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Background Major Depressive Disorder (MDD) is prevalent, often chronic, and requires ongoing monitoring of symptoms to track response to treatment and identify early indicators of relapse. Remote Measurement Technologies (RMT) provide an opportunity to transform the measurement and management of MDD, via data collected from inbuilt smartphone sensors and wearable devices alongside app-based questionnaires and tasks. A key question for the field is the extent to which participants can adhere to research protocols and the completeness of data collected. We aimed to describe drop out and data completeness in a naturalistic multimodal longitudinal RMT study, in people with a history of recurrent MDD. We further aimed to determine whether those experiencing a depressive relapse at baseline contributed less complete data. Methods Remote Assessment of Disease and Relapse – Major Depressive Disorder (RADAR-MDD) is a multi-centre, prospective observational cohort study conducted as part of the Remote Assessment of Disease and Relapse – Central Nervous System (RADAR-CNS) program. People with a history of MDD were provided with a wrist-worn wearable device, and smartphone apps designed to: a) collect data from smartphone sensors; and b) deliver questionnaires, speech tasks, and cognitive assessments. Participants were followed-up for a minimum of 11 months and maximum of 24 months. Results Individuals with a history of MDD (n = 623) were enrolled in the study,. We report 80% completion rates for primary outcome assessments across all follow-up timepoints. 79.8% of people participated for the maximum amount of time available and 20.2% withdrew prematurely. We found no evidence of an association between the severity of depression symptoms at baseline and the availability of data. In total, 110 participants had > 50% data available across all data types. Conclusions RADAR-MDD is the largest multimodal RMT study in the field of mental health. Here, we have shown that collecting RMT data from a clinical population is feasible. We found comparable levels of data availability in active and passive forms of data collection, demonstrating that both are feasible in this patient group.

Most smartphones and wearables are nowadays equipped with location sensing (using Global Positioning System and mobile network information) that enable continuous location tracking of their users. Several studies have reported that the amount of time an individual experiencing symptoms of Major Depressive Disorder (MDD) spends at home a day (i.e., home stay), as well as various mobility related metrics, are associated with symptom severity in MDD. Due to the use of small and homogeneous cohorts of participants, it is uncertain whether the findings reported in those studies generalize to a broader population of individuals with the MDD symptoms. In the present study, we examined the relationship between overall severity of the depressive symptoms, as assessed by the eight-item Patient Health Questionnaire (PHQ-8), and median daily home stay over the two weeks preceding the completion of a questionnaire in individuals with MDD. We used questionnaire and geolocation data of 164 participants collected in the observational Remote Assessment of Disease and Relapse – Major Depressive Disorder (RADAR-MDD) study. Participant age and severity of the MDD symptoms were found to be significantly related to home stay, with older and more severely affected individuals spending more time at home. The association between home stay and symptom severity appeared to be stronger on weekdays than on weekends. Furthermore, we found a significant modulation of home stay by occupational status, with employment reducing home stay. Our findings suggest that home stay is associated with symptom severity in MDD and demonstrate the importance of accounting for confounding factors in future MDD studies.

We propose a novel computational approach to automatically identify the fetal heart rate patterns (fHRPs), which are reflective of sleep/awake states. By combining these patterns with presence or absence of movements, a fetal behavioral state (fBS) was determined. The expert scores were used as the gold standard and objective thresholds for the detection procedure were obtained using Receiver Operating Characteristics (ROC) analysis. To assess the performance, intraclass correlation was computed between the proposed approach and the mutually agreed expert scores. The detected fHRPs were then associated to their corresponding fBS based on the fetal movement obtained from fetal magnetocardiogaphic (fMCG) signals. This approach may aid the clinicians in objectively assessing the fBS and monitoring the fetal wellbeing.

