Electrical impedance tomography as a bedside assessment tool for COPD treatment during hospitalization.

For patients with chronic obstructive pulmonary disease (COPD), the assessment of the treatment efficacy during hospitalization is of importance to the optimization of clinical treatments. Conventional spirometry might not be sensitive enough to capture the regional lung function development. The study aimed to evaluate the feasibility of using electrical impedance tomography (EIT) as an objective bedside evaluation tool for the treatment of acute exacerbation of COPD (AECOPD). Consecutive patients who required hospitalization due to AECOPD were included prospectively. EIT measurements were conducted at the time of admission and before the discharge simultaneously when a forced vital capacity maneuver was conducted. EIT-based heterogeneity measures of regional lung function were calculated based on the impedance changes over time. Surveys for attending doctors and patients were designed to evaluate the ease of use, feasibility, and overall satisfaction level to understand the acceptability of EIT measurements. Patient-reported outcome assessments were conducted. User's acceptance of EIT technology was investigated with a five-dimension survey. A total of 32 patients were included, and 8 patients were excluded due to the FVC maneuver not meeting the ATS criteria. Spirometry-based lung function was improved during hospitalization but not significantly different (FEV1 %pred.: 35.8% ± 6.7% vs. 45.3% ± 8.8% at admission vs. discharge; p = 0.11. FVC %pred.: 67.8% ± 0.4% vs. 82.6% ± 5.0%; p = 0.15. FEV1/FVC: 0.41 ± 0.09 vs. 0.42 ± 0.07, p = 0.71). The symptoms of COPD were significantly improved, but the correlations between the improvement of symptoms and spirometry FEV1 and FEV1/FVC were low (R = 0.1 and -0.01, respectively). The differences in blood gasses and blood tests were insignificant. All but one EIT-based regional lung function parameter were significantly improved after hospitalization. The results highly correlated with the patient-reported outcome assessment (R > 0.6, p < 0.001). The overall acceptability score of EIT measurement for both attending physicians and patients was high (4.1 ± 0.8 for physicians, 4.5 ± 0.5 for patients out of 5). These results demonstrated that it was feasible and acceptable to use EIT as an objective bedside evaluation tool for COPD treatment efficacy.

Visualizing pursed lips breathing of patients with chronic obstructive pulmonary disease through evaluation of global and regional ventilation using electrical impedance tomography.

Objective. This study aims to explore the possibility of using electrical impedance tomography (EIT) to assess pursed lips breathing (PLB) performance of patients with chronic obstructive pulmonary disease (COPD).Methods. 32 patients with COPD were assigned equally to either the conventional group or the EIT guided group. All patients were taught to perform PLB by a physiotherapist without EIT in the conventional group or with EIT in the EIT guided group for 10 min. The ventilation of all patients in the final test were continuously monitored using EIT and the PLB performances were rated by another physiotherapist before and after reviewing EIT. The global and regional ventilation between two groups as well as between quite breathing (QB) and PLB were compared and rating scores with and without EIT were also compared.Results.For global ventilation, the inspiratory depth and the ratio of expiratory-to-inspiratory time during PLB was significantly larger than those during QB for both group (P< 0.001). The inspiratory depth and the ratio of expiratory-to-inspiratory time during PLB in the EIT guided group were higher compared to those in the conventional group (P< 0.001), as well as expiratory flow expiratory uniformity and respiratory stability were better (P< 0.001). For regional ventilation, center of ventilation significantly decreased during PLB (P< 0.05). The expiratory time constant during PLB in the EIT guided group was greater than that in the conventional group (P< 0.001). Additionally, Bland-Altman plots analysis suggested a high concordance between subjective rating and rating with the help of EIT, but the score rated after EIT observation significantly lower than that rated subjectively in both groups (score drop of -2.68 ± 1.1 in the conventional group and -1.19 ± 0.72 in the EIT guided group,P< 0.01).Conclusion.EIT could capture the details of PLB maneuver, which might be a potential tool to quantitatively evaluate PLB performance and thus assist physiotherapists to teach PLB maneuver to patients.

Evaluation of adjacent and opposite current injection patterns for a wearable chest electrical impedance tomography system.

