in 91 IDC patients and 49 healthy subjects (CON). The patients were stratified by their SCD risk as high risk (IDCHR) when after two years the subject either died or suffered life-threatening complications, and as low risk (IDCLR) when the subject remained stable during this period. Values were extracted from ECG and BP signals, the beat-to-beat interval, and systolic and diastolic blood pressure, and analyzed using the segmented Poincaré plot analysis (SPPA), the high-resolution joint symbolic dynamics (HRJSD) and the normalized short time partial directed coherence methods. Support vector machine (SVM) models were built to classify these patients according to SCD risk. IDCHR patients presented lowered HRV and increased BPV compared to both IDCLR patients and the control subjects, suggesting a decrease in their vagal activity and a compensation of sympathetic activity. Both, the cardio -systolic and -diastolic coupling strength was stronger in high-risk patients when comparing with low-risk patients. The cardio-systolic coupling analysis revealed that the systolic influence on heart rate gets weaker as the risk increases. The SVM IDCLR vs. IDCHR model achieved 98.9% accuracy with an area under the curve (AUC) of 0.96. The IDC and the CON groups obtained 93.6% and 0.94 accuracy and AUC, respectively. To simulate a circumstance in which the original status of the subject is unknown, a cascade model was built fusing the afore, Postprint (published version)

To optimize long-term nocturnal non-invasive ventilation in patients with chronic obstructive pulmonary disease, surface diaphragm electromyography (EMGdi) might be helpful to detect patient-ventilator asynchrony. However, visual analysis is labor-intensive and EMGdi is heavily corrupted by electrocardiographic (ECG) activity. Therefore, we developed an automatic method to detect inspiratory onset from EMGdi envelope using fixed sample entropy (fSE) and a dynamic threshold based on kernel density estimation (KDE). Moreover, we combined fSE with adaptive filtering techniques to reduce ECG interference and improve onset detection. The performance of EMGdi envelopes extracted by applying fSE and fSE with adaptive filtering was compared to the root mean square (RMS)-based envelope provided by the EMG acquisition device. Automatic onset detection accuracy, using these three envelopes, was evaluated through the root mean square error (RMSE) between the automatic and mean visual onsets (made by two observers). The fSE-based method provided lower RMSE, which was reduced from 298 ms to 264 ms when combined with adaptive filtering, compared to 301 ms provided by the RMS-based method. The RMSE was negatively correlated with the proposed EMGdi quality indices. Following further validation, fSE with KDE, combined with adaptive filtering when dealing with low quality EMGdi, indicates promise for detecting the neural onset of respiratory drive., Peer Reviewed, Postprint (published version)

Studies based on the cardiac and respiratory system have allowed a better knowledge of their behavior to contribute with the diagnosis and treatment of diseases associated with them. The main goal of this project was to analyze the behavior of the cardiorespiratory system in healthy subjects, depending on the body position. The electrocardiography and respiratory flow signals were recorded in two positions, supine and sitting. Each signal was analyzed considering sliding windows of 30 s, with and overlapping of 50%. Temporal and spectral features were extracted from each signal. A total of 187 features were extracted for each window. According to statistical analysis, 148 features showed significant differences when comparing the position of the subject. Afterwards, the classifications methods based on decision trees, k-nearest neighbor and support vector machines were applied to identify the best classification model. The most advantageous performance model was obtained with a linear support vector machine method, with an accuracy of 99.5%, a sensitivity of 99.2% and a specificity of 99.6%. In conclusion, we have observed that the position of the body (supine or sitting) could modulate the cardiac and respiratory system response. New statistical models might provide new tools to analyze the behavior of these systems and the cardiorespiratory interaction complexity, Peer Reviewed, Postprint (author's final draft)

© 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works., Obstructive sleep apnea (OSA) is a prevalent disease, but most patients remain undiagnosed and untreated. Recently, mHealth tools are being proposed to screen OSA patients at home. In this work, we analyzed full-night audio signals recorded with a smartphone microphone. Our objective was to develop an automatic detector to identify silence events (apneas or hypopneas) and compare its performance to a commercial portable system for OSA diagnosis (ApneaLink™, ResMed). To do that, we acquired signals from three subjects with both systems simultaneously. A sleep specialist marked the events on smartphone and ApneaLink signals. The automatic detector we developed, based on the sample entropy, identified silence events similarly than manual annotation. Compared to ApneaLink, it was very sensitive to apneas (detecting 86.2%) and presented an 83.4% positive predictive value, but it missed about half the hypopnea episodes. This suggests that during some hypopneas the flow reduction is not reflected in sound. Nevertheless, our detector accurately recognizes silence events, which can provide valuable respiratory information related to the disease. These preliminary results show that mHealth devices and simple microphones are promising non-invasive tools for personalized sleep disorders management at home, Postprint (published version)

