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The paintings of the hermit saints of Puebla, Mexico belong to a series of thirteen canvases based on the Flemish engravings of Maarten de Vos and on themes derived from the Vida Antonii. These scenes, character-ized by forested environments, show a number of anchorites organized in lauras, and others in the postures of strict penance, characteristic of primi-tive monasticism. The comparison of these works with biographies shed light upon the iconological reading of the works and made it possible to identify what was included and omitted from the pictures. However, two distinct sty-listic groups were observed in the creation of the works, as well as paintings that had been created by several authors, among them Diego de Borgraf.

The electrocardiogram (ECG) is a powerful tool to measure the electrical activity of the heart, and the analysis of its data can be useful to assess the patient’s health. In particular, the computational analysis of electrocardiogram data, also called ECG signal processing, can reveal specific patterns or heart cycle trends which otherwise would be unnoticeable by medical experts. When performing ECG signal processing, however, it is easy to make mistakes and generate inflated, overoptimistic, or misleading results, which can lead to wrong diagnoses or prognoses and, in turn, could even contribute to bad medical decisions, damaging the health of the patient. Therefore, to avoid common mistakes and bad practices, we present here ten easy guidelines to follow when analyzing electrocardiogram data computationally. Our ten recommendations, written in a simple way, can be useful to anyone performing a computational study based on ECG data and eventually lead to better, more robust medical results.

This article analyzes a painting by Maarten de Vos (1532–1603), the most distinguished Flemish painter before the Baroque period. Although relatively unknown among jurists, its legal iconography is remarkable. It combines a portrait of the members of a guild court and a highly elaborated allegory of justice: a Iustitia among Moses, Iustinianus, Numa Pompilius and Lycurgus. First, the painting is described according to the art-historical literature, which is mainly in Dutch. The critical comment which follows focuses on the identification of Lycurgus. In contrast to the other three ancient legislators, Lycurgus cannot be identified by an extract from a legal source but only by a depiction of animals. Until now, therefore, the view has prevailed that the representation is about Pliny the Elder and his »Naturalis Historia«. Contrary to this view, the article tries to demonstrate that the depiction of animals (a dog is eating from a bowl, another is hunting a deer) refers to a parable which Lycurgus, as handed down by Plutarch, had invented to illustrate the political importance of education. Other visualizations of this parable by Caesar B. van Everdingen, Otto van Veen and Jan Saenredam are consulted for the purpose of comparison. Finally, the painting of de Vos is put into the tradition of Iustitia-allegories and group portraits, especially in Holland, Italy and France.

The diagnosis of epilepsy can be confirmed in-hospital via video-electroencephalography (vEEG). Currently, long-term monitoring is limited to self-reporting seizure occurrences by the patients. In recent years, the development of wearable sensors has allowed monitoring patients outside of specialized environments. The application of wearable EEG devices for monitoring epileptic patients in ambulatory environments is still dampened by the low performance achieved by automated seizure detection frameworks. In this work, we present the results of a seizure detection grand challenge, organized as an attempt to stimulate the development of automated methodologies for detection of seizures on wearable EEG. The main drawbacks for developing wearable EEG seizure detection algorithms is the lack of data needed for training such frameworks. In this challenge, we provided participants with a large dataset of 42 patients with focal epilepsy, containing continuous recordings of behind-the-ear (bte) EEG. We challenged participants to develop a robust seizure classifier based on wearable EEG. Additionally, we proposed a subtask in order to motivate data-centric approaches to improve the training and performance of seizure detection models. An additional dataset, containing recordings with a bte-EEG wearable device, was employed to evaluate the work submitted by participants. In this paper, we present the five best scoring methodologies. The best performing approach was a feature-based decision tree ensemble algorithm with data augmentation via Fourier Transform surrogates. The organization of this challenge is of high importance for improving automated EEG analysis for epilepsy diagnosis, working towards implementing these technologies in clinical practice.

