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The quality of heart rate (HR) measurements extracted from human photoplethysmography (PPG) signals are known to deteriorate under appreciable human motion. Auxiliary signals, such as accelerometer readings, are usually employed to detect and suppress motion artifacts. A 2019 study by Yifan Zhang and his coinvestigatorsused the noise components extracted from an infrared PPG signal to denoise a green PPG signal from which HR was extracted. Until now, this approach was only tested on "micro-motion" such as finger tapping. In this study, we extend this technique to allow accurate calculation of HR under high-intensity full-body repetitive "macro-motion". Our Dual Wavelength (DWL) framework was tested on PPG data collected from 14 human participants while running on a treadmill. The DWL method showed the following attributes: (1) it performed well under high-intensity full-body repetitive "macro-motion", exhibiting high accuracy in the presence of motion artifacts (as compared to the leading accelerometer-dependent HR calculation techniques TROIKA and JOSS); (2) it used only PPG signals; auxiliary signals such as accelerometer signals were not needed; and (3) it was computationally efficient, hence implementable in wearable devices. DWL yielded a Mean Absolute Error (MAE) of 1.22|0.57 BPM, Mean Absolute Error Percentage (MAEP) of 0.95|0.38%, and performance index (PI) (which is the frequency, in percent, of obtaining an HR estimate that is within ±5 BPM of the HR ground truth) of 95.88|4.9%. Moreover, DWL yielded a short computation period of 3.0|0.3 s to process a 360-second-long run.

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Computer-Assisted Semen Analysis (CASA) enables reliable analysis of semen images, and is designed to process large number of images with high consistency, accuracy, and repeatability. Design and testing of CASA algorithms can be accelerated greatly if reliable simulations of semen images under a variety of conditions and sample quality modes are available. Using life-like simulation of semen images can quantify the performance of existing and proposed CASA algorithms, since the parameters of the simulated image are known and controllable. We present simulation models for sperm cell image and swimming modes observed in real 2D (top-down) images of sperm cells in laboratory specimen. The models simulate human sperm using four (4) types of swimming, namely linear mean, circular, hyperactive, and immotile (or dead). The simulation models are used in studying algorithms for segmentation, localization, and tracking of sperm cells. Several segmentation and localization algorithms were tested under varying levels of noise, and then compared using precision, recall, and the optimal subpattern assignment (OSPA) metric. Images of real human semen sample were used to validate the segmentation and localization observations obtained from simulations. An example is given of sperm cell tracking on simulated semen images of cells using the different tracking algorithms (nearest neighbor (NN), global nearest neighbor (GNN), probabilistic data association filter (PDAF), and joint probabilistic data association filter (JPDAF)). Tracking performance was evaluated through multi-object tracking precision (MOTP) and multi-object tracking accuracy (MOTA). Simulation models enable objective assessments of semen image processing algorithms. We demonstrate the use of a new simulation tool to assess and compare segmentation, localization, and tracking methods. The simulation software allows testing along a large spectrum of parameter values that control the appearance and behavior of simulated semen images. Users can generate scenarios of different characteristics and assess the effectiveness of different CASA algorithms in these environments. The simulation was used to assess and compare algorithms for segmentation and tracking of sperm cells in semen images.

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Calculation of peripheral capillary oxygen saturation [Formula: see text] levels in humans is often made with a pulse oximeter, using photoplethysmography (PPG) waveforms. However, measurements of PPG waveforms are susceptible to motion noise due to subject and sensor movements. In this study, we compare two [Formula: see text]-level calculation techniques, and measure the effect of pre-filtering by a heart-rate tuned comb peak filter on their performance. These techniques are: (1) "Red over Infrared," calculating the ratios of AC and DC components of the red and infrared PPG signals,[Formula: see text], followed by the use of a calibration curve to determine the [Formula: see text] level Webster (in: Design of pulse oximeters, CRC Press, Boca Raton, 1997); and (2) a motion-resistant algorithm which uses the Discrete Saturation Transform (DST) (Goldman in J Clin Monit Comput 16:475-83, 2000). The DST algorithm isolates individual "saturation components" in the optical pathway, which allows separation of components corresponding to the [Formula: see text] level from components corresponding to noise and interference, including motion artifacts. The comparison we provide here (employing the two techniques with and without pre-filtering) addresses two aspects: (1) accuracy of the [Formula: see text] calculations; and (2) computational complexity. We used both synthetic data and experimental data collected from human subjects. The human subjects were tested at rest and while exercising; while exercising, their measurements were subject to the impacts of motion. Our main conclusion is that if an uninterrupted high-quality heart rate measurement is available, then the "Red over Infrared" approach preceded by a heart-rate tuned comb filter provides the preferred trade-off between [Formula: see text]-level accuracy and computational complexity. A modest improvement in [Formula: see text] estimate accuracy at very low SNR environments may be achieved by switching to the pre-filtered DST-based algorithm (up to 6% improvement in [Formula: see text] level accuracy at -10 dB over unfiltered DST algorithm and the filtered "Red over Infrared" approach). However, this improvement comes at a significant computational cost.

