Hemodynamic responses to low-level transcutaneous auricular nerve stimulation in young volunteers.

Objectives: The aim of this study was to characterize cardiovascular autonomic responses during two constant current intensities below sensory threshold of transcutaneous auricular nerve stimulation (taNS). On this basis, a protocol for taNS with autonomic modulatory potential could be proposed. Subjects and methods: We included 26 men and 24 women, mean age 26. Data were collected during three randomly allocated 20-minute right tragus stimulation sessions - a) no-stimulation (sham), b) 90 µA (arbitrary), and c) 130 µA (near the lowest sensory threshold in majority). Stimulation was 20 Hz, rectangular pulse width of 2 ms, duty cycle 2-second on/off. To assess autonomic responses, we continuously recorded ECG, non-invasive arterial blood pressure (BP) and thoracic impedance cardiography data. Ten-minute data were compared. Fast Fourier transform of RR intervals was performed on 10-minute recordings as well. Low frequency and high frequency power spectra were calculated. Friedman test or one-way ANOVA for repeated measurements and Mann-Whitney or Wilcoxon's signed-rank test, or t-test were carried out. P < 0.05 was considered significant. Results: At 130 µA stimulation, cardiac output significantly decreased (p < 0.05), driven by significant heart rate drop in women, and stroke volume and contractility drop in men, pointing to a gender-related autonomic responses. We observed no significant changes in BP, or variability parameters. Significantly higher body size and BP were found in men, as expected. Conclusions: It seems that tested taNS protocol has a potential for cardiac autonomic modulation in majority of young healthy men as well as women. Further studies are however needed to prove the therapeutic potential of this stimulation protocol in different patient groups.

Cardiovascular responses to low-level transcutaneous vagus nerve stimulation.

AIMS: The aim was to determine cardiovascular responses to an arbitrary protocol of transcutaneous low-level vagus nerve electrical stimulation (tVNS). METHODS: Study was performed in 15 male volunteers, mean age 23 years. Data were collected during two sessions - sham stimulation (no stimulation) and stimulation. Each session included one-hour resting phase followed by 15-min autonomic nervous system testing phase (Valsalva, deep breathing, wet-cold face tests), all in supine position. The right tragus stimulation parameters were: 20 Hz, constant current at sensation threshold, 1 ms rectangular pulse width. The ECG, noninvasive arterial blood pressure and thoracic impedance cardiography measurements were recorded and analyzed continuously with the Task Force® Monitor (CNSystems Medizintechnik GmbH, Graz, Ver. 2.2.10.0). t-Test for paired samples, paired Wilcoxon signed-rank, and one-way ANOVA for repeated measurements were carried out. P < 0.05 was considered significant. RESULTS: We demonstrated significant reductions of left ventricular contractility and output parameters, a trend for heart rate reduction, and resulting beneficial reduction of left ventricular work load. However, significant increases of blood pressure and total peripheral resistance were recognized, possibly as a reflex response. CONCLUSION: It seems that our tVNS protocol has a potential for cardiac autonomic modulation. This gives us opportunity to advance our stimulation parameters with participant-specific adjustments. Further studies are however needed to prove the therapeutic potential of such approach in different patient groups.

Framework for Personalized Real-Time Control of Hidden Temperature Variables in Therapeutic Knee Cooling.

The paper formalizes, implements and evaluates a framework for personalized real-time control of inner knee temperature during cryotherapy after knee surgery. Studies have shown that the cryotherapy should be controlled depending on the individual patient's feedback on the cooling, which raises the need for smart personalized therapy. The framework is based on the feedback control loop that uses predicted instead of measured inner temperatures because measurements are not feasible or would introduce invasiveness into the system. It uses machine learning to construct a predictive model for estimation of the controlled inner temperature variable based on other variables whose measurement is more feasible - temperatures on the body surface. The machine learning method uses data generated from computer simulation of the therapeutic treatment for different input simulation parameters. A fuzzy proportional-derivative controller is designed to provide adequate near real-time control of the inner knee temperature by controlling the cooling temperature. The framework is evaluated for robustness and controllability. The results show that controlled cooling is essential for small-sized (and large-sized) knees that are significantly more (less) sensitive to the cooling compared to average-sized knees. Moreover, the framework recognizes dynamic physiological changes and potential changes in the system settings, such as extreme changes in the blood flow or changed target inner knee temperature, and consequently adapts the cooling temperature to reach the target value.