Identification of risk factors of treatment resistance may be useful to guide treatment selection, avoid inefficient trial-and-error, and improve major depressive disorder (MDD) care. We extended the work in predictive modeling of treatment resistant depression (TRD) via partition of the data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) cohort into a training and a testing dataset. We also included data from a small yet completely independent cohort RIS-INT-93 as an external test dataset. We used features from enrollment and level 1 treatment (up to week 2 response only) of STAR*D to explore the feature space comprehensively and applied machine learning methods to model TRD outcome at level 2. For TRD defined using QIDS-C16 remission criteria, multiple machine learning models were internally cross-validated in the STAR*D training dataset and externally validated in both the STAR*D testing dataset and RIS-INT-93 independent dataset with an area under the receiver operating characteristic curve (AUC) of 0.70-0.78 and 0.72-0.77, respectively. The upper bound for the AUC achievable with the full set of features could be as high as 0.78 in the STAR*D testing dataset. Model developed using top 30 features identified using feature selection technique (k-means clustering followed by χ2 test) achieved an AUC of 0.77 in the STAR*D testing dataset. In addition, the model developed using overlapping features between STAR*D and RIS-INT-93, achieved an AUC of > 0.70 in both the STAR*D testing and RIS-INT-93 datasets. Among all the features explored in STAR*D and RIS-INT-93 datasets, the most important feature was early or initial treatment response or symptom severity at week 2. These results indicate that prediction of TRD prior to undergoing a second round of antidepressant treatment could be feasible even in the absence of biomarker data.

Intrauterine growth restriction (IUGR) is a fetal condition characterized by growth-rate reduction. Afflicted fetuses tend to display abnormalities in heart rate.To study the differences in the heart-rate variability of low-risk fetuses and IUGR fetuses during different behavioral states.A total of 40 fetal magnetocardiograms were analyzed from 20 low-risk and 20 IUGR fetuses recorded using a 151-sensor SQUID-array system. The maternal cardiac signals were attenuated using signal-space projection. Fetal R waves were identified using an adaptive Hilbert transform approach and fetal heart rate was calculated. In each three-minute window, the heart rate was classified into patterns reflective of quiet sleep (pattern A) and active sleep (pattern B) using the criteria of Nijhuis. Two adjacent 3-min windows exhibiting the same pattern were selected for analysis from every dataset. Heart-rate variability in that 6-min window was characterized using three measures, standard deviation of normal to normal (SDNN), root mean square of successive differences (RMSSD) and phase plane area (PPA).All three measures tended to be lower in the IUGR group compared to the low-risk group. However, when the measures were analyzed in patterns, only PPA showed significant difference between the risk groups in pattern A, whereas both PPA and SDNN showed highly significant risk-group differences in pattern B. RMSSD did not show any significant risk-group difference.The result signifies that the heart-rate variability of IUGR fetuses is different from that of low-risk fetuses, and only PPA was able to capture the HRV differences in both quiet and active states. The difference between these two groups of fetuses shows that the fetal-activity states are potential confounders when characterizing heart-rate variability.

Fetal magnetoencephalography (fMEG) recordings are contaminated by maternal and fetal magnetocardiography (MCG) signals and by other biological and environmental interference. Currently, all methods for the attenuation of these signals are based on a time-domain approach. We have developed and tested a frequency dependent procedure for removal of MCG and other interference from the fMEG recordings. The method uses a set of reference channels and performs subtraction of interference in the frequency domain (SUBTR). The interference-free frequency domain signals are converted back to the time domain. We compare the performance of the frequency dependent approach with our present approach for MCG attenuation based on orthogonal projection (OP). SUBTR has an advantage over OP and similar template approaches because it removes not only the MCG but also other small amplitude biological interference, avoids the difficulties with inaccurate determination of the OP operator, provides more consistent and stable fMEG results, does not cause signal redistribution, and if references are selected judiciously, it does not reduce fMEG signal amplitude. SUBTR was found to perform well in simulations and on real fMEG recordings, and has a potential to improve the detection of fetal brain signals. The SUBTR removes interference without the need for a model of the individual interference sources. The method may be of interest for any sensor array noise reduction application where signal-free reference channels are available.

Acute lung injury (ALI) is a devastating complication of acute illness and one of the leading causes of multiple organ failure and mortality in the intensive care unit (ICU). The detection of this syndrome is limited due to the complexity of the disease, insufficient understanding of its development and progression, and the large amount of risk factors and modifiers. In this preliminary study, we present a novel mathematical model for ALI detection. It is constructed based on clinical and research knowledge using three complementary techniques: rule-based fuzzy inference systems, Bayesian networks, and finite state machines. The model is developed in Matlab(®)'s Simulink environment and takes as input pre-ICU and ICU data feeds of critically ill patients. Results of the simulation model were validated against actual patient data from an epidemiologic study. By appropriately combining all three techniques the performance attained is in the range of 71.7-92.6% sensitivity and 60.3-78.4% specificity.