Sleep abnormalities can have severe health consequences. Automated sleep staging, i.e. labelling the sequence of sleep stages from the patient’s physiological recordings, could simplify the diagnostic process. Previous work on automated sleep staging has achieved great results, mainly relying on the EEG signal. However, often multiple sources of information are available beyond EEG. This can be particularly beneficial when the EEG recordings are noisy or even missing completely. In this paper, we propose CoRe-Sleep, a Coordinated Representation multimodal fusion network that is particularly focused on improving the robustness of signal analysis on imperfect data. We demonstrate how appropriately handling multimodal information can be the key to achieving such robustness. CoRe-Sleep tolerates noisy or missing modalities segments, allowing training on incomplete data. Additionally, it shows state-of-the-art performance when testing on both multimodal and unimodal data using a single model on SHHS-1, the largest publicly available study that includes sleep stage labels. The results indicate that training the model on multimodal data does positively influence performance when tested on unimodal data. This work aims at bridging the gap between automated analysis tools and their clinical utility.

ObjectivesThis study aimed to validate a sleep staging algorithm using in-hospital video-electroencephalogram (EEG) in children without epilepsy, with well-controlled epilepsy (WCE), and with drug-resistant epilepsy (DRE).MethodsOvernight video-EEG, along with electrooculogram (EOG) and chin electromyogram (EMG), was recorded in children between 4 and 18 years of age. Classical sleep staging was performed manually as a ground truth. An end-to-end hierarchical recurrent neural network for sequence-to-sequence automatic sleep staging (SeqSleepNet) was used to perform automated sleep staging using three channels: C4-A1, EOG, and chin EMG.ResultsIn 176 children sleep stages were manually scored: 47 children without epilepsy, 74 with WCE, and 55 with DRE. The 5-class sleep staging accuracy of the automatic sleep staging algorithm was 84.7% for the children without epilepsy, 83.5% for those with WCE, and 80.8% for those with DRE (Kappa of 0.79, 0.77, and 0.73 respectively). Performance per sleep stage was assessed with an F1 score of 0.91 for wake, 0.50 for N1, 0.83 for N2, 0.84 for N3, and 0.86 for rapid eye movement (REM) sleep.ConclusionWe concluded that the tested algorithm has a high accuracy in children without epilepsy and with WCE. Performance in children with DRE was acceptable, but significantly lower, which could be explained by a tendency of more time spent in N1, and by abundant interictal epileptiform discharges and intellectual disability leading to less recognizable sleep stages. REM sleep time, however, significantly affected in children with DRE, can be detected reliably by the algorithm.Clinical trial registration: ClinicalTrials.gov, identifier NCT04584385.

The article examines the use of Maarten de Vos' book illustrations for the publications printed by pressman Jan Moretus I. It first discusses De Vos' missal designs and demonstrates the extensive utilization of his compositions. It then focuses on De Vos' unknown projects for book illustrations that were executed for the Plantin Press and traces them from the illustrations commissioned to follow Moretuses' publications. Finally, it concludes that designs which were traditionally attributed to De Vos are not really his original works.

Background and aims Pulmonary hypertension due to left heart disease (PH-LHD) is the most frequent form of PH. As differential diagnosis with pulmonary arterial hypertension (PAH) has therapeutic implications, it is important to accurately and noninvasively differentiate PH-LHD from PAH before referral to PH centres. The aim was to develop and validate a machine learning (ML) model to improve prediction of PH-LHD in a population of PAH and PH-LHD patients. Methods Noninvasive PH-LHD predictors from 172 PAH and 172 PH-LHD patients from the PH centre database at the University Hospitals of Leuven (Leuven, Belgium) were used to develop an ML model. The Jacobs score was used as performance benchmark. The dataset was split into a training and test set (70:30) and the best model was selected after 10-fold cross-validation on the training dataset (n=240). The final model was externally validated using 165 patients (91 PAH, 74 PH-LHD) from Erasme Hospital (Brussels, Belgium). Results In the internal test dataset (n=104), a random forest-based model correctly diagnosed 70% of PH-LHD patients (sensitivity: n=35/50), with 100% positive predicted value, 78% negative predicted value and 100% specificity. The model outperformed the Jacobs score, which identified 18% (n=9/50) of the patients with PH-LHD without false positives. In external validation, the model had 64% sensitivity at 100% specificity, while the Jacobs score had a sensitivity of 3% for no false positives. Conclusions ML significantly improves the sensitivity of PH-LHD prediction at 100% specificity. Such a model may substantially reduce the number of patients referred for invasive diagnostics without missing PAH diagnoses.