Medical-Grade ECG Sensor for Long-Term Monitoring.

The recent trend in electrocardiogram (ECG) device development is towards wireless body sensors applied for patient monitoring. The ultimate goal is to develop a multi-functional body sensor that will provide synchronized vital bio-signs of the monitored user. In this paper, we present an ECG sensor for long-term monitoring, which measures the surface potential difference between proximal electrodes near the heart, called differential ECG lead or differential lead, in short. The sensor has been certified as a class IIa medical device and is available on the market under the trademark Savvy ECG. An improvement from the user's perspective-immediate access to the measured data-is also implemented into the design. With appropriate placement of the device on the chest, a very clear distinction of all electrocardiographic waves can be achieved, allowing for ECG recording of high quality, sufficient for medical analysis. Experimental results that elucidate the measurements from a differential lead regarding sensors' position, the impact of artifacts, and potential diagnostic value, are shown. We demonstrate the sensors' potential by presenting results from its various areas of application: medicine, sports, veterinary, and some new fields of investigation, like hearth rate variability biofeedback assessment and biometric authentication.

A model for potential non-contact ski injuries of the knee.

Broadly accepted is that most knee injuries result from increased vertical forces, usually induced by an incidental ski fall, collision, or a high jump. We present a new non-contact knee injury mechanism that can happen during a ski turn. Such an injury is governed by a sudden inward turn of the inner ski and consequent swing of the inner leg followed by a nearly instant stop when locked by hip and knee joints. The model provides predictive results for a lateral tibial plateau compression fracture because several simplifications have been made. We confirmed that the modelled compression stresses at typical skiing conditions and with typical skiing equipment can provoke serious knee injuries. The awareness of skiers and skiing equipment industry of the described knee injury mechanism can act as an important injury-prevention factor.

Cardiac autonomic regulation and PR interval determination for enhanced atrial fibrillation risk prediction after cardiac surgery.

BACKGROUND: Changes in cardiac autonomic regulation and P-wave characteristics are associated with the occurrence of atrial fibrillation. The purpose of this study was to evaluate whether combined preoperative non-invasive determination of cardiac autonomic regulation and PR interval allows for the identification of patients at risk of new-onset atrial fibrillation after cardiac surgery. METHODS: RR, PR and QT intervals, and linear and non-linear heart rate variability parameters from 20 min high-resolution electrocardiographic recordings were determined one day before surgery in 150 patients on chronic beta blockers undergoing elective coronary artery bypass grafting, aortic valve replacement, or both, electively. RESULTS: Thirty-one patients (21%) developed postoperative atrial fibrillation. In the atrial fibrillation group, more arterial hypertension, a greater age, a higher EuroSCORE II, a higher heart rate variability index (pNN50: 9 ±â€¯20 vs. 4 ±â€¯10, p = 0.050), a short PR interval (156 ±â€¯23 vs. 173 ±â€¯31 ms; p = 0.011), and a reduced short-term scaling exponent of the detrended fluctuation analysis (DFA1, 0.96 ±â€¯0.36 vs. 1.11 ±â€¯0.30 ms; p = 0.032) were found compared to the sinus rhythm group. Logistic regression modeling confirmed PR interval, DFA1 and age as the strongest preoperative predictors of postoperative atrial fibrillation (area under the receiver operating characteristic curve = 0.804). CONCLUSIONS: Patients developing atrial fibrillation after cardiac surgery presented with severe cardiac autonomic derangement and a short PR interval preoperatively. The observed state characterizes both altered heart rate regulation and arrhythmic substrate and is strongly related to an increased risk of postoperative atrial fibrillation.