Changes in fetal magnetocardiographic (fMCG) signals are indicators for fetal body movement. We propose a novel approach to reliably extract fetal body movements based on the field strength of the fMCG signal independent of its frequency. After attenuating the maternal MCG, we use a Hilbert transform approach to identify the R-wave. At each R-wave, we compute the center-of-gravity (cog) of the coordinate positions of MCG sensors, each weighted by the magnitude of the R-wave amplitude recorded at the corresponding sensor. We then define actogram as the distance between the cog computed at each R-wave and the average of the cog from all the R-waves in a 3-min duration. By applying a linear de-trending approach to the actogram we identify the fetal body movement and compare this with the synchronous occurrence of the acceleration in the fetal heart rate. Finally, we apply this approach to the fMCG recorded simultaneously with ultrasound from a single subject and show its improved performance over the QRS-amplitude based approach in the visually verified movements. This technique could be applied to transform the detection of fetal body movement into an objective measure of fetal health and enhance the predictive value of prevalent clinical testing for fetal wellbeing.

The fetal magnetoencephalogram (fMEG) is measured in the presence of large interference from maternal and fetal magnetocardiograms (mMCG and fMCG). These cardiac interferences can be attenuated by orthogonal projection (OP) technique of the corresponding spatial vectors. However, the OP technique redistributes the fMEG signal among the channels and also leaves some cardiac residuals (partially attenuated mMCG and fMCG) due to loss of stationarity in the signal. In this paper, we propose a novel way to extract and localize the neonatal and fetal spontaneous brain activity by using independent component analysis (ICA) technique. In this approach, we perform ICA on a small subset of sensors for 1-min duration. The independent components obtained are further investigated for the presence of discontinuous patterns as identified by the Hilbert phase analysis and are used as decision criteria for localizing the spontaneous brain activity. In order to locate the region of highest spontaneous brain activity content, this analysis is performed on the sensor subsets, which are traversed across the entire sensor space. The region of the spontaneous brain activity as identified by the proposed approach correlated well with the neonatal and fetal head location. In addition, the burst duration and the inter-burst interval computed for the identified discontinuous brain patterns are in agreement with the reported values.

We propose a novel approach based on Hilbert phase to identify the burst in the uterine myometrial activity. We apply this approach to 24 serial magnetomyographic signals recorded from four pregnant women using a 151 SQUID array system. The bursts identified with this approach are evaluated for duration and are correlated with the gestational age. In all four subjects, we find a decrease in the duration of burst as the subject approaches active labor. As was shown in animal studies, this result indicates a faster conduction time between the muscle cells which activate a larger number of muscle units in a synchronous manner.

We propose a novel method to characterize the spontaneous brain signals using Hilbert phases. The Hilbert phase of a signal exhibits phase slips when the magnitude of the successive phase difference exceeds pi. To this end we use standard deviation (sigmaDeltatau) of the time (Deltatau) between successive phase slips to characterize the signals. We demonstrate the application of this approach to neonatal and fetal magnetoencephalographic signals recorded using a 151-sensor array to identify the sensors containing the neonatal and fetal brain signals. To this end we propose a spatial filter using sigma(Deltatau) as weights to reconstruct the brain signals.

The discontinuous patterns in neonatal magnetoencephalographic (MEG) data are quantified with a novel Hilbert phase (HP) based approach. The expert neurologists' scores were used as the gold standard. The performance of this approach was analyzed using a receiver operating characteristic (ROC) curve, and it was compared with two other approaches, namely spectral ratio (SR) and discrete wavelet transform (DWT) that have been proposed for the detection of discontinuous patterns in neonatal EEG. The area under the ROC curve (AUC) was used as a performance measure. AUCs obtained for SR, HP, and DWT were 0.87, 0.80, and 0.56, respectively. Although the performance of HP was lower than SR, it carries information about the frequency content of the signal that helps to distinguish brain patterns from artifacts such as cardiac residuals. Based on this property, the HP approach was extended to fetal MEG data. Further, using the frequency property of the HP approach, burst duration and interburst interval were computed for the discontinuous patterns detected and they are in agreement with reported values.