Objective.Wearable electrical impedance tomography (EIT) can be used to monitor regional lung ventilation and perfusion at the bedside. Due to its special system architecture, the amplitude of the injected current is usually limited compared to stationary EIT system. This study aims to evaluate the performance of current injection patterns with various low-amplitude currents in healthy volunteers.Approach.A total of 96 test sets of EIT measurement was recorded in 12 healthy subjects by employing adjacent and opposite current injection patterns with four amplitudes of small current (i.e. 1 mA, 500 uA, 250 uA and 125 uA). The performance of the two injection patterns with various currents was evaluated in terms of signal-to-noise ratio (SNR) of thorax impedance, EIT image metrics and EIT-based clinical parameters.Main results.Compared with adjacent injection, opposite injection had higher SNR (p< 0.01), less inverse artifacts (p< 0.01), and less boundary artifacts (p< 0.01) with the same current amplitude. In addition, opposite injection exhibited more stable EIT-based clinical parameters (p< 0.01) across the current range. For adjacent injection, significant differences were found for three EIT image metrics (p< 0.05) and four EIT-based clinical parameters (p< 0.01) between the group of 125 uA and the other groups.Significance.For better performance of wearable pulmonary EIT, currents greater than 250 uA should be used in opposite injection, 500 uA in adjacent one, to ensure a high level of SNR, a high quality of reconstructed image as well as a high reliability of clinical parameters.

Upregulation of a Small-World Brain Network Improves Inhibitory Control: An fNIRS Neurofeedback Training Study.

The aim of this study was to investigate the inner link between the small-world brain network and inhibitory control. Functional near-infrared spectroscopy (fNIRS) was used to construct a neurofeedback (NF) training system and regulate the frontal small-world brain network. The small-world network downregulation group (DOWN, n = 17) and the small-world network upregulation group (UP, n = 17) received five days of fNIRS-NF training and performed the color-word Stroop task before and after training. The behavioral and functional brain network topology results of both groups were analyzed by a repeated-measures analysis of variance (ANOVA), which showed that the upregulation training helped to improve inhibitory control. The upregulated small-world brain network exhibits an increase in the brain network regularization, links widely dispersed brain resources, and reduces the lateralization of brain functional networks between hemispheres. This suggests an inherent correlation between small-world functional brain networks and inhibitory control; moreover, dynamic optimization under cost efficiency trade-offs provides a neural basis for inhibitory control. Inhibitory control is not a simple function of a single brain region or connectivity but rather an emergent property of a broader network.

The Influence of Breathing Exercises on Regional Ventilation in Healthy and Patients with Chronic Obstructive Pulmonary Disease.

We hypothesized that the respiratory exercises have uniform effects on ventilation in healthy subjects but the effects varied in patients with chronic obstructive pulmonary disease (COPD). In this study, a total of 30 healthy volunteers and 9 patients with COPD were included. Data were recorded continuously during (1) diaphragmatic breathing; (2) pursed lip breathing with full inhalation; (3) pursed lip combining diaphragmatic breathing. The sequence of the three breathing exercises was randomized using machine generated random permutation. Spatial and temporal ventilation distributions were evaluated with electrical impedance tomography. Results showed that, tidal volume was significantly larger during various breathing exercises compared to quiet tidal breathing, in both healthy and COPD (p < 0.01). However, for other EIT-based parameters, statistical significances were only observed in healthy volunteers, not in patients. Diaphragmatic breathing alone might not be able to decrease functional residual capacity in COPD and the effect varied largely from patient to patient (6:3, decrease vs. increase). Ventilation distribution moved toward ventral regions in healthy during breathing exercises (p < 0.0001). Although this trend was observed in the COPD, the differences were not significant. Ventilation became more homogeneous when diaphragmatic breathing technique was implemented (p < 0.0001). Again, the improvements were not significant in COPD. Regional ventilation delay was relatively high in COPD and comparable in various breathing periods. In conclusions, the impact of pursed lip and diaphragmatic breathing varied in different patients with COPD. Breathing exercise may need to be individualized to maximize the training efficacy with help of EIT.

Synergistic effects of transcutaneous vagus nerve stimulation and inhibitory control training on electrophysiological performance in healthy adults.