Continuous remote monitoring of COPD patients-justification and explanation of the requirements and a survey of the available technologies.

Remote patient monitoring should reduce mortality rates, improve care, and reduce costs. We present an overview of the available technologies for the remote monitoring of chronic obstructive pulmonary disease (COPD) patients, together with the most important medical information regarding COPD in a language that is adapted for engineers. Our aim is to bridge the gap between the technical and medical worlds and to facilitate and motivate future research in the field. We also present a justification, motivation, and explanation of how to monitor the most important parameters for COPD patients, together with pointers for the challenges that remain. Additionally, we propose and justify the importance of electrocardiograms (ECGs) and the arterial carbon dioxide partial pressure (PaCO2) as two crucial physiological parameters that have not been used so far to any great extent in the monitoring of COPD patients. We cover four possibilities for the remote monitoring of COPD patients: continuous monitoring during normal daily activities for the prediction and early detection of exacerbations and life-threatening events, monitoring during the home treatment of mild exacerbations, monitoring oxygen therapy applications, and monitoring exercise. We also present and discuss the current approaches to decision support at remote locations and list the normal and pathological values/ranges for all the relevant physiological parameters. The paper concludes with our insights into the future developments and remaining challenges for improvements to continuous remote monitoring systems. Graphical abstract ᅟ.

Cardiovagal and adrenergic function tests in unilateral carotid artery stenosis patients-a Valsalva manoeuvre tool to show an autonomic dysfunction?

BACKGROUND: The stability of an arterial baroreflex depends also upon the integrity of the afferent limb. For its quantification, we can use a noninvasive test such as baroreceptor sensitivity estimation during Valsalva manoeuvre. The aim of this study was to evaluate potential autonomic dysfunction in patients with unilateral severe carotid disease and compare the results to the results obtained from an age and gender matched group of healthy volunteers. METHODS: We evaluated dynamic changes during Valsalva manoeuvre (Valsalva ratio, cardiovagal and adrenergic baroreceptor sensitivity, sympathetic indexes and its dynamic ranges) in 41 patients (29 males; 62.9 ± 7.4 years) and compared the results to results obtained from volunteers (62.8 ± 7.0 years). RESULTS: Valsalva ratio between the patients and control group revealed no significant difference, as well as cardiovagal and adrenergic baroreceptor sensitivity. Sympathetic indexes, except for sympathetic index 2, reflecting the sympathetic vasoconstrictor baroreceptor response in late phase 2 of Valsalva manoeuvre (7.1 ± 13.1 mmHg in patients vs. 11.4 ± 10.2 mmHg in control group; p = 0.012) showed no significant differences between the studied groups. The most prominent dynamic range between the groups was within the sympathetic index 2. CONCLUSION: With some Valsalva manoeuvre test results, we were not able to show severe autonomic dysfunction in unilateral severe carotid stenosis patients except for lower vasoconstriction response within the late phase 2 of the manoeuvre.

On the Convergence of Stresses in Fretting Fatigue.

Fretting is a phenomenon that occurs at the contacts of surfaces that are subjected to oscillatory relative movement of small amplitudes. Depending on service conditions, fretting may significantly reduce the service life of a component due to fretting fatigue. In this regard, the analysis of stresses at contact is of great importance for predicting the lifetime of components. However, due to the complexity of the fretting phenomenon, analytical solutions are available for very selective situations and finite element (FE) analysis has become an attractive tool to evaluate stresses and to study fretting problems. Recent laboratory studies in fretting fatigue suggested the presence of stress singularities in the stick-slip zone. In this paper, we constructed finite element models, with different element sizes, in order to verify the existence of stress singularity under fretting conditions. Based on our results, we did not find any singularity for the considered loading conditions and coefficients of friction. Since no singularity was found, the present paper also provides some comments regarding the convergence rate. Our analyses showed that the convergence rate in stress components depends on coefficient of friction, implying that this rate also depends on the loading condition. It was also observed that errors can be relatively high for cases with a high coefficient of friction, suggesting the importance of mesh refinement in these situations. Although the accuracy of the FE analysis is very important for satisfactory predictions, most of the studies in the literature rarely provide information regarding the level of error in simulations. Thus, some recommendations of mesh sizes for those who wish to perform FE analysis of fretting problems are provided for different levels of accuracy.