IntroductionAs our attention is becoming a commodity that an ever-increasing number of applications are competing for, investing in modern day tools and devices that can detect our mental states and protect them from outside interruptions holds great value. Mental fatigue and distractions are impacting our ability to focus and can cause workplace injuries. Electroencephalography (EEG) may reflect concentration, and if EEG equipment became wearable and inconspicuous, innovative brain-computer interfaces (BCI) could be developed to monitor mental load in daily life situations. The purpose of this study is to investigate the potential of EEG recorded inside and around the human ear to determine levels of attention and focus.MethodsIn this study, mobile and wireless ear-EEG were concurrently recorded with conventional EEG (cap) systems to collect data during tasks related to focus: an N-back task to assess working memory and a mental arithmetic task to assess cognitive workload. The power spectral density (PSD) of the EEG signal was analyzed to isolate consistent differences between mental load conditions and classify epochs using step-wise linear discriminant analysis (swLDA).Results and discussionResults revealed that spectral features differed statistically between levels of cognitive load for both tasks. Classification algorithms were tested on spectral features from twelve and two selected channels, for the cap and the ear-EEG. A two-channel ear-EEG model evaluated the performance of two dry in-ear electrodes specifically. Single-trial classification for both tasks revealed above chance-level accuracies for all subjects, with mean accuracies of: 96% (cap-EEG) and 95% (ear-EEG) for the twelve-channel models, 76% (cap-EEG) and 74% (in-ear-EEG) for the two-channel model for the N-back task; and 82% (cap-EEG) and 85% (ear-EEG) for the twelve-channel, 70% (cap-EEG) and 69% (in-ear-EEG) for the two-channel model for the arithmetic task. These results suggest that neural oscillations recorded with ear-EEG can be used to reliably differentiate between levels of cognitive workload and working memory, in particular when multi-channel recordings are available, and could, in the near future, be integrated into wearable devices.

Abstract Background Parameters from maximal expiratory flow-volume curves (MEFVC) have been linked to CT-based parameters of COPD. However, the association between MEFVC shape and phenotypes like emphysema, small airways disease (SAD) and bronchial wall thickening (BWT) has not been investigated. Research question We analyzed if the shape of MEFVC can be linked to CT-determined emphysema, SAD and BWT in a large cohort of COPDGene participants. Study design and methods In the COPDGene cohort, we used principal component analysis (PCA) to extract patterns from MEFVC shape and performed multiple linear regression to assess the association of these patterns with CT parameters over the COPD spectrum, in mild and moderate-severe COPD. Results Over the entire spectrum, in mild and moderate-severe COPD, principal components of MEFVC were important predictors for the continuous CT parameters. Their contribution to the prediction of emphysema diminished when classical pulmonary function test parameters were added. For SAD, the components remained very strong predictors. The adjusted R2 was higher in moderate-severe COPD, while in mild COPD, the adjusted R2 for all CT outcomes was low; 0.28 for emphysema, 0.21 for SAD and 0.19 for BWT. Interpretation The shape of the maximal expiratory flow-volume curve as analyzed with PCA is not an appropriate screening tool for early disease phenotypes identified by CT scan. However, it contributes to assessing emphysema and SAD in moderate-severe COPD.

Abstract In neonates with hypoxic ischemic encephalopathy, the computation of wavelet coherence between electroencephalogram (EEG) power and regional cerebral oxygen saturation (rSO2) is a promising method for the assessment of neurovascular coupling (NVC), which in turn is a promising marker for brain injury. However, instabilities in arterial oxygen saturation (SpO2) limit the robustness of previously proposed methods. Therefore, we propose the use of partial wavelet coherence, which can eliminate the influence of SpO2. Furthermore, we study the added value of the novel NVC biomarkers for identification of brain injury compared to traditional EEG and NIRS biomarkers. 18 neonates with HIE were monitored for 72 h and classified into three groups based on short-term MRI outcome. Partial wavelet coherence was used to quantify the coupling between C3–C4 EEG bandpower (2–16 Hz) and rSO2, eliminating confounding effects of SpO2. NVC was defined as the amount of significant coherence in a frequency range of 0.25–1 mHz. Partial wavelet coherence successfully removed confounding influences of SpO2 when studying the coupling between EEG and rSO2. Decreased NVC was related to worse MRI outcome. Furthermore, the combination of NVC and EEG spectral edge frequency (SEF) improved the identification of neonates with mild vs moderate and severe MRI outcome compared to using EEG SEF alone. Partial wavelet coherence is an effective method for removing confounding effects of SpO2, improving the robustness of automated assessment of NVC in long-term EEG-NIRS recordings. The obtained NVC biomarkers are more sensitive to MRI outcome than traditional rSO2 biomarkers and provide complementary information to EEG biomarkers.