In vitro surrogate models of human cardiac tissue hold great promise in disease modeling, cardiotoxicity testing, and future applications in regenerative medicine. However, the generation of engineered human cardiac constructs with tissue-like functionality is currently thwarted by difficulties in achieving efficient maturation at the cellular and/or tissular level. Here, we report on the design and implementation of a platform for the production of engineered cardiac macrotissues from human pluripotent stem cells (PSCs), which we term “CardioSlice.” PSC-derived cardiomyocytes, together with human fibroblasts, are seeded into large 3D porous scaffolds and cultured using a parallelized perfusion bioreactor with custom-made culture chambers. Continuous electrical stimulation for 2 weeks promotes cardiomyocyte alignment and synchronization, and the emergence of cardiac tissue-like properties. These include electrocardiogram-like signals that can be readily measured on the surface of CardioSlice constructs, and a response to proarrhythmic drugs that is predictive of their effect in human patients., Peer Reviewed, Postprint (published version)

© 2018 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting /republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works, This paper presents a 1.2 V 36 µW reconfigurable analog front-end (R-AFE) as a general-purpose low-cost IC for multiple-mode biomedical signals acquisition. The R-AFE efficiently reuses a reconfigurable preamplifier, a current generator (CG), and a mixed signal processing unit, having an area of 1.1 mm2 per R-AFE while supporting five acquisition modes to record different forms of cardiovascular and respiratory signals. The R-AFE can interface with voltage-, current-, impedance-, and light-sensors and hence can measure electrocardiography (ECG), bio-impedance (BioZ), photoplethysmogram (PPG), galvanic skin response (GSR), and general-purpose analog signals. Thanks to the chopper preamplifier and the low-noise CG utilizing dynamic element matching, the R-AFE mitigates 1/f noise from both the preamplifier and the CG for improved measurement sensitivity. The IC achieves competitive performance compared to the state-of-the-art dedicated readout ICs of ECG, BioZ, GSR, and PPG, but with approximately 1.4×-5.3× smaller chip area per channel., Peer Reviewed, Postprint (author's final draft)

The assessment of respiratory muscle activity by surface electromyography (sEMG) is a promising noninvasive technique for the diagnosis and monitoring of chronic obstructive pulmonary disease. The diaphragm is the most important muscle in breathing, although in forced inspiration other muscles, such as sternocleidomastoid, are activated and contribute to the respiratory process. The measurement of the sEMG in these muscles (sEMGdi and sEMGscm, respectively) by means of two electrodes in conventional bipolar configuration (BEs) is a common practice to evaluate the respiratory muscle activity and allows to indirectly quantify the level of muscular activation. However, the resulting signals are usually contaminated by electrocardiographic (ECG) activity, hindering the assessment of the activity of these muscles. sEMG signals can also be recorded using concentric ring electrodes (CREs). CREs have greater spatial resolution and attenuate distant bioelectrical interferences. In this scenario, the objective of this work has been to evaluate the applicability of CREs for the acquisition of sEMGdi and sEMGscm. For this purpose, both sEMG signals were recorded simultaneously with BEs and CREs in healthy subjects while performing an inspiratory load protocol. To evaluate the effect of the cardiac interference, the ratio between the mean power in inspiratory segments without ECG and the mean power in expiratory segments with ECG (Rcardio) was calculated. Additionally, the ratio between the mean power in inspiratory segments without ECG and the mean power in expiratory segments without ECG (Rinex) was also calculated. The results revealed that the Rcardio and bandwidth is greater in sEMG signals acquired with the CREs, while the Rinex is higher in the signals acquired with BEs. These results suggest that the use of CREs is a recommended alternative for the acquisition of sEMG in muscles with high cardiac interference, such as the diaphragm muscle., Postprint (author's final draft)

Postprint (published version)

The relationship between surface diaphragm mechanomyography (sMMGdi), as a noninvasive measure of inspiratory muscle mechanical activation, and crural diaphragm electromyography (oesEMGdi), as the invasive gold standard measure of diaphragm electrical activation, had not previously been examined. To investigate this relationship, oesEMGdi and sMMGdi were measured simultaneously in 6 healthy subjects during an incremental inspiratory threshold loading protocol, and analyzed using fixed sample entropy (fSampEn). A positive curvilinear relationship was observed between mean fSampEn sMMGdi and oesEMGdi (r = 0.67). Accordingly, an increasing electromechanical ratio was also observed with increasing inspiratory load. These findings suggest that sMMGdi could provide useful noninvasive measures of inspiratory muscle mechanical activation., Peer Reviewed, Postprint (published version)

We describe the data processing employed to match EMG signals with the categorized behavioral movements obtained from video recordings in awake rats while reaching and grasping pellets. We want to determine whether or not, the forelimb muscles follow a temporal synchronized pattern of activity during reaching and grasping. Data processing included raw data filtering and obtaining the first derivate. We found consistency in this procedure between attempts, indicating the utility for studying the brain to spinal cord function underlying volitional and skilled movements in the rat., Peer Reviewed, Postprint (author's final draft)

The determination of the optimal time of the patients in weaning trial process from Mechanical Ventilation (MV), between patients capable of maintaining spontaneous breathing and patients that fail to maintain spontaneous breathing, is a very important task in intensive care unit. Symbolic Dynamic (SD) and Neural Networks (NN) techniques were applied in order to develop a classifier for the study of patients on weaning trial process. The respiratory pattern of each patient was characterized through different time series. In order to reduce the dimensionality of the system Forward Selection is implemented, obtaining a classification performance result of 85,96 ±6,26% with 64 variables differentiating between 3 classes analyzed at same time. © 2018 IEEE., Peer Reviewed, Postprint (published version)