Simple cardiovagal and adrenergic function tests in carotid artery stenosis patients as a potential tool for determining a transient autonomic dysfunction.

PURPOSE: The arterial baroreflex depends on the integrity of the afferent limb, which can be quantified using the baroreceptor's sensitivity (BRS) during the Valsalva maneuver (VM). The aim of this study was to evaluate, using autonomic nervous system tests, the autonomic function in patients after a carotid artery angioplasty (CAS). METHODS: We evaluated the changes in blood pressure (BP) during the VM (Valsalva ratio, BRS, sympathetic indexes) in 41 patients with symptomatic, unilateral, internal carotid artery stenosis. RESULTS: The Valsalva ratio between the baseline and the post-procedural day (1.3 ± 0.1 vs 1.44 ± 0.3; P = 0.002) and the post-procedural day and a month later (1.44 ± 0.3 vs 1.3 ± 0.3; P = 0.0002) revealed significant differences. This was confirmed with a cardiovagal BRS test. However, the adrenergic BRS did not reveal any differences. Sympathetic indexes [BP fall (SI1) and recovery during phase 2 (SI2)] showed differences for the periods before and a day after the treatment (36.9 ± 18.0 vs 27.2 ± 21.4 and 7.1 ± 13.1 vs 3.0 ± 8.2, respectively; P = 0.004) and for SI1 a day and a month after the treatment (27.2 ± 21.4 vs 37.1 ± 21.8; P = 0.036). The dynamic ranges between S1 and S3 (the difference in the BP between the baseline and the end of phase 2) were also different (P = 0.007 and P = 0.044, respectively). CONCLUSION: We found heterogeneous responses in the BP regulation obtained with the Valsalva maneuver in our patients; however, we could not confirm that CAS provoked any long-term autonomic dysfunction, except for 1 day after the procedure.

Non-invasive real-time prediction of inner knee temperatures during therapeutic cooling.

The paper addresses the issue of non-invasive real-time prediction of hidden inner body temperature variables during therapeutic cooling or heating and proposes a solution that uses computer simulations and machine learning. The proposed approach is applied on a real-world problem in the domain of biomedicine - prediction of inner knee temperatures during therapeutic cooling (cryotherapy) after anterior cruciate ligament (ACL) reconstructive surgery. A validated simulation model of the cryotherapeutic treatment is used to generate a substantial amount of diverse data from different simulation scenarios. We apply machine learning methods on the simulated data to construct a predictive model that provides a prediction for the inner temperature variable based on other system variables whose measurement is more feasible, i.e. skin temperatures. First, we perform feature ranking using the RReliefF method. Next, based on the feature ranking results, we investigate the predictive performance and time/memory efficiency of several predictive modeling methods: linear regression, regression trees, model trees, and ensembles of regression and model trees. Results have shown that using only temperatures from skin sensors as input attributes gives excellent prediction for the temperature in the knee center. Moreover, satisfying predictive accuracy is also achieved using short history of temperatures from just two skin sensors (placed anterior and posterior to the knee) as input variables. The model trees perform the best with prediction error in the same range as the accuracy of the simulated data (0.1°C). Furthermore, they satisfy the requirements for small memory size and real-time response. We successfully validate the best performing model tree with real data from in vivo temperature measurement from a patient undergoing cryotherapy after ACL reconstruction.

Smart wireless sensor for physiological monitoring.

Presented is a wireless body sensor capable of measuring local potential differences on a body surface. By using on-sensor signal processing capabilities, and developed algorithms for off-line signal processing on a personal computing device, it is possible to record single channel ECG, heart rate, breathing rate, EMG, and when three sensors are applied, even the 12-lead ECG. The sensor is portable, unobtrusive, and suitable for both inpatient and outpatient monitoring. The paper presents the sensor's hardware and results of power consumption analysis. The sensor's capabilities of recording various physiological parameters are also presented and illustrated. The paper concludes with envisioned sensor's future developments and prospects.