Although medication use during pregnancy is common, most available products lack sufficient safety information. As prospective data collection and perinatal pharmacoepidemiologic research on medication safety in pregnancy did not exist in Belgium yet, the BELpREG data registration system was developed. BELpREG enables comprehensive “real-world” data collection on perinatal medication use and mother-infant outcomes via online questionnaires that are completed by pregnant women every 4 weeks during pregnancy and in the first 8 weeks after childbirth. This paper describes the development and current design of the BELpREG system, including the list of BELpREG variables. To compile this list of variables, relevant documents were explored, followed by consultation of an interdisciplinary expert panel. The included variables were structured in seven categories: 1) Sociodemographic characteristics; 2) Information on the current pregnancy and health status; 3) Maternal-obstetric history; 4) Use of medicines, folic acid/pregnancy vitamins and other health products; 5) Substance use; 6) Pregnancy outcomes; and 7) Neonatal outcomes. An electronic informed consent and linkage to medication databases, with images of drug packages and underlying structured data fields, are built into the system. Data collection has officially started in November 2022. Based on its rigorous design, BELpREG holds the potential to be a successful and sustainable research tool, enabling perinatal pharmacoepidemiologic research in Belgium and beyond.

Background and objectiveSpirometry patterns can suggest that a patient has a restrictive ventilatory impairment; however, lung volume measurements such as total lung capacity (TLC) are required to confirm the diagnosis. The aim of the study was to train a supervised machine learning model that can accurately estimate TLC values from spirometry and subsequently identify which patients would most benefit from undergoing a complete pulmonary function test.MethodsWe trained three tree-based machine learning models on 51,761 spirometry data points with corresponding TLC measurements. We then compared model performance using an independent test set consisting of 1,402 patients. The best-performing model was used to retrospectively identify restrictive ventilatory impairment in the same test set. The algorithm was compared against different spirometry patterns commonly used to predict restriction.ResultsThe prevalence of restrictive ventilatory impairment in the test set is 16.7% (234/1402). CatBoost was the best-performing machine learning model. It predicted TLC with a mean squared error (MSE) of 560.1 mL. The sensitivity, specificity, and F1-score of the optimal algorithm for predicting restrictive ventilatory impairment was 83, 92, and 75%, respectively.ConclusionA machine learning model trained on spirometry data can estimate TLC to a high degree of accuracy. This approach could be used to develop future smart home-based spirometry solutions, which could aid decision making and self-monitoring in patients with restrictive lung diseases.

Goal: Smartphone and wearable devices may act as powerful tools to remotely monitor physical function in people with neurodegenerative and autoimmune diseases from out-of-clinic environments. Detection of progression onset or worsening of symptoms is especially important in people living with multiple sclerosis (PwMS) in order to enable optimally adapted therapeutic strategies. MS symptoms typically follow subtle and fluctuating disease courses, patient-to-patient, and over time. Current in-clinic assessments are often too infrequently administered to reflect longitudinal changes in MS impairment that impact daily life. This work, therefore, explores how smartphones can administer daily two-minute walking assessments to monitor PwMS physical function at home. Methods: Remotely collected smartphone inertial sensor data was transformed through state-of-the-art Deep Convolutional Neural Networks, to estimate a participant's daily ambulatory-related disease severity, longitudinally over a 24-week study. Results: This study demonstrated that smartphone-based ambulatory severity outcomes could accurately estimate MS level of disability, as measured by the EDSS score ($r^{2}$: 0.56,$p< $0.001). Furthermore, longitudinal severity outcomes were shown to accurately reflect individual participants' level of disability over the study duration. Conclusion: Smartphone-based assessments, that can be performed by patients from their home environments, could greatly augment standard in-clinic outcomes for neurodegenerative diseases. The ability to understand the impact of disease on daily-life between clinical visits, through objective digital outcomes, paves the way forward to better measure and identify signs of disease progression that may be occurring out-of-clinic, to monitor how different patients respond to various treatments, and to ultimately enable the development of better, and more personalised care.