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INTRODUCTION: The negative effects of hypoxia on human cognitive function have been well documented. In this study we assess the correlation of performance in the SynWin cognitive Multi-Task Battery (MTB) and the onset of hypoxia and describe the use of cognitive assessment scores for real-time hypoxia detection.METHODS: We performed a correlation analysis between MTB scores (Arithmetic, Memory, Audio Monitoring, Video Monitoring tasks) and blood oxygen saturation levels to discover if the scores are good candidates to detect hypoxia. Since this analysis showed positive correlation, we proceeded to develop a parallel decision fusion system that uses these cognitive scores for real-time hypoxia detection using the Neyman-Pearson criterion.RESULTS: We demonstrate that MTB scores have considerable hypoxia detection potential and can be used (if measurable passively) in a real-time detection framework. Analysis of receiver operating characteristic (ROC) curves established a hierarchy of importance of the various MTB modules. The Arithmetic task module had the most significant contribution toward correct hypoxia detection (improvement of ∼13.5% and ∼13.9% in detection accuracy under global false alarms of 0.1 and 0.05, respectively), followed by the Memory and Audio Monitoring modules. Fusion of multiple cognitive assessment scores resulted in significantly higher detection accuracy (>86%) than using any one of the scores by itself.DISCUSSION: When available, cognitive assessment scores can be a useful tool for real-time hypoxia detection. Since these MTB tests also assess neuropsychological functioning, study of distributed detection systems based on MTB scores could help in designing tests that are more useful for detecting hypoxic symptoms.Rajasekar A, Acharya S, Shender BS, Rorres C, Hrebien L, Kam M. Correlation of cognitive scores and the onset of hypoxia. Aerosp Med Hum Perform. 2019; 90(5):429-439.

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Humans who operate in high altitudes for prolonged durations often suffer from hypoxia. The commencement of physiological and cognitive changes due to the onset of hypoxia may not be immediately apparent to the exposed individual. These changes can go unrecognized for minutes and even hours and may lead to serious performance degradation or complete incapacitation. A dynamic system capable of monitoring and detecting decreased physiologic states due to the onset of hypoxia has the potential to prevent adverse outcomes. In this study, we develop a real-time hypoxia monitoring system based on a parallel M -ary decision fusion architecture. Blood oxygen saturation levels and altitude readings are the inputs and estimates of the level of hypoxia are the outputs. We develop new temporal evolution models for blood oxygen saturation and functional impairment with respect to varying altitude. The proposed models enable accurate tracking of various hypoxia levels based on the duration of stay of the subject at an altitude. Using a Bayesian decision-making formulation, the system generates global estimates of the degree of hypoxia. The detection system is tested against synthetic and real datasets to demonstrate applicability and accuracy.

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We present a fully automated multi-sperm tracking algorithm. It has the demonstrated capability to detect and track simultaneously hundreds of sperm cells in recorded videos while accurately measuring motility parameters over time and with minimal operator intervention. Algorithms of this kind may help in associating dynamic swimming parameters of human sperm cells with fertility and fertilization rates. Specifically, we offer an image processing method, based on radar tracking algorithms, that detects and tracks automatically the swimming paths of human sperm cells in timelapse microscopy image sequences of the kind that is analyzed by fertility clinics. Adapting the well-known joint probabilistic data association filter (JPDAF), we automatically tracked hundreds of human sperm simultaneously and measured their dynamic swimming parameters over time. Unlike existing CASA instruments, our algorithm has the capability to track sperm swimming in close proximity to each other and during apparent cell-to-cell collisions. Collecting continuously parameters for each sperm tracked without sample dilution (currently impossible using standard CASA systems) provides an opportunity to compare such data with standard fertility rates. The use of our algorithm thus has the potential to free the clinician from having to rely on elaborate motility measurements obtained manually by technicians, speed up semen processing, and provide medical practitioners and researchers with more useful data than are currently available.