Transcutaneous vagal nerve stimulation (tVNS) is a non-invasive nerve stimulation technique that exerts a positive "exogenous" online neuromodulatory effect on inhibitory control (IC). Additionally, IC training (ICT) is an effective approach for enhancing IC via the "endogenous" activation of brain regions implicated in this process. The aim of the present study was to examine the synergistic effects of tVNS and ICT on IC enhancement. For this, we measured the changes in neural activity in frontal, fronto-central, and central regions in the time domain of the N2 component and the frequency domain of alpha power during the stop signal task. A total of 58 participants were randomly divided into four groups that received five sessions of either ICT or sham ICT with either online tVNS or sham tVNS. No differences in N2 amplitude were detected after any of the interventions. However, N2 latency shortened after tVNS + ICT in frontal, fronto-central, and central regions. N2 latency shortened after the intervention of sham tVNS + ICT in frontal region. Moreover, alpha power after tVNS + ICT intervention was larger than those of the other interventions in frontal, fronto-central, and central regions. The obtained electrophysiological data suggested that combining tVNS with ICT has synergistic ameliorative effects on IC, and provide evidence supporting the IC-enhancing potential of tVNS combined with ICT.

The neuroelectrophysiological and behavioral effects of transcranial direct current stimulation on executive vigilance under a continuous monotonous condition.

A prolonged period of vigilance task will lead to vigilance decrement and a drop in cognitive efficiency. Although transcranial direct current stimulation (tDCS) can be used to improve cognitive performance following vigilance decrement, the findings in this area of study are inconsistent. This study aims to identify the neuroelectrophysiological and behavioral effects of tDCS over the left dorsolateral prefrontal cortex (DLPFC) on executive vigilance under a continuous monotonous condition. We recruited 29 participants who randomly received 30 min active or sham tDCS before the vigilance task (anode electrode at the left DLPFC, cathode electrode at the right supraorbital area). Participants completed four sessions of vigilance task and five sessions of self-report sleepiness, Oddball task, and Go/Nogo task, for a total of about 5 h. EEG was acquired in real-time throughout the experiment. Repeated measures of ANOVA were utilized to analyze the evolution of each metric with task-on-time. The results demonstrated that subjective arousal state, vigilance performance, event-related potentials (ERPs), and EEG power were significantly affected by time on task. Brain stimulation did not significantly affect the evolution of subjective and objective executive vigilance performance, but significantly modulated spontaneous activity in the alpha and beta bands across the entire brain. The continuous enhancement of the prefrontal cortex increased P2 amplitude for the Oddball task, which was associated with the enhancement of the early stage of information processing. P3 amplitude had a temporary enhancement effect, which significantly decreased following a cognitive fatigue. tDCS had a continuous enhancement effect on N2 amplitude for the Go/Nogo task, which was associated with the enhanced inhibition of distracting stimuli. Together, the current data suggest that anodal tDCS over left DLPFC possibly enhances the early stage of relevant information processing and the inhibitory control of distracting stimuli during a continuous and monotonous vigilance task.

Assessment of Low Back Pain in Helicopter Pilots Using Electrical Bio-Impedance Technique: A Feasibility Study.

Low back pain (LBP) is known to pose a serious threat to helicopter pilots. This study aimed to explore the potential of electrical bio-impedance (EBI) technique with the advantages of no radiation, non-invasiveness and low cost, which is intended to be used as a daily detection tool to assess LBP in primary aviation medical units. The LBP scales (severity) in 72 helicopter pilots were assessed using a pain questionnaire, while the bilateral impedance measurements of the lumbar muscle were carried out with a high precision EBI measurement system. Results showed that the modulus of lumbar muscle impedance increased with LBP scale whereas the phase angle decreased. For different LBP scales, significant differences were found in the modulus of lumbar muscle impedance sum on both sides (Z sum ), as well as in the modulus and phase angle of lumbar muscle impedance difference between both sides (Z diff and ϕ diff ), respectively (P < 0.05). Moreover, Spearman's correlation analysis manifested a strong correlation between Z sum and LBP scale (R = 0.692, P < 0.01), an excellent correlation between Z diff and LBP scale (R = 0.86, P < 0.01), and a desirable correlation between ϕ diff and LBP scale (R = -0.858, P < 0.01). In addition, receiver operator characteristic analysis showed that for LBP prediction, the area under receiver operator characteristic curve of Z sum , Z diff , and ϕ diff were 0.931, 0.992, and 0.965, respectively. These findings demonstrated that EBI could sensitively and accurately detect the state of lumbar muscle associated with LBP, which might be the potential tool for daily detection of LBP in primary aviation medical units.