Heart disease is the leading cause of mortality worldwide, and it is of utmost importance that clinicians and researchers understand the dynamics of the heart. As an electrical measure of the heart’s activity, the electrocardiogram, or ECG, is the gold standard for recording the cardiac state, whether monitoring the structure of the traces that make up the ECG or indicating key metrics such as heart rate variability. Long-term monitoring of ECG is often required to identify cardiovascular issues but proves impractical; therefore, patients will remotely collect their data. However, ECG signals can become contaminated with various noise sources during data collection. This paper proposes a custom loss function capable of denoising electrode motion artefact in ECG data to a higher standard than other, more common loss functions. We implement our custom loss function with a convolutional neural network to return high-quality ECG, suitable for calculating the aforementioned key metrics from a previously unobtainable state. The proposed model improves ECG signals overall signal-to-noise ratio and preserves the R waves structure. The model outperforms a standard mean squared error loss function with an improvement of 0.5 dB in terms of signal to noise ratio and improves the heart rate estimation by 25%.

Introduction Objective cough frequency is a key clinical end-point but existing wearable monitors are limited to 24-h recordings. Albus Home uses contactless motion, acoustic and environmental sensors to monitor multiple metrics, including respiratory rate and cough without encroaching on patient lifestyle. The aim of this study was to evaluate measurement characteristics of nocturnal cough monitoring by Albus Home compared to manual counts. Methods Adults with respiratory conditions underwent overnight monitoring using Albus Home in their usual bedroom environments. Participants set-up the plug-and-play device themselves. For reference counts, each audio recording was counted by two annotators, and cough defined as explosive phases audio-visually labelled by both. In parallel, recordings were processed by a proprietary Albus system, comprising a deep-learning algorithm with a human screening step for verifying or excluding occasional events that mimic cough. Performance of the Albus system in detecting individual cough events and reporting hourly cough counts was compared against reference counts. Results 30 nights from 10 subjects comprised 375 hours of recording. Mean±sd coughs per night were 90±76. Coughs per hour ranged from 0 to 129. Albus counts were accurate across hours with high and low cough frequencies, with median sensitivity, specificity, positive predictive value and negative predictive values of 94.8, 100.0, 99.1 and 100.0%, respectively. Agreement between Albus and reference was strong (intra-class correlation coefficient (ICC) 0.99; 95% CI 0.99–0.99; p

Having previously seen an item helps uncover the item another time, given a perceptual or cognitive cue. Oftentimes, however, it may be difficult to quantify or test the existence and size of a perceptual or cognitive effect, in general, and a priming effect, in particular. This is because to examine the existence of and quantify the effect, one needs to compare two outcomes: the outcome had one previously seen the item vs. the outcome had one not seen the item. But only one of the two outcomes is observable. Here, we argue that the potential outcomes framework is useful to define, quantify, and test the causal priming effect. To demonstrate its efficacy, we apply the framework to study the priming effect using data from a between-subjects study involving English word identification. In addition, we show that what has been used intuitively by experimentalists to assess the priming effect in the past has a sound mathematical foundation. Finally, we examine the links between the proposed method in studying priming and the multinomial processing tree (MPT) model, and how to extend the method to study experimental paradigms involving exclusion and inclusion instructional conditions.

Patients with absence epilepsy fail to report almost 90% of their seizures. The clinical gold standard to assess absence seizures is video-electroencephalography (vEEG) recorded in the hospital, an expensive and obtrusive procedure which requires also extended reviewing time. Wearable sensors, which allow the recording of electroencephalography (EEG), accelerometer and gyroscope have been used to monitor epileptic patients in their home environment for the first time. We developed a pipeline for accurate and robust absence seizure detection while reducing the review time of the long recordings. Our results show that multimodal analysis of absence seizures can improve the robustness to false alarms, while retaining a high sensitivity in seizure detection.