Electrocardiographic systems with reduced numbers of leads-synthesis of the 12-lead ECG.

Systems with reduced numbers of leads that can synthesize the 12-lead electrocardiogram (ECG) with an insignificant or a small loss of diagnostic information have been proposed. The advantage over standard 12-lead ECG systems is the smaller number of measurement sites (i.e., electrodes) and, consequently, fewer wires. In this paper, we review all the important systems with reduced numbers of leads together with the methodology for synthesizing the leads. The fundamental theoretical background necessary to understand the most important concepts related to the synthesis is included. The presented theoretical and experimental justifications for the synthesis show that it is not necessary to measure a large number of leads directly, because the standard 12-lead ECG and arbitrary additional leads can be synthesized. Various approaches to evaluating the synthesized 12-lead ECG are defined and explained, and a number of systems that synthesize 12-lead ECG are presented as they were introduced in the literature. We cover the developments and improvements from the 1940s to the present day. The systems are classified on the basis of the synthesis method used, the approach to the evaluation of the synthesized ECG (depending on the measurement sites used), and on the number and types of leads employed. Based on a detailed assessment of state-of-the-art systems, open problems and challenges are highlighted, while further developments of electrocardiographic systems are envisaged.

Knee temperatures measured in vivo after arthroscopic ACL reconstruction followed by cryotherapy with gel-packs or computer controlled heat extraction.

PURPOSE: To obtain in vivo data about intra- and extra-articular knee temperatures to assess the effectiveness of two cryotherapeutic methods-conventional cooling with gel-packs and computer controlled cryotherapy following anterior cruciate ligament (ACL) reconstructive surgery. METHODS: Twenty patients were arbitrarily assigned for cryotherapy after ACL reconstruction: 8 patients with frozen gel-packs and 12 patients with computer controlled cryotherapy with constant temperatures of the cooling liquid in the knee pads. The treatment was performed for 12 h. Temperatures were measured with two thermo sensors in catheters placed intraarticularly and subcutaneously, four sensors on the skin and one sensor under protective bandage, every second for 16 h after surgery. RESULTS: In the first 2 h of treatment, there were no significant differences (n.s.) between the groups in temperatures in the intracondylar notch. After 4 h of cryotherapy, the temperatures were significantly lower on the skin (24.6 ± 2.8 and 31.4 ± 1.3 °C, p < 0.01) and in the subcutaneous tissue (28.6 ± 5.7 and 34.6 ± 1.4 °C, p = 0.01), and the difference between the temperature in the intracondylar notch and the subcutaneous tissue was significantly greater (4.0 ± 3.0 and 0.8 ± 0.6 °C, p = 0.01) in the computer controlled cryotherapy group compared to the gel-pack group. CONCLUSIONS: The cooling effect of the arthroscopy irrigation fluid on the knee temperature is evident in the first 2 h of treatment. The energy extraction is significantly more effective and controllable by computer controlled cryotherapy than with frozen gel-packs. LEVEL OF EVIDENCE: Prospective comparative study, Level II.

Exact parallel maximum clique algorithm for general and protein graphs.

A new exact parallel maximum clique algorithm MaxCliquePara, which finds the maximum clique (the fully connected subgraph) in undirected general and protein graphs, is presented. First, a new branch and bound algorithm for finding a maximum clique on a single computer core, which builds on ideas presented in two published state of the art sequential algorithms is implemented. The new sequential MaxCliqueSeq algorithm is faster than the reference algorithms on both DIMACS benchmark graphs as well as on protein-derived product graphs used for protein structural comparisons. Next, the MaxCliqueSeq algorithm is parallelized by splitting the branch-and-bound search tree to multiple cores, resulting in MaxCliquePara algorithm. The ability to exploit all cores efficiently makes the new parallel MaxCliquePara algorithm markedly superior to other tested algorithms. On a 12-core computer, the parallelization provides up to 2 orders of magnitude faster execution on the large DIMACS benchmark graphs and up to an order of magnitude faster execution on protein product graphs. The algorithms are freely accessible on http://commsys.ijs.si/~matjaz/maxclique.