Training and Transfer Effects of Combining Inhibitory Control Training With Transcutaneous Vagus Nerve Stimulation in Healthy Adults.

Inhibitory control training (ICT) is a promising method to improve individual performance of inhibitory control (IC). Recent studies have suggested transcutaneous vagus nerve stimulation (tVNS) as a novel approach to affect cognitive function owing to its ability to modulate the locus coeruleus-noradrenaline system. To examine the synergistic effects of combining ICT with tVNS, 58 young males in college were randomly assigned to four groups: ICT + tVNS, ICT + sham tVNS, sham ICT + tVNS, and sham ICT + sham tVNS. Participants were instructed to complete three sessions that comprised pre-training tests, a training session, and post-training tests sequentially. Results showed that the ICT + tVNS group significantly improved training and near-transfer effects on the stop-signal and Go/No-go tasks, and these effects were larger than those of the other groups. However, none of the groups exhibited the far-transfer effect on the color-word Stroop task. These results suggest that tVNS augments the intervention effects of training and similar inhibition tasks to achieve the synergistic effect; however, it does not modulate the effects of non-training tasks and obtain the far-transfer effect. ICT combined with tVNS may be a valuable intervention for improving IC in healthy individuals in certain industries and offers novel research ideas for using tVNS for cognitive improvement.

The effects of emotional trait factors on simulated flight performance under an acute psychological stress situation.

Objective. Pilots are commonly exposed to some sources of emotional and cognitive stressors, especially for flight cadets, which have an important influence on flight safety. The present study aimed to study the relationship between emotional trait factors, emotional state, mental workload and simulated flight performance (SFP) under an acute psychological stress situation. Methods. Fifty-five undergraduates were included in the study. The Wong and Law emotional intelligence scale (WLEIS), state-trait anxiety inventory (STAI), stress rating questionnaire (SRQ) and National Aeronautics and Space Administration task load index (NASA-TLX) were used as data collection tools. Nine hours of simulated flight training were conducted in a simulator of the Type-6 Primary Trainer (Aviation University Air Force, China). The simulated flight assessment was taken as the acute psychological stressor. Results. SFP was negatively correlated with tensity and state anxiety. Emotional intelligence (EI) indirectly affected the SFP mediated by emotional state and workload, and emotional state had a mediating effect on the relationship between trait anxiety and SFP. Conclusions. The findings indicated that emotional trait factors (EI and trait anxiety) may indirectly affect SFP under an acute psychological stress situation, and emotional state (tensity and state anxiety) and mental workload played an important mediating role.

A new method for identifying the acute respiratory distress syndrome disease based on noninvasive physiological parameters.

Early diagnosis and prevention play a crucial role in the treatment of patients with ARDS. The definition of ARDS requires an arterial blood gas to define the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2 ratio). However, many patients with ARDS do not have a blood gas measured, which may result in under-diagnosis of the condition. Using data from MIMIC-III Database, we propose an algorithm based on patient non-invasive physiological parameters to estimate P/F levels to aid in the diagnosis of ARDS disease. The machine learning algorithm was combined with the filter feature selection method to study the correlation of various noninvasive parameters from patients to identify the ARDS disease. Cross-validation techniques are used to verify the performance of algorithms for different feature subsets. XGBoost using the optimal feature subset had the best performance of ARDS identification with the sensitivity of 84.03%, the specificity of 87.75% and the AUC of 0.9128. For the four machine learning algorithms, reducing a certain number of features, AUC can still above 0.8. Compared to Rice Linear Model, this method has the advantages of high reliability and continually monitoring the development of patients with ARDS.

[Research on algorithms for identifying the severity of acute respiratory distress syndrome patients based on noninvasive parameters].