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This study documents the results of a controlled experiment designed to quantify the abilities of forensic document examiners (FDEs) and laypersons to detect simulations in handwritten documents. Nineteen professional FDEs and 26 laypersons (typical of a jury pool) were asked to inspect test packages that contained six (6) known handwritten documents written by the same person and two (2) questioned handwritten documents. Each questioned document was either written by the person who wrote the known documents, or written by a different person who tried to simulate the writing of the person who wrote the known document. The error rates of the FDEs were smaller than those of the laypersons when detecting simulations in the questioned documents. Among other findings, the FDEs never labeled a questioned document that was written by the same person who wrote the known documents as "simulation." There was a significant statistical difference between the responses of the FDEs and layperson for documents without simulations.

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The possible onset of Cytokine Release Syndrome (CRS) is an important consideration in the development of monoclonal antibody (mAb) therapeutics. In this study, several machine learning approaches are used to analyze CRS data. The analyzed data come from a human blood in vitro assay which was used to assess the potential of mAb-based therapeutics to produce cytokine release similar to that induced by Anti-CD28 superagonistic (Anti-CD28 SA) mAbs. The data contain 7 mAbs and two negative controls, a total of 423 samples coming from 44 donors. Three (3) machine learning approaches were applied in combination to observations obtained from that assay, namely (i) Hierarchical Cluster Analysis (HCA); (ii) Principal Component Analysis (PCA) followed by K-means clustering; and (iii) Decision Tree Classification (DTC). All three approaches were able to identify the treatment that caused the most severe cytokine response. HCA was able to provide information about the expected number of clusters in the data. PCA coupled with K-means clustering allowed classification of treatments sample by sample, and visualizing clusters of treatments. DTC models showed the relative importance of various cytokines such as IFN-γ, TNF-α and IL-10 to CRS. The use of these approaches in tandem provides better selection of parameters for one method based on outcomes from another, and an overall improved analysis of the data through complementary approaches. Moreover, the DTC analysis showed in addition that IL-17 may be correlated with CRS reactions, although this correlation has not yet been corroborated in the literature.

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A link-adaptive frequency division multiplexing (OFDM) ultrasonic physical layer is proposed for high-data-rate communications through metal walls. The ultrasonic link allows for communication without physical penetration of the metal barrier. Link-adaptive OFDM mitigates the severe frequency- selective fading of the ultrasonic channel and greatly improves throughput over impulse or narrowband communication systems. Throughput improvements of 300% are demonstrated over current narrowband low-frequency techniques, and show improved spectral efficiency over high-frequency techniques found in the literature.

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Continuous glucose monitoring systems are an integral component of diabetes management. Efforts to improve the accuracy and robustness of these systems are at the forefront of diabetes research. Towards this goal, a multi-sensor approach was evaluated in hospitalized patients. In this paper, we report on a multi-sensor fusion algorithm to combine glucose sensor measurements in a retrospective fashion. The results demonstrate the algorithm's ability to improve the accuracy and robustness of the blood glucose estimation with current glucose sensor technology.

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Analysis of multicolor flow cytometric data is traditionally based on the judgment of an expert, generally time consuming, sometimes incomplete and often subjective in nature. In this article, we investigate another statistical method using a Sequential Univariate Gating (SUG) algorithm to identify regions of interest between two groups of multivariate flow cytometric data. The metric used to differentiate between the groups of univariate distributions in SUG is the Kolmogorov-Smirnov distance (D) statistic. The performance of the algorithm is evaluated by applying it to a known three-color data set looking at activation of CD4+ and CD8+ lymphocytes with anti-CD3 antibody treatment and comparing the results to the expert analysis. The algorithm is then applied to a four-color data set used to study the effects of recombinant human erythropoietin (rHuEPO) on several murine bone marrow populations. SUG was used to identify regions of interest in the data and results compared to expert analysis and the current state-of-the-art statistical method, Frequency Difference Gating (FDG). Cluster analysis was then performed to identify subpopulations responding differently to rHuEPO. Expert analysis, SUG and FDG identified regions in the data that showed activation of CD4+ and CD8+ lymphocytes with anti-CD3 treatment. In the rHuEPO treated data sets, the expert and SUG identified a dose responsive expansion of only the erythroid precursor population. In contrast, FDG resulted in identification of regions of interest both in the erythroid precursors as well as in other bone marrow populations. Clustering within the regions of interest defined by SUG resulted in identification of four subpopulations of erythroid precursors that are morphologically distinct and show a differential response to rHuEPO treatment. Greatest expansion is seen in the basophilic and poly/orthochromic erythroblast populations with treatment. Identification of populations of interest can be performed using SUG in less subjective, time efficient, biologically interpretable manner that corroborates with the expert analysis. The results suggest that basophilic erythroblasts cells or their immediate precursors are an important target for the effects of rHuEPO in murine bone marrow. The MATLAB implementation of the method described in the article, both experimental data and other supplemental materials are freely available at http://web.mac.com/acidrap18.

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BACKGROUND: Cellular binding of annexin V and membrane permeability to 7-aminoactinomycin D (7AAD) are important tools for studying apoptosis and cell death by flow cytometry. Combining viability markers with cell surface marker expression is routinely used to study various cell lineages. Current classification methods using strict thresholds, or "gates," on the fluorescent intensity of these markers are subjective in nature and may not fully describe the phenotypes of interest. We have developed objective criteria for phenotypic boundary recognition through the application of statistical pattern recognition. This task was achieved using artificial neural networks (ANNs) that were trained to recognize subsets of cells with known phenotypes, and then used to determine decision boundaries based on statistical measures of similarity. This approach was then used to test the hypothesis that erythropoietin (EPO) inhibits apoptosis and cell death in erythroid precursor cells in murine bone marrow. METHODS: Our method was developed for classification of viability using an in vitro cell system and then applied to an ex vivo analysis of murine late-stage erythroid progenitors. To induce apoptosis and cell death in vitro, an EPO-dependent human leukemic cell line, UT-7(EPO) cells were incubated without recombinant human erythropoietin (rhEPO) for 72 h. Five different ANNs were trained to recognize live, apoptotic, and dead cells using a "known" subset of the data for training, and a K-fold cross validation procedure for error estimation. The ANNs developed with the in vitro system were then applied to classify cells from an ex vivo study of rhEPO treated mice. Tg197 (human tumor necrosis-alpha transgenic mice, a model of anemia of chronic disease) received a single s.c. dose of 10,000 U/kg rhEPO and femoral bone marrow was collected 1, 2, 4, and 8 days after dosing. Femoral bone marrow cells were stained with TER-119 PE, CD71 APC enable identification of erythroid precursors, and annexin V FITC and 7AAD to identify the apoptotic and dead cells. During classification forward and side angle light scatter were also input to all pattern recognition systems. RESULTS: Similar decision boundaries between live, apoptotic, and dead cells were consistently identified by the neural networks. The best performing network was a radial basis function multi-perceptron that produced an estimated average error rate of 4.5% +/- 0.9%. Using these boundaries, the following results were reached: depriving UT-7(EPO) cells of rhEPO induced apoptosis and cell death while the addition of rhEPO rescued the cells in a dose-dependent manner. In vivo, treatment with rhEPO resulted in an increase of live erythroid cells in the bone marrow to 119.8% +/- 9.8% of control at the 8 day time point. However, a statistically significant transient increase in TER-119(+) CD71(+) 7AAD(+) dead erythroid precursors was observed at the 1 and 2 day time points with a corresponding decrease in TER-119(+) CD71(+) 7AAD(-) Annexin V(-) live erythroid precursors, and no change in the number of TER-119(+) CD71(+) annexin V(+) 7AAD(-) apoptotic erythroid precursors in the bone marrow. CONCLUSIONS: A statistical pattern recognition approach to viability classification provides an objective rationale for setting decision boundaries between "positive" and "negative" intensity measures in cytometric data. Using this approach we have confirmed that rhEPO inhibits apoptosis and cell death in an EPO dependent cell line in vitro, but failed to do so in vivo, suggesting EPO may not act as a simple antiapoptotic agent in the bone marrow. Rather, homeostatic mechanisms may regulate the pharmacodynamic response to rhEPO.

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One of the major concerns in detecting changes in higher moments is these changes may be due to outliers or process errors that are not biologically significant. For example, a larger variance observed in the expression levels may simply due to the larger variation in the data collecting process. Several outliers, which exhibit some extreme expression levels than the rest of the samples, may also increase the variance or skewness of the expression levels significantly. So it is very important to reduce the effect of outliers and process errors by proper experimental designs [27], such as technical replicates and biological replicates, before high sensitivity criterion, such as ADS, can be applied. We have presented and demonstrated the operation of two new criteria, ADS and the MDS, for identifying differentially expressed genes. These two criteria were compared with several commonly used criteria, namely WTS, WRS, FCS, and ICE. Experiments with simulated data show ADS to be more powerful than the WTS. When high-sensitivity screening is required, ADS appears to be preferable to WTS. When an FPR similar to WTS is desired, MDS should be used. The popular Wilcoxon rank sum is a more conservative approach that should be employed when the lowest FPR is desired, even at the expense of lower TPRs. ICE is a less desirable criterion because it does not perform well for data generated by the normal model. FCS gave results similar to those of WTS. Evaluation of these algorithms using real biological datasets showed that ADS and MDS flagged several biologically significant genes that were missed by WTS, besides selecting most of the genes that are also selected by WTS.

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BACKGROUND: Insulin pharmacokinetics models describe the distribution and elimination of insulin in the body. These models can be useful in designing infusion schemes to produce a desired plasma insulin profile. METHODS: We evaluated the pharmacokinetics of intravenous insulin delivery in five human subjects with type 1 diabetes; one subject was studied on three separate occasions for a total of seven experiments. Each subject consumed an identical 829 Kcal meal of solid food for breakfast and lunch, followed by exercise on a stationary bicycle. Regular human insulin was infused into a peripheral vein at a basal rate (0.5 U/h) for the entire study. Coinciding with the consumption of each meal, insulin was infused at a higher rate for 120 min (average dose 8.5 +/- 2.1 U). The bolus dose was based upon preprandial and 60-min postprandial blood glucose measurements and a sliding scale regimen. Blood glucose levels were allowed to fluctuate throughout the protocol (mean 174 mg/dL, range 55-340 mg/dL). Human insulin levels were measured from plasma samples obtained every 10 min throughout the 8.5-h protocol. A total of 346 plasma samples were assayed to measure the concentration of human insulin. RESULTS AND CONCLUSIONS: Data were used to compare (previously developed) insulin kinetics models consisting of one, two, and three first-order linear differential equations. The ability of each model to simulate the input/output data (intravenous insulin infusion rate/plasma insulin concentration) was assessed. Our main finding is that the first-order linear insulin kinetics model was sufficient to describe the clinical data. The model had a fractional insulin loss rate of 0.112 +/- 0.063 min(1) and a distribution volume of 15.6 +/- 4.0 L.

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Several federal district court judges have recently referred to the purported lack of information on the proficiency of forensic document examiners (FDEs) in identifying writers of hand-printed documents. In order to provide the necessary information, we have re-analyzed data on writer identification that were collected in 1996 from 90 forensic document examiners and 34 laypersons. These data were used previously to assess the proficiency of FDEs using handwritten documents in several different types of writing. In the new analysis we separated data on hand-printed (HP) documents from data on non-hand-printed (NHP) documents and compiled error rates and statistics in each category. The main findings are: (1) whether or not the documents were hand-printed, the performance of FDEs was much better than that of laypersons; (2) statistical tests found no difference between the data provided by the FDEs in the HP and NHP categories; (3) statistical tests found no difference between the data provided by laypersons in the HP and NHP categories; and (4) statistical tests found differences between the data provided by the FDEs and the laypersons in both the HP and NHP categories. Similar results were obtained when hand-printed documents were compared to cursive documents and when cursive documents were compared to non-cursive documents. All the evidence indicates that in our proficiency test the performance of FDEs in writer identification was much better than the performance of laypersons in each one of the following document categories: (1) hand-printed; (2) non-hand-printed; (3) cursive; and (4) non-cursive.

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We investigate automation and control options for the neck flexibility tester (NFT) (P. McClure et al., 1998), a device originally used to measure the flexibility of the human cervical spine. The motivation is to lay the foundations for design and implementation of investigative devices that would allow studies of mechanical properties of the spine under repetitive dynamic loading. We derive the equations of motion for an automated NFT (ANFT) using a Lagrangian formulation. These equations, which represent a simplified first-order model of the dynamics, are used to simulate the ANFT using the software package Simulink. Two control schemes are examined: proportional plus integral plus derivative (PID) control and dynamic inversion. Both are simulated for setpoint and tracking control. It appears that PID control is preferred due to its simplicity of design and relative insensitivity to the dynamic model of the ANFT.

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