Abstract The emergence of digital technologies such as smartphones in healthcare applications have demonstrated the possibility of developing rich, continuous, and objective measures of multiple sclerosis (MS) disability that can be administered remotely and out-of-clinic. Deep Convolutional Neural Networks (DCNN) may capture a richer representation of healthy and MS-related ambulatory characteristics from the raw smartphone-based inertial sensor data than standard feature-based methodologies. To overcome the typical limitations associated with remotely generated health data, such as low subject numbers, sparsity, and heterogeneous data, a transfer learning (TL) model from similar large open-source datasets was proposed. Our TL framework leveraged the ambulatory information learned on human activity recognition (HAR) tasks collected from wearable smartphone sensor data. It was demonstrated that fine-tuning TL DCNN HAR models towards MS disease recognition tasks outperformed previous Support Vector Machine (SVM) feature-based methods, as well as DCNN models trained end-to-end, by upwards of 8–15%. A lack of transparency of “black-box” deep networks remains one of the largest stumbling blocks to the wider acceptance of deep learning for clinical applications. Ensuing work therefore aimed to visualise DCNN decisions attributed by relevance heatmaps using Layer-Wise Relevance Propagation (LRP). Through the LRP framework, the patterns captured from smartphone-based inertial sensor data that were reflective of those who are healthy versus people with MS (PwMS) could begin to be established and understood. Interpretations suggested that cadence-based measures, gait speed, and ambulation-related signal perturbations were distinct characteristics that distinguished MS disability from healthy participants. Robust and interpretable outcomes, generated from high-frequency out-of-clinic assessments, could greatly augment the current in-clinic assessment picture for PwMS, to inform better disease management techniques, and enable the development of better therapeutic interventions.

Background Artefact removal in neonatal electroencephalography (EEG) by visual inspection generally depends on the expertise of the operator, is time consuming and is not a consistent pre-processing step to the pipeline for the automated EEG analysis. Therefore, there is the need for the automated detection and removal of artefacts in neonatal EEG, especially of distinct and predominant artefacts such as flat line segments (mainly caused by instrumental error where contact between electrodes and head box is lost) and large amplitude fluctuations (related to neonatal movements). Method A threshold-based algorithm for the automated detection and removal of flat line segments and large amplitude fluctuations in neonatal EEG of infants at term-equivalent age is developed. The algorithm applies thresholds to the absolute second difference, absolute amplitude, absolute first difference and the ratio between the frequency content above 50 Hz and the frequency content across all frequencies. Results The algorithm reaches a median accuracy of 0.91, a median hit rate of 0.91 and a median false discovery rate of 0.37. Also, a significant improvement (≈10%) in the performance of a four-stage sleep classifier is observed after artefact removal with the proposed algorithm as compared to before its application. Significance An automated artefact removal method contributes to the pipeline of automated EEG analysis. The proposed algorithm has shown to have good performance and to be effective in neonatal EEG applications.

Long-term home monitoring of people living with epilepsy cannot be achieved using the standard full-scalp electroencephalography (EEG) coupled with video. Wearable seizure detection devices, such as behind-the-ear EEG (bte-EEG), offer an unobtrusive method for ambulatory follow-up of this population. Combining bte-EEG with electrocardiography (ECG) can enhance automated seizure detection performance. However, such frameworks produce high false alarm rates, making visual review necessary. This study aimed to evaluate a semi-automated multimodal wearable seizure detection framework using bte-EEG and ECG. Using the SeizeIT1 dataset of 42 patients with focal epilepsy, an automated multimodal seizure detection algorithm was used to produce seizure alarms. Two reviewers evaluated the algorithm’s detections twice: (1) using only bte-EEG data and (2) using bte-EEG, ECG, and heart rate signals. The readers achieved a mean sensitivity of 59.1% in the bte-EEG visual experiment, with a false detection rate of 6.5 false detections per day. Adding ECG resulted in a higher mean sensitivity (62.2%) and a largely reduced false detection rate (mean of 2.4 false detections per day), as well as an increased inter-rater agreement. The multimodal framework allows for efficient review time, making it beneficial for both clinicians and patients.