Acute respiratory distress syndrome (ARDS) is a serious threat to human life and health disease, with acute onset and high mortality. The current diagnosis of the disease depends on blood gas analysis results, while calculating the oxygenation index. However, blood gas analysis is an invasive operation, and can't continuously monitor the development of the disease. In response to the above problems, in this study, we proposed a new algorithm for identifying the severity of ARDS disease. Based on a variety of non-invasive physiological parameters of patients, combined with feature selection techniques, this paper sorts the importance of various physiological parameters. The cross-validation technique was used to evaluate the identification performance. The classification results of four supervised learning algorithms using neural network, logistic regression, AdaBoost and Bagging were compared under different feature subsets. The optimal feature subset and classification algorithm are comprehensively selected by the sensitivity, specificity, accuracy and area under curve (AUC) of different algorithms under different feature subsets. We use four supervised learning algorithms to distinguish the severity of ARDS (P/F ≤ 300). The performance of the algorithm is evaluated according to AUC. When AdaBoost uses 20 features, AUC = 0.832 1, the accuracy is 74.82%, and the optimal AUC is obtained. The performance of the algorithm is evaluated according to the number of features. When using 2 features, Bagging has AUC = 0.819 4 and the accuracy is 73.01%. Compared with traditional methods, this method has the advantage of continuously monitoring the development of patients with ARDS and providing medical staff with auxiliary diagnosis suggestions.

Subacute onset leukodystrophy and visual-spatial disorders revealing phenylketonuria combined with homocysteinmia in adulthood: A case report.

RATIONALE: Phenylketonuria (PKU) is a metabolic disorder, which manifests a progressive irreversible neurological impairment during infancy and childhood. Hyperhomocysteinemia also showed that it might be involved in pathophysiology of many neuropsychiatric disorders. The late-onset clinical manifestations of these 2 diseases have not been reported elsewhere. We speculated that the late-onset PKU is caused by 2 kinds of metabolic dysfunction synergistically, especially a short period of irregular diet directly caused clinical symptoms. PATIENT CONCERNS: A 21-year old Asian male patient demonstrated subacute leukodystrophy and visual-spatial disorders of late onset in adulthood. DIAGNOSES: Phenylketonuria combined with homocysteinmia, who presented with heterozygous mutations in gene encoding PAH p.G247R (c.739G>C) and p.Y204C (c.611A>G), along with homozygous mutation of gene encoding MTHFR c.677C>T. INTERVENTIONS: The patient was treated with cobalamine (500 µg/day), vitamin B6 (30 mg/day), folate (5 mg/day) and encouraged to follow a protein-restricted diet. OUTCOMES: Visual disorientation and cognitive function showed improvement. Head MR showed similar resolution with the original lesion. Serum homocysteine and folate analysis were normal with decreased phenylalanine level. LESSONS: This case suggests that neurological involvement of progressive nervous system dysfunction could be caused by more than one kind of inherited metabolic disturbances, and each one can induce or deteriorate the manifestations of another metabolic disorders.

[Relapsing-remitting multiple sclerosis at remission stage treated with acupuncture:a randomized controlled trial].

OBJECTIVE: To evaluate the differences in the therapeutic effects on relapsing-remitting multiple sclerosis (RRMS) at remission stage between acupuncture at acupoints and shallow needling therapy at the nearby points. METHODS: Forty-two patients of RRMS were randomized into an observation group and a control group, 21 cases in each one. In the observation group, besides the basic treatment, acupuncture was applied according to WANG Leting's empirical prescriptions as "the empirical ten needles" "thirteen needles of the governor vessel" "twelve needles of hand and foot" as well as the symptomatic points. In the control group, the basic treatment was given. Additionally, the shallow needling therapy was given at the sites 0.2 to 0.3 cun lateral to the acupoints, and the arrival of qi was not required. In the two groups, acupuncture was given once a day for 5 days a week, continuously for 2 weeks. At the intervals of 2 weeks, totally the treatment of 3 months was required. The follow-up visit was conducted for 2 years. Separately, the scores of the expanded disability status scale (EDSS) before and in follow-up after treatment, the annual recurrent rate before and after treatment and recurrent interval after treatment were observed in the patients of the two groups. RESULTS: In the observation group, EDSS scores in 3-month and 6-month follow-up were reduced as compared with those before treatment (both P<0.05) and those in the 12-month and 24-month follow-up were increased (both P<0.05). In the control group, EDSS scores were increased in tendency continuously in 3-month, 6-month, 12-month and 24-month follow-up (all P<0.05). In each time point of follow-up, the different value of EDSS scores in the observation group was lower than that in the control group (P<0.05, P<0.01). The annual recurrent rates after treatment were reduced as compared with those before treatment in the two groups (both P<0.01) and the value in the observation group was lower than that in the control group (P<0.01). The recurrent interval in the observation group was longer than that in the control group[(441.56±65.37) d vs (382.78±59.33) d, P<0.01]. CONCLUSIONS: Acupuncture achieves the significant therapeutic effects on RRMS at the remission stage. This therapy relieves the symptoms of neural functional deficits, delays the time of occurrence and reduces the annual recurrent rate.

[Research on malignant arrhythmia detection algorithm using neural network optimized by genetic algorithm].

Detection and classification of malignant arrhythmia are key tasks of automated external defibrillators. In this paper, 21 metrics extracted from existing algorithms were studied by retrospective analysis. Based on these metrics, a back propagation neural network optimized by genetic algorithm was constructed. A total of 1,343 electrocardiogram samples were included in the analysis. The results of the experiments indicated that this network had a good performance in classification of sinus rhythm, ventricular fibrillation, ventricular tachycardia and asystole. The balanced accuracy on test dataset reached up to 99.06%. It illustrates that our proposed detection algorithm is obviously superior to existing algorithms. The application of the algorithm in the automated external defibrillators will further improve the reliability of rhythm analysis before defibrillation and ultimately improve the survival rate of cardiac arrest.

[Adaptive Cardiopulmonary Resuscitation Artifacts Elimination Algorithm Based on Empirical Mode Decomposition and Independent Component Analysis].

Artifacts produced by chest compression during cardiopulmonary resuscitation(CPR)seriously affect the reliability of shockable rhythm detection algorithms.In this paper,we proposed an adaptive CPR artifacts elimination algorithm without needing any reference channels.The clean electrocardiogram(ECG)signals can be extracted from the corrupted ECG signals by incorporating empirical mode decomposition(EMD)and independent component analysis(ICA).For evaluating the performance of the proposed algorithm,a back propagation neural network was constructed to implement the shockable rhythm detection.A total of 1 484 corrupted ECG samples collected from pigs were included in the analysis.The results of the experiments indicated that this method would greatly reduce the effects of the CPR artifacts and thereby increase the accuracy of the shockable rhythm detection algorithm.

[Development and animal tests of a miniaturized electrical chest compression device].

This paper introduces the development and animal tests of a miniaturized electrical chest compression device. Based on pulse width modulation technology produced by micro control unit, the device can control the frequency and depth of the compression accurately, as well as perform real-time adjustment. Therefore, it can perform continuous and stable chest compression for long time, which may increase the successful rate of cardiopulmonary resuscitation (CPR). Besides, the device can also produce different types of compression waveforms, including trapezoidal and triangular waveforms. Then, the performance and efficacy of the device was assessed with a rat model of asphyxial cardiac arrest (CA).

The determination and fate of disinfection by-products from ozonation of polluted raw water.

The major disinfection by-products (DBPs) resulting from ozone treatment of polluted surface water were investigated. By-products of either health concern or which may contribute to biological instability of treated drinking water were investigated. The major DBPs were analyzed in two fractions: carbonyl compounds and brominated organic compounds. The natural organic matter (NOM) was also isolated and fractionated from polluted water for subsequent ozonation and DBPs identification under conditions of typical drinking treatment. The main identified carbonyl compounds were low molecular weight carboxylic acids, benzoic compounds, aliphatic aldehydes and odorous aldehydes, respectively. Brominated organics were also found in ozonated water, including bromoform (CHBr3), monobromoacetic acid (MBAA), dibromoacetic acid (DBAA), 2,4-dibromophenol (2,4-DBP) and dibromoacetonitrile (DBAN), respectively. It was also found that the characteristic of organic precursors have significant influences on brominated organic by-products formation. Humic acid demonstrated the highest CHBr3, DBAA and 2,4-DBP formations, whereas hydrophilic neutral produced less CHBr3 and 2,4-DBP than the rest of the organic fractions but produced the highest amount of DBAN. In addition to the other target compounds, a total of 59 different organic compounds were detected by means of gas chromatograph/high-resolution electron-impact mass spectrometry (GC/EI-MS) detection and tentatively identified using mass spectral library searching, mainly aromatics, acids/esters, alcohols, aldehydes, phthalates and amines/amino acids were analyzed. The percentage of elimination or formation levels reached during ozonation is also discussed in this study.