Estimating the Universal Positions of Wireless Body Electrodes for Measuring Cardiac Electrical Activity.

A methodology is presented for estimating the wireless body electrode (WE) positions and for calculating the linear transformations that enable the synthesis of a 12-lead ECG or a multichannel ECG from three WEs, which in turn simplifies and improves the acquisition of ECGs. We present, compare, and evaluate three approaches to the synthesis: fully personalized, fully universal, and combined with universal leads and personalized transformations. The evaluation results show that WEs are an acceptable alternative to the standard 12-lead ECG device for patients with chronic myocardial ischemia, if either the fully personalized or combined approach is used. The median correlation coefficients are all higher than 0.94 and 0.92 for the fully personalized and combined approaches, respectively. The corresponding kappa and percentual diagnostic agreements between the synthesized and target 12-lead ECGs are 0.88 (95%) and 0.83 (92%), respectively. The evaluation additionally shows that the personalization of the transformations has more impact on the quality of the synthesized ECGs than the personalization of the WEs' positions.

Asynchronous master-slave parallelization of differential evolution for multi-objective optimization.

In this paper, we present AMS-DEMO, an asynchronous master-slave implementation of DEMO, an evolutionary algorithm for multi-objective optimization. AMS-DEMO was designed for solving time-intensive problems efficiently on both homogeneous and heterogeneous parallel computer architectures. The algorithm is used as a test case for the asynchronous master-slave parallelization of multi-objective optimization that has not yet been thoroughly investigated. Selection lag is identified as the key property of the parallelization method, which explains how its behavior depends on the type of computer architecture and the number of processors. It is arrived at analytically and from the empirical results. AMS-DEMO is tested on a benchmark problem and a time-intensive industrial optimization problem, on homogeneous and heterogeneous parallel setups, providing performance results for the algorithm and an insight into the parallelization method. A comparison is also performed between AMS-DEMO and generational master-slave DEMO to demonstrate how the asynchronous parallelization method enhances the algorithm and what benefits it brings compared to the synchronous method.

Two proximal skin electrodes--a respiration rate body sensor.

We propose a new body sensor for extracting the respiration rate based on the amplitude changes in the body surface potential differences between two proximal body electrodes. The sensor could be designed as a plaster-like reusable unit that can be easily fixed onto the surface of the body. It could be equipped either with a sufficiently large memory for storing the measured data or with a low-power radio system that can transmit the measured data to a gateway for further processing. We explore the influence of the sensor’s position on the quality of the extracted results using multi-channel ECG measurements and considering all the pairs of two neighboring electrodes as potential respiration-rate sensors. The analysis of the clinical measurements, which also include reference thermistor-based respiration signals, shows that the proposed approach is a viable option for monitoring the respiration frequency and for a rough classification of breathing types. The obtained results were evaluated on a wireless prototype of a respiration body sensor. We indicate the best positions for the respiration body sensor and prove that a single sensor for body surface potential difference on proximal skin electrodes can be used for combined measurements of respiratory and cardiac activities.

Parallel-ProBiS: fast parallel algorithm for local structural comparison of protein structures and binding sites.

The ProBiS algorithm performs a local structural comparison of the query protein surface against the nonredundant database of protein structures. It finds proteins that have binding sites in common with the query protein. Here, we present a new parallelized algorithm, Parallel-ProBiS, for detecting similar binding sites on clusters of computers. The obtained speedups of the parallel ProBiS scale almost ideally with the number of computing cores up to about 64 computing cores. Scaling is better for larger than for smaller query proteins. For a protein with almost 600 amino acids, the maximum speedup of 180 was achieved on two interconnected clusters with 248 computing cores. Source code of Parallel-ProBiS is available for download free for academic users at http://probis.cmm.ki